Home Life Sciences Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
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Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer

  • Lei Xia , Xiaowei Song , Guanghai Yan , Jishan Quan EMAIL logo and Guangyu Jin EMAIL logo
Published/Copyright: August 15, 2022
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Open Life Sciences
From the journal Open Life Sciences Volume 17 Issue 1

Abstract

This study aims to synthesize a magnetic resonance imaging (MRI) contrast agent that can specifically target the asialoglycoprotein receptor of liver cancer cells and evaluate its ability as a targeted MRI contrast agent. Lactobionic acid (LA) and polyethylene glycol (PEG) were used to modify superparamagnetic iron oxide nanoparticles (SPION) to obtain LA-PEG-SPION. LA-PEG-SPION was uniformly spherical under the electron microscope, with regular morphology and good dispersion. The particle size of LA-PEG-SPION was about 30 ± 4.5 nm, and its surface potential was about 31 ± 1.5 mV. LA-PEG-SPION had no toxicity or low toxicity to HepG2 cells and HeLa cells, even at 400 μg/mL. The uptake of LA-PEG-SPION by HepG2 cells was higher than that of SPION, with increased blue-stained particles. The fluorescent labeling rate of HepG2 cells reached 68.8%, which was higher than that of the control group. In vitro, MRI showed that the T2-weighted signal intensity of HepG2 cells was lower than that of the control group. Conclusively, LA-PEG-SPION nanoparticles are synthesized in a simple and efficient way. They are successfully applied to the T2-weighted contrast-enhanced MRI in liver cancer in vitro, and they have the potential to be used for in vivo research and clinical studies.

Keywords: liver cancer; asialoglycoprotein receptor; superparamagnetic iron oxide nanoparticles; MRI contrast agent

1 Introduction

Superparamagnetic iron oxide nanoparticle (SPION) is a new type of magnetic resonance imaging (MRI) contrast agent, which has good biodegradability and no accumulation in the body [1]. SPION can be used not only as an MRI contrast agent but also for magnetic thermotherapy and drug delivery systems through the effect of external magnetic fields [2]. In 1988, SPION was used for MRI of liver cancer because it could be taken up by Kupffer cells [3]. The high sensitivity and specificity of SPION as a targeted contrast agent can greatly improve the early diagnosis of liver cancer.

There are many surface modifiers of SPION. Polyethylene glycol (PEG) was first used to modify bovine serum proteins to change their immune properties [4], and is non-toxic and non-charged. It can avoid electrostatic interaction with plasma proteins and avoid recognition and engulfment by the reticuloendothelial system [5]. In addition, the molecular weight of PEG-modified SPION is significantly increased, exceeding the ability of glomerular filtration, and thereby, effectively increasing the circulation of SPION in the body [6]. Studies have shown that PEG-modified drugs have significant improvements in the following aspects: (1) increased solubility or dispersibility; (2) prolonged half-life; (3) reduced in vivo phagocytosis and enzymatic degradation, and (4) reduced toxicity [7,8]. SPION with different particle diameters has different effects. SPION, with a diameter of more than 200 nm, is easily taken up by the reticuloendothelial system of the liver and spleen and thus can be used as a contrast agent for the MRI of the liver and spleen, which is also called a passive targeted contrast agent [9]. SPION with a diameter of below 200 nm can avoid the phagocytosis of the reticuloendothelial system and achieve active targeting through binding with the surface receptors of diseased cells [10,11].

Asialoglycoprotein receptor (ASGP-R) is a receptor protein that is specifically expressed on the surface of liver cells. It can efficiently recognize ligands with galactose residues and promote their uptake by liver cells [12]. Studies have found a large amount of ASGP-R on liver cancer cells, and their expression levels are different among liver cancers of different malignant degrees [13,14]. ASGP-R is a receptor specifically expressed by normal and cancerous liver cells, and it is rarely expressed in other tissues [15]. Therefore, molecular probes mediated by ASGP-R can not only be used for targeted imaging of liver cancer but also for targeted imaging of some metastatic cancers originating from liver cancer or free liver cancer cells. Lactobionic acid (LA) contains galactose groups, which can bind to ASGP-Rs on the cell surface and serves as an exogenous specific ligand for active targeting of liver cancer [16]. It has the advantages of easy modification and low cost as a small molecule and is easy to couple with SPION. There has been no report on the preparation of a targeted MRI contrast agent for liver cancer using ASGP-R as the target.

In this study, a contrast agent, LA-PEG-SPION, for liver MRI was constructed, and its physical and chemical characteristics were evaluated. In addition, its effect on targeted imaging was examined by in vitro cellular experiments. Our findings provide experimental evidence for using LA-PEG-SPION in in vivo research and clinical practice.

2 Materials and methods

2.1 Synthesis and characterization of LA-PEG-SPION

First, the precursor LA-PEG-COOH was prepared. The carboxyl group on the surface of lactic acid was activated by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC)/N-hydroxysuccinimide (NHS) system, and then the lactic acid was combined with NH2-PEG-COOH by condensation reaction to form LA-PEG-COOH. SPION was fully dispersed in 20 mL of deoxygenated water and sonicated for 30 min. Then, 100 μL of 3-aminopropyltriethoxysilane (Sigma-Aldrich Co., St. Louis, MO, US) was slowly added dropwise under magnetic stirring. The whole process was protected by nitrogen, and the reaction was performed under stirring at room temperature for 24 h. An acylated SPION solid was obtained after dialysis and freeze-drying. LA-PEG-COOH and EDC were mixed and dissolved in 20 mL of ultrapure water, and the reaction was carried out under magnetic stirring at room temperature for 30 min. The above solution was slowly added dropwise to a beaker containing NHS, and the reaction was performed under stirring at room temperature for 3 h. The acylated SPION was fully dispersed in 20 mL of ultrapure water under ultrasonic vibration. Then, the two groups of solutions were evenly mixed, and the reaction was performed under magnetic stirring for 12 h with the protection of nitrogen. The reacted solution was dialyzed in a dialysis bag of MW8000 (Spectrum, CA, USA) at 4°C, and freeze-dried to obtain solid LA-PEG-SPION powder.

