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Protein secondary structure prediction (PSSP) is a pivotal research endeavour that plays a crucial role in the comprehensive elucidation of protein functions and properties. Current prediction methodologies are focused on deep-learning techniques, particularly focusing on multi-factor features. Diverging from existing approaches, in this study, we placed special emphasis on the effects of amino acid properties and protein secondary structure propensity scores (SSPs) on secondary structure during the meticulous selection of multi-factor features. This differential feature-selection strategy results in a distinctive and effective amalgamation of the sequence and property features. To harness these multi-factor features optimally, we introduced a hybrid deep feature extraction model. The model initially employs mechanisms such as dilated convolution (D-Conv) and a channel attention network (SENet) for local feature extraction and targeted channel enhancement. Subsequently, a combination of recurrent neural network variants (BiGRU and BiLSTM), along with a transformer module, was employed to achieve global bidirectional information consideration and feature enhancement. This approach to multi-factor feature input and multi-level feature processing enabled a comprehensive exploration of intricate associations among amino acid residues in protein sequences, yielding a Q3 accuracy of 84.9% and an Sov score of 85.1%. The overall performance surpasses that of the comparable methods. This study introduces a novel and efficient method for determining the PSSP domain, which is poised to deepen our understanding of the practical applications of protein molecular structures.

Summary: Background: Green space is an important part of the human living environment, with many epidemiological studies estimating its impact on human health. However, no study has quantitatively assessed the credibility of the existing evidence, impeding their translations into policy decisions and hindering researchers from identifying new research gaps. This overview aims to evaluate and rank such evidence credibility. Methods: Following the PRISMA guideline, we systematically searched PubMed, Web of Science, and Embase databases for systematic reviews with meta-analyses concerning green spaces and health outcomes published up to January 15, 2024. We categorized the credibility of meta-analytical evidence from interventional studies into four levels (i.e., high, moderate, low, and very low) using the Grading of Recommendation, Assessment, Development and Evaluations framework, based on five domains including risk of bias, inconsistency, indirectness, imprecision, and publication bias. Further, we recalculated all the meta-analyses from observational studies and classified evidence into five levels (i.e., convincing, highly suggestive, suggestive, weak, and non-significant) by considering stringent thresholds for P-values, sample size, robustness, heterogeneity, and testing for biases. Findings: In total, 154 meta-analysed associations (interventional = 44, observational = 110) between green spaces and health outcomes were graded. Among meta-analyses from interventional studies, zero, four (wellbeing, systolic blood pressure, negative affect, and positive affect), 20, and 20 associations between green spaces and health outcomes were graded as high, moderate, low, and very low credibility evidence, respectively. Among meta-analyses from observational studies, one (cardiovascular disease mortality), four (prevalence/incidence of diabetes mellitus, preterm birth, and small for gestational age infant, and all-cause mortality), 12, 22, and 71 associations were categorized as convincing, highly suggestive, suggestive, weak, and non-significant evidence, respectively. Interpretation: The current evidence largely confirms beneficial associations between green spaces and human health. However, only a small subset of these associations can be deemed to have a high or convincing credibility. Hence, future better designed primary studies and meta-analyses are still needed to provide higher quality evidence for informing health promotion strategies. Funding: The National Natural Science Foundation of China of China; the Guangzhou Science and Technology Program; the Guangdong Medical Science and Technology Research Fund; the Research Grant Council of the Hong Kong SAR; and Sino-German mobility program.

Abstract Background Living in higher greenness level community has many benefits for pregnancy outcomes, however, few research have explored the relationship between greenness and spontaneous abortion (SAB). We aimed to analyze relationships between SAB and community greenness in Chinese pregnant women, and further assessed the modifying effects from air pollutants. Methods We studied 90 890 pregnant women from the China Birth Cohort Study from February 2018 to December 2021. We diagnosed SAB by certified obstetricians and gynecologists. The level of exposure to greenness during the first trimester was measured using the normalized difference vegetation index (NDVI) and the enhanced vegetation index (EVI). Particulate matter ≤ 2.5 μm (PM2.5), nitrogen dioxide (NO2) and ozone (O3) were used as proxies of ambient air pollution. Time-dependent multivariable adjusted Cox proportional hazards models, with gestational weeks as the time scale, were used to analyze the association between SAB and greenness. We additionally performed subgroup analyses stratified by age, urbanicity, research location, season of birth, temperature, humidity and air pollution levels. Results Lower SAB prevalence was related to living in greener places. A 0.1 unit increase in NDVI500m and EVI500m was significantly associated with a 12.3% (95% CI 9.9%, 15.5%) and 16.2% (95% CI 11.4%, 20.6%) lower risks of SAB, respectively. In sensitivity analysis, these relationships remained consistent. The associations were stronger among older, participants lived in the north of China and lived in places with higher PM2.5 and lower NO2 levels. Conclusions Our findings indicate significantly inverse associations between community greenness and SAB in Chinese pregnant women, especially for older and participants who live in the north of China, the PM2.5 and NO2 may modify the effects of greenness on SAB.

Abstract The authors aimed to investigate the association between outdoor light at night (LAN) intensity and blood pressure. The study included 13 507 participants aged 45 and above from the 2011–2012 China Health and Retirement Longitudinal Study baseline survey. Blood pressure measurements were obtained by averaging the last two readings recorded (three measurements with an interval of 45–60 s between each measurement) during the survey. Outdoor LAN intensity was assessed using Defense Meteorological Satellite Program data. The study categorized participants based on quartiles of outdoor LAN intensity and employed statistical methods like linear regression, restricted cubic splines, and logistic models to analyze the connections. After adjusting for potential confounding factors, higher levels of outdoor LAN intensity were associated with increase in systolic blood pressure (0.592 mmHg/interquartile range [IQR], 95% confidence interval [CI]: 0.027,1.157), diastolic blood pressure (0.853 mmHg/IQR, 95% CI: 0.525,1.180) and mean arterial pressure (0.766 mmHg/IQR, 95% CI: 0.385,1.147). Interestingly, the relationship between LAN intensity and odds of hypertension followed a non‐linear pattern, resembling a reverse “L” shape on cubic splines. Participants with the highest quartile of outdoor LAN intensity had 1.31‐fold increased odds of hypertension (95% CI: 1.08–1.58) compared to the lowest quartile. Additionally, there was an observable trend of rising odds for high‐normal blood pressure with higher levels of LAN intensity in the crude model, but no statistically significant differences were observed after adjusting for confounding factors. In conclusion, this study underscores a significant connection between outdoor LAN intensity and the prevalence of hypertension.

