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Abstract The pathogenesis of doxorubicin-induced cardiomyopathy remains unclear. This study was carried out to test our hypothesis that ADAM17 aggravates cardiomyocyte apoptosis induced by doxorubicin and inhibition of ADAM17 may ameliorate doxorubicin-induced cardiomyopathy. C57BL/6J mice were intraperitoneally injected with a cumulative dose of doxorubicin to induce cardiomyopathy. Cardiomyocyte-specific ADAM17-knockout (A17α-MHCKO) and ADAM17-overexpressing (AAV9-oeA17) mice were generated. In addition, RNA sequencing of the heart tissues in different mouse groups and in vitro experiments in neonatal rat cardiomyocytes (NRCMs) receiving different treatment were performed. Mouse tumor models were constructed in A17fl/fl and A17α-MHCKO mice. In addition, cardiomyocyte-specific TRAF3-knockdown and TRAF3-overexpressing mice were generated. ADAM17 expression and activity were markedly upregulated in doxorubicin-treated mouse hearts and NRCMs. A17α-MHCKO mice showed less cardiomyocyte apoptosis induced by doxorubicin than A17fl/fl mice, and cardiomyocyte ADAM17 deficiency did not affect the anti-tumor effect of doxorubicin. In contrast, AAV9-oeA17 mice exhibited markedly aggravated cardiomyocyte apoptosis relative to AAV9-oeNC mice after doxorubicin treatment. Mechanistically, doxorubicin enhanced the expression of transcription factor C/EBPβ, leading to increased expression and activity of ADAM17 in cardiomyocyte, which enhanced TNF-α shedding and upregulated the expression of TRAF3. Increased TRAF3 promoted TAK1 autophosphorylation, resulting in activated MAPKs pathway and cardiomyocyte apoptosis. ADAM17 acted as a positive regulator of cardiomyocyte apoptosis and cardiac remodeling and dysfunction induced by doxorubicin by upregulating TRAF3/TAK1/MAPKs signaling. Thus, targeting ADAM17/TRAF3/TAK1/MAPKs signaling holds a promising potential for treating doxorubicin-induced cardiotoxicity.

DNA holds immense potential as an emerging data storage medium. However, the recovery of information in DNA storage systems faces challenges posed by various errors, including IDS errors, strand breaks, and rearrangements, inevitably introduced during synthesis, amplification, sequencing, and storage processes. Sequence reconstruction, crucial for decoding, involves inferring the DNA reference from a cluster of erroneous copies. While most methods assume equal contributions from all reads within a cluster as noisy copies of the same reference, they often overlook the existence of contaminated sequences caused by DNA breaks, rearrangements, or mis-clustering reads. To address this issue, we propose RobuSeqNet, a robust multi-read reconstruction neural network specifically designed to robustly reconstruct multiple reads, accommodating noisy clusters with strand breakage, rearrangements, and mis-clustered strands. Leveraging the attention mechanism and an elaborate network design, RobuSeqNet exhibits resilience to highly-noisy clusters and effectively deals with in-strand IDS errors. The effectiveness and robustness of the proposed method are validated on three representative next-generation sequencing datasets. Results demonstrate that RobuSeqNet maintains high sequence reconstruction success rates of 99.74%, 99.58%, and 96.44% across three datasets, even in the presence of noisy clusters containing up to 20% contaminated sequences, outperforming known sequence reconstruction models. Additionally, in scenarios without contaminated sequences, it exhibits comparable performance to existing models, achieving success rates of 99.88%, 99.82%, and 97.68% across the three datasets.

ObjectiveTo examine the association between physical activity and risk of all-cause mortality and related mediators in middle-aged and elderly people in China to provide evidence for reducing mortality in the population. MethodsData were collected from 5 727 individuals aged ≥ 45 years who completed baseline and 3 follow-up surveys in the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2018. We used multivariable Cox proportional hazards regression models and restricted cubic spline models to examine the association between physical activity levels and risk of all-cause mortality. In addition, we conducted a mediation analysis based on body mass index (BMI), blood pressure, and blood biochemical indicators collected during follow-up. ResultsOf all the individuals analyzed, 1 813 (31.66%) were classified as having physical activity (measured in metabolic equivalents [METs]-min/week) in the lowest quartile (

Abstract Metabolic syndrome (MetS) is becoming prevalent in the pediatric population. The existing pediatric MetS definitions (e.g., the International Diabetes Federation (IDF) definition and the modified National Cholesterol Education Program (NCEP) definition) involve complex cut-offs, precluding fast risk assessment in clinical practice. We proposed a simplified definition for assessing MetS risk in youths aged 6–17 years, and compared its performance with two existing widely used pediatric definitions (the IDF definition, and the NCEP definition) in 10 pediatric populations from 9 countries globally (n = 19,426) using the receiver operating characteristic (ROC) curve analyses. In general, the total MetS prevalence of 6.2% based on the simplified definition was roughly halfway between that of 4.2% and 7.7% estimated from the IDF and NCEP definitions, respectively. The ROC curve analyses showed a good agreement between the simplified definition and two existing definitions: the total area under the curve (95% confidence interval) of the proposed simplified definition for identifying MetS risk achieved 0.91 (0.89–0.92) and 0.79 (0.78–0.81) when using the IDF or NCEP definition as the gold standard, respectively. The proposed simplified definition may be useful for pediatricians to quickly identify MetS risk and cardiometabolic risk factors (CMRFs) clustering in clinical practice, and allow direct comparison of pediatric MetS prevalence across different populations, facilitating consistent pediatric MetS risk monitoring and the development of evidence-based pediatric MetS prevention strategies globally.

Electroactive polyvinylidene fluoride (PVDF) with predominantly the β-phase is now challenging the fabricating of PVDF toward energy storage applications. Here, the comprehensive effect of BaTiO3 nano-particles and mechanical stretching on the improvement of the β-phase of PVDF was investigated. In situ synchrotron wide-angle X-ray diffraction (WAXD) and small-angle X-ray scattering (SAXS) measurements were performed to investigate this behavior. Consequently, the transformation rate of β-crystal for both pure PVDF (BT0) and PVDF/BaTiO3 (90/10) nanocomposites (BT1) decreases as the stretching temperature increases, implying that the high temperature is unfavorable to the formation of β-crystal phase. A synergistic enhancement of the β-phase of nano-particle additives and stretching was discovered. It was surprisingly observed that α-phase of PVDF would completely transform into β-crystal in BT1 sample at 100 °C during stretching. The mechanism of the synergistic effect of BaTiO3 nano-particles and mechanical stretching was proposed. Moreover, machine learning was implemented to predict the fraction of β-crystal phase (F(β)) of the PVDF/BaTiO3 composites under various uni-axial stretching conditions by Python 3.8. The results show that the machine learning technique can rapidly and efficiently discover the ideal value of F(β) and the optimal multivariate coupling conditions.

ObjectiveTo investigate the association between serum vitamin B12 (VB12) level and cognitive impairment in elderly Chinese individuals for the prevention and control of cognitive decline in the population. MethodsThe data of 924 residents aged 65 years and older were extracted from the dataset of Chinese Longitudinal Healthy Longevity Survey (CLHLS) conducted in 2012 and 2014. Cognitive function was assessed using the Mini-Mental State Examination (MMSE), with participants scoring below 24 considered to have cognitive impairment. Participants were categorized into tertiles based on their serum VB12 concentrations, and comparisons were made between major characteristics of participants in different groups. Generalized estimation equation (GEE) models were employed to explore the association of serum VB12 level with cognitive function and its risk. ResultsThe mean level of serum VB12 was 408.93 ± 197.60 pmol/L for all the participants aged 81.21 ± 11.14 years and with nearly equal numbers of men and women. After adjusting for potential confounders, the GEE model analyses revealed that compared to individuals with serum VB12 levels in the first tertile, the participants with higher serum VB12 levels exhibited increased MMSE scores (β = 1.12, 95% confidence interval [95%CI]: 0.40 – 1.85 for the second tertile; β = 1.34, 95%CI = 0.52 – 2.16 for the third tertile), as well as a reduced risk of cognitive impairment (odds ratio [OR] = 0.52, 95%CI: 0.32 – 0.86 for the second tertile; OR = 0.56, 95%CI: 0.33 – 0.94 for the third tertile). However, further subgroup analysis indicated that the decreased risk of cognitive impairment was statistically significant only among female participants. ConclusionThe presence of serum vitamin B12 deficiency is significantly associated with cognitive impairment in elderly female residents in China.