The morphology of LA-PEG-SPION was observed with an electron microscope at a working voltage of 80 kV (JSM-100S; Electronics Corporation, Japan). The particle size and surface potential of LA-PEG-SPION were measured by a laser particle size analyzer (Chengdu Jingxin Powder Testing Equipment Co., Ltd, Chengdu, China) and a precision potentiometric titrator (Metrohm Co., Switzerland), respectively.

2.2 MTT assay

HepG2 and HeLa cells were seeded to a 96-well plate (Corning, USA) at a concentration of 5 × 104/mL and cultured in DMEM for 24 h. LA-PEG-SPION with different concentrations (25, 50, 100, 200, and 400 μg/mL) were fully dispersed in the serum-free culture medium and added to the wells. After 24 h of treatment, 20 μL of MTT solution (5 mg/mL; Aladdin, China) was added to each well and incubated under dark conditions for 4 h, according to the previous description [17]. Then, after washing, 150 μL of DMSO (Sigma, St. Louis USA) was added to each well. The optical density of each well at 490 nm was measured using a microplate reader (Tecan Sunrise, Switzerland). The untreated cells were used as a control. The absorbance of untreated cells was used as the reference value for calculating 100% cell viability. All experiments were repeated in triplicate with three parallel samples in each measurement.

2.3 Prussian blue staining

HepG2 cells were cultured on coverslips in 6-well plates with 5 × 104 cells per well. Each well was added with 20 μg/mL of SPION and LA-PEG-SPION. After culturing overnight, cells were washed and fixed with 2 mL of 4% paraformaldehyde. After washing again, Prussian blue staining was performed using the Prussian Blue Staining Kit (Solarbio life science, Beijing, China) according to the kit instructions. After that, slides were mounted with neutral gum and observed under a microscope (BX51FC, OLYMPUS, Tokyo, Japan).

Preparation of the sample for cytometry: HepG2 and HeLa cells were seeded into two 6-well plates at 5 × 105 cells per well. In the 6-well plates, 9 wells were seeded with HepG2 cells, and 3 wells were seeded with HeLa cells. Three wells of HepG2 cells were set as control, three wells of HepG2 cells were set as competition control, and 1.08 mg of LA was added. After being cultured for 24 h, the other three wells of HepG2 cells were added with LA-PEG-fluorescein isothiocyanate (FITC) at a concentration of 20 μg/mL. Meanwhile, 20 μg/mL LA-PEG-FITC was also added to the competition control well and the wells with HeLa cells, respectively. The cells were cultured in the dark for 4 h, then collected and analyzed by flow cytometry.

2.4 Flow cytometry

Flow cytometry was performed as previously described [18]. Fluorescein FITC coupled to LA-PEG was used to verify the targeting function of the probe, and flow cytometry (Thermofisher, USA) was used to detect the fluorescence intensity of cells in different groups. First, the blank group was analyzed to record the fluorescence distribution of blank control cells and draw the target area for comparison. Then, 0.36 mg/mL HepG2 cell group, 0.36 mg/mL HeLa group, 0.54 mg/mL HepG2 group, 0.54 mg/mL Hela group, and competition group were added sequentially. The fluorescence labeling rate of each group was recorded.

2.5 In vitro MRI

HepG2 and HeLa cells were seeded and cultured as described above. One well of HepG2 cells and one well of HeLa cells were used as control without contrast. The remaining two wells of HepG2 cells and HeLa cells were added with 20 and 40 μg/mL of LA-PEG-SPION suspension, respectively. After 4 h of incubation, NaOH solution (0.01 M) was added to lyse the cells. The cell fragment was mixed with a layer of 1% agarose gel, and a total of 500 μL of each sample was placed in a tube. After cell preparation, MRI was performed with a Siemens 3.0T MRI scanner for horizontal axis scanning. A T2 weighted sequence was performed. The specific parameters were: TR = 2,300, TE = 88, layer thickness = 0.6 mm, number of excitation = 1, field of view = 12 cm × 12 cm, matrix = 320 × 300. The region of interest of the same area was delineated in the same layer, and the T2WI signal intensity of three consecutive layers in each tube was measured [19].

3 Results

3.1 Synthesis and characterization of LA-PEG-SPION

The reaction equation of LA-PEG-COOH is shown in Figure 1a. The 1H-NMR was used to verify the chemical structure of the synthesized LA-PEG-COOH (Figure 1b). The chemical bonds in the LA-PEG-COOH chemical structure were numbered 1–31. According to the analysis, the peak near 7–8 ppm in the map belonged to No. 17 NH bond, and the peak near 3–4 ppm represented the chemical bonds 1, 2, 27, 28, 25, 24, and 23, respectively. The peak near 2–3 ppm represented the chemical bonds 13, 6, 7, 8, 4, 5, 12, 11, 20, and 19, respectively. The result of 1H-NMR demonstrated that LA-PEG-COOH was successfully synthesized.

Figure 1 Reaction equation and 1H-NMR. (a) The reaction equation of LA-PEG-COOH and (b) the 1H-NMR of LA-PEG-COOH.
Figure 1

Reaction equation and 1H-NMR. (a) The reaction equation of LA-PEG-COOH and (b) the 1H-NMR of LA-PEG-COOH.

LA-PEG-SPION was synthesized by the condensation reaction of LA-PEG-COOH and SPION using the chemical coupling agent EDC/NHS (Figure 2). Zeta potential analysis of SPION and LA-PEG-SPION showed that the surface potential of SPION was approximately (28 ± 1.5) mV, while that of LA-PEG-SPION increased slightly, to approximately (31 ± 1.5) mV. This suggests that both SPION and LA-PEG-SPION can form stable magnetic fluids in dispersed systems.