Charcoal is commonly preserved in both natural and artificial sediments, and is intensively used in paleontological, paleoenvironmental, and archaeological studies due to the abundant bio-information it contains. The biochemical properties of charcoal are also used for paleoclimatic reconstruction; however, the reliability of this approach has been challenged due to a lack of clarity on how physicochemical properties change during the charring process, as well as the temperatures required for charcoalification. To address this lack, in this study, Qinghai spruce and Chinese pine wood samples from the northeastern Tibetan Plateau were heated at different temperatures and for different lengths of time under restricted oxygen conditions. The reflectance; carbon, nitrogen, and oxygen content; and tracheid morphology were quantified before and after heating to assess changes related to the charring process. Archaeological charcoal remains were then evaluated to determine the charcoalification temperatures by comparing with the experimental results. The minimum temperature required for wood charcoalification was ∼300 °C, while temperatures recorded by archaeological charcoal were concentrated at 400–500 °C. During the charring experiments, the tracheid cell walls gradually homogenized, and tracheid cell wall thickness and lumen area decreased by ∼20%. On average, 50% mass losses were observed; the carbon and oxygen content (% wt.) approximately changed from 47% to 60% and 48% to 35% respectively, while the nitrogen content (% wt.) fluctuated around 0.2%. The reflectance increased slightly from 0% to 0.5%. We propose that the charcoalification of wood tissue refers to charring (in restricted air) and carbonization (in the almost absence of air) when the wood is exposed to a heat source, which then finally transforms into a black, inert solid. This quantitative study provided valuable data and a thorough assessment of the process of wood charcoalification, as well as accurately estimated the feasibility of using charcoal physicochemical properties in paleoclimatic research.

BackgroundPrevious research indicated that isomers and alternatives of per- and polyfluoroalkyl substances (PFAS) probably disturb glucose metabolism; however, current epidemiological evidence on the associations of PFAS with fasting blood glucose is inconsistent. Besides, studies on the joint association of multiple components of PFAS and fasting blood glucose as well as the key component are scarce. ObjectiveTo evaluate the associations of PFAS isomers and alternatives with fasting blood glucose and their joint effects, as well as identify the key component among population without glucose metabolism problems. MethodsWe selected 923 adults without glucose metabolism problems or missing data from the Isomers of C8 Health Project in China (2015—2016). Serum PFAS isomers and alternatives and fasting blood glucose were measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry (UPLC-MS/MS) and automatic biochemical analyzer. We applied multiple linear regression to explore the associations of 16 pollutants which were detected among over 80% participants with fasting blood glucose. Meanwhile, we utilized qgcomp and Bayesian kernel machine regression (BKMR) models to explore the joint effects of PFAS isomers and alternatives mixture on target outcome indicators and identify the key component. ResultsThe average age among the 923 participants in this study was (62.4±13.8) years old, including 472 men (51.1%) and 451 women (48.9%). Among selected PFAS isomers and alternatives, the highest serum concentration was ∑3+4+5m-PFOS (perfluoro-3/4/5-methylheptanesulfonate) with a median concentration of 10.20 ng·mL−1. The concentrations of linear perfluorooctane sulfonate (n-PFOS, 9.61 ng·mL−1), perfluorooctanoic acid (PFOA, 4.55 ng·mL−1), linear perfluorohexane sulfonic acid (n-PFHxS, 2.48 ng·mL−1), 6:2 chlorinated polyfluorinated ethersulfonic acid (6:2 Cl-PFESA, 1.90 ng·mL−1), perfluoro-6-methylheptanesulfonate (iso-PFOS, 1.85 ng·mL−1), perfluorobutanoic acid (PFBA, 1.81 ng·mL−1), perfluorinated n-nonanoic acid (PFNA, 1.39 ng·mL−1), and perfluoro-1-methylheptanesulfonate (1m-PFOS, 1.27 ng·mL−1) were higher than 1.00 ng·mL−1. After being adjusted for selected confounders, PFAS isomers and alternatives were positively associated with fasting blood glucose. With 1 ln unit concentration increment of 6:2 Cl-PFESA and PFNA, the estimated changes of fasting blood glucose were 0.18 (95%CI: 0.13, 0.23) mmol·L−1 and 0.24 (95%CI: 0.18, 0.30) mmol·L−1, respectively. The multi-pollutant models indicated a joint association of PFAS isomers and alternatives mixture with fasting blood glucose. The BKMR models reveals that as the quantiles of mixture elevated from the 50th to the 75th percentile, the values of fasting blood glucose increased 0.25 (95%CI: 0.21, 0.30) mmol·L−1, and the posterior inclusion probability of PFNA was 0.92, implying that PFNA was the key component. ConclusionPFAS isomers and alternatives are positively associated with fasting blood glucose. PFNA is the key component of the joint association.

Abstract Background Domestication and introduction of dairy animals facilitated the permanent human occupation of the Tibetan Plateau. Yet the history of dairy pastoralism in the Tibetan Plateau remains poorly understood. Little is known how Tibetans adapted to milk and dairy products. Results We integrated archeological evidence and genetic analysis to show the picture that the dairy ruminants, together with dogs, were introduced from West Eurasia into the Tibetan Plateau since ~ 3600 years ago. The genetic admixture between the exotic and indigenous dogs enriched the candidate lactase persistence (LP) allele 10974A > G of West Eurasian origin in Tibetan dogs. In vitro experiments demonstrate that − 13838G > A functions as a LP allele in Tibetans. Unlike multiple LP alleles presenting selective signatures in West Eurasians and South Asians, the de novo origin of Tibetan-specific LP allele − 13838G > A with low frequency (~ 6–7%) and absence of selection corresponds − 13910C > T in pastoralists across eastern Eurasia steppe. Conclusions Results depict a novel scenario of genetic and cultural adaptations to diet and expand current understanding of the establishment of dairy pastoralism in the Tibetan Plateau.

Background: Limited evidence exists regarding the link between air pollution exposure and cognitive function in developing countries, particularly in areas with abundant natural sources of particulate matter. Objectives: To investigate this association in a large representative sample of the elderly in northwestern China. Methods: We performed a cross-sectional study among 176,345 participants aged 60–100 years in northwestern China in 2020. A satellite-based spatiotemporal model was applied to assess three-year annual averages of particulate matter with an aerodynamic diameter ≤ 2.5 µm (PM2.5), ≤ 10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) at residential address. Poor cognitive function was assessed using the Mini-Mental State Examination (MMSE). Generalized linear mixed models were used to assess associations. Results: Compared with participants with the lowest quartiles of PM2.5, PM10, and O3 levels, those with the second, third, and highest quartiles of air pollutants consistently showed increased odds of poor cognitive function and decreased MMSE scores. The odds ratios of poor cognitive function associated with a 10 μg/m3 increment in PM2.5, PM10, and O3 were 1.26 (95 % confidence interval [CI]: 1.17, 1.36), 1.06 (95 %CI: 1.04, 1.08), and 2.76 (95 %CI: 2.11, 3.62), respectively. Subgroup analyses suggested stronger associations between air pollution exposures and poor cognitive function among participants who were younger, were non-Uyghur and were physically active. Conclusion: Long-term exposures to PM2.5, PM10 and O3 were associated with poor cognitive function in elders. Our results suggest that reducing air pollution may alleviate the burden of poor cognitive function in the elderly.

