Measuring General Health Literacy in Chinese adults: validation of the HLS19-Q12 instrument.

BACKGROUND: Health literacy measurement lays a solid foundation to identify associations with health outcomes and monitor population health literacy levels over time. In mainland China, most existing health literacy instruments are either knowledge-based or practice-based, making health literacy results incomparable between China and other countries. This study aimed to examine the reliability and validity of the 12-item Health Literacy Population Survey (HLS19-Q12) in a general population of Chinese adults. METHODS: A cross-sectional study was conducted to recruit primary carers of students from 11 schools in Zhengzhou, Henan Province, using convenience cluster sampling. Participants completed an online self-administered survey that collected information on key sociodemographics, health literacy (HLS19-Q12 and a comparison tool: Health Literacy Questionnaire (HLQ)), and health-related outcomes. Using the COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) checklist as a guideline, we tested internal consistency, test-retest reliability, content validity, structural validity, concurrent predictive validity, and convergent validity of the HLS19-Q12. RESULTS: Overall, 14,184 participants completed the full survey. The HLS19-Q12 showed excellent internal consistency (Cronbach's α = 0.93), moderate test-retest reliability (intra-class correlation coefficient = 0.54), satisfactory content validity (based on the 12-matrix health literacy model), and strong structural validity (comparative fit index = 0.94, Tucker and Lewis's index of fit = 0.93, root mean square error of approximation = 0.095). Concurrent predictive validity results showed health literacy was associated with both health determinants and health-related outcomes. The HLS19-Q12 had weak to strong correlations (coefficients = 0.24 to 0.42) with the nine scales of the HLQ. Respondents had an average score of 81.6 (± 23.0) when using the HLS19-Q12, with 35.0% and 7.5% having problematic and inadequate levels of health literacy, respectively. CONCLUSIONS: The HLS19-Q12 is a reliable and valid instrument to measure health literacy in our sample. Further validation is needed with a more nationally representative sample of Chinese adults. The HLS19-Q12 could be used as a comprehensive, skills-based, and easy-to-administer health literacy assessment tool integrated into population surveys and intervention evaluations.

Lifestyle behaviors and risk of cardiovascular disease and prognosis among individuals with cardiovascular disease: a systematic review and meta-analysis of 71 prospective cohort studies.

BACKGROUND: Healthy lifestyle behaviors (LBs) have been widely recommended for the prevention and management of cardiovascular disease (CVD). Despite a large number of studies exploring the association between combined LBs and CVD, a notable gap exists in integration of relevant literatures. We conducted a systematic review and meta-analysis of prospective cohort studies to analyze the correlation between combined LBs and the occurrence of CVD, as well as to estimate the risk of various health complications in individuals already diagnosed with CVD. METHODS: Articles published up to February 10, 2023 were sourced through PubMed, EMBASE and Web of Science. Eligible prospective cohort studies that reported the relations of combined LBs with pre-determined outcomes were included. Summary relative risks (RRs) and 95% confidence intervals (CIs) were estimated using either a fixed or random-effects model. Subgroup analysis, meta-regression, publication bias, and sensitivity analysis were as well performed. RESULTS: In the general population, individuals with the healthiest combination of LBs exhibited a significant risk reduction of 58% for CVD and 55% for CVD mortality. For individuals diagnosed with CVD, adherence to the healthiest combination of LBs corresponded to a significant risk reduction of 62% for CVD recurrence and 67% for all-cause mortality, when compared to those with the least-healthy combination of LBs. In the analysis of dose-response relationship, for each increment of 1 healthy LB, there was a corresponding decrease in risk of 17% for CVD and 19% for CVD mortality within the general population. Similarly, among individuals diagnosed with CVD, each additional healthy LB was associated with a risk reduction of 27% for CVD recurrence and 27% for all-cause mortality. CONCLUSIONS: Adopting healthy LBs is associated with substantial risk reduction in CVD, CVD mortality, and adverse outcomes among individuals diagnosed with CVD. Rather than focusing solely on individual healthy LB, it is advisable to advocate for the adoption of multiple LBs for the prevention and management of CVD. TRIAL REGISTRATION: PROSPERO: CRD42023431731.

Lacticaseibacillus rhamnosus HF01 fermented yogurt alleviated high-fat diet-induced obesity and hepatic steatosis via the gut microbiota-butyric acid-hepatic lipid metabolism axis.