Figure 2 The reaction equations for LA-PEG-SPION synthesis.
Figure 2

The reaction equations for LA-PEG-SPION synthesis.

The electronic microscopic images showed that SPION and LA-PEG-SPION were both spherical particles. The LA-PEG-SPION particles were relatively uniform, with a core particle diameter of about 13 ± 1.5 nm (Figure 3a). No apparent agglomeration was observed. In addition, thin blurred aperture shadows were observed on the surface of the particles. This is because a thin film was formed on the particle surface after SPION was modified with LA-PEG. On the other hand, SPION was evenly dispersed in water without evident agglomeration (Figure 3b). The core particle size was about 10 nm, which was slightly smaller than LA-PEG-SPION. This may be related to the modified layer. These results indicate that the LA-PEG-SPION has a regular morphology, and its core particle size increases slightly, which is still in the appropriate range.

Figure 3 TEM images of (a) LA-PEG-SPION (magnification: 30k×) (scale bar = 100 nm) and (b) SPION (magnification: 30k×) (scale bar = 100 nm).
Figure 3

TEM images of (a) LA-PEG-SPION (magnification: 30k×) (scale bar = 100 nm) and (b) SPION (magnification: 30k×) (scale bar = 100 nm).

3.2 Cytotoxicity of the particles

MTT method is more widely used in the toxicity analysis of molecular imaging probes than some new cytotoxicity experiments [20]. To determine the cytotoxicity of the particles, an MTT assay was performed. As shown in Figure 4, both HepG2 and HeLa cells had high viability after treatment with various concentrations (25–400 μg/mL) of SPION, PEG-SPION, and LA-PEG-SPION, suggesting no evident cytotoxicity on both HepG2 and HeLa cells. Cells treated with PEG-SPION and LA-PEG-SPION had higher viability than those with SPION, indicating that PEG-SPION and LA-PEG-SPION may have lower cytotoxicity than SPION. In addition, at a high concentration of 400 μg/mL, the viability of HepG2 and HeLa cells treated by LA-PEG-SPION was as high as 90%, which shows that SPION, PEG-SPION, and LA-PEG-SPION are non-toxic or low-toxic at high concentrations. These results indicate that the modification of SPION, especially by PEG with high biocompatibility, could significantly reduce the cytotoxicity of the nanoparticles.

Figure 4 Viability of (a) HepG2 and (b) HeLa cells detected by the MTT assay. The cells were treated with different concentrations (25, 50, 100, 200, and 400 μg/mL) of LA-PEG-SPION for 24 h.
Figure 4

Viability of (a) HepG2 and (b) HeLa cells detected by the MTT assay. The cells were treated with different concentrations (25, 50, 100, 200, and 400 μg/mL) of LA-PEG-SPION for 24 h.

3.3 The SPIONs are taken up by liver cells

To observe the uptake of SPION by cells, Prussian blue staining was performed. HepG2 cells were treated with 20 μg/mL LA-PEG-SPION or SPION. As shown in Figure 5, a large amount of blue-dyed iron particles were observed in the HepG2 cells treated with LA-PEG-SPION, while the cells treated with SPION had only a few blue particles. This indicates that LA-PEG-SPION is easier to be taken up by HepG2 cells than SPION, and that, to a certain extent, LA-PEG-SPION may have a targeting effect on liver cancer cells.

Figure 5 Images of Prussian blue staining. Prussian blue staining of (a) HepG2 and (b) HeLa cells cultured with LA-PEG-SPION.
Figure 5

Images of Prussian blue staining. Prussian blue staining of (a) HepG2 and (b) HeLa cells cultured with LA-PEG-SPION.

3.4 Cell uptake of FITC labeled particles

To detect the uptake of fluorescent labeled particles by cells, flow cytometry was performed. The results showed that no fluorescence was detected in the HepG2 cells of the blank control group (Figure 6a). The HeLa cells incubated with 20 μg/mL LA-PEG-FITC had an uptake rate of only 10.09% (Figure 6b and e), while that of the HepG2 cells was as high as 66.81% (Figure 6c and e). The HepG2 cells of the competition group showed a fluorescence labeling rate of 48.82% (Figure 6d and e), which was lower than that of the non-competitive group. This may be because the concentration of the drug used was not high enough to occupy all the ASGP-R receptors. The flow cytometry results showed that the order of the uptake rate of LA-PEG-FITC in the cells was HepG2 cells > HepG2 cells of the competition group > HeLa cells. This indicates that LA-PEG-FITC highly targets the ASGP-R high-expressing tumor cells.

Figure 6 Flow cytometry for the uptake of fluorescent markers by cells. (a) Blank control; (b) HeLa cells; (c) HepG2 cells; and (d) LA competition group. (e) Quantification of the cell uptake of LA-PEG-SPION.
Figure 6

Flow cytometry for the uptake of fluorescent markers by cells. (a) Blank control; (b) HeLa cells; (c) HepG2 cells; and (d) LA competition group. (e) Quantification of the cell uptake of LA-PEG-SPION.

3.5 LA-PEG-SPION shows targeted MRI imaging

To verify the tumor-targeted ability of LA-PEG-SPION in MRI contrast imaging, the MRI enhancement test in vitro was performed. As shown in Figure 7, the signal intensities of the blank control groups of the two cell lines were basically the same, and their brightness was not evidently different from that of the ultrapure water control group. With the increase in LA-PEG-SPION concentration, the image brightness of HepG2 cells decreased. The relative gray value was lower than that in the control group. At a concentration of 40 μg/mL, the cell image brightness was extremely low, and the outline of the border could not be clearly observed on a black background. The brightness of HeLa cell images was not apparently decreased with the increase in LA-PEG-SPION concentration. As a comparison, the two cell lines showed apparent differences in image signal intensity at the same LA-PEG-SPION concentration. The HepG2 cells showed an evidently darker image than the HeLa cells, indicating that its T2-weighted signal intensity decreases more and that the uptake of LA-PEG-SPION by HepG2 cells is higher than HeLa cells.