Gynecomastia can be caused by neurofibromas but has rarely been reported. The present case report describes the clinical appearance, diagnosis, and therapy of a rare combination of a 14 year-old adolescent male unilateral severe gynecomastia with NF-1 neurofibromatosis. In this particular case, we successfully performed minimally invasive surgery using endoscopic mastectomy, which not only resulted in a satisfactory appearance but also confirmed the presence of neurofibroma type 1 by detecting typical immunohistochemical indicators associated with the disease. Additionally, we analyzed the gene responsible for the disease, c.1431del: p. F477Lfs*21, based on the patient’s family history.

Abstract Background Waist-to-height ratio (WHtR) has been proposed as a simple and effective screening tool for assessing central obesity and cardiometabolic risk in both adult and pediatric populations. However, evidence suggests that the use of a uniform WHtR cut-off of 0.50 may not be universally optimal for pediatric populations globally. We aimed to determine the optimal cut-offs of WHtR in children and adolescents with increased cardiometabolic risk across different countries worldwide. Methods We used ten population-based cross-sectional data on 24,605 children and adolescents aged 6–18 years from Brazil, China, Greece, Iran, Italy, Korea, South Africa, Spain, the UK, and the USA for establishing optimal WHtR cut-offs. We performed an external independent test (9,619 children and adolescents aged 6–18 years who came from other six countries) to validate the optimal WHtR cut-offs based on the predicting performance for at least two or three cardiometabolic risk factors. Results Based on receiver operator characteristic curve analyses of various WHtR cut-offs to discriminate those with ≥ 2 cardiometabolic risk factors, the relatively optimal percentile cut-offs of WHtR in the normal weight subsample population in each country did not always coincide with a single fixed percentile, but varied from the 75th to 95th percentiles across the ten countries. However, these relatively optimal percentile values tended to cluster irrespective of sex, metabolic syndrome (MetS) criteria used, and WC measurement position. In general, using ≥ 2 cardiometabolic risk factors as the predictive outcome, the relatively optimal WHtR cut-off was around 0.50 in European and the US youths but was lower, around 0.46, in Asian, African, and South American youths. Secondary analyses that directly tested WHtR values ranging from 0.42 to 0.56 at 0.01 increments largely confirmed the results of the main analyses. In addition, the proposed cut-offs of 0.50 and 0.46 for two specific pediatric populations, respectively, showed a good performance in predicting ≥ 2 or ≥ 3 cardiometabolic risk factors in external independent test populations from six countries (Brazil, China, Germany, Italy, Korea, and the USA). Conclusions The proposed international WHtR cut-offs are easy and useful to identify central obesity and cardiometabolic risk in children and adolescents globally, thus allowing international comparison across populations.

Chinese Baijiu is a famous fermented alcoholic beverage in China. Interactions between key microorganisms, i.e., Saccharomyces cerevisiae and Lactiplantibacillus plantarum, have recently been reported at specific temperatures. However, empirical evidence of their interactions at various temperatures during fermentation is lacking. The results of this study demonstrated that S. cerevisiae significantly suppressed the viability and lactic acid yield of L. plantarum when they were cocultured above 15 °C. On the other hand, L. plantarum had no pronounced effect on the growth and ethanol yield of S. cerevisiae in coculture systems. S. cerevisiae was the main reducing sugar consumer. Inhibition of lactic acid production was also observed when elevated cell density of L. plantarum was introduced into the coculture system. A proteomic analysis indicated that the enzymes involved in glycolysis, lactate dehydrogenase, and proteins related to phosphoribosyl diphosphate, ribosome, and aminoacyl-tRNA biosynthesis in L. plantarum were less abundant in the coculture system. Collectively, our data demonstrated the antagonistic effect of S. cerevisiae on L. plantarum and provided insights for effective process management in light-flavor Baijiu fermentation.

Abstract Endothelial dysfunction represents a major cardiovascular risk factor for hypertension. Sp1 and Sp3 belong to the specificity protein and Krüppel-like transcription factor families. They are ubiquitously expressed and closely associated with cardiovascular development. We investigate the role of Sp1 and Sp3 in endothelial cells in vivo and evaluate whether captopril, an angiotensin-converting enzyme inhibitor (ACEI), targets Sp1/Sp3 to exert its effects. Inducible endothelial-specific Sp1/Sp3 knockout mice are generated to elucidate their role in endothelial cells. Tamoxifen-induced deletion of endothelial Sp1 and Sp3 in male mice decreases the serum nitrite/nitrate level, impairs endothelium-dependent vasodilation, and causes hypertension and cardiac remodeling. The beneficial actions of captopril are abolished by endothelial-specific deletion of Sp1/Sp3, indicating that they may be targets for ACEIs. Captopril increases Sp1/Sp3 protein levels by recruiting histone deacetylase 1, which elevates deacetylation and suppressed degradation of Sp1/Sp3. Sp1/Sp3 represents innovative therapeutic target for captopril to prevent cardiovascular diseases.

Abstract Previous studies suggested a beneficial effect of natriuretic peptides in animal models of cardiovascular disease, but the role of natriuretic peptide receptor C (NPRC) in the pathogenesis of atherosclerosis (AS) remains unknown. This study was designed to test the hypothesis that NPRC may promote AS lesion formation and instability by enhancing oxidative stress, inflammation, and apoptosis via protein kinase A (PKA) signaling. ApoE−/− mice were fed chow or Western diet for 12 weeks and NPRC expression was significantly increased in the aortic tissues of Western diet-fed mice. Systemic NPRC knockout mice were crossed with ApoE−/− mice to generate ApoE−/−NPRC−/− mice, and NPRC deletion resulted in a significant decrease in the size and instability of aortic atherosclerotic lesions in ApoE−/−NPRC−/− versus ApoE−/− mice. In addition, endothelial cell-specific NPRC knockout attenuated atherosclerotic lesions in mice. In contrast, endothelial cell overexpression of NPRC aggravated the size and instability of atherosclerotic aortic lesions in mice. Experiments in vitro showed that NPRC knockdown in human aortic endothelial cells (HAECs) inhibited ROS production, pro-inflammatory cytokine expression and endothelial cell apoptosis, and increased eNOS expression. Furthermore, NPRC knockdown in HAECs suppressed macrophage migration, cytokine expression, and phagocytosis via its effects on endothelial cells. On the contrary, NPRC overexpression in endothelial cells resulted in opposite effects. Mechanistically, the anti-inflammation and anti-atherosclerosis effects of NPRC deletion involved activation of cAMP/PKA pathway, leading to downstream upregulated AKT1 pathway and downregulated NF-κB pathway. In conclusion, NPRC deletion reduced the size and instability of atherosclerotic lesions in ApoE−/− mice via attenuating inflammation and endothelial cell apoptosis and increasing eNOS expression by modulating cAMP/PKA-AKT1 and NF-κB pathways. Thus, targeting NPRC may provide a promising approach to the prevention and treatment of atherosclerosis.

Abstract Background Understanding the temporal trends in the burden of overall and type-specific cardiovascular diseases (CVDs) in youths and young adults and its attributable risk factors is important for effective and targeted prevention strategies and measures. We aimed to provide a standardized and comprehensive estimation of the prevalence, incidence, disability-adjusted life years (DALY), and mortality rate of CVDs and its associated risk factors in youths and young adults aged 15–39 years at global, regional, and national levels. Methods We applied Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 analytical tools to calculate the age-standardized incidence, prevalence, DALY, and mortality rate of overall and type-specific CVDs (i.e., rheumatic heart disease, ischemic heart disease, stroke, hypertensive heart disease, non-rheumatic valvular heart disease, cardiomyopathy and myocarditis, atrial fibrillation and flutter, aortic aneurysm, and endocarditis) among youths and young adults aged 15–39 years by age, sex, region, sociodemographic index and across 204 countries/territories from 1990 to 2019, and proportional DALY of CVDs attributable to associated risk factors. Results The global age-standardized DALY (per 100,000 population) for CVDs in youths and young adults significantly decreased from 1257.51 (95% confidence interval 1257.03, 1257.99) in 1990 to 990.64 (990.28, 990.99) in 2019 with an average annual percent change (AAPC) of − 0.81% (− 1.04%, − 0.58%, P

Tracking and detection have brought great challenges to network security. Therefore, this paper proposes a monitoring method of stealthy complex network attacks considering security situation awareness. By constructing a tracking model of invisible complex network attacks, public monitoring nodes are selected for monitoring. The cost of a single monitoring node is calculated by the algorithm, and the monitoring node is determined by the monitoring node algorithm, so as to reduce the resource occupancy rate of the monitoring node and improve the monitoring accuracy. The simulation results show that this method is stable in the range of 1000 to 4000 nodes, and can effectively monitor the complex network attacks of stealing secrets.

