Microcystin-LR Induces Estrogenic Effects at Environmentally Relevant Concentration in Black-Spotted Pond Frogs (Pelophylax nigromaculatus): In Situ, In Vivo, In Vitro, and In Silico Investigations.

Harmful cyanobacterial blooms are frequent and intense worldwide, creating hazards for aquatic biodiversity. The potential estrogen-like effect of Microcystin-LR (MC-LR) is a growing concern. In this study, we assessed the estrogenic potency of MC-LR in black-spotted frogs through combined field and laboratory approaches. In 13 bloom areas of Zhejiang province, China, the MC-LR concentrations in water ranged from 0.87 to 8.77 µg/L and were correlated with sex hormone profiles in frogs, suggesting possible estrogenic activity of MC-LR. Tadpoles exposed to 1 µg/L, an environmentally relevant concentration, displayed a female-biased sex ratio relative to controls. Transcriptomic results revealed that MC-LR induces numerous and complex effects on gene expression across multiple endocrine axes. In addition, exposure of male adults significantly increased the estradiol (E2)/testosterone (T) ratio by 3.5-fold relative to controls. Downregulation of genes related to male reproductive endocrine function was also identified. We also showed how MC-LR enhances the expression of specific estrogen receptor (ER) proteins, which induce estrogenic effects by activating the ER pathway and hypothalamic-pituitary-gonadal (HPG) axis. In aggregate, our results reveal multiple lines of evidence demonstrating that, for amphibians, MC-LR is an estrogenic endocrine disruptor at environmentally relevant concentrations. The data presented here support the need for a shift in the MC-LR risk assessment. While hepatoxicity has historically been the focus of MC-LR risk assessments, our data clearly demonstrate that estrogenicity is a major mode of toxicity at environmental levels and that estrogenic effects should be considered for risk assessments on MC-LR going forward.

Tetrabromobisphenol A reduces male rats reproductive organ coefficients and disrupting sexual hormone by causing oxidative stress.

Tetrabromobisphenol A (TBBPA) has become a topic of public attention due to its pervasive detection in the environment and organisms in recent decades. However, limited information is available regarding the toxicity of TBBPA on reproductive ability of male mammals. Herein, the reproductive toxicity of TBBPA was investigated in male rats to fill the knowledge gap. In this study, male rats were exposed to TBBPA (0, 10, 100, and 1000mg/kg) for 6 weeks. Subsequently, body and organ indexes, histopathological evaluation of testis and epididymis, ultrastructural observation of sperm, testosterone and progesterone levels, and oxidative stress indicators were conducted to reveal corresponding mechanisms. Results obtained showed that compare to the control group, the body weight, testes weight, epididymis weight, seminal vesicle and coagulation glands weight of rats in the 1000mg/kg group lost 8.30%, 16.84%, 20.16%, 19.72% and 26.42%, respectively. Intriguingly, exposure to TBBPA (10, 100, 100mg/kg) resulted in substantial pathological damage in testis, epididymis and sperm. TBBPA exposure also increased malondialdehyde (MDA) and hydrogen peroxide (H2O2) contents, as well as superoxide dismutase (T-SOD) and catalase (CAT) activities in testicular tissue. What's more, the testosterone and progesterone levels in male rat serum were significantly decreased after exposure to TBBPA for 6 weeks. Meanwhile, results of molecular docking showed that TBBPA has a strong affinity with estrogen receptors (ERs). These findings demonstrated that TBBPA exposure negatively impacts the reproductive ability of male rats, thus providing new insights for risk assessment for reproductive health under TBBPA exposure.

Enhanced recognition of G-quadruplex DNA oxidative damage based on DNA-mediated charge transfer.

