Association of increased participation in social activity in later life with risk of all-cause mortality and heart diseases in older people: results from the Chinese Longitudinal Healthy Longevity Survey (CLHLS)

BackgroundPrevious studies have shown social activity is associated with reduced risk of health outcomes. However, among older people (≥65 years) who were socially inactive at baseline, limited study explored whether increased participation in social activity in later life was associated with reduced risk of health outcomes; therefore, using the data from the Chinese Longitudinal Healthy Longevity Survey, the study was performed.MethodsThe study outcomes were 10-year all-cause mortality (sample number = 9,984) and 10-year heart diseases (sample number = 7,496). The exposure was the change of social activity frequency. Cox regression analysis was used for data analysis.ResultsDuring the follow-up, there were 6,407 all-cause mortalities and 1,035 heart diseases, respectively. Kaplan–Meier analysis demonstrated that cumulative incidences of all-cause mortality were significantly lower in participants with changes into more frequent social activity (log-rank p < 0.001), while no significant difference was observed for heart diseases (log-rank p = 0.330). Compared with the subgroup who never participated in social activity at baseline, adjusted HRs of all-cause mortality were 0.79 (95% CI: 0.70–0.90, p < 0.001), 0.78 (95% CI: 0.63–0.96, p = 0.019), 0.74 (0.59–0.92, p = 0.006), and 0.70 (95% CI: 0.56–0.88, p = 0.002) for the subgroup of switching to sometimes, the subgroup of switching to once a month, the subgroup of switching to once a week, and the subgroup of switching to everyday, respectively. The corresponding HRs of heart diseases were 0.83 (95% CI: 0.65–1.08, p = 0.170), 0.82 (95% CI: 0.51–1.31, p = 0.412), 0.91 (0.58–1.42, p = 0.675) and 0.75 (95% CI: 0.47–1.20, p = 0.227), respectively. Stratified and sensitivity analyses revealed similar results.ConclusionAmong older people who never participated in social activity, increased participation in social activity in later life was associated with reduced risk of all-cause mortality, but was not associated with reduced risk of heart diseases

Relationships between triglyceride-glucose index and incident gestational diabetes mellitus: a prospective cohort study of a Korean population using publicly available data

BackgroundThe connection between the triglyceride-glucose index (TyG index) and gestational diabetes mellitus (GDM) is currently debated. Our study aimed to investigate the connection between the TyG index and GDM within the Korean population.MethodsUsing publically accessible data in Korea, we performed a secondary study on a sample of 589 pregnant women who were carrying a single fetus. The analysis employed a binary logistic regression model, some sensitivity analyses, and subgroup analysis to investigate the association between the TyG index and the occurrence of GDM. To assess the TyG index’s potential to predict GDM, a receiver operating characteristic (ROC) study was also carried out.ResultsThe mean age of the pregnant women was 32.065 ± 3.798 years old, while the mean TyG index was 8.352 ± 0.400. The prevalence rate of GDM was found to be 6.112%. Upon adjusting for potential confounding variables, a positive association was detected between the TyG index and incident GDM (OR = 12.923, 95%CI: 3.581–46.632, p = 0.00009). The validity of this connection was further confirmed by subgroup analysis and sensitivity analyses. With an area under the ROC curve of 0.807 (95%CI: 0.734–0.879), the TyG index showed strong predictive power for GDM. The TyG index’s ideal cutoff value for detecting GDM was found to be 8.632, with a sensitivity of 78.7% and a specificity of 72.2%.ConclusionThe findings of our study provide evidence that an increased TyG index is significantly associated with the occurrence of GDM. Utilizing the TyG index during the 10–14 week gestational period may be a valuable tool in identifying pregnant individuals at a heightened risk for developing GDM. Early detection enables timely and efficacious interventions, thereby enhancing the prognosis of affected individuals

Regulation of B-cell development and tolerance by different members of the miR-17∼1/492 family microRNAs

The molecular mechanisms that regulate B-cell development and tolerance remain incompletely understood. In this study, we identify a critical role for the miR-17∼1/492 microRNA cluster in regulating B-cell central tolerance and demonstrate that these miRNAs control early B-cell development in a cell-intrinsic manner. While the cluster member miR-19 suppresses the expression of Pten and plays a key role in regulating B-cell tolerance, miR-17 controls early B-cell development through other molecular pathways. These findings demonstrate differential control of two closely linked B-cell developmental stages by different members of a single microRNA cluster through distinct molecular pathwaysThis study is supported by the PEW Charitable Trusts, Cancer Research Institute, Lupus Research Institute and National Institute of Health (R01AI087634, R01AI089854, R56AI110403 and R56AI121155 to C.X.

