Associations of short-term ambient temperature exposure with lung function in middle-aged and elderly people: A longitudinal study in China.

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 [FEV1], 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, FEV1, 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, FEV1, and PEF in the low-temperature zone (

Analysis of public opinion on employment issues using a combined approach: a case study in China.

To analyze the public opinion related to the employment situation, a combined approach is proposed to study the valuable ideas from social media. Firstly, the popularity of public opinion was analyzed according to the time series from a statistical point of view. Secondly, the feature extraction was carried out on the public opinion information, and the thematic analysis of the employment environment was carried out based on the Latent Dirichlet Allocation model. Thirdly, the Bert model was used to analyze the sentiment classification and trend of the employment-related public opinion data. Finally, the employment public opinion texts in different regions were studied based on the spatial sequence popularity analysis, keyword difference analysis. A case study in China is conducted to verify the effectiveness of proposed combined approach. Results shown that the popularity of employment public opinion reached the highest level in March 2022. Public opinions towards employment situation are negative. There is a specific relationship between the popularity of employment public opinion in different provinces.

Stable composition of gut microbiome in the Asian ladybeetle Coccinella septempunctata reared on natural and artificial diets.

The Asian ladybeetle, Coccinella septempunctata, is an important insect of predatory natural enemy, which has a strong control effect and application prospects for aphids, whiteflies, mealybugs, and other small-sized pests of agriculture and forestry crops. Gut microbiota composition posed impacts on development of insects. In order to clarify the effect of artificial feed feeding on the intestinal microbial species and structure of C. septempunctata, we compared the intestinal microbial flora of C. septempunctata reared on bean aphids and artificial food for 15 days. Results show that Proteobacteria was the dominant component in all groups at phylum level, Rhodobacter, Methylovigula, Burkholderia, and Bradyrhizobium were the dominant bacteria among all groups at genus level. As to the differences in bacterial community structure and diversity, there is no significant difference between Shannon index and Simpson index, the principal components analysis of the bacterial communities, and the samples were roughly distributed in different regions. After 15 days of feeding, artificial diet did not significantly reduce the microbial diversity of the gut of C. septempunctata compared to the aphid group, and there was no significant effect on the abundance of dominant flora in the gut of C. septempunctata, C. septempunctata gut has a similar core microbiota. This study clarifies the effects in intestinal microbial diversity and composition structure of the C. septempunctata with artificial diet, and provides a theoretical basis for understanding the intestinal microorganisms and optimizating the artificial diet of C. septempunctata.

Bidirectional Association Between Cardiovascular Disease and Lung Cancer in a Prospective Cohort Study.

INTRODUCTION: The study aimed to prospectively investigate the bidirectional association between cardiovascular disease (CVD) and lung cancer, and whether this association differs across genetic risk levels. METHODS: This study prospectively followed 455,804 participants from the United Kingdom Biobank cohort who were free of lung cancer at baseline. Cox proportional hazard models were used to estimate the hazard ratio (HR) for incident lung cancer according to CVD status. In parallel, similar approaches were used to assess the risk of incident CVD according to lung cancer status among 478,756 participants free of CVD at baseline. The bidirectional causal relations between these conditions were assessed using Mendelian randomization analysis. Besides, polygenic risk scores were estimated by integrating genome-wide association studies identified risk variants. RESULTS: During 4,007,477 person-years of follow-up, 2006 incident lung cancer cases were documented. Compared with participants without CVD, those with CVD had HRs (95% confidence interval [CI]) of 1.49 (1.30-1.71) for NSCLC, 1.80 (1.39-2.34) for lung squamous cell carcinoma (LUSC), and 1.25 (1.01-1.56) for lung adenocarcinoma (LUAD). After stratification by smoking status, significant associations of CVD with lung cancer risk were observed in former smokers (HR = 1.44, 95% CI: 1.20-1.74) and current smokers (HR = 1.38, 95% CI: 1.13-1.69), but not in never-smokers (HR = 0.98, 95% CI: 0.60-1.61). In addition, CVD was associated with lung cancer risk across each genetic risk level (pheterogeneity = 0.336). In the second analysis, 32,974 incident CVD cases were recorded. Compared with those without lung cancer, the HRs (95% CI) for CVD were 2.33 (1.29-4.21) in NSCLC, 3.66 (1.65-8.14) in LUAD, and 1.98 (0.64-6.14) in LUSC. In particular, participants with lung cancer had a high risk of incident CVD at a high genetic risk level (HR = 3.79, 95% CI: 1.57-9.13). No causal relations between these conditions were observed in Mendelian randomization analysis. CONCLUSIONS: CVD is associated with an increased risk of NSCLC including LUSC and LUAD. NSCLC, particularly LUAD, is associated with a higher CVD risk. Awareness of this bidirectional association may improve prevention and treatment strategies for both diseases. Future clinical demands will require a greater focus on cardiac oncology.

