Toxin-antitoxin system gene mutations driving Mycobacterium tuberculosis transmission revealed by whole genome sequencing.

Background: The toxin-antitoxin (TA) system plays a vital role in the virulence and pathogenicity of Mycobacterium tuberculosis (M. tuberculosis). However, the regulatory mechanisms and the impact of gene mutations on M. tuberculosis transmission remain poorly understood. Objective: To investigate the influence of gene mutations in the toxin-antitoxin system on M. tuberculosis transmission dynamics. Method: We performed whole-genome sequencing on the analyzed strains of M. tuberculosis. The genes associated with the toxin-antitoxin system were obtained from the National Center for Biotechnology Information (NCBI) Gene database. Mutations correlating with enhanced transmission within the genes were identified by using random forest, gradient boosting decision tree, and generalized linear mixed models. Results: A total of 13,518 M. tuberculosis isolates were analyzed, with 42.29% (n = 5,717) found to be part of genomic clusters. Lineage 4 accounted for the majority of isolates (n = 6488, 48%), followed by lineage 2 (n = 5133, 37.97%). 23 single nucleotide polymorphisms (SNPs) showed a positive correlation with clustering, including vapB1 G34A, vapB24 A76C, vapB2 T171C, mazF2 C85T, mazE2 G104A, vapB31 T112C, relB T226A, vapB11 C54T, mazE5 T344C, vapB14 A29G, parE1 (C103T, C88T), and parD1 C134T. Six SNPs, including vapB6 A29C, vapB31 T112C, parD1 C134T, vapB37 G205C, Rv2653c A80C, and vapB22 C167T, were associated with transmission clades across different countries. Notably, our findings highlighted the positive association of vapB6 A29C, vapB31 T112C, parD1 C134T, vapB37 G205C, vapB19 C188T, and Rv2653c A80C with transmission clades across diverse regions. Furthermore, our analysis identified 32 SNPs that exhibited significant associations with clade size. Conclusion: Our study presents potential associations between mutations in genes related to the toxin-antitoxin system and the transmission dynamics of M. tuberculosis. However, it is important to acknowledge the presence of confounding factors and limitations in our study. Further research is required to establish causation and assess the functional significance of these mutations. These findings provide a foundation for future investigations and the formulation of strategies aimed at controlling TB transmission.

The luminescent Nb2C MXene nanosheet-based whispering gallery mode-enhanced ECL strategy for miRNA-214 detection.

MiRNA-214 can regulate the expression of their downstream target genes after post-transcriptional and are involved in the biological processes of triple negative breast cancer (TNBC). In this work, the small-sized luminescent Nb2C nanosheet-based whispering gallery mode-enhanced electrochemiluminescence (ECL) strategy was successfully constructed to detect miRNA-214 in TNBC. Firstly, we have synthesized small-sized luminescent Nb2C nanosheets from Nb2AlC MXene. The Nb2C nanosheets not only exhibited more stable chemical properties and reduced the defects of the large sheet structures, but also possessed the quantum confinement effect with the discrete energy level. As a result, the prepared small-sized Nb2C nanosheets had unique luminescent and electrochemical properties. Furthermore, in order to improve the ECL performance of Nb2C nanosheets, SiO2 microspheres were self-assembled on the electrode surface by gas-liquid interface method to form whispering gallery mode structure. Because the light was continuously reflected at the interface of the microcavity in the whispering gallery mode, the ECL signal of Nb2C luminescent nanosheets was amplified largely. Finally, the whispering gallery mode-based ECL sensing platform was established. The results showed that the biosensor had a good linear correlation between the ECL intensity and the logarithm of concentration of miRNA-214 in the range of 10 fM to 100 nM with a limit of detection of 2.5 fM. The actual detection of miRNA-214 content in clinical TNBC tissue samples was realized successfully.

Fine-tuning large language models for chemical text mining.