The objective of this study was to investigate the anti-obesity effects and underlying mechanism of Lacticaseibacillus rhamnosus HF01 fermented yogurt (HF01-Y). Herein, obesity was induced in mice through a high-fat diet and the changes in the gut microbiota were evaluated using 16S rRNA gene sequencing, combined with the expression levels of the liver AMPK signaling pathway to analyze the potential relationship between HF01-Y-mediated gut microbiota and obesity. The results showed that supplementation with HF01-Y improved obesity-related phenotypes in mice, including reduced body weight, improved serum lipid profiles, and decreased hepatic lipid droplet formation. In addition, HF01-Y altered the composition of the gut microbiota in obese mice, significantly upregulated norank_f__Muribaculaceae, unclassified_c__Clostridia, Blautia, unclassified_o__Bacteroidales, and Rikenellaceae_RC9_gut_group, while downregulating unclassified_f__Desulfovibrionaceae, Colidextribacter, and unclassified_f__Oscillospiraceae. These alterations led to an increase of the cecum butyric acid content, which in turn indirectly promoted the activation of the AMPK signaling pathway, subsequently, inhibited fat synthesis, and promoted fatty acid oxidation related gene expression. Therefore, HF01-Y was likely to alleviate hepatic fat and relieve obesity by modulating the gut microbiota-butyric acid-hepatic lipid metabolism axis, ultimately promoting host health.

Higher Circulating Lymphocytes and the Incidence of Pre-eclampsia and Eclampsia.

Excessive immune activation contributes to the onset of early dysfunction of the maternal-fetal interface, and it is closely linked to the development of pre-eclampsia. However, the effect of specific immune cells on the risk of pre-eclampsia and eclampsia remains controversial. We investigated the causal relationship between immune cells and pre-eclampsia and eclampsia. For exposure, we extracted genetic variants associated with immune cell-related traits, and for outcomes, we used summary genetic data of pre-eclampsia/eclampsia. A two-sample Mendelian randomization (MR) analysis was then performed to assess the causal relationship. Robustness of the MR results was then evaluated through colocalization analysis. We found that genetically proxied circulating lymphocyte absolute count was causally associated with total eclampsia (odds ratio (OR) = 1.53, 95% confidence interval (CI) (1.31-1.79), p = 1.15E - 07) and pre-eclampsia (OR = 1.50, 95% CI (1.28-1.77), p = 9.18E - 07); T cell absolute count was causally associated with total eclampsia (OR = 1.49, 95% CI (1.28-1.73), p = 2.73E - 07) and pre-eclampsia (OR = 1.47, 95% CI (1.25-1.72), p = 1.76E - 06). And CD28- CD25+ CD8+ T cell absolute count was causally associated with total eclampsia (OR = 1.83, 95% CI (1.44-2.32), p = 7.11E - 07) and pre-eclampsia (OR = 1.77, 95% CI (1.38-2.26), p = 6.55E - 06). Colocalization analysis revealed that immune cell-related traits shared the same variant with pre-eclampsia/eclampsia. Our study suggested causal effects of genetic predisposition to high lymphocyte absolute count levels, T cell absolute count, and CD28- CD25+ CD8+ T cell absolute count on eclampsia, particularly pre-eclampsia risk, providing crucial new insights into the potential prevention target for eclampsia and pre-eclampsia.

Quantifying the Adverse Effects of Long COVID on Individuals' Health After Infection: A Propensity Score Matching Design Study.

Objective: To evaluate the prevalence and influencing factors of long COVID, and measure the difference in health status between long COVID and non-long COVID cases. Methods: A cross-sectional survey was conducted from February 1 to 8, 2023, using a stratified random sampling method in four regions (eastern [Changzhou], central [Zhengzhou], western [Xining] and northeastern [Mudanjiang]) of China. The survey collected COVID-19 patients' socio-demographic characteristics and lifestyles information. The scores of lifestyles and health status range from 5 to 21 and 0 to 100 points, respectively. The criteria of "persistent health problems after 4 weeks of COVID-19 infection" issued by the US Centers for Disease Control and Prevention was used to assess long COVID. Multiple linear regression was used to analyze the influencing factors of the health. The bootstrap method was used to analyze the lifestyles' mediating effect. Propensity score matching (PSM) was used to evaluate the net difference in health scores between long COVID and non-long COVID cases. Results: The study included 3165 COVID-19 patients, with 308 (9.73%) long COVID cases. The health score of the long COVID cases (74.79) was lower than that of the non-long COVID cases (81.06). After adjusting for potential confounding variables, we found that never focused on mental decompression was a common risk factor for the health of both groups. Lifestyles was the mediating factor on individuals' health. After PSM, the non-long COVID cases' health scores remained higher than that of long COVID cases. Conclusion: The proportion of long COVID cases was low, but they were worse off in health. Given the positive moderating effect of healthy lifestyles on improving the health of long COVID cases, healthy lifestyles including mental decompression should be considered as the core strategy of primary prevention when the epidemic of COVID-19 is still at a low level.