Figure 7 In vitro MRI. (a) T2WI images of in vitro MRI. (b) Quantification of the MRI signal by gray value. DDW, deuterium depleted water.
Figure 7

In vitro MRI. (a) T2WI images of in vitro MRI. (b) Quantification of the MRI signal by gray value. DDW, deuterium depleted water.

4 Discussion

The average particle diameter of SPION was 30 ± 3.5 nm, while the particle diameter of LA-PEG-SPION was 33 ± 5.5 nm, which was slightly larger than that of SPION. This may be due to the fact that a thin coating layer was formed in solution after SPION was modified with LA-PEG, which slightly increases the hydrated particle size of the product. Studies have shown that SPION should have a nucleus particle size of about 10 nm, but the smallest pore size of permeable microvessels in normal tissues is about 10 nm. If the particle sizes are too small, there will be drug leakage, affecting their effects [21,22]. Therefore, special treatment is needed for SPION to obtain a suitable size for use. According to the electron microscope image, the core particle diameter of LA-PEG-SPION was about 10 nm, which meets the requirements of superparamagnetism. The hydrated particle size measured by the laser particle sizer is in line with the true particle size of the nanoparticles in the solution. Gupta and Gupta [23] showed that modified magnetic nanoparticles with a particle size between 10 and 100 nm had good stability and superparamagnetism, and thus were the most effective drug delivery carriers.

Lactic acid has a high affinity for ASGP-R, and PEG can effectively prolong the half-life of drugs in vivo and improve biocompatibility. Meanwhile, PEG can also reduce the formation of protein crowns and avoid the covering of active targeting groups. Flow cytometry results showed that the uptake of LA-PEG in hepatocellular carcinoma cells was higher than that in cervical cancer cells, and the cell labeling rate was more than 66%, even at a lower dose (20 μg/mL). The results of MR enhancement imaging of LA-PEG-SPION in vitro were consistent with that of flow cytometry. This part demonstrates that a new type of actively targeted magnetic resonance contrast agent has been constructed, which can provide a reference for the development of MR molecular imaging.

The safety of contrast agents is the most important prerequisite for its clinical application. In this study, the cytotoxicity of LA-PEG-SPION was detected by the MTT method. The results showed that LA-PEG-SPION had no evident toxicity to HepG2 and HeLa cells, and the toxicity of LA-PEG-SPION was lower than that of SPION, which might be due to the high biocompatibility and safety of PEG. PEG not only prolongs the retention time of the drug in blood but also protects human tissues [24,25]. In this study, Prussian blue staining and flow cytometry were used to detect the targeting ability of LA-PEG-SPION for liver cancer cells. Potassium ferricyanide in Prussian blue dye can combine with iron particles to form blue insoluble ferricyanide Prussian blue. This is also a major feature of SPION. It can visually display the distribution of probes from the tissue level, which is not available in other types of nanoparticles.

5 Conclusion

In this study, an MRI contrast agent LA-PEG-SPION that could specifically target liver cancer cell surface receptor ASGP-R was successfully synthesized. It had a regular circular shape and a stable surface potential and could form magnetic fluid in solution. It was low-toxic or non-toxic to HepG2 and HeLa cells. In vitro experiments showed that LA-PEG-SPION had specific targeting for liver cancer cells and may serve as a potential T2-weighted negative contrast in MRI. LA-PEG-SPION has the necessary conditions to become a targeted MRI contrast agent for liver cancer, and this study provides a basis for further in vivo evaluation and clinical studies.

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  1. Funding information: This work was supported by the National Science Foundation of China [Grant No. 81860304 and 82160329] and the Natural Science Research Foundation of Jilin Province for Sciences and Technology [Grant No. 20200201511JC].

  2. Author contributions: Guangyu Jin and Jishan Quan contributed to the conception of the study; Lei Xia performed the experiments and wrote the manuscript; Guanghai Yan contributed significantly to data analysis and manuscript preparation; Xiaowei Song performed the data analyses. All authors read and approved the final version of the 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: 2021-09-03
Revised: 2022-03-09
Accepted: 2022-03-10
Published Online: 2022-08-15