Short-term effects of exposure to ambient PM2.5 and its components on hospital admissions for threatened and spontaneous abortions: A multicity case-crossover study in China.

BACKGROUND: The adverse effects of short-term exposure to PM2.5 and its components on hospital admissions for threatened and spontaneous abortions (TSAB) are still controversial. METHODS: Data on daily hospitalizations for TSAB and PM2.5 and its components, including sulfate (SO42-), nitrate (NO3-), ammonium salt (NH4+), organic matter (OM), and black carbon (BC), were collected from January 2015 to December 2021 (total 2,557 days) in five cities in China. Case-crossover analyses were conducted to investigate the short-term associations between PM2.5 and its components and TSAB. Additionally, the modification effects by age (<35 and ≥35 years), season (cold and warm seasons), and the "Three-Year Action Plan to Win the Blue Sky Defense War" (before and after implementation) on the above associations were further conducted. RESULTS: For each 10 µg/m3 (1 µg/m3 for BC) increase, the strongest relative risks (95% confidence intervals) of hospitalization for TSAB were 1.011 (1.001-1.021) for PM2.5 in lag02, 1.060 (1.003-1.120) for SO42- in lag02, 1.035 (1.000-1.070) for NO3- in lag02, 1.065 (1.009-1.124) for NH4+ in lag02, 1.047 (1.008-1.088) for OM in lag01 and 1.029 (1.005-1.054) for BC in lag02 (all P <0.05). Furthermore, significant modifying effects of age and the Action Plan were found. The effects of NO3- (lag2), NH4+ (lag2), and BC (lag2) were more pronounced in mothers aged ≥35 years and the effects of PM2.5 (lag4), NO3- (lag4), NH4+ (lag4), OM (lag4), and BC (lag4) was more pronounced in the period before the Action Plan was implemented (all P modification <0.05). CONCLUSION: Short-term exposure to ambient PM2.5 and its components (SO42-, NO3-, NH4+, OM, and BC) was related to increased risks of hospitalization for TSAB. The effects were more pronounced in mothers aged ≥35 years and the period before the Action Plan.

Puerarin protects against acetaminophen-induced oxidative damage in liver through activation of the Keap1/Nrf2 signaling pathway.

Puerarin (Pue) is a kind of isoflavone compound extracted from Pueraria lobata, which has significant antioxidant activity. Excessive use of acetaminophen (APAP) can cause oxidative stress in the liver and eventually lead to acute liver injury. The purpose of this study was to investigate the protective effect and the mechanism of puerarin on APAP-induced liver oxidative damage. In in vitro experiments, puerarin significantly increased the cell activity of HepG2 cells, reduced the ROS accumulation, alleviated the oxidative damage and mitochondrial dysfunction. In in vivo studies, our results showed that puerarin enhanced antioxidant activity and alleviated histopathological damage. Further studies showed that puerarin decreased the expression of Keap1, promoted the nuclear migration of Nrf2, and up-regulated the expression of GCLC, GCLM, HO-1 and NQO1. This study demonstrated that puerarin can protect APAP-induced liver injury via alleviating oxidative stress and mitochondrial dysfunction by affecting the nuclear migration of Nrf2 via inhibiting Keap1.

Synthesis of pyrimidine-fused skeletons through copper-catalyzed consecutive Sonogashira coupling and aminocyclization.

