Bioinformatics-based analysis of the roles of basement membrane-related gene AGRN in systemic lupus erythematosus and pan-cancer development

IntroductionSystemic lupus erythematosus (SLE) is an autoimmune disease involving many systems and organs, and individuals with SLE exhibit unique cancer risk characteristics. The significance of the basement membrane (BM) in the occurrence and progression of human autoimmune diseases and tumors has been established through research. However, the roles of BM-related genes and their protein expression mechanisms in the pathogenesis of SLE and pan-cancer development has not been elucidated.MethodsIn this study, we applied bioinformatics methods to perform differential expression analysis of BM-related genes in datasets from SLE patients. We utilized LASSO logistic regression, SVM-RFE, and RandomForest to screen for feature genes and construct a diagnosis model for SLE. In order to attain a comprehensive comprehension of the biological functionalities of the feature genes, we conducted GSEA analysis, ROC analysis, and computed levels of immune cell infiltration. Finally, we sourced pan-cancer expression profiles from the TCGA and GTEx databases and performed pan-cancer analysis.ResultsWe screened six feature genes (AGRN, PHF13, SPOCK2, TGFBI, COL4A3, and COLQ) to construct an SLE diagnostic model. Immune infiltration analysis showed a significant correlation between AGRN and immune cell functions such as parainflammation and type I IFN response. After further gene expression validation, we finally selected AGRN for pan-cancer analysis. The results showed that AGRN’s expression level varied according to distinct tumor types and was closely correlated with some tumor patients’ prognosis, immune cell infiltration, and other indicators.DiscussionIn conclusion, BM-related genes play a pivotal role in the pathogenesis of SLE, and AGRN shows immense promise as a target in SLE and the progression of multiple tumors

Theabrownin ameliorates liver inflammation, oxidative stress, and fibrosis in MCD diet-fed C57BL/6J mice

IntroductionNonalcoholic steatohepatitis (NASH), also known as metabolic steatohepatitis, is a clinical syndrome with pathological changes like alcoholic hepatitis but without a history of excessive alcohol consumption. NASH is closely related to metabolic disorders such as obesity, insulin resistance, type 2 diabetes mellitus, and hyperlipidemia. Its main characteristics are hepatocyte steatosis with hepatocyte injury and inflammation. In severe cases, it can develop into liver cirrhosis. At present, there is no special treatment for NASH. Theabrownin (TB) is the main pigment substance in fermented tea. Theabrownin has beneficial effects on lipid metabolism and intestinal flora. However, the effect of theabrownin on NASH has not been studied. MethodsThis study was aimed at exploring the effects of theabrownin from Fuzhuan brick tea on NASH. 8-week-old mice were randomly assigned to three groups and fed with chow diet (CD), methionine and choline sufficient (MCS) diet (MCS Ctrl), which is a Methionine/choline deficient (MCD) control diet, and MCD diet. After 5 weeks of feeding, the MCD group mice were randomly divided into two groups and were gavaged with double distilled water (MCD Ctrl) or theabrownin (MCD TB) (200mg/kg body weight, dissolved in double distilled water) every day for another 4 weeks respectively, while continuing MCD diet feeding.ResultsWe found that theabrownin treatment could not improve liver mass loss and steatosis. However, theabrownin ameliorated liver injury and decreased liver inflammatory response. Theabrownin also alleviated liver oxidative stress and fibrosis. Furthermore, our results showed that theabrownin increased hepatic level of fibroblast growth factor 21 (FGF21) and reduced the phosphorylation of mitogen-activated protein kinase p38 in MCD diet-fed mice

Genome-wide Association Study Identifies New Loci Associated With Risk Of HBV Infection And Disease Progression

Background: Recent studies have identified susceptibility genes of HBV clearance, chronic hepatitis B, liver cirrhosis, hepatocellular carcinoma, and showed the host genetic factors play an important role in these HBV-related outcomes. Results: In order to discover new susceptibility genes for HBV-related outcomes, we conducted a genome-wide association study in 1031 Chinese participants, including 275 HBV clearance subjects, 92 asymptomatic persistence infection carriers (ASPI), 93 chronic hepatitis B patients (CHB), 188 HBV-related decompensated cirrhosis patients (DC), 214 HBV-related hepatocellular carcinoma patients (HCC) and 169 healthy controls (HC). In the case-control study, we observed novel locus significantly associated with CHB (SNP: rs1264473, Gene: GRHL2, P = 1.57×10-6) and HCC (SNP: rs2833856, Gene: EVA1C, P = 1.62×10-6; SNP: rs4661093, Gene: ETV3, P = 2.26×10-6). In the trend study across progressive stages post HBV infection, one novel locus (SNP: rs1537862, Gene: LACE1, P = 1.85×10-6), and three MHC loci (HLA-DRB1, HLA-DPB1, HLA-DPA2) showed significant increased progressive risk from ASPI to CHB. Interestingly, underlying the evolutionary study of HBV-related genes in public database, we found that the derived allele of two HBV clearance related locus, rs3077 and rs9277542, are under strong selection in European population. Conclusions: In this study, we identified several novel candidate genes associated with individual HBV infectious outcomes, progressive stages, and liver enzymes. Moreover, we identified two SNPs that show selective significance (HLA-DPA1, HLA-DPB1) in non-East Asian (European, American, South Asian) versus East Asian, indicating that host genetic factors contribute to the ethnic disparities of susceptibility of HBV infection. Taken together, these findings provided a new insight into the role of host genetic factors in HBV related outcomes and progression