Abstract Background Evidence on the effect of gut microbiota on the number of metabolic syndrome (MetS) risk factors among children is scarce. We aimed to examine the alterations of gut microbiota with different numbers of MetS risk factors among children. Methods Data were collected from a nested case–control study at the baseline of the Huantai Childhood Cardiovascular Health Cohort Study in Zibo, China. We compared the differences in gut microbiota based on 16S rRNA gene sequencing among 72 children with different numbers of MetS risk factors matched by age and sex (i.e., none, one, and two-or-more MetS risk factors; 24 children for each group). Results The community richness (i.e., the total number of species in the community) and diversity (i.e., the richness and evenness of species in the community) of gut microbiota decreased with an increased number of MetS risk factors in children (P for trend

Abstract Background The American Heart Association recently updated its construct of what constitutes cardiovascular health (CVH), called Life’s Essential 8. We examined the association of total and individual CVH metrics according to Life’s Essential 8 with all-cause and cardiovascular disease (CVD)-specific mortality later in life. Methods Data were from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 at baseline linked to the 2019 National Death Index records. Total and individual CVH metric scores including diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure were classified as 0–49 (low level), 50–74 (intermediate level), and 75–100 (high level) points. The total CVH metric score (the average of the 8 metrics) as a continuous variable was also used for dose–response analysis. The main outcomes included all-cause and CVD-specific mortality. Results A total of 19,951 US adults aged 30–79 years were included in this study. Only 19.5% of adults achieved a high total CVH score, whereas 24.1% had a low score. During a median follow-up of 7.6 years, compared with adults with a low total CVH score, those with an intermediate or high total CVH score had 40% (adjusted hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.51–0.71) and 58% (adjusted HR 0.42, 95% CI 0.32–0.56) reduced risk of all-cause mortality. The corresponding adjusted HRs (95%CIs) were 0.62 (0.46–0.83) and 0.36 (0.21–0.59) for CVD-specific mortality. The population-attributable fractions for high (score ≥ 75 points) vs. low or intermediate (score

Abstract Background Maternal hypertensive disorders during pregnancy (HDP) have been suggested to contribute to the development of offspring cardiovascular disease later in life, but empirical evidence remains inconsistent. This study was aimed to assess the association of maternal overall and type-specific HDPs with diabetes in offspring from childhood to early adulthood. Methods Using Danish national health registers, a total of 2,448,753 individuals born in Denmark from 1978 to 2018 were included in this study. Maternal HDP included chronic hypertension, gestational hypertension, and preeclampsia. The outcome of interest was diabetes in offspring (including type 1, type 2, and gestational diabetes). The follow-up of offspring started at birth and ended at the first diagnosis of diabetes, emigration from Denmark, death, or time end on 31 December 2018, whichever came first. Cox proportional hazards regression was used to evaluate the hazard ratios (HRs) with 95% confidence intervals (CIs) of the association between maternal HDP and diabetes (including type 1, type 2, and gestational diabetes) in offspring from birth to young adulthood (up to 41 years), with the offspring’s age as the time scale. Results During a follow-up of up to 41 (median: 19.3) years, 1247 offspring born to mothers with HDP and 23,645 offspring born to mothers without HDP were diagnosed with diabetes. Compared with offspring born to mothers without HDP, those born to mothers with HDP had an increased risk for overall diabetes (HR=1.27, 95% CI=1.20–1.34), as well as for type 2 diabetes (HR=1.57, 95% CI=1.38–1.78) and gestational diabetes (HR=1.37, 95% CI=1.25–1.49). We did not observe obvious increased risk for type 1 diabetes (HR=1.08, 95% CI=0.98–1.18). Offspring of mothers with gestational hypertension (HR=1.37, 95% CI=1.00–1.88) or preeclampsia (HR=1.62, 95% CI=1.41–1.87) had higher risks of type 2 diabetes. The strongest association was observed for severe preeclampsia, with a 2-fold risk of type 2 diabetes (HR=2.00, 95% CI=1.42–2.82). The association between maternal HDP and type 1 diabetes did not reach statistical significance, except for maternal gestational hypertension (HR=1.41, 95%CI=1.17–1.71). In addition, we found that offspring born to mothers with any subtypes of maternal HDP had higher risk of gestational diabetes, and the corresponding HRs (95%CIs) for chronic hypertension, gestational hypertension, and preeclampsia were 1.60 (1.06–2.41), 1.29 (1.04–1.59), and 1.38 (1.24–1.53), respectively. We also observed stronger associations among offspring of mothers with HDP and comorbid diabetes (HR=4.64, 95%CI=3.85–5.60) than offspring of mothers with HDP or diabetes alone. Conclusions Offspring of mothers with HDP, especially mothers with comorbid diabetes, had an increased risk of diabetes later in their life. Our findings suggest that timely and effective prevention of HDP in women of childbearing age should be taken into consideration as diabetes prevention and control strategies for their generations.

Abstract Myocardial infarction (MI) remains the leading cause of death worldwide. Cardiac fibroblasts (CFs) are abundant in the heart and are responsible for cardiac repair post‐MI. NF‐κB‐repressing factor (NKRF) plays a significant role in the transcriptional inhibition of various specific genes. However, the NKRF action mechanism in CFs remains unclear in cardiac repair post‐MI. This study investigates the NKRF mechanism in cardiac remodeling and dysfunction post‐MI by establishing a CF‐specific NKRF‐knockout (NKRF‐CKO) mouse model. NKRF expression is downregulated in CFs in response to pathological cardiac remodeling in vivo and TNF‐α in vitro. NKRF‐CKO mice demonstrate worse cardiac function and survival and increased infarct size, heart weight, and MMP2 and MMP9 expression post‐MI compared with littermates. NKRF inhibits CF migration and invasion in vitro by downregulating MMP2 and MMP9 expression. Mechanistically, NKRF inhibits human antigen R (HuR) transcription by binding to the classical negative regulatory element within the HuR promoter via an NF‐κB‐dependent mechanism. This decreases HuR‐targeted Mmp2 and Mmp9 mRNA stability. This study suggests that NKRF is a therapeutic target for pathological cardiac remodeling.

BackgroundSeveral cardiovascular (CV) risk factors are reported to be associated with abnormal cardiac structure in children and adults. However, no study has assessed the association between clustering of multiple CV risk factors and left ventricular geometric (LVG) remodeling. We examined the association between clustering of CV risk factors and LVG remodeling among Chinese children.MethodsThis cross-sectional study included 1,406 children aged 6–11 years. Clustering of CV risk factors was quantified as the sum of the number of five CV risk factors (abdominal obesity, elevated blood pressure, high fasting blood glucose, high triglycerides and low high-density lipoprotein cholesterol). Based on left ventricular mass index and relative wall thickness (RWT), left ventricular hypertrophy (LVH), high RWT and LVG remodeling [concentric remodeling (CR), eccentric hypertrophy (EH) and concentric hypertrophy (CH)] were defined.ResultsCompared to participants without CV risk factor, those with 1, 2 and ≥3 risk factors were at increased risk of LVH [ORs (95% CIs): 3.49 (2.19–5.56), 5.53 (3.20–9.55), and 19.19 (9.67–38.08), respectively]; corresponding values for high RWT were 2.47 (1.63–3.74), 3.76 (2.25–6.27), and 5.47 (2.65–11.28). Similar associations between clustering of CV risk factors and LVG remodeling were found [CR: 1.71 (1.06–2.76), 2.83 (1.54–5.18), and 3.82 (1.37–10.62); EH: 2.42 (1.42–4.11), 4.23 (2.24–7.96), and 16.86 (7.70–36.92); CH: 14.92 (4.41–50.47), 23.15 (6.32–84.83), and 71.19 (17.09–296.56)].ConclusionCV risk factors in isolation and combination were associated with an increased risk of LVH, high RWT and LVG remodeling among children, emphasizing the need to consider multiple risk factors when assessing the risk of cardiac outcomes.