Extracting knowledge from complex and diverse chemical texts is a pivotal task for both experimental and computational chemists. The task is still considered to be extremely challenging due to the complexity of the chemical language and scientific literature. This study explored the power of fine-tuned large language models (LLMs) on five intricate chemical text mining tasks: compound entity recognition, reaction role labelling, metal-organic framework (MOF) synthesis information extraction, nuclear magnetic resonance spectroscopy (NMR) data extraction, and the conversion of reaction paragraphs to action sequences. The fine-tuned LLMs demonstrated impressive performance, significantly reducing the need for repetitive and extensive prompt engineering experiments. For comparison, we guided ChatGPT (GPT-3.5-turbo) and GPT-4 with prompt engineering and fine-tuned GPT-3.5-turbo as well as other open-source LLMs such as Mistral, Llama3, Llama2, T5, and BART. The results showed that the fine-tuned ChatGPT models excelled in all tasks. They achieved exact accuracy levels ranging from 69% to 95% on these tasks with minimal annotated data. They even outperformed those task-adaptive pre-training and fine-tuning models that were based on a significantly larger amount of in-domain data. Notably, fine-tuned Mistral and Llama3 show competitive abilities. Given their versatility, robustness, and low-code capability, leveraging fine-tuned LLMs as flexible and effective toolkits for automated data acquisition could revolutionize chemical knowledge extraction.

Effects of a Tai Chi rehabilitation program implemented using a hybrid online and offline mode on oxidative stress and inflammatory responses in patients with coronary heart disease: a randomized controlled trial.

Background: Coronary heart disease (CHD) is the leading cause of death in both developed and many developing countries. Exercise training is a fundamental component of cardiac rehabilitation programs for patients with CHD. This study aims to investigate the effects of a Tai Chi rehabilitation program, which is provided through a hybrid online and offline mode, on oxidative stress and inflammatory responses in patients with CHD. Methods: A total of 34 patients with coronary heart disease were randomly assigned to two groups: an experiment group (n = 14, age 62.07 ± 9.076 years) and a control group (n = 20, age 61.90 ± 9.700 years). The experiment group underwent a 12-week Tai Chi cardiac rehabilitation program (TCCRP), while the control group followed a conventional exercise rehabilitation program (CERP) consisting of 1-h sessions, 3 times per week, for a total of 36 sessions. Participants were studied at baseline and post-intervention. The main assessments include the levels of Malondialdehyde (MDA), Superoxide dismutase (SOD), Tumor necrosis factor (TNF-α) and Interleukin-10 (IL - 10) in blood samples. Pearson correlation analysis was used, and the differences between the two groups were subsequently tested using two-way repeated ANOVA. Statistical significance was defined as a two-sided p-value of <0.05. Results: The key finding of the study reveals that MDA was significantly reduced by 1.027 nmoL/mL. Additionally, the TCCRP showed significant improvements in SOD and IL-10, with values of 10.110 U/mL and 2.441 pg./mL, respectively. Notably, a significant positive correlation was found between SOD and IL-10 (r = 0.689, p = 0.006), while MDA showed a significant positive correlation with TNF-a (r = 0.542, p = 0.045). In contrast, the ECRP group only showed a significant improvement in SOD. Conclusion: The study conducted a 12-week program on TCCRP, which utilized a hybrid online and offline model for individuals with coronary heart disease. The program showed promising results in alleviating oxidative stress and inflammation, possibly by regulating the balance between oxidative and antioxidative factors, as well as pro-inflammatory and anti-inflammatory factors.

Association between chronic kidney disease and age-related macular degeneration: a Mendelian randomization study.