Background: Greenspace is known to have a positive impact on human health and well-being, but its potential effects on visual acuity have not been extensively studied. Objectives: Our aim was to examine the relationship between long-term greenspace exposure and visual acuity in children, while also exploring the potential mechanisms in this association. Methods: We conducted this prospective cohort study based on the Children’s growth environment, lifestyle, physical, and mental health development project (COHERENCE), which screened 286,801 schoolchildren in Guangzhou, China, starting in the 2016/17 academic year and followed them up for three academic years (2017/18-2019/20). Visual acuity was measured using a standardized logarithmic chart, and visual impairment was defined as visual acuity worse than 0.0 logarithm of the minimum angle of resolution (LogMAR) units in the better eye. We used the Normalized Difference Vegetation Index (NDVI), the Soil-Adjusted Vegetation Index (SAVI), and the Enhanced Vegetation Index (EVI) to assess the greenspace surrounding child's geocoded home and school at each visit. Results: Our analysis indicated that higher greenspace exposure was associated with greater visual acuity z-score at baseline and with slower decline in visual acuity z-score during the 3-year follow-up. An interquartile range increase in home-school-based NDVI 300m was associated with a 7% decrease [hazard ratios (HRs): 0.93, 95% confidence interval (CI): 0.92, 0.94] in the risk of visual impairment. We also found that air pollution, physical activity, outdoor time, and recreational screen time partially mediated the greenspace-visual acuity association. Conclusion: Our findings suggest that increasing greenspace exposure could benefit children’s visual acuity development and reduce the risk of visual impairment by reducing air pollution and recreational screen time while increasing physical activity and outdoor time. All results could have potential policy implications, given the individual and societal burdens associated with visual impairment.

Perfluorooctane sulfonate (PFOS), an endocrine-disrupting chemical pollutant, affects embryonic heart development; however, the mechanisms underlying its toxicity have not been fully elucidated. Here, Single-cell RNA sequencing (scRNA-seq) was used to investigate the overall effects of PFOS on myocardial differentiation from human embryonic stem cells (hESCs). Additionally, apoptosis, mitochondrial membrane potential, and ATP assays were performed. Downregulated cardiogenesis-related genes and inhibited cardiac differentiation were observed after PFOS exposure in vitro. The percentages of cardiomyocyte and cardiac progenitor cell clusters decreased significantly following exposure to PFOS, while the proportion of primitive endoderm cell was increased in PFOS group. Moreover, PFOS inhibited myocardial differentiation and blocked cellular development at the early- and middle-stage. A Gene Ontology analysis and pseudo-time trajectory illustrated that PFOS disturbed multiple processes related to cardiogenesis and oxidative phosphorylation in the mitochondria. Furthermore, PFOS decreased mitochondrial membrane potential and induced apoptosis. These results offer meaningful insights into the cardiogenic toxicity of PFOS exposure during heart formation as well as the adverse effects of PFOS on mitochondria.

Accumulating evidence strongly suggests that exposure to ambient air pollution is linked with increased frailty. However, little is known about the effect of improved air quality on frailty progression. We aimed to investigate whether improvements in air quality (PM1, PM2.5, PM10, NO2, and O3) can alleviate frailty progression, particularly in the aftermath of implementation of the “Clean Air Action” policy in China. The study involved 12,891 participants with geocoded environmental data from the nationwide China Health and Retirement Longitudinal Study (CHARLS) during the period from May 2011 to August 2015. Multivariate logistic regression models were used to analyze the association of air pollution improvements and frailty progression. The protective effects were noted for PM1, PM2.5, PM10, and NO2 indices, with an aOR (adjusted odds ratio) ranging from 0.72 to 0.79. Air quality improvement in PM1, PM2.5, PM10, and NO2 could alleviate the progression of frailty. The study is the first to examine the association between the improvement of air quality and the progression of frailty, setting a precedent for the importance of a nationwide clean air policy and its impact on healthy ageing.

Single-cell RNA sequencing (scRNA-seq) is widely used to interpret cellular states, detect cell subpopulations, and study disease mechanisms. In scRNA-seq data analysis, cell clustering is a key step that can identify cell types. However, scRNA-seq data are characterized by high dimensionality and significant sparsity, presenting considerable challenges for clustering. In the high-dimensional gene expression space, cells may form complex topological structures. Many conventional scRNA-seq data analysis methods focus on identifying cell subgroups rather than exploring these potential high-dimensional structures in detail. Although some methods have begun to consider the topological structures within the data, many still overlook the continuity and complex topology present in single-cell data. We propose a deep learning framework that begins by employing a zero-inflated negative binomial (ZINB) model to denoise the highly sparse and over-dispersed scRNA-seq data. Next, scZAG uses an adaptive graph contrastive representation learning approach that combines approximate personalized propagation of neural predictions graph convolution (APPNPGCN) with graph contrastive learning methods. By using APPNPGCN as the encoder for graph contrastive learning, we ensure that each cell’s representation reflects not only its own features but also its position in the graph and its relationships with other cells. Graph contrastive learning exploits the relationships between nodes to capture the similarity among cells, better representing the data’s underlying continuity and complex topology. Finally, the learned low-dimensional latent representations are clustered using Kullback–Leibler divergence. We validated the superior clustering performance of scZAG on 10 common scRNA-seq datasets in comparison to existing state-of-the-art clustering methods.

Traditional GIS-based statistical models are intended to extrapolate patterns of settlements and their interactions with the environment. They contribute significantly to our knowledge of past human–land relationships. Yet, these models are often criticized for their empiricism, lopsided specific factors, and for overlooking the synergy between variables. Though largely untested, machine learning and artificial intelligence methods have the potential to overcome these shortcomings comprehensively and objectively. The northeastern Tibetan Plateau (NETP) is characterized by diverse environments and significant changes to the social system from the Neolithic to Bronze Age. In this study, this area serves as a representative case for assessing the complex relationships between settlement locations and geographic environments, taking full advantages of these new models. We have explored a novel modeling case by employing GIS and random forests to consider multiple factors, including terrain, vegetation, soil, climate, hydrology, and land suitability, to construct classification models identifying environmental variation across different cultural periods. The model exhibited strong performance and a high archaeological prediction value. Potential living maps were generated for each cultural stage, revealing distinct environmental selection strategies from the Neolithic to Bronze Age. The key environmental parameters of elevation, climate, soil erosion, and cultivated land suitability were calculated with high weights, influencing human environmental decisions synergistically. Furthermore, we conducted a quantitative analysis of temporal dynamics in climate and subsistence to understand driving mechanisms behind environmental strategies. These findings suggest that past human environmental strategies were based on the comprehensive consideration of various factors, coupled with their social economic scenario. Such subsistence-oriented activities supported human beings in overcoming elevation limitation, and thus allowed them to inhabit wider pastoral areas. This study showcases the potential of machine learning in predicting archaeological probabilities and in interpreting the environmental influence on settlement patterns.