A copper-catalyzed sequence involving a Sonogashira coupling reaction and 5-exo-dig aminocyclization between a terminal alkyne and a 2-(2-bromophenyl)pyrimidine analog based on six-membered rings is presented. This protocol provides a controlled and modular approach to access a variety of synthetically useful pyrimidine-fused skeletons with high efficiency, broad substrate scope, and excellent functional group compatibility. Under acidic conditions, the (Z)-configuration of products spontaneously converts into (E)-9-benzylidene-1,9-dihydro-11H-pyrazolo[4',3':4,5]pyrimido[2,1-a]isoindol-11-ones.

Fabrication of Nitrogen-Doped Carbon@Magnesium Silicate Composite by One-Step Hydrothermal Method and Its High-Efficiency Adsorption of As(V) and Tetracycline.

Tetracycline (TC) and arsenic contaminants are two main pollutants in aquaculture and livestock husbandry, and they have drawn worldwide attention. To address this issue, a novel N-doped carbon@magnesium silicate (CMS) was fabricated via a facile and low-cost hydrothermal route, adopting glucose and ammonia as C and N sources, respectively. The synergetic combination of carbon and magnesium silicate makes CMS possess a high surface area of 201 m2/g and abundant functional groups. Due to the abundant C- and N-containing functional groups and Mg-containing adsorptive sites, the maximum adsorption capacity values of CMS towards As(V) and TC are 498.75 mg/g and 1228.5 mg/g, respectively. The type of adsorption of As(V) and TC onto CMS is monolayer adsorption. An adsorption kinetic study revealed that the mass transfer and intraparticle process dominates the sorption rate of As(V) and TC adsorption onto CMS, respectively. Various functional groups synthetically participate in the adsorption process through complexion, π-π EDA interactions, and hydrogen bonds. This work provides a one-step, low-cost route to fabricate a N-doped carbonaceous adsorbent with a high surface area and abundant functional groups, which has great potential in the application of practical sewage treatment.

Construction of Phenanthridinone Skeletons through Palladium-Catalyzed Annulation.

Herein, a straightforward synthetic approach for the construction of phenanthridin-6(5H)-one skeletons is disclosed. The developed protocol relies on palladium catalysis, providing controlled access to a range of functionalized phenanthridin-6(5H)-ones in 59-88% yields. Furthermore, plausible reaction pathways are proposed based on mechanistic experiments.

In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk, and Cancer Incidence in Adulthood: A Prospective Cohort Study.

OBJECTIVE: To evaluate the association of early-life tobacco smoke exposure, especially interacting with cancer genetic variants, with adult cancer. PARTICIPANTS AND METHODS: We examined the associations of in utero tobacco smoke exposure, age of smoking initiation, and their interaction with genetic risk levels with cancer incidence in 393,081 participants from the UK Biobank. Information on tobacco exposure was obtained by self-reported questionnaires. A cancer polygenic risk score was constructed by weighting and integrating 702 genome-wide association studies-identified risk variants. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for overall cancer and organ-specific cancer incidence. RESULTS: During 11.8 years of follow-up, 23,450 (5.97%) and 23,413 (6.03%) incident cancers were included in the analyses of in utero exposure and age of smoking initiation, respectively. The HR (95% CI) for incident cancer in participants with in utero exposure to tobacco smoke was 1.04 (1.01-1.07) for overall cancer, 1.59 (1.44-1.75) for respiratory cancer, and 1.09 (1.03-1.17) for gastrointestinal cancer. The relative risk of incident cancer increased with earlier smoking initiation (Ptrend<.001), with the HR (95% CI) of 1.44 (1.36-1.51) for overall cancer, 13.28 (11.39-15.48) for respiratory cancer, and 1.72 (1.54-1.91) for gastrointestinal cancer in smokers with initiation in childhood compared with never smokers. Importantly, a positive additive interaction between age of smoking initiation and genetic risk was observed for overall cancer (Padditive=.04) and respiratory cancer (Padditive=.003) incidence. CONCLUSION: In utero exposure and earlier smoking initiation are associated with overall and organ-specific cancer, and age of smoking initiation interaction with genetic risk is associated with respiratory cancer.