Abstract Background Smokeless tobacco use is popular in some regions worldwide, but it receives less attention compared to cigarette smoking. We aimed to estimate the recent prevalence of, and trends in, smokeless tobacco use and to examine its associated factors among adolescents aged 12–16 years in 138 countries/territories (hereafter “countries”) from 1999 to 2019. Methods Data from the Global Youth Tobacco Survey conducted in 138 countries in 2010–2019 and the National Youth Tobacco Survey conducted in the United States in 2019 were used to calculate the prevalence of current smokeless tobacco use and investigate its associated factors among adolescents aged 12–16 years. We also assessed the trend in the prevalence of smokeless tobacco use in 100 countries that had conducted more than one survey from 1999 to 2019. Results The overall prevalence of current smokeless tobacco use was 4.4% (95% confidence interval [CI] 4.0–4.9), with 5.7% (5.1–6.3) for boys, 3.1% (2.6–3.5) for girls, 3.9% (3.5–4.4) for adolescents aged 12–14 years and 5.4% (4.8–5.9) for those aged 15–16 years. The prevalence was highest in the South-East Asian region (6.1%, 4.4–7.7) and lowest in the Western Pacific region (2.0%, 1.7–2.4). The prevalence of smokeless tobacco use decreased in 57 of 100 countries, increased in 32 countries, and remained unchanged in 11 countries. Current cigarette smoking (odds ratio [OR]=2.00, 95% CI=1.68–2.39), other tobacco product use (OR=6.03, 95% CI=4.92–7.40), tobacco advertisement exposure (OR=1.44, 95% CI=1.19–1.74), being offered free tobacco products (OR=2.01, 95% CI=1.66–2.42), and not being taught about dangers of smoking (OR=1.28, 95% CI=1.09–1.50) were all positively associated with current smokeless tobacco use. Conclusions Smokeless tobacco use among adolescents remains a public health concern worldwide. Although the prevalence among adolescents decreased in most countries, it remains high especially in the South-East Asian region. More strict and effective strategies and measures are needed to further curb the smokeless tobacco use among adolescents.

Abstract Background The empirical evidence remains inconclusive for an association between diabetes mellitus (DM) in children and early-onset kidney disease later in life, and little is known about the effects of DM types (i.e., type 1 diabetes [T1DM] and type 2 diabetes [T2DM]) in childhood on type-specific kidney diseases. We aimed to evaluate the association of childhood DM with overall and type-specific early-onset kidney diseases later in life. Methods The population-based matched cohort study included 9356 individuals with DM (T1DM: 8470, T2DM: 886) diagnosed in childhood (

BackgroundThis study was aimed to examine the association between cigarette smoking in childhood and mortality in adulthood, and the impact of non-smoking duration among smokers who subsequently quit smoking.MethodsWe used data from 472,887 adults aged 18–85 years examined once in the US National Health Interview Survey in 1997–2014, which was linked to mortality data from the National Death Index up to 31 December 2015. Cigarette smoking status in childhood (age 6 to 17 years) and adulthood (age 18 to 85 years) was self-reported using a standard questionnaire at the time of participation in the survey. The vital status of participants due all-causes, cardiovascular disease (CVD), cancer and chronic lower respiratory diseases was obtained using mortality data from the National Death Index.ResultsDuring the mean follow-up of 8.75 years, compared with never smoking in childhood and adulthood, the risk of all-cause mortality among current adult smokers decreased slightly according to increasing age at smoking initiation: hazard ratios (HRs; 95% confidence intervals, CIs) were 2.54 (2.24–2.88) at age of 6–9 years, 2.44 (2.31–2.57) at age of 10–14 years, and 2.21 (2.12–2.31) at age of 15–17 years. Smoking cessation before the age of 30 years was not associated with increased risk of all-cause and cause-specific mortality (all p > 0.05) compared to never smoking.ConclusionMortality risk was higher in individuals who started smoking at an earlier age in childhood. Inversely, smoking cessation before the age of 30 years was not associated with an increased risk of mortality compared to never smoking.

BackgroundThe recently published “Life’s Essential 8” (LE8) by the American Heart Association has overcome some limitations in evaluating cardiovascular health (CVH) in the previous “Life’s Simple 7.” ObjectiveWe aimed to examine the secular trends in CVH, as assessed by the LE8, in US adults from 2005 to 2018. MethodsUsing cross-sectional data from the National Health and Nutrition Examination Survey between 2005-2006 and 2017-2018, we calculated the age-standardized mean scores of overall CVH and each of the LE8 components, where a higher score (range 0-100 points) means a better health status. A total of 21,667 adults aged 20-79 years were included in this analysis. ResultsThe overall CVH did not significantly change between 2005-2006 and 2017-2018 (65.5, 95% CI 63.9-67.1 to 65.0, 95% CI 62.8-67.1; P=.82). The individual metrics did not significantly change for diet (41.0, 95% CI 38.0-43.9 to 41.5, 95% CI 36.5-46.6; P=.94), physical activity (57.5, 95% CI 53.0-61.9 to 53.0, 95% CI 48.7-57.3; P=.26), and blood pressure (68.4, 95% CI 65.2-71.5 to 68.6, 95% CI 65.3-71.9, P=.35), improved for nicotine exposure (64.7, 95% CI 61.1-68.4 to 71.9, 95% CI 67.7-76.2; P

Background: The effects of fine particulate matter (PM2.5) on acute myocardial infarction (AMI) have been widely recognized. However, no studies have comprehensively evaluated future PM2.5-attributed AMI burdens under different climate mitigation and population change scenarios. We aimed to quantify the PM2.5-AMI association and estimate the future change in PM2.5-attributed AMI incident cases under six integrated scenarios in 2030 and 2060 in Shandong Province, China. Methods: Daily AMI incident cases and air pollutant data were collected from 136 districts/counties in Shandong Province from 2017 − 2019. A two-stage analysis with a distributed lag nonlinear model was conducted to quantify the baseline PM2.5-AMI association. The future change in PM2.5-attributed AMI incident cases was estimated by combining the fitted PM2.5-AMI association with the projected daily PM2.5 concentrations under six integrated scenarios. We further analyzed the factors driving changes in PM2.5-related AMI incidence using a decomposition method. Results: Each 10 μg/m3 increase in PM2.5 exposure at lag05 was related to an excess risk of 1.3 % (95 % confidence intervals: 0.9 %, 1.7 %) for AMI incidence from 2017 − 2019 in Shandong Province. The estimated total PM2.5-attributed AMI incident cases would increase by 10.9−125.9 % and 6.4–244.6 % under Scenarios 1 − 3 in 2030 and 2060, whereas they would decrease by 0.9–5.2 % and 33.0–46.2 % under Scenarios 5 – 6 in 2030 and 2060, respectively. Furthermore, the percentage increases in PM2.5-attributed female cases (2030: −0.3 % to 135.1 %; 2060: −33.2 % to 321.5 %) and aging cases (2030: 15.2–171.8 %; 2060: −21.5 % to 394.2 %) would wholly exceed those in male cases (2030: −1.8 % to 133.2 %; 2060: −41.1 % to 264.3 %) and non-aging cases (2030: −41.0 % to 45.7 %; 2060: −89.5 % to −17.0 %) under six scenarios in 2030 and 2060. Population aging is the main driver of increased PM2.5-related AMI incidence under Scenarios 1 − 3 in 2030 and 2060, while improved air quality can offset these negative effects of population aging under the implementation of the carbon neutrality and 1.5 °C targets. Conclusion: The combination of ambitious climate policies (i.e., 1.5 °C warming limits and carbon neutrality targets) with stringent clean air policies is necessary to reduce the health impacts of air pollution in Shandong Province, China, regardless of population aging.

BackgroundIt is well documented that birth weight and childhood weight are associated with the blood pressure (BP) levels in childhood. However, the impact of weight status change from birth to childhood on BP among children is less well described. We aimed to assess the association between changes in weight status from birth to childhood and high BP in childhood.Methods and resultsData were obtained from a cross-sectional survey conducted in Jinan, China, and a total of 5,546 children aged 6–17 years were included in this study. Based on the birth weight status [high weight (> 4,000 g) vs. normal weight (2,500–4,000 g)] and childhood weight status during the survey period [high weight (overweight and obesity) vs. normal weight], children were assigned into four groups: persistently normal weight (normal birth weight and normal childhood weight), resolved high weight (high birth weight but normal childhood weight), incident high weight (normal birth weight but high childhood weight), and persistently high weight (high birth weight and high childhood weight). After adjustment for sex and age, BP in childhood was more responsive to current body mass index (BMI) than birth weight. After adjustment for the potential covariates, compared with children who had persistently normal weight from birth to childhood, those with incident high weight (odds ratio [OR] = 3.88, 95% confidence interval [CI] = 3.29–4.57) and persistently high weight (OR = 3.52, 95% CI = 2.71–4.57) were associated with the increased odds of childhood high BP. However, children who had resolved high weight did not have significantly increased odds of high BP in childhood (OR = 0.86, 95% CI = 0.59–1.25).ConclusionThe association of BP with recent BMI was stronger than with birth weight. Children who had incident or persistently high weight from birth to childhood had increased odds of high BP in childhood, whereas the odds was not significantly increased among those with high birth weight but changed to normal weight in childhood. Our findings highlight the importance of maintaining an appropriate weight in the early lifetime for the prevention of high BP and other related diseases, especially for those with high birth weight.

