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Abstract Background Previous studies have shown the association between tuberculosis (TB) and meteorological factors/air pollutants. However, little information is available for people living with HIV/AIDS (PLWHA), who are highly susceptible to TB. Method Data regarding TB cases in PLWHA from 2014 to2020 were collected from the HIV antiviral therapy cohort in Guangxi, China. Meteorological and air pollutants data for the same period were obtained from the China Meteorological Science Data Sharing Service Network and Department of Ecology and Environment of Guangxi. A distribution lag non-linear model (DLNM) was used to evaluate the effects of meteorological factors and air pollutant exposure on the risk of TB in PLWHA. Results A total of 2087 new or re-active TB cases were collected, which had a significant seasonal and periodic distribution. Compared with the median values, the maximum cumulative relative risk (RR) for TB in PLWHA was 0.663 (95% confidence interval [CI]: 0.507–0.866, lag 4 weeks) for a 5-unit increase in temperature, and 1.478 (95% CI: 1.116–1.957, lag 4 weeks) for a 2-unit increase in precipitation. However, neither wind speed nor PM10 had a significant cumulative lag effect. Extreme analysis demonstrated that the hot effect (RR = 0.638, 95%CI: 0.425–0.958, lag 4 weeks), the rainy effect (RR = 0.285, 95%CI: 0.135–0.599, lag 4 weeks), and the rainless effect (RR = 0.552, 95%CI: 0.322–0.947, lag 4 weeks) reduced the risk of TB. Furthermore, in the CD4(+) T cells

BackgroundPrevious studies showed the conflicting associations between circulating micronutrient levels and systemic lupus erythematosus (SLE). Therefore, we aimed to clarify the causal association between circulating micronutrient levels and the risk of SLE by two-sample Mendelian randomization (MR) analysis.Methods56 single nucleotide polymorphisms (SNPs) significantly associated with 14 circulating micronutrients (vitamin A, B6, B9, B12, C, D and E, phosphorus, calcium, magnesium, copper, iron, zinc, and selenium) in published genome-wide association studies (GWAS) were used as instrumental variables (IVs). And summary statistics related to SLE were obtained from the IEU OpenGWAS database. We used the MR Steiger test to estimate the possible causal direction between circulating micronutrients and SLE. In the MR analysis, inverse variance weighting (IVW) method and the Wald ratio was as the main methods., Moreover, the MR-Pleiotropy residuals and outliers method (MR-PRESSO), Cochrane’s Q-test, MR-Egger intercept method and leave-one-out analyses were applied as sensitivity analyses. Additionally, we conducted a retrospective analysis involving the 20,045 participants from the Third National Health and Nutritional Examination Survey (NHANES III). Weight variables were provided in the NHANES data files. Univariate and multivariate logistic regression analyses were performed to determine the associations between circulating micronutrients and SLE.ResultsThe MR estimates obtained from the IVW method revealed potential negative correlations between circulating calcium (OR: 0.06, 95% CI: 0.01–0.49, P = 0.009), iron levels (OR: 0.63, 95% CI: 0.43–0.92, P = 0.016) and the risk of SLE. The results remained robust, even under various pairs of sensitivity analyses. Our retrospective analysis demonstrated that the levels of vitamin D, serum total calcium, and serum iron were significantly lower in SLE patients (N = 40) when compared to the control group (N = 20,005). Multivariate logistic regression analysis further established that increased levels of vitamin D and serum total calcium served as protective factors against SLE.ConclusionOur results provided genetic evidence supporting the potential protective role of increasing circulating calcium in the risk of SLE. Maintaining adequate levels of calcium may help reduce the risk of SLE.

Abstract Background Growing evidence from observational studies and clinical trials suggests that the gut microbiota is associated with tuberculosis (TB). However, it is unclear whether any causal relationship exists between them and whether causality is bidirectional. Methods A bidirectional two-sample Mendelian randomization (MR) analysis was performed. The genome-wide association study (GWAS) summary statistics of gut microbiota were obtained from the MiBioGen consortium, while the GWAS summary statistics of TB and its specific phenotypes [respiratory tuberculosis (RTB) and extrapulmonary tuberculosis (EPTB)] were retrieved from the UK Biobank and the FinnGen consortium. And 195 bacterial taxa from phylum to genus were analyzed. Inverse variance weighted (IVW), MR-Egger regression, maximum likelihood (ML), weighted median, and weighted mode methods were applied to the MR analysis. The robustness of causal estimation was tested using the heterogeneity test, horizontal pleiotropy test, and leave-one-out method. Results In the UK Biobank database, we found that 11 bacterial taxa had potential causal effects on TB. Three bacterial taxa genus.Akkermansia, family.Verrucomicrobiacea, order.Verrucomicrobiales were validated in the FinnGen database. Based on the results in the FinnGen database, the present study found significant differences in the characteristics of gut microbial distribution between RTB and EPTB. Four bacterial taxa genus.LachnospiraceaeUCG010, genus.Parabacteroides, genus.RuminococcaceaeUCG011, and order.Bacillales were common traits in relation to both RTB and TB, among which order.Bacillales showed a protective effect. Additionally, family.Bacteroidacea and genus.Bacteroides were identified as common traits in relation to both EPTB and TB, positively associating with a higher risk of EPTB. In reverse MR analysis, no causal association was identified. No significant heterogeneity of instrumental variables (IVs) or horizontal pleiotropy was found. Conclusion Our study supports a one-way causal relationship between gut microbiota and TB, with gut microbiota having a causal effect on TB. The identification of characteristic gut microbiota provides scientific insights for the potential application of the gut microbiota as a preventive, diagnostic, and therapeutic tool for TB.