© 2022 Lei Xia et al., published by De Gruyter

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

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  24. Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
  25. Comparison of axon extension: PTFE versus PLA formed by a 3D printer
  26. Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
  27. A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
  28. Study on the mechanism of inhibiting patulin production by fengycin
  29. SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
  30. Relationship between blood clots and COVID-19 vaccines: A literature review
  31. Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
  32. Bioinformatics network analyses of growth differentiation factor 11
  33. NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
  34. Expression of Zeb1 in the differentiation of mouse embryonic stem cell
  35. Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
  36. Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
  37. Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
  38. Genetic susceptibility to high myopia in Han Chinese population
  39. Potential biomarkers and molecular mechanisms in preeclampsia progression
  40. Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
  41. Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
  42. The significance of PAK4 in signaling and clinicopathology: A review
  43. Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
  44. Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
  45. Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
  46. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
  47. MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
  48. Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
  49. BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
  50. Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
  51. Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
  52. A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
  53. Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
  54. Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
  55. Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
  56. A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
  57. β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
  58. Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
  59. BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
  60. Mucormycosis co-infection in COVID-19 patients: An update
  61. Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
  62. Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
  63. Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
  64. Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
  65. Nasopharyngeal tuberculosis: A case report
  66. Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
  67. Aberrant pulmonary immune response of obese mice to periodontal infection
  68. Bacteriospermia – A formidable player in male subfertility
  69. In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma
  70. Effects of KCa channels on biological behavior of trophoblasts
  71. Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice
  72. Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report
  73. Prognostic signature related to the immune environment of oral squamous cell carcinoma
  74. Primary and metastatic squamous cell carcinoma of the thyroid gland: Two case reports
  75. Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats
  76. Role of MMP-2 and CD147 in kidney fibrosis
  77. Geometric basis of action potential of skeletal muscle cells and neurons
  78. Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review
  79. Role of cerebellar cortex in associative learning and memory in guinea pigs
  80. Application of metagenomic next-generation sequencing technique for diagnosing a specific case of necrotizing meningoencephalitis caused by human herpesvirus 2
  81. Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male
  82. Long non-coding RNA NEAT1 promotes angiogenesis in hepatoma carcinoma via the miR-125a-5p/VEGF pathway
  83. Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments
  84. Knockdown of SHMT2 enhances the sensitivity of gastric cancer cells to radiotherapy through the Wnt/β-catenin pathway
  85. Continuous renal replacement therapy combined with double filtration plasmapheresis in the treatment of severe lupus complicated by serious bacterial infections in children: A case report
  86. Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
  87. Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
  88. One case of iodine-125 therapy – A new minimally invasive treatment of intrahepatic cholangiocarcinoma
  89. S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model
  90. Early cancer detection by a targeted methylation assay of circulating tumor DNA in plasma
  91. Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis
  92. Evaluation of prognostic markers in patients infected with SARS-CoV-2
  93. N6-Methyladenosine-related alternative splicing events play a role in bladder cancer
  94. Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats
  95. Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells
  96. Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China
  97. Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report
  98. Aggravated renal fibrosis is positively associated with the activation of HMGB1-TLR2/4 signaling in STZ-induced diabetic mice
  99. Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay
  100. SRPX2 attenuated oxygen–glucose deprivation and reperfusion-induced injury in cardiomyocytes via alleviating endoplasmic reticulum stress-induced apoptosis through targeting PI3K/Akt/mTOR axis
  101. Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients
  102. Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
  103. Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats
  104. Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep
  105. Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial–mesenchymal transition in clear-cell renal cell carcinoma
  106. PHF8 promotes osteogenic differentiation of BMSCs in old rat with osteoporosis by regulating Wnt/β-catenin pathway
  107. A review of the current state of the computer-aided diagnosis (CAD) systems for breast cancer diagnosis
  108. Bilateral dacryoadenitis in adult-onset Still’s disease: A case report
  109. A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma
  110. The role of erythrocytes and erythroid progenitor cells in tumors
  111. Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
  112. Abnormal methylation caused by folic acid deficiency in neural tube defects
  113. Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats
  114. Plant Sciences
  115. Seasonal succession of bacterial communities in cultured Caulerpa lentillifera detected by high-throughput sequencing
  116. Cloning and prokaryotic expression of WRKY48 from Caragana intermedia
  117. Novel Brassica hybrids with different resistance to Leptosphaeria maculans reveal unbalanced rDNA signal patterns
  118. Application of exogenous auxin and gibberellin regulates the bolting of lettuce (Lactuca sativa L.)
  119. Phytoremediation of pollutants from wastewater: A concise review
  120. Genome-wide identification and characterization of NBS-encoding genes in the sweet potato wild ancestor Ipomoea trifida (H.B.K.)
  121. Alleviative effects of magnetic Fe3O4 nanoparticles on the physiological toxicity of 3-nitrophenol to rice (Oryza sativa L.) seedlings
  122. Selection and functional identification of Dof genes expressed in response to nitrogen in Populus simonii × Populus nigra
