Startseite Effects of phytoestrogens combined with cold stress on sperm parameters and testicular proteomics in rats
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Effects of phytoestrogens combined with cold stress on sperm parameters and testicular proteomics in rats

  • Zhang Panpan , Nurbiah Alifu , Meiheriguli Sataer , Adilijiang Yiming EMAIL logo , Siyiti Amuti , Ma Wenjing und Wang Binghua
Veröffentlicht/Copyright: 24. Januar 2023
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Aus der Zeitschrift Open Life Sciences Band 18 Heft 1

Abstract

Phytoestrogens and cold negatively influence male fertility. However, the combined effects of these two factors on male reproduction remain unknown. Herein, we studied the changes of sperm parameters and identify potential biomarkers involved in testis of rats, which were intervened by phytoestrogens combined with cold stress. Male Sprague–Dawley rats were randomly divided into control and model groups. The rats in the model group were fed an estrogen diet and placed in a climate chamber [10 ± 2°C; humidity of 75 ± 5%] for 12 h/daily. When compared with the control group after 24 weeks, the rats in the model group showed increased food intake, urine and stool outputs, and higher estradiol and follicle-stimulating hormone levels. However, lower sperm concentration, motility, and viability, and reduced testosterone levels were detected. The epithelial cells of the seminiferous tubules and epididymal ducts presented morphological abnormalities. Proteomic analysis showed that 24 testicular proteins were upregulated and 15 were downregulated. The identified proteins were involved in reticulophagy and stress response. Our findings suggest that the phytoestrogens combined with cold stress had negative effects on the reproductive function of male rats and provide the basis for the establishment of “course simulation” type of oligospermia animal model.

Keywords: phytoestrogens; cold; testicular proteomics

1 Introduction

The World Health Organization estimated an approximately 9% of couples suffer from infertility, with the male factor contributing to 50% [1]. Spermatogenesis, which occurs in the seminiferous epithelium in the testis, consists of the differentiation process of the spermatogonia cells to mature spermatozoa. During spermatogenesis and spermatozoon maturation until their combination with the ova, sperm undergoes a series of alterations in morphology and function, each of which is affected by several elements, including genetic, immune, environmental, and neuroendocrine factors. These factors can cause spermatogenic disorders and abnormal sperm motility. Specific proteins in the testis play important physiological roles in sperm generation, maturation, and acquisition. Different pathogenic and environmental factors can cause significant dysregulation of these proteins, thus affecting the spermatogenetic process.

Exposure to environmental estrogen pollution can significantly affect the male reproductive system. Phytoestrogens are natural heterocyclic phenol compounds, which possess structural similarity with estrogen steroids and present estrogenic activity. The classical phytoestrogens, so far known, constitute a group of plant-derived compounds which include mainly isoflavones, lignans, coumestanes, stilbenes, and the flavonoids quercetin and kaempherol. Aliments, such as spinach, bean sprouts, soybeans, cabbage, and hops, contain high levels of phytoestrogens. Several preclinical experiments have demonstrated that the ingestion of high levels of phytoestrogens can negatively affect male reproduction, leading to decreased semen quality and an increase in congenital malformations, such as hypospadias and cryptorchidism. Moreover, phytoestrogens can adversely affect brain differentiation and reproductive development in rodents during embryogenesis [2] and can also increase the incidence of testicular cancer in humans [3].

Cold is one of the strongest physical and psychological environmental stressors, leading to a significant defense response in the body, known as the cold shock response. The body responds to cold shock with long-term adaptive changes in metabolic, physiological, biochemical, and hormonal parameters [4,5,6]. The cold shock causes sympathetic activation and constriction of peripheral blood vessels [7]. Because of their large surface-to-mass ratios, small mammals experience a huge thermoregulatory burden at low temperatures, which in turn induces reproductive inhibition to a certain extent [8,9]. This inhibitory effect of cold on various reproductive parameters has been repeatedly demonstrated in rodents [10].

Xinjiang is located at the following geographical coordinates: 73°40′ E∼96°23′ E, 34°22′ N∼49°10′ N. In this location, the winter season is cold and long. Additionally, environmental pollution has become increasingly serious and estrogen pollutants (both synthetic and naturally derived) are part of the environmental contaminants.

In this study, phytoestrogens combined with cold stress intervention were experimentally reproduced, and changes in sperm parameters in rats were evaluated. Alterations of the testis proteins were detected using label-free proteomic technology. This study aims to set the basis for establishing a “course simulation” type of oligospermia animal model and preliminarily identify its molecular mechanism.

2 Methods

2.1 Animal models

The experimental animals were bred and provided by the Animal Experiment Center of Xinjiang Medical University. In a 24-week phytoestrogen and cold stress intervention study, 8-week-old Sprague–Dawley rats (180–220 g) were randomly assigned to two groups of 12 males each. Group N served as the control group. Rats in group M were fed phytoestrogens – diet (70% conventional rat diet and 30% spinach seed diet) – and placed, every day for 24 weeks, in a climate chamber [temperature of 10 ± 2°C; humidity at 75 ± 5%] from 9 in the morning to 21 o ‘clock in the evening (total 12 h) [11,12]. Body weight, daily food and water intake, and daily weight of urine and stool were measured before sampling.

  1. Ethical approval: The research related to animal use has been complied with all the relevant national regulations and institutional policies for the care and use of animals and in accordance with the Animal Care and Use Committee of Xinjiang Medical University (Res: IACUC-20210302-46).