Purpose: Observational studies have reported inconsistent results on the relationship between chronic kidney disease (CKD) and age-related macular degeneration (AMD). The primary objective of this study was to investigate the causal relationships between estimated glomerular filtration rate (eGFR), CKD, its common causes, and AMD among participants of European descent. Methods: Genetic variants associated with eGFR, CKD and its common causes, encompassing diabetic nephropathy (DN), immunoglobulin A nephropathy (IgAN), and membranous nephropathy (MN) were obtained from previously published genome-wide association studies (GWAS) and FinnGen database. Summary statistics for early AMD, AMD, dry AMD, and wet AMD were acquired from the GWAS and FinnGen database. Inverse-variance-weighted (IVW) method was the main MR analysis. Sensitivity analyses were performed with Cochran's Q, MR-Egger intercept, and leave-one-out analysis. In addition, RadialMR was utilized to identify and remove outliers. Results: IVW results showed that CKD, eGFR were not associated with any type of AMD (p > 0.05). DN (OR: 1.042, 95% CI: 1.002-1.083, p = 0.037) and MN (OR: 1.023, 95% CI: 1.007-1.040, p = 0.005) were associated with an increased risk of earl AMD. DN (OR: 1.111, 95% CI: 1.07-1.154, p = 4.87 × 10-8), IgAN (OR: 1.373, 95% CI: 1.097-1.719, p = 0.006), and MN (OR: 1.036, 95% CI: 1.008-1.064, p = 0.012) were associated with an increased risk of AMD. DN (OR: 1.090, 95% CI: 1.042-1.140, p = 1.57 × 10-4) and IgAN (OR: 1.480, 95% CI: 1.178-1.858, p = 7.55 × 10-4) were associated with an increased risk of dry AMD. The risk of wet AMD was associated with DN (OR: 1.107, 95% CI: 1.043-1.174, p = 7.56 × 10-4) and MN (OR: 1.071, 95% CI: 1.040-1.103, p = 5.48 × 10-6). Conclusion: This MR study found no evidence of causal relationship between CKD and AMD. DN, IgAN, and MN may increase risk of AMD. This findings underscore the importance of ocular examinations in patients with DN, MN, and IgAN. More studies are needed to support the findings of our current study.

PE/PPE mutations in the transmission of Mycobacterium tuberculosis in China revealed by whole genome sequencing.

OBJECTIVE: This study aims to examine the impact of PE/PPE gene mutations on the transmission of Mycobacterium tuberculosis (M. tuberculosis) in China. METHODS: We collected the whole genome sequencing (WGS) data of 3202 M. tuberculosis isolates in China from 2007 to 2018 and investigated the clustering of strains from different lineages. To evaluate the potential role of PE/PPE gene mutations in the dissemination of the pathogen, we employed homoplastic analysis to detect homoplastic single nucleotide polymorphisms (SNPs) within these gene regions. Subsequently, logistic regression analysis was conducted to analyze the statistical association. RESULTS: Based on nationwide M. tuberculosis WGS data, it has been observed that the majority of the M. tuberculosis burden in China is caused by lineage 2 strains, followed by lineage 4. Lineage 2 exhibited a higher number of transmission clusters, totaling 446 clusters, of which 77 were cross-regional clusters. Conversely, there were only 52 transmission clusters in lineage 4, of which 9 were cross-regional clusters. In the analysis of lineage 2 isolates, regression results showed that 4 specific gene mutations, PE4 (position 190,394; c.46G > A), PE_PGRS10 (839,194; c.744 A > G), PE16 (1,607,005; c.620T > G) and PE_PGRS44 (2,921,883; c.333 C > A), were significantly associated with the transmission of M. tuberculosis. Mutations of PE_PGRS10 (839,334; c.884 A > G), PE_PGRS11 (847,613; c.1455G > C), PE_PGRS47 (3,054,724; c.811 A > G) and PPE66 (4,189,930; c.303G > C) exhibited significant associations with the cross-regional clusters. A total of 13 mutation positions showed a positive correlation with clustering size, indicating a positive association. For lineage 4 strains, no mutations were found to enhance transmission, but 2 mutation sites were identified as risk factors for cross-regional clusters. These included PE_PGRS4 (338,100; c.974 A > G) and PPE13 (976,897; c.1307 A > C). CONCLUSION: Our results indicate that some PE/PPE gene mutations can increase the risk of M. tuberculosis transmission, which might provide a basis for controlling the spread of tuberculosis.

Application of near-infrared spectroscopy to assess the effect of the cupping size on the spatial hemodynamic response from the area inside and outside the cup of the biceps.

