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Background: Previous studies involving risk-benefit analysis of trastuzumab deruxtecan (DS-8201) have indicated the benefit of this treatment, although it may increase the risk of interstitial lung disease (ILD) and/or pneumonitis in certain patients. This study aimed to assess the safety of DS-8201., Methods: A search was done for relevant articles in four electronic databases: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. All reports published up until November 2, 2022, were included, and study types were restricted to clinical trials; the last search was then updated to January 10, 2023. We also assessed the quality of the literature with the Cochrane Handbook for Systematic Reviews of Interventions and the Methodological Index for Non-Randomized Studies tool, and then performed a meta-analysis with R version 4.2.1., Results: A total of 1428 patients reported in 13 articles were included in this study. The analysis revealed that the most common all-grade treatment-emergent adverse events (TEAEs) were nausea and fatigue. The most common TEAE of grade 3 or above (grade ≥3) was neutropenia. The incidences of ILD and/or pneumonitis for all-grade and grade ≥3 TEAEs were 12.5% and 2.2%, respectively., Conclusions: This comprehensive summary of the incidence of TEAEs associated with DS-8201 in clinical trials provides an important guide for clinicians. The most common TEAEs were gastrointestinal reactions and fatigue; meanwhile, the most common grade ≥3 TEAE was hematological toxicity. ILD and/or pneumonitis were specific adverse drug reactions associated with DS-8201, of which physicians should be particularly aware for their higher morbidity and rates of grade ≥3 TEAEs., (© 2024 American Cancer Society.)

Background: There are a few reports on the associations between fine particulate matter (PM 2.5 )-bound heavy metals and lung function., Objectives: To evaluate the associations of single and mixed PM 2.5 -bound heavy metals with lung function., Methods: This study included 316 observations of 224 Chinese adults from the Wuhan-Zhuhai cohort over two study periods, and measured participants' personal PM 2.5 -bound heavy metals and lung function. Three linear mixed models, including the single constituent model, the PM 2.5 -adjusted constituent model, and the constituent residual model were used to evaluate the association between single metal and lung function. Mixed exposure models including Bayesian kernel machine regression (BKMR) model, weighted quantile sum (WQS) model, and Explainable Machine Learning model were used to assess the relationship between PM 2.5 -bound heavy metal mixtures and lung function., Results: In the single exposure analyses, significant negative associations of PM 2.5 -bound lead, antimony, and cadmium with peak expiratory flow (PEF) were observed. In the mixed exposure analyses, significant decreases in forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC), maximal mid-expiratory flow (MMF), and forced expiratory flow at 75% of the pulmonary volume (FEF75) were associated with the increased PM 2.5 -bound heavy metal mixture. The BKMR models suggested negative associations of PM 2.5 -bound lead and antimony with lung function. In addition, PM 2.5 -bound copper was positively associated with FEV1/FVC, MMF, and FEF75. The Explainable Machine Learning models suggested that FEV1/FVC, MMF, and FEF75 decreased with the elevated PM 2.5 -bound lead, manganese, and vanadium, and increased with the elevated PM 2.5 -bound copper., Conclusions: The negative relationships were detected between PM 2.5 -bound heavy metal mixture and FEV1/FVC, MMF, as well as FEF75. Among the PM 2.5 -bound heavy metal mixture, PM 2.5 -bound lead, antimony, manganese, and vanadium were negatively associated with FEV1/FVC, MMF, and FEF75, while PM 2.5 -bound copper was positively associated with FEV1/FVC, MMF, and FEF75., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: The predominant immune cells in solid tumors are M2-like tumor-associated macrophages (M2-like TAMs), which significantly impact the promotion of epithelial-mesenchymal transition (EMT) in tumors, enhancing stemness and facilitating tumor invasion and metastasis. However, the contribution of M2-like TAMs to tumor progression in gallbladder cancer (GBC) is partially known., Methods: Immunohistochemistry was used to evaluate the expression of M2-like TAMs and cancer stem cell (CSC) markers in 24 pairs of GBC and adjacent noncancerous tissues from patients with GBC. Subsequently, GBC cells and M2-like TAMs were co-cultured to examine the expression of CSC markers, EMT markers, and migratory behavior. Proteomics was performed on the culture supernatant of M2-like TAMs. The mechanisms underlying the induction of EMT, stemness, and metastasis in GBC by M2-like TAMs were elucidated using proteomics and transcriptomics. GBC cells were co-cultured with undifferentiated macrophages (M0) and analyzed. The therapeutic effect of gemcitabine combined with a chemokine (C-C motif) receptor 2 (CCR2) antagonist on GBC was observed in vivo., Results: The expression levels of CD68 and CD163 in M2-like TAMs and CD44 and CD133 in gallbladder cancer stem cells (GBCSCs) were increased and positively correlated in GBC tissues compared with those in neighboring noncancerous tissues. M2-like TAMs secreted a significant amount of chemotactic cytokine ligand 2 (CCL2), which activated the MEK/extracellular regulated protein kinase (ERK) pathway and enhanced SNAIL expression after binding to the receptor CCR2 on GBC cells. Activation of the ERK pathway caused nuclear translocation of ELK1, which subsequently led to increased SNAIL expression. GBCSCs mediated the recruitment and polarization of M0 into M2-like TAMs within the GBC microenvironment via CCL2 secretion. In the murine models, the combination of a CCR2 antagonist and gemcitabine efficiently inhibited the growth of subcutaneous tumors in GBC., Conclusions: The interaction between M2-like TAMs and GBC cells is mediated by the chemokine CCL2, which activates the MEK/ERK/ELK1/SNAIL pathway in GBC cells, promoting EMT, stemness, and metastasis. A combination of a CCR2 inhibitor and gemcitabine effectively suppressed the growth of subcutaneous tumors. Consequently, our study identified promising therapeutic targets and strategies for treating GBC., (© 2024. The Author(s).)

In this study, the concentration of inorganic ions (SO 4 2- , NH 4 + , NO 3 - and NO 2 - ) and morphological characteristics of condensable particulate matter (CPM) were investigated to elucidate the formation mechanism of inorganic CPM from ultra-low emission coal-fired power plants. The concentration of inorganic ions increased with the increase of H 2 O content and concentration of inorganic gaseous contaminants (SO 2 , NO X and NH 3 ), and decrease of condensation temperature, indicating the enhancement of heterogenous reaction in the saturated flue gas. Furthermore, NO X and SO 2 could undergo redox reactions, leading to an elevation in the concentration of SO 4 2- and NO 3 - . Additionally, the introduction of NH 3 resulted in increased concentrations of SO 4 2- , NO 3 - , and NO 2 - , highlighting the significant role of NH 3 neutralization in CPM nucleation. The condensation of SO 3 /sulfuric acid aerosols was enhanced under saturation conditions, and SO 2 and SO 3 /sulfuric acid aerosols could contribute synergistically to the formation of SO 4 2- . Moreover, morphological analysis revealed the presence of both well-aggregated solid CPM and dispersed liquid CPM, confirming the formation of inorganic CPM during fast condensation. Furthermore, the detected CPM were composed of S and O, which identified the significant role of sulfates in the inorganic CPM. These findings provide valuable insights for the control of inorganic CPM in flue gas systems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

A few studies found polycyclic aromatic hydrocarbons (PAHs) were associated with serum uric acid (SUA) or hyperuricemia (HUA). However, the longitudinal study is vacant, and the underlying mechanisms remain unclear. We aimed to assess the cross-sectional and longitudinal associations of urinary PAHs metabolites with SUA levels and HUA risk, and explore the mediating effects of oxidative stress and inflammation. 10 urinary mono-hydroxylated PAHs metabolites and SUA levels were measured among 4047 Chinese urban residents at baseline and 1496 individuals at 6-year follow-up. Biomarkers of oxidative damage and inflammation in urine/plasma were determined at baseline. We adopted generalized linear mixed models and logistic regression to assess the associations of PAHs metabolites with SUA and HUA, weighted quantile sum regression and adaptive elastic net regression to evaluate the overall effects of multi-PAHs mixture, and mediation analysis to estimate the mediating roles of the biomarkers. In the cross-sectional study, each 1-unit increase in the ln-transformed values of 2-OHNa, 2-OHFlu, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 4.10-, 3.90-, 6.42-, 7.33-, 4.85-, 5.43-, 4.47-, 7.67-, and 5.22-μmol/L increase in SUA, respectively. Meanwhile, each 1-unit increase in the ln-transformed values of 1-OHNa, 2-OHNa, 4-OHPh, 9-OHPh, 3-OHPh, 2-OHPh, ΣOHNa, ΣOHPh, and ΣOHPAHs was associated with a 17, 14, 15, 22, 14, 19, 18, 27, and 21% increment in HUA risk, respectively. After 6 years, individuals with persistent high level of 9-OHPh had a 12.5 μmol/L increase in SUA compared with those with persistent low level. The overall effects of multi-PAHs mixture on SUA and HUA remain positive. 8-hydroxy-deoxyguanosine mediated the associations of PAHs metabolites with SUA and HUA, and the mediated proportion ranged from 5.39% to 15.34%. PAHs exposure was associated with the elevated SUA levels and increased HUA risk, and oxidative DNA damage may be one of the underlying mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Objective: Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cancer and currently lacks effective biomarkers. This research aims to analyze and identify RNA editing profile associated with ccRCC prognosis through bioinformatics and in vitro experiments., Methods: Transcriptome data and clinical information for ccRCC were retrieved from the TCGA database, and RNA editing files were obtained from the Synapse database. Prognostic models were screened, developed, and assessed using consistency index analysis and independent prognostic analysis, etc. Internal validation models were also constructed for further evaluation. Differential genes were investigated using GO, KEGG, and GSEA enrichment analyses. Furthermore, qPCR was performed to determine gene expression in human renal tubular epithelial cells HK-2 and ccRCC cells A-498, 786-O, and Caki-2., Results: An RNA editing-based risk score, that effectively distinguishes between high and low-risk populations, has been identified. It includes CHD3| chr17:7815229, MYO19| chr17:34853704, OIP5-AS1| chr15:41590962, MRI1| chr19:13883962, GBP4| chr1:89649327, APOL1| chr22:36662830, FCF1| chr14:75203040 edited sites or genes and could serve as an independent prognostic factor for ccRCC patients. qPCR results showed significant up-regulation of CHD3, MYO19, MRI1, APOL1, and FCF1 in A-498, 786-O, and Caki-2 cells, while the expression of OIP5-AS1 and GBP4 was significantly down-regulated., Conclusion: RNA editing site-based prognostic models are valuable in differentiating between high and low-risk populations. The seven identified RNA editing sites may be utilized as potential biomarkers for ccRCC., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Chen, Li, Huang, Su, Wang and Liang.)