2.2 Sperm analysis

At the end of the experiment, after fasting for 12 h, the rats were anesthetized by intraperitoneal injection of 1% pentobarbital sodium (50 mg/kg). The left epididymis cauda was removed, and sperm suspension was prepared by mincing the tissue with scissors in 4 mL of M199 medium (containing 2% BSA). After incubation at 37°C for 15 min, the tissue fragments were removed from the suspension. Semen analysis was performed according to World Health Organization guidelines (WHO, 2010). The sperm concentration was determined using a Neubauer counting chamber. An aliquot of the sperm suspension was charged into the counting chamber, and spermatozoa were counted. The sperm count was expressed in millions per mL. Sperm motility was determined by placing a drop of 10 µL of the sperm suspension on a 37°C prewarmed slide and covered with a cover slip. At least 200 sperm were assessed for each semen sample using a bright-field microscope, and the percentage of motile sperm was calculated. Sperm viability was assessed using the eosin–nigrosin staining technique, where the dead cells were stained. A sample of 10 µL of sperm suspension was mixed with 0.5 μL of eosin for 30 s, then added 3 μL nigrosin staining solution, and a smear was made on a prewarmed slide. The slides were examined under a microscope with oil immersion (×1,000 magnification) to determine the percentage of viable sperms.

2.3 Serum sex hormone level measurement

Blood was collected from the abdominal aorta, and samples were centrifuged at 3,000 × g for 15 min at 4°C. The collected serum samples were stored at −80°C. Serum sex hormone levels of testosterone (T), estradiol (E2), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin (PRL) were measured by using radioimmunoassay kits (Beijing North Institute of Biology Technology, Beijing, China) according to the manufacturer’s instructions.

2.4 Morphological observation of testis and epididymis

The right testis and epididymis were collected from both experimental groups. The tissue was fixed with 4% paraformaldehyde, embedded in paraffin, sectioned, and evaluated by Periodic Acid-Schiff-hematoxylin (PAS-H) staining and immunofluorescence staining. The left testis was cryopreserved at −80°C for proteomic studies, Western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) analysis.

2.5 Proteomic detection

Testicular tissues were lysed in the presence of protease inhibitors, and total protein was extracted. Protein concentration was determined using a bicinchoninic acid (BCA) kit (Solarbio, PC0020, Beijing, China), and protein quality was detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS–PAGE). The proteins were hydrolyzed via enzymatic digestion using trypsin. After trypsin digestion, the peptides were resuspended in 25 μL solvent A (A: ACN with 0.1% formic acid), separated by nanoLC, and analyzed by online electrospray tandem mass spectrometry (MS/MS). The experiments were performed on a NanoAquity UPLC system (Waters Corporation, Milford, MA, USA) connected to a Q Exactive hybrid quadrupole Orbitrap-mass spectrometer (Thermo Fisher Scientific, San Jose, CA, USA) equipped with an online nano-electrospray ion source. An aliquot of the peptide sample (8 μL) was loaded onto a Thermo Scientific Ac-claim PepMap C18 column (100 μm x 2 cm, 3 μm particle size), with a flow rate of 10 μL/min for 3 min, and subsequently separated on an analytical column (Acclaim PepMap C18, 75 μm × 15 cm) with a linear gradient from 5% B to 45% B in 75 min. The column was re-equilibrated under initial conditions for 15 min. The column flow rate was maintained at 300 nL/min, and the column temperature was maintained at 40°C. An electrospray voltage of 1.9 kV versus the inlet of the mass spectrometer was used. The Q Exactive mass spectrometer was operated in the data-dependent mode to automatically switch between MS and MS/MS acquisition. Survey full-scan MS spectra (m/z 300–1,200) were acquired at a mass resolution of 70 K, followed by 15 sequential high-energy collisional dissociation (HCD) MS/MS scans at a resolution of 17.5 K. In all cases, one microscope was recorded using a dynamic exclusion of 30 s. For MS/MS, precursor ions were activated using 27% normalized collision energy.

Comparisons between the two groups were conducted using two-sided unpaired t-tests. The selection criteria for differentially expressed testicular proteins were a fold change ≥1.2 or ≤0.8 and a P-value < 0.05. All results are expressed as mean ± standard deviation.

2.6 Bioinformatics analysis

For functional annotation, the biological process, cellular component, and molecular function of the differentially expressed proteins were analyzed using the Gene Ontology (GO) database. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used to identify the pathways that involved target proteins.

2.7 Verification

2.7.1 Western blot analysis

Testicular tissues from each rat were separately homogenized and lysed in ice-cold radio-immunoprecipitation assay lysis buffer (Solarbio, R0010, Beijing, China). After centrifugation at 12,000 × g for 10 min at 4°C, the supernatants were collected. The protein concentration was determined using the standard BCA kit (Solarbio, PC0020, Beijing, China). Then, 40 µg of each protein sample was loaded and separated by 10% sodium dodecyl SDS–PAGE and transferred to polyvinylidene fluoride (PVDF) membranes (Millipore, Billerica, MA, USA). After blocking in 5% nonfat milk for 2 h at 37°C, the membrane was incubated with the primary antibody overnight at 4°C: integrin alpha 6 (ITGA6) (1:1,000; Boster, BA3356, Wuhan, China), alpha 1 chains of type VI collagen (Col6α1) (1:1,000; Boster, BM4748, Wuhan, China), alpha 2 chains of type VI collagen (Col6α2) (1:500; Affinity, DF3552, Zhenjiang, China), then with a Peroxidase-conjugated AffiniPure Goat Anti-Rabbit IgG(H + L) secondary antibody (1:5,000; ZSGB-BIO, ZB2301, Beijing, China) for 2 h at 37°C. Finally, the membrane was washed with tris base solution-tweet (TBST) and visualized using enhanced chemiluminescence detection (ProteinSimple Flour Chem. E). Afterward, the protein bands were quantified and analyzed using ImageJ software.