Immunomodulatory role of spleen tyrosine kinase in chronic inflammatory and autoimmune diseases.

BACKGROUND: The high prevalence of chronic inflammatory diseases or autoimmune reactions is a major source of concern and affects the quality of life of patients. Chronic inflammatory or autoimmune diseases are associated with many diseases in humans, including asthma, rheumatoid arthritis, systemic lupus erythematosus, inflammatory bowel disease and cancer. Splenic tyrosine kinase (SYK) is a non-receptor tyrosine kinase that plays an important role in immune receptor signalling in immune and inflammatory responses. METHODS: This is a review article in which we searched for keywords "splenic tyrosine kinase", "inflammation" and "autoimmune diseases" in published literature such as Pubmed and Web of Science to collect relevant information and then conducted a study focusing on the latest findings on the involvement of SYK in chronic inflammatory or autoimmune diseases. RESULTS: This paper reviews the regulation of Fcγ, NF-κB, B cell and T cell-related signalling pathways by SYK, which contributes to disease progression in chronic inflammatory and autoimmune diseases such as airway fibrosis, inflammatory skin disease and inflammatory bowel disease. CONCLUSION: This paper shows that SYK plays an important role in chronic inflammatory and autoimmune diseases. syk targets hematological, autoimmune and other inflammatory diseases and therefore, inhibition of SYK expression or blocking its related pathways may provide new ideas for clinical prevention and treatment of inflammatory or autoimmune diseases.

Ambient temperature exposure causes lung function impairment: The evidence from Controlled Temperature Study in Healthy Subjects (CTSHS).

BACKGROUND: The effect of non-optimal ambient temperatures (low and high temperatures) on lung function and the underlying mechanisms remains unclear. METHODS: Forty-three (20 males, 23 females) healthy non-obese volunteers with an average of 23.9 years participated in the controlled temperature study. All volunteers underwent three temperature exposures in a sequence (moderate [18 °C], low [6 °C], and high [30 °C] temperatures) lasting 12 h with air pollutants controlled. lung function parameters (forced vital capacity [FVC], forced expiratory volume in 1 s [FEV1], and peak expiratory flow [PEF]) were determined in each exposure. Blood and urine samples were collected after each exposure and assayed for inflammatory markers [C-reactive protein (CRP), procalcitonin (PCT), platelet-lymphocyte ratio (PLR), and neutrophil-lymphocyte ratio (NLR)] and oxidative damage markers [protein carbonylation (PCO), 4-hydroxy-2-nominal-mercapturic acid (HNE-MA), 8-iso-prostaglandin-F2α (8-isoPGF2α), and 8-hydroxy-2-deoxyguanosine (8-OHdG)]. Mixed-effects models were constructed to assess the changes of the above indexes under low or high temperatures relative to moderate temperature, and then the repeated measures correlation analyses were performed. RESULTS: Compared with moderate temperature, a 2.20% and 2.59% net decrease in FVC, FEV1, and a 5.68% net increase for PEF were observed under low-temperature exposure, while a 1.59% net decrease in FVC and a 7.29% net increase in PEF under high-temperature exposure were found (all P < 0.05). In addition, low temperature elevated inflammatory markers (PCT, PLR, and NLR) and oxidative damage markers (8-isoPGF2α, 8-OHdG), and high temperature elevated HNE-MA. Repeated measures correlation analyses revealed that PCT (r = -0.33) and NLR (r = -0.31) were negatively correlated with FVC and HNE-MA (r = -0.35) and 8-OHdG (r = -0.31) were negatively correlated with the FEV1 under low-temperature exposure (all P < 0.05). CONCLUSION: Non-optimal ambient temperatures exposure alters lung function, inflammation, and oxidative damage. Inflammation and oxidative damage might be involved in low temperature-related lung function reduction.

Interaction of metabolism-related pathway gene variants with bisphenol A exposure on serum lipid profiles.