Background: Norovirus is the predominant pathogen causing foodborne illnesses and acute gastroenteritis (AGE) outbreaks worldwide, imposing a significant disease burden. This study aimed to investigate the epidemiological characteristics and genotypic diversity of norovirus outbreaks in Hongshan District, Wuhan City., Methods: A total of 463 AGE cases from 39 AGE-related outbreaks in Hongshan District between January 1, 2021, and June 30, 2023, were included in the study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to identify norovirus types GI and GII in anal swab samples from all cases. Norovirus-positive samples were sequenced and analyzed for the open reading frame (ORF) 1/ORF2 hinge region., Results: 26 norovirus infectious outbreaks were reported among 39 acute diarrheal outbreaks, including 14 outbreaks in kindergartens, 8 in elementary schools, and 4 in universities. Based on clinical symptoms and epidemiological investigations, a total of 1295 individuals were identified as having been exposed to norovirus, yielding an attack rate of 35.75 %. A higher proportion of outbreaks was observed during the winter and spring seasons (38.46 %). Additionally, norovirus-positive samples were subjected to sequencing and analysis of the open reading frame (ORF) 1/ORF2 hinge region. Genotypic data for norovirus was successfully obtained from 18 (69.23 %) of the infectious outbreaks, revealing 10 distinct recombinant genotypes. GII.4 Sydney 2012 [P31] and GII.17[P17] were the predominant strains in 2021 and 2022, GII.3 [P12] emerged as the dominant strain in 2023., Conclusion: Norovirus outbreaks in Hongshan District predominantly occurred in crowded educational institutions, with peaks in the cold season and a high attack rate in universities. GII.3 [P12] has become the locally predominant strain., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Environmental exposure to crystalline silica (CS) particles is common and occurs during natural, industrial, and agricultural activities. Prolonged inhalation of CS particles can cause silicosis, a serious and incurable pulmonary fibrosis disease. However, the underlying mechanisms remain veiled. Herein, we aim to elucidate the novel mechanisms of interleukin-11 (IL-11) driving fibroblast metabolic reprogramming during the development of silicosis. We observed that CS exposure induced lung fibrosis in mice and activated fibroblasts, accompanied by increased IL-11 expression and metabolic reprogramming switched from mitochondrial respiration to glycolysis. Besides, we innovatively uncovered that elevated IL-11 promoted the glycolysis process, thereby facilitating the fibroblast-myofibroblast transition (FMT). Mechanistically, CS-stimulated IL-11 activated the extracellular signal-regulated kinase (ERK) pathway and the latter increased the expression of hypoxia inducible factor-1α (HIF-1α) via promoting the translation and delaying the degradation of the protein. HIF-1α further facilitated glycolysis, driving the FMT process and ultimately the formation of silicosis. Moreover, either silence or neutralization of IL-11 inhibited glycolysis augmentation and attenuated CS-induced lung myofibroblast generation and fibrosis. Overall, our findings elucidate the role of IL-11 in promoting fibroblast metabolic reprogramming through the ERK-HIF-1α axis during CS-induced lung fibrosis, providing novel insights into the molecular mechanisms and potential therapeutic targets of silicosis., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Gallstone disease (GS) is an important risk factor for Gallbladder cancer (GBC). However, the mechanisms of the progression of GS to GBC remain unclear. Long non-coding RNA (lncRNA), modulates DNA/RNA/proteins at epigenetic, pre-transcriptional, transcriptional and posttranscriptional levels, and plays a potential therapeutic role in various diseases. This study aims to identify lncRNAs that have a potential impact on GS-promoted GBC progression., Methods and Results: Six GBC patients without GS, six normal gallbladder tissues, nine gallstones and nine GBC patients with GS were admitted to our hospital. The next-generation RNA-sequencing was performed to analyze differentially expressed (DE) lncRNA and messenger RNA (mRNA) in four groups. Then overlapping and specific molecular signatures were analyzed. We identified 29 co-DEGs and 500 co-DElncRNAs related to gallstone or GBC. The intersection and concatenation of co-DEGs and co-DElncRNA functionally involved in focal adhesion, Transcriptional misregulation in cancers, Protein digestion and absorption, and ECM-receptor interaction signaling pathways may contribute to the development of gallbladder cancer. Further exploration is necessary for early diagnosis and the potential treatment of GBC. FXYD2, MPZL1 and PAH were observed in both co-DEGs and co-DElncRNA and validated by qRT-PCR., Conclusion: Our data identified a series of DEGs and DElncRNAs, which were involved in the progression of GBC and GS-related metabolism pathways. Compared to GBC, the GS profile was more similar to para-tumor tissues in transcriptome level and lower risk of cancer. Further exploration is necessary from GBC patients with different periods of follow-up gallstone., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Wang et al.)

Polychlorinated biphenyls (PCBs) are endocrine-disrupting chemicals that have been associated with various adverse health conditions. Herein we explored the associations of PCBs with dyslipidemia and further assessed the modification effect of genetic susceptibility and lifestyle factors. Six serum PCBs (PCB-28, 101, 118, 138, 153, 180) were determined in 3845 participants from the Wuhan-Zhuhai cohort. Dyslipidemia, including hyper-total cholesterol (HyperTC), hyper-triglyceride (HyperTG), hyper-low density lipoprotein cholesterol (HyperLDL-C), and hypo-high density lipoprotein cholesterol (HypoHDL-C) were determined, and lipid-specific polygenic risk scores (PRS) and healthy lifestyle score were constructed. We found that all six PCB congeners were positively associated with the prevalence of dyslipidemias, and ΣPCB level was associated with HyperTC, HyperTG, and HyperLDL-C in dose-response manners. Compared with the lowest tertiles of ΣPCB, the odds ratios (95% confidence intervals) in the highest tertiles were 1.490 (1.258, 1.765) for HyperTC, 1.957 (1.623, 2.365) for HyperTG, and 1.569 (1.316, 1.873) for HyperLDL-C, respectively. Compared with those with low ΣPCB, healthy lifestyle, and low genetic risk, participants with high ΣPCB, unfavorable lifestyle, and high genetic risk had the highest odds of HyperTC, HyperTG, and HyperLDL-C. Our study provided evidence that high PCB exposure exacerbated the association of genetic risk and unhealthy lifestyle with dyslipidemia., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Noise pollution has grown to be a major public health issue worldwide. We sought to profile serum metabolite expression changes related to occupational noise exposure by untargeted metabolomics, as well as to evaluate the potential roles of serum metabolites in occupational noise-associated arterial stiffness (AS). Our study involved 30 noise-exposed industrial personnel (Lipo group) and 30 noise-free controls (Blank group). The untargeted metabolomic analysis was performed by employing a UPLC-HRMS. The associations of occupational noise and significant differential metabolites (between Blank/Lipo groups) with AS were evaluated using multivariable-adjusted generalized linear models. We performed the least absolute shrinkage and selection operator regression analysis to further screen for AS's risk metabolites. We explored 177 metabolites across 21 categories significantly differentially expressed between Blank/Lipo groups, and these metabolites were enriched in 20 metabolic pathways. Moreover, 15 metabolites in 4 classes (including food, glycerophosphocholine, sphingomyelin [SM] and triacylglycerols [TAG]) were adversely associated with AS (all P < 0.05). Meanwhile, five metabolites (homostachydrine, phosphatidylcholine (PC) (32:1e), PC (38:6p), SM (d41:2) and TAG (45:1) have been proven to be useful predictors of AS prevalence. However, none of these 15 metabolites were found to have a mediating influence on occupational noise-induced AS. Our study reveals specific metabolic changes caused by occupational noise exposure, and several metabolites may have protective effects on AS. However, the roles of serum metabolites in noise-AS association remain to be validated in future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Association of circulating glycoprotein acetyls (GlycA), a systemic inflammation biomarker, with lung function and respiratory diseases remain to be investigated. We examined the genetic correlation, shared genetics, and potential causality of GlycA (N = 115,078) with lung function and respiratory diseases (N = 497,000). GlycA showed significant genetic correlation with FEV1 (r g  = -0.14), FVC (r g  = -0.18), asthma (r g  = 0.21) and COPD (r g  = 0.31). We consistently identified ten shared loci (including chr3p21.31 and chr8p23.1) at both SNP and gene level revealing potential shared biological mechanisms involving ubiquitination, immune response, Wnt/β-catenin signaling, cell growth and differentiation in tissues or cells including blood, epithelium, fibroblast, fetal thymus, and fetal intestine. Genetically elevated GlycA was significantly correlated with lung function and asthma susceptibility (354.13 ml decrement of FEV1, 442.28 ml decrement of FVC, and 144% increased risk of asthma per SD increment of GlycA) from MR analyses. Our findings provide insights into biological mechanisms of GlycA in relating to lung function, asthma, and COPD., (© 2024. The Author(s).)

