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Background: Kashin-Beck disease (KBD) is an endemic osteoarthropathy characterized by excessive chondrocytes apoptosis. T-2 toxin exposure has been proved to be its etiology. Connective tissue growth factor (CTGF) exerts a profound influence on cartilage growth and metabolism. We investigated the potential role of CTGF in KBD development and examined CTGF alterations under T-2 toxin stimulation. Methods: The levels of CTGF and chondrocyte apoptosis-related markers in cartilage and primary chondrocytes from KBD and control groups were measured using qRT-PCR, Western blotting, immunohistochemistry, and immunofluorescence. We analyzed expression changes of these genes in response to T-2 toxin. Apoptosis rates of chondrocytes induced by T-2 toxin were measured by flow cytometry and TUNEL assay. The active pharmaceutical ingredient targeting CTGF was screened through Comparative Toxicogenomics Database, and molecular docking was performed using AutoDock Tools. Results: The CTGF levels in KBD cartilage and chondrocytes were significantly elevated and positively associated with the levels of apoptosis-related genes. T-2 toxin exposure increased CTGF and apoptosis-related gene levels in chondrocytes, with apoptosis rates rising alongside T-2 toxin concentration. Curcumin was identified as targeting CTGF and exhibited effective binding. It could down-regulate CTGF, apoptosis-related genes, such as Cleaved caspase 3 and BAX, and also significantly reduce apoptosis rate in chondrocytes treated with T-2 toxin. Conclusion: CTGF plays a crucial role in the development of KBD. Curcumin has shown potential in inhibiting CTGF levels and reducing chondrocyte apoptosis, highlighting its promise as a therapeutic agent for preventing cartilage damage in KBD. Our findings provided valuable insights into the pathogenesis of KBD and could promote the development of novel therapeutic strategies for this debilitating disease.

Background: Genetic factors and environmental exposures, including air pollution, contribute to the risk of depression and anxiety. While the association between air pollution and depression and anxiety has been established in the UK Biobank, there has been limited research exploring this relationship from a genetic perspective. Methods: Based on individual genotypic and phenotypic data from a cohort of 104,385 participants in the UK Biobank, a polygenic risk score for depression and anxiety was constructed to explore the joint effects of nitric oxide (NO), nitrogen dioxide (NO2), particulate matter (PM) with a diameter of ⩽2.5 μm (PM2.5) and 2.5–10 μm (PMcoarse) with depression and anxiety by linear and logistic regression models. Subsequently, a genome-wide gene-environmental interaction study (GWEIS) was performed using PLINK 2.0 to identify the genes interacting with air pollution for depression and anxiety. Results: A substantial risk of depression and anxiety development was detected in participants exposed to the high air pollution concomitantly with high genetic risk. GWEIS identified 166, 23, 18, and 164 significant candidate loci interacting with NO, NO2, PM2.5, and PMcoarse for Patient Health Questionnaire-9 (PHQ-9) score, and detected 44, 10, 10, and 114 candidate loci associated with NO, NO2, PM2.5, and PMcoarse for General Anxiety Disorder (GAD-7) score, respectively. And some significant genes overlapped among four air pollutants, like TSN (rs184699498, PNO2 = 3.47 × 10−9; rs139212326, PPM2.5 = 1.51 × 10−8) and HSP90AB7P(rs150987455, PNO2 = 1.63 × 10−11; rs150987455, PPM2.5 = 7.64 × 10−11), which were common genes affecting PHQ-9 score for both NO2 and PM2.5. Conclusion: Our study identified the joint effects of air pollution with genetic susceptibility on the risk of depression and anxiety, and provided several novel candidate genes for the interaction, contributing to an understanding of the genetic architecture of depression and anxiety.

Heart failure (HF) is a complex clinical syndrome with impaired ventricular ability due to structural or functional cardiac disorders. A traditional Chinese formula named Xinshubao tablet (XSB) is reported to protect cardiomyocytes and decrease the risk of HF clinically; however, the underlying mechanism of XSB on decreasing HF risk is not elucidated yet. Therefore, our study aimed to investigate the therapeutic efficacy and underlying mechanism of XSB by using HF model rats and H9c2 cells with oxygen glucose deprivation. Echocardiographic and pathological features of animal experiment showed that XSB treatment effectively improved cardiac function and ameliorated myocardial injury after 4 weeks of treatment. Cellular experiments indicated that XSB pretreatment significantly inhibited apoptosis and increased mitochondrial energy metabolism. Furthermore, in vivo and in vitro experiments both demonstrated that XSB suppressed oxidative stress and inflammatory response. Our results further revealed that the potential protective mechanism of XSB was closely associated with the DCN/PPARα/PGC-1α/P300 signaling pathway. Our findings provide novel mechanistic insights for HF treatment and a pharmacological basis for the therapeutic application of XSB against cardiovascular disorders.