Antigen-specific chemokine profiles as biomarkers for detecting Mycobacterium tuberculosis infection.

Background: Latent tuberculosis (TB) infection can progress to active TB, which perpetuates community transmission that undermines global TB control efforts. Clinically, interferon-γ release assays (IGRAs) are commonly used for active TB case detection. However, low IGRA sensitivity rates lead to false-negative results for a high proportion of active TB cases, thus highlighting IGRA ineffectiveness in differentiating MTB-infected individuals from healthy individuals. Methods: Participants enrolled at Beijing Chest Hospital from May 2020-April 2022 were assigned to healthy control (HC), LTBI, IGRA-positive TB, and IGRA-negative TB groups. Screening cohort MTB antigen-specific blood plasma chemokine concentrations were measured using Luminex xMAP assays then were verified via testing of validation cohort samples. Results: A total of 302 individuals meeting study inclusion criteria were assigned to screening and validation cohorts. Testing revealed significant differences in blood plasma levels of CXCL9, CXCL10, CXCL16, CXCL21, CCL1, CCL19, CCL27, TNF-α, and IL-4 between IGRA-negative TB and HC groups. Levels of CXCL9, CXCL10, IL-2, and CCL8 biomarkers were predictive for active TB, as reflected by AUC values of ≥0.9. CXCL9-based enzyme-linked immunosorbent assay sensitivity and specificity rates were 95.9% (95%CI: 91.7-98.3) and 100.0% (92.7-100.0), respectively. Statistically similar AUC values were obtained for CXCL9 and CXCL9-CXCL10 assays, thus demonstrating that combined analysis of CXCL10 and CXCL9 levels did not improve active TB diagnostic performance. Conclusion: The MTB antigen stimulation-based CXCL9 assay may compensate for low IGRA diagnostic accuracy when used to diagnose IGRA-negative active TB cases and thus is an accurate and sensitive alternative to IGRAs for detecting MTB infection.

How urban versus rural population relates to COVID-19 booster vaccine hesitancy: A propensity score matching design study.

During the COVID-19 pandemic, the vaccine hesitancy has significantly affected the vaccination. To evaluate the booster vaccine hesitancy and its influencing factors among urban and rural residents, as well as to estimate the net difference of booster vaccine hesitancy between urban and rural residents. We conducted a nationwide, cross-sectional Internet survey on 1-8 February 2023, and employed stratified random sampling technique to select participants (≥18 years old) from urban and rural areas. Multivariate logistic regression was used to determine the factors impacting booster vaccine hesitancy. Propensity Score Matching was used to estimate the net difference of COVID-19 booster vaccine hesitancy between urban and rural residents. The overall COVID-19 booster vaccine hesitancy rate of residents was 28.43%. The COVID-19 booster vaccine hesitancy rate among urban residents was found to be 34.70%, among rural residents was 20.25%. Chronic diseases, infection status, vaccination benefits, and trust in vaccine developers were associated with booster vaccine hesitancy among urban residents. Barriers of vaccination were associated with booster vaccine hesitancy among rural residents. PSM analysis showed that the urban residents have a higher booster vaccine hesitancy rate than rural residents, with a net difference of 6.20%. The vaccine hesitancy rate increased significantly, and the urban residents have a higher COVID-19 booster vaccine hesitancy than rural residents. It becomes crucial to enhance the dissemination of information regarding the advantages of vaccination and foster greater trust among urban residents toward the healthcare system.

Temporal changes in factors associated with COVID-19 vaccine hesitancy among Chinese adults: Repeated nationally representative survey.