Objective: Whether coal mine dust exposure increases cardiovascular diseases (CVDs) risk was rarely explored. Our objective was to examine the association between coal mine dust exposure and cardiovascular risk., Methods: We estimated cumulative coal mine dust exposure (CDE) for 1327 coal miners by combining data on workplace dust concentrations and work history. We used brachial-ankle pulse wave velocity (baPWV, a representative indicator of arterial stiffness) and ten-year atherosclerotic cardiovascular disease (ASCVD) risk to assess potential CVD risk, exploring their associations with CDE., Results: Positive dose-response relationships of CDE with baPWV and ten-year ASCVD risk were observed after adjusting for covariates. Specifically, each 1 standard deviation (SD) increase in CDE was related to a 0.27 m/s (95% CI: 0.21, 0.34) increase in baPWV and a 1.29 (95% CI: 1.14, 1.46) elevation in OR (odds ratio) of risk of abnormal baPWV. Moreover, each 1 SD increase in CDE was associated with a 0.74% (95% CI: 0.63%, 0.85%) increase in scores of ten-year ASCVD and a 1.91 (95% CI: 1.62, 2.26) increase in OR of risk of ten-year ASCVD. When compared with groups unexposed to coal mine dust, significant increase in the risk of arterial stiffness and ten-year ASCVD in the highest CDE groups were detected., Conclusion: The study suggested that cumulative exposure to coal mine dust was associated with elevated arterial stiffness and ten-year ASCVD risk in a dose-response manner. These findings contribute valuable insights for cardiovascular risk associated with coal mine dust., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Silicosis is an occupational lung disease because of exposure to silica dust in the workplace. Evidence on the spatiotemporal change of silicosis burden worldwide remains limited. This study utilized data extracted from the Global Burden of Disease Study 2019 to examine the numbers and age-standardized rates of incidence (ASIR), mortality (ASMR), and disability-adjusted life years (DALYs) caused by silicosis between 1990 and 2019. Average annual percentage changes (AAPCs) were calculated to evaluate the temporal trends of age-standardized indicators by sex, region, and socio-demographic index (SDI) since 1990. Results indicated an increase in new silicosis cases globally, rising by 64.61% from 84,426 in 1990 to 138,971 in 2019, with a sustained high number of DALYs attributed to this disease. Although the global age-standardized rates of incidence, mortality, and DALYs of silicosis have decreased since 1990, the number of new cases has increased in 168 countries and territories, and the ASIR of silicosis has also risen in 118 countries and territories, primarily in developing countries. Since 1990, the burden of silicosis among the elderly has significantly increased. Countries with higher SDI experienced a more rapid decline in the silicosis burden. Silicosis remains a public health problem that requires significant attention. Programs for prevention and elimination of this public health issue need to be established in more countries and territories. Protecting young workers from silica dust exposure is crucial to prevent the onset of silicosis in their later years and to reduce the disease burden among older workers., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Aims: We aimed to evaluate the association of occupational noise with metabolic syndrome (MetS) and its components, and to assess the potential role of miRNAs in occupational noise-associated MetS., Methods: A total of 854 participants were enrolled in our study. Cumulative noise exposure (CNE) was estimated in conjunction with workplace noise test records and research participants' employment histories. Logistic regression models adjusted for potential confounders were used to assess the association of CNE and miRNAs with MetS and its components., Results: We observed linear positive dose-response associations between occupational noise exposure and the prevalence of MetS (OR: 1.031; 95 % CI: 1.008, 1.055). And linear and nonlinear relationship were also found for the association of occupational noise exposure with high blood pressure (OR: 1.024; 95 % CI: 1.007, 1.041) and reduced high-density lipoprotein (OR: 1.051; 95 % CI: 1.031, 1.072), respectively. MiR-200a-3p, miR-92a-3p and miR-21-5p were inversely associated with CNE, or the prevalence of MetS and its components (all P < 0.05). However, we did not find any statistically significant mediation effect of miRNAs in the associations of CNE with MetS. Furthermore, the prevalence of bilateral hearing loss in high-frequency increased (OR: 1.036; 95 % CI: 1.008, 1.067) with CNE level rising, and participants with bilateral hearing loss in high-frequency had a significantly higher risk of MetS (OR: 1.727; 95 % CI: 1.048, 2.819)., Conclusion: Our study suggests that occupational noise exposure is associated with MetS and its components, and the role of miRNAs in noise-induced increasing MetS risk needs to be confirmed in future studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

China has been continuously improving its monitoring methods and strategies to address key infectious diseases (KIDs). After the severe acute respiratory syndrome epidemic in 2003, China established a comprehensive reporting system for infectious diseases (IDs) and public health emergencies. The relatively lagging warning thresholds, limited warning information, and outdated warning technology are insufficient to meet the needs of comprehensive monitoring for modern KIDs. Strengthening early monitoring and warning capabilities to enhance the public health system has become a top priority, with increasing demand for early warning thresholds, information, and techniques, thanks to constant innovation and development in molecular biology, bioinformatics, artificial intelligence, and other identification and analysis technologies. A panel of 31 experts has recommended a fourth-generation comprehensive surveillance system targeting KIDs (41 notifiable diseases and emerging IDs). The aim of this surveillance system is to systematically monitor the epidemiology and causal pathogens of KIDs in hosts such as humans, animals, and vectors, along with associated environmental pathogens. By integrating factors influencing epidemic spread and risk assessment, the surveillance system can serve to detect, predict, and provide early warnings for the occurrence, development, variation, and spread of known or novel KIDs. Moreover, we recommend comprehensive ID monitoring based on the fourth-generation surveillance system, along with a data-integrated monitoring and early warning platform and a consortium pathogen detection technology system. This series of considerations is based on systematic and comprehensive monitoring across multiple sectors, dimensions, factors, and pathogens that is supported by data integration and connectivity. This expert consensus will provides an opportunity for collaboration in various fields and relies on interdisciplinary application to enhance comprehensive monitoring, prediction, and early warning capabilities for the next generation of ID surveillance. This expert consensus will serve as a reference for ID prevention and control as well as other related activities., (© 2024 The Authors.)

Objective: The primary objective of this study is to investigate the mechanism by which Bacillus coagulans TBC169 accelerates intestinal function recovery in patients who have undergone gynecological laparoscopic surgery, using metabolomics and gut microbiota analysis., Methods: A total of 20 subjects were selected and randomly divided into two groups: the intervention group ( n  = 10) receiving Bacillus coagulans TBC169 Tablets (6 pills, 1.05 × 10 8  CFU), and the control group ( n  = 10) receiving placebos (6 pills). After the initial postoperative defecation, fecal samples were collected from each subject to analyze their gut microbiota and metabolic profiles by high-throughput 16S rRNA gene sequencing analysis and untargeted metabonomic., Results: There were no statistically significant differences observed in the α-diversity and β-diversity between the two groups; however, in the intervention group, there was a significant reduction in the relative abundance of unclassified&#95;Enterobacteriaceae at the genus level. Furthermore, the control group showed increased levels of Holdemanella and Enterobacter , whereas the intervention group exhibited elevated levels of Intestinimonas . And administration of Bacillus coagulans TBC169 led to variations in 2 metabolic pathways: D-glutamine and D-glutamate metabolism, and arginine biosynthesis., Conclusion: This study demonstrated that consuming Bacillus coagulans TBC169 after gynecological laparoscopic surgery might inhibit the proliferation of harmful Enterobacteriaceae ; mainly influence 2 pathways including D-glutamine and D-glutamate metabolism, and arginine biosynthesis; and regulate metabolites related to immunity and intestinal motility; which can help regulate immune function, maintain intestinal balance, promote intestinal peristalsis, and thus accelerate the recovery of intestinal function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gao, Yan, Guan, Zhang and Chen.)

Background: Kidney damage is common in patients with Fabry disease (FD), but more accurate information about the risk of progression to kidney failure is needed for clinical decision-making. In particular, FD patients with mild renal involvement often lack timely intervention and treatment. We aimed to utilize a model to predict the risk of renal progression in FD patients., Methods: Between November 2011 and November 2019, ERT-naive patients with FD were recruited from three medical centers in China. To assess the risk of a 50% decline in the estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD), Cox proportional hazards models were utilized. The performance of these models was assessed using discrimination, calibration, and reclassification., Results: A total of 117 individuals were enrolled. The mean follow-up time was 4.8 years, during which 35 patients (29.9 %) progressed to the composite renal outcomes. Male sex, baseline proteinuria, eGFR and globotriaosylsphingosine (Lyso-Gb3) were found to be independent risk factors for kidney progression by the Cox model, based on which a combined model containing those clinical variables and Lyso-Gb3 and clinical models including only clinical indicators were constructed. The two prediction models had relatively good performance, with similar model fit measured by R 2 (59.8 % vs. 61.1 %) and AIC (51.54 vs. 50.08) and a slight increase in the C statistic (0.949 vs. 0.951). Calibration curves indicated closer alignment between predicted and actual renal outcomes in the combined model. Furthermore, subgroup analysis revealed that Lyso-Gb3 significantly improved the predictive performance of the combined model for kidney prognosis in low-risk patients with a baseline eGFR over 60 ml/min/1.73 m 2 or proteinuria levels less than 1 g/d when compared to the clinical model., Conclusions: Lyso-Gb3 improves the prediction of kidney outcomes in FD patients with a low risk of progression, suggesting that these patients may benefit from early intervention to assist in clinical management. These findings need to be externally validated., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The OpenVigil database can be used to assess medications that may cause supraventricular tachycardia (SVT) and to produce a reference for their safe use in clinical settings., Methods: We analyzed first-quarter data from 2004 to 2023, obtained by searching the OpenVigil database using the keyword "supraventricular tachycardia." Trade names and generic names were obtained by querying the RxNav database, and the proportions were summarized. The proportionate reporting ratio (PRR), reporting odds ratio, and chi-square values were also summarized. We created Asahi diagrams and set the screening criteria to drug events ≥30, PRR >2, and chi-square >4. Outcomes were evaluated using the Side Effect Resource database, several scientific literature databases, and the Hangzhou Yiyao Rational Medication System., Results: A total of 2435 distinct medications were found to induce SVT between the first quarter of 2004 and 2023, leading to 22,375 documented adverse events related to SVT. Further investigation revealed that salbutamol, paroxetine, formoterol, paclitaxel, venlafaxine, and theophylline were most likely to cause SVT., Conclusion: We conducted signal mining of adverse drug events using the OpenVigil database and evaluated the six drugs most likely to cause SVT. The results of this research can serve as a drug safety reference in the clinic., Competing Interests: Declaration of conflicting interestThe authors declare that there is no conflict of interest.

The short-term associations of ambient temperature exposure with lung function in middle-aged and elderly Chinese remain obscure. The study included 19,128 participants from the Dongfeng-Tongji cohort's first (2013) and second (2018) follow-ups. The lung function for each subject was determined between April and December 2013 and re-assessed in 2018, with three parameters (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV 1 ], and peak expiratory flow [PEF]) selected. The China Meteorological Data Sharing Service Center provided temperature data during the study period. In the two follow-ups, a total of 25,511 records (average age: first, 64.57; second, 65.80) were evaluated, including 10,604 males (41.57%). The inversely J-shaped associations between moving average temperatures (lag01-lag07) and FVC, FEV 1 , and PEF were observed, and the optimum temperatures at lag04 were 16.5 °C, 18.7 °C, and 16.2 °C, respectively. At lag04, every 1 °C increase in temperature was associated with 14.07 mL, 9.78 mL, and 62.72 mL/s increase in FVC, FEV 1 , and PEF in the low-temperature zone (modification < 0.05). Non-optimal temperatures may cause lung function decline. Several individual characters and lifestyles have effect modification on the temperature effects., Competing Interests: The authors have no relevant financial or non-financial interests to disclose., (© 2024 The Author(s).)

