BackgroundZoonotic diseases remain a significant public health challenge in China. This study examines the temporal trends, disease burden, and demographic patterns of major zoonoses from 2010 to 2023.MethodsThis study analyzed data from China’s National Notifiable Infectious Disease Reporting System (NNIDRS, 2010–2023) on nine major zoonoses, including echinococcosis, brucellosis, leptospirosis, anthrax, leishmaniasis, encephalitis (Japanese encephalitis), hemorrhagic fever, rabies, and schistosomiasis. Joinpoint regression was applied to assess annual trends in incidence rates, while autoregressive integrated moving average (ARIMA) and exponential smoothing models were used to forecast incidence trends from 2024 to 2035. To assess the performance of the Global Burden of Disease (GBD) 2021 model in China, disease-specific multipliers—defined as the ratio of GBD estimates to national surveillance data—along with their corresponding 95% confidence intervals (CIs) were calculated to quantify discrepancies and evaluate the consistency between modeled estimates and empirical observations.ResultsFrom 2010 to 2023, the incidence rates of leptospirosis [average annual percent change (AAPC) = − 5.527%, 95% CI: − 11.054, − 0.485], encephalitis (AAPC = − 16.934%, 95% CI: − 23.690, − 11.245), hemorrhagic fever (AAPC = − 5.384%, 95% CI: − 7.754, − 2.924), rabies (AAPC = − 20.428%, 95% CI: − 21.076, − 19.841), and schistosomiasis (AAPC = − 28.378%, 95% CI: − 40.688, − 15.656) showed a declining trend in China. In contrast, brucellosis exhibited a modest but statistically significant increase (AAPC = 0.151%, 95% CI: 0.031, 0.272). For most diseases, incidence rates were consistently higher in males than females. Children aged 0–5 years accounted for a substantial proportion of encephalitis and leishmaniasis cases, while adults aged 14–65 years represented the primary affected group across the majority of diseases. Occupationally, farmers and herders were the most affected populations. Compared to national surveillance data, the GBD 2021 model substantially overestimated the burden of zoonotic diseases in China, particularly for echinococcosis (by 3.611–7.409 times) and leishmaniasis (by 3.054–10.500 times).ConclusionThe study revealed significant decline in several major zoonoses in China, while brucellosis showed a continued upward trend. These findings highlight the urgent need for a One Health-based prevention and control system to interrupt cross-species transmission and reduce long-term public health risks.

BackgroundDiabetes mellitus (DM) is an important public health problem that seriously affects the health of Chinese residents. Exploring the incidence of DM and its influencing factors in Chinese adults could help develop prevention and control strategies and measures. However, there was few national cohort study on DM incidence and its influencing factors in China. Based on the national representative data, we investigated the incidence and influencing factors of DM in Chinese adults.MethodsBased on 2010 China Chronic Disease and Risk Factors Surveillance (CCDRFS), a follow-up survey was conducted in 20 monitoring points from ten provinces of China in 2016–2017. Incident cases of DM were identified through questionnaires. Influencing factors for DM were collected at baseline using questionnaires, physical measurements and laboratory tests. Cox regression models were used to analyze the influencing factors of DM. Sensitivity analysis was conducted to confirm the associations between the influencing factors and DM.ResultsA total of 7048 people were included in this study. During the follow-up period, 699 DM patients were diagnosed (313 males and 386 females), with a total follow-up of 40022.82 person-years. The incidence density of DM was 17.5/1000 person-years. The Cox regression results showed that age 45–59 years (HR = 1.32, 95% CI: 1.10 ~ 1.59) and ≥ 60 years (HR = 1.48, 95% CI: 1.17 ~ 1.88), divorce/widowhood (HR = 1.45, 95% CI: 1.15 ~ 1.82), overweight (overweight with no central obesity: HR = 1.26, 95% CI: 1.03 ~ 1.54; overweight and central obesity: HR = 1.62, 95% CI: 1.34 ~ 1.97), hypertension (HR = 1.35, 95% CI: 1.15 ~ 1.59), hypertriglyceridemia (HR = 1.57, 95% CI: 1.28 ~ 1.91), high LDL-C (HR = 1.20, 95% CI: 1.02 ~ 1.40), sitting > 6 h for men (HR = 1.51, 95% CI: 1.11 ~ 2.06), and family history (HR = 1.55, 95% CI: 1.17 ~ 2.06) were risk factors for DM.ConclusionsThe incidence of DM for Chinese adults from 10 provinces was 17.5/1000 person-years. Age > 44 years, divorced/widowed, overweight, central obesity, hypertension, dyslipidemia, a sedentary lifestyle and a family history of diabetes were risk factors for DM. Comprehensive preventive measures centered on a healthy diet, adequate physical exercise, and maintaining a healthy weight should be further promoted to prevent diabetes in China.