G-quadruplex (G4) DNA is present in human telomere oligonucleotide sequences. Oxidative damage to telomeric DNA accelerates telomere shortening, which is strongly associated with aging and cancer. Most of the current analyses on oxidative DNA damage are based on ds-DNA. Here, we developed a electrochemiluminescence (ECL) probe for enhanced recognition of oxidative damage in G4-DNA based on DNA-mediated charge transfer (CT), which could specifically recognize damaged sites depending on the position of 8-oxoguanine (8-oxoG). First, a uniform G4-DNA monolayer interface was fabricated; the G4-DNA mediated CT properties were examined using an iridium(III) complex [Ir(ppy)2(pip)]PF6 stacked with G4-DNA as an indicator. The results showed that G4-DNA with 8-oxoG attenuated DNA CT. The topological effects of oxidative damage at different sites of G4-DNA and their effects on DNA CT were revealed. The sensing platform was also used for the sensitive and quantitative detection of 8-oxoG in G4-DNA, with a detection limit of 28.9 fmol. Overall, these findings present a sensitive platform to study G4-DNA structural and stability changes caused by oxidative damage as well as the specific and quantitative detection of oxidation sites. The different damage sites in the G-quadruplex could provide detailed clues for understanding the function of G4-associated telomere functional enzymes.

Association between serum uric acid and cardiovascular fitness among US adults: A cross-sectional study.

Background: While serum uric acid (SUA) is known as a cardiovascular disease risk factor and is associated with increased cardiovascular mortality, the relationship between SUA and cardiovascular adaptability under exercise stress remains unclear. Aims: This study aims to elucidate the relationship between SUA levels and cardiovascular fitness, particularly as manifested during cardiopulmonary exercise testing. Methods: Utilizing data from the National Health and Nutrition Examination Survey (NHANES) 1999-2004, this study included 5765 participants aged 12-49 years. Heart rate recovery (HRR) during cardiopulmonary exercise testing was measured as an indicator of cardiovascular fitness. Multivariate linear regression analysis was used to explore the association between SUA levels and heart rate recovery at 1 min (HRR1) and 2 min (HRR2) post-exercise. Results: After adjusting for potential confounders, an inverse relationship was found between SUA levels and both HRR1 and HRR2. Multivariate adjusted smoothing spline plots demonstrated a decrease in HRR1 and HRR2 with increasing SUA levels. This negative correlation was observed across nearly all subgroups. Conclusions: Elevated SUA levels are indicative of poorer cardiovascular adaptability in the adult US population.

Bisphenols and brominated bisphenols induced endothelial dysfunction via its disruption of endothelial nitric oxide synthase.

Emerging literatures have concentrated on the association between cardiovascular diseases risk of typical endocrine disruptor bisphenols, which also put forward the further studies need respect to the potential mechanism. Herein, we investigated the endothelial dysfunction effects of bisphenols and brominated bisphenols involved in aortic pathological structure, endothelial nitric oxide synthase (eNOS) protein phosphorylation, synthase activity and nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) and C57BL/6 mice. Bisphenol A (BPA) and bisphenol S (BPS) increased NO production by 85.7% and 68.8% at 10-6 M level in vitro and 74.3%, 41.5% in vivo, respectively, while tetrabromobisphenol S (TBBPS) significantly inhibited NO by 55.7% at 10-6 M in vitro and 28.9% in vivo at dose of 20 mg/kg BW/d. Aortic transcriptome profiling revealed that the process of 'regulation of NO mediated signal transduction' was commonly induced. The mRNA and protein expression of phosphorylated eNOS at Ser1177 were promoted by BPA and BPS but decreased by TBBPA and TBBPS in HUVECs. Phosphorylation and enzymatic activity of eNOS were significantly increased by 43.4% and 13.8% with the treatment of BPA and BPS at 10-7 M, but decreased by 16.9% after exposure to TBBPS at 10-6 M in vitro. Moreover, only TBBPS was observed to increase aorta thickness significantly in mice and induce endothelial dysfunction. Our work suggests that bisphenols and brominated bisphenols may exert adverse outcome on vascular health differently in vitro and in vivo, and emphasizes areas of public health concern similar endocrine disruptors vulnerable on the vascular endothelial function.

Effect of alkali metal ions introduction on the fluorescence properties of Er-Tm-Yb synergistically sensitized phosphors.