Background: COVID-19 vaccine hesitancy has been cited as one of the main obstacles impacting vaccine coverage. However, factors that affect hesitancy may change over time. Understanding these evolving concerns and adapting strategies accordingly are crucial for effectively addressing vaccine hesitancy effectively and promoting public health. We aimed to explore the temporal changes in factors associated with COVID-19 VH during the COVID-19 pandemic and assess the dynamic evolution of VH. Methods: In August 2022 and February 2023, repeated online surveys were undertaken to collect information from 5378 adults across four regions of China. Multiple linear regression models assessed the influencing factors of COVID-19 VH. The association between protective motive theory (PMT) (perceived severity, susceptibility, benefits, barriers, and self-efficacy) and VH was evaluated by structural equation modeling (SEM). Results: Repeated measures showed that 573 (10.7%) and 1598 (29.7%) of the 5378 participants reported COVID-19 VH in the baseline and follow-up surveys, respectively. Educational levels, chronic disease, history of allergy, COVID-19 infection, and trust in medical staff and vaccine developers were positively associated with COVID-19 VH (P＜0.05). The application of SEM revealed that perceived severity, susceptibility, vaccination barriers, and self-efficacy in the PMT directly impacted on VH (P＜0.05). In addition, severity, susceptibility, benefits, and barriers had a significant direct effect on self-efficacy as ß = 0.113, ß = 0.070, ß = 0.722, ß = -0.516 respectively with P < 0.001. Conclusion: The prevalence of COVID-19 VH was relatively low in the baseline survey and much higher in the follow-up survey, with a significant increase in hesitancy rates among mainland Chinese residents. Acknowledging the substantial impact on the shaping of COVID-19 VH, one must consider factors including perceived severity, susceptibility, vaccination barriers, and self-efficacy.

Plant-derived nanovesicles: Further exploration of biomedical function and application potential.

Extracellular vesicles (EVs) are phospholipid bilayer vesicles actively secreted by cells, that contain a variety of functional nucleic acids, proteins, and lipids, and are important mediums of intercellular communication. Based on their natural properties, EVs can not only retain the pharmacological effects of their source cells but also serve as natural delivery carriers. Among them, plant-derived nanovesicles (PNVs) are characterized as natural disease therapeutics with many advantages such as simplicity, safety, eco-friendliness, low cost, and low toxicity due to their abundant resources, large yield, and low risk of immunogenicity in vivo. This review systematically introduces the biogenesis, isolation methods, physical characterization, and components of PNVs, and describes their administration and cellular uptake as therapeutic agents. We highlight the therapeutic potential of PNVs as therapeutic agents and drug delivery carriers, including anti-inflammatory, anticancer, wound healing, regeneration, and antiaging properties as well as their potential use in the treatment of liver disease and COVID-19. Finally, the toxicity and immunogenicity, the current clinical application, and the possible challenges in the future development of PNVs were analyzed. We expect the functions of PNVs to be further explored to promote clinical translation, thereby facilitating the development of a new framework for the treatment of human diseases.

Transcriptome-wide association study reveals novel susceptibility genes for coronary atherosclerosis.

Background: Genetic risk factors substantially contributed to the development of coronary atherosclerosis. Genome-wide association study (GWAS) has identified many risk loci for coronary atherosclerosis, but the translation of these loci into therapeutic targets is limited for their location in non-coding regions. Here, we aimed to screen the potential coronary atherosclerosis pathogenic genes expressed though TWAS (transcriptome wide association study) and explore the underlying mechanism association. Methods: Four TWAS approaches (PrediXcan, JTI, UTMOST, and FUSION) were used to screen genes associated with coronary atherosclerosis. Enrichment analysis of TWAS-identified genes was applied through the Metascape website. The summary-data-based Mendelian randomization (SMR) analysis was conducted to provide the evidence of causal relationship between the candidate genes and coronary atherosclerosis. At last, the cell type-specific expression of the intersection genes was examined by using human coronary artery single-cell RNA-seq, interrogating the immune microenvironment of human coronary atherosclerotic plaque at different stages of maturity. Results: We identified 19 genes by at least three approaches and 1 gene (NBEAL1) by four approaches. Enrichment analysis enriching the genes identified at least by two TWAS approaches, suggesting that these genes were markedly enriched in asthma and leukocyte mediated immunity reaction. Further, the summary-data-based Mendelian randomization (SMR) analysis provided the evidence of causal relationship between NBEAL1 gene and coronary atherosclerosis, confirming the protecting effects of NBEAL1 gene and coronary atherosclerosis. At last, the single cell cluster analysis demonstrated that NBEAL1 gene has differential expressions in macrophages, plasma cells and endothelial cells. Conclusion: Our study identified the novel genes associated with coronary atherosclerosis and suggested the potential biological function for these genes, providing insightful guidance for further biological investigation and therapeutic approaches development in atherosclerosis-related diseases.