Recent population and animal studies have revealed a correlation between fat content and the severity of benzene-induced hematologic toxicity. However, the precise impact of lipid deposition on benzene-induced hematotoxicity and the underlying mechanisms remain unclear. In this study, we established a mouse model with moderate lipid accumulation by subjecting the mice to an 8-week high-fat diet (45% kcal from fat, HFD), followed by 28-day inhalation of benzene at doses of 0, 1, 10, and 100 ppm. The results showed that benzene exposure caused a dose-dependent reduction of peripheral white blood cell (WBC) counts in both diet groups. Notably, this reduction was less pronounced in the HFD-fed mice, suggesting that moderate lipid accumulation mitigates benzene-related hematotoxicity. To investigate the molecular basis for this effect, we performed bioinformatics analysis of high-throughput transcriptome sequencing data, which revealed that moderate lipid deposition alters mouse metabolism and stress tolerance towards xenobiotics. Consistently, the expression of key metabolic enzymes, such as Cyp2e1 and Gsta1, were upregulated in the HFD-fed mice upon benzene exposure. Furthermore, we utilized a real-time exhaled breath detection technique to monitor exhaled benzene metabolites, and the results indicated that moderate lipid deposition enhanced metabolic activation and increased the elimination of benzene metabolites. Collectively, these findings demonstrate that moderate lipid deposition confers reduced susceptibility to benzene-induced hematotoxicity in mice, at least in part, by accelerating benzene metabolism and clearance.

BackgroundEssential and non-essential elements have an important impact on the development of the central nervous system during fetal development. Due to their less developed brain, preterm infants are more sensitive to element exposure, and are high-risk groups of neurodevelopmental abnormalities. However, it is not clear whether the effects of element exposure in utero on postpartum neurodevelopment are different between full-term infants and preterm infants. ObjectiveTo evaluate the effects of element exposure levels during pregnancy on neurodevelopment of children aged 6-24 months (of corrected age), and compare the effects between preterm and full-term children. MethodsA prospective study design was adopted and this study was conducted based on the Maoming Birth Cohort Study (MBCS) in Maoming City, Guangdong Province. Twenty elements in cord blood of 197 preterm infants and 297 full-term infants were measured, including 11 essential trace elements [vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), selenium (Se), strontium (Sr), tin (Sn), and iron (Fe)], and 9 non-essential trace elements [aluminum (Al), arsenic (As), thallium (Tl), lead (Pb), uranium (U), cerium (Ce), antimony (Sb), cadmium (Cd), and yttrium (Y)]. The neurodevelopment of the children at 6, 12, and 24 months were evaluated by the Ages and Stages Questionnaires-the Third Edition (ASQ-3). A generalized estimating equation (GEE) model was adopted to evaluate the associations between elements and neurodevelopment in full-term and preterm children separately. ResultsThe positive rates of 10 elements (Mn, Cu, Zn, Se, Sr, Fe, Sb, Tl, Pb, and As) in cord blood were greater than 80%. Among the preterm birth children, the results of GEE analysis showed that after adjusting for the covariates, for each increase of interquartile range (IQR) in ln-transformed concentration, As was associated with problems/delay in the communication and problem-solving sub-scales, with the adjusted odds ratios (OR) and 95% confidence intervals (CI) of 1.36 (1.03-1.80) and 1.55 (1.10-2.20), respectively; the adjusted OR (95%CI) of problems/delay in the fine motor and problem-solving sub-scales were 1.44 (1.00-2.07) and 1.76 (1.09-2.84) for Sb, respectively; the adjusted OR (95%CI) of problems/delay in the communication sub-scale was 1.37 (1.09-1.74) for Se. No statistically significant associations between umbilical cord blood element concentrations and neurodevelopment indicators were observed among full-term children. The results of stratified analysis by sex showed that the associations between umbilical cord blood element concentrations and neurodevelopment problems/delay were only significant among female preterm children. ConclusionExposures to As, Se, and Sb during pregnancy may increase the risk of neurodevelopment problems/delay in preterm children aged 6-24 months, and female seem to be more vulnerable.

A metagenome contains all DNA sequences from an environmental sample, including viruses, bacteria, archaea, and eukaryotes. Since viruses are of huge abundance and have caused vast mortality and morbidity to human society in history as a type of major pathogens, detecting viruses from metagenomes plays a crucial role in analyzing the viral component of samples and is the very first step for clinical diagnosis. However, detecting viral fragments directly from the metagenomes is still a tough issue because of the existence of a huge number of short sequences. In this study a hybrid Deep lEarning model for idenTifying vIral sequences fRom mEtagenomes (DETIRE) is proposed to solve the problem. First, the graph-based nucleotide sequence embedding strategy is utilized to enrich the expression of DNA sequences by training an embedding matrix. Then, the spatial and sequential features are extracted by trained CNN and BiLSTM networks, respectively, to enrich the features of short sequences. Finally, the two sets of features are weighted combined for the final decision. Trained by 220,000 sequences of 500 bp subsampled from the Virus and Host RefSeq genomes, DETIRE identifies more short viral sequences (

Summary: Evidence concerning PM1 exposure, maternal blood pressure (BP), and hypertensive disorders of pregnancy (HDP) is sparse. We evaluated the associations using 105,063 participants from a nationwide cohort. PM1 concentrations were evaluated using generalized additive model. BP was measured according to the American Heart Association recommendations. Generalized linear mixed models were used to assess the PM1-BP/HDP associations. Each 10 μg/m3 higher first-trimester PM1 was significantly associated with 1.696 mmHg and 1.056 mmHg higher first-trimester SBP and DBP, and with 11.4% higher odds for HDP, respectively. The above associations were stronger among older participants (> 35 years) or those educated longer than 17 years or those with higher household annual income (> 400,000 CNY). To conclude, first-trimester PM1 were positively associated with BP/HDP, which may be modified by maternal age, education level, and household annual income. Further research is warranted to provide more information for both health management of HDP and environmental policies enactment.

Research on the environmental occurrence of long-chain chlorinated paraffins (LCCPs) in ambient fine particulate matter (PM2.5) is still scarce. In the present study, short-chain chlorinated paraffins (SCCPs), medium-chain chlorinated paraffins (MCCPs) and LCCPs were simultaneously quantified and profiled in PM2.5 samples collected from 96 primary or secondary schools in the Pearl River Delta of South China. SCCPs, MCCPs and LCCPs were detected in higher than 90% samples with concentrations in the range of 0.832–109, 1.02–110, and 0.173–17.4 ng/m3, respectively. The dominant congener groups of SCCPs, MCCPs and LCCPs were C13Cl6-8, C14Cl7-8, and C18Cl7-9, respectively. The concentrations of SCCPs and MCCPs were higher in summer than in winter, while an opposite seasonal trend was observed for LCCPs. Principal components analysis showed there were seasonal variations in the congener group patterns with C13Cl6-7 and C14Cl7 more abundant in summer than in winter. Concentrations of CPs also exhibited slight spatial variations. Exposure risk assessment based on different age groups suggested exposure to PM2.5-associated CPs would not pose significant health risk. The present study expands the existing knowledge of CPs contamination in atmospheric environment.