Cupping therapy is a popular intervention for improving muscle recovery after exercise although clinical evidence is weak. Previous studies demonstrated that cupping therapy may improve microcirculation of the soft tissue to accelerate tissue healing. However, it is unclear whether the cupping size could affect the spatial hemodynamic response of the treated muscle. The objective of this study was to use 8-channel near-infrared spectroscopy to assess this clinical question by assessing the effect of 3 cupping sizes (35, 40, and 45 mm in inner diameter of the circular cup) under -300 mmHg for 5 min on the muscle hemodynamic response from the area inside and outside the cup, including oxyhemoglobin and deoxy-hemoglobin in 18 healthy adults. Two-way factorial design was used to assess the interaction between the cupping size (35, 40, and 45 mm) and the location (inside and outside the cup) and the main effects of the cupping size and the location. The two-way repeated measures ANOVA demonstrated an interaction between the cupping size and the location in deoxy-hemoglobin (P = 0.039) but no interaction in oxyhemoglobin (P = 0.100), and a main effect of the cup size (P = 0.001) and location (P = 0.023) factors in oxyhemoglobin. For the cupping size factor, the 45-mm cup resulted in a significant increase in oxyhemoglobin (5.738±0.760 µM) compared to the 40-mm (2.095±0.312 µM, P<0.001) and 35-mm (3.134±0.515 µM, P<0.01) cup. Our findings demonstrate that the cupping size and location factors affect the muscle hemodynamic response, and the use of multi-channel near-infrared spectroscopy may help understand benefits of cupping therapy on managing musculoskeletal impairment.

The potential impact of removing a ban on electronic nicotine delivery systems using the Mexico smoking and vaping model (SAVM).

Objective: To develop the Mexico Smoking and Vaping Model (Mexico SAVM) to estimate cigarette and electronic nicotine delivery systems (ENDS) prevalence and the public health impact of legalizing ENDS use. Methods: SAVM, a cohort-based discrete-time simulation model, compares two scenarios. The ENDS-Restricted Scenario estimates smoking prevalence and associated mortality outcomes under the current policy of an ENDS ban, using Mexico-specific population projections, death rates, life expectancy, and smoking and e-cigarette prevalence. The ENDS-Unrestricted Scenario projects smoking and vaping prevalence under a hypothetical scenario where ENDS use is allowed. The impact of legalizing ENDS use is estimated as the difference in smoking- and vaping-attributable deaths (SVADs) and life-years lost (LYLs) between the ENDS-Restricted and Unrestricted scenarios. Results: Compared to a national ENDS ban, The Mexico SAVM projects that legalizing ENDS use could decrease smoking prevalence by 40.1% in males and 30.9% in females by 2049 compared to continuing the national ENDS ban. This reduction in prevalence would save 2.9 (2.5 males and 0.4 females) million life-years and avert almost 106 (91.0 males and 15.5 females) thousand deaths between 2025 and 2049. Public health gains decline by 43% to 59,748 SVADs averted when the switching rate is reduced by half and by 24.3% (92,806 SVADs averted) with a 25% ENDS risk level from that of cigarettes but increased by 24.3% (121,375 SVADs averted) with the 5% ENDS risk. Conclusions: Mexico SAVM suggests that greater access to ENDS and a more permissive ENDS regulation, simultaneous with strong cigarette policies, would reduce smoking prevalence and decrease smoking-related mortality. The unanticipated effects of an ENDS ban merit closer scrutiny, with further consideration of how specific ENDS restrictions may maximize public health benefits.

Biological fermentation pilot-scale systems and evaluation for commercial viability towards sustainable biohydrogen production.

Featuring high caloric value, clean-burning, and renewability, hydrogen is a fuel believed to be able to change energy structure worldwide. Biohydrogen production technologies effectively utilize waste biomass resources and produce high-purity hydrogen. Improvements have been made in the biohydrogen production process in recent years. However, there is a lack of operational data and sustainability analysis from pilot plants to provide a reference for commercial operations. In this report, based on spectrum coupling, thermal effect, and multiphase flow properties of hydrogen production, continuous pilot-scale biohydrogen production systems (dark and photo-fermentation) are established as a research subject. Then, pilot-scale hydrogen production systems are assessed in terms of sustainability. The system being evaluated, consumes 171,530 MJ of energy and emits 9.37 t of CO2 eq when producing 1 t H2, and has a payback period of 6.86 years. Our analysis also suggests future pathways towards effective biohydrogen production technology development and real-world implementation.