BackgroundIt is well-known that secondhand smoke exposure in childhood or adolescence is positively associated with morbidity and mortality. However, less is known about the current status of and most recent trends in secondhand smoke exposure among adolescents in China. ObjectiveWe aimed to assess recent changes in the prevalence of secondhand smoke exposure among adolescents in China using nationally representative data. MethodsWe used data from 2 repeated national cross-sectional surveys conducted in 2013-2014 and 2019. A total of 155,117 students (median age 13.5 years) in 2013-2014 and 147,270 students (median age 13.1 years) in 2019 were included in this study. Sociodemographic factors and secondhand smoke exposure information were collected via a standardized questionnaire. Exposure was defined as secondhand smoke exposure ≥1 day during the past 7 days at home or in public places. Other frequencies of secondhand smoke exposure (ie, ≥3 days, ≥5 days, and every day) during the past 7 days were also assessed. The weighted prevalence of secondhand smoke exposure was calculated according to the complex sample design for surveys. ResultsThe prevalence of secondhand smoke exposure in any place (home or public places ≥1 day during the past 7 days) decreased from 2013-2014 (72.9%, 95% CI 71.5%-74.3%) to 2019 (63.2%, 95% CI 62%-64.5%), as did exposure at home (2013-2014: 44.4%, 95% CI 43.1%-45.7%; 2019: 34.1%, 95% CI 33.1%-35.2%) and in public places (2013-2014: 68.3%, 95% CI 66.9%-69.6%; 2019: 57.3%, 95% CI 56%-58.6%). The prevalence of secondhand smoke exposure decreased with increased gross domestic product per capita in each of the 2 survey years irrespective of exposure frequency or location. The prevalence of exposure at other frequencies (ie, ≥3 days, ≥5 days, or every day during the past 7 days) also decreased in any place, at home, and in public places. Secondhand smoke exposure was associated with higher school grade level (ninth vs seventh grade: odds ratio [OR] 1.76, 95% CI 1.68-1.84), gender (boys vs girls: OR 1.18, 95% CI 1.15-1.22), urban status (urban vs rural: OR 1.10, 95% CI 1.01-1.19), and cigarette smoking (yes vs no: OR 6.67, 95% CI 5.83-7.62). ConclusionsAlthough the prevalence of secondhand smoke exposure among Chinese adolescents declined from 2013-2014 to 2019, it remains unacceptably high. More effective strategies and stronger action are needed in China to further, and dramatically, curb secondhand smoke exposure among adolescents.

Summary: Background: Association of timing and intensity of maternal smoking during pregnancy with all-cause and cause-specific infant death remains inconclusive. We aimed to examine the dose–response association of maternal smoking during each of the three trimesters of pregnancy with all-cause and cause-specific infant death. Methods: In this nationwide, population-based, retrospective cohort study, data were extracted from the U.S. National Vital Statistics System, 2015–2019. We included mother–infant pairs after excluding twin or multiple births, newborns with gestation age

Abstract Background The associations of maternal cigarette smoking with congenital anomalies in offspring have been inconsistent. This study aimed to clarify the associations of the timing and intensity of maternal cigarette smoking with 12 subtypes of birth congenital anomalies based on a nationwide large birth cohort in the USA. Methods We used nationwide birth certificate data from the US National Vital Statistics System during 2016–2019. Women reported the average daily number of cigarettes they consumed 3 months before pregnancy and in each subsequent trimester during pregnancy. Twelve subtypes of congenital anomalies were identified in medical records. Poisson regression analysis was used to estimate the risk ratios (RRs) with 95% confidence intervals (CIs) for 12 subtypes of congenital anomalies associated with the timing (i.e., before pregnancy, and during three different trimesters of pregnancy) and intensity (i.e., number of cigarettes consumed per day) of maternal cigarette smoking. Results Among the 12,144,972 women included, 9.3% smoked before pregnancy and 7.0%, 6.0%, and 5.7% in the first, second, and third trimester, respectively. Maternal smoking before or during pregnancy significantly increased the risk of six subtypes of birth congenital anomalies (i.e., congenital diaphragmatic hernia, gastroschisis, limb reduction defect, cleft lip with or without cleft palate, cleft palate alone, and hypospadias), even as low as 1–5 cigarettes per day. The adjusted RRs (95% CIs) for overall birth congenital anomalies (defined as having any one of the congenital malformations above significantly associated with maternal cigarette smoking) among women who smoked 1–5, 6–10, and ≥ 11 cigarettes per day before pregnancy were 1.31 (1.22–1.41), 1.25 (1.17–1.33), and 1.35 (1.28–1.43), respectively. Corresponding values were 1.23 (1.14–1.33), 1.33 (1.24–1.42), 1.33 (1.23–1.43), respectively, for women who smoked cigarettes in the first trimester; 1.32 (1.21–1.44), 1.36 (1.26–1.47), and 1.38 (1.23–1.54), respectively, for women who smoked cigarettes in the second trimester; and 1.33 (1.22–1.44), 1.35 (1.24–1.47), and 1.35 (1.19–1.52), respectively, for women who smoked cigarettes in the third trimester. Compared with women who kept smoking before and throughout pregnancy, women who never smoked had significantly lower risk of congenital anomalies (RR 0.77, 95% CI 0.73–0.81), but women who smoked before pregnancy and quitted during each trimester of pregnancy had no reduced risk (all P > 0.05). Conclusions Maternal smoking before or during pregnancy increased the risk of several birth congenital anomalies, even as low as 1–5 cigarettes per day. Maternal smokers who stopped smoking in the subsequent trimesters of pregnancy were still at an increased risk of birth congenital anomalies. Our findings highlighted that smoking cessation interventions should be implemented before pregnancy.

Abstract There is no consistent conclusion on which adiposity measure is best to predict cardiovascular risk factors in youth. The present study aims to assess the performance of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) in predicting abnormal left ventricular structure in Chinese hypertensive youth. A total of 1180 youth aged 6–17 years with hypertension from the China Child and Adolescent Cardiovascular Health Study were included in this study. Logistic regression model, receiver operator characteristic (ROC) curve analysis and net reclassification improvement (NRI) method were used to assess performance of BMI, WC, and WHtR in predicting left ventricular hypertrophy (LVH) and left ventricular geometry (LVG). A 1-standard deviation increment in any of three indexes in predicting LVH and LVG were similar, e.g., with the odds ratios and 95% confidence intervals of 1.34 (1.16–1.55), 1.25 (1.08–1.45) and 1.40 (1.20–1.62), respectively. In addition, ROC analysis and NRI method confirmed the similar performance of three adiposity indexes in predicting LVH and LVG. In conclusion, BMI, WC and WHtR had similar performance in predicting abnormal left ventricular structure in Chinese hypertensive youth, but all three indexes had limited value in prediction. WHtR is a simple and convenient adiposity index for screening youth at high risk of target organ damage.

We aimed to evaluate the association between leisure-time physical activity (PA) and mortality risk in adults with major chronic diseases. A total of 170,579 adults with major chronic diseases aged 30–84 years from the U.S. National Health Interview Surveys (1997–2014) with linkage to the National Death Index (NDI) through December 31, 2015 were included in this study. During a median follow-up of 7.25 years, 36,914 adults with chronic diseases died from all causes, 8,767 died from cardiovascular disease (CVD), and 9,090 died from cancer. Compared with participants with no leisure-time PA, those with a low level (10–59 min/week) of total leisure-time PA had a 23% [hazard ratio (HR) 0.77, 95% confidence interval (CI) 0.73–0.82] reduced risk of all-cause mortality. Adults with higher levels of leisure time had more reduced risk of all-cause mortality, as well as CVD-specific and cancer-specific mortality. Adults with leisure-time PA ≥ 1,500 min/week had more reduced risk of CVD-specific mortality (61%) but less reduced risk of cancer-specific mortality (29%) compared with the reduced risk of all-cause mortality (43%). There was an inversely non-linear dose-response relationship between leisure-time PA and all-cause and cause-specific mortality. Reduced risk of all-cause and cancer-specific mortality between leisure-time light-to-moderate PA and vigorous-intensity PA time were largely comparable. Low and high levels of leisure-time PA showed substantial survival benefits compared with no leisure-time PA in adults with major chronic diseases. The light-to-moderate-intensity leisure-time PA is largely comparable with vigorous PA to provide survival benefits for all-cause and cancer-specific mortality.