Individual-based morphological brain network organization and its association with autistic symptoms in young children with autism spectrum disorder

Individual-based morphological brain networks built from T1-weighted magnetic resonance imaging (MRI) reflect synchronous maturation intensities between anatomical regions at the individual level. Autism spectrum disorder (ASD) is a socio-cognitive and neurodevelopmental disorder with high neuroanatomical heterogeneity, but the specific patterns of morphological networks in ASD remain largely unexplored at the individual level. In this study, individual-based morphological networks were constructed by using high-resolution structural MRI data from 40 young children with ASD (age range: 2-8 years) and 38 age-, gender-, and handedness-matched typically developing children (TDC). Measurements were recorded as threefold. Results showed that compared with TDC, young children with ASD exhibited lower values of small-worldness (i.e., sigma) of individual-level morphological brain networks, increased morphological connectivity in cortico-striatum-thalamic-cortical (CSTC) circuitry, and decreased morphological connectivity in the cortico-cortical network. In addition, morphological connectivity abnormalities can predict the severity of social communication deficits in young children with ASD, thus confirming an associational impact at the behavioral level. These findings suggest that the morphological brain network in the autistic developmental brain is inefficient in segregating and distributing information. The results also highlight the crucial role of abnormal morphological connectivity patterns in the socio-cognitive deficits of ASD and support the possible use of the aberrant developmental patterns of morphological brain networks in revealing new clinically-relevant biomarkers for ASD.China Postdoctoral Science Foundation, Grant/Award Number: 2019M660236; National Natural Science Foundation of China, Grant/Award Numbers: 61901129, 62036003, 81871432, U1808204; The Basque Foundation for Science and from Ministerio de Economia, Industria y Competitividad (Spain) and FEDER, Grant/Award Number: DPI2016-79874-R; the Fundamental Research Funds for the Central Universities, Grant/Award Numbers: 2672018ZYGX2018J079, ZYGX2019Z017; the Sichuan Science and Technology Program, Grant/Award Number: 2019YJ018

Molecular epizootiology of porcine reproductive and respiratory syndrome virus in the Xinjiang Uygur Autonomous Region of China

Rapid evolution of porcine reproductive and respiratory syndrome virus (PRRSV) is the bottleneck for effective prevention and control of PRRS. Thus, understanding the prevalence and genetic background of PRRSV strains in swine-producing regions is important for disease prevention and control. However, there is only limited information about the epizootiological situation of PRRS in the Xinjiang Uygur Autonomous Region, China. In this study, blood or lung tissue samples were collected from 1,411 PRRS-suspected weaned pigs from 9 pig farms in Changji, Shihezi, and Wujiaqu cities between 2020 and 2022. The samples were first tested by RT-quantitative PCR, yielding a PRRSV-2 positive rate of 53.6%. Subsequently, 36 PRRSV strains were isolated through initial adaptation in bone marrow-derived macrophages followed by propagation in grivet monkey Marc-145 cells. Furthermore, 28 PRRSV-positive samples and 20 cell-adapted viruses were selected for high-throughput sequencing (HTS) to obtain the entire PRRSV genome sequences. Phylogenetic analysis based on the nucleotide sequences of the ORF5 gene of the PRRSV strains identified in this study grouped into sub-lineages 1.8 and 8.7 the former being the dominant strain currently circulating in Xinjiang. However, the NSP2 proteins of the Xinjiang PRRSV strains shared the same deletion patterns as sub-lineage 1.8 prototype strain NADC30 with the exception of 4 strains carrying 2-3 additional amino acid deletions. Further analysis confirmed that recombination events had occurred in 27 of 37 PRRSVs obtained here with the parental strains belonging to sub-lineages 1.8 and 8.7, lineages 3 and 5, with the recombination events having occurred most frequently in the 5' and 3' termini of ORF1a and 5' terminus of ORF1b

Metformin improves polycystic ovary syndrome in mice by inhibiting ovarian ferroptosis

Background and objectivePCOS is a common metabolic disorder in women of reproductive age, which pathogenesis is very complex. The role of ferroptosis in PCOS is a novel finding, and the mechanistic studies are not clear. Metformin is a commonly used drug of PCOS but few studies on whether metformin can improve the follicle development and ovarian function in PCOS. We aims to use PCOS mouse model to study the effect of metformin on PCOS based on the ovarian function and explored the regulation of metformin in PCOS mice by intervening in ferroptosis pathway.Materials and methodsC57 BL/6J female mice aged 4-5 weeks were purchased and gavaged with letrozole (1 mg/kg/day) combined with high-fat diet for 21days to establish PCOS model, and control group was set up. After modeling, the mice were divided into PCOS model group and metformin treatment group (Met) (n=6).The Met group were gavaged metformin (200 mg/kg/day) for 28 days. The body weight, estrous cycle, glucose tolerance test (OGTT)and insulin resistance test (ITT) were monitored. Then, The mice were euthanized to collect serum and ovaries. Elisa was used to detect changes in related serum hormones (E2, LH, FSH, TP). Ovaries used for molecular biology experiments to detect changes in GPX4, SIRT3, AMPK/p-AMPK, and mTOR/p-mTOR by Western blot and qPCR.ResultsCompared with the model group mice, body weight was significantly reduced, and their estrous cycle was restored in Met group. The results of OGTT and ITT showed an improvment of glucose tolerance and insulin resistance. Morphological results showed that after metformin treatment, polycystic lesions in ovaries were reduced, the ovarian function was restored, and the expressions of SIRT3 and GPX4 were elevated. WB results demonstrated that the expressions of p-mTOR and p-AMPK in ovaries were significantly reduced in Model group, but reversed in MET group.ConclusionOur study confirmed metformin could not only improve body weight and metabolism disorders, but also improve ovarian dysfunction in PCOS mice.In addition, we explored metformin could regulate ferroptosis to improve PCOS via the SIRT3/AMPK/mTOR pathway. Our study complements the mechanisms by which metformin improves PCOS