Osteoporosis, a condition that is characterized by low bone mineral density (BMD), is a serious health concern worldwide. This study aims to explore the relationship between whole egg consumption and BMD levels in the US population. This study involves 19 208 participants with valid BMD and egg consumption data from the National Health and Nutrition Examination Survey (NHANES) during 2005-2006, 2007-2008, 2009-2010, 2013-2014 and 2017-2018. Linear regression analysis was conducted to evaluate the association between whole egg consumption and BMD levels. Mediation analysis was used to investigate the role of serum alkaline phosphatase (ALP) in the above relationship. After multivariate adjustment, participants consuming whole eggs over 3.53 ounce per day in their diet were found to have elevated BMD levels in the femur (0.013 g cm -2 with 95% CI: 0.004, 0.022) and lumbar spine (0.013 g cm -2 with 95% CI: 0.002, 0.024) ( P trend < 0.05). The additive interaction of egg consumption and body mass index (BMI) on the BMD of both the femur and lumbar spine ( P interaction < 0.05) was also analyzed. The association between whole egg consumption and BMD of both the femur and lumbar spine were significantly mediated by ALP with 71.8% and 83.3% mediation proportion, respectively. In general, higher whole egg consumption is positively related to an increase in the BMD scores of both the femur and lumbar spine among the US population.

Background: Gallbladder cancer (GBC), a highly malignant gastrointestinal tumor, lacks effective therapies. Foxhead box A2 (FOXA2) is a tumor suppressor that is poorly expressed in various human malignancies. This study aimed to ascertain FOXA2 expression in GBC and its relevance to tumor metastasis, and to elucidate its regulatory mechanism with epithelial-mesenchymal transition (EMT) as an entry point, in the hope of providing a potential therapeutic target for GBC., Methods: FOXA2 expression in GBC tissues was first detected using immunohistochemistry (IHC), followed by correlation analysis with clinicopathological characteristics and survival prognosis. Subsequently, the effects of FOXA2 on GBC cell migration and invasion, as well as EMT induction, were evaluated by scratch, Transwell, RT-PCR, and Western blot assays, together with animal experimentation. Ultimately, mRNA sequencing was carried out to identify the key downstream target genes of FOXA2 in controlling the EMT process in GBC cells, and dual-luciferase reporter and chromatin immunoprecipitation assays were used to determine its regulatory mechanism., Results: FOXA2 was underexpressed in GBC tissues and inversely correlated with tumor node metastasis stage, lymph node metastasis, and poor patient prognosis. FOXA2 exerts suppressive effects on EMT and metastasis of GBC in vivo and in vitro. FOXA2 can impede GBC cell migratory and invasive functions and EMT by positively mediating serine protein kinase inhibitor B5 (SERPINB5) expression., Conclusion: FOXA2 directly binds to the SERPINB5 promoter region to stimulate its transcription, thereby modulating the migration and invasion behaviors of GBC cells as well as the EMT process, which might be an effective therapeutic target against GBC., (© 2023 Wiley Periodicals LLC.)

Aims: To explore the association of dietary vitamin intake from food and/or supplement with mortality in US adults with diabetes., Materials and Methods: This prospective cohort study was conducted on 5418 US adults with diabetes from the National Health and Nutrition Examination Survey 1999-2018. Vitamin intake from food and supplements was estimated via dietary recall. Sufficient intake from food or food + supplement was defined as ≥ estimated average requirement (EAR) and ≤ tolerable upper intake level (UL), insufficient intake, < EAR; and excess intake, > UL. Medium supplementary intake was classified as > median level and ≤75th percentile; low intake, ≤ median level; and high intake, >75th percentile, as reported by supplement users., Results: A total of 1601 deaths occurred among the participants over a median follow-up of 11.0 years. Cox regression analysis of the single-vitamin model demonstrated that sufficient vitamin A and folate intake from food and food + supplement and medium vitamin A and folate intake from supplement; sufficient riboflavin, niacin, and vitamin B 6 intake from food and food + supplement; and sufficient thiamin and vitamin E intake from food + supplement were significantly associated with reduced all-cause mortality (all p < 0.05). In the multivitamin model, sufficient vitamin A and folate intake from food and food + supplement, medium vitamin A and folate intake from the supplement, and sufficient niacin intake from food and food + supplement were inversely associated with mortality (all p < 0.05)., Conclusions: Vitamin A and folate intake from food or supplement and niacin intake from food were significantly associated with reduced mortality in US adults with diabetes., (© 2023 John Wiley & Sons Ltd.)

Background: Pancreatic cancer (PC) is a fatal human malignancy with a poor prognosis. Corosolic acid (CRA) is a triterpenoid, has been reported to have inhibitory effects on tumor growth. However, the role of CRA on PC has not been explored. Here, we aimed to uncover the molecular mechanisms of CRA in PC progression., Methods: Cell viability, lactate dehydrogenase (LDH) release, cell apoptosis and senescence were detected by cell counting kit-8 (CCK-8), LDH, flow cytometry and senescence associated-β-galactosidase (SA-β-gal) assay. Levels of relevant proteins and oxidative stress (OS) markers were evaluated by Western blot and enzyme-linked immunosorbent assay (ELISA). A xenograft tumor model was established to explore the in vivo effects of CRA on PC., Results: We found that CRA inhibited PC cell viability and promoted LDH release in a dose-dependent manner, but had no significant effect on human normal pancreatic ductal epithelial cells HPDE6C7. CRA increased OS-induced cell apoptosis and senescence in HAPC and SW1990 cells. And CRA decreased the levels of anti-apoptotic protein Bcl-2, and elevated the expression of pro-apoptotic protein Bax and senescence-associated proteins P21 and P53. Besides, CRA decreased tumor growth in xenograft models. Furthermore, CRA inactivated the Janus kinase-2 (JAK2)/Signal Transducer and Activator of Transcription 3 (STAT3) signaling pathway in HAPC and SW1990 cells. Functional experiments demonstrated that activation of the JAK2/STAT3 pathway by the JAK2 activator coumermycin A1 (C-A1) or the STAT3 activator colivelin (col) reduced the contribution effect of OS, apoptosis and senescence by CRA., Conclusion: Taken together, our findings indicated that CRA exerted anti-cancer effects in PC by inhibiting the JAK2/STAT3 pathway., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Acute lymphoblastic leukemia (ALL) is one of the most common malignant tumor types of the circulatory system. Dexamethasone (DEX) acts on the glucocorticoid (GC) receptor (GR) and is a first-line chemotherapy drug for ALL. However, long-term or high-dose applications of the drug can not only cause adverse reactions, such as osteoporosis and high blood pressure, but can also cause downregulation of GR and lead to drug resistance. In the present study, reverse transcription-quantitative PCR, western blotting and LysoTracker Red staining were used to observe the effects of DEX and andrographolide (AND; a botanical with antitumorigenic properties) combined treatment. It was found that AND enhanced the sensitivity of CEM-C1 cells, a GC-resistant cell line, to DEX, and synergistically upregulated GR both at the transcriptional and post-transcriptional level with DEX. The combination of AND with DEX synergistically alkalized lysosomal lumen and downregulated the expression of autophagy-related genes Beclin1 and microtubule-associated 1 protein light chain 3 (LC3), thereby inhibiting autophagy. Knocking down LC3 expression enhanced GR expression, suggesting that GR was regulated by autophagy. Furthermore, compared with the monotherapy group (AND or DEX in isolation), AND interacted with DEX to activate the autophagy-dependent PI3K/AKT/mTOR signaling pathway by enhancing the phosphorylation of PI3K, AKT and mTOR, thereby decreasing GR degradation and increasing the sensitivity of cells to GCs. In conclusion, the present study demonstrated that AND exhibited a synergistic anti-ALL effect with DEX via upregulation of GR, which was orchestrated by the autophagy-related PI3K/AKT/mTOR signaling pathway. The results of the present study therefore provided novel research avenues and strategies for the treatment of ALL., Competing Interests: The authors are named inventors on Chinese patent, ZL202010550895.1, entitled ‘The application of the combination of andrographolide and dexamethasone in the preparation of compound anti-acute lymphoblastic leukemia drugs’ held by Guilin Medical University (Guilin, China) for the combination of andrographolide and dexamethasone as a treatment for acute lymphoblastic leukemia, which was approved on April 13, 2021., (Copyright: © Li et al.)

Fatigue driving is a serious threat to road safety, which is why accurately identifying fatigue driving behavior and warning drivers in time are of great significance in improving traffic safety. However, accurately recognizing fatigue driving is still challenging due to large intra-class variations in facial expression, continuity of behaviors, and illumination conditions. A fatigue driving recognition method based on feature parameter images and a residual Swin Transformer is proposed in this paper. First, the face region is detected through spatial pyramid pooling and a multi-scale feature output module. Then, a multi-scale facial landmark detector is used to locate 23 key points on the face. The aspect ratios of the eyes and mouth are calculated based on the coordinates of these key points, and a feature parameter matrix for fatigue driving recognition is obtained. Finally, the feature parameter matrix is converted into an image, and the residual Swin Transformer network is presented to recognize fatigue driving. Experimental results on the HNUFD dataset show that the proposed method achieves an accuracy of 96.512%, thus outperforming state-of-the-art methods.