Identify risk drivers is the key condition in air pollution control, and biological effect-directed analysis is the most commented method for combing chemical identify and human health. The water-soluble organic matter contained in PM2.5 plays an important role in human health, while it is also the most difficult to identify its chemical information. Exploring the structural characteristics and pollution sources of its key toxic components is the optimized strategy to meet this question. In this study, the induction of apoptosis by the water-soluble fractions (WSF) of PM2.5 samples collected in 10 major cities in China over a period of 1 year was observed in vitro in Beas-2b cells. Organic carbon structures were examined using nuclear magnetic resonance; air potential sources were identified using δ13C and 14C isotopic markers. Apoptosis induction by WSF in PM2.5 was generally stronger in northern cities than in southern cities, and in winter than in summer. Organic compounds with aromatic and double-bond carbon structures from secondary products of motor vehicle exhausts, coal-derived emissions, and emissions derived from the burning of core residues may be primarily responsible for apoptosis induction by PM2.5. Our results will contribute to understanding the toxic substances contained in WSF and provide basic data for accurate pollution control.

Abstract Background Hand, foot, and mouth disease (HFMD) is an epidemic infectious disease in China. Relationship of neighborhood greenness with human health has been widely studied, yet its association with severe HFMD has not yet been established. Methods Individual HFMD cases that occurred in Guangdong province in 2010 were recruited and were categorised into mild and severe cases. Residential greenness was assessed using global land cover data. We used a case-control design (i.e., severe versus mild cases) with logistic regression models to assess the association between neighborhood greenness and HFMD severity. Effect modification was also examined. Results A total of 131,606 cases were included, of whom 130,840 were mild cases and 766 were severe cases. In an unadjusted model, HFMD severity increased with higher proportion of neighborhood greenness (odds ratio, OR = 1.029, 95%CI: 1.009–1.050). The greenness-HFMD severity association remained (OR = 1.031, 95%CI: 1.006–1.057) after adjusting for population density, demographic variables and climate variables. Both population density (Z = 4.148, P 5 & ≤7: OR = 1.071, 95%CI: 1.024–1.120; subgroup of > 7: OR = 1.065, 95%CI: 1.034–1.097) on HFMD severity. As to relative humidity, statistically significant association between greenness and HFMD severity was only observed in the subgroup of being lower than and equal to 76% (OR = 1.059, 95%CI: 1.023–1.096). Conclusions Our study found that HFMD severity is associated with the neighborhood greenness in Guangdong, China. This study provides evidence on developing a prevention strategy of discouraging the high-risk groups from going to the crowded green spaces during the epidemic period.

Abstract Background Chronic obstructive pulmonary disease (COPD) is the third-leading cause of death worldwide with continuous rise. Limited studies indicate that COPD was associated with major storms and related power outages (PO). However, significant gaps remain in understanding what PO’s role is on the pathway of major storms-COPD. This study aimed to examine how PO mediates the major storms-COPD associations. Methods In this time-series study, we extracted all hospital admissions with COPD as the principal diagnosis in New York, 2001–2013. Using distributed lag nonlinear models, the hospitalization rate during major storms and PO was compared to non-major storms and non-PO periods to determine the risk ratios (RRs) for COPD at each of 0–6 lag days respectively after controlling for time-varying confounders and concentration of fine particulate matter (PM2.5). We then used Granger mediation analysis for time series to assess the mediation effect of PO on the major storms-COPD associations. Results The RRs of COPD hospitalization following major storms, which mainly included flooding, thunder, hurricane, snow, ice, and wind, were 1.23 to 1.49 across lag 0–6 days. The risk was strongest at lag3 and lasted significantly for 4 days. Compared with non-outage periods, the PO period was associated with 1.23 to 1.61 higher risk of COPD admissions across lag 0–6 days. The risk lasted significantly for 2 days and was strongest at lag2. Snow, hurricane and wind were the top three contributors of PO among the major storms. PO mediated as much as 49.6 to 65.0% of the major storms-COPD associations. Conclusions Both major storms and PO were associated with increased hospital admission of COPD. PO mediated almost half of the major storms-COPD hospitalization associations. Preparation of surrogate electric system before major storms is essential to reduce major storms-COPD hospitalization.

Background: Although power outage (PO) is one of the most important consequences of increasing weather extremes and the health impact of POs has been reported previously, studies on the neighborhood environment underlying the population vulnerability in such situations are limited. This study aimed to identify dominant neighborhood environmental predictors which modified the impact of POs on multiple health outcomes in New York State. Methods: We applied a two-stage approach. In the first stage, we used time series analysis to determine the impact of POs (versus non-PO periods) on multiple health outcomes in each power operating division in New York State, 2001-2013. In the second stage, we classified divisions as risk-elevated and non-elevated, then developed predictive models for the elevation status based on 36 neighborhood environmental factors using random forest and gradient boosted trees. Results: Consistent across different outcomes, we found predictors representing greater urbanization, particularly, the proportion of residents having access to public transportation (importance ranging from 4.9–15.6%), population density (3.3–16.1%), per capita income (2.3–10.7%), and the density of public infrastructure (0.8–8.5%), were associated with a higher possibility of risk elevation following power outages. Additionally, the percent of minority (-6.3–27.9%) and those with limited English (2.2–8.1%), the percent of sandy soil (6.5–11.8%), and average soil temperature (3.0–15.7%) were also dominant predictors for multiple outcomes. Spatial hotspots of vulnerability generally were located surrounding New York City and in the northwest, the pattern of which was consistent with socioeconomic status. Conclusion: Population vulnerability during power outages was dominated by neighborhood environmental factors representing greater urbanization.

Summary: A high point of Tibetan Plateau (TP) civilization, the expansive Tubo Empire (618–842 AD) wielded great influence across ancient western China. However, whether the Tubo expansion was cultural or demic remains unclear due to sparse ancient DNA sampling. Here, we reported ten ancient genomes at 0.017- to 0.867-fold coverages from the Dulan site with typical Tubo archaeological culture dating to 1308–1130 BP. Nine individuals from three different grave types have close relationship with previously reported ancient highlanders from the southwestern Himalayas and modern core-Tibetan populations. A Dulan-related Tubo ancestry contributed overwhelmingly (95%–100%) to the formation of modern Tibetans. A genetic outlier with dominant Eurasian steppe-related ancestry suggesting a potential population movement into the Tubo-controlled regions from Central Asia. Together with archeological evidence from burial styles and customs, our study suggested the impact of the Tubo empire on the northeast edge of the TP involved both cultural and demic diffusion.