Prediction and bioactivity of small-molecule antimicrobial peptides from Protaetia brevitarsis Lewis larvae.

Antimicrobial peptides (AMPs) are widely recognized as promising natural antimicrobial agents. Insects, as the group of animals with the largest population, have great potential as a source of AMPs. Thus, it is worthwhile to investigate potential novel AMPs from Protaetia brevitarsis Lewis larvae, which is a saprophagous pest prevalent in China. In this study, comparing the whole-genome sequence of Protaetia brevitarsis Lewis larvae with the Antimicrobial Peptide Database (APD3) led to the identification of nine peptide templates that were potentially AMPs. Next, based on the peptide templates, 16 truncated sequences were predicted to the AMPs by bioinformatics software and then underwent structural and physicochemical property analysis. Thereafter, candidate small-molecule AMPs were artificially synthesized and their minimal inhibitory concentration (MIC) values were assessed. A candidate peptide, designated FD10, exhibited strong antimicrobial activity against both bacteria and fungi comprising Escherichia coli (MIC: 8 µg/mL), Pseudomonas aeruginosa (MIC: 8 µg/mL), Bacillus thuringiensis (MIC: 8 µg/mL), Staphylococcus aureus (MIC: 16 µg/mL), and Candida albicans (MIC: 16 µg/mL). Additionally, two other candidate peptides, designated FD12 and FD15, exhibited antimicrobial activity against both E. coli (MIC: both 32 µg/mL) and S. aureus (MIC: both 16 µg/mL). Moreover, FD10, FD12, and FD15 killed almost all E. coli and S. aureus cells within 1 h, and the hemolytic effect of FD10 (0.31%) and FD12 (0.40%) was lower than that of ampicillin (0.52%). These findings indicate that FD12, FD15, and especially FD10 are promising AMPs for therapeutic application. This study promoted the development of antibacterial drugs and provided a theoretical basis for promoting the practical application of antimicrobial peptides in the Protaetia brevitarsis Lewis larvae.

Analysis of Xpert MTB/RIF results in retested patients with very low initial bacterial loads: A retrospective study in China.

BACKGROUND: The Xpert MTB/RIF (Xpert) assay has been widely used to diagnose suspected active tuberculosis (TB) and rifampicin-resistant TB cases. Despite its excellent performance record, false-positive Xpert rifampicin (RIF) resistance results are obtained for specimens with extremely low bacterial loads. OBJECTIVE: We aimed to study the feasibility of repeat Xpert testing as a strategy for reducing the odds of obtaining false-positive results when testing paucibacillary TB patients. METHODS: We enrolled previously tested TB patients with very low initial bacterial loads from May 2016 to February 2022 for Xpert retesting. A total of 251 TB patients were retested using the Xpert assay. RESULTS: RIF resistance was noted in 65 (25.9 %) patients when tested by Xpert at initial diagnosis. Only 107 (42.6 %) of 251 patients tested positive for MTB when retested via Xpert. The majority (98.6 %) of RIF-susceptible cases were still susceptible to RIF when retested. Initial Xpert testing yielded 35 positive results for MTB in the RIF-resistant group, of whom 25 (71.4 %) still exhibited RIF resistance when retested. All culture-positive MTB isolates in the RIF-susceptible group were also RIF-susceptible by phenotypic DST. In the RIF-resistant group, 10 of 14 culture-positive MTB isolates exhibited RIF resistance, of which 4 isolates were deemed RIF-susceptible by phenotypic DST. The proportion of double mutations within the MTB rpoB RRDR sequence, as detected by hybridization of Xpert D and E probes, was significantly higher in the RIF-susceptible group than in the RIF-susceptible group. CONCLUSIONS: Our results demonstrated that initial RIF-susceptible results were more accurate than RIF-resistant results. Additionally, patients with double mutations that delayed probe D/E hybridization were more likely to have false-positive Xpert results. Our findings emphasize that repeat Xpert MTB/RIF testing is necessary for TB patients with extremely low bacterial loads who are at high risk for RIF-resistant TB.

White blood cells and coronary heart disease: A mendelian randomization study.