Blood metabolites and chronic kidney disease: a Mendelian randomization study.

BACKGROUND: Human blood metabolites have demonstrated close associations with chronic kidney disease (CKD) in observational studies. Nonetheless, the causal relationship between metabolites and CKD is still unclear. This study aimed to assess the associations between metabolites and CKD risk. METHODS: We applied a two-sample Mendelian randomization (MR) analysis to evaluate relationships between 1400 blood metabolites and eight phenotypes (outcomes) (CKD, estimated glomerular filtration rate(eGFR), urine albumin to creatinine ratio, rapid progress to CKD, rapid decline of eGFR, membranous nephropathy, immunoglobulin A nephropathy, and diabetic nephropathy). The inverse variance weighted (IVW), MR-Egger, and weighted median were used to investigate the causal relationship. Sensitivity analyses were performed with Cochran's Q, MR-Egger intercept, MR-PRESSO Global test, and leave-one-out analysis. Bonferroni correction was used to test the strength of the causal relationship. RESULTS: Through the MR analysis of 1400 metabolites and eight clinical phenotypes, a total of 48 metabolites were found to be associated with various outcomes. Among them, N-acetylleucine (OR = 0.923, 95%CI: 0.89-0.957, PIVW = 1.450 × 10-5) has a strong causal relationship with lower risk of CKD after the Bonferroni-corrected test, whereas Glycine to alanine ratio has a strong causal relationship with higher risk of CKD (OR = 1.106, 95%CI: 1.063-1.151, PIVW = 5.850 × 10-7). No horizontal pleiotropy and heterogeneity were detected. CONCLUSION: Our study offers groundbreaking insights into the integration of metabolomics and genomics to reveal the pathogenesis of and therapeutic strategies for CKD. It underscores 48 metabolites as potential causal candidates, meriting further investigation.

Trends in the Notification Rates and Treatment Outcome of Tuberculosis in Shandong Province, China, 2005-2021.

Purpose: To analyze the time trends in the notification rates of registered tuberculosis (TB) and bacteriologically confirmed TB in Shandong Province. And analyze the changes in TB treatment outcomes during 2005-2021. Patients and Methods: The information of TB patients registered in the Shandong Information Center for Disease Control and Prevention (CDC) was collected during 2005-2021. We calculated the notification rates of registered TB and bacteriologically confirmed TB. Moreover, we calculated the year-to-year change rate of TB in treatment outcomes before and after COVID-19. The time trends were analyzed using the joinpoint regression method and illustrated as the annual percentage change (APC) of notification rates. Results: A total of 236,898 cases of TB were diagnosed during 2005-2021, of which 51.11% were bacteriologically confirmed cases. Since 2008, the notification rates of registered TB have declined. The notification rates of bacteriologically confirmed TB had been declining during 2005-2016, then remained stable after 2016. In subgroup, the notification rates of both registered TB and bacteriologically confirmed TB were higher among men, rural residents, and people aged ≥ 60 years. Compared with clinically confirmed TB, bacteriologically confirmed TB has shown higher rates of poor outcomes since 2008 and higher case fatality rate since 2005. The rate of poor outcomes remained stable during 2008-2019. However, after the COVID-19 outbreak, the rate of poor outcomes and case fatality rate of TB has risen significantly. Conclusion: After unremitting efforts to fight against TB, the notification rates of registered TB and bacteriologically confirmed TB declined in Shandong Province. The rate of poor outcomes remained stable during 2008-2019, then rise significantly after the COVID-19 outbreak. In the context of the long-term existence of COVID-19, further efforts should be made in TB diagnosis and treatment among high-risk population, especially with regard to males, rural residents and older adults.