Upconversion fluoride phosphors Na1-xMxY1-a-b-cF4:Er3+a, Tm3+b, Yb3+c (M = Li+/K+) have been synthesized by low-temperature combustion method. The optimal doping ratios of ions in the matrix lattice were determined by orthogonal experiments with the control variable method. It was found that when a certain amount of Tm3+ ions were doped into the lattice of Er3+ ions, the upconversion fluorescence intensity and red-to-green ratio of the samples were significantly enhanced. When a small amount of Yb3+ ions was introduced into the Er3+-Tm3 + ions co-doped samples, the upconversion fluorescence intensity of the samples was continued to be enhanced, but the red-to-green ratio was slightly decreased. The mechanism of the influence of the upconversion fluorescence intensity and the red-to-green ratio of the multidoped samples with lanthanide ions was also systematically investigated. Based on the results of orthogonal experiments, the optimal component formulations were determined and alkali metal ions were further introduced. The upconversion fluorescence enhancement mechanism of the samples after the introduction of alkali metal ions was systematically investigated. In this work, the upconversion fluorescence intensity of the prepared samples was significantly enhanced by synergistic sensitization between the ions. In addition, by adjusting the red-to-green ratio of the fluorescence of the samples, a new idea is provided for the preparation of upconversion phosphors with high color purity.

Luminescent lanthanide complexes based on 4,5-di(3,5-dicarboxylphenoxy)phthalic acid as enhanced fluorescence probes for highly selective detection of lead(II) ions in water.

Six novel lanthanide complexes ([Nd2(L)(H2O)6]n·4.58n(H2O) (1), [Ln(H3L)(H2O)]n·0.5n(H2O), Ln = Sm (2), Eu (3), Gd (4), Tb (5), Eu0.18Gd0.62Tb0.20 (6)) have been hydrothermally synthesized based on the ligand 4,5-di(3,5-dicarboxylphenoxy)phthalic acid (H6L). Single crystal X-ray diffraction reveals that complexes 1-6 are 2D structures, where 2-6 are isomorphic. Complexes 3 and 5 exhibit the characteristic fluorescence of Eu(III) and Tb(III) ions respectively, while complex 4 shows blue-green light emission based on the ligand. In particular, the ternary Eu/Gd/Tb complex 6 shows white light emission with a CIE (Commission International del'Eclairage) chromaticity coordinate of (0.330, 0.339) and hence close to pure white light emission. Moreover, complexes 3 and 5 display specific fluorescence-enhanced detection performance for Pb2+ ions: The interaction between Pb2+ ions and the ligand enhances the charge transfer efficiency between the ligand and the Eu(III) and Tb(III) ions and thus leads to fluorescence enhancement of complexes 3 and 5. More importantly, complex 3 exhibits the lowest detection limit of 4.72 nM for Pb2+ ions among the existing complex fluorescent probes. In addition, both complexes 3 and 5 show good performance for recycling and for the detection of Pb2+ in real water samples.

The association between lead exposure and dental caries ─ a systematic review.

INTRODUCTION: Dental caries has declined over the years, but it remains a major public health issue. This review aimed to investigate the association between lead and caries experience in either deciduous or permanent teeth. METHODS: A comprehensive search of PubMed, EMBASE, and Google Scholar was conducted to identify relevant studies published up until December 2022. Included were human observational studies that investigated the association between lead exposure and dental caries. The review adhered to the PRISMA guideline. RESULTS: Sixteen studies were included in this review, with nine focusing on deciduous teeth, thirteen on permanent teeth, and six examining both types of teeth. Most of the studies (5 of 6) found a positive association between blood lead (PbB) levels and caries in deciduous teeth, while the findings for permanent teeth were less conclusive, with only 3 of 10 studies finding an association. One of the two studies assessing salivary lead (PbSa) levels found a weak association for permanent teeth. All four studies that examined lead (Pb) concentration in teeth found a positive association for both deciduous and permanent teeth. CONCLUSION: Many published studies indicated a positive association between Pb exposure and caries experience in deciduous dentition. Children with elevated PbB level should be considered as having higher caries experience. Due to lack of consensus on measurement and examination technique, there remains insufficient evidence to make any definitive conclusions especially in permanent teeth, and so more studies are warranted.

Effects and mechanisms of bisphenols exposure on neurodegenerative diseases risk: A systemic review.