Regulating the catalytic activity of nanozymes is significant for their applications in various fields. Here, we demonstrate a new strategy to achieve reversible regulation of the nanozyme's activity for sensing purpose. This strategy involves the use of zero-dimensional MoS2 quantum dots (MQDs) as the building blocks of nanozymes which display very weak peroxidase (POD)-like activity. Interestingly, such POD-like activity of the MQDs largely enhances in the presence of Fe3+ while diminishes with the addition of captopril thereafter. Further investigations identify the mechanism of Fe3+-mediated aggregation-induced enhancement of the POD-like activity and the inhibitory effect of captopril on the enhancement, which is highly dependent on their concentrations. Based on this finding, a colorimetric method for the detection of captopril is developed. This sensing approach exhibits the merits of simplicity, rapidness, reliability, and low cost, which has been successfully applied in quality control of captopril in pharmaceutical products. Moreover, the present sensing platform allows smartphone read-out, which has promising applications in point-of-care testing devices for clinical diagnosis and drug analysis.

Background: Gut microbiome and inflammatory bowel disease (IBD) are implicated in the development of depression, but the effect of their interactions on the risk of depression remains unclear. We aim to analyze the effect of interactions between gut microbiome and IBD on the risk of depression, and explore candidate genes involving the interactions. Methods: Using the individual genotype and depression traits data from the UK Biobank, we calculated the polygenetic risk scores (PRS) of 114 gut microbiome, ulcerative colitis (UC), Crohn's disease (CD), and total IBD (CD + UC) respectively. The effects of interactions between gut microbiome and IBD on depression were assessed through a linear regression model. Moreover, for observed significant interactions between gut microbiome PRS and IBD PRS, PLINK software was used to test pair-wise single nucleotide polymorphisms (SNPs) interaction of corresponding gut microbiome PRS and IBD PRS on depression. Results: We found 64 candidate interactions between gut microbiome and IBD on four phenotypes of depression, such as F_Lachnospiraceae (RNT) × (CD + UC) for patient health questionnaire-9 (PHQ-9) score (P = 1.48 × 10−3), F_Veillonellaceae (HB) × UC for self-reported depression (P = 2.83 × 10−3) and P_Firmicutes (RNT) × CD for age at first episode of depression (P = 8.50 × 10−3). We observed interactions of gut-microbiome-associated SNPs × IBD-associated SNPs, such as G_Alloprevotella (HB)-associated rs147650986 (GPM6A) × IBD-associated rs114471990 (QRICH1) (P = 2.26 × 10−4). Conclusion: Our results support the effects of interactions between gut microbiome and IBD on depression risk, and reported several novel candidate genes for depression.

Primary central nervous system lymphoma (PCNSL) is a group of extranodal non-Hodgkin lymphoma that exhibits specific biological characteristics and clinical behavior, with an aggressive disease course and unsatisfactory patient outcomes. It is of great importance to identify aberrant genetic loci and important molecular pathways that might suggest potential targets for new therapeutics and provide prognostic information. In this review, we listed various genetic and epigenetic alterations that are involved in PCNSL pathogenesis. In the aspect of treatment, we summarized the related literatures and evaluated the efficacy of surgery, induction chemotherapy, radiotherapy, intrathecal chemotherapy, and autologous stem cell transplantation in PCNSL. We also proposed the possible new agents for recurrent and relapse PCNSL based on the result of recent clinical researches.

Few data are available on the risk of SAEs in corticosteroid users in IgAN populations. We describe the prevalence and risk factors of corticosteroid-related SAEs in a Chinese cohort. Methods: A total of 1034 IgAN patients were followed up in our renal center from 2003 to 2014. Prevalence of corticosteroid use and corticosteroid-related SAEs were noted. Logistic regression was used to search for risk factors of SAEs in corticosteroid users. Results: Of the 369 patients with steroids therapy, 46 patients (12.5%) with 58 events suffered SAEs, whereas only 18 patients (2.7%) without corticosteroids suffered SAEs (OR: 5.45; 95% CI: 3.07–9.68; P