Silica particles are commonly encountered in natural and industrial activities. Long-term environmental exposure to silica can result in silicosis, which is characterized by chronic inflammation and abnormal tissue repair in lung. To uncover the role of m 6 A modification in silica-induced pulmonary inflammation, we conducted this study using established mouse and macrophage models. In this study, the aerodynamic diameter of silica particles was approximately 1-2 µm. We demonstrated that silica exposure in mice caused pulmonary inflammation and increased global m 6 A modification levels, the downregulation of alkB homolog 5 (ALKBH5) might contribute to this alteration. Besides, we found that F4/80, a macrophage-specific biomarker, was co-expressed with ALKBH5 through dual immunofluorescent staining. In vitro studies using MeRIP assays suggested that Slamf7 was a target gene regulated by m 6 A modification, and specific inhibition of ALKBH5 increased Slamf7 expression. Mechanistically, ALKBH5 promoted m 6 A modification of Slamf7, which decreased Slamf7 mRNA stability in an m 6 A-dependent manner, ultimately regulating Slamf7 expression. In addition, silica exposure activated PI3K/AKT and induced macrophage autophagy. Inhibition of Slamf7 promoted autophagy, reduced the secretion of pro-inflammatory cytokines, and improved silica-induced pulmonary inflammation. In summary, ALKBH5 can regulate silica-induced pulmonary inflammation by modulating Slamf7 m 6 A modification and affecting the function of macrophage autophagy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Evidence on the association between occupational noise exposure and blood pressure is inconsistent, and the underlying mechanism remains unknown. This study aimed to evaluate the association between occupational noise exposure and blood pressure, and explore the potential role of miRNAs in the association. A total of 894 subjects from two companies in Wuhan, China were included. Occupational noise exposure was assessed using cumulative noise exposure (CNE), and six candidate plasma miRNAs (miR-92a-3p, miR-21-5p, miR-200a-3p, miR-200b-3p, miR-200c-3p, and miR-1-3p) which were not only associated with blood pressure/hypertension but also related to oxidative stress were selected according to previous studies and tested. A linear dose-response relationship was found between occupational noise exposure and blood pressure, including systolic blood pressure (SBP) and diastolic blood pressure (DBP). Each 1-unit increase in CNE levels was significantly associated with a 0.130 (95 % confidence interval [CI] = 0.026, 0.234) unit increase in SBP and a 0.141 (95 % CI = 0.063, 0.219) unit increase in DBP. However, the association between occupational noise and hypertension is not statistically significant (P > 0.05). In the meanwhile, occupational noise exposure was negatively associated with miRNA-92a-3p (β = -0.019, 95 % CI = -0.032, -0.006) and miRNA-21-5p (β = -0.031, 95 % CI = -0.052, -0.010), and miRNA-92a-3p mediated 24.66 % of the association between occupational noise exposure and DBP. In addition, bilateral high-frequency hearing loss was not only positively associated with occupational noise exposure (OR = 1.974, 95 % CI = 1.084, 3.702) but also DBP (β = 2.546, 95 % CI = 0.160, 4.932). Our study suggests that occupational noise exposure is positively associated with SBP and DBP, and miRNA-92a-3p partially mediate the association between occupational noise exposure and DBP., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

To quantify the association of polycyclic aromatic hydrocarbons (PAHs) and the polygenic risk score (PRS) with lung function decline, we developed a repeated-measures study with 4681 observations from baseline and 6-year follow-up of the Wuhan-Zhuhai cohort. Lung function and urinary monohydroxylated PAH metabolites (OH-PAHs) were measured for each observation. The PRS was derived from 246 lung function-associated genetic variants weighted by the effect size of the decreasing ratio of forced expiratory volume in 1 s by forced vital capacity (FEV1/FVC). Linear mixed models were used to estimate the longitudinal exposure-response relationships between OH-PAHs and lung function, and to evaluate the interactions between OH-PAHs and PRS on the longitudinal change of lung function. We found that each 1-unit increase in log-transformed values of 9-hydroxyfluorene, 2-hydroxyfluorene, 4-hydroxyphenanthrene, 9-hydroxyphenanthrene, 2-hydroxyphenanthrene, 1-hydroxyphenanthrene, 1-hydroxypyrene, low molecular weight OH-PAHs (ΣLMW-OH-PAHs), and total OH-PAHs (ΣOH-PAHs) was associated with an annual change in FEV1/FVC of -0.140, -0.112, -0.260, -0.300, -0.159, -0.220, -0.145, -0.156, and -0.177 %/year, respectively. Interactions on the annual decline of FEV1/FVC were detected between ΣLMW-OH-PAHs and PRS (-0.010 %/year, 95% confidence interval -0.018 to -0.001, P int  = 0.0228), and between ΣOH-PAHs and PRS (-0.010 %/year, -0.018 to -0.001, P int  = 0.0203). These results indicated that specific and total urinary OH-PAHs were associated with the longitudinal FEV1/FVC decline, and ΣLMW-OH-PAHs as well as ΣOH-PAHs interacted with PRS on the annual decline of FEV1/FVC., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Objective: To estimate the pooled prevalence, as well as the spatial and temporal distribution, of urolithiasis among subjects in China., Materials and Methods: We conducted a comprehensive search of both Chinese and English databases to retrieve literature pertaining to the prevalence of urolithiasis in the indigenous Chinese population. A random-effects meta-analysis model was employed to calculate the pooled prevalence of urolithiasis. Subgroup analyses were conducted based on factors such as time, region, gender, and sample size. Prevalence and spatial distribution maps were created based on provinces and latitude/longitude coordinates., Results: A total of 46 studies conducted in 22 provinces across China were included in this meta-analysis and the pooled prevalence of urolithiasis, kidney stones, ureteric calculi, urethral and bladder stones were 8.1% (95% confidence interval [CI] 5.6-11.1%), 7.8% (95% CI 5.8-10.0%), 3.2% (95% CI 0.6-5.7%), 0.5% (95% CI 0.1-0.9%). Most of the urolithiasis prevalence screening in China was concentrated between 100° E and 120° E, with higher rates observed in low latitude areas. Subgroup analysis of kidney stones revealed that Guangdong (12.7%) and Guangxi (10.3%) had the highest prevalence, with the eastern developed area exhibiting higher rates compared to the west. The prevalence in males was higher than in females (odds ratio 1.67, 95% CI 1.46-1.92), although the gender gap has significantly reduced since 2006. Moreover, a greater sample size is associated with a decreased prevalence of urolithiasis., Conclusions: The prevalence of urolithiasis is increasing in China, and there are noteworthy regional or provincial disparities in occurrence. It is worth noting that the current number of screening studies in some areas is insufficient. Additional investigations with appropriate sample sizes should be supplemented in time., (© 2023 BJU International.)

Exposure of dichlorodiphenyltrichloroethane (DDT) pesticide was suggested to be associated with adverse effects on the respiratory system. However, the effects of DDT exposure on lung function remain unclear. Our objectives were to investigate the potential associations of internal levels of DDT and its metabolites including dichlorodiphenyldichloroethylene (DDE) and dichlorodiphenyldichloroethane (DDD) with lung function. Serum DDT, DDE, and DDD concentrations and lung function were measured among 3968 general adults from the Wuhan-Zhuhai cohort. The cross-sectional and longitudinal associations of serum DDT and its metabolites with lung function were assessed using linear mixed models. The results showed negative dose-response relationships of serum DDT, DDE, and DDD levels with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ). In the cross-sectional analyses, each 1-unit increase in natural log-transformed values of p,p'-DDE, o,p'-DDT, o,p'-DDE, or p,p'-DDD was significantly associated with a 25.77-, 44.84-, 51.13-, or 43.44-mL decrease in FVC, respectively. Each 1-unit increase in natural log-transformed values of o,p'-DDT, o,p'-DDE, o,p'-DDD, or p,p'-DDD was significantly associated with a 35.72-, 31.87-, 29.54-, or 36.80-mL decrease in FEV 1 , respectively. In the three-year longitudinal analyses, each 1-unit increase in natural log-transformed serum p,p'-DDT and p,p'-DDE was significantly associated with a 35.10 mL and 36.38 mL decrease in FVC, and a 26.32 mL and 32.37 mL decrease in FEV 1 , respectively. In conclusion, DDT and its metabolites exposure were associated with lung function decline in the general Chinese adult population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Using a new method of η 5 -Li and η 6 -Mg atoms capping the faces of the classical fullerene-like borospherene T d B 40 , we theoretically predict an exohedral metalloborospherene T d Mg 10 Li 12 &B 40 molecule. Remarkably, a newfangled endoexo cage isomerism is proposed. Further, embedding Mg atoms in the T d B 40 cage forms endohedral derivatives. Due to the intramolecular pull-push electron transfer relay, these obtained molecules possess unequal multilayered and alternant spherical charge distribution. The outer is an excess electron layer, bringing a molecular nonlinear switch character and an electron reservoir behavior with strong electron-donating and -accepting abilities. The middle (Mg 2+ ) 10 (Li + ) 12 and the outer layers together constitute an electric double layer, presenting the behavior of a molecular capacitor where the electronic charge-discharge process occurs in the outer excess electron layer. The inner part is an empty cage B 40 26- with a strong negative electric field. The valence electrons of the embedded Mg atoms are transformed into new excess electrons and added in the outer excess electron layer, also exhibiting the charging behavior of the molecular capacitor. Considering the chemical reaction in the inner cage, the embedded Mg atom is ionized, forming an Mg 2+ cation and 2e under the strong negative electric field; meanwhile, 2e is powerfully pushed into the outer excess electron layer. This chemical process shows a generalized Coulomb explosion, and thus the exohedral metalloborospherene molecules with cage B 40 26- may act as molecular reactors. The new species mark the genesis of classical fullerene-like borospherene chemistry and stimulate their applications in molecular nonlinear optical and nanoelectronics.

Background: TGF-β is related to the function of T cells in the tumor microenvironment. However, the characteristics of TGF-β affecting the function of CD8 + T cells in hepatocellular carcinoma (HCC) have not been clearly resolved., Methods: In this study, flow cytometry, mass cytometry, immunohistochemistry, RNA-seq, single-cell RNA-seq, assay for transposase-accessible chromatin with high throughput sequencing, chromatin immunoprecipitation, and dual-luciferase reporter gene assay were used to study the regulatory effect and molecular mechanism of TGF-β on HCC infiltrating CD8 + T cells., Results: Here, we demonstrated that the overall effect of TGF-β on CD8 + T cells in HCC was to activate p-p38 to induce exhaustion, but it also initiated cell-intrinsic resistance mechanisms: 1) TGF-β upregulated the levels of p-STAT1 (S727) and promoted LAIR2 secretion; 2) the TGF-β-p-STAT1-LAIR2 axis relieved CD8 + T cells from exhaustion, which we called "self-rescue"; 3) this "self-rescue" behavior showed time and dose limitations on TGF-β stimulation, which was easily masked by stronger inhibitory signals; 4) the function of CD8 + T cells was improved by using TAK-981 to amplify "self-rescue" signal., Conclusion: Our study describes a "self-rescue" mechanism of CD8 + T cells in HCC against exhaustion and the good effects from amplifying this signal., (© 2023. Springer Nature Switzerland AG.)

