Abstract
The application of fertilizers and soil quality are crucial for grape fruit quality. However, the molecular data linking different fertilizer (or soil conditioner [SC]) treatments with grape fruit quality is still lacking. In this study, we investigated three soil treatments, namely inorganic fertilizer (NPK, 343.5 kg/hm2 urea [N ≥ 46%]; 166.5 kg/hm2 P2O5 [P2O5 ≥ 64%]; 318 kg/hm2 K2O [K2O ≥ 50%]), organic fertilizer (Org, 9 t/hm2 [organic matter content ≥ 35%, N + P2O5 + K2O ≥ 13%]), and SC (SC, 3 t/hm2 [humic acid ≥ 38.5%; C, 56.1%; H, 3.7%; N, 1.5%; O, 38%; S, 0.6%]), on 4-year-old Cabernet Sauvignon grapevines. Compared with the NPK- and Org-treated groups, the SC significantly improved the levels of soluble solids, tannins, anthocyanins, and total phenols in the grape berries, which are important biochemical indicators that affect wine quality. Furthermore, we conducted RNA-seq analysis on the grapevine roots from each of the three treatments and used weighted gene co-expression network analysis to identify five hub genes that were associated with the biochemical indicators of the grape berries. Furthermore, we validated the expression levels of three hub genes (ERF, JP, and SF3B) and five selected genes related to anthocyanin biosynthesis (UFGT1, UFGT2, UFGT3, GST, and AT) by using quantitative reverse transcription-polymerase chain reaction. Compared to the NPK and Org treatment groups, the SC treatment resulted in a significant increase in the transcription levels of three hub genes as well as VvUFGT1, VvUFGT3, VvGST, and VvAT. These results suggest that the SC can improve grape fruit quality by altering gene transcription patterns in grapevine roots and further influence the biochemical indices of grape fruits, particularly anthocyanin content. This study reveals that the application of SC can serve as an important measure for enhancing vineyard SC and elevating grape quality.
1 Introduction
Grape (Vitis vinifera L.) is a widely cultivated and economically significant crop worldwide. Owing to its elevated nutritional value, exceptional flavor profile, and substantial profitability, grapes have garnered unprecedented popularity [1,2]. Wine, being the most paramount product of grape processing, exhibits certain effects in anti-aging [3], cerebrovascular protection [4,5], anti-cancerous [6], and so on. As the realization of wine’s significance grew, its demand in China has experienced a rapid increase, propelling China to the helm of the fastest-growing wine consumer nation globally [7]. Currently, emphasis is being placed on wine quality, thereby rendering the improvement of grape quality a topic of great scholarly interest in the domain of grape cultivation research.
The composition of grapes, such as soluble solids, phenolic compounds, tannins, titratable acids, and sugar to acid ratios, largely determines the quality, texture, and aroma of wine [1]. The judicious application of fertilizers can considerably impact the composition and flavor compound of wine grape fruits. Foliar application of different types of nitrogen can have different effects on the formation of mature fruit components, such as ammonium sulfate can significantly increase the content of soluble solids, anthocyanins, and total phenols;, phenylalanine can significantly increase the content of titratable acid and tannins in grape fruits; and urea can increase the contents of total anthocyanins, flavanols, and flavonol in grape skins [8]. Compared with conventional fertilization, foliar spraying with iron (ferrous sulfate, ferric ethylenediaminetetraacetic acid, ferric citrate, ferric gluconate, and ferric sugar alcohol) increased berry sugar content and reduced acid content [9]. In addition, preharvest applications of phenolic acids, such as benzoic acid, oxalic acid, and citric acid (CA), had significant effects on the quality properties of the grapes [10]. These studies indicate that the use of fertilizers can control the biosynthesis of compounds that affect the quality of grape fruit.
However, the excessive and continuous application of traditional chemical fertilizers, especially nitrogen fertilizers, causes soil compaction, decreases soil fertility, accelerates soil acidification, increases the likelihood of pest infestations, and leads to a reduction in organic matter load, humus load, and beneficial organisms [11,12]. Reducing the reliance on conventional chemical fertilizers, increasing the utilization of organic fertilizers, and improving soil quality have become increasingly popular approaches for grape cultivation. Increasing organic fertilizer usage in grape management can significantly improve soil nutrient levels and microbial community composition [13,14], as well as increase the soluble solid content of grape berries, reduce the pH value of grape juice, and enhance the diversity of fungi and the relative abundance of beneficial fungi on grape berry surfaces [15]. In addition, soil conditioners (SC), such as vermicompost, have been shown to effectively reduce copper phytotoxicity in young grapevines grown in soils with high copper contents, as well as enhance the utilization of certain important micronutrients [16]. Cataldo et al. demonstrated that soil amendments can significantly improve the efficiency of grapevines in utilizing soil nutrients and water, reduce their fertilizer requirements, and, most importantly, improve the quality of the grapes [17]. However, these previous studies have focused on the effects of different types of fertilizers or SCs on the related biochemical parameters that affect grape quality, lacking research on the molecular mechanisms of grape under different treatments.
In the present study, Cabernet Sauvignon, a wine grape variety widely cultivated in the foothills of Helan Mountain in China, was used as the plant material. Using RNA-seq technology, we aimed to explore the effects of different soil management measures (conventional inorganic fertilizer, organic fertilizer, and SC) on grapevine root gene expression and to clarify the relationship between molecular effects and grape quality traits. The findings will establish a vital molecular basis for enhancing grape quality and guide future soil management strategies in vineyards.
2 Materials and methods
2.1 Plant materials and treatments
In this experiment, 4-year-old Cabernet Sauvignon grapevines were cultivated in 2021 at Lilan Chateau (105°58′20ʺ E, 38°16′38ʺ N) located in Ningxia, China. The vineyard is situated at an elevation of approximately 1,160 m and experiences an average annual temperature of 8.5°C. The vineyard soil was classified as sandy loam. The planting direction of the plants was north–south, with an inclined upper frame shape. The plant row spacing was 0.6 m × 3.5 m, and drip irrigation was used as the irrigation method.