2.7.2 Immunofluorescence staining

Paraffin-embedded testicular Section (4 µm thick) were dewaxed with dimethylbenzene and gradient ethanol and then washed with phosphate-buffered saline (PBS). After incubation with 3% hydrogen peroxide, antigen retrieval was performed using 0.01 mol/L sodium citrate buffer (pH 7.0). The sections were then washed thrice with TBST and blocked with goat serum. Primary antibody was incubated overnight at 4°C: ITGA6 (1:200; Boster, BA3356, Wuhan, China), Col6α1 (1:100; Boster, BM4748, Wuhan, China), and Col6α2 (1:100; Affinity, DF3552, Zhenjiang, China). After washing three times, the samples were incubated with a secondary antibody to fluorescein isothiocyanate (FITC)-conjugated anti-rabbit IgG for 30 min at 37°C (1:1,000; abcam, ab150077, Cambridge, UK) and washed three times with TBST; 4′,6′-diamidino-2-phenylindole (DAPI) was used to stain the nuclei of cells in the testis, and the sections were observed for epifluorescence using a Leica Microsystems CMS GmbH microscope.

2.7.3 RNA extraction and qRT-PCR

Testicular tissues from each group (n = 10) were randomly selected, and total RNA was isolated using an RNA Easy Fast Animal Tissue Total RNA Extraction Kit (Tiangen, DP431, Beijing, China). Total RNA concentration was measured using a Nanodrop 2,000 spectrophotometer. RNA (1 µg) was then converted to cDNA using a FastKing RT Kit (with gDNase) (Tiangen, KR116-02, Beijing, China) in a 20 μL reaction mixture. Aliquots of 1 μL cDNA samples were subjected to quantitative PCR (qPCR) in a total volume of 10 μL using SuperReal PreMix Plus (SYBR Green) (Tiangen, FP205, Beijing, China) in a QuantStudio 6 Flex. The primers used were GAPDH F-TGAATACGGCTACAGCAACAGG, R-GTGAGGGAGATGCTCAGTGTTG, ITGA6 F-CGCCGCCGCTCAGAATATCAAG, and R-CAAGCACAGCCAGGAGGATGATC, Col6α1 F-CCTCCTGGTCCCTCCCTCTTTG, R-TTGTCTCTGCTTGCTGCCGTTAC, Col6α2 F-TCCTCCTCCTCTTCCTCCTCCTC, R-AGCAAGTTCCAGAACAGTCAAGGC. GAPDH mRNA was used as an internal control.

2.8 Statistical analyses

Comparison between experimental groups was performed by the independent two-tailed t-test using SPSS version 26.0 software (IBM), and P < 0.05 was considered significant.

3 Results

3.1 Estrogen-enriched diet and cold shock reduced spermatogenesis

To determine the effect of estrogen pollution combined with cold shock, 12 rats were exposed to a diet rich in estrogen and placed for 12 h daily at a lower temperature (10 ± 2°C) for 24 weeks (group M) and were compared with a control group (N, including 12 rats). Body weight, daily food and water intake, and urine and stool weights were measured. Compared with the control group, no apparent changes in the final body weight were observed. However, significant increase in daily food intake, weight of urine output, and stool output as well as reduction in water intake were detected (P < 0.05, Table 1).

Table 1

Body weight, testis and epididymis weight, daily food and water intake, and daily weight of urine and stool

Group Parameters Group N Group M
Body weight (g) 625.25 ± 47.48 619.00 ± 69.43
Food intake (g) 37.00 ± 11.47 47.91 ± 5.39**
Water intake (mL) 50.83 ± 12.99 40.00 ± 4.82*
Weight of urine (g) 13.08 ± 3.92 27.75 ± 3.51***
Testis (g) 1.76 ± 0.21 1.39 ± 0.49*
Epididymis (g) 0.84 ± 0.10 0.62 ± 0.16**
Testis index 0.002822 ± 0.000357 0.002206 ± 0.000649**
Epididymis index 0.001347 ± 0.000213 0.000998 ± 0.000259**

Values are expressed as mean ± SD. Statistical significance is indicated as * P < 0.05, ** P < 0.01, and *** P < 0.001 in comparison with control group.

Note: Testis index = Testis Weight/Body Weight. Epididymis index = Epididymis Weight/Body Weight.

Moreover, tissue analysis revealed that the weight of the testis and epididymis decreased dramatically compared with the control group (P < 0.05, Table 1). The size of the testis and epididymis is shown in Figure 1a and b. Furthermore, evaluation of the sperm quality parameters showed that compared with control group (N), sperm concentration (P < 0.01), motility (P < 0.001), and viability (P < 0.05) in the model group (M) were significantly lower (Table 2). The eosin/nigrosin staining is shown in Figure 1c.