Environmental bisphenols (BPs) pose a global threat to human health because of their extensive use as additives in plastic products. BP residues are increasing in various environmental media (i.e., water, soil, and indoor dust) and biological and human samples (i.e., serum and brain). Both epidemiological and animal studies have determined an association between exposure to BPs and an increased risk of neurodegenerative diseases (e.g., Parkinson's disease, Alzheimer's disease, and amyotrophic lateral sclerosis), including cognitive abnormalities and behavioral disturbances. Hence, understanding the biological responses to different BPs is essential for prevention, and treatment. This study provides an overview of the underlying pathogenic molecular mechanisms as a valuable basis for understanding neurodegenerative disease responses to BPs, including accumulation of misfolded proteins, reduction of tyrosine hydroxylase and dopamine, abnormal hormone signaling, neuronal death, oxidative stress, calcium homeostasis, and inflammation. These findings provide new insights into the neurotoxic potential of BPs and ultimately contribute to a comprehensive health risk evaluation.

Effects of Tail Vegetable Fermented Feed on the Growth and Rumen Microbiota of Lambs.

This study explored the impact of integrating fermented feed into the starter diet of lambs, focusing on growth, health, serum antioxidants, immune markers, rumen fermentation, and microbial communities. Thirty-six ten-day-old female Tail Han lambs were randomly divided into three experimental groups, which were separately fed with alfalfa hay (LA group), tail vegetable fermented feed (LB group), and tail vegetable fermented feed supplemented with 0.1% microbial inoculants (LC group) during the experimental period. This study assessed the influence of fermented feed on various parameters, including growth performance, fiber degradation, rumen fermentation, enzymatic activities, and ruminal histomorphology. The results indicate that compared to the control group, the addition of fermented feed can increase the daily weight gain of lambs. Simultaneously, the addition of fermented feed can enhance the total antioxidant capacity of serum (p < 0.05). The addition of fermented feed promoted the increased height of villi in the duodenum or jejunum of lambs (p < 0.05), and the ratio of villi height to crypt depth in the LB and LC groups was also improved (p < 0.05). The addition of fermented feed increased the richness and diversity of the rumen microbial community in lambs (p < 0.05), primarily increasing the relative abundance of Ruminococcus_1, Ruminococcaceae_UCG-005, Lachnospiraceae, and Lachnospiraceae_NK4A136_group.

New energy electric vehicle battery health state prediction based on vibration signal characterization and clustering.

The health status of the battery of new energy electric vehicles is related to the quality of vehicle use, so it is of high practical application value to predict the health status of the battery of electric vehicles. In order to predict the health status of lithium battery, this study proposes to optimize the empirical modal decomposition method and obtain the ensemble empirical modal decomposition algorithm, and use this algorithm to collect the vibration signal of the battery, then use wavelet transform to pre-process the collected signal, and finally combine K-mean clustering and particle swarm algorithm to cluster the signal types to complete the prediction of battery State of Health. The experimental results show that the ensemble empirical modal decomposition algorithm proposed in this study can effectively perform signal acquisition for different state types of batteries, and the K-mean clustering-particle swarm algorithm predicts a 63 % decrease in the health state of the battery at 600 cycles, with a prediction error of 2.6 %. Therefore, the algorithm proposed in this study is feasible in predicting the battery health state.

Research progress on the characteristics, sources, and environmental and potential health effects of water-soluble organic compounds in atmospheric particulate matter.

Water-soluble organic compounds (WSOCs) have received extensive attention due to their indistinct chemical components, complex sources, negative environmental impact, and potential health effects. To the best of our knowledge, until now, there has been no comprehensive review focused on the research progress of WSOCs. This paper reviewed the studies on chemical constituent and characterization, distribution condition, sources, environmental impact, as well as the potential health effects of WSOCs in the past 13 years. Moreover, the main existing challenges and directions for the future research on WSOCs were discussed from several aspects. Because of the complex composition of WSOCs and many unknown individual components that have not been detected, there is still a need for the identification and quantification of WSOCs. As modern people spend more time in indoor environments, it is meaningful to fill the gaps in the component characteristics and sources of indoor WSOCs. In addition, although in vitro cell experiments have shown that WSOCs could induce cellular oxidative stress and trigger the inflammatory response, the corresponding mechanisms of action need to be further explored. The current population epidemiology research of WSOCs is missing. Prospectively, we propose to conduct a comprehensive and simultaneous analysis strategy for concentration screening, source apportionment, potential health effects, and action mechanisms of WSOCs based on high throughput omics coupled with machine learning simulation and prediction.