Three treatments were set up in this experiment, including inorganic fertilizer (NPK), organic fertilizer (Org), and SC (specific components and doses are shown in Table S1). Each treatment consisted of three replicates, and each replicate included at least 20 grapevines. Fertilization and SC were applied by backfilling the excavated pits of 40 cm once a year prior to plant cultivation. Other management measures, such as irrigation, pruning, and pest control, were kept consistent.
2.2 Determination of grape fruit quality
As previously described [8], soluble solids were measured by using a handheld sugar meter, titratable acid content was determined by using a standard 0.1 mol L−1 NaOH method, soluble sugars were measured by the anthrone reagent method, and total phenol was measured via the Foling-Shocka method. The pH differential method was used to test anthocyanins, while the Flynn-Dennis method was used to evaluate tannins.
2.3 RNA extraction and sequencing
Total RNA was extracted by TRIzol reagent (Invitrogen, Thermo Fisher Scientific Inc., USA) from each root tissue, followed by DNase I digestion (Takara, Dalian, China) as per the manufacturer’s instructions. Subsequently, the integrity of RNAs was determined by checking the ratio of optical density at 260 nm to that at 280 nm (OD260/280 = 1.8–2.0) using an ultraviolet spectrophotometer (Hoefer, MA, USA), as well as visually assessing the integrity of 18s and 28s ribosomal RNAs by electrophoresis in an agarose gel. Agilent 2100 Bioanalyzer (Agilent Technologies, Palo Alto, CA, USA) and Qubit 2.0 Fluorometer (Agilent Technologies) were used for the determination of library quality. The Illumina Hiseq pair-end 150 platform was employed for the sequencing.
2.4 Data processing and gene expression analysis
Downloaded sequencing data (FASTQ files) were proceeded using FastQC (v1.11.5; http://www.bioinformatics.babraham.ac.uk/projects/fastqc/). Clean data were then extracted after removing low-quality reads and adapters. The ribosome RNA sequences with >5 mismatch bases were removed. The mapping of clean reads to reference V. vinifera genome was performed using TopHat2 software [18]. Cufflinks software was used to calculate gene FPKM values (mean fragments per kilobase of transcript per million mapped reads) [19]. Novel genes (with length ≥200 bp and exon number ≥2) were annotated against the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO). Principal component analysis (PCA) and Pearson’s correlation analysis were performed based on the FPKM value of each gene. Differentially expressed genes (DEGs) between groups were calculated with the criteria of false discovery rate p value <0.05.
2.5 Construction of gene co-expression network modules
As described by Langfelder and Horvath [20], a weighted gene co-expression network analysis (WGCNA) was introduced in this study to simplify genes into co-expression modules. Specifically, the FPKM values were normalized to create an adjacency matrix, and then the phenotype data were inputted into the WGCNA package to compute the correlation-based associations between gene modules and phenotypes. Within WGCNA, the adjacency matrix was transformed into a topology overlap matrix. Based on the network construction, transcripts exhibiting similar expression patterns were grouped into co-expression modules, and unique genes from these modules were identified. Genes were exported into Cytoscape 3.7.1 using the default parameters from all modules [21].
2.6 Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) validation for transcriptome data
Based on the key modules of WGCNA analysis, the gene network was constructed and five hub genes were selected for qRT-PCR. Primers were designed by using Genscript Primer Design online tool (https://www.genscript.com.cn/tools/real-time-pcr-taqman-primer-design-tool). The cDNA was synthesized and subjected to qRT-PCR using gene-specific primers and ChamQ Universal SYBR qPCR Master Mix (Q711-02, Vazyme, Nanjing, China). Vvactin was used as a reference gene [22] (all the primers are listed in Supplement data 1: Table S4). The qRT-PCR was conducted with three biological and technical replicates. The relative expression levels were determined by applying the 2−ΔΔCT method.
2.7 Data analysis
Three biological replicates were set up throughout the study. We used SPSS for Windows (Chicago, IL, USA) for statistical analyses. The averages (±SE) were submitted for analysis of variance with the Tukey–Kramer test.
3 Results
3.1 Effect of different treatments on grape berry quality
Compared to NPK and Org treatments, SC significantly improved grape fruit quality. Here, six quality indicators of grape fruit were investigated, including soluble solids, titratable acid, soluble sugars, tannins, anthocyanins, and total phenols. Specifically, the average content of soluble solids in the NPK-, Org-, and SC-treated group was 22.4, 22.9, and 24.9%, respectively, with the SC-treated group significantly higher than the other two fertilizer treatments (Figure 1a). There were no significant differences in the titratable acidity levels among the three treatments (Figure 1b). Regarding the soluble sugar content, the SC treatment exhibited a significant increase of 13.4% compared to the NPK treatment, while no significant difference was detected between the SC and NPK treatments (Figure 1c). Moreover, the tannin and anthocyanin levels in grape fruits treated with SC were significantly higher compared to those treated with NPK or Org (Figure 1d and e). The total phenolic level of fruits treated with SC was significantly higher than that of the NPK treatment group, but no significant difference was observed compared to the Org treatment group (Figure 1f).

Effect of different treatments on grape berry quality indicators. The levels of soluble solid (a), titratable acid (b), soluble sugar (c), tannins (d), anthocyanins (e), and total phenols (f) in grape berries were measured. The average values (±SE) followed by different letters indicate significant difference at p value <0.05 using analysis of variance with the Tukey–Kramer test.
3.2 RNA-seq profiles
To gain a comprehensive understanding of the differences in gene expression within grapevine roots, nine RNA-seq libraries (NPK1, NPK2, NPK3, Org1, Org2, Org3, SC1, SC2, and SC3) were generated. Each library yielded over 45 million clean reads, with more than 70% of these reads mapping to either unique or multiple genomic locations (Table S2).