Figure 1 Effects of phytoestrogens combined with cold stress on the sperm viability and morphology of testis and epididymis in rats. At the end of the 24-week treatment, right testes, epididymis, and sperm were collected from 12 rats exposed to estrogen-enriched diet and cold (group M), and 12 rats control (group N). (a) Size of testis. (b) Size of epididymis. (c) Eosin/nigrosin staining of sperms of rats in each group (×1000). The staining was used to define sperm viability. Stained sperms were dead (black arrows), unstained were alive (white arrows). (d) Histological evaluation of testis by Periodic Acid–Schiff–hematoxylin (PAS-H) staining (×400). Spermatogonia (SG), primary spermatocyte (ST); spermatid (SD); early-stage sperm (S); reduced sperm density (*). (e) Histological evaluation of epididymis by Periodic Acid–Schiff–hematoxylin (PAS-H) staining (×200). Group M showed increased vacuoles in the cytoplasm (V) and reduced sperm density (*) in the lumen (L).
Figure 1

Effects of phytoestrogens combined with cold stress on the sperm viability and morphology of testis and epididymis in rats. At the end of the 24-week treatment, right testes, epididymis, and sperm were collected from 12 rats exposed to estrogen-enriched diet and cold (group M), and 12 rats control (group N). (a) Size of testis. (b) Size of epididymis. (c) Eosin/nigrosin staining of sperms of rats in each group (×1000). The staining was used to define sperm viability. Stained sperms were dead (black arrows), unstained were alive (white arrows). (d) Histological evaluation of testis by Periodic Acid–Schiff–hematoxylin (PAS-H) staining (×400). Spermatogonia (SG), primary spermatocyte (ST); spermatid (SD); early-stage sperm (S); reduced sperm density (*). (e) Histological evaluation of epididymis by Periodic Acid–Schiff–hematoxylin (PAS-H) staining (×200). Group M showed increased vacuoles in the cytoplasm (V) and reduced sperm density (*) in the lumen (L).

Table 2

Sperm quality parameters measured in group N and M

Sperm quality parameters Group N Group M
Sperm concentration (106/mL) 62.53 ± 14.09 45.19 ± 11.94**
Motility (%) 62.42 ± 4.33 39.94 ± 11.10***
Viable sperm (%) 80.12 ± 8.23 68.64 ± 16.08*

Values are expressed as mean ± SD. Statistical significance is indicated as * P < 0.05, ** P < 0.01, and *** P < 0.001 in comparison with the control group.

3.2 Changes in serum sex hormone levels

To define the effect of exposure to phytoestrogens and cold on physiological reproductive parameters of the rats, serum sex hormone levels of testosterone (T), estradiol (E2), LH, FSH, and PRL were measured. Compared with group N, T levels in group M were significantly decreased, whereas E2 and FSH levels were increased (P < 0.05). However, no significant change in LH and PRL levels was observed (Table 3).

Table 3

Serum sex hormone levels

Group N Group M
T (ng/mL) 1.67 ± 0.79 0.47 ± 0.30***
E2 (µIU/mL) 37.97 ± 6.15 49.68 ± 16.72*
LH (mIU/mL) 4.57 ± 1.60 5.64 ± 2.29
FSH (mIU/mL) 5.10 ± 2.82 11.05 ± 6.46**
PRL (pg/mL) 84.49 ± 41.82 102.54 ± 37.83

Values are expressed as mean ± SD. Statistical significance is indicated as * P < 0.05, ** P < 0.01, and *** P < 0.001 in comparison with the control group.

3.3 Morphological variations of testis and epididymis

Histological analysis of the testes revealed that the spermatogenic tubules in group N were abundant, various levels of spermatogenic cells were neatly arranged into 5–8 layers, and Sertoli cells were visible. However, the number of spermatogenic cells in group M was significantly lower than that in group N (Figure 1d). Moreover, the epididymis duct showed vacuolar denaturalization of the cytoplasm in the epididymal epithelium. The lumen contained fewer sperm in group M (Figure 1c).

3.4 Differentially expressed testicular proteins

Proteomic analysis of testis tissues from N and M groups was performed, and 4,750 proteins were extracted from 32,479 unique peptides. A total of 3,455 proteins were common between the two groups. Moreover, 24 proteins were upregulated and 15 downregulated in group M. The top ten upregulated proteins, based on the highest fold change (FC), included alpha 5 chains of type VI collagen (Col6α5, FC = 10.7, P = 0.005), H1.2 linker histone (FC = 9.3, P = 0.04), alpha 1 chain of type VI collagen (Col6α1, FC = 8.7, P = 0.01), alpha 2 chain of type VI collagen (Col6α2, FC = 6.8, P = 0.04), 40 S ribosomal protein S6-like (FC = 3.6, P = 0.04), immunoglobulin heavy constant mu (FC = 2.9, P = 0.03), macroH2A.1 histone (FC = 2.8, P = 0.03), sorbin and SH3 domain-containing 2 (FC = 2.4, P = 0.04), B-cell receptor-associated protein 31 (FC = 2.6, P = 0.004), and transgelin (FC = 2.6, P = 0.02). The top ten downregulated proteins included the hypothetical LOC287798 (FC = 0.4, P = 0.04), translocase of the outer mitochondrial membrane 70,3′(2′) (FC = 0.5, P = 0.02), 5′-bisphosphate nucleotidase 1 (FC = 0.5, P = 0.01), structure-specific recognition protein 1 (FC = 0.6, P = 0.008), dynein light chain LC8-type 1 (FC = 0.6, P = 0.009), coiled-coil domain containing 58 (FC = 0.6, P = 0.04), doublecortin domain containing 2 C (FC = 0.6, P = 0.02), similar to 60 S ribosomal protein L38 (FC = 0.6, P = 0.04), TOR signaling pathway regulator, and metallothionein 3 (FC = 0.6, P = 0.04, Figure 2). The upregulated proteins Col6α1, Col6α2, and downregulated proteins integrin alpha 6 (ITGA6) were validated by Western blotting, immunofluorescence, and real-time quantitative reverse transcription (qRT-PCR; Figure 3).