BackgroundCardiovascular diseases (CVD) and type 2 diabetes (T2D) account for the majority of the burden of noncommunicable disease caused by low physical activity (LPA). In order to inform future interventions, this study aims to assess the burden and trends in mortality and disability-adjusted life years (DALYs) of CVD and T2D attributable to LPA by year, location, sex, and age from 1990 to 2019.MethodsMortality, DALYs, and their age-standardised rates (ASMR, ASDR) for CVD and T2D attributable to LPA were retrieved from Global Burden of Disease (GBD) 2019. The estimated annual percentage changes (EAPCs) were calculated using linear regression model to describe the trend over time.ResultsFrom 1990 to 2019, the number of deaths caused by both CVD and T2D due to LPA increased significantly globally. However, the overall ASMR and ASDR for CVD declined over this same period [EAPC for ASMR (CVD) = −1.44 (95% CI: −1.50–1.38), EAPC for ASDR (CVD) = −1.30 (95% CI: −1.35 to −1.25)]. In terms of disparities, ASMR (CVD) and ASDR (CVD) in North Africa and the Middle East were consistently higher than the global average; also, the sex difference in ASMR was greatest in Central Asia. ASMR among people aged 25–44 in high Socio-Demographic Index (SDI) region has increased significantly over the past three decades. ASMR (T2D) due to LPA showed an increasing trend year by year, with EAPC = 0.26 (95% CI: 0.13–0.39), and this rate increased faster in males than in females. Consistent with cardiovascular diseases, ASMR of type 2 diabetes attributable to LPA increased among people aged 25–44, while decreased in other age groups in high SDI region.ConclusionInterventions targeting LPA are warranted in controlling the burden of cardiovascular diseases and type 2 diabetes. Countries should adapt strategies to their local contexts, considering the sex and age differences among their populations. The 25–44 age group should be given special attention to prevent the disease burden from worsening among younger people.

The type VI secretion system was recently reported to be involved in zinc acquisition, but the underlying mechanism remains unclear. Here, we report that Burkholderia thailandensis T6SS4 is involved in zinc acquisition via secretion of a zinc-scavenging protein, TseZ, that interacts with the outer membrane heme transporter HmuR. We find that HmuR is a redox-regulated dual-functional transporter that transports heme iron under normal conditions but zinc upon sensing extracellular oxidative stress, triggered by formation of an intramolecular disulfide bond. Acting as the first line of defense against oxidative stress, HmuR not only guarantees an immediate response to the changing environment but also provides a fine-tuned mechanism that allows a gradual response to perceived stress. The T6SS/HmuR-mediated active zinc transport system is also involved in bacterial virulence and contact-independent bacterial competition. We describe a sophisticated bacterial zinc acquisition mechanism affording insights into the role of metal ion transport systems.

Abstract The transition between the planktonic state and the biofilm-associated state is a key developmental decision for pathogenic bacteria. Biofilm formation by Yersinia pestis is regulated by hmsHFRS genes (β-1, 6-N-acetyl-D-glucosamine synthesis operon) in its flea vector and in vitro. However, the mechanism of biofilm formation in Yersinia pseudotuberculosis remains elusive. In this study, we demonstrate that the LysR-type regulator RovM inversely regulates biofilm formation and motility in Y. pseudotuberculosis by acting as a transcriptional regulator of these two functions. RovM is strongly induced during growth in minimal media but strongly repressed in complex media. On one hand, RovM enhances bacterial motility by activating the expression of FlhDC, the master regulator of flagellar genes, via the recognition of an operator upstream of the flhDC promoter. On the other hand, RovM represses β-GlcNAc production under nutrition-limited conditions, negatively regulating hmsHFRS expression by directly binding to the −35 element of its promoter. Compared to wild-type bacteria, the rovM mutant established denser biofilms and caused more extensive mortality in mice and silkworm larvae. These results indicate that RovM acts as a molecular switch to coordinate the expression of genes involved in biofilm formation and motility in response to the availability of nutrients.