Genes with an average abundance and variance of at least five FPKM were selected to undergo PCA and hierarchical clustering. The first and second principal components accounted for 31.8 and 17.2% of the total variation, respectively (Figure 2a). Pearson correlation analysis revealed strong correlations among the samples between pairwise treatments (Figure 2b).

DEG in V. vinifera roots after different treatments. (a) PCA analysis of RNA-Seq expression profiles in different treatment conditions. (b) Correlation of RNA-Seq expression profiles of samples in different conditions. Venn diagram of up-regulated genes (c) and down-regulated genes (d) identified under different conditions. (e) Cluster analysis of DEGs in different treatment conditions.
To investigate the molecular mechanisms underlying the differences between SC and the other two fertilizer treatments, we used the DESeq2 “v1.14.1” package to identify DEGs in different treatments [23]. The selection criteria for DEGs were based on previous study [24]. Compared to the NPK and Org treatment groups, the SC treatment group had 2,943 and 997 up-regulated DEGs, respectively, with 918 overlapping DEGs (Figure 2c). In addition, compared to the NPK and Org treatment groups, the SC treatment group had 2,491 and 974 down-regulated DEGs, respectively, with 808 overlapping DEGs (Figure 2d). Cluster analysis revealed highly similar gene expression profiles among the different treatments, especially within the NPK or SC treatment groups (Figure 2e).
3.3 Functional analysis of DEGs
To analyze the response of genes with different expression levels to different soil treatments, GO was used to enrich for DEGs. As shown in Figure 3, the top 30 GO enrichment entries were categorized into three types: “biological process,” “cellular component,” and “molecular function.” In the results of comparing the SC and NPK treatments (SC vs NPK), the biological process category of GO terms included organonitrogen compound metabolic process (GO:1901564), biosynthetic process (GO:0009058), organic substance biosynthetic process (GO:1901576), and others. The cellular component category mainly contained entries such as cellular anatomical entity (GO:0110165), intracellular (GO:0005622), organelle (GO:0043226), and so on, while the molecular function category included terms such as structural molecule activity (GO:0005198) and structural constituent of ribosome (GO:0003735) (Figure 3a, Supplement data 2: Table S3). The GO enrichment analysis of DEGs from comparing the SC and Org treatment groups (SC vs Org) showed that the biological process category includes terms such as biosynthetic process (GO:0009058), organic substance biosynthetic process (GO:1901576), and cellular biosynthetic process (GO:0044249). The cellular component category includes terms such as cellular anatomical entity (GO:0110165), intracellular (GO:0005622), and organelle (GO:0043226). In addition, the molecular function category mainly includes entries such as structural molecule activity (GO:0005198), structural constituent of ribosome (GO:0003735), and transcription regulator activity (GO:0140110) (Figure 3b, Supplement data 2: Table S5). We further divided the GO enrichment analysis of DEGs from SC vs NPK and SC vs Org treatment groups into up- and down-regulated expression (Supplement data 2: Table S4, Table S6). The results showed that the majority of the DEGs obtained from the two compared groups were concentrated in up-regulated expression regulation.

GO enrichment analysis of DEGs: (a) SC vs NPK and (b) SC vs Org.
DEGs were also employed to identify KEGG pathways. The comparison between the SC-treated group and the NPK-treated group revealed that up-regulated DEGs were primarily enriched in KEGG pathways such as ribosome (vvi03010), protein processing in endoplasmic reticulum (vvi04141), glutathione metabolism (vvi00480), oxidative phosphorylation (vvi00190), spliceosome (vvi03040), protein export (vvi03060), endocytosis (vvi04144), SNARE interactions in vesicular transport (vvi04130), and galactose metabolism (vvi00052) (Figure 4a, Supplement data 1: Table S3). In contrast, down-regulated DEGs were mainly enriched in pathways like fatty acid metabolism (vvi01212), fatty acid biosynthesis (vvi00061), and starch and sucrose metabolism (vvi00500) (Figure 4b, Supplement data 1: Table S3). The comparison between the SC-treated group and the Org-treated group revealed that up-regulated DEGs were mainly concentrated in KEGG pathways such as ribosome (vvi03010), spliceosome (vvi03040), oxidative phosphorylation (vvi00190), endocytosis (vvi04144), galactose metabolism (vvi00052), sulfur relay system (vvi04122), protein export (vvi03060), and protein processing in endoplasmic reticulum (vvi04141) (Figure 4c, Supplement data 1: Table S3). On the other hand, down-regulated DEGs were primarily enriched in pathways like carotenoid biosynthesis (vvi00906), circadian rhythm (vvi04712), and porphyrin and chlorophyll metabolism (vvi00860) (Figure 4d, Supplement data 1: Table S3).

KEGG enrichment analysis of DEGs: (a) and (b) SC vs NPK; (c) and (d) SC vs Org.
3.4 Co-expression network
In order to explore the association between the regulatory network of grapevine root genes and berry phenotypes (soluble solid, titratable acid, soluble sugar, tannin, anthocyanin, and total phenols), WGCNA analysis was performed to globally identify highly correlated hub genes within highly connected gene networks based on the complete set of transcripts. Thirty-one modules were identified by applying the DynamicTreeCut function, and each module was visually distinguished by a series of color schemes (Figure 5a). By conducting Pearson correlation coefficient analysis, co-expression modules were identified for each grape fruit quality trait. The analysis results showed that the purple module, which contained 599 genes, had the highest correlation with soluble solids, soluble sugars, tannins, and anthocyanins (Figure 5b). Furthermore, we investigated key genes in the purple module. Through gene network construction, we obtained five hub genes, encoding Josephin-like protein (JP), 60S ribosomal protein L18a (60S), uncharacterized protein LOC100262900, and two transcription factors, namely, ethylene-responsive transcription factor (ERF) and splicing factor 3B subunit 6 (SF3B) (Figure 5c).