BackgroundLimited studies have assessed the recent proportion and trend in the age of cigarette smoking initiation among adolescent smoking experiencers globally. We aimed to assess the recent global proportion, associated factors and the long-term trend of the initiated age of cigarette smoking among adolescent smoking experiencers.MethodsWe used data from the most recent Global Youth Tobacco Survey on 99,728 adolescent smoking experiencers aged 13–15 years from 144 countries/territories (hereafter “countries”) that had conducted at least one survey in 2010–20, to assess the recent proportion of the age of cigarette smoking initiation. Additionally, we used data from 148 countries that had conducted ≥2 surveys between 1999 and 2020, to assess the trend in the average age of cigarette smoking initiation.ResultsAmong 99,728 adolescent smoking experiencers aged 13–15 years, the proportions of initiating cigarette smoking when aged ≤ 9 years, 10–11 years, 12–13 years, and 14–15 years were 22.8% (95%CI 21.3–24.4), 18.8% (17.3–20.2), 36.8% (34.5–39.2), and 21.6% (19.9–23.2), respectively. The average age of cigarette smoking initiation decreased by 0.44 years per 5 calendar-years averagely in 17 (11.5%) of 148 countries, was unchanged in 95 (64.2%) countries, and increased by 0.38 years per 5 calendar-years averagely in 36 (24.3%) countries. Higher income category (reference group: low-income countries; lower-middle-income: OR = 0.44, 95%CI = 0.28–0.70; upper-middle-income: OR = 0.56, 95%CI = 0.38–0.83; high-income: OR = 0.35, 95%CI = 0.22–0.53) and Framework Convention on Tobacco Control ratification (OR = 0.51, 95%CI = 0.42–0.63) were inversely associated with early cigarette smoking initiation.ConclusionsA substantial proportion (~80%) of adolescent smoking experiencers aged 13–15 years initiated cigarette smoking before 13 years, and the average age of cigarette smoking initiation decreased or remained unchanged in nearly three quarters of the countries surveyed. These findings emphasize that national governments around the world need to strengthen intervention strategies and measures aimed at children and adolescents to prevent smoking up-take.

IntroductionTo describe the recent prevalence of, and trends in, waterpipe smoking and to examine its associated factors among adolescents aged 12–16 years in 73 countries/territories (hereafter “countries”).MethodsData from 72 countries that had conducted a Global Youth Tobacco Survey (GYTS) in 2010–2019 and from the National Youth Tobacco Survey in the United States in 2019 were used to assess the recent prevalence of waterpipe smoking and to examine its associated factors among adolescents aged 12–16 years. Data from 38 countries that had carried out at least 2 surveys from 2000 to 2019 were used to determine trends in the prevalence of waterpipe smoking among adolescents.ResultsThe recent prevalence of current waterpipe smoking (on 1 day during the past 30 days) among adolescents was 6.9% (95%CI 6.4–7.5). The prevalence was highest in the European region (10.9%, 9.9–11.8) and Eastern Mediterranean region (10.7%, 9.5–11.9), but lowest in the Western Pacific region (1.9%, 1.4–2.4). The prevalence of current waterpipe smoking increased or remained unchanged in 19 (50%) of 38 countries, but decreased in the remaining 19 countries (50%). Parental smoking, closest friends' smoking, secondhand smoke exposure, tobacco advertisement exposure, not being taught the dangers of smoking, particularly cigarette smoking, were positively associated with adolescent waterpipe smoking.DiscussionWaterpipe smoking among adolescents remains a major public health issue worldwide, especially in the regions of Europe and the Eastern Mediterranean. Effective prevention and control strategies and measures are needed to curb the epidemic of adolescent waterpipe smoking.

Glutamine supplementation has been reported to affect blood pressure (BP). However, its role in the progression of hypertension induced by high salt diet (HSD) has not been elucidated. Male normotensive Wistar rats were exposed to high salt diet and treated with different doses of glutamine supplementation. Rats aged 6 weeks were assigned to five groups: (1) Normal-salt diet (0.3% NaCl, NSD); (2) High-salt diet (8% NaCl, HSD); (3) High-salt + low-dose diet (8% NaCl, 0.5 g of L-glutamine/kg body weight, HSLGD); (4) High-salt + middle-dose diet (8% NaCl, 1.5 g of L-glutamine/kg body weight, HSMGD); and (5) High-salt + high-dose diet (8% NaCl, 2.5 g of L-glutamine/kg body weight, HSHGD). After supplementing different doses of glutamine to male Wistar 6-week-old rats fed with HSD for 7 weeks, we found no difference in body weight among groups. Importantly, we showed that dietary L-glutamine supplementation could prevent the development of hypertension in a dose-dependent manner [dramatically lowering systolic blood pressure (SBP) and slightly reducing diastolic blood pressure (DBP) of hypertensive rats, while the differences of DBP between groups did not reach statistical significance]. Our data further elucidated that dietary glutamine supplementation mildly alleviated the degree of left ventricular hypertrophy, including interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in hypertensive rats. Together, our results offer evidence that the dietary uptake of glutamine may be associated with attenuating the development of high salt-induced hypertension and slightly alleviating the degree of left ventricular hypertrophy in hypertensive rats. Therefore, glutamine supplementation may act as a prospective dietary intervention for the treatment of hypertension.

A disintegrin and metalloprotease domain family protein 17 (ADAM17) is a new member of renin-angiotensin system (RAS) but its role in the pathogenesis of diabetic cardiomyopathy (DCM) is obscure. To test the hypothesis that ADAM17 knockdown mitigates while ADAM17 overexpression aggravates cardiac fibrosis via regulating ACE2 shedding and myofibroblast transformation in diabetic mice, ADAM17 gene was knocked down and overexpressed by means of adenovirus-mediated short-hairpin RNA (shRNA) and adenovirus vector carrying ADAM17 cDNA, respectively, in a mouse model of DCM. Two-dimensional and Doppler echocardiography, histopathology and immunohistochemistry were performed in all mice and in vitro experiments conducted in primary cardiofibroblasts. The results showed that ADAM17 knockdown ameliorated while ADAM17 overexpression worsened cardiac dysfunction and cardiac fibrosis in diabetic mice. In addition, ADAM17 knockdown increased ACE2 while reduced AT1R expression in diabetic hearts. Mechanistically, ADAM17 knockdown decreased while ADAM17 overexpression increased cardiac fibroblast-to-myofibroblast transformation through regulation of TGF-β1/Smad3 signaling pathway. In conclusion, ADAM17 knockdown attenuates while ADAM17 overexpression aggravates cardiac fibrosis via regulating ACE2 shedding and myofibroblast transformation through TGF-β1/Smad3 signaling pathway in diabetic mice. Targeting ADAM17 may provide a promising approach to the prevention and treatment of cardiac fibrosis in DCM.

In this Perspective, Bo Xi and Costan Magnussen discuss the trends in smoking prevalence in China reported by Mei Zhang and colleagues, and the need for effective tobacco control strategies.

Lysobacter species have attracted increasing attention in recent years due to their capacities to produce diverse secondary metabolites against phytopathogens. In this research, we analyzed the genomic and transcriptomic patterns of Lysobacter capsici CK09. Our data showed that L. capsici CK09 harbored various contact-independent biocontrol traits, such as fungal cell wall lytic enzymes and HSAF/WAP-8294A2 biosynthesis, as well as several contact-dependent machineries, including type 2/4/6 secretion systems. Additionally, a variety of hydrolytic enzymes, particularly extracellular enzymes, were found in the L. capsici CK09 genome and predicted to improve its adaption in soil. Furthermore, several systems, including type 4 pili, type 3 secretion system and polysaccharide biosynthesis, can provide a selective advantage to L. capsici CK09, enabling the species to live on the surface in soil. The expression of these genes was then confirmed via transcriptomic analysis, indicating the activities of these genes. Collectively, our research provides a comprehensive understanding of the biocontrol potential and soil adaption of L. capsici CK09 and implies the potential of this strain for application in the future.

BackgroundLocal governments in China took restrictive measures after the outbreak of COVID-19 to control its spread, which unintentionally resulted in reduced anthropogenic emission sources of air pollutants. In this study, we intended to examine the effects of the COVID-19 lockdown policy on the concentration levels of particulate matter with aerodynamic diameters of ≤1 μm (PM1), ≤2.5 μm (PM2.5), and ≤10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO) and the potential subsequent reductions in the incidence of ischemic and hemorrhagic stroke in Shandong Province, China.MethodsA difference-in-difference model combining the daily incidence data for ischemic and hemorrhagic stroke and air pollutant data in 126 counties was used to estimate the effect of the COVID-19 lockdown on the air pollutant levels and ischemic and hemorrhagic stroke incident counts. The avoided ischemic stroke cases related to the changes in air pollutant exposure levels were further estimated using concentration-response functions from previous studies.ResultsThe PM1, PM2.5, PM10, NO2, and CO levels significantly decreased by −30.2, −20.9, −13.5, −46.3, and −13.1%, respectively. The O3 level increased by 11.5% during the lockdown compared with that in the counterfactual lockdown phase of the past 2 years. There was a significant reduction in population-weighted ischemic stroke cases (−15,315, 95% confidence interval [CI]: −27,689, −2,942), representing a reduction of 27.6% (95% CI: −49.9%, −5.3%). The change in the number of hemorrhagic stroke cases was not statistically significant. The total avoided PM1-, PM2.5-, PM10-, NO2-, and CO–related ischemic stroke cases were 739 (95% CI: 641, 833), 509 (95% CI: 440, 575), 355 (95% CI: 304, 405), 1,132 (95% CI: 1,024, 1,240), and 289 (95% CI: 236, 340), respectively.ConclusionThe COVID-19 lockdown indirectly reduced the concentration levels of PM1, PM2.5, PM10, NO2, and CO and subsequently reduced the associated ischemic stroke incidence. The health benefits due to the lockdown are temporary, and long-term measures should be implemented to increase air quality and related health benefits in the post-COVID-19 period.