Figure 2 Altered expression of proteins in testis exposed to estrogen-enriched diet and cold for 24 weeks. (a) Volcano plot showing proteins differentially expressed between control group (Group N) and model group (Group M). In the volcano plot, the X-axis represents the log2 (fold-change (FC)) and the Y-axis is the P value. Data points in the upper right (FC > 2.0) and upper left (FC < 0.5) with P < 0.05 represent proteins that significantly altered. (b) Heatmap of proteins with altered abundance in testis. Rows represent the individual samples. Red color represents upregulated proteins and the green color represents downregulated proteins. Black indicates no difference in protein quantity.
Figure 2

Altered expression of proteins in testis exposed to estrogen-enriched diet and cold for 24 weeks. (a) Volcano plot showing proteins differentially expressed between control group (Group N) and model group (Group M). In the volcano plot, the X-axis represents the log2 (fold-change (FC)) and the Y-axis is the P value. Data points in the upper right (FC > 2.0) and upper left (FC < 0.5) with P < 0.05 represent proteins that significantly altered. (b) Heatmap of proteins with altered abundance in testis. Rows represent the individual samples. Red color represents upregulated proteins and the green color represents downregulated proteins. Black indicates no difference in protein quantity.

Figure 3 ITGA6 was downregulated, Col6α1 and Col6α2 were upregulated in the testis of the model group exposed to an estrogen-enriched diet and cold for 24 weeks. (a) Immunofluorescence staining for ITGA6 (red, 200×), Col6α1 (green, 100×), Col6α2 (red, 100×); nuclei were stained with DAPI (blue). (b, c, and d) Representative western blot results for ITGA6, Col6α1, Col6α2. (e, f, and g) Relative expression of ITGA6, Col6α1, Col6α2 compared with GAPDH. Protein lysates were obtained from the testis of either model (M) or control rat group (N). Protein expression of ITGA6, Col6α1, and Col6α2 was evaluated by western blotting using specific antibodies for the target proteins, and the signal was then quantified using Image J. (h, i, and j) qRT-PCR of ITGA6, Col6α1, and Col6α2 in the testis of rats in the two groups. Values are expressed as the mean ± SD. Statistical significance is indicated as * P < 0.05, ** P < 0.01, and *** P < 0.001 compared to the control group.
Figure 3

ITGA6 was downregulated, Col6α1 and Col6α2 were upregulated in the testis of the model group exposed to an estrogen-enriched diet and cold for 24 weeks. (a) Immunofluorescence staining for ITGA6 (red, 200×), Col6α1 (green, 100×), Col6α2 (red, 100×); nuclei were stained with DAPI (blue). (b, c, and d) Representative western blot results for ITGA6, Col6α1, Col6α2. (e, f, and g) Relative expression of ITGA6, Col6α1, Col6α2 compared with GAPDH. Protein lysates were obtained from the testis of either model (M) or control rat group (N). Protein expression of ITGA6, Col6α1, and Col6α2 was evaluated by western blotting using specific antibodies for the target proteins, and the signal was then quantified using Image J. (h, i, and j) qRT-PCR of ITGA6, Col6α1, and Col6α2 in the testis of rats in the two groups. Values are expressed as the mean ± SD. Statistical significance is indicated as * P < 0.05, ** P < 0.01, and *** P < 0.001 compared to the control group.

3.5 GO enrichment and pathway analyses

Gene Ontology (GO) enrichment analysis was performed to classify the biological processes, cellular components, and molecular functions of these proteins (Figure 4a). The differentially expressed proteins were mainly involved in reticulophagy, response to stimulus, regulation of neuron migration, regulation of necrotic cell death, regulation of membrane repolarization during action potential, regulation of lymphocyte activation, regulation of immune system processes, regulation of cell adhesion, cell migration, and positive regulation of the toll-like receptor 3 signaling pathway (Figure 4b).

Figure 4 Effects of phytoestrogens combined with cold stress on testicular proteomics in rats. (a) All enriched gene ontology (GO) terms of the proteins between the model group and the control. The enriched terms of molecular function, cellular component, and biological process categories were identified. (b) GO functional significance enrichment analysis. (c) The enriched Kyoto encyclopedia of genes and genomes (KEGG) pathways of proteins between the model group and the control.
Figure 4

Effects of phytoestrogens combined with cold stress on testicular proteomics in rats. (a) All enriched gene ontology (GO) terms of the proteins between the model group and the control. The enriched terms of molecular function, cellular component, and biological process categories were identified. (b) GO functional significance enrichment analysis. (c) The enriched Kyoto encyclopedia of genes and genomes (KEGG) pathways of proteins between the model group and the control.

Pathway analysis of the differentially expressed proteins was performed using the KEGG. The top five pathways containing the largest number of proteins were focal adhesion (FAs), human papillomavirus infection, PI3K-Akt signaling pathway, metabolic pathway, and cancer proteoglycan (Figure 4c). Specifically, three upregulated proteins (Col6α5, Col6α1, and Col6α2) and two downregulated proteins (integrin subunit ITGA6 and receptor tyrosine kinase (RTK)) were involved in the PI3K-Akt signaling pathway. Moreover, four upregulated proteins (Col6α1, Col6α2, caveolin, and filamin) and three downregulated proteins (ITGA6, Rho GTPase activation protein (RhoGAP)), and Parvin were involved in the FA signaling pathway included.