Background: The causal direction and magnitude of the associations between blood cell count and coronary heart disease (CHD) remain uncertain due to susceptibility of reverse causation and confounding. This study aimed to investigate the associations between blood cell count and CHD using Mendelian randomization (MR). Methods: In this two-sample MR study, we identified independent blood cell count associated genetic variants from a genome-wide association studies (GWAS) among European ancestry individuals. Summary level data of CHD was obtained from a GWAS consisting of 547261 subjects. Methods of inverse variance weighted (IVW), Mendelian Randomization-Egger (MR-Egger), weighted median, and outlier test (MR-PRESSO) were conducted to investigate the associations between blood cell and CHD. Results: Among all cardiovascular outcomes of interest, blood cell counts were only associated with CHD. Our findings indicated that white blood cell count and neutrophil cell count were significantly associated with increased risk of CHD [odds ratio (OR) = 1.07, 95% confidence interval (CI), 1.01-1.14; OR = 1.09, 1.02-1.16). However, there was no significant association between monocyte cell count, basophil cell count, lymphocyte cell count, eosinophil cell count, and CHD (p > 0.05). The results after excluding outliers were consistent with main results and the sensitivity analyses showed no evidence of pleiotropy (MR-Egger intercept, p > 0.05). Conclusion: Our MR study suggested that greater white blood cell count and neutrophil cell count were associated with a higher risk of CHD. Future studies are still warranted to validate the results and investigate the mechanisms underlying these associations.

Accuracy of Xpert® MTB/RIF Ultra test for posterior oropharyngeal saliva for the diagnosis of paucibacillary pulmonary tuberculosis: a prospective multicenter study.

BACKGROUND: Posterior oropharyngeal saliva (POS) is increasingly recognized as an alternative specimen for detecting respiratory pathogens. The accuracy of Xpert® MTB/RIF Ultra (X-Ultra), when performed on POS obtained from patients with paucibacillary pulmonary tuberculosis (TB) is unclear. METHODS: We consecutively recruited adults with symptoms suggestive of pulmonary TB who were negative by both smear microscopy and Xpert MTB/RIF (X-Classic). Each participant was required to provide one bronchoalveolar lavage fluid (BALF) and one POS specimen, respectively. Diagnostic performances of X-Ultra and X-Classic on POS were compared against clinical and mycobacterial reference standards. FINDINGS: 686 participants meeting inclusion criteria were consecutively enrolled into the study. The overall diagnostic sensitivities of X-Ultra and X-Classic on POS samples were 78.9% [95% confidence interval (CI): 72.8-83.8] and 56.4% (95% CI: 49.7-62.9), respectively; the specificities were 96.6% (95% CI: 94.3-98.1) for X-Ultra and 97.6 (95CI: 95.5-98.8) for X-Classic in POS specimens. Notably, the sensitivity of X-Ultra on POS was as sensitive as X-Classic on BALF against microbiological reference standard (78.9% VS 73.1%). Against clinical diagnosis as a reference standard, the sensitivities of X-Ultra and X-Classic on POS were 55.9% (95% CI: 50.5-61.2; 193/345) and 40.0% (95% CI: 34.8-45.4; 138/345), respectively. The risk of negative results with POS was dramatically increased with decreasing bacterial loads. CONCLUSIONS: The testing of POS using X-Ultra shows promise as a tool to identify patients with paucibacillary TB. Considering that bronchoscopy is a semi-invasive procedure, POS testing ahead of bronchoscopy, may decrease the need for bronchoscopic procedures, and the cost of care.

Predominance of Escherichia-Shigella in Gut Microbiome and Its Potential Correlation with Elevated Level of Plasma Tumor Necrosis Factor Alpha in Patients with Tuberculous Meningitis.

Tuberculous meningitis (TBM), the most lethal and disabling form of tuberculosis (TB), may be related to gut microbiota composition, warranting further study. Here we systematically compared gut microbiota compositions and blood cytokine profiles of TBM patients, pulmonary TB patients, and healthy controls. Notably, the significant gut microbiota dysbiosis observed in TBM patients was associated with markedly high proportions of Escherichia-Shigella species as well as increased blood levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6). Next, we obtained a fecal bacterial isolate from a TBM patient and administered it via oral gavage to mice in order to develop a murine gut microbiota dysbiosis model for use in exploring mechanisms underlying the observed relationship between gut microbial dysbiosis and TBM. Thereafter, cells of commensal Escherichia coli (E. coli) were isolated and administered to model mice by gavage and then mice were inoculated with Mycobacterium tuberculosis (M. tuberculosis). Subsequently, these mice exhibited increased blood TNF-α levels accompanied by downregulated expression of tight junction protein claudin-5, increased brain tissue bacterial burden, and elevated central nervous system inflammation relative to corresponding indicators in controls administered PBS by gavage. Thus, our results demonstrated that a signature dysbiotic gut microbiome profile containing a high proportion of E. coli was potentially associated with an increased circulating TNF-α level in TBM patients. Collectively, these results suggest that modulation of dysbiotic gut microbiota holds promise as a new strategy for preventing or alleviating TBM. IMPORTANCE As the most severe form of tuberculosis, the pathogenesis of tuberculous meningitis (TBM) is still unclear. Gut microbiota dysbiosis plays an important role in a variety of central nervous system diseases. However, the relationship between gut microbiota and TBM has not been identified. In our study, significant dysbiosis in gut microbiota composition with a high proportion of E. coli and increased levels of TNF-α in plasma was noted in TBM patients. A commensal E. coli was isolated and shown to increase the plasma level of TNF-α and downregulate brain tight junction protein claudin-5 in the murine model. Gavage administration of E. coli aggravated the bacterial burden and increased the inflammatory responses in the central nervous system after M. tuberculosis infection. Dysbiosis of gut microbiota may be a promising therapeutic target and biomarker for TBM prevention or treatment.