Objective: The tumor microenvironment plays a critical role in the radiotherapy and immunotherapy response of cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC). Radioresistance is a key factor in treatment failure among patients who receive radical radiotherapy. Thus, new immune-related biomarkers associated with radiotherapy response in CESC are needed. Methods: In this study, the CIBERSORT and ESTIMATE methods were applied to determine the percentage of tumor-infiltrating cells and the number of immune components in 103 CESCs treated with radiotherapy from The Cancer Genome Atlas (TCGA) database. The main dysregulated genes were subjected to multivariate and univariate analyses. The prognostic value of this system was studied via receiver operating characteristic curve and survival analysis. For further confirmation, the biomarkers' expression levels and predictive value were validated by immunohistochemistry (IHC) and qRT-PCR. The CIBERSORT algorithm was used to calculate the compositional patterns of 22 types of immune cells in cervical cancer patients treated with radiation therapy. Results: Data for 17 radioresistant and 86 radiosensitive tumors were obtained from the The Cancer Genome Atlas database. 53 immune-related DEGs were identified. GO and KEGG analyses revealed that the DEGs were enriched in protein kinase B signaling, growth factors in cytokines, the MAPK pathway and the PI3K-Akt pathway. Then, 14 key immune-related genes built a risk scoring model were deemed prognostic in CESC with radiotherapy. The area under the curve (AUC) of the model was 0.723, and the high-risk group presented worse outcomes than the low-risk group. In addition, the high-risk group tended to have persistent tumors ( p = 0.001). The high expression of WT1 and SPOUYT4 were associated with relapse, the high expression of Angiotensinogen and MIEN1 were associated with nonrelapse. Analysis of the immune microenvironment indicated that M0 macrophages, M2 macrophages, activated mast cells and resting memory CD4 + T cells were positively correlated with the risk score ( p < 0.05). Conclusion: The novel immune-related risk scoring system has some advantages in predicting the prognosis and treatment response of cervical cancer patients treated with radiotherapy. Moreover, it might provide novel clues for providing targeted immune therapy to these patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wu, Lin, Sheng, Chen, Liang, Wu and Ke.)

Objective: Our study aimed to explore the causal effect of depression on the risk of gallstone disease, and the mediation effects of metabolic traits., Methods: A retrospective cohort study on Chinese elderly from the Dongfeng-Tongji cohort (including 18,141 individuals) was conducted to estimate the adverse effect of probable depression on the risk of gallstone disease. Two-sample Mendelian randomization was performed in European and East-Asian ancestries, to verify the causal relationship between major depression and gallstone disease. We further applied two-step Mendelian randomization to explore the mediation effects of metabolic traits., Results: In the cohort study, probable depression was associated with an increased risk of gallstone disease within 5 years, with RR (95% CI) of 1.33 (1.12, 1.58) in multivariable regression, and 1.34 (1.11, 1.61) following propensity score weighting. Bidirectional Mendelian randomization in European ancestry revealed a positive causal effect (OR: 1.21; 95% CI: 1.07 to 1.37) of genetically predicted major depression liability on gallstone disease, based on the inverse variance weighted method. Little evidence was presented from other complementary approaches, and the analysis in East-Asian ancestry (IVW estimated OR: 1.03; 95% CI: 0.92 to 1.15). The indirect effect via waist circumference and HDL-C were 1.06 (95% CI: 1.02 to 1.10) and 1.01 (95% CI: 1.00 to 1.01) respectively, which mediated 25.8% and 3.78% of the causal relationship., Conclusions: Our study suggested a higher risk of gallstone disease in the population with probable depression, while the two-sample Mendelian randomization provided weak evidence for the causal relationship, which was moderately mediated by abdominal obesity., Competing Interests: Declaration of Competing Interest All authors declare that they have no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Patients with head and neck cancer (HNC) often experience various types and degrees of complications and functional impairment following surgery or radiotherapy. Consequently, these patients require extensive postdischarge rehabilitation, either at home or in the community. Numerous studies have shown the advantages of mobile Health (mHealth) technology in assisting patients with cancer with self-management and rehabilitation during the postdischarge period. However, few reviews have focused on the intervention, management, and evaluation of mHealth technology in postdischarge patients with HNC., Objective: This study aimed to conduct a scoping review of mHealth technology apps and interventions currently available to patients discharged from hospitals after receiving treatment for HNC. This study sought to identify and summarize the types and effectiveness of existing mHealth interventions as well as the differences in their outcome assessments., Methods: The PubMed, Embase, Web of Science, and CINAHL databases were used to identify studies with no publication time limits. The keywords "mobile health technology" and "head and neck cancer" were combined to address the main concepts of the research questions., Results: Of the 1625 papers identified, 13 (0.8%) met the inclusion and exclusion criteria. Most studies (n=8, 61.5%) were randomized controlled trials (RCTs) and cohort studies. These studies were conducted in 6 countries. The main aims of the mHealth interventions in these studies are as follows: (1) symptom monitoring and assessment, (2) rehabilitation training, (3) access to medical health information, (4) telehealth advisers, (5) peer communication and support, and (6) follow-up/review reminders. The outcome evaluations of the 13 included studies were grouped into 4 categories: (1) technology usability and patient satisfaction, (2) self-management of symptoms and patient-reported outcome-related indicators, (3) adherence, and (4) health-related quality of life., Conclusions: A limited number of studies have investigated the use of mHealth technology in the postdischarge self-management of patients with HNC. The existing literature suggests that mHealth technology can effectively assist patients with HNC in self-management and postdischarge interventions. It plays an important role in addressing patients' health information needs, reducing both their somatic and psychological burdens, and improving their overall quality of life. Future research should prioritize conducting additional high-quality RCTs to evaluate the usability and analyze the cost-effectiveness of mHealth technology., (©Yufei Li, Weihong Chen, Yanjing Liang, Ling Yang, Lili Hou. Originally published in JMIR mHealth and uHealth (https://mhealth.jmir.org), 23.10.2023.)

Benzo(a)pyrene was sparsely studied for its early respiratory impairment. The non-canonical ligand WNT5A play a role in pneumonopathy, while its function during benzo(a)pyrene-induced adverse effects were largely unexplored. Individual benzo(a)pyrene, plasma WNT5A, and spirometry 24-hour change for 87 residents from Wuhan-Zhuhai cohort were determined to analyze potential role of WNT5A in benzo(a)pyrene-induced lung function alternation. Normal bronchial epithelial cell lines were employed to verify the role of WNT5A after benzo(a)pyrene treatment. RNA sequencing was adopted to screen for benzo(a)pyrene-related circulating microRNAs and differentially expressed microRNAs between benzo(a)pyrene-induced cells and controls. The most potent microRNA was selected for functional experiments and target gene validation, and their mechanistic link with WNT5A-mediated non-canonical Wnt signaling was characterized through rescue assays. We found significant associations between increased benzo(a)pyrene and reduced 24-hour changes of FEF 50% and FEF 75% , as well as increased WNT5A. The benzo(a)pyrene-induced inflammation and epithelial-mesenchymal transition in BEAS-2B and 16HBE cells were attenuated by WNT5A silencing. hsa-miR-122-5p was significantly and positively associated with benzo(a)pyrene and elevated after benzo(a)pyrene induction, and exerted its effect by downregulating target gene TP53. Functionally, WNT5A participates in benzo(a)pyrene-induced lung epithelial injury via non-canonical Wnt signaling modulated by hsa-miR-122-5p/TP53 axis, showing great potential as a preventive and therapeutic target., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Objective . Although convolutional neural networks (CNN) and Transformers have performed well in many medical image segmentation tasks, they rely on large amounts of labeled data for training. The annotation of medical image data is expensive and time-consuming, so it is common to use semi-supervised learning methods that use a small amount of labeled data and a large amount of unlabeled data to improve the performance of medical imaging segmentation. Approach . This work aims to enhance the segmentation performance of medical images using a triple-teacher cross-learning semi-supervised medical image segmentation with shape perception and multi-scale consistency regularization. To effectively leverage the information from unlabeled data, we design a multi-scale semi-supervised method for three-teacher cross-learning based on shape perception, called Semi-TMS. The three teacher models engage in cross-learning with each other, where Teacher A and Teacher C utilize a CNN architecture, while Teacher B employs a transformer model. The cross-learning module consisting of Teacher A and Teacher C captures local and global information, generates pseudo-labels, and performs cross-learning using prediction results. Multi-scale consistency regularization is applied separately to the CNN and Transformer to improve accuracy. Furthermore, the low uncertainty output probabilities from Teacher A or Teacher C are utilized as input to Teacher B, enhancing the utilization of prior knowledge and overall segmentation robustness. Main results . Experimental evaluations on two public datasets demonstrate that the proposed method outperforms some existing semi-segmentation models, implicitly capturing shape information and effectively improving the utilization and accuracy of unlabeled data through multi-scale consistency. Significance . With the widespread utilization of medical imaging in clinical diagnosis, our method is expected to be a potential auxiliary tool, assisting clinicians and medical researchers in their diagnoses., (© 2023 Institute of Physics and Engineering in Medicine.)

Evidence on liver injury and non-alcoholic fatty liver disease (NAFLD) from volatile organic compounds (VOCs) exposure is insufficient. A cross-sectional study including 3011 US adults from the National Health and Nutrition Examination Survey was conducted to explore the associations of urinary exposure biomarkers (EBs) for 13 VOCs (toluene, xylene, ethylbenzene, styrene, acrylamide, N,N-dimethylformamide, acrolein, crotonaldehyde, 1,3-butadiene, acrylonitrile, cyanide, propylene oxide, and 1-bromopropane) with liver injury biomarkers and the risk of NAFLD by performing single-chemical (survey weight regression) and mixture (Bayesian kernel machine regression [BKMR] and weighted quantile sum [WQS]) analyses. We found significant positive associations of EBs for toluene and 1-bromopropane with alanine aminotransferase (ALT), EBs for toluene, crotonaldehyde, and 1,3-butadiene with asparate aminotransferase (AST), EBs for 1,3-butadiene and cyanide with alkaline phosphatase (ALP), EBs for xylene and cyanide with hepamet fibrosis score (HFS), EBs for the total 13 VOCs (except propylene oxide) with United States fatty liver index (USFLI), and EBs for xylene, N,N-dimethylformamide, acrolein, crotonaldehyde, and acrylonitrile with NALFD; and significant inverse associations of EBs for ethylbenzene, styrene, acrylamide, acrolein, crotonaldehyde, 1,3-butadiene, acrylonitrile, cyanide, and propylene oxide with total bilirubin, EBs for ethylbenzene, styrene, acrylamide, acrolein, 1,3-butadiene, acrylonitrile, and cyanide with albumin (ALB), EBs for ethylbenzene, styrene, acrylamide, N,N-dimethylformamide, acrolein, crotonaldehyde, 1,3-butadiene, acrylonitrile, cyanide, and propylene oxide with total protein (TP), and EB for 1-bromopropane with AST/ALT (all P-FDR<0.05). In BKMR and WQS, the mixture of VOC-EBs was significantly positively associated with ALT, AST, ALP, HFS, USFLI, and the risk of NAFLD, while significantly inversely associated with TBIL, ALB, TP, and AST/ALT. VOCs exposure was associated with liver injury and increased risk of NAFLD in US adults. These findings highlight that great attention should be paid to the potential risk of liver health damage from VOCs exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Arsenic-related oxidative stress and resultant diseases have attracted global concern, while longitudinal studies are scarce. To assess the relationship between arsenic exposure and systemic oxidative damage, we performed two repeated measures among 5236 observations (4067 participants) in the Wuhan-Zhuhai cohort at the baseline and follow-up after 3 years. Urinary total arsenic, biomarkers of DNA oxidative damage (8-hydroxy-2'-deoxyguanosine (8-OHdG)), lipid peroxidation (8-isoprostaglandin F2alpha (8-isoPGF2α)), and protein oxidative damage (protein carbonyls (PCO)) were detected for all observations. Here we used linear mixed models to estimate the cross-sectional and longitudinal associations between arsenic exposure and oxidative damage. Exposure-response curves were constructed by utilizing the generalized additive mixed models with thin plate regressions. After adjusting for potential confounders, arsenic level was significantly and positively related to the levels of global oxidative damage and their annual increased rates in dose-response manners. In cross-sectional analyses, each 1% increase in arsenic level was associated with a 0.406% (95% confidence interval (CI): 0.379% to 0.433%), 0.360% (0.301% to 0.420%), and 0.079% (0.055% to 0.103%) increase in 8-isoPGF2α, 8-OHdG, and PCO, respectively. More importantly, arsenic was further found to be associated with increased annual change rates of 8-isoPGF2α (β: 0.147; 95% CI: 0.130 to 0.164), 8-OHdG (0.155; 0.118 to 0.192), and PCO (0.050; 0.035 to 0.064) in the longitudinal analyses. Our study suggested that arsenic exposure was not only positively related with global oxidative damage to lipid, DNA, and protein in cross-sectional analyses, but also associated with annual increased rates of these biomarkers in dose-dependent manners., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Competing Interests: No conflicts of interest.