Bisphenol A (BPA) can be metabolized by metabolic enzymes and may induce abnormal lipid metabolism. We hypothesized that BPA exposure and its interaction with metabolism-related genes might be associated with serum lipid profiles. We performed a two-stage study among 955 middle-aged and elderly participants in Wuhan, China. Urinary BPA level was estimated without (BPA, µg/L) or with (BPA/Cr, µg/g) adjustments for urinary creatinine and ln-transformed values (ln-BPA or ln-BPA/Cr) were used to normalize the asymmetrical distributions. A total of 412 metabolism-related gene variants were selected and used for gene-BPA interaction analysis. Multiple linear regression was used to analyze the interactions between BPA exposure and metabolism-related genes on serum lipid profiles. In the discovery stage, both ln-BPA and ln-BPA/Cr was associated with decreased high-density lipoprotein cholesterol (HDL-C). Gene-urinary BPA interaction for IGFBP7 rs9992658 was observed to associate with HDL-C levels in both discovery and validation stages, with Pinteraction equal to 9.87 × 10-4 (ln-BPA) and 1.22 × 10-3 (ln-BPA/Cr) in combined analyses. In addition, the inverse association of urinary BPA with HDL-C levels was only observed among individuals carrying rs9992658 AA genotype, but not in individuals carrying rs9992658 AC or CC genotypes. The interaction between BPA exposure and metabolism-related gene IGFBP7 (rs9992658) was associated with HDL-C levels.

Triclosan is associated with breast cancer via oxidative stress and relative telomere length.

Introduction: Triclosan (TCS), a widely prescribed broad-spectrum antibacterial agent, is an endocrine-disrupting chemical. The relationship and biological mechanisms between TCS exposure and breast cancer (BC) are disputed. We aimed to examine the correlation between urinary TCS exposure and BC risk and estimated the mediating effects of oxidative stress and relative telomere length (RTL) in the above association. Methods: This case-control study included 302 BC patients and 302 healthy individuals in Wuhan, China. We detected urinary TCS, three common oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], and RTL in peripheral blood mononuclear cells. Results: Significant associations were observed between log-transformed urinary concentrations of TCS, 8-OHdG, HNE-MA, 8-isoPGF2α, RTL, and BC risk, with the odds ratios (95% confidence intervals) being 1.58 (1.32-1.91), 3.08 (1.55-6.23), 3.39 (2.45-4.77), 3.99 (2.48-6.54), and 1.67 (1.35-2.09), respectively. Continuous TCS exposure was significantly positively correlated with RTL, HNE-MA, and 8-isoPGF2α (all p<0.05) but not with 8-OHdG (p = 0.060) after adjusting for covariates. The mediated proportions of 8-isoPGF22α and RTL in the relationship between TCS and BC risk were 12.84% and 8.95%, respectively (all p<0.001). Discussion: In conclusion, our study provides epidemiological evidence to confirmed the deleterious effects of TCS on BC and indicated the mediating effect of oxidative stress and RTL on the correlation between TCS and BC risk. Moreover, exploring the contribution of TCS to BC can clarify the biological mechanisms of TCS exposure, provide new clues for the pathogenesis of BC, which is of great significance to improving public health systems.

Birthweight, genetic risk, and gastrointestinal cancer incidence: a prospective cohort study.