  123. Study on pecan seed germination influenced by seed endocarp
  124. Identification of active compounds in Ophiopogonis Radix from different geographical origins by UPLC-Q/TOF-MS combined with GC-MS approaches
  125. The entire chloroplast genome sequence of Asparagus cochinchinensis and genetic comparison to Asparagus species
  126. Genome-wide identification of MAPK family genes and their response to abiotic stresses in tea plant (Camellia sinensis)
  127. Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in Caragana intermedia
  128. Cloning and expression analysis of SERK1 gene in Diospyros lotus
  129. Integrated metabolomic and transcriptomic profiling revealed coping mechanisms of the edible and medicinal homologous plant Plantago asiatica L. cadmium resistance
  130. A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion
  131. Assessment of drought tolerance indices in faba bean genotypes under different irrigation regimes
  132. The entire chloroplast genome sequence of Asparagus setaceus (Kunth) Jessop: Genome structure, gene composition, and phylogenetic analysis in Asparagaceae
  133. Food Science
  134. Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model
  135. Binge eating disorder during COVID-19
  136. Potential of honey against the onset of autoimmune diabetes and its associated nephropathy, pancreatitis, and retinopathy in type 1 diabetic animal model
  137. FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation
  138. Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage
  139. Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin
  140. Functional constituents of plant-based foods boost immunity against acute and chronic disorders
  141. Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
  142. Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
  143. Ecology and Environmental Sciences
  144. Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
  145. Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
  146. Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
  147. Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
  148. Plant volatile organic compounds attractive to Lygus pratensis
  149. Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
  150. Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
  151. Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
  152. Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
  153. Bioengineering and Biotechnology
  154. Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
  155. Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
  156. Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
  157. Agriculture
  158. Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
  159. Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
  160. Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
  161. Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
  162. Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
  163. Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
  164. Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
  165. Animal Sciences
  166. Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
  167. Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
  168. SI: A Scientific Memoir
  169. Suggestions on leading an academic research laboratory group
  170. My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
  171. Erratum
  172. Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
  173. Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
  174. Retraction
  175. Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
https://doi.org/10.1515/biol-2022-0074
Keywords for this article
liver cancer; asialoglycoprotein receptor; superparamagnetic iron oxide nanoparticles; MRI contrast agent
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Effects of direct oral anticoagulants dabigatran and rivaroxaban on the blood coagulation function in rabbits
  3. The mother of all battles: Viruses vs humans. Can humans avoid extinction in 50–100 years?
  4. Knockdown of G1P3 inhibits cell proliferation and enhances the cytotoxicity of dexamethasone in acute lymphoblastic leukemia
  5. LINC00665 regulates hepatocellular carcinoma by modulating mRNA via the m6A enzyme
  6. Association study of CLDN14 variations in patients with kidney stones
  7. Concanavalin A-induced autoimmune hepatitis model in mice: Mechanisms and future outlook
  8. Regulation of miR-30b in cancer development, apoptosis, and drug resistance
  9. Informatic analysis of the pulmonary microecology in non-cystic fibrosis bronchiectasis at three different stages
  10. Swimming attenuates tumor growth in CT-26 tumor-bearing mice and suppresses angiogenesis by mediating the HIF-1α/VEGFA pathway
  11. Characterization of intestinal microbiota and serum metabolites in patients with mild hepatic encephalopathy
  12. Functional conservation and divergence in plant-specific GRF gene family revealed by sequences and expression analysis
  13. Application of the FLP/LoxP-FRT recombination system to switch the eGFP expression in a model prokaryote
  14. Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium
  15. Intravenous infusion of the exosomes derived from human umbilical cord mesenchymal stem cells enhance neurological recovery after traumatic brain injury via suppressing the NF-κB pathway
  16. Effect of dietary pattern on pregnant women with gestational diabetes mellitus and its clinical significance
  17. Potential regulatory mechanism of TNF-α/TNFR1/ANXA1 in glioma cells and its role in glioma cell proliferation
  18. Effect of the genetic mutant G71R in uridine diphosphate-glucuronosyltransferase 1A1 on the conjugation of bilirubin
  19. Quercetin inhibits cytotoxicity of PC12 cells induced by amyloid-beta 25–35 via stimulating estrogen receptor α, activating ERK1/2, and inhibiting apoptosis
  20. Nutrition intervention in the management of novel coronavirus pneumonia patients
  21. circ-CFH promotes the development of HCC by regulating cell proliferation, apoptosis, migration, invasion, and glycolysis through the miR-377-3p/RNF38 axis
  22. Bmi-1 directly upregulates glucose transporter 1 in human gastric adenocarcinoma
  23. Lacunar infarction aggravates the cognitive deficit in the elderly with white matter lesion
  24. Hydroxysafflor yellow A improved retinopathy via Nrf2/HO-1 pathway in rats
  25. Comparison of axon extension: PTFE versus PLA formed by a 3D printer
  26. Elevated IL-35 level and iTr35 subset increase the bacterial burden and lung lesions in Mycobacterium tuberculosis-infected mice
  27. A case report of CAT gene and HNF1β gene variations in a patient with early-onset diabetes
  28. Study on the mechanism of inhibiting patulin production by fengycin
  29. SOX4 promotes high-glucose-induced inflammation and angiogenesis of retinal endothelial cells by activating NF-κB signaling pathway
  30. Relationship between blood clots and COVID-19 vaccines: A literature review
  31. Analysis of genetic characteristics of 436 children with dysplasia and detailed analysis of rare karyotype
  32. Bioinformatics network analyses of growth differentiation factor 11
  33. NR4A1 inhibits the epithelial–mesenchymal transition of hepatic stellate cells: Involvement of TGF-β–Smad2/3/4–ZEB signaling
  34. Expression of Zeb1 in the differentiation of mouse embryonic stem cell
  35. Study on the genetic damage caused by cadmium sulfide quantum dots in human lymphocytes
  36. Association between single-nucleotide polymorphisms of NKX2.5 and congenital heart disease in Chinese population: A meta-analysis