4 Discussion

Spermatogenesis in mammals is a cyclic process of spermatogenic cell development occurring in the seminiferous tubules. The formation, maturation, and capacitation of spermatogenic cells are susceptible to dietary changes and environmental factors. Temporary sterility syndrome in livestock (ewes) is associated with high phytoestrogen intake during grazing [13]. Humans and rodents consume high doses of phytoestrogens, which can cause decreased testicular weight, sperm count, and motility [14]. In this study, the rats in the model group showed indeed these listed phenotypes. Androgen plays an important role in testicular development and sperm parameters, thus decreased testicular weight and sperm parameters might be linked to the reduction in serum testosterone caused by phytoestrogens [15].

Temperature is an important environmental factor affecting the metabolism and reproduction of small mammals [16]. The inhibition of reproductive function in winter occurs commonly among small mammals living in temperate zones [17]. In some rodents, it has been shown that cold exposure not only could suppress growth but also delay the onset of breeding [18]. In this study, the model rats that were placed in a cold environment showed that food intake, weight of urine output, and stool output significantly increased, whereas body weight continued to slowly grow. It has been reported that animals increase energy intake and thermogenesis to maintain energy balance in order to respond to cold conditions. They might allocate less energy to the development of reproductive organs [19].

Morphological study of the testis and epididymis showed that the epithelial cells of seminiferous tubules and ductus epididymis were obviously different between the control and model groups. Compared with group N, the number of sperm in the lumen of the epididymis decreased dramatically. The changes in hormone levels were responsible for abnormal morphology. Serum sex hormone results showed that the testosterone level in the model group significantly decreased, whereas the E2 and FSH levels increased after treatment with phytoestrogens combined with cold stress. This is related to the competitive binding of phytoestrogens to the estrogen receptor, which inhibited its negative feedback regulation, promoted the positive feedback regulation of LH secretion, and stimulated the secretion of E2. FSH is essential for the initiation of spermatogenesis, but the abnormal increase of serum FSH level often means that the seminiferous epithelium has been damaged. At the same time, when testicular cells were exposed to a high-estrogen environment, the expression of steroid synthase decreased, which could also lead to a further decrease in T level [20]. In addition, long-term cold stimulation can cause a chronic stress response that disturbs the balance of hormones and eventually results in reproductive damage.

Further proteomic studies identified 39 testicular proteins differentially expressed between the two experimental groups. Among these proteins, integrin α6 (ITGA6) and collagen6 (chain α1 (Col6α1) and chain α2 (Col6α2)) were detected with a high fold-change. Integrins play a key role in cell adhesion to extracellular matrix (ECM) ligands and adjacent cells and serve as links between extracellular contacts and the intracellular cytoskeleton. In addition, integrins work together with receptor tyrosine kinases to communicate bidirectional signals between cells and ECM [21]. They are important for the regulation of cell proliferation, differentiation, survival, and migration of cells [22]. ITGA6 is a spermatogonia-specific marker and receptor subunit of laminin that participates in the formation of the seminiferous tubule basement membrane and spermatogonial stem cells (SSCs). Spermatogenesis was reconstituted in infertile male mice after colonization assays in recipient testes using testis cells expressing ITGA6 [23]. Additionally, ITGA6 plays an essential role in the PI3K/AKT pathway, which is closely related to spermatogenic function. So, the low expression of ITGA6 is responsible for the decreased number of germ cells in the testes of group M. Col6 is a major ECM protein that forms a microfibrillar network in many tissues, including skeletal muscle, cartilage, tendon, lung, nervous system, adipose tissue, skin, eye, heart, and vasculature [24]. This protein is composed of three major chains: α1(VI), α2(VI), and α3(VI). Biosynthesis of type VI collagen requires these three chains to be assembled intracellularly into monomers, dimers, and tetramers, which are then secreted and beaded into extracellular microfilaments and then deposited in the ECM [25,26]. Recently, three new chains similar to α3(VI) were discovered: α4(VI), α5(VI), and α6(VI) [27]. Their distribution is limited to specific tissues, such as skeletal muscles, cardiac muscles, and reproductive organs. Testicular collagen consists of several types of collagen and is thought to play a significant role in the structural organization of seminiferous tubules and interstitial tissues. Sertoli cells and SSCs attach to the basement membrane in the seminiferous epithelium. Moreover, pathological studies have shown that the basement membrane of the seminiferous tubule is thickened and the interstitial tissue is increased in male infertility patients, children with cryptorchidism, and prostate cancer patients [28,29,30]. It has been indicated that the collagen content was increased in the testes of such patients [31]. Although its specific function in the testes has not yet been reported, in this study, the expression of Col6α1 and Col6α2 were all increased in the basement membrane of the seminiferous tubule in group M, and the upregulated Col6 would negatively affect the attachment of spermatogenic cells and sertoli cells to the basement membrane, then affecting the sperm spermatogenesis and sperm capacitation. Further research is needed to reveal this mechanism.

GO enrichment analysis showed that the differentially expressed proteins were mainly involved in reticulophagy and response to stimulus. The endoplasmic reticulum (ER) is a biosynthetic organelle in eukaryotic cells. Its capacity to produce proteins, lipids, and oligosaccharides responds to physiological and pathologic demands [32]. Reticulophagy refers to the increase in unfolded or misfolded proteins in the ER when the internal and external environments of cells change, leading to an ER stress response. Changes in ER function disrupt cellular homeostasis and then activate selective autophagy to remove damaged endoplasmic reticulum or segments in cells. Overactivated reticulophagy in testicular tissue can also remove normal endoplasmic reticulum structures and luminal fragments from spermatogenic cells, resulting in spermatogenesis disorders.