This study investigated the effect of sustained loading on the cumulative damage of a newly developed smart cement-based self-healing composite material (SMA-ECC). SMA-ECC is composed of engineered cementitious composite (ECC) and shape memory alloy (SMA) fibers. A uniaxial compressive test with five predefined loading levels (0%, 30%, 40%, 50%, and 60% of compressive strength) was conducted on SMA-ECC hollow-cylindrical specimens and ECC control hollow-cylindrical specimens. The cumulative damage was mainly determined by changes in the total water absorption of different groups of specimens during three different periods (not loaded, at a predefined loading level, and after unloading). A normalized water content index was proposed to couple the effects of self-healing, sustained loading, and cumulative damage. The test results indicate that the cumulative water absorption of SMA-ECC was 35% lower than that of ECC, which may indicate less irreparable damage. In addition, the self-healing ability of SMA-ECC specimens under different compression load levels was evaluated through normalized water content analysis. SMA-ECC exhibited a 100% repair rate at load levels of 30% and 40%. At a higher load level of 60%, the repair rate of SMA-ECC was 76%. These results collectively emphasize the significant impermeability and self-healing performance of SMA-ECC after unloading.

The longitudinal relationships of polychlorinated biphenyls (PCBs) exposure with glucose homeostasis and type 2 diabetes (T2D) risk among Chinese population have not been assessed, and interactions of PCB exposure with genetic susceptibility and lifestyle are unclear. In this prospective cohort study, fasting plasma glucose (FPG) and insulin (FPI) and seven serum indicator-PCBs were measured for each participant. We constructed polygenic risk score (PRS) of T2D and healthy lifestyle score. Each 1-unit increment of ln-transformed PCB-118 was related with a 0.141 mmol/L, 11.410 pmol/L, 0.661, and 74.5% increase in FPG, FPI, homeostasis model assessment of insulin resistance, and incident T2D risk over 6 years, respectively. Each 1-unit increment in T2D-PRS was related with a 0.169 mmol/L elevation of FPG and 65.5% elevation of incident T2D risk during 6 years. Compared with participants who had low T2D-PRS and low PCB-118, participants with high T2D-PRS and high PCB-118 showed a significant increase in FPG (0.162 mmol/L; P for interaction <0.001) and incident T2D risk [hazard ratio (HR)= 2.222]. Participants with low PCB-118, low PRS, and healthy lifestyle had the lowest incident T2D risk (HR=0.232). Our findings highlighted the significance of reducing PCB exposure and improvement in lifestyle for T2D prevention and management, especially for individuals with higher genetic risk of T2D., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: Preeclampsia (PE) is a serious condition in pregnant women and hence an important topic in obstetrics. The current research aimed to recognize the potential and significant immune-related diagnostic biomarkers for PE. Methods: From the Gene Expression Omnibus (GEO) data sets, three public gene expression profiles (GSE24129, GSE54618, and GSE60438) from the placental samples of PE and normotensive pregnancy were downloaded. Differentially expressed genes (DEGs) were selected and determined among 73 PE and 85 normotensive control pregnancy samples. The DEGs were used for Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Disease Ontology (DO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). The candidate biomarkers were identified by the least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE) analysis. The receiver operating characteristic curve (ROC) was applied to evaluate diagnostic ability. For further confirmation, the expression levels and diagnostic value of biomarkers in PE were verified in the GSE75010 data set (80 PE and 77 controls) and validated by qRT-RCR, Western blot, and immunohistochemistry (IHC). The CIBERSORT algorithm was used to calculate the compositional patterns of 22 types of immune cells in PE. Results: In total, 15 DEGs were recognized. The GO and KEGG analyses revealed that the DEGs were enriched in the steroid metabolic process, receptor ligand activity, GnRH secretion, and neuroactive ligand-receptor interaction. The recognized DEGs were primarily implicated in cell-type benign neoplasm, kidney failure, infertility, and PE. Gene sets related to hormone activity, glycosylation, multicellular organism process, and response to BMP were activated in PE. The LEP gene was distinguished as a diagnostic biomarker of PE (AUC = 0.712) and further certified in the GSE75010 data set (AUC = 0.850). The high expression of LEP was associated with PE in clinical samples. In addition, the analysis of the immune microenvironment showed that gamma delta T cells, memory B cells, M0 macrophages, and regulatory T cells were positively correlated with LEP expression ( P < 0.05). Conclusion: LEP expression can be considered to be a diagnostic biomarker of PE and can offer a novel perspective for future studies regarding the occurrence and molecular mechanisms of PE., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Ke, Chen, Wu, Zhuang, Lin, Shi and Wu.)