  37. Assessment of the anesthetic effect of modified pentothal sodium solution on Sprague-Dawley rats
  38. Genetic susceptibility to high myopia in Han Chinese population
  39. Potential biomarkers and molecular mechanisms in preeclampsia progression
  40. Silencing circular RNA-friend leukemia virus integration 1 restrained malignancy of CC cells and oxaliplatin resistance by disturbing dyskeratosis congenita 1
  41. Endostar plus pembrolizumab combined with a platinum-based dual chemotherapy regime for advanced pulmonary large-cell neuroendocrine carcinoma as a first-line treatment: A case report
  42. The significance of PAK4 in signaling and clinicopathology: A review
  43. Sorafenib inhibits ovarian cancer cell proliferation and mobility and induces radiosensitivity by targeting the tumor cell epithelial–mesenchymal transition
  44. Characterization of rabbit polyclonal antibody against camel recombinant nanobodies
  45. Active legumain promotes invasion and migration of neuroblastoma by regulating epithelial-mesenchymal transition
  46. Effect of cell receptors in the pathogenesis of osteoarthritis: Current insights
  47. MT-12 inhibits the proliferation of bladder cells in vitro and in vivo by enhancing autophagy through mitochondrial dysfunction
  48. Study of hsa_circRNA_000121 and hsa_circRNA_004183 in papillary thyroid microcarcinoma
  49. BuyangHuanwu Decoction attenuates cerebral vasospasm caused by subarachnoid hemorrhage in rats via PI3K/AKT/eNOS axis
  50. Effects of the interaction of Notch and TLR4 pathways on inflammation and heart function in septic heart
  51. Monosodium iodoacetate-induced subchondral bone microstructure and inflammatory changes in an animal model of osteoarthritis
  52. A rare presentation of type II Abernethy malformation and nephrotic syndrome: Case report and review
  53. Rapid death due to pulmonary epithelioid haemangioendothelioma in several weeks: A case report
  54. Hepatoprotective role of peroxisome proliferator-activated receptor-α in non-cancerous hepatic tissues following transcatheter arterial embolization
  55. Correlation between peripheral blood lymphocyte subpopulations and primary systemic lupus erythematosus
  56. A novel SLC8A1-ALK fusion in lung adenocarcinoma confers sensitivity to alectinib: A case report
  57. β-Hydroxybutyrate upregulates FGF21 expression through inhibition of histone deacetylases in hepatocytes
  58. Identification of metabolic genes for the prediction of prognosis and tumor microenvironment infiltration in early-stage non-small cell lung cancer
  59. BTBD10 inhibits glioma tumorigenesis by downregulating cyclin D1 and p-Akt
  60. Mucormycosis co-infection in COVID-19 patients: An update
  61. Metagenomic next-generation sequencing in diagnosing Pneumocystis jirovecii pneumonia: A case report
  62. Long non-coding RNA HOXB-AS1 is a prognostic marker and promotes hepatocellular carcinoma cells’ proliferation and invasion
  63. Preparation and evaluation of LA-PEG-SPION, a targeted MRI contrast agent for liver cancer
  64. Proteomic analysis of the liver regulating lipid metabolism in Chaohu ducks using two-dimensional electrophoresis
  65. Nasopharyngeal tuberculosis: A case report
  66. Characterization and evaluation of anti-Salmonella enteritidis activity of indigenous probiotic lactobacilli in mice
  67. Aberrant pulmonary immune response of obese mice to periodontal infection
  68. Bacteriospermia – A formidable player in male subfertility
  69. In silico and in vivo analysis of TIPE1 expression in diffuse large B cell lymphoma
  70. Effects of KCa channels on biological behavior of trophoblasts
  71. Interleukin-17A influences the vulnerability rather than the size of established atherosclerotic plaques in apolipoprotein E-deficient mice
  72. Multiple organ failure and death caused by Staphylococcus aureus hip infection: A case report
  73. Prognostic signature related to the immune environment of oral squamous cell carcinoma
  74. Primary and metastatic squamous cell carcinoma of the thyroid gland: Two case reports
  75. Neuroprotective effects of crocin and crocin-loaded niosomes against the paraquat-induced oxidative brain damage in rats
  76. Role of MMP-2 and CD147 in kidney fibrosis
  77. Geometric basis of action potential of skeletal muscle cells and neurons
  78. Babesia microti-induced fulminant sepsis in an immunocompromised host: A case report and the case-specific literature review
  79. Role of cerebellar cortex in associative learning and memory in guinea pigs
  80. Application of metagenomic next-generation sequencing technique for diagnosing a specific case of necrotizing meningoencephalitis caused by human herpesvirus 2
  81. Case report: Quadruple primary malignant neoplasms including esophageal, ureteral, and lung in an elderly male
  82. Long non-coding RNA NEAT1 promotes angiogenesis in hepatoma carcinoma via the miR-125a-5p/VEGF pathway
  83. Osteogenic differentiation of periodontal membrane stem cells in inflammatory environments
  84. Knockdown of SHMT2 enhances the sensitivity of gastric cancer cells to radiotherapy through the Wnt/β-catenin pathway
  85. Continuous renal replacement therapy combined with double filtration plasmapheresis in the treatment of severe lupus complicated by serious bacterial infections in children: A case report
  86. Simultaneous triple primary malignancies, including bladder cancer, lymphoma, and lung cancer, in an elderly male: A case report
  87. Preclinical immunogenicity assessment of a cell-based inactivated whole-virion H5N1 influenza vaccine
  88. One case of iodine-125 therapy – A new minimally invasive treatment of intrahepatic cholangiocarcinoma
  89. S1P promotes corneal trigeminal neuron differentiation and corneal nerve repair via upregulating nerve growth factor expression in a mouse model
  90. Early cancer detection by a targeted methylation assay of circulating tumor DNA in plasma
  91. Calcifying nanoparticles initiate the calcification process of mesenchymal stem cells in vitro through the activation of the TGF-β1/Smad signaling pathway and promote the decay of echinococcosis
  92. Evaluation of prognostic markers in patients infected with SARS-CoV-2
  93. N6-Methyladenosine-related alternative splicing events play a role in bladder cancer
  94. Characterization of the structural, oxidative, and immunological features of testis tissue from Zucker diabetic fatty rats
  95. Effects of glucose and osmotic pressure on the proliferation and cell cycle of human chorionic trophoblast cells
  96. Investigation of genotype diversity of 7,804 norovirus sequences in humans and animals of China
  97. Characteristics and karyotype analysis of a patient with turner syndrome complicated with multiple-site tumors: A case report
  98. Aggravated renal fibrosis is positively associated with the activation of HMGB1-TLR2/4 signaling in STZ-induced diabetic mice
  99. Distribution characteristics of SARS-CoV-2 IgM/IgG in false-positive results detected by chemiluminescent immunoassay
  100. SRPX2 attenuated oxygen–glucose deprivation and reperfusion-induced injury in cardiomyocytes via alleviating endoplasmic reticulum stress-induced apoptosis through targeting PI3K/Akt/mTOR axis
  101. Aquaporin-8 overexpression is involved in vascular structure and function changes in placentas of gestational diabetes mellitus patients
  102. Relationship between CRP gene polymorphisms and ischemic stroke risk: A systematic review and meta-analysis
  103. Effects of growth hormone on lipid metabolism and sexual development in pubertal obese male rats