Iron-related gene mutations driving global Mycobacterium tuberculosis transmission revealed by whole-genome sequencing.

BACKGROUND: Iron plays a crucial role in the growth of Mycobacterium tuberculosis (M. tuberculosis). However, the precise regulatory mechanism governing this system requires further elucidation. Additionally, limited studies have examined the impact of gene mutations related to iron on the transmission of M. tuberculosis globally. This research aims to investigate the correlation between mutations in iron-related genes and the worldwide transmission of M. tuberculosis. RESULTS: A total of 13,532 isolates of M. tuberculosis were included in this study. Among them, 6,104 (45.11%) were identified as genomic clustered isolates, while 8,395 (62.04%) were classified as genomic clade isolates. Our results showed that a total of 12 single nucleotide polymorphisms (SNPs) showed a positive correlation with clustering, such as Rv1469 (ctpD, C758T), Rv3703c (etgB, G1122T), and Rv3743c (ctpJ, G676C). Additionally, seven SNPs, including Rv0104 (T167G, T478G), Rv0211 (pckA, A302C), Rv0283 (eccB3, C423T), Rv1436 (gap, G654T), ctpD C758T, and etgB C578A, demonstrated a positive correlation with transmission clades across different countries. Notably, our findings highlighted the positive association of Rv0104 T167G, pckA A302C, eccB3 C423T, ctpD C758T, and etgB C578A with transmission clades across diverse regions. Furthermore, our analysis identified 78 SNPs that exhibited significant associations with clade size. CONCLUSIONS: Our study reveals the link between iron-related gene SNPs and M. tuberculosis transmission, offering insights into crucial factors influencing the pathogenicity of the disease. This research holds promise for targeted strategies in prevention and treatment, advancing research and interventions in this field.

Association Between Serum Anion Gap and Mortality in Critically Ill Patients with COPD in ICU: Data from the MIMIC IV Database.

Background: Serum anion gap (AG) has been proven to be associated with prognosis in critically ill patients. However, few studies have investigated the association between AG and all-cause mortality in critically ill patients with chronic obstructive pulmonary disease (COPD). Objective: We hypothesized that the initial AG level would predict the mortality risk in critically ill patients with COPD. Methods: This retrospective cohort study was based on the Medical Information Mart for Intensive Care (MIMIC) IV database. We extracted demographics, vital signs, laboratory tests, comorbidity, and scoring systems from the first 24 hours after patient ICU admission. Multivariable logistic regression analysis models were used to explore the association between serum AG levels and mortality. Interaction and stratified analyses were conducted including age, gender and comorbidity. Results: A total of 5531 critically ill patients with COPD were enrolled, composed of 53.6% male and 46.4% female with a median age of 73 years. The all-cause mortality of these patients during ICU hospitalization was 13.7%. The risk of all-cause mortality increased as the AG level increased in the univariate logistic regression analysis (OR=1.13, 95% CI: 1.11-1.15, p<0.01). After adjusting for all the covariates in multivariate logistic regression analysis, the odds ratio was 1.06 (95% CI: 1.04-1.09, p<0.01). Compared with the lowest AG group Q1 (≤11mmol/L), the adjusted OR value for AG and mortality in Q2 (12-13mmol/L) was 0.89 (95% CI: 0.63-1.25, p=0.502), Q3 (14-15mmol/L) was 0.95 (95% CI: 0.68-1.34, p=0.788), and Q4 (≥16mmol/L) was 1.49 (95% CI: 1.10-2.02, p=0.009) respectively. In addition, the results of the subgroup and stratified analyses were robust. Conclusion: AG is positively related to all-cause mortality in critically ill patients with COPD.

Heterovalent Metal Pair Sites on Metal-Organic Framework Ordered Macropores for Multimolecular Co-Activation.