Deazaflavin-dependent nitroreductase (Ddn) is a crucial enzyme involved in mycolic acid biosynthesis, a vital component of the cell wall in Mycobacterium tuberculosis (MTB)—the bacterial pathogen responsible for tuberculosis. Over the past two decades, nitroimidazole oxazine scaffold (NOS) derivatives have been investigated as potential therapeutic agents targeting Ddn in MTB, with a focus on enhancing drug efficacy, minimizing toxicity, and combating drug resistance. In this study, we performed an extensive theoretical investigation combining three-dimensional quantitative structure–activity relationship (3D-QSAR) studies, all-atom molecular docking, and atomic-level molecular dynamics (MD) simulations. Additionally, we analyzed the binding free energies and their decomposed terms between inhibitors and Ddn to elucidate the structure–activity relationships (SARs) and mechanisms of a series of NOS derivatives developed for MTB inhibition. The CoMFA and CoMSIA models demonstrated strong performance, with cross-validation coefficients (Rcv2) of 0.591 and 0.629, respectively, and prediction coefficients (Rpred2) of 0.7698 and 0.6848 for CoMFA and CoMSIA, respectively. These models effectively predicted the minimum inhibitory concentration (MIC) values of the compounds against MTB based on the NOS scaffold. Molecular docking followed by MD simulations was employed to validate the binding modes of these derivatives at the active site of Ddn, providing detailed insights into their interaction patterns. Notably, our analysis revealed that residues Tyr65, Ser78, Tyr130, Tyr133, and Tyr136 played critical roles in determining the potency of the compounds by contributing significantly to their binding energies. These findings provide valuable guidance for the rational design of novel NOS inhibitors with enhanced potential as effective anti-tuberculosis agents.

BackgroundCardiovascular-renal-metabolic (CKM) syndrome substantially elevates the risk of cardiovascular disease (CVD). Environmental air pollution, especially particulate matter (PM), is a key contributor, yet its long-term effects across CKM stages remain unclear.ObjectivesThis study aimed to evaluate the association between long-term exposure to different sizes of particulate matter (PM1, PM2.5, PM10) and CVD risk across the four stages of CKM syndrome.MethodsWe conducted a nationwide prospective cohort study using data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2018), including 5,824 participants aged 45 years or older. CKM stages (0 to 3) were classified according to American Heart Association guidelines. Annual average concentrations of PM1, PM2.5, and PM10 were used to estimate individual exposure. Cox proportional hazards models were used to calculate adjusted hazard ratios (HRs), and population attributable fractions (PAFs) were estimated to assess the burden of air pollution on CVD.ResultsDuring a median follow-up of 7 years, participants in the highest exposure group of PM2.5 had significantly increased CVD risk (HR = 2.31, 95% CI: 2.00–2.66). The risk rose progressively with CKM stage, peaking in stage 3 for PM1 (HR = 3.32, 95% CI: 2.24–4.92). PM1 and PM2.5 showed nonlinear exposure–response patterns, with sharply increasing CVD risk at higher concentrations. The highest PAF (~ 38%) occurred in CKM stage 2 under high PM2.5 exposure, indicating substantial burden among intermediate and advanced CKM stages. Among patients with chronic kidney disease, the association was attenuated, potentially due to medication use.ConclusionsLong-term exposure to ambient particulate matter significantly increases CVD risk, especially among individuals in advanced CKM stages.ImplicationsThese findings support incorporating CKM staging into environmental health risk assessments and highlight the need for targeted cardiovascular screening and pollution control strategies in high-exposure regions.Clinical trial numberNot applicable.