Delamanid suppresses CXCL10 expression via regulation of JAK/STAT1 signaling and correlates with reduced inflammation in tuberculosis patients.

Background: Apart from bactericidal effects, anti-tuberculosis drugs can interfere with the host's immune system. In this study, we analyzed the role of delamanid (DLM), an inhibitor of mycolic acid synthesis of mycobacterial cell wall, on human macrophages. Methods: Based on a cohort of multidrug-resistant tuberculosis (MDR-TB) patients treated with DLM, the levels of C-reaction protein (CRP) and cytokines in the plasma were monitored using immunoturbidimetric assay and flow cytometry, respectively. We investigated the role of DLM on CXCL10 expression in U937 cell model using the following methods: cell viability assay, reverse transcription-quantitative polymerase chain reaction, enzyme linked immunosorbent assay, immunoblot, and transwell co-culture assay. Results: A total of 23 MDR-TB patients were included, comprising of 13 patients treated with optimized background therapeutic regimen (OBR) plus DLM regimen (OBR+DLM) and 10 patients treated with OBR plus placebo. DLM administration was associated with a significant reduce in circulating CRP level. Correspondingly, after treatment, the level of CXCL10 in patients treated with OBR+DLM was significantly lower than that with control. Using cell model, DLM dramatically suppressed CXCL10 expression, which majorly depended on inhibiting the JAK/STAT pathway, and impaired the migration of PBMCs. Conclusion: Our data firstly demonstrate that DLM suppresses CXCL10 expression via regulation of JAK2/STAT1 signaling and correlates with reduced inflammation in MDR-TB patients. DLM could be used as a potential drug for immunotherapy of patients with overactive immune response due to CXCL10.

Microflora for improving the Auricularia auricula spent mushroom substrate for Protaetia brevitarsis production.

Mushroom cultivation is a sustainable agricultural waste utilization method, but the lack of high-value utilization of the produced spent mushroom substrate (SMS) has hindered the development of mushroom cultivation-based circular agricultural systems. Conversion and utilization of SMS via Protaetia brevitarsis larvae (PBL) have proven to be a high-value AASMS utilization strategy. However, Auricularia auricula SMS (AASMS), which contains woodchips, is less palatable and digestible for PBL. To solve this problem, in this investigation, we screened out microflora (MF) for AASMS fermentation by comparing the fermentation performance as well as the effect on PBL feed intake, weight gain, and AASMS phytotoxic compound removal efficiency. In addition, by bacterial community analysis, the genera Luteimonas, Moheibacter, and Pseudoxanthomonas were predicted to be functional bacteria for AASMS fermentation and contribute to palatability and digestibility improvement.

High Incidence of Psychiatric Disorders Associated with Cycloserine Treatment of Multidrug-Resistant Tuberculosis Patients: A Cohort Study in Beijing, China.