WGCNA identified gene networks. (a) Hierarchical clusters represent 31 distinct modules with co-expressed genes. Each leaflet in the tree represents an individual gene. (b) Pearson correlation-based module trait relationship. The color grids from green to red represent the r 2 value (−1 to 1). (c) Gene network of purple module. Hub genes are highlighted by triangles, and transcription factors are shown in green.
3.5 qRT-PCR analysis of anthocyanin synthesis genes
Considering that the application of SC resulted in higher anthocyanin content in grape berries compared to the two fertilization treatments, and that WGCNA analysis revealed a module of genes highly correlated with anthocyanin levels, we selected and validated the expression levels of five genes related to anthocyanin synthesis (three UDP-glucuronosyltransferases, glutathione-S-transferase, and anthocyanin acyltransferase) based on previous study [2]. In addition, we selected three genes for validation of their root transcription levels among the five hub genes identified in the gene network.
The qRT-PCR results showed that the expression levels of the three hub genes, VvERF, VvJP, and VvSF3B, were significantly higher in the SC-treated group than in the NPK- and Org-treated groups (Figure 6a–c). In addition, among the five genes related to anthocyanin synthesis, the transcript levels of VvUFGT1 and VvUFGT3 in the roots of grapevines treated with SC were significantly higher than those in the other two fertilizer-treated groups (Figure 6e and f). Moreover, the expression level of VvGST in the roots of the SC treatment group was significantly higher than that in the NPK treatment group (Figure 6g). The expression level of VvAT in the SC-treated group was significantly higher than that in the Org-treated group (Figure 6h). The transcript level of another UDP-glucuronosyltransferase gene, VvUFGT2, did not show significant differences between the SC-treated group and the other two treatment groups (Figure 6e).

Expression levels of five genes involved in anthocyanin biosynthesis and three hub genes were validated by qRT-PCR. Three biological replicates are used for qRT-PCR validation. The averages (±SE) following different letters indicate significant difference at p value <0.05 using analysis of variance with the Tukey–Kramer test.
4 Discussion
With increasing planting years, soil quality in wine grape vineyards deteriorates, particularly in terms of physical structure, chemical composition, and microbial diversity [25,26]. Failure to address these issues promptly reduces production capacity and lowers wine grape quality [27]. Therefore, rational soil management measures are urgently needed to improve soil quality and provide a favorable growth environment for grapevines. This study investigates the effects of three soil management measures on grapevine root system and fruit quality, with a focus on the advantages of SC compared to other two conventional fertilizers.
Soluble solids, titratable acidity, soluble sugars, tannins, anthocyanins, and total phenolics are considered important indicators of grape and wine quality [28], and fertilizers can have a significant impact on these quality indicators [2,8]. In this study, a SC was applied [29], which was formed by simple processing of lignite and contained approximately 38.5% humic acid. Grapes grown in soil treated with the SC had a higher proportion of soluble solids and soluble sugars compared to those grown in soil treated with inorganic and organic fertilizers, and their content of tannins, anthocyanins, and total phenolics also significantly increased (Figure 1). SCs can improve the physical and chemical properties of soil, and the humic acid they contain is known to stimulate plant growth and enhance nutrient uptake from the soil [30–32]. This can benefit root nutrient absorption and root system development, ultimately affecting fruit nutrient accumulation [33]. Under drought conditions, the application of humic acid at a concentration of 100–200 mg/L significantly enhanced the yield, dry weight, and root–shoot ratio of foxtail millet, while increasing the concentration of essential mineral elements such as P, Fe, Cu, Zn, and Mg in grains [34]. Humic acid has cytokinin, auxin, gibberellin-like activities, and contains 3-indoleacetic acid, which promote root growth and increase nutrient and water absorption surface area [35–37]. Thus, the use of humic acid as a foliar and soil application has been found to improve the growth, yield, and quality of coffee [37]. Moreover, humic acid can regulate soil microbial community, physical and chemical properties, and secondary metabolites in the bayberry rhizosphere, providing a novel strategy for managing bayberry decline disease [38]. Similarly, applying soil amendment in continuously cropped soil could lead to changes in the gene expression patterns in strawberry plant roots, such as an overall increase in the expression of nutrient transport genes and a decrease in the expression of defense response genes [39–41]. In this study, compared to the two fertilizer treatments, SC exerted distinct effects on the transcription levels of certain genes in grapevine roots (Figure 2). Among the up- and down-regulated DEGs, the most enriched GO terms showed that many up-regulated DEGs were associated with the biosynthesis of substances (Figure 3). KEGG pathway analysis revealed that SC promoted protein synthesis (Figure 4).
Anthocyanins are water-soluble flavonoids that contribute to the colors of plants. Key enzymes in the anthocyanin biosynthetic pathway include AT, UFGT, and GST. Potassium fertilizer application significantly increases the transcript levels of these enzymes in grape berries [2,42,43]. Similarly, in this study, treatment with SC significantly increased the transcript levels of UFGT1, UFGT3, GST, and AT in grapevine roots, potentially promoting potassium uptake and enhancing anthocyanin accumulation in grape berries [2]. Gene network analysis identified hub genes, including ERF, JP, and SF3B, which were significantly up-regulated in the SC treatment [2]. These genes play roles in regulating plant stress resistance and mRNA splicing [44–50]. Soil amendments can alleviate soil environmental stress, allowing plants to redistribute defense resources to development [39]. The utilization of SC may have impacted the microbial communities in the soil, leading to the activation of plant root genes responsible for stress resistance [51]. Further investigation is needed to understand the underlying molecular mechanisms [2,39,44–51].