Maternal exposure to chemical elements, including essential and non-essential elements, have been found to be associated with preterm births (PTB). However, few studies have measured element concentrations in cord whole blood, which reflects activity at the maternal-fetal interface and may be biologically associated with PTBs. In this study, we determined concentrations of 21 elements in cord whole blood and explored the associations between element concentrations and PTB in a nested case-control study within a birth cohort in Guangdong, China. Finally, 515 preterm infants and 595 full-term infants were included. We performed single-element and multi-element logistic regressions to evaluate linear relationships between element concentrations and PTB. According to the results of single-element models, most essential elements (including K, Ca, Si, Zn, Se, Sr and Fe) were negatively associated with PTB, while Cu, V, Co and Sn were positively associated with PTB. Of the non-essential elements, Sb, Tl, and U were positively associated with PTB, while Pb was negatively associated with PTB. The multi-element model results for most elements were similar, except that the association between Mg and PTB was shown to be significantly positive, and the association for Cu became much larger. A possible explanation is that the effects of Mg and Cu may be influenced by other elements. We performed restricted cubic spline (RCS) regressions and found significantly non-linear exposure-response relationships for Mg, Se, Sr, K and Sb, indicating that the effects of these elements on PTB are not simply detrimental or beneficial. We also examined the joint effect using a Bayesian kernel machine regression (BKMR) model and found the risk of PTB decreased significantly with element mixture concentration when lnC was larger than the median. Bivariate interaction analysis suggested antagonistic effects of Sb on Zn and Sr, which may be attributed to Sb negating the antioxidant capacity of Zn and Sr. This study provides additional evidence for the effect of element exposures on PTB, and will have implications for the prevention of excessive exposures or inappropriate element supplementation during pregnancy.

Biofilm plays important roles in the life cycle of Bacillus species, such as promoting host and object surface colonization and resisting heavy metal stress. This study utilized transcriptomics to evaluate the impacts of cadmium on the components, morphology, and function of biofilms of Bacillus subtilis strain 1JN2. Under cadmium ion stress, the morphology of the B. subtilis 1JN2 biofilm was flattened, and its mobility increased. Moreover, differential gene expression analysis showed that the main regulator of biofilm formation, Spo0A, decreased in expression under cadmium ion stress, thereby inhibiting extracellular polysaccharide synthesis through the SinI/SinR two-component regulatory system and the AbrB pathway. Cadmium ion treatment also increased the SigD content significantly, thereby increasing the expression of the flagella encoding and assembly genes in the strain. This promoted poly-γ-glutamic acid production via the DegS/DegU two-component regulatory system and the conversion of biofilm extracellular polysaccharide to poly-γ-glutamic acid. This conferred cadmium stress tolerance in the strain. Additionally, the cadmium ion-mediated changes in the biofilm composition affected the colonization of the strain on the host plant root surface. Cadmium ions also induced surfactin synthesis. These findings illustrate the potential of Bacillus species as biocontrol strains that can mitigate plant pathogenic infections and heavy metal stress. The results also provide a basis for the screening of multifunctional biocontrol strains.

Several literatures have examined the risk of chronic respiratory diseases in association with short-term ambient PM2.5 exposure in China. However, little evidence has examined the chronic impacts of PM2.5 exposure on morbidity of chronic respiratory diseases in cohorts from high pollution countries. Our study aims to investigate the associations. Based on a retrospective cohort among adults in northern China, a Cox regression model with time-varying PM2.5 exposure and a concentration-response (C-R) curve model were performed to access the relationships between incidence of chronic respiratory diseases and long-term PM2.5 exposure during a mean follow-up time of 9.8 years. Individual annual average PM2.5 estimates were obtained from a satellite-based model with high resolution. The incident date of a chronic respiratory disease was identified according to self-reported physician diagnosis time and/or intake of medication for treatment. Among 38,047 urban subjects analyzed in all-cause chronic respiratory disease cohort, 482 developed new cases. In CB (38,369), asthma (38,783), and COPD (38,921) cohorts, the onsets were 276, 89, and 14, respectively. After multivariable adjustment, hazard ratio and 95% confidence interval for morbidity of all-cause chronic respiratory disease, CB, asthma, and COPD were 1.15 (1.01, 1.31), 1.20 (1.00, 1.42), 0.76 (0.55, 1.04), and 0.66 (0.29, 1.47) with each 10 μg/m3 increment in PM2.5, respectively. Stronger effect estimates were suggested in alcohol drinkers across stratified analyses. Additionally, the shape of C-R curve showed an increasing linear relationship before 75.00 μg/m3 concentrations of PM2.5 for new-onset all-cause chronic respiratory disease, and leveled off at higher levels. These findings indicated that long-term exposure to high-level PM2.5 increased the risks of incident chronic respiratory diseases in China. Further evidence of C-R curves is warranted to clarify the associations of adverse chronic respiratory outcomes involving air pollution.

Human livelihoods provided a crucial economic foundation for social development in ancient times and were influenced by various factors including environmental change, agricultural origin and intensification, as well as long-distance exchange and culinary tradition. The effect of geopolitical change on human subsistence, especially the shifts between agricultural and nomadic regimes, has not been well understood due to the absence of detailed historical records and archaeological evidence. During the 12th century, the control of the Zhengding area in Hebei Province of north-central China changed from the Northern Song (960–1127 CE) to the Jurchen Jin Dynasty (Jin Dynasty; 1115–1234 CE). Recent excavation of the Zhengding Kaiyuan Temple South (ZKS) site in the area provides a rare opportunity to study human livelihood transformation in relation to geopolitical change. In total, 21,588 charred crop caryopses including foxtail millet, wheat, broomcorn millet, hulled barley, and rice, and other carbonized remains including 55.15 g of boiled foxtail millet and 353.5 g of foxtail millet caryopses were identified, and nine AMS 14C dates of crop remains were obtained from the Northern Song and Jin layers at the ZKS site. This revealed that the dominant plant subsistence transformed from wheat to foxtail millet during the change from the Northern Song to the Jin Dynasties in Zhengding area. By comparing with historical documents and paleoclimate records, we propose that this abnormal shift of primary staple food from the relatively high-yield wheat to low-yield foxtail millet was induced by the traditional dietary preference for foxtail millet in the nomadic Jin society. The Jin government levied foxtail millet as taxation and promoted massive immigration from northeastern China to north-central China to consolidate their rule, which resulted in the adoption of foxtail millet as the most important crop in Zhengding area. The advantage for the cultivation of this frost-sensitive crop in north-central China over northeast China was probably enhanced by notable cold events during the 12th century, while the primary influencing factor for the transformation of human livelihoods in north-central China during that period was geopolitics rather than climate change.