The effects of triazine herbicides on glucose metabolism remain unclear. In this study, we aimed to assess the associations between serum triazine herbicides and glycemia-related risk indicators in general adults, and to evaluate the mediating role of natural immunoglobulin M antibodies (IgM) in the above associations among uninfected participants. We measured the concentrations of atrazine, cyanazine, and IgM in serum, as well as fasting plasma glucose (FPG), and fasting plasma insulin in 4423 adult participants from the Wuhan-Zhuhai cohort baseline population, enrolled in 2011-2012. Generalized linear models were used to evaluate the associations of serum triazine herbicides with glycemia-related risk indicators, and mediation analyses were performed to evaluate the mediating role of serum IgM in the above associations. The median levels of serum atrazine and cyanazine were 0.0237 μg/L and 0.0786 μg/L, respectively. Our study found significant positive associations of serum atrazine, cyanazine, and Σtriazine with FPG levels, risk of impaired fasting glucose (IFG), abnormal glucose regulation (AGR), and type 2 diabetes (T2D). Additionally, serum cyanazine and Σtriazine were found to be significant positive associated with the homeostatic model assessment of insulin resistance (HOMA-IR) levels. Significant negative linear relationships were observed in associations of serum IgM with serum triazine herbicides, FPG, HOMA-IR levels, the prevalence of T2D, and AGR (P < 0.05). Furthermore, we observed a significant mediating role by IgM in the associations of serum triazine herbicides with FPG, HOMA-IR, and AGR, with the proportions ranging from 2.96% to 7.71%. To ensure the stability of our findings, we conducted sensitivity analyses in normoglycemic participants and found that the association of serum IgM with FPG and the mediating role by IgM remained stable. Our results suggest that triazine herbicides exposure is positively associated with abnormal glucose metabolism, and decreasing serum IgM may partly mediate these associations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: The World Health Organization (WHO) and the International Labour Organization (ILO) are developing joint estimates of the work-related burden of disease and injury (WHO/ILO Joint Estimates), with contributions from a large number of individual experts. Evidence from human, animal and mechanistic data suggests that occupational exposure to dusts and/or fibres (silica, asbestos and coal dust) causes pneumoconiosis. In this paper, we present a systematic review and meta-analysis of the prevalences and levels of occupational exposure to silica, asbestos and coal dust. These estimates of prevalences and levels will serve as input data for estimating (if feasible) the number of deaths and disability-adjusted life years that are attributable to occupational exposure to silica, asbestos and coal dust, for the development of the WHO/ILO Joint Estimates., Objectives: We aimed to systematically review and meta-analyse estimates of the prevalences and levels of occupational exposure to silica, asbestos and coal dust among working-age (≥ 15 years) workers., Data Sources: We searched electronic academic databases for potentially relevant records from published and unpublished studies, including Ovid Medline, PubMed, EMBASE, and CISDOC. We also searched electronic grey literature databases, Internet search engines and organizational websites; hand-searched reference lists of previous systematic reviews and included study records; and consulted additional experts., Study Eligibility and Criteria: We included working-age (≥ 15 years) workers in the formal and informal economy in any WHO and/or ILO Member State but excluded children (< 15 years) and unpaid domestic workers. We included all study types with objective dust or fibre measurements, published between 1960 and 2018, that directly or indirectly reported an estimate of the prevalence and/or level of occupational exposure to silica, asbestos and/or coal dust., Study Appraisal and Synthesis Methods: At least two review authors independently screened titles and abstracts against the eligibility criteria at a first stage and full texts of potentially eligible records at a second stage, then data were extracted from qualifying studies. We combined prevalence estimates by industrial sector (ISIC-4 2-digit level with additional merging within Mining, Manufacturing and Construction) using random-effects meta-analysis. Two or more review authors assessed the risk of bias and all available authors assessed the quality of evidence, using the ROB-SPEO tool and QoE-SPEO approach developed specifically for the WHO/ILO Joint Estimates., Results: Eighty-eight studies (82 cross-sectional studies and 6 longitudinal studies) met the inclusion criteria, comprising > 2.4 million measurements covering 23 countries from all WHO regions (Africa, Americas, Eastern Mediterranean, South-East Asia, Europe, and Western Pacific). The target population in all 88 included studies was from major ISCO groups 3 (Technicians and Associate Professionals), 6 (Skilled Agricultural, Forestry and Fishery Workers), 7 (Craft and Related Trades Workers), 8 (Plant and Machine Operators and Assemblers), and 9 (Elementary Occupations), hereafter called manual workers. Most studies were performed in Construction, Manufacturing and Mining. For occupational exposure to silica, 65 studies (61 cross-sectional studies and 4 longitudinal studies) were included with > 2.3 million measurements collected in 22 countries in all six WHO regions. For occupational exposure to asbestos, 18 studies (17 cross-sectional studies and 1 longitudinal) were included with > 20,000 measurements collected in eight countries in five WHO regions (no data for Africa). For occupational exposure to coal dust, eight studies (all cross-sectional) were included comprising > 100,000 samples in six countries in five WHO regions (no data for Eastern Mediterranean). Occupational exposure to silica, asbestos and coal dust was assessed with personal or stationary active filter sampling; for silica and asbestos, gravimetric assessment was followed by technical analysis. Risk of bias profiles varied between the bodies of evidence looking at asbestos, silica and coal dust, as well as between industrial sectors. However, risk of bias was generally highest for the domain of selection of participants into the studies. The largest bodies of evidence for silica related to the industrial sectors of Construction (ISIC 41-43), Manufacturing (ISIC 20, 23-25, 27, 31-32) and Mining (ISIC 05, 07, 08). For Construction, the pooled prevalence estimate was 0.89 (95% CI 0.84 to 0.93, 17 studies, I 2 91%, moderate quality of evidence) and the level estimate was rated as of very low quality of evidence. For Manufacturing, the pooled prevalence estimate was 0.85 (95% CI 0.78 to 0.91, 24 studies, I 2 100%, moderate quality of evidence) and the pooled level estimate was rated as of very low quality of evidence. The pooled prevalence estimate for Mining was 0.75 (95% CI 0.68 to 0.82, 20 studies, I 2 100%, moderate quality of evidence) and the pooled level estimate was 0.04 mg/m 3 (95% CI 0.03 to 0.05, 17 studies, I 2 100%, low quality of evidence). Smaller bodies of evidence were identified for Crop and animal production (ISIC 01; very low quality of evidence for both prevalence and level); Professional, scientific and technical activities (ISIC 71, 74; very low quality of evidence for both prevalence and level); and Electricity, gas, steam and air conditioning supply (ISIC 35; very low quality of evidence for both prevalence and level). For asbestos, the pooled prevalence estimate for Construction (ISIC 41, 43, 45,) was 0.77 (95% CI 0.65 to 0.87, six studies, I 2 99%, low quality of evidence) and the level estimate was rated as of very low quality of evidence. For Manufacturing (ISIC 13, 23-24, 29-30), the pooled prevalence and level estimates were rated as being of very low quality of evidence. Smaller bodies of evidence were identified for Other mining and quarrying (ISIC 08; very low quality of evidence for both prevalence and level); Electricity, gas, steam and air conditioning supply (ISIC 35; very low quality of evidence for both prevalence and level); and Water supply, sewerage, waste management and remediation (ISIC 37; very low quality of evidence for levels). For coal dust, the pooled prevalence estimate for Mining of coal and lignite (ISIC 05), was 1.00 (95% CI 1.00 to 1.00, six studies, I 2 16%, moderate quality of evidence) and the pooled level estimate was 0.77 mg/m 3 (95% CI 0.68 to 0.86, three studies, I 2 100%, low quality of evidence). A small body of evidence was identified for Electricity, gas, steam and air conditioning supply (ISIC 35); with very low quality of evidence for prevalence, and the pooled level estimate being 0.60 mg/m 3 (95% CI -6.95 to 8.14, one study, low quality of evidence)., Conclusions: Overall, we judged the bodies of evidence for occupational exposure to silica to vary by industrial sector between very low and moderate quality of evidence for prevalence, and very low and low for level. For occupational exposure to asbestos, the bodies of evidence varied by industrial sector between very low and low quality of evidence for prevalence and were of very low quality of evidence for level. For occupational exposure to coal dust, the bodies of evidence were of very low or moderate quality of evidence for prevalence, and low for level. None of the included studies were population-based studies (i.e., covered the entire workers' population in the industrial sector), which we judged to present serious concern for indirectness, except for occupational exposure to coal dust within the industrial sector of mining of coal and lignite. Selected estimates of the prevalences and levels of occupational exposure to silica by industrial sector are considered suitable as input data for the WHO/ILO Joint Estimates, and selected estimates of the prevalences and levels of occupational exposure to asbestos and coal dust may perhaps also be suitable for estimation purposes. Protocol identifier: https://doi.org/10.1016/j.envint.2018.06.005. PROSPERO registration number: CRD42018084131., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Professor Vivi Schlünssen was the Chair of the Danish Quality Committee for Occupational Exposure Limits of the Danish Working Environment Authority from the year 2016, up until 30 June 2022. The other authors declare no conflicts of interest., (Copyright © 2023 World Health Organization, International Labour Organization. Published by Elsevier Ltd.. All rights reserved.)

The present study aimed to investigate the potential causal pathways and temporal relationships of glucose metabolism and diabetes with heart rate variability (HRV). This cohort study was conducted among a sample of 3858 Chinese adults. At baseline and 6 years follow-up, participants underwent HRV measurement (low frequency [LF], high frequency [HF], total power [TP], standard deviation of all normal-to-normal intervals [SDNN], and square root of the mean squared difference between adjacent normal-to-normal intervals [r-MSSD]) and determination of glucose homeostasis (fasting plasma glucose [FPG] and insulin [FPI], homeostatic model assessment for insulin resistance [HOMA-IR]). The temporal relationships of glucose metabolism and diabetes with HRV were evaluated using cross-lagged panel analysis. FPG, FPI, HOMA-IR, and diabetes were cross-sectionally negatively associated with HRV indices at baseline and follow-up (P < 0.05). Cross-lagged panel analyses demonstrated significant unidirectional paths from baseline FPG to follow-up SDNN (β = -0.06), and baseline diabetes to follow-up low TP group (β = 0.08), low SDNN group (β = 0.05), and low r-MSSD group (β = 0.10) (P < 0.05). No significant path coefficients were observed from baseline HRV to follow-up impaired glucose homeostasis or diabetes. These significant findings persisted even after excluding participants who were taking antidiabetic medication. The results support that elevated FPG and the presence of diabetes may be the causes rather than the consequences of HRV reduction over time., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The adverse health effects of ozone pollution have been a globally concerned public health issue. Herein we aim to investigate the association between ozone exposure and glucose homeostasis, and to explore the potential role of systemic inflammation and oxidative stress in this association. A total of 6578 observations from the Wuhan-Zhuhai cohort (baseline and two follow-ups) were included in this study. Fasting plasma glucose (FPG) and insulin (FPI), plasma C-reactive protein (CRP, biomarker for systemic inflammation), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG, biomarker for oxidative DNA damage), and urinary 8-isoprostane (biomarker for lipid peroxidation) were repeatedly measured. After adjusting for potential confounders, ozone exposure was positively associated with FPG, FPI, and homeostasis model assessment of insulin resistance (HOMA-IR), and negatively associated with HOMA of beta cell function (HOMA-β) in cross-sectional analyses. Each 10 ppb increase in cumulative 7-days moving average ozone was associated with a 13.19%, 8.31%, and 12.77% increase in FPG, FPI, and HOMA-IR, respectively, whereas a 6.63% decrease in HOMA-β (all P < 0.05). BMI modified the associations of 7-days ozone exposure with FPI and HOMA-IR, and the effects were stronger in subgroup whose BMI ≥24 kg/m 2 . Consistently high exposure to annual average ozone was associated with increased FPG and FPI in longitudinal analyses. Furthermore, ozone exposure was positively related to CRP, 8-OHdG, and 8-isoprostane in dose-response manner. Increased CRP, 8-OHdG, and 8-isoprostane could dose-dependently aggravate glucose homeostasis indices elevations related to ozone exposure. Increased CRP and 8-isoprostane mediated 2.11-14.96% of ozone-associated glucose homeostasis indices increment. Our findings suggested that ozone exposure could cause glucose homeostasis damage and obese people were more susceptible. Systemic inflammation and oxidative stress might be potential pathways in glucose homeostasis damage induced by ozone exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The associations and potential mechanisms of low to moderate arsenic exposure with fasting plasma glucose (FPG) and type 2 diabetes mellitus (T2DM) are still unclear. To assess the effects of short-term and long-term arsenic exposure on hyperglycemia and the mediating effect of oxidative damage on such association, three repeated-measures studies with 9938 observations were conducted in the Wuhan-Zhuhai cohort. The levels of urinary total arsenic, FPG, urinary 8-iso-prostaglandin F2alpha (8-iso-PGF2α), urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and plasma protein carbonyls (PCO) were measured. Generalized linear mixed models were used to evaluate the exposure-response relationships of urinary total arsenic with FPG and the prevalent risks of impaired fasting glucose (IFG), T2DM, and abnormal glucose regulation (AGR). Cox regression models were applied to assess the associations of arsenic exposure with incident risks of IFG, T2DM, and AGR. Mediation analyses were performed to assess the mediating effects of 8-iso-PGF2α, 8-OHdG, and PCO. In cross-sectional analyses, each one-unit increase in natural log-transformed urinary total arsenic was associated with a 0.082 (95% CI: 0.047 to 0.118) mmol/L increase in FPG, as well as a 10.3% (95% CI: 1.4%-20.0%), 4.4% (95% CI: 5.3%-15.2%), and 8.7% (95% CI: 1.2%-16.6%) increase in prevalent risks of IFG, T2DM, and AGR, respectively. In longitudinal analyses, arsenic exposure was further associated with the annual increased rate of FPG with a β (95% CI) of 0.021 (95% CI: 0.010 to 0.033). The incident risks of IFG, T2DM, and AGR were increased without statistical significance when arsenic levels increased. Mediation analyses showed that 8-iso-PGF2α and PCO mediated 30.04% and 10.02% of the urinary total arsenic-associated FPG elevation, respectively. Our study indicated that arsenic exposure was associated with elevated level and progression rate of FPG among general Chinese adults, where lipid peroxidation and oxidative protein damage might be the potential mechanisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)