5 Conclusion
In this study, we compared the effects of three soil management practices on grapevines, demonstrating that SC significantly improved grape fruit quality and altered the gene expression patterns in the plants compared to inorganic and organic fertilizers. Specifically, the application of SC significantly increased the soluble solids, soluble sugars, tannins, anthocyanins, and total phenols in grape fruits. Through WGCNA analysis of the transcriptomic data from the root of Cabernet Sauvignon, a module highly correlated with features such as anthocyanin was identified, with five hub genes identified within. We further validated three hub genes and specifically investigated five genes related to anthocyanin synthesis. The results showed that the expression levels of the three hub genes and VvUFGT1 and VvUFGT3 were significantly increased in the roots treated with SC. These findings suggest that improvements in soil quality, particularly with the application of SC, can effectively enhance grape quality.
Acknowledgements
The authors thank their colleagues for their comments regarding this article and the journal’s editors and anonymous reviewers for their critical reviews and comments regarding this manuscript.
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Funding information: This work was supported by the Leading Talents Fund in Science and Technology Innovation in Ningxia Province (2022GKLRLX09), the Ningxia Natural Science Foundation (grant number: 2023AAC03432), the Key Research and Development Program of Ningxia (grant number: 2020BCF01003), and Ningxia Agricultural Science and Technology Innovation Project (grant number: NKYZZ-J-19-04).
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Author contributions: R.W. and P.J. conceived and designed the experiments; P.J. and X.W. performed most of the experiments; P.J., R.W., and X.W. analyzed the RNA-seq data; R.W. organized the data and wrote the manuscript.
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Conflict of interest: Authors state no conflict of interest.
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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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This work is licensed under the Creative Commons Attribution 4.0 International License.
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Articles in the same Issue
- Biomedical Sciences
- Constitutive and evoked release of ATP in adult mouse olfactory epithelium
- LARP1 knockdown inhibits cultured gastric carcinoma cell cycle progression and metastatic behavior
- PEGylated porcine–human recombinant uricase: A novel fusion protein with improved efficacy and safety for the treatment of hyperuricemia and renal complications
- Research progress on ocular complications caused by type 2 diabetes mellitus and the function of tears and blepharons
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- Brucella infection combined with Nocardia infection: A case report and literature review
- Detection of serum interleukin-18 level and neutrophil/lymphocyte ratio in patients with antineutrophil cytoplasmic antibody-associated vasculitis and its clinical significance
- Ang-1, Ang-2, and Tie2 are diagnostic biomarkers for Henoch-Schönlein purpura and pediatric-onset systemic lupus erythematous
- PTTG1 induces pancreatic cancer cell proliferation and promotes aerobic glycolysis by regulating c-myc
- Role of serum B-cell-activating factor and interleukin-17 as biomarkers in the classification of interstitial pneumonia with autoimmune features
- Effectiveness and safety of a mumps containing vaccine in preventing laboratory-confirmed mumps cases from 2002 to 2017: A meta-analysis
- Low levels of sex hormone-binding globulin predict an increased breast cancer risk and its underlying molecular mechanisms
- A case of Trousseau syndrome: Screening, detection and complication
- Application of the integrated airway humidification device enhances the humidification effect of the rabbit tracheotomy model
- Preparation of Cu2+/TA/HAP composite coating with anti-bacterial and osteogenic potential on 3D-printed porous Ti alloy scaffolds for orthopedic applications
- Aquaporin-8 promotes human dermal fibroblasts to counteract hydrogen peroxide-induced oxidative damage: A novel target for management of skin aging
- Current research and evidence gaps on placental development in iron deficiency anemia
- Single-nucleotide polymorphism rs2910829 in PDE4D is related to stroke susceptibility in Chinese populations: The results of a meta-analysis
- Pheochromocytoma-induced myocardial infarction: A case report
- Kaempferol regulates apoptosis and migration of neural stem cells to attenuate cerebral infarction by O‐GlcNAcylation of β-catenin
- Sirtuin 5 regulates acute myeloid leukemia cell viability and apoptosis by succinylation modification of glycine decarboxylase
- Apigenin 7-glucoside impedes hypoxia-induced malignant phenotypes of cervical cancer cells in a p16-dependent manner
- KAT2A changes the function of endometrial stromal cells via regulating the succinylation of ENO1
- Current state of research on copper complexes in the treatment of breast cancer
- Exploring antioxidant strategies in the pathogenesis of ALS
- Helicobacter pylori causes gastric dysbacteriosis in chronic gastritis patients
- IL-33/soluble ST2 axis is associated with radiation-induced cardiac injury
- The predictive value of serum NLR, SII, and OPNI for lymph node metastasis in breast cancer patients with internal mammary lymph nodes after thoracoscopic surgery
- Carrying SNP rs17506395 (T > G) in TP63 gene and CCR5Δ32 mutation associated with the occurrence of breast cancer in Burkina Faso
- P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy
- Probiotics for inflammatory bowel disease: Is there sufficient evidence?