The Tuyuhun Kingdom (AD 313–663) was one of the most famous regimes in northwest China during the early medieval period. However, the lifestyle and spiritual pursuit of their descendants who became allied with the Tang Dynasty remain enigmatic. The excavation of the Chashancun cemetery, a Tuyuhun royal descendant (AD 691) cemetery in the Qilian Mountains in northwest China, reveals a large amount of uncharred plant remains. These remains provided a rare opportunity to explore the geographical origin of the buried crops and their social implications. In total, 253,647 crops and 12,071 weeds were identified. Foxtail millet and broomcorn millet represent 61.99 and 30.83% of the total plant remains, with the rest being barley, buckwheat, beans, and hemp. The oxygen isotope and trace elements of the crop and weed remains suggest that broomcorn millet, foxtail millet, barley, buckwheat, and hemp were sourced from different regions. The assemblage of plant remains in the Chashancun cemetery suggests that millet cultivation played an important role in the livelihoods of Tuyuhun descendants, and the location of the elite Tuyuhun cemetery and multisources of different buried crops may reflect their memory of ancestors and homelands. This case study provides a unique perspective to understand the interactions among human subsistence strategy, geopolitical patterns, and local natural environments in northwest China during the late 7th century.

Alkaline pH can induce triacylglyceride accumulation in microalgae, however its molecular mechanism remains elusive. Here, we investigated the effect of 2-[N-cyclohexylamino]-ethane-sulfonic acid (CHES) -induced intracellular alkalization on the lipid production in Phaeodactylum tricornutum. Intracellular pH was increased upon CHES treatment, displaying a high BCECF fluorescence ratio. CHES treatment significantly induced lipid accumulation but had no change in cell density and biomass. The expression of genes involved in photoreaction, carbon fixation, glycolysis, pentose phosphate pathway, amino acid catabolism, GS/GOGAT cycle, TCA cycle, triacylglyceride assembly, de novo fatty acid synthesis were up-regulated, while that in amino acid biosynthesis were down-regulated under CHES conditions. Correspondingly, the activity of phosphoribulokinase, carbonic anhydrase, pyruvate dehydrogenase and acetaldehyde dehydrogenase were enhanced by CHES treatment. Chloroplast-specific biological processes were activated by CHES treatment in P. tricornutum, which redirects the flux of carbon into lipid biosynthesis, meanwhile stimulates de novo fatty acid biosynthesis, leading to lipid accumulation under CHES conditions. These indicate an enhancement of intermediate metabolism, resulting in lipid accumulation by CHES.

Broomcorn and foxtail millet were the most important crops in northern China during the Neolithic period. Although the significance of broomcorn millet in human subsistence exceeded that of foxtail millet during the early Neolithic, this pattern was reversed by the end of Neolithic period. However, the process underlying this shift remains unclear. The recent excavation of the Gedachuan (GDC) in Zhangjiachuan county has revealed an abundance of relics including millet crop remains from relatively continuous strata of the Yangshao and Qijia cultures, and therefore provides a unique opportunity to examine how and when foxtail millet replaced broomcorn millet as the dominant crop in the western Loess Plateau during the Neolithic period. In this study, we identify 1,738 and 2,686 broomcorn and foxtail millet remains, respectively, from 74 flotation samples, accounting for 38.81% and 59.98% of total plant remains, respectively. Compared with 23 direct dates of carbonized crop grains in GDC, we propose that the weight of foxtail millet in plant subsistence of GDC first exceeded that of broomcorn millet as early as ∼5,500 BP, filling an important gap in the archaeobotanical record from the western Loess Plateau. Further comparative analysis of multidisciplinary data suggests the shift in significance of these two millet crops during the late Neolithic may have been triggered by variations in human settlement intensity and climate change in the western Loess Plateau. The results of this study also suggest that the Banpo Phase of Yangshao Culture survived in the western Loess Plateau as late as ∼5,600 BP.

Benzene is a ubiquitous pollutant and mainly accumulates in adipose tissue which has important roles in metabolic diseases. The latest studies reported that benzene exposure was associated with many metabolic disorders, while the effect of benzene exposure on adipose tissue remains unclear. We sought to investigate the effect using in vivo and in vitro experiments. Male adult C57BL/6J mice were exposed to benzene at 0, 1, 10 and 100 mg/kg body weight by intragastric gavage for 4 weeks. Mature adipocytes from 3T3-L1 cells were exposed to hydroquinone (HQ) at 0, 1, 5 and 25 μM for 24 hours. Besides the routine hematotoxicity, animal experiments also displayed significant body fat content decrease from 1 mg/kg. Interestingly, the circulating non-esterified fatty acid (NEFA) level increased from the lowest dose (ptrend < 0.05). Subsequent analysis indicated that body fat content decrease may be due to atrophy of white adipose tissue (WAT) upon benzene exposure. The average adipocyte area of WAT decreased significantly even from 1 mg/kg with no significant changes in total number of adipocytes. The percentages of small and large adipocytes in WAT began to significantly increase or decrease from 1 mg/kg (all p < 0.05), respectively. Critical genes involved in lipogenesis and lipolysis were dysregulated, which may account for the disruption of lipid homeostasis. The endocrine function of WAT was also disordered, manifested as significant decrease in adipokine levels, especially the leptin. In vitro cell experiments displayed similar findings in decreased fat content, dysregulated critical lipid metabolism genes, and disturbed endocrine function of adipocytes after HQ treatment. Pearson correlation analysis showed positive correlations between white blood cell (WBC) count with WAT fat content and plasma leptin level (r = 0.330, 0.344, both p < 0.05). This study shed light on the novel aspect that benzene exposure could induce lipodystrophy and disturb endocrine function of WAT, and the altered physiology of WAT might in turn affect benzene-induced hematotoxicity and metabolic disorders. The study provided new insight into understanding benzene-induced toxicity and the relationship between benzene and adipose tissue.

The study of human and animal paleodiets, representing the unique subsistence strategies and human-environment interactions adopted over evolutionary time, has attracted intensive research attention. Historically, the western Loess Plateau (WLP) served as a key area for the evolution of human-land relationship. The human subsistence patterns in the WLP changed significantly from prehistoric to historical periods based on archaeobotanical data. However, the trajectory and influencing factors of ancient human and animal diets in the WLP remain unclear, mainly due to the lack of isotopic data in the upper reaches of the Wei River. In this paper, we reported 172 human and animal isotope samples (C and N) and 23 radiocarbon dates from three sites in the middle-lower reaches of the Hulu River Valley (HRV). At least three periods of dietary patterns for humans were observed in the WLP from the late Neolithic to Ming Dynasty. During 5300–4000 Before Present (BP), humans and domesticated animals such as pigs and dogs consumed a greater proportion of millets and millet byproducts. Between 3000 and 2200 BP, the diets of pigs and dogs remained largely comprised of C4 foods, while humans consumed both C3 and C4 foods, which contradicted the evidence of an overwhelming proportion of wheat and barley (C3 crops) from the contemporaneous cultural sediment. The contradictions between plant remains and human diets are probably related to geopolitical factors. Between 1000–500 BP, human diets were more diverse and heterogeneous in this region. Combined with environmental and archaeological evidence, the changes in diets and subsistence strategies over the three periods can be attributed to the comprehensive influence of regional cultural development, geopolitics and technological innovation. This paper not only reveals the trajectory and influencing factors of ancient human and animal diets in the middle-lower HRV, but also explores how subsistence strategies, particularly in terms of dietary structure, will change in the context of cultural exchange and diffusion, and emphasizes the important influence of geopolitical interactions in the WLP.