Developing a safe and effective vaccine remains a global priority for ending the human immunodeficiency virus (HIV) pandemic. All HIV vaccine trials with protein, DNA, non-replication vector or their combinations failed in the past. We constructed the HIV-1 CN54 env, gag, and pol genes into both DNA and replicating vaccinia virus Tiantan vectors. In phase Ia, 12 healthy adults were given high (n = 6) or low (n = 6) doses of recombinant vaccinia virus Tiantan vaccine (rTV), to test its safety dose. In phase Ib, 36 healthy adults were assigned to the DNA (n = 6), DNA-L/rTV (n = 12), DNA-H/rTV (n = 12), and placebo (n = 6) groups. The DNA vaccine was injected intramuscularly at weeks 0, 4, and 8 and rTV with a bifurcated needle at week 12. All vaccines tested were safe and well-tolerated; most of the adverse events (AEs) were mild to moderate. The most commonly observed AEs were redness and papule at rTV vaccination sites and axillary enlarged lymph nodes at the same rTV vaccination arm. Smaller cutaneous lesions and shorter healing time were observed in smallpox vaccine experienced subjects. The DNA prime-rTV boost regimen induced anti-gp120 IgG and polyfunctional CD4+ T cells. No significant differences of anti-HIV IgG and T cell responses were found between the two prime-boost groups with high and low DNA doses. Moreover, smallpox vaccine naïve subjects elicited higher T cell responses and anti-gp120 antibodies. The result of this trial supports further development of HIV vaccine with DNA and replicating vaccinia vector for advanced clinical trials.

Neglected Tropical Diseases (NTDs) and malaria, as tropical diseases, have long been major global public health challenges, particularly in low-income countries. Although the burden of NTDs and malaria has declined in recent years, significant health inequalities persist across regions. In the future, climate change may further exacerbate the burden of NTDs and malaria, with these burdens likely to disproportionately concentrate in low-income countries. This study aims to describe the global trends in the burden of NTDs and malaria, reveal health inequalities, and forecast future disease burdens. This study utilizes the latest data from the Global Burden of Disease Study (GBD) 2021 to assess the global trends and spatial distribution of NTDs and malaria burden from 1990 to 2021. Inequality analyses and frontier analysis were employed to evaluate disparities in disease burden and governance potential across countries, and the interactive effects between environmental risks and socio-economic factors on the burden of NTDs and malaria were explored in depth. Furthermore, the Bayes Age-Prior-Cohort model was used to forecast changes in disease burden from 2022 to 2041. From 1990 to 2021, the age-standardized DALY rate for NTDs and malaria declined from 1506.54 to 1020.27 per 100,000. Western Sub-Saharan Africa remains the most affected, contributing 51.18% of the global burden. Males have lower incidence but higher mortality rates compared to females. Despite improvements in global inequality, regional disparities persist. Environmental and socio-economic factors interact significantly, exacerbating the burden in vulnerable regions. The NTDs and malaria burden is projected to increase over the next 20 years, particularly in Middle and Low-middle Socio-Demographic Index (SDI) regions. Despite a global decline in the burden of NTDs and malaria, low-income countries, particularly in Western Sub-Saharan Africa, continue to experience significant health inequalities. Global climate change may exacerbate this burden, and these burdens will be disproportionately concentrated in tropical, poverty-stricken countries.

BackgroundTrichloroethylene (TCE) is a ubiquitous pollutant with potential capacity to induce congenital heart disease (CHD). However, the mechanisms underlying TCE-induced CHD are largely unraveled.MethodsWe exposed zebrafish embryos to TCE to investigate its cardiac development toxicity and related response factor through bulk RNA sequencing. We constructed transgenic fluorescent fish and employed the CRISPR/dCas9 system along with single-cell RNA sequencing to identify the genetic cause of TCE-induced CHD.ResultsWe found that early-stage exposure to TCE induced significant cardiac defects characterized by elongated SV-BA distance, thinned myocardium, and attenuated contractility. Gremlin1 encoding gene, grem1a, a putative target showing high expression at the beginning of cardiac development, was sharply down-regulated by TCE. Consistently, grem1a knockdown in zebrafish induced cardiac phenotypes generally like those of the TCE-treated group, accompanying the disarrangement of myofibril structure. Single-cell RNA-seq depicted that mitochondrial respiration in grem1a-repressed cardiomyocytes was greatly enhanced, ultimately leading to a branch from the normal trajectory of myocardial development. Accordingly, in vitro results demonstrated that GREM1 repression increased mitochondrial content, ATP production, mitochondrial reactive oxygen species, mitochondrial membrane potential, and disrupted myofibril expansion in hPSC-CMs.ConclusionsThese results suggested that TCE-induced gremlin1 repression could result in mitochondrial hyperfunction, thereby hampering cardiomyocyte development and causing cardiac defects in zebrafish embryos. This study not only provided a novel insight into the etiology for environmental stressor-caused cardiac development defects, but also offered a potential therapeutic and preventive target for TCE-induced CHD.