- Identification of KDM4C as a gene conferring drug resistance in multiple myeloma
- Microbial perspective on the skin–gut axis and atopic dermatitis
- Thymosin α1 combined with XELOX improves immune function and reduces serum tumor markers in colorectal cancer patients after radical surgery
- Highly specific vaginal microbiome signature for gynecological cancers
- Sample size estimation for AQP4-IgG seropositive optic neuritis: Retinal damage detection by optical coherence tomography
- The effects of SDF-1 combined application with VEGF on femoral distraction osteogenesis in rats
- Fabrication and characterization of gold nanoparticles using alginate: In vitro and in vivo assessment of its administration effects with swimming exercise on diabetic rats
- Mitigating digestive disorders: Action mechanisms of Mediterranean herbal active compounds
- Distribution of CYP2D6 and CYP2C19 gene polymorphisms in Han and Uygur populations with breast cancer in Xinjiang, China
- VSP-2 attenuates secretion of inflammatory cytokines induced by LPS in BV2 cells by mediating the PPARγ/NF-κB signaling pathway
- Factors influencing spontaneous hypothermia after emergency trauma and the construction of a predictive model
- Long-term administration of morphine specifically alters the level of protein expression in different brain regions and affects the redox state
- Application of metagenomic next-generation sequencing technology in the etiological diagnosis of peritoneal dialysis-associated peritonitis
- Clinical diagnosis, prevention, and treatment of neurodyspepsia syndrome using intelligent medicine
- Case report: Successful bronchoscopic interventional treatment of endobronchial leiomyomas
- Preliminary investigation into the genetic etiology of short stature in children through whole exon sequencing of the core family
- Cystic adenomyoma of the uterus: Case report and literature review
- Mesoporous silica nanoparticles as a drug delivery mechanism
- Dynamic changes in autophagy activity in different degrees of pulmonary fibrosis in mice
- Vitamin D deficiency and inflammatory markers in type 2 diabetes: Big data insights
- Lactate-induced IGF1R protein lactylation promotes proliferation and metabolic reprogramming of lung cancer cells
- Meta-analysis on the efficacy of allogeneic hematopoietic stem cell transplantation to treat malignant lymphoma
- Mitochondrial DNA drives neuroinflammation through the cGAS-IFN signaling pathway in the spinal cord of neuropathic pain mice
- Application value of artificial intelligence algorithm-based magnetic resonance multi-sequence imaging in staging diagnosis of cervical cancer
- Embedded monitoring system and teaching of artificial intelligence online drug component recognition
- Investigation into the association of FNDC1 and ADAMTS12 gene expression with plumage coloration in Muscovy ducks
- Yak meat content in feed and its impact on the growth of rats
- A rare case of Richter transformation with breast involvement: A case report and literature review
- First report of Nocardia wallacei infection in an immunocompetent patient in Zhejiang province
- Rhodococcus equi and Brucella pulmonary mass in immunocompetent: A case report and literature review
- Downregulation of RIP3 ameliorates the left ventricular mechanics and function after myocardial infarction via modulating NF-κB/NLRP3 pathway
- Evaluation of the role of some non-enzymatic antioxidants among Iraqi patients with non-alcoholic fatty liver disease
- The role of Phafin proteins in cell signaling pathways and diseases
- Ten-year anemia as initial manifestation of Castleman disease in the abdominal cavity: A case report
- Coexistence of hereditary spherocytosis with SPTB P.Trp1150 gene variant and Gilbert syndrome: A case report and literature review
- Utilization of convolutional neural networks to analyze microscopic images for high-throughput screening of mesenchymal stem cells
- Exploratory evaluation supported by experimental and modeling approaches of Inula viscosa root extract as a potent corrosion inhibitor for mild steel in a 1 M HCl solution
- Imaging manifestations of ductal adenoma of the breast: A case report
- Gut microbiota and sleep: Interaction mechanisms and therapeutic prospects
- Isomangiferin promotes the migration and osteogenic differentiation of rat bone marrow mesenchymal stem cells
- Prognostic value and microenvironmental crosstalk of exosome-related signatures in human epidermal growth factor receptor 2 positive breast cancer
- Circular RNAs as potential biomarkers for male severe sepsis
- Knockdown of Stanniocalcin-1 inhibits growth and glycolysis in oral squamous cell carcinoma cells
- The expression and biological role of complement C1s in esophageal squamous cell carcinoma
- A novel GNAS mutation in pseudohypoparathyroidism type 1a with articular flexion deformity: A case report
- Predictive value of serum magnesium levels for prognosis in patients with non-small cell lung cancer undergoing EGFR-TKI therapy
- HSPB1 alleviates acute-on-chronic liver failure via the P53/Bax pathway
- IgG4-related disease complicated by PLA2R-associated membranous nephropathy: A case report
- Baculovirus-mediated endostatin and angiostatin activation of autophagy through the AMPK/AKT/mTOR pathway inhibits angiogenesis in hepatocellular carcinoma
- Metformin mitigates osteoarthritis progression by modulating the PI3K/AKT/mTOR signaling pathway and enhancing chondrocyte autophagy
- Evaluation of the activity of antimicrobial peptides against bacterial vaginosis
- Atypical presentation of γ/δ mycosis fungoides with an unusual phenotype and SOCS1 mutation
- Analysis of the microecological mechanism of diabetic kidney disease based on the theory of “gut–kidney axis”: A systematic review
- Omega-3 fatty acids prevent gestational diabetes mellitus via modulation of lipid metabolism
- Refractory hypertension complicated with Turner syndrome: A case report
- Interaction of ncRNAs and the PI3K/AKT/mTOR pathway: Implications for osteosarcoma
- Association of low attenuation area scores with pulmonary function and clinical prognosis in patients with chronic obstructive pulmonary disease
- Long non-coding RNAs in bone formation: Key regulators and therapeutic prospects
- The deubiquitinating enzyme USP35 regulates the stability of NRF2 protein
- Neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio as potential diagnostic markers for rebleeding in patients with esophagogastric variceal bleeding
- G protein-coupled receptor 1 participating in the mechanism of mediating gestational diabetes mellitus by phosphorylating the AKT pathway