Abstract The performance of different BP readings and their combinations at a visit to identify children and adolescents with pediatric hypertension remains controversial. We aimed to assess the utility of different blood pressure (BP) readings and their combinations obtained at the initial screening visit for identifying Chinese children and adolescents with hypertension. Participants were 7831 children and adolescents aged 6‐17 years measured as part of a cross‐sectional survey conducted in Jinan, China between September 2012 and November 2014. BP was measured three times at up to three visits. Elevated BP at the initial visit was defined as systolic BP and/or diastolic BP ≥ age‐ and sex‐specific 95th percentiles using the Chinese BP references for children and adolescents based on different BP readings and their combinations. Participants with elevated BP using (BP2+BP3)/2 across three visits were defined as having hypertension. Of the different readings or combinations examined, the mean of the last two readings at the initial visit had the best predictive utility for children and adolescents with hypertension (sensitivity: 100.0%; specificity: 86.9%; positive predictive value: 27.6%; negative predictive value: 100.0%). This was also reflected in the area under the curve being highest for the mean of the last two readings (0.93, 95% confidence interval: 0.93‐0.94) compared with any of the other readings or combinations (BP1, BP2, BP3, [BP1+BP2]/2, [BP1+BP3]/2, and [BP1+BP2+BP3]/3; all p

Background: Tobacco use, secondhand smoke (SHS) exposure and household solid fuel use in women of reproductive age can cause morbidity and mortality for both women and offspring. Objectives: We aimed to determine the prevalence of tobacco use, SHS exposure at home and household solid fuel use among women in low- and middle-income countries (LMICs) and their secular trends between 2000 and 2018. Methods: We used the most recent data from the Demographic and Health Surveys in 57 LMICs (n = 1,598,111) that were completed between 2010 and 2018 to assess the prevalence of tobacco use, SHS exposure at home and household solid fuel use among women of reproductive age (15–49 years). We also used data from 41 selected LMICs that had data from two or more surveys completed between 2000 and 2018 to assess secular trends in the prevalence of tobacco use and household solid fuel use among women. Results: In 2010–2018, the overall prevalence of tobacco use, daily SHS exposure at home and household solid fuel use among women in 57 LMICs was 3.2% (95 %CI = 3.1–3.3), 23.0% (22.8–23.2), and 65.6% (65.3–65.9), respectively. The prevalence of tobacco use was lower among pregnant women than non-pregnant women (2.1% vs. 3.3%), but the prevalence of daily SHS exposure at home (24.4% vs. 22.8%) and household solid fuel use (69.1% vs. 65.3%) was higher among pregnant women than non-pregnant women. About 16% of the women presented two or three simultaneous risk factors. Between 2000 and 2018, the prevalence of tobacco use decreased in 24 (64.9%) of 37 countries, and the prevalence of household solid fuel use decreased in 20 (50.0%) of 40 countries. Conclusions: Tobacco use among women was much low in LMICs, but SHS exposure at home was more common. Although the prevalence of household solid fuel use decreased over time in most LMICs, these recent estimates remained unacceptably high.

BackgroundGestational weight gain (GWG) reflects maternal nutrition during pregnancy. However, the associations between maternal GWG and adverse birth outcomes are inconclusive.ObjectiveWe aimed to examine the associations between maternal GWG and adverse birth outcomes according to maternal pre-pregnancy body mass index (BMI) categories in a large, multiethnic and diverse population in the U.S.Study DesignWe used nationwide birth certificate data from the National Vital Statistics System to examine the association of GWG (below, within and above the Institute of Medicine [IOM] guidelines) with six adverse birth outcomes (preterm birth, low birthweight, macrosomia, small for gestational age [SGA], large for gestational age [LGA], and low Apgar score) according to the pre-pregnancy BMI categories (underweight to obesity grade 3). Multivariable logistic regression analyses were performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs).ResultsA total of 9,191,842 women aged 18–49 years at delivery with live singleton births were included. Among them, 24.5% of women had GWG below IOM guidelines, 27.6% within the guidelines, and 47.9% above the guidelines. Compared with maternal GWG within guidelines, GWG below guidelines was associated with higher odds of preterm birth (OR = 1.52, 95%CI = 1.51–1.53), low birthweight (OR = 1.46, 95%CI = 1.45–1.47) and SGA (OR = 1.44, 95%CI = 1.43–1.45). In contrast, maternal GWG above guidelines was associated with higher odds of macrosomia (OR = 2.12, 95%CI = 2.11–2.14) and LGA (OR = 2.12, 95%CI = 2.11–2.14). In addition, maternal GWG below or above guidelines had slightly higher odds of low Apgar score (below guidelines: OR = 1.04, 95%CI = 1.03–1.06, above guidelines: OR = 1.17, 95%CI = 1.15–1.18). The results were largely similar among women with GWG below or above guidelines across pre-pregnancy BMI categories of underweight, overweight, and obesity grade 1 to grade 3.ConclusionPregnant women with GWG below or above the IOM guidelines have increased odds of selected adverse infant birth outcomes. Monitoring maternal GWG could enable physicians to provide tailored nutrition and exercise advice as well as prenatal care to pregnant women to reduce the likelihood of adverse birth outcomes.

Background and AimsInfant adverse birth outcomes have been suggested to contribute to neonatal morbidity and mortality and may cause long-term health consequences. Although evidence suggests maternal prepregnancy body mass index (BMI) categories associate with some birth outcomes, there is no consensus on these associations. We aimed to examine the associations of maternal prepregnancy BMI categories with a wide range of adverse birth outcomes.MethodsData were from a population-based retrospective cohort study of 9,282,486 eligible mother–infant pairs in the U.S. between 2016 and 2018. Maternal prepregnancy BMI was classified as: underweight (

Summary: Background: Secondhand smoke exposure can cause morbidity and premature mortality. However, the global prevalence of, and trends in, secondhand smoke exposure among adolescents are poorly documented. We aimed to assess the prevalence of, and trends in, secondhand smoke exposure among adolescents from 1999 to 2018. Methods: We did an analysis of the most recent data from the Global Youth Tobacco Survey (GYTS), a nationally representative, self-administered, school-based cross-sectional survey of tobacco use and related factors among adolescents aged 12–16 years worldwide. Data from 142 countries and territories that had done a GYTS between 2010 and 2018, comprising 711 366 participants, were used to assess the prevalence of secondhand smoke exposure. Data from 131 countries and territories that had done two or more surveys between 1999 and 2018, comprising 1 405 458 participants, were used to assess trends in secondhand smoke exposure. The frequency of secondhand smoke exposure at home, in public places, or in any place was defined as follows, based on students' responses: 1 or more days, 3 or more days, 5 or more days, or daily during the past 7 days. Findings: Based on the most recent surveys done in 142 countries between Jan 1, 2010, and Dec 31, 2018, the global prevalence of secondhand smoke exposure in any place was 62·9% (95% CI 61·7–64·1) on 1 or more days, 51·0% (49·8–52·1) on 3 or more days, 40·1% (38·9–41·2) on 5 or more days, and 32·5% (31·5–33·6) daily during the past 7 days. The prevalence of secondhand smoke exposure at home was 33·1% (95% CI 32·1–34·1) on 1 or more days, 20·1% (19·3–20·9) on 3 or more days, 14·9% (14·2–15·7) on 5 or more days, and 12·3% (11·7–13·0) daily during the past 7 days; and in public places the prevalence of secondhand smoke exposure was 57·6% (56·4–58·8) on 1 or more days, 43·4% (42·2–44·6) on 3 or more days, 30·3% (29·2–31·5) on 5 or more days, and 23·5% (22·5–24·5) daily during the past 7 days. Between Jan 1, 1999, and Dec 31, 2018, the prevalence of secondhand smoke exposure (on ≥1 day during the past 7 days) in any place decreased in 57 (43·5%) of 131 countries, increased in 27 (20·6%), and remained unchanged in 47 (35·9%). Although the prevalence of secondhand smoke exposure at home decreased in 86 (65·6%) countries, the prevalence in public places did not change in 46 (35·1%) countries and increased in 40 (30·5%). Interpretation: Secondhand smoke exposure among adolescents remains a serious public health challenge worldwide. Although the prevalence of secondhand smoke exposure at home decreased in most countries, the prevalence in public places increased or remained unchanged in most countries between 1999 and 2018. These findings emphasise the need to strengthen smoke-free policies, especially in public places. Funding: Youth Team of Humanistic and Social Science of Shandong University, Jinan, China. Translation: For the Chinese translation of the abstract see Supplementary Materials section.