Pathway analysis showed that the differentially expressed proteins were involved in 51 signaling pathways, among which the PI3K-Akt signaling pathway, FA signaling pathway, metabolic pathway, protein digestion, and absorption pathways involved more proteins. Several studies have shown that the PI3K/Akt pathway plays an essential role in the self-renewal of SSCs and the differentiation of spermatogonia [33]. In Akt−/− mice, apoptotic sperms increased [34]. In addition, the PI3K/Akt signaling pathway has protective effects and contributes to the survival of germ cells in mice after toxic testicular injury. In asthenospermia, changes in the expression of PI3K/AKT and cAMP-mediated PKA signaling pathways lead to flagellin phosphorylation and abnormal sperm motility [35,36,37]. Moreover, the PI3K-Akt signaling pathway is related to FSH regulation of the proliferation process in testicular cells [38]. In this study, the abnormal FSH levels, the decrease in spermatogenic cells, and poor sperm motility might be due to deregulated PI3K/Akt pathway. Integrins are the major transmembrane receptors at sites of cell adhesion to the ECM. The ECM, in turn, is linked to the actin cytoskeleton via peripheral proteins. These specialized attachments and signaling complexes are known as FAs [39]. FA signaling is linked with cell proliferation, differentiation, and cell activity. It regulates gene expression and cell survival and participates in the construction of cell membrane acceptors and the actin cytoskeleton [40]. During sperm capacitation, actin aggregation and cytoskeleton remodeling require focus-binding kinases [41,42,43]. Cell adhesion permits the attachment of developing germ cells to Sertoli cells and the basement membrane in the seminiferous epithelium. All aforementioned findings suggested that the deregulated FA pathways would have led to the decrease of spermatogenic cells and abnormal shedding of germ cells. Proteins involved in both PI3K/AKT and FA signaling pathways included ITGA6, which we found downregulated, and α1 and α2 chains of type VI collagen, upregulated in the model group. These three proteins may, therefore, represent potential biomarkers for oligospermia.

5 Conclusion

Rats treated with phytoestrogens combined with cold stress showed higher food intake, increased urine and stool output, and lower sperm concentration, motility, viability, and testosterone level. The epithelial cells of seminiferous tubules and epididymis presented abnormal morphology. Moreover, ITGA6 downregulation and upregulation of alpha 1 and alpha 2 chains of type VI collagen in the testis suggest that alterations of PI3K/AKT and FA pathways might represent the molecular mechanism behind the estrogen/cold-induced infertility. Therefore, this study lays the foundation for the establishment of “course simulation” type of oligospermia animal model.

  1. Funding information: This work was financially supported by the National Natural Science Foundation of Xinjiang Uygur Autonomous Region in China; Project No. 2017D01C181.

  2. Author contributions: A.Y. designed the study. Z.P., N.A., and M.S. conducted experiments. Z.P. drafted the manuscript. S.A. analyzed the data. M.W. and W.B. revised the manuscript accordingly. All the authors have read and approved the final manuscript.

  3. Conflict of interest: Authors state no conflict of interest.

  4. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Received: 2022-07-26
Revised: 2022-10-05
Accepted: 2022-11-02
Published Online: 2023-01-24

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

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  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
https://doi.org/10.1515/biol-2022-0531
Schlagwörter für diesen Artikel
phytoestrogens; cold; testicular proteomics
Creative Commons
BY 4.0