Serum zinc concentration and dietary zinc intake in relation to cognitive function: an analysis of the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort.

PURPOSE: There are several pathways by which zinc may be a modifiable factor to slow age-related cognitive decline. We investigated the associations between serum and dietary zinc and cognitive impairment in a longitudinal cohort. METHODS: We used data from the REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort (n = 30,239) and the REGARDS Trace Element Study (n = 2666). Baseline serum zinc concentrations (2003-2007) were measured using inductively coupled plasma mass spectrometry. Baseline dietary zinc intake was measured via the Block food frequency questionnaire. Serum zinc concentrations and dietary zinc intake were categorized into quartiles. The outcome of interest was impairment on the Six-Item Screener (SIS), a measure of global cognitive functioning administered annually. The Enhanced Cognitive Battery (ECB), a more comprehensive series of tests assessing memory and fluency, was administered every two years and considered a secondary outcome. Associations between zinc and incident impairment were assessed using multivariable logistic regression. RESULTS: Among 2065 participants with serum zinc data, 184 individuals developed impairment over 10 years of follow-up. In adjusted models, there was no significant association between serum zinc and impairment as assessed by the SIS or the ECB. Among 18,103 participants who had dietary data, 1424 experienced incident impairment on the SIS. Dietary zinc intake was not significantly associated with impairment as assessed by the SIS or the ECB in adjusted models. CONCLUSION: Findings from this U.S. cohort did not support the hypothesis that serum zinc concentration or dietary zinc intake is associated with the risk of cognitive impairment.

A magnetically reusable Ce-MOF/GO/Fe3O4 composite for effective photocatalytic degradation of chlortetracycline.

Herein, we report a novel 1/GO/Fe3O4 photocatalyst, comprising Ce(BTB)(H2O) (MOF-1, H3BTB = 1,3,5-benzenetrisbenzoic acid), graphene oxide (GO), and iron oxide (Fe3O4) for photocatalytic degradation of chlortetracycline (CTC). This design enables the effective transfer of electrons from the MOF to GO, thereby reducing the photoelectron-hole recombination rate. Therefore, the optimized 1/GO/Fe3O4 photocatalyst with H2O2 shows the highest photocatalytic activity toward CTC. The kinetic constant is 5.4 times that in the system of MOF-1 and hydrogen peroxide, which usually acted as efficient electron acceptors to improve the photocatalytic performance of MOFs. More importantly, light absorption is extended from the ultraviolet to the visible region. Furthermore, 1/GO/Fe3O4 can be quickly recycled under an applied magnetic field and displays outstanding stability and reusability. According to the radical trapping experiments and electron paramagnetic resonance results, hydroxyl radicals, superoxide radicals, and holes all contribute to excellent photocatalytic activity. The possible catalytic mechanism of 1/GO/Fe3O4 is tentatively proposed. This work aims to explore the synergistic effect between metal-organic frameworks (MOFs) and GO, and provide a theoretical basis for MOF-based composites to remove antibiotic contaminants in the environment.

Paternal p,p'-DDE exposure and pre-pubertal high-fat diet increases the susceptibility to fertility impairment and sperm Igf2 DMR2 hypo-methylation in male offspring.