The precise design of catalytic metal centers with multiple chemical states to facilitate sophisticated reactions involving multimolecular activation is highly desirable but challenging. Herein, we report an ordered macroporous catalyst with heterovalent metal pair (HMP) sites comprising CuII-CuI on the basis of a microporous metal-organic framework (MOF) system. This macroporous HMP catalyst with proximity heterovalent dual copper sites, whose distance is controlled to ∼2.6 Å, on macropore surface exhibits a co-activation behavior of ethanol at CuII and alkyne at CuI, and avoids microporous restriction, thereby promoting additive-free alkyne hydroboration reaction. The desired yield enhances dramatically compared with the pristine MOF and ordered macroporous MOF both with solely isovalent CuII-CuII sites. Density functional theory calculations reveal that the Cu-HMP sites can stabilize the Bpin-CuII-CuI-alkyne intermediate and facilitate C-B bond formation, resulting in a smooth alkyne hydroboration process. This work provides new perspectives to design multimolecular activation catalysts for sophisticated matter transformations.

Multidrug-resistant Mycobacterium tuberculosis transmission in Shandong, China.

Multidrug-resistant tuberculosis (MDR-TB) has imposed a significant economic and health burden worldwide, notably in China. Using whole genome sequence, we sought to understand the mutation and transmission of MDR-TB in Shandong. A retrospective study of patients diagnosed with pulmonary tuberculosis in Shandong from 2009 to 2018 was conducted. To explore transmission patterns, we performed whole genome sequencing on MDR-TB isolates, identified genomic clusters, and assessed the drug resistance of TB isolates. Our study analyzed 167 isolates of MDR-TB, finding that 100 were clustered. The predominant lineage among MDR-TB isolates was lineage 2, specifically with a notable 88.6% belonging to lineage 2.2.1. Lineage 4 constituted a smaller proportion, accounting for 4.2% of the isolates. We discovered that Shandong has a significant clustering percentage for MDR-TB, with Jining having the highest percentage among all Shandong cities. The clustering percentages of MDR-TB, pre-extensively drug-resistant tuberculosis, and extensively drug-resistant tuberculosis were 59.9%, 66.0%, and 71.4%, respectively, and the clustering percentages increased with the expansion of the anti-TB spectrum. Isolates from genomic clusters 1 and 3 belonged to lineage 2.2.1 and showed signs of cross-regional transmission. The distribution of rrs A1401G and katG S315T mutations in lineage 2.2.1 and 2.2.2 strains differed significantly (P < .05). MDR-TB isolates with rpoB I480V, embA-12C > T, and rrs A1401G mutations showed a higher likelihood of clustering (P < .05). Our findings indicate a significant problem of local transmission of MDR-TB in Shandong, China. Beijing lineage isolates and some drug-resistant mutations account for the MDR-TB transmission in Shandong.

Enhancement of biohydrogen production by photo-fermentation of corn stover via visible light catalyzed titanium dioxide/activated carbon fiber.

In this study, titanium dioxide/activated carbon fiber (TiO2/ACF) was synthesized by liquid-phase deposition method and the effect of TiO2/ACF on the performance of photo-fermentation biohydrogen production (PFHP) from corn stover under visible light catalysis was discussed. Results show the maximum cumulative hydrogen yield (CHY) obtained under the optimal conditions was 74.0 ± 1.3 mL/g TS with TiO2/ACF addition of 100 mg/L, which was twice that without TiO2/ACF addition (36.9 ± 1.0 mL/g TS). Initial pH value had the most significant effect on CHY. The addition of TiO2/ACF promoted the metabolic pathway of nitrogenase to reduce H+ produced by consuming acetic acid and butyric acid to hydrogen, and also shortened the photo-fermentation period. By scanning electron microscopy and X-ray diffraction analysis, the morphology and phase structure of TiO2/ACF after PFHP did not change significantly. This study laid the foundation for the reuse of TiO2 and its practical application in PFHP.

The Ratio of Red Blood Cell Distribution Width to Albumin as a Predictor for Rehospitalization Risk and Rehospitalization All-Cause Mortality in Middle-Aged and Elderly Survivors with Sepsis: An Ambispective ICU Cohort Study.