- LL37-mtDNA regulates viability, apoptosis, inflammation, and autophagy in lipopolysaccharide-treated RLE-6TN cells by targeting Hsp90aa1
- The analgesic effect of paeoniflorin: A focused review
- Chemical composition’s effect on Solanum nigrum Linn.’s antioxidant capacity and erythrocyte protection: Bioactive components and molecular docking analysis
- Knockdown of HCK promotes HREC cell viability and inner blood–retinal barrier integrity by regulating the AMPK signaling pathway
- The role of rapamycin in the PINK1/Parkin signaling pathway in mitophagy in podocytes
- Laryngeal non-Hodgkin lymphoma: Report of four cases and review of the literature
- Clinical value of macrogenome next-generation sequencing on infections
- Overview of dendritic cells and related pathways in autoimmune uveitis
- TAK-242 alleviates diabetic cardiomyopathy via inhibiting pyroptosis and TLR4/CaMKII/NLRP3 pathway
- Hypomethylation in promoters of PGC-1α involved in exercise-driven skeletal muscular alterations in old age
- Profile and antimicrobial susceptibility patterns of bacteria isolated from effluents of Kolladiba and Debark hospitals
- The expression and clinical significance of syncytin-1 in serum exosomes of hepatocellular carcinoma patients
- A histomorphometric study to evaluate the therapeutic effects of biosynthesized silver nanoparticles on the kidneys infected with Plasmodium chabaudi
- PGRMC1 and PAQR4 are promising molecular targets for a rare subtype of ovarian cancer
- Analysis of MDA, SOD, TAOC, MNCV, SNCV, and TSS scores in patients with diabetes peripheral neuropathy
- SLIT3 deficiency promotes non-small cell lung cancer progression by modulating UBE2C/WNT signaling
- The relationship between TMCO1 and CALR in the pathological characteristics of prostate cancer and its effect on the metastasis of prostate cancer cells
- Heterogeneous nuclear ribonucleoprotein K is a potential target for enhancing the chemosensitivity of nasopharyngeal carcinoma
- PHB2 alleviates retinal pigment epithelium cell fibrosis by suppressing the AGE–RAGE pathway
- Anti-γ-aminobutyric acid-B receptor autoimmune encephalitis with syncope as the initial symptom: Case report and literature review
- Comparative analysis of chloroplast genome of Lonicera japonica cv. Damaohua
- Human umbilical cord mesenchymal stem cells regulate glutathione metabolism depending on the ERK–Nrf2–HO-1 signal pathway to repair phosphoramide mustard-induced ovarian cancer cells
- Electroacupuncture on GB acupoints improves osteoporosis via the estradiol–PI3K–Akt signaling pathway
- Renalase protects against podocyte injury by inhibiting oxidative stress and apoptosis in diabetic nephropathy
- Review: Dicranostigma leptopodum: A peculiar plant of Papaveraceae
- Combination effect of flavonoids attenuates lung cancer cell proliferation by inhibiting the STAT3 and FAK signaling pathway
- Renal microangiopathy and immune complex glomerulonephritis induced by anti-tumour agents: A case report
- Correlation analysis of AVPR1a and AVPR2 with abnormal water and sodium and potassium metabolism in rats
- Gastrointestinal health anti-diarrheal mixture relieves spleen deficiency-induced diarrhea through regulating gut microbiota
- Myriad factors and pathways influencing tumor radiotherapy resistance
- Exploring the effects of culture conditions on Yapsin (YPS) gene expression in Nakaseomyces glabratus
- Screening of prognostic core genes based on cell–cell interaction in the peripheral blood of patients with sepsis
- Coagulation factor II thrombin receptor as a promising biomarker in breast cancer management
- Ileocecal mucinous carcinoma misdiagnosed as incarcerated hernia: A case report
- Methyltransferase like 13 promotes malignant behaviors of bladder cancer cells through targeting PI3K/ATK signaling pathway
- The debate between electricity and heat, efficacy and safety of irreversible electroporation and radiofrequency ablation in the treatment of liver cancer: A meta-analysis
- ZAG promotes colorectal cancer cell proliferation and epithelial–mesenchymal transition by promoting lipid synthesis
- Baicalein inhibits NLRP3 inflammasome activation and mitigates placental inflammation and oxidative stress in gestational diabetes mellitus
- Impact of SWCNT-conjugated senna leaf extract on breast cancer cells: A potential apoptotic therapeutic strategy
- MFAP5 inhibits the malignant progression of endometrial cancer cells in vitro
- Major ozonated autohemotherapy promoted functional recovery following spinal cord injury in adult rats via the inhibition of oxidative stress and inflammation
- Axodendritic targeting of TAU and MAP2 and microtubule polarization in iPSC-derived versus SH-SY5Y-derived human neurons
- Differential expression of phosphoinositide 3-kinase/protein kinase B and Toll-like receptor/nuclear factor kappa B signaling pathways in experimental obesity Wistar rat model
- The therapeutic potential of targeting Oncostatin M and the interleukin-6 family in retinal diseases: A comprehensive review
- BA inhibits LPS-stimulated inflammatory response and apoptosis in human middle ear epithelial cells by regulating the Nf-Kb/Iκbα axis
- Role of circRMRP and circRPL27 in chronic obstructive pulmonary disease
- Investigating the role of hyperexpressed HCN1 in inducing myocardial infarction through activation of the NF-κB signaling pathway
- Characterization of phenolic compounds and evaluation of anti-diabetic potential in Cannabis sativa L. seeds: In vivo, in vitro, and in silico studies
- Quantitative immunohistochemistry analysis of breast Ki67 based on artificial intelligence
- Ecology and Environmental Science
- Screening of different growth conditions of Bacillus subtilis isolated from membrane-less microbial fuel cell toward antimicrobial activity profiling
- Degradation of a mixture of 13 polycyclic aromatic hydrocarbons by commercial effective microorganisms
- Evaluation of the impact of two citrus plants on the variation of Panonychus citri (Acari: Tetranychidae) and beneficial phytoseiid mites
- Prediction of present and future distribution areas of Juniperus drupacea Labill and determination of ethnobotany properties in Antalya Province, Türkiye
- Population genetics of Todarodes pacificus (Cephalopoda: Ommastrephidae) in the northwest Pacific Ocean via GBS sequencing
- A comparative analysis of dendrometric, macromorphological, and micromorphological characteristics of Pistacia atlantica subsp. atlantica and Pistacia terebinthus in the middle Atlas region of Morocco