BackgroundThe health benefits of physical activity (PA) have been well recognized, while which types of PA are most beneficial are still unclear, especially for older adults. The study aimed to explore associations of different PAs (physical work, regular exercise, and leisure activities) with mortality among Chinese older adults, considering genetic risk.MethodsA total of 9690 older adults from the Chinese Longitudinal Health Longevity Survey (CLHLS, 1998–2018) were included. Self-reported PAs information on physical work, regular exercise, and leisure activities were collected through face-to-face interviews. Leisure activities were interviewed about their engagement in 6 typical activities (i.e., housework tasks, personal outdoor activities, gardening, rearing domestic animals/pets, playing cards/mahjong, and attending in social activities). A weighted genetic risk score (GRS) was constructed based on 11 lifespan-related loci and divided into two groups according to the median scores (0.21). The Cox proportional risk model was used to assess the association between different types of PAs and genetic risk with all-cause mortality.ResultsDuring 63,832 person-years of follow-up, 5678 deaths were documented. The hazard ratios (HRs) for all-cause mortality between different PAs (lowest activity vs highest activity) were 0.85 (95% CI 0.79–0.92) for leisure activities, 0.93 (95% CI 0.87–0.99) for regular exercise, and 0.93 (95% CI 0.86–1.01) for physical work, respectively. Compared with low leisure activities, high leisure activities were associated with 16% reduction in all-cause mortality for individuals with low longevity GRS (HR 0.84, 95% CI 0.76–0.93), and 14% reduction in all-cause mortality for individuals with high longevity GRS (HR 0.86, 95% CI 0.78–0.96). Adherence to regular exercise was associated with 11% reduction in all-cause mortality for individuals with high longevity GRS (HR 0.89, 95% CI 0.81–0.97), while there was no statistically significance for those with low longevity GRS (HR 0.97, 95% CI 0.89–1.06) compared with those without regular exercise. There was no additive or multiplicative interaction between PAs and longevity genetics (Pinteraction > 0.05).ConclusionsLeisure activities, as a low-risk, low-intensity, simple and inexpensive PA, rather than regular exercise, might bring the greatest health benefits, even for individuals with less longevity genes, highlighting the importance of providing individualized PA recommendations for older adults.

BackgroundAlthough dietary patterns rich in plant-based food have been linked to lower frailty risk in older adults, the relationship between vegetarian diet and incident frailty has been understudied. Therefore, this study aimed to investigate the association between vegetarian diet and risk of frailty in a nationwide representative cohort of Chinese community-dwelling older adults (≥ 65 years old).MethodsIncluded were 27,917 participants (age range: 65–122 years; mean age: 86.9 ± 11.0 years) free of frailty at study entry, from the Chinese Longitudinal Healthy Longevity Survey initiated in 1998. According to the consumption of meat, fish, eggs, and milk products assessed by the food frequency questionnaire at each survey, participants were categorized as omnivores (n = 23,541) or vegetarians (n = 4376), among which were further classified as pesco-vegetarians (n = 1547), ovo-lacto-vegetarians (n = 1745), and vegans (n = 1084). Diet trajectory (from baseline to the first follow-up survey, median interval: 2.8 years) categories included Stick-To-Omnivorous, Stick-To-Vegetarian, Omnivorous-To-Vegetarian, and Vegetarian-To-Omnivorous. Frailty was defined by a frailty index > 0.25 based on 40 variables reflecting health deficits. We used multivariable time-varying Cox proportional hazard models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs) of frailty risk according to different diet groups and diet trajectories.ResultsDuring a median follow-up of 3.0 (IQR: 1.83–5.33) years, vegetarians showed a higher risk of incident frailty (HR [95% CI]: 1.13 [1.07, 1.20]) compared to omnivores. Similar patterns were observed across subgroups of vegetarian diet, including pesco-vegetarians (HR [95% CI]: 1.15 [1.05, 1.26]), ovo-lacto-vegetarians (HR [95% CI]: 1.11 [1.02, 1.20]), and vegans (HR [95% CI]: 1.12 [1.01, 1.25]). In terms of diet trajectory, maintaining vegetarian diets (HR [95% CI]: 1.19 [1.03, 1.38]), transition from the omnivorous diet to vegetarian diets (HR [95% CI]: 1.16 [1.04, 1.30]), and transition from vegetarian diets to the omnivorous diet (HR [95% CI]: 1.14 [1.02, 1.27]) were all associated with higher risks of frailty, compared with maintaining an omnivorous diet.ConclusionsIn this prospective study, vegetarian diets were observed to be associated with higher frailty risk, compared to the omnivorous diet in Chinese older adults. Future research is needed to confirm our observations.