Response of soil bacterial communities in wheat rhizosphere to straw mulching and N fertilization

Straw mulching and N fertilization are effective in augmenting crop yields. Since their combined effects on wheat rhizosphere bacterial communities remain largely unknown, our aim was to assess how the bacterial communities respond to these agricultural measures. We studied wheat rhizosphere microbiomes in a split-plot design experiment with maize straw mulching (0 and 8,000 kg straw ha−1) as the main-plot treatment and N fertilization (0, 120 and 180 kg N ha−1) as the sub-plot treatment. Bacterial communities in the rhizosphere were analyzed using 16S rRNA gene amplicon sequencing and quantitative PCR. Most of the differences in soil physicochemical properties and rhizosphere bacterial communities were detected between the straw mulching (SM) and no straw mulching (NSM) treatments. The contents of soil organic C (SOC), total N (TN), NH4+-N, available N (AN), available P (AP) and available K (AK) were higher with than without mulching. Straw mulching led to greater abundance, diversity and richness of the rhizosphere bacterial communities. The differences in bacterial community composition were related to differences in soil temperature and SOC, AP and AK contents. Straw mulching altered the soil physiochemical properties, leading to greater bacterial diversity and richness of the rhizosphere bacterial communities, likely mostly due to the increase in SOC content that provided an effective C source for the bacteria. The relative abundance of Proteobacteria was high in all treatments and most of the differentially abundant OTUs were proteobacterial. Multiple OTUs assigned to Acidobacteria, Chloroflexi and Actinobacteria were enriched in the SM treatment. Putative plant growth promoters were enriched both in the SM and NSM treatments. These findings indicate potential strategies for the agricultural management of soil microbiomes

Choroidal Thickness in the Subtypes of Angle Closure: An EDI-OCT Study

PURPOSE. To evaluate choroidal thickness (CT) in the subtypes of angle-closure (AC) disease compared with CT in a healthy control. METHODS. A total of 297 subjects (eyes) were enrolled in the study: 87 were nonglaucoma controls and 210 were AC subtype eyes (primary AC suspect [PACS] Enhanced depth imaging spectral-domain optical coherence tomography (EDI-OCT) was used to measure the macular CT in the subtypes of AC disease and in healthy control subjects. The average CT was compared among the five groups. RESULTS. Thinner CT was associated with older age and longer axial length (AL) (all P < 0.001). All AC groups had thicker subfoveal CT (SFCT) compared with the control eyes (all P < 0.05), even after controlling for age and the AL factor. Acute primary angle-closure eyes had the thickest SFCT and were 61.9-lm thicker than healthy eyes, while PACS, PAC, and PACG eyes were 32.9-, 30.9-, and 25.4-lm thicker than healthy eyes, respectively. No significant difference was observed among the PACS, PAC, and PACG groups. CONCLUSIONS. Increased CT might be another anatomic characteristic of AC eyes. These findings may support the hypotheses that choroidal expansion is a contributing factor to the development of AC disease

Multi-Scale Modeling for Predicting the Stiffness and Strength of Hollow-Structured Metal Foams with Structural Hierarchy

This work was inspired by previous experiments which managed to establish an optimal template-dealloying route to prepare ultralow density metal foams. In this study, we propose a new analytical–numerical model of hollow-structured metal foams with structural hierarchy to predict its stiffness and strength. The two-level model comprises a main backbone and a secondary nanoporous structure. The main backbone is composed of hollow sphere-packing architecture, while the secondary one is constructed of a bicontinuous nanoporous network proposed to describe the nanoscale interactions in the shell. Firstly, two nanoporous models with different geometries are generated by Voronoi tessellation, then the scaling laws of the mechanical properties are determined as a function of relative density by finite volume simulation. Furthermore, the scaling laws are applied to identify the uniaxial compression behavior of metal foams. It is shown that the thickness and relative density highly influence the Young’s modulus and yield strength, and vacancy defect determines the foams being self-supported. The present study provides not only new insights into the mechanical behaviors of both nanoporous metals and metal foams, but also a practical guide for their fabrication and application

Isolation and Mechanistic Characterization of a Novel Zearalenone-Degrading Enzyme

Zearalenone (ZEN) and its derivatives pose a serious threat to global food quality and animal health. The use of enzymes to degrade mycotoxins has become a popular method to counter this threat. In this study, Aspergillus niger ZEN-S-FS10 extracellular enzyme solution with ZEN-degrading effect was separated and purified to prepare the biological enzyme, FSZ, that can degrade ZEN. The degradation rate of FSZ to ZEN was 75–80% (pH = 7.0, 28 °C). FSZ can function in a temperature range of 28–38 °C and pH range of 2.0–7.0 and can also degrade ZEN derivatives (α-ZAL, β-ZOL, and ZAN). According to the enzyme kinetics fitting, ZEN has a high degradation rate. FSZ can degrade ZEN in real samples of corn flour. FSZ can be obtained stably and repeatedly from the original strain. One ZEN degradation product was isolated: FSZ−P(C18H26O4), with a relative molecular weight of 306.18 g/mol. Amino-acid-sequencing analysis revealed that FSZ is a novel enzyme (homology < 10%). According to the results of molecular docking, ZEN and ZAN can utilize their end-terminal carbonyl groups to bind FSZ residues PHE307, THR55, and GLU129 for a high-degradation rate. However, α-ZAL and β-ZOL instead contain hydroxyl groups that would prevent binding to GLU129; thus, the degradation rate is low for these derivatives