The hypothesis of paternal origins of health and disease (POHaD) indicates that paternal exposure to adverse environment could alter the epigenetic modification in germ line, increasing the disease susceptibility in offspring or even in subsequent generations. p,p'-Dichlorodiphenyldichloroethylene (p,p'-DDE) is an anti-androgenic chemical and male reproductive toxicant. Gestational p,p'-DDE exposure could impair reproductive development and fertility in male offspring. However, the effect of paternal p,p'-DDE exposure on fertility in male offspring remains uncovered. From postnatal day (PND) 35 to 119, male rats (F0) were given 10 mg/body weight (b.w.) p,p'-DDE or corn oil by gavage. Male rats were then mated with the control females to generate male offspring. On PND35, the male offspring were divided into 4 groups according whether to be given the high-fat diet (HF): corn oil treatment with control diet (C-C), p,p'-DDE treatment with control diet (DDE-C), corn oil treatment with high-fat diet (C-HF) or p,p'-DDE treatment with high-fat diet (DDE-HF) for 35 days. Our results indicated that paternal p,p'-DDE exposure did not affect the male fertility of male offspring directly, but decreased sperm quality and induced testicular apoptosis after the high-fat diet treatment. Further analysis demonstrated that paternal exposure to p,p'-DDE and pre-pubertal high-fat diet decreased sperm Igf2 DMR2 methylation and gene expression in male offspring. Hence, paternal exposure to p,p'-DDE and pre-pubertal high-fat diet increases the susceptibility to male fertility impairment and sperm Igf2 DMR2 hypo-methylation in male offspring, posing a significant implication in the disease etiology.

DNA methylation reprogramming mediates transgenerational diabetogenic effect induced by early-life p,p'-DDE exposure.

Increasing evidence shows that an adverse environment during the early fetal development can affect the epigenetic modifications on a wide range of diabetes-related genes, leading to an increased diabetic susceptibility in adulthood or even in subsequent generations. p,p'-Dichlorodiphenoxydichloroethylene (p,p'-DDE) is a break-down product of the pesticide dichlorodiphenyltrichloroethane (DDT). p,p'-DDE has been associated with various health concerns, such as diabetogenic effect. However, the precise molecular mechanism remains unclear. In this study, p,p'-DDE was given by gavage to pregnant rat dams from gestational day (GD) 8 to GD15 to generate male germline to investiagate the transgenerational effects. We found that early-life p,p'-DDE exposure increased the transgenerational diabetic susceptibility through male germline inheritance. In utero exposure to p,p'-DDE altered the sperm DNA methylome in F1 progeny, and a significant number of those differentially methylated genes could be inherited by F2 progeny. Furthermore, early-life p,p'-DDE exposure altered DNA methylation in glucose metabolic genes Gck and G6pc in sperm and the methylation modification were also found in liver of the next generation. Our study demonstrate that DNA methylation plays a critical role in mediating transgenerational diabetogenic effect induced by early-life p,p'-DDE exposure.

More homework improve mathematics achievement? Differential effects of homework time on different facets of students' mathematics achievement: A longitudinal study in China.

BACKGROUND: Mathematics homework is highly prevalent in East Asia. Teachers and parents expect mathematics homework to improve students' performance; however, studies have not clearly defined the effectiveness of the assignment of different amounts of homework. AIMS: This study analyses the differential effect of homework amount on various facets of Chinese students' mathematics achievement using a longitudinal design. It aims, thereby, to contribute to the existing knowledge of homework effectiveness and mathematics learning and to provide insights for student development. SAMPLE: The sample included 2383 grade 9 students from a mid-sized city with a moderate level of economic and educational development in central China. METHODS: We administered a student-reported questionnaire, collected school reports of mathematics achievements to track retrospective longitudinal variations in mathematics over half a year and analysed the differential effectiveness of homework on mathematics achievement at four hierarchical cognitive levels with Hierarchical Linear Model. RESULTS: The results indicated that assigning more homework at the class level could enhance students' mathematics achievement at a low cognitive level, although this effectiveness tended to disappear when the set homework time reached about 1.5-2 h. We did not find evidence that assigning more homework enhances students' mathematics achievement at higher cognitive levels. CONCLUSIONS: Overall, this study provides evidence on the effectiveness of homework and offers implications for educational practice and future research.

Smoking Modifies the Association Between Radon Exposure and Incident Ischemic Stroke: The REGARDS Study.