- Macrofungal sporocarp community in the lichen Scots pine forests
- Assessing the proximate compositions of indigenous forage species in Yemen’s pastoral rangelands
- Food Science
- Gut microbiota changes associated with low-carbohydrate diet intervention for obesity
- Reexamination of Aspergillus cristatus phylogeny in dark tea: Characteristics of the mitochondrial genome
- Differences in the flavonoid composition of the leaves, fruits, and branches of mulberry are distinguished based on a plant metabolomics approach
- Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera
- Non-linear associations between cardiovascular metabolic indices and metabolic-associated fatty liver disease: A cross-sectional study in the US population (2017–2020)
- Knockdown of USP7 alleviates atherosclerosis in ApoE-deficient mice by regulating EZH2 expression
- Utility of dairy microbiome as a tool for authentication and traceability
- Agriculture
- Enhancing faba bean (Vicia faba L.) productivity through establishing the area-specific fertilizer rate recommendation in southwest Ethiopia
- Impact of novel herbicide based on synthetic auxins and ALS inhibitor on weed control
- Perspectives of pteridophytes microbiome for bioremediation in agricultural applications
- Fertilizer application parameters for drip-irrigated peanut based on the fertilizer effect function established from a “3414” field trial
- Improving the productivity and profitability of maize (Zea mays L.) using optimum blended inorganic fertilization
- Application of leaf multispectral analyzer in comparison to hyperspectral device to assess the diversity of spectral reflectance indices in wheat genotypes
- Animal Sciences
- Knockdown of ANP32E inhibits colorectal cancer cell growth and glycolysis by regulating the AKT/mTOR pathway
- Development of a detection chip for major pathogenic drug-resistant genes and drug targets in bovine respiratory system diseases
- Exploration of the genetic influence of MYOT and MB genes on the plumage coloration of Muscovy ducks
- Transcriptome analysis of adipose tissue in grazing cattle: Identifying key regulators of fat metabolism
- Comparison of nutritional value of the wild and cultivated spiny loaches at three growth stages
- Transcriptomic analysis of liver immune response in Chinese spiny frog (Quasipaa spinosa) infected with Proteus mirabilis
- Disruption of BCAA degradation is a critical characteristic of diabetic cardiomyopathy revealed by integrated transcriptome and metabolome analysis
- Plant Sciences
- Effect of long-term in-row branch covering on soil microorganisms in pear orchards
- Photosynthetic physiological characteristics, growth performance, and element concentrations reveal the calcicole–calcifuge behaviors of three Camellia species
- Transcriptome analysis reveals the mechanism of NaHCO3 promoting tobacco leaf maturation
- Bioinformatics, expression analysis, and functional verification of allene oxide synthase gene HvnAOS1 and HvnAOS2 in qingke
- Water, nitrogen, and phosphorus coupling improves gray jujube fruit quality and yield
- Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots
- Role of Embinin in the reabsorption of nucleus pulposus in lumbar disc herniation: Promotion of nucleus pulposus neovascularization and apoptosis of nucleus pulposus cells
- Revealing the effects of amino acid, organic acid, and phytohormones on the germination of tomato seeds under salinity stress
- Combined effects of nitrogen fertilizer and biochar on the growth, yield, and quality of pepper
- Comprehensive phytochemical and toxicological analysis of Chenopodium ambrosioides (L.) fractions
- Impact of “3414” fertilization on the yield and quality of greenhouse tomatoes
- Exploring the coupling mode of water and fertilizer for improving growth, fruit quality, and yield of the pear in the arid region
- Metagenomic analysis of endophytic bacteria in seed potato (Solanum tuberosum)
- Antibacterial, antifungal, and phytochemical properties of Salsola kali ethanolic extract
- Exploring the hepatoprotective properties of citronellol: In vitro and in silico studies on ethanol-induced damage in HepG2 cells
- Enhanced osmotic dehydration of watermelon rind using honey–sucrose solutions: A study on pre-treatment efficacy and mass transfer kinetics
- Effects of exogenous 2,4-epibrassinolide on photosynthetic traits of 53 cowpea varieties under NaCl stress
- Comparative transcriptome analysis of maize (Zea mays L.) seedlings in response to copper stress
- An optimization method for measuring the stomata in cassava (Manihot esculenta Crantz) under multiple abiotic stresses
- Fosinopril inhibits Ang II-induced VSMC proliferation, phenotype transformation, migration, and oxidative stress through the TGF-β1/Smad signaling pathway
- Antioxidant and antimicrobial activities of Salsola imbricata methanolic extract and its phytochemical characterization
- Bioengineering and Biotechnology
- Absorbable calcium and phosphorus bioactive membranes promote bone marrow mesenchymal stem cells osteogenic differentiation for bone regeneration
- New advances in protein engineering for industrial applications: Key takeaways
- An overview of the production and use of Bacillus thuringiensis toxin
- Research progress of nanoparticles in diagnosis and treatment of hepatocellular carcinoma
- Bioelectrochemical biosensors for water quality assessment and wastewater monitoring
- PEI/MMNs@LNA-542 nanoparticles alleviate ICU-acquired weakness through targeted autophagy inhibition and mitochondrial protection
- Unleashing of cytotoxic effects of thymoquinone-bovine serum albumin nanoparticles on A549 lung cancer cells
- Erratum
- Erratum to “Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM”
- Erratum to “Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation”
- Retraction
- Retraction to “MiR-223-3p regulates cell viability, migration, invasion, and apoptosis of non-small cell lung cancer cells by targeting RHOB”
- Retraction to “A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis”
- Special Issue on Advances in Neurodegenerative Disease Research and Treatment
- Transplantation of human neural stem cell prevents symptomatic motor behavior disability in a rat model of Parkinson’s disease
- Special Issue on Multi-omics
- Inflammasome complex genes with clinical relevance suggest potential as therapeutic targets for anti-tumor drugs in clear cell renal cell carcinoma
- Gastroesophageal varices in primary biliary cholangitis with anti-centromere antibody positivity: Early onset?