Artikel in diesem Heft

  1. Biomedical Sciences
  2. Systemic investigation of inetetamab in combination with small molecules to treat HER2-overexpressing breast and gastric cancers
  3. Immunosuppressive treatment for idiopathic membranous nephropathy: An updated network meta-analysis
  4. Identifying two pathogenic variants in a patient with pigmented paravenous retinochoroidal atrophy
  5. Effects of phytoestrogens combined with cold stress on sperm parameters and testicular proteomics in rats
  6. A case of pulmonary embolism with bad warfarin anticoagulant effects caused by E. coli infection
  7. Neutrophilia with subclinical Cushing’s disease: A case report and literature review
  8. Isoimperatorin alleviates lipopolysaccharide-induced periodontitis by downregulating ERK1/2 and NF-κB pathways
  9. Immunoregulation of synovial macrophages for the treatment of osteoarthritis
  10. Novel CPLANE1 c.8948dupT (p.P2984Tfs*7) variant in a child patient with Joubert syndrome
  11. Antiphospholipid antibodies and the risk of thrombosis in myeloproliferative neoplasms
  12. Immunological responses of septic rats to combination therapy with thymosin α1 and vitamin C
  13. High glucose and high lipid induced mitochondrial dysfunction in JEG-3 cells through oxidative stress
  14. Pharmacological inhibition of the ubiquitin-specific protease 8 effectively suppresses glioblastoma cell growth
  15. Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1
  16. Age-related changes in peripheral T-cell subpopulations in elderly individuals: An observational study
  17. Single-cell transcription analysis reveals the tumor origin and heterogeneity of human bilateral renal clear cell carcinoma
  18. Identification of iron metabolism-related genes as diagnostic signatures in sepsis by blood transcriptomic analysis
  19. Long noncoding RNA ACART knockdown decreases 3T3-L1 preadipocyte proliferation and differentiation
  20. Surgery, adjuvant immunotherapy plus chemotherapy and radiotherapy for primary malignant melanoma of the parotid gland (PGMM): A case report
  21. Dosimetry comparison with helical tomotherapy, volumetric modulated arc therapy, and intensity-modulated radiotherapy for grade II gliomas: A single‑institution case series
  22. Soy isoflavone reduces LPS-induced acute lung injury via increasing aquaporin 1 and aquaporin 5 in rats
  23. Refractory hypokalemia with sexual dysplasia and infertility caused by 17α-hydroxylase deficiency and triple X syndrome: A case report
  24. Meta-analysis of cancer risk among end stage renal disease undergoing maintenance dialysis
  25. 6-Phosphogluconate dehydrogenase inhibition arrests growth and induces apoptosis in gastric cancer via AMPK activation and oxidative stress
  26. Experimental study on the optimization of ANM33 release in foam cells
  27. Primary retroperitoneal angiosarcoma: A case report
  28. Metabolomic analysis-identified 2-hydroxybutyric acid might be a key metabolite of severe preeclampsia
  29. Malignant pleural effusion diagnosis and therapy
  30. Effect of spaceflight on the phenotype and proteome of Escherichia coli
  31. Comparison of immunotherapy combined with stereotactic radiotherapy and targeted therapy for patients with brain metastases: A systemic review and meta-analysis
  32. Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation
  33. Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy
  34. The role of IL-31 and IL-34 in the diagnosis and treatment of chronic periodontitis
  35. Triple-negative mouse breast cancer initiating cells show high expression of beta1 integrin and increased malignant features
  36. mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study
  37. The apatinib and pemetrexed combination has antitumor and antiangiogenic effects against NSCLC
  38. Radiotherapy for primary thyroid adenoid cystic carcinoma
  39. Design and functional preliminary investigation of recombinant antigen EgG1Y162–EgG1Y162 against Echinococcus granulosus
  40. Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial
  41. Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics
  42. Performance comparison of three scaling algorithms in NMR-based metabolomics analysis
  43. PI3K/AKT/mTOR pathway and its related molecules participate in PROK1 silence-induced anti-tumor effects on pancreatic cancer
  44. The altered expression of cytoskeletal and synaptic remodeling proteins during epilepsy
  45. Effects of pegylated recombinant human granulocyte colony-stimulating factor on lymphocytes and white blood cells of patients with malignant tumor
  46. Prostatitis as initial manifestation of Chlamydia psittaci pneumonia diagnosed by metagenome next-generation sequencing: A case report
  47. NUDT21 relieves sevoflurane-induced neurological damage in rats by down-regulating LIMK2
  48. Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis
  49. Exosomal HBV-DNA for diagnosis and treatment monitoring of chronic hepatitis B
  50. Shear stress leads to the dysfunction of endothelial cells through the Cav-1-mediated KLF2/eNOS/ERK signaling pathway under physiological conditions
  51. Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection
  52. Meta-analysis of the rs231775 locus polymorphism in the CTLA-4 gene and the susceptibility to Graves’ disease in children
  53. Cloning, subcellular localization and expression of phosphate transporter gene HvPT6 of hulless barley
  54. Coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome
  55. Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis
  56. Whole-exome sequencing applications in prenatal diagnosis of fetal bowel dilatation
  57. Gemella morbillorum infective endocarditis: A case report and literature review
  58. An unusual ectopic thymoma clonal evolution analysis: A case report
  59. Severe cumulative skin toxicity during toripalimab combined with vemurafenib following toripalimab alone
  60. Detection of V. vulnificus septic shock with ARDS using mNGS
  61. Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing
  62. The influence and mechanistic action of sperm DNA fragmentation index on the outcomes of assisted reproduction technology
  63. Novel compound heterozygous mutations in TELO2 in an infant with You-Hoover-Fong syndrome: A case report and literature review
  64. ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis
  65. Diagnosis of primary amoebic meningoencephalitis by metagenomic next-generation sequencing: A case report
  66. Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools
  67. Collagen changes in rabbit conjunctiva after conjunctival crosslinking
  68. Effects of NM23 transfection of human gastric carcinoma cells in mice
  69. Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia
  70. Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation
  71. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling
  72. Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report
  73. Giant duplication of the transverse colon in an adult: A case report and literature review
  74. Ectopic thyroid tissue in the breast: A case report
  75. SDR16C5 promotes proliferation and migration and inhibits apoptosis in pancreatic cancer
  76. Vaginal metastasis from breast cancer: A case report
  77. Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine
  78. Inhibition of TAZ impairs the migration ability of melanoma cells
  79. Molecular complexity analysis of the diagnosis of Gitelman syndrome in China
  80. Effects of maternal calcium and protein intake on the development and bone metabolism of offspring mice
  81. Identification of winter wheat pests and diseases based on improved convolutional neural network
  82. Ultra-multiplex PCR technique to guide treatment of Aspergillus-infected aortic valve prostheses
  83. Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2
  84. Immune checkpoint inhibitors in cancer patients with COVID-19
  85. Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses
  86. Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma
  87. Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy
  88. DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway
  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
  99. Tanshinone IIA alleviates chondrocyte apoptosis and extracellular matrix degeneration by inhibiting ferroptosis
  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
  102. HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy
  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
  104. Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients
  105. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials
  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
  108. Research progress on gas signal molecular therapy for Parkinson’s disease
  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
  112. CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa
  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
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© 2025 De Gruyter Brill
Heruntergeladen am 6.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0531/html
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