BACKGROUND: The epidemiologic studies investigating the association of birthweight and genetic factors with gastrointestinal cancer remain scarce. The study aimed to prospectively assess the interactions and joint effects of birthweight and genetic risk levels on gastrointestinal cancer incidence in adulthood. METHODS: A total of 254,997 participants were included in the UK Biobank study. We used multivariate restricted cubic splines and Cox regression models to estimate the hazard ratios (HRs) and 95% confidential intervals (CI) for the association between birthweight and gastrointestinal cancer risk, then constructed a polygenic risk score (PRS) to assess its interaction and joint effect with birthweight on the development of gastrointestinal cancer. RESULTS: We documented 2512 incident cases during a median follow-up of 8.88 years. Compare with participants reporting a normal birthweight (2.5-4.5 kg), multivariable-adjusted HR of gastrointestinal cancer incidence for participants with high birthweight (≥4.5 kg) was 1.17 (95%CI: 1.01-1.36). Such association was remarkably observed in pancreatic cancer, with an HR of 1.82 (95%CI: 1.26-2.64). No statistically significant association was observed between low birth weight and gastrointestinal cancers. Participants with high birthweight and high PRS had the highest risk of gastrointestinal cancer (HR: 2.95, 95%CI: 2.19-3.96). CONCLUSION: Our findings highlight that high birthweight is associated with a higher incidence of gastrointestinal cancer, especially for pancreatic cancer. Benefits would be obtained from birthweight control, particularly for individuals with a high genetic risk.KEY MESSAGESThe epidemiologic studies investigating the association of birthweight and genetic factors with gastrointestinal cancer remain scarce.This cohort study of 254,997 adults in the United Kingdom found an association of high birthweight with the incidence of gastrointestinal cancer, especially for pancreatic cancer, and also found that participants with high birthweight and high polygenic risk score had the highest risk of gastrointestinal cancer.Our data suggests a possible effect of in utero or early life exposures on adulthood gastrointestinal cancer, especially for those with a high genetic risk.

Short-term impacts of air pollution on the platelet-lymphocyte ratio and neutrophil-lymphocyte ratio among urban adults in China.

The short-term impacts of urban air pollution on the platelet-lymphocyte ratio (PLR) and neutrophil-lymphocyte ratio (NLR) remain obscure. In this study, we included 3487 urban adults from the Wuhan-Zhuhai cohort. Individual inhalation exposure to air pollutants was estimated by combining participants' daily breath volume and ambient concentrations of six air pollutants (including fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), carbon monoxide (CO) and ozone (O3)). The cumulative impacts were assessed by applying lag structures of up to 7 days before the survey date. Associations of air pollutants with PLR and NLR were assessed using a linear mixed model and Bayesian kernel machine regression (BKMR) model. We found that PLR was negatively related to PM2.5 (lag02-lag06), PM10 (lag02-lag07), NO2 (lag02-lag07), and SO2 (lag03-lag05) and NLR was negatively related to PM10 (lag05 and lag07). In the BKMR model, a negative joint association between the six-air-pollutant mixture and PLR and NLR was observed, whereas PM10 and NO2 appeared to be more important than the other pollutants in the mixture. The negative impact of air pollutants was stronger in males, participants with lower body mass index (< 24 kg/m2), those cooking meals at home, drinkers, and non-exercisers. In conclusion, short-term exposure to air pollutants is significantly related to PLR and NLR in peripheral blood. PLR and NLR may provide new insight into the molecular mechanism underlying the adverse health impact of air pollutants.

In Utero and Childhood/Adolescence Exposure to Tobacco Smoke, Genetic Risk, and Lung Cancer Incidence and Mortality in Adulthood.

Rationale: The individual effects of early-life tobacco smoke exposure and its interactions with genetic factors on lung cancer in adulthood remain unclear. Objectives: To investigate the associations of early-life tobacco exposures as well as their interactions with polygenic risk scores (PRSs) with lung cancer incidence and mortality. Methods: A total of 432,831 participants from the UK Biobank study were included. We estimated the associations of in utero exposure to tobacco smoke, the age of smoking initiation and their interactions with PRSs with lung cancer incidence and mortality in adulthood using Cox proportional hazard models. Measurements and Main Results: Lung cancer incidence (hazard ratio [HR]: 1.59, 95% confidence interval [CI], 1.44-1.76) increased among participants with in utero tobacco exposure. Multivariable-adjusted HRs (with 95% CIs) of lung cancer incidence for smoking initiation in adulthood, adolescence, and childhood (versus never-smokers) were 6.10 (5.25-7.09), 9.56 (8.31-11.00), and 15.15 (12.90-17.79) (Ptrend < 0.001). Similar findings were observed in lung cancer mortality. Participants with high PRSs and in utero tobacco exposure (versus low PRSs participants without in utero exposure) had an HR of 2.35 for lung cancer incidence (95% CI, 1.97-2.80, Pinteraction = 0.089) and 2.43 for mortality (95% CI, 2.05-2.88, Pinteraction = 0.032). High PRSs with smoking initiation in childhood (versus never-smokers with low PRSs) had HRs of 18.71 for incidence (95% CI, 14.21-24.63, Pinteraction = 0.004) and 19.74 for mortality (95% CI, 14.98-26.01, Pinteraction = 0.033). Conclusions: In utero and childhood/adolescence exposure to tobacco smoke and its interaction with genetic factors may substantially increase the risks of lung cancer incidence and mortality in adulthood.