Objective: Cycloserine (CS) is a group B anti-tuberculosis (TB) drug endorsed by the World Health Organization (WHO) for the treatment of drug-resistant (DR)-TB. Despite CS widespread acceptance and known efficacy, the high potential of drug-associated psychiatric disorders is a major concern to multidrug-resistant (MDR)-TB patients. In this study, we investigated CS-associated psychiatric disorders in a cohort of MDR-TB patients in Beijing, China. Our aim was to determine psychiatric disorder prevalence rates and associated risk factors in this population. Methods: This MDR-TB cohort study was conducted at Beijing Chest Hospital between February 2018 and February 2021. All patients received individualized treatment regimens that included CS at some point during the full treatment course. Patient psychological status was assessed using the Symptom Checklist (SCL-90) questionnaire during the post-treatment follow-up period. Results: Two hundred and thirty-seven MDR-TB patients were included in the final analysis. Overall, psychiatric disorders were recorded in 22 (9.28%) of the 237 patients in our cohort, with severity grades of 1 or 2 observed for the majority (8.44%) of psychiatric adverse events. As compared to results obtained for control group patients who were ≥40 years of age, patients who were <40 years of age (77.3%, 17/22) were more likely to experience psychiatric disorders [adjusted odds ratio (aOR) = 3.060; 95% CI (1.060-8.828)]. Additionally, patients with body mass index (BMI)s of <18.5 kg/m2 [aOR = 3.824; 95% CI (1.502-9.739)] had significantly higher odds of being afflicted with psychiatric disorders as compared with patients with BMIs that were ≥18.5 kg/m2. Conclusion: Our results demonstrated that approximately one-tenth of Chinese MDR-TB patients experienced psychiatric disorders during CS treatment, with the majority of adverse events of moderate severity. In addition, low BMI and age <40 years were identified as independent risk factors for psychiatric disorders in MDR-TB patients receiving CS therapy.

Effects of Site-Directed Mutagenesis of Cysteine on the Structure of Sip Proteins.

Bacillus thuringiensis, a gram-positive bacteria, has three insecticidal proteins: Vip (vegetative insecticidal protein), Cry (crystal), and Sip (secreted insecticidal protein). Of the three, Sip proteins have insecticidal activity against larvae of Coleoptera. However, the Sip1Aa protein has little solubility in the supernatant because of inclusion bodies. This makes it more difficult to study, and thus research on Sip proteins is limited, which hinders the study of their mechanistic functions and insecticidal mechanisms. This highlights the importance of further investigation of the Sip1Aa protein. Disulfide bonds play an important role in the stability and function of proteins. Here, we successfully constructed mutant proteins with high insecticidal activity. The tertiary structure of the Sip1Aa protein was analyzed with homologous modeling and bioinformatics to predict the conserved domain of the protein. Cysteine was used to replace amino acids via site-directed mutagenesis. We successfully constructed Sip149-251, Sip153-248, Sip158-243, and Sip178-314 mutant proteins with higher solubility than Sip1Aa. Sip153-248 and Sip158-243 were the most stable compared to Sip1Aa, followed by Sip149-251 and Sip178-314. The insecticidal activity of Sip153-248 (Sip158-243) was 2.76 (2.26) times higher than that of Sip1Aa. The insecticidal activity of Sip149-251 and Sip178-314 did not differ significantly from that of Sip1Aa. Basic structural properties, physicochemical properties, and the spatial structure of the mutation site of Sip1Aa and the mutant proteins were analyzed. These results provide a molecular basis for using Sip1Aa to control Coleopteran insects and contribute to the study of the Sip1Aa insecticidal mechanism.

Impact of Paenarthrobacter ureafaciens ZF1 on the soil enzyme activity and microbial community during the bioremediation of atrazine-contaminated soils.

Bioremediation of atrazine-contaminated soil is considered a safe and effective approach in removing contaminates from the soil. However, the effects of adding foreign organisms to assist bioremediation on soil environmental quality and ecosystem are unclear. Here, the ecological remediation potential of strain Paenarthrobacter ureafaciens ZF1 on atrazine-contaminated soil was investigated through miniature experiments using variations in soil enzymes and bacterial communities as indicators. The results showed that strain ZF1 accelerated atrazine degradation, which could completely degrade atrazine at concentrations of 100 mg·L- 1 atrazine within 2 h in liquid medium and could remove up to 99.3% of atrazine (100 mg·kg- 1 in soil) within 6 days. During soil bioremediation, atrazine promoted the activities of urease and cellulase, and inhibited the activities of sucrase and catalase, while the strain ZF1 significantly promoted the activities of these four enzymes. High-throughput sequencing of 16S rRNA genes showed that ZF1 affected the relative abundance and bacterial community structure, and promoted bacterial diversity and evenness. Furthermore, redundancy analysis revealed a certain correlation among the strain ZF1, atrazine residue, soil enzyme activity, and soil bacterial community. The strain ZF1 in this work demonstrated remarkable potential for ecological restoration, and can be an effective and environmentally friendly alternative in remediating atrazine-contaminated soil.