BACKGROUND: Exposure to radon has been linked to lung cancer and other lung diseases. Although biologically plausible, research of residential radon exposure in relation to stroke risk is scarce. METHODS: Study participants were from the REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort (n=30 239), which consisted of male and female non-Hispanic Black and White adults aged 45 and older. After excluding participants with baseline stroke and transient ischemic attack, and missing information on exposure and outcome of interest, the final sample size was 26 950. The primary outcome was time to the first ischemic stroke through September 30, 2020. County-level radon measures from Lawrence Berkeley National Laboratory were linked to each participant based on their geocoded residential history. We used Cox proportional hazards regression models with a time-dependent exposure to estimate hazard ratios and 95% CIs for the association. RESULTS: After controlling for potential confounding factors including demographic, lifestyle, clinical variables, and PM2.5, radon exposure was significantly associated with incident ischemic stroke among never-smokers (hazard ratio, 1.39 [95% CI, 1.01-1.90]) but not ever-smokers. The results were generally consistent in the sensitivity analysis when using radon measures from state/Environmental Protection Agency residential radon survey. CONCLUSIONS: Findings from this study suggest that the association between residential radon exposure and incidence of ischemic stroke varies by smoking status and may be prominent in never-smokers. Further studies incorporating indoor-radon measures are needed to confirm these findings.

Genotypic and spatial analysis of transmission dynamics of tuberculosis in Shanghai, China: a 10-year prospective population-based surveillance study.

Background: With improved tuberculosis (TB) control programs, the incidence of TB in China declined dramatically over the past few decades, but recently the rate of decrease has slowed, especially in large cities such as Shanghai. To help formulate strategies to further reduce TB incidence, we performed a 10-year study in Songjiang, a district of Shanghai, to delineate the characteristics, transmission patterns, and dynamic changes of the local TB burden. Methods: We conducted a population-based study of culture-positive pulmonary TB patients diagnosed in Songjiang during 2011-2020. Genomic clusters were defined with a threshold distance of 12-single-nucleotide-polymorphisms based on whole-genome sequencing, and risk factors for clustering were identified by logistic regression. Transmission inference was performed using phybreak. The distances between the residences of patients were compared to the genomic distances of their isolates. Spatial patient hotspots were defined with kernel density estimation. Findings: Of 2212 enrolled patients, 74.7% (1652/2212) were internal migrants. The clustering rate (25.2%, 558/2212) and spatial concentrations of clustered and unclustered patients were unchanged over the study period. Migrants had significantly higher TB rates but less clustering than residents. Clustering was highest in male migrants, younger patients and both residents and migrants employed in physical labor. Only 22.1% of transmission events occurred between residents and migrants, with residents more likely to transmit to migrants. The clustering risk decreased rapidly with increasing distances between patient residences, but more than half of clustered patient pairs lived ≥5 km apart. Epidemiologic links were identified for only 15.6% of clustered patients, mostly in close contacts. Interpretation: Although some of the TB in Songjiang's migrant population is caused by strains brought by infected migrants, local, recent transmission is an important driver of the TB burden. These results suggest that further reductions in TB incidence require novel strategies to detect TB early and interrupt urban transmission. Funding: Shanghai Municipal Science and Technology Major Project (ZD2021CY001), National Natural Science Foundation of China (82272376), National Research Council of Science and Technology Major Project of China (2017ZX10201302-006).

Mechanism of Polygonum capitatum intervention in pulmonary fibrosis based on network pharmacology and molecular docking technology: A review.

Pulmonary fibrosis (PF) is a serious interstitial disease that includes diffuse collagen deposition of lung tissue. Polygonum capitatum Buch.-Ham. ex D. Don (THL) is a traditional vaccine that has antibacterial and anti-inflammatory effects. In this research, to investigate the mechanism of action of THL in the intervention of pulmonary fibrosis by network pharmacology and molecular docking related research methods, in order to provide a theoretical basis for expanding the scope of THL medication. A total of 49 active ingredients were analyzed and screened in Cephalus cephalusis, including 35 pulmonary fibrosis targets, and 10 key targets such as ALB, EGFR were screened after software analysis. The molecular docking results showed that there were 44 binding energies less than -3 kcal·mol-1 in the 60 docking results, indicating that most proteins had strong binding energies with compounds. The key targets of KEGG enrichment analysis were mainly enriched in 20 core action pathways, such as hemostasis-related pathway, regulation of kinase activity. This study shows that based on network pharmacology, the multicomponent-multitarget-multipathway effect of THL intervention in pulmonary fibrosis is discussed.