Several prospective cohort studies have assessed the association between multimorbidity and all-cause mortality, but the findings have been inconsistent. In addition, limited studies have assessed the association between multimorbidity and cause-specific mortality. In this study, we used the population based cohort study of National Health Interview Survey (1997–2014) with linkage to the National Death Index records to 31 December 2015 to examine the trends in prevalence of multimorbidity from 1997 to 2014, and its association with the risk of all-cause and cause-specific mortality in the U.S. population. A total of 372,566 adults aged 30–84 years were included in this study. From 1997 to 2014, the age-standardized prevalence of specific chronic condition and multimorbidity increased significantly (P < 0.0001). During a median follow-up of 9.0 years, 50,309 of 372,566 participants died from all causes, of which 11,132 (22.1%) died from CVD and 13,170 (26.2%) died from cancer. Compared with participants without the above-mentioned chronic conditions, those with 1, 2, 3, and ≥4 of chronic conditions had 1.41 (1.37–1.45), 1.94 (1.88–2.00), 2.64 (2.54–2.75), and 3.68 (3.46–3.91) higher risk of all-cause mortality after adjustment for important covariates. Similarly, a higher risk of CVD-specific and cancer-specific mortality was observed as the number of chronic conditions increased, with the observed risk stronger for CVD-mortality compared with cancer-specific mortality. Given the prevalence of multimorbidity tended to increase from 1997 to 2014, our data suggest effective prevention and intervention programs are necessary to limit the increased mortality risk associated with multimorbidity.

Background: Anemia remains a major public health issue, particularly for children and women in low- and middle-income countries (LMICs). However, the current prevalence and recent changes of anemia among young children and women of reproductive age, particularly for pregnant women in different trimesters are unclear. We examined the current prevalence of anemia among children aged less than 5 years by age (6-35 months vs. 36-59 months) and women of reproductive age by pregnant status (pregnant vs. non-pregnant) and trimesters (the third vs. the second vs. the first trimester) between 2010 and 2018 and further examined changes in the prevalence from 2000-2009 to 2010-2018. Methods: Data were from the cross-sectional Demographic and Health Surveys performed between 2000 and 2018. A total of 47 countries were included to examine the current prevalence of anemia (weighted prevalence and 95% confidence interval [CI]) among young children aged less than 5 years (N = 459,785) and 46 countries among women of reproductive age (N = 1,079,805) between 2010 and 2018. To examine changes in the prevalence of anemia, a total of 29 countries with at least two Demographic and Health Surveys performed between 2000 and 2009 (children: N = 130,772; women: N = 371,845) and 2010-2018 (children: N = 386,202; women: N = 928,889) were included. Modified Poisson regression analyses with robust error variance were used to examine changes in anemia between 2000-2009 and 2010-2018 in participants by child age (6-5 months vs. 36-59 months), women pregnant status (pregnant vs. non-pregnant), trimesters (the second or third trimester vs. the first trimester) with the adjustment for potential covariates. Findings: In 47 LMICs for children aged less than 5 years between 2010 and 2018, the total prevalence of anemia was 56.5% (95% CI 56.2, 56.8). Younger children aged 6-35 months were more likely to have anemia than older children aged 36-59 months (adjusted odds ratio [OR] 1.38, 95% CI 1.36-1.39, P

BackgroundPrevious studies have shown that waist-to-height ratio (WHtR) performed similarly well when compared to body mass index (BMI) and waist circumference (WC) for identifying cardiovascular risk factors. However, to our knowledge, the performance of these three adiposity indices for identifying left ventricular hypertrophy (LVH) and left ventricular geometric (LVG) remodeling in youth has not been assessed. We aimed to determine the utility of BMI, WC and WHtR for identifying LVH and LVG in Chinese children.MethodsThis study included 1,492 Chinese children aged 6-11 years. Adiposity indices assessed were BMI, WC and WHtR. LVH and high relative wall thickness (RWT) were defined using sex- and age-specific 90th percentile values of left ventricular mass index and RWT, respectively, based on the current population. LVG remodeling included concentric remodeling (CR), eccentric hypertrophy (EH) and concentric hypertrophy (CH), which was defined based on the combination of LVH and high RWT.ResultsThe magnitude of association of central obesity defined by WHtR with LVH [odds ratio (OR) =10.09, 95% confidence interval (CI) =6.66-15.29] was similar with general obesity defined by BMI (OR=10.49, 95% CI=6.97-15.80), and both were higher than central obesity defined by WC (OR=6.87, 95% CI=4.57-10.33). Compared with BMI, WHtR had better or similar predictive utility for identifying LVH, EH, and CH [the area under the curve (AUC): 0.84 vs. 0.79; 0.84 vs. 0.77; 0.87 vs. 0.88, respectively]; WC had worse or similar discriminatory utility with AUCs of 0.73, 0.70, 0.83, respectively.ConclusionWHtR performed similarly or better than BMI or WC for identifying LVH and LVG remodeling among Chinese children. WHtR provides a simple and convenient measure of central obesity that might improve the discrimination of children with cardiac structural damage.

Because of the limitation of body mass index (BMI) in distinguishing adipose mass from muscle, the tri-ponderal mass index (TMI) has been proposed as a new indicator for better assessing adiposity in children and adolescents. However, it remains unclear whether TMI performs better than BMI or other adiposity indices in predicting obesity status in childhood and obesity-related cardiovascular risk factors (CVRFs) in childhood or adulthood. We searched PubMed, Cochrane Library, and Web of Science for eligible publications until June 15, 2021. A total of 32 eligible studies were included in this systematic review. We found that TMI had a similar or better ability to predict body fat among children and adolescents than BMI. However, most of the included studies suggested that TMI was similar to BMI in identifying metabolic syndrome although TMI was suggested to be a useful tool when used in combination with other indicators (e.g., BMI and waist circumference). In addition, limited evidence showed that TMI did not perform better than BMI for identifying specific CVRFs, including insulin resistance, high blood pressure, dyslipidemia, and inflammation in children and adolescents, as well as CVRFs in adults.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero, CRD42021260356.

Background: Maternal height has been confirmed to be associated with offspring stunting in low- and middle-income countries (LMICs), but only limited studies have examined the paternal-offspring association, and few studies have examined the joint effect of maternal and paternal height on stunting.Objective: To investigate the association between parental height and stunting of children aged under five in LMICs.Methods: We obtained data from the Demographic and Health Surveys (DHS) conducted in 14 LMICs from 2006 to 2016. The association between maternal and paternal height and height-for-age z score (HAZ) of children aged under five was analyzed using a linear regression model in consideration of complex survey design, and regression coefficients (β) with 95% confidence intervals (CIs) were reported. Then, the association between maternal and paternal height quintile and child stunting was analyzed using a modified Poisson regression approach with robust error variance in consideration of complex survey design with adjustment for covariates. The effect estimates were expressed as relative risks (RRs) with 95% CIs.Results: A total of 50,372 singleton children were included and the weighted prevalence of stunting was 34.5%. Both maternal height and paternal height were associated with child HAZ (β = 0.047; 95% CI, 0.043, 0.050; and β = 0.022; 95% CI, 0.018, 0.025, respectively). Compared with those born to the tallest mothers and fathers, children from the shortest mothers and the shortest fathers had higher risks of stunting (adjusted RR = 1.89; 95% CI, 1.78, 2.01; adjusted RR = 1.56; 95% CI, 1.47, 1.65, respectively). The mother-offspring associations are substantively larger than the father-offspring associations for each corresponding height quintile. Children from the shortest parents had the highest risk of stunting compared with children from the tallest parents (adjusted RR = 3.23; 95% CI, 2.83, 3.68).Conclusions: Offspring born to short parents are at increased risk of stunting in LMICs, and this intergenerational effect is partly driven by maternal intrauterine influence. This suggests the importance of improving the nutritional status of children and adults in LMICs, especially female caregivers.