  104. Cloning and identification of the CTLA-4IgV gene and functional application of vaccine in Xinjiang sheep
  105. Antitumor activity of RUNX3: Upregulation of E-cadherin and downregulation of the epithelial–mesenchymal transition in clear-cell renal cell carcinoma
  106. PHF8 promotes osteogenic differentiation of BMSCs in old rat with osteoporosis by regulating Wnt/β-catenin pathway
  107. A review of the current state of the computer-aided diagnosis (CAD) systems for breast cancer diagnosis
  108. Bilateral dacryoadenitis in adult-onset Still’s disease: A case report
  109. A novel association between Bmi-1 protein expression and the SUVmax obtained by 18F-FDG PET/CT in patients with gastric adenocarcinoma
  110. The role of erythrocytes and erythroid progenitor cells in tumors
  111. Relationship between platelet activation markers and spontaneous abortion: A meta-analysis
  112. Abnormal methylation caused by folic acid deficiency in neural tube defects
  113. Silencing TLR4 using an ultrasound-targeted microbubble destruction-based shRNA system reduces ischemia-induced seizures in hyperglycemic rats
  114. Plant Sciences
  115. Seasonal succession of bacterial communities in cultured Caulerpa lentillifera detected by high-throughput sequencing
  116. Cloning and prokaryotic expression of WRKY48 from Caragana intermedia
  117. Novel Brassica hybrids with different resistance to Leptosphaeria maculans reveal unbalanced rDNA signal patterns
  118. Application of exogenous auxin and gibberellin regulates the bolting of lettuce (Lactuca sativa L.)
  119. Phytoremediation of pollutants from wastewater: A concise review
  120. Genome-wide identification and characterization of NBS-encoding genes in the sweet potato wild ancestor Ipomoea trifida (H.B.K.)
  121. Alleviative effects of magnetic Fe3O4 nanoparticles on the physiological toxicity of 3-nitrophenol to rice (Oryza sativa L.) seedlings
  122. Selection and functional identification of Dof genes expressed in response to nitrogen in Populus simonii × Populus nigra
  123. Study on pecan seed germination influenced by seed endocarp
  124. Identification of active compounds in Ophiopogonis Radix from different geographical origins by UPLC-Q/TOF-MS combined with GC-MS approaches
  125. The entire chloroplast genome sequence of Asparagus cochinchinensis and genetic comparison to Asparagus species
  126. Genome-wide identification of MAPK family genes and their response to abiotic stresses in tea plant (Camellia sinensis)
  127. Selection and validation of reference genes for RT-qPCR analysis of different organs at various development stages in Caragana intermedia
  128. Cloning and expression analysis of SERK1 gene in Diospyros lotus
  129. Integrated metabolomic and transcriptomic profiling revealed coping mechanisms of the edible and medicinal homologous plant Plantago asiatica L. cadmium resistance
  130. A missense variant in NCF1 is associated with susceptibility to unexplained recurrent spontaneous abortion
  131. Assessment of drought tolerance indices in faba bean genotypes under different irrigation regimes
  132. The entire chloroplast genome sequence of Asparagus setaceus (Kunth) Jessop: Genome structure, gene composition, and phylogenetic analysis in Asparagaceae
  133. Food Science
  134. Dietary food additive monosodium glutamate with or without high-lipid diet induces spleen anomaly: A mechanistic approach on rat model
  135. Binge eating disorder during COVID-19
  136. Potential of honey against the onset of autoimmune diabetes and its associated nephropathy, pancreatitis, and retinopathy in type 1 diabetic animal model
  137. FTO gene expression in diet-induced obesity is downregulated by Solanum fruit supplementation
  138. Physical activity enhances fecal lactobacilli in rats chronically drinking sweetened cola beverage
  139. Supercritical CO2 extraction, chemical composition, and antioxidant effects of Coreopsis tinctoria Nutt. oleoresin
  140. Functional constituents of plant-based foods boost immunity against acute and chronic disorders
  141. Effect of selenium and methods of protein extraction on the proteomic profile of Saccharomyces yeast
  142. Microbial diversity of milk ghee in southern Gansu and its effect on the formation of ghee flavor compounds
  143. Ecology and Environmental Sciences
  144. Effects of heavy metals on bacterial community surrounding Bijiashan mining area located in northwest China
  145. Microorganism community composition analysis coupling with 15N tracer experiments reveals the nitrification rate and N2O emissions in low pH soils in Southern China
  146. Genetic diversity and population structure of Cinnamomum balansae Lecomte inferred by microsatellites
  147. Preliminary screening of microplastic contamination in different marine fish species of Taif market, Saudi Arabia
  148. Plant volatile organic compounds attractive to Lygus pratensis
  149. Effects of organic materials on soil bacterial community structure in long-term continuous cropping of tomato in greenhouse
  150. Effects of soil treated fungicide fluopimomide on tomato (Solanum lycopersicum L.) disease control and plant growth
  151. Prevalence of Yersinia pestis among rodents captured in a semi-arid tropical ecosystem of south-western Zimbabwe
  152. Effects of irrigation and nitrogen fertilization on mitigating salt-induced Na+ toxicity and sustaining sea rice growth
  153. Bioengineering and Biotechnology
  154. Poly-l-lysine-caused cell adhesion induces pyroptosis in THP-1 monocytes
  155. Development of alkaline phosphatase-scFv and its use for one-step enzyme-linked immunosorbent assay for His-tagged protein detection
  156. Development and validation of a predictive model for immune-related genes in patients with tongue squamous cell carcinoma
  157. Agriculture
  158. Effects of chemical-based fertilizer replacement with biochar-based fertilizer on albic soil nutrient content and maize yield
  159. Genome-wide identification and expression analysis of CPP-like gene family in Triticum aestivum L. under different hormone and stress conditions
  160. Agronomic and economic performance of mung bean (Vigna radiata L.) varieties in response to rates of blended NPS fertilizer in Kindo Koysha district, Southern Ethiopia
  161. Influence of furrow irrigation regime on the yield and water consumption indicators of winter wheat based on a multi-level fuzzy comprehensive evaluation
  162. Discovery of exercise-related genes and pathway analysis based on comparative genomes of Mongolian originated Abaga and Wushen horse
  163. Lessons from integrated seasonal forecast-crop modelling in Africa: A systematic review
  164. Evolution trend of soil fertility in tobacco-planting area of Chenzhou, Hunan Province, China
  165. Animal Sciences
  166. Morphological and molecular characterization of Tatera indica Hardwicke 1807 (Rodentia: Muridae) from Pothwar, Pakistan
  167. Research on meat quality of Qianhua Mutton Merino sheep and Small-tail Han sheep
  168. SI: A Scientific Memoir
  169. Suggestions on leading an academic research laboratory group
  170. My scientific genealogy and the Toronto ACDC Laboratory, 1988–2022
  171. Erratum
  172. Erratum to “Changes of immune cells in patients with hepatocellular carcinoma treated by radiofrequency ablation and hepatectomy, a pilot study”
  173. Erratum to “A two-microRNA signature predicts the progression of male thyroid cancer”
  174. Retraction
  175. Retraction of “Lidocaine has antitumor effect on hepatocellular carcinoma via the circ_DYNC1H1/miR-520a-3p/USP14 axis”
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