Liquid-Metal-Induced Hydrogen Insertion in Photoelectrodes for Enhanced Photoelectrochemical Water Oxidation.

Fast charge separation and transfer (CST) is essential for achieving efficient solar conversion processes. This CST process requires not only a strong driving force but also a sufficient charge carrier concentration, which is not easily achievable with traditional methods. Herein, we report a rapid hydrogenation method enabled by gallium-based liquid metals (GBLMs) to modify the prototypical WO3 photoelectrode to enhance the CST for a PEC process. Protons in solution are controllably embedded into the WO3 photoanode accompanied by electron injection due to the strong reduction capability of GBLMs. This process dramatically increases the carrier concentration of the WO3 photoanode, leading to improved charge separation and transfer. The hydrogenated WO3 photoanode exhibits over a 229% improvement in photocurrent density with long-term stability. The effectiveness of GBLMs treatment in accelerating the CST process is further proved using other more general semiconductor photoelectrodes, including Nb2O5 and TiO2.

Ectonucleoside triphosphate diphosphohydrolase-1 (CD39) impacts TGF-ß1 responses: insights into cardiac fibrosis and function following myocardial infarction.

Extracellular purine nucleotides and nucleosides released from activated or injured cells influence multiple aspects of cardiac physiology and pathophysiology. Ectonucleoside triphosphate diphosphohydrolase-1 (ENTPD1; CD39) hydrolyzes released nucleotides and thereby regulates the magnitude and duration of purinergic signaling. However, the impact of CD39 activity on post-myocardial infarction (MI) remodeling is incompletely understood. We measured the levels and activity of ectonucleotidases in human left ventricular samples from control and ischemic cardiomyopathy (ICM) hearts and examined the impact of ablation of Cd39 expression on post-myocardial infarction remodeling in mice. We found that human CD39 levels and activity are significantly decreased in ICM hearts (n = 5) compared with control hearts (n = 5). In mice null for Cd39, cardiac function and remodeling are significantly compromised in Cd39-/- mice following myocardial infarction. Fibrotic markers including plasminogen activator inhibitor-1 (PAI-1) expression, fibrin deposition, α-smooth muscle actin (αSMA), and collagen expression are increased in Cd39-/- hearts. Importantly, we found that transforming growth factor ß1 (TGF-ß1) stimulates ATP release and induces Cd39 expression and activity on cardiac fibroblasts, constituting an autocrine regulatory pathway not previously appreciated. Absence of CD39 activity on cardiac fibroblasts exacerbates TGF-ß1 profibrotic responses. Treatment with exogenous ectonucleotidase rescues this profibrotic response in Cd39-/- fibroblasts. Together, these data demonstrate that CD39 has important interactions with TGF-ß1-stimulated autocrine purinergic signaling in cardiac fibroblasts and dictates outcomes of cardiac remodeling following myocardial infarction. Our results reveal that ENTPD1 (CD39) regulates TGF-ß1-mediated fibroblast activation and limits adverse cardiac remodeling following myocardial infarction.NEW & NOTEWORTHY We show that CD39 is a critical modulator of TGF-ß1-mediated fibroblast activation and cardiac remodeling following myocardial infarction via modulation of nucleotide signaling. TGF-ß1-induced CD39 expression generates a negative feedback loop that attenuates cardiac fibroblast activation. In the absence of CD39 activity, collagen deposition is increased, elastin expression is decreased, and diastolic dysfunction is worsened. Treatment with ecto-apyrase attenuates the TGF-ß1-induced profibrotic cardiac fibroblast phenotype, revealing a novel approach to combat post-myocardial infarction cardiac fibrosis.