Objective: To explore the relationship between red blood cell distribution width to albumin (RDW/ALB) ratio (RAR) and the risk of rehospitalization and rehospitalization all-cause mortality in middle-aged and elderly survivors with sepsis based on an ambispective longitudinal cohort from the Intensive Care Unit (ICU). Methods: Between 2017 and 2022, 455 adults who survived the first-episode severe sepsis without recurrence for at least 3 months were included in this study. All participants were followed up every 4 weeks for 12 months. According to the tertiles of RAR, participants were divided into three groups: low-level (≤0.36, n = 152), moderate-level (0.37-0.44, n = 152), and high-level (≥0.45, n = 151). The relationship between RAR and the risk of rehospitalization and rehospitalization all-cause mortality was evaluated. Results: Out of 455 participants, 156 experienced rehospitalization (34.3%), of which 44 (28.2%) died. Receiver operating characteristic (ROC) analysis showed that the RAR cut-off values for rehospitalization and rehospitalization all-cause mortality were 0.4251 and 0.4743, respectively. Multivariate Cox regression analysis indicated that the RAR was positively associated with rehospitalization (P = 0.011) and all-cause mortality (P = 0.006). Compared with the low-level, the high-level RAR presented a higher dose-dependent rehospitalization risk (P = 0.02) and rehospitalization all-cause mortality (P = 0.044). The stratified analysis displayed that compared to the low-level, with the RAR increasing by 1.0, the risk for rehospitalization increased 3.602-fold in aged <65 patients (P = 0.002) and 1.721-fold in female patients (P = 0.014). Kaplan-Meier survival analysis implied a significant positive association between the RAR and the cumulative incidence of rehospitalization and rehospitalization all-cause mortality (log-rank, all P < 0.001). Conclusion: RAR has a reliable predictive value for the risk of rehospitalization and rehospitalization all-cause mortality in patients with sepsis. Consequently, monitoring RAR for at least 1 year after surviving sepsis in female patients aged <65 in clinical practice is critical.

Urolithin A exerts a protective effect on lipopolysaccharide-induced acute lung injury by regulating HMGB1-mediated MAPK and NF-κB signaling pathways.

Acute lung injury (ALI) is a severe inflammatory disorder that has a high morbidity and mortality rate. Urolithin A (UA) is reported to have anti-inflammatory and anti-oxidative effects in ALI. However, its molecular mechanisms in ALI remain to be explored. Mice and BEAS-2B cells were administrated with lipopolysaccharide (LPS) to mimic the ALI model in vivo and in vitro. Hematoxylin-eosin (HE) staining was used to detect the pathological injury of lung tissues. The levels of proinflammatory cytokines in bronchoalveolar lavage fluid (BALF) and culture supernatant and the levels of oxidative stress markers in lung tissues were measured using ELISA. DCFH-DA probe was used to assess the reactive oxygen species (ROS) level. TUNEL staining and flow cytometry were performed to determine cell apoptosis. The key targets and pathways were confirmed by immunohistochemistry (IHC) and western blot. UA suppressed the pathologic damage, wet/dry weight ratio, and total protein and inflammatory cells in BALF. UA decreased neutrophil infiltration and proinflammatory cytokines production. UA reduced the level of malondialdehyde (MDA) and increased the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in pulmonary tissues. UA also inhibited cell apoptosis in lung tissues by decreasing Bax expression and increasing Bcl-2 expression. In addition, UA suppressed LPS-induced inflammatory factor production, ROS level, and cell apoptosis in BEAS-2B. Importantly, UA decreased the expression of HMGB1 in LPS-treated mice and BEAS-2B cells. HMGB1 overexpression greatly abrogated the inhibition of UA on inflammation, ROS, and cell apoptosis in LPS-administrated BEAS-2B. Furthermore, UA treatment suppressed the phosphorylated levels of p38, JNK, ERK, and p65 in LPS-administrated mice and BEAS-2B cells. UA alleviated lung inflammation, oxidative stress, and apoptosis in ALI by targeting HMGB1 to inactivate the MAPK/NF-κB signaling, suggesting the potential of UA to treat ALI.