Zinc finger and SCAN domain containing 1, ZSCAN1, is a novel stemness-related tumor suppressor and transcriptional repressor in breast cancer targeting TAZ

IntroductionCancer stem cells (CSCs) targeted therapy holds the potential for improving cancer management; identification of stemness-related genes in CSCs is necessary for its development.MethodsThe Cancer Genome Atlas (TCGA) and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) datasets were used for survival analysis. ZSCAN1 correlated genes was identified by Spearman correlation analysis. Breast cancer stem-like cells (BCSLCs) were isolated by sorting CD44+CD24- cells from suspension cultured breast cancer (BC) spheroids. The sphere-forming capacity and sphere- and tumor-initiating capacities were determined by sphere formation and limiting dilution assays. The relative gene expression was determined by qRT-PCR, western blot. Lentivirus system was used for gene manipulation. Nuclear run-on assay was employed to examine the levels of nascent mRNAs. DNA pull-down and Chromatin immunoprecipitation (ChIP) assays were used for determining the interaction between protein and target DNA fragments. Luciferase reporter assay was used for evaluating the activity of the promoter.Results and discussionZSCAN1 is aberrantly suppressed in BC, and this suppression indicates a bad prognosis. Ectopic expression of ZSCAN1 inhibited the proliferation, clonogenicity, and tumorigenicity of BC cells. ZSCAN1-overexpressing BCSLCs exhibited weakened stemness properties. Normal human mammary epithelial (HMLE) cells with ZSCAN1 depletion exhibited enhanced stemness properties. Mechanistic studies showed that ZSCAN1 directly binds to -951 ~ -925bp region of WWTR1 (encodes TAZ) promoter, inhibits WWTR1 transcription, thereby inhibiting the stemness of BCSCs. Our work thus revealed ZSCAN1 as a novel stemness-related tumor suppressor and transcriptional repressor in BC

Inhibition of HIV-1 entry by extracts derived from traditional Chinese medicinal herbal plants

<p>Abstract</p> <p>Background</p> <p>Highly active anti-retroviral therapy (HAART) is the current HIV/AIDS treatment modality. Despite the fact that HAART is very effective in suppressing HIV-1 replication and reducing the mortality of HIV/AIDS patients, it has become increasingly clear that HAART does not offer an ultimate cure to HIV/AIDS. The high cost of the HAART regimen has impeded its delivery to over 90% of the HIV/AIDS population in the world. This reality has urgently called for the need to develop inexpensive alternative anti-HIV/AIDS therapy. This need has further manifested by recent clinical trial failures in anti-HIV-1 vaccines and microbicides. In the current study, we characterized a panel of extracts of traditional Chinese medicinal herbal plants for their activities against HIV-1 replication.</p> <p>Methods</p> <p>Crude and fractionated extracts were prepared from various parts of nine traditional Chinese medicinal herbal plants in Hainan Island, China. These extracts were first screened for their anti-HIV activity and cytotoxicity in human CD4+ Jurkat cells. Then, a single-round pseudotyped HIV-luciferase reporter virus system (HIV-Luc) was used to identify potential anti-HIV mechanisms of these extracts.</p> <p>Results</p> <p>Two extracts, one from <it>Euphorbiaceae</it>, <it>Trigonostema xyphophylloides </it>(TXE) and one from <it>Dipterocarpaceae</it>, <it>Vatica astrotricha </it>(VAD) inhibited HIV-1 replication and syncytia formation in CD4+ Jurkat cells, and had little adverse effects on host cell proliferation and survival. TXE and VAD did not show any direct inhibitory effects on the HIV-1 RT enzymatic activity. Treatment of these two extracts during the infection significantly blocked infection of the reporter virus. However, pre-treatment of the reporter virus with the extracts and treatment of the extracts post-infection had little effects on the infectivity or gene expression of the reporter virus.</p> <p>Conclusion</p> <p>These results demonstrate that TXE and VAD inhibit HIV-1 replication likely by blocking HIV-1 interaction with target cells, i.e., the interaction between gp120 and CD4/CCR5 or gp120 and CD4/CXCR4 and point to the potential of developing these two extracts to be HIV-1 entry inhibitors.</p