Abstract Background China had the second largest proportion of preterm birth (PTB) internationally. However, only 11% of pregnant women in China meet international guidelines for maternal physical activity, a significantly lower proportion than that in Western countries. This study aims to examine the association between outdoor physical exercise during pregnancy and PTB among Chinese women in Wuhan, China. Methods A case-control study was conducted among 6656 pregnant women (2393 cases and 4263 controls) in Wuhan, China from June 2011 to June 2013. Self-reported measures of maternal physical exercise (frequency per week and per day in minutes) were collected. Adjusted odds ratios were estimated using Bayesian hierarchical logistic regression and a generalized additive mixed model (GAMM). Results Compared to women not involved in any physical activity, those who participated in physical exercise 1–2 times, 3–4 times, and over five times per week had 20% (aOR: 0.80, 95% credible interval [95% CI]: 0.68–0.92), 30% (aOR: 0.70, 95% CI: 0.60–0.82), and 32% (aOR: 0.68, 95% CI: 0.59–0.78) lower odds of PTB, respectively. The Bayesian GAMM showed that increasing physical exercise per day was associated with lower risk of PTB when exercise was less than 150 min per day; however, this direction of association is reversed when physical exercise was more than 150 min per day. Conclusion Maternal physical exercise, at a moderate amount and intensity, is associated with lower PTB risk. More data from pregnant women with high participation in physical exercise are needed to confirm the reported U-shape association between the physical exercise and risk of preterm birth.

The relationship between the evolution of human societies and their living environments has been discussed intensively in recent decades. It is important to understand the patterns and mechanisms of human–environment interaction and evolution in order to cope with rapidly changing environments in the modern world. We reviewed the results of dating, archaeobotanical, and zooarchaeological studies from 139 prehistoric sites in the Northeast Tibetan Plateau (NETP) and contiguous regions (NETP-CR: i.e., the Hexi Corridor and western margin of the Chinese Loess Plateau) and compared them with paleoenvironmental records to study variations in spatiotemporal patterns of social development in the area and their relationships with climate and vegetation changes. Our results show that hunter-gatherer groups occupied vast areas of the NETP at low intensities during ~15,000–5500 BP (years before present). This was directly related to forest cover and climate change. An increase in temperature and precipitation turnover of vegetation from desert steppe to alpine meadow/subalpine shrub, and recovery of animal population on the Tibetan Plateau created more food resources and space for hunter-gatherers. Millet farmers settled extensively below 2500 ​m a.s.l. (meters above sea level) in the NETP-CR between ~5500 and 3600 BP, and might have coexisted with hunting groups above 2500 ​m a.s.l. via subsistence exchange. The distribution of human settlements during that period was affected by climate change, with the relatively warm and wet climate promoting the expansion of millet agriculture to the NETP-CR during 5500–4500 BP, while climate deterioration caused humans to retreat to lower altitudes. During 3600–2200 BP, a range of livelihoods emerged in different regions of the NETP-CR. This was promoted by early trans-Eurasian exchange and the development of an agro-pastoral economy that utilized cold-tolerant crops and livestock. This eventually promoted the expansion of permanent human settlements to high-altitude areas in the NETP. This study found that human societies adopted various strategies to adapt to the changing living environment throughout late prehistoric times in the NETP-CR. The results provide a long-term perspective on the trajectory of regional socio-environmental co-evolution.

Northern China contains some of the world’s earliest farming societies. Here, authors use 55 ancient genomes to trace the genetic history of human migrations across northern China for the last 7500 years, and document genetic changes mirroring shifts in subsistence strategy.

Abstract Background Caloric restriction (CR) is known to improve health and extend lifespan in human beings. The effects of CR on adverse health outcomes in response to particulate matter (PM) exposure and the underlying mechanisms have yet to be defined. Results Male C57BL/6 J mice were fed with a CR diet or ad libitum (AL) and exposed to PM for 4 weeks in a real-ambient PM exposure system located at Shijiazhuang, China, with a daily mean concentration (95.77 μg/m3) of PM2.5. Compared to AL-fed mice, CR-fed mice showed attenuated PM-induced pulmonary injury and extra-pulmonary toxicity characterized by reduction in oxidative stress, DNA damage and inflammation. RNA sequence analysis revealed that several pulmonary pathways that were involved in production of reactive oxygen species (ROS), cytokine production, and inflammatory cell activation were inactivated, while those mediating antioxidant generation and DNA repair were activated in CR-fed mice upon PM exposure. In addition, transcriptome analysis of murine livers revealed that CR led to induction of xenobiotic metabolism and detoxification pathways, corroborated by increased levels of urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and decreased cytotoxicity measured in an ex vivo assay. Conclusion These novel results demonstrate, for the first time, that CR in mice confers resistance against pulmonary injuries and extra-pulmonary toxicity induced by PM exposure. CR led to activation of xenobiotic metabolism and enhanced detoxification of PM-bound chemicals. These findings provide evidence that dietary intervention may afford therapeutic means to reduce the health risk associated with PM exposure.

How the Asian monsoon, earth surface processes and human development interact is not well known. Here, a new record of dust storm intensity shows a relationship between the stability of dynasties and dust storm activity for the last ~2200 years, which argues for a strong human control of dust storms in East Asia over this time.

Background: Accumulating evidence suggests that environmental pollutants may contribute to the occurrence of congenital heart defects (CHDs). However, no previous studies have evaluated the impact of perfluoroalkyl substances (PFAS), persistent environmental pollutants, on CHDs. This exploratory study aimed to generate testable hypotheses of the association between gestational PFAS and the risk of CHDs. Methods: A nested case-control study was conducted in a cohort of 11,578 newborns. Exposure odds ratios were compared between 158 CHD cases and 158 non-malformed controls delivered at the same hospital, individually matched by maternal age (±5 years) and parity. Concentrations of 27 PFAS, including linear and branched isomers, were determined in maternal peripheral blood and cord blood plasma collected before and during delivery using a ultra-performance liquid chromatography coupled to mass spectrometry. Conditional logistic regression was utilized to evaluate associations between individual PFAS and the risk of CHDs, adjusted for confounding variables. Results: Maternal gestational exposure to the highly branched perfluorooctanesulfonate (PFOS) isomer potassium 6-trifluoromethyperfluoroheptanesulfonate [6 m-PFOS, adjusted odds ratio (aOR) (95% CI) = 2.47(1.05,5.83)] and perfluorodecanoic acid [PFDA, aOR (95% CI) = 2.33(1.00,5.45)] were associated with increased odds of septal defects with statistical significance, while linear PFOS [aOR (95% CI) = 3.65(1.09,12.16)] and perfluoro-n-dodecanoic acid [PFDoA, aOR (95% CI) = 6.82(1.75, 26.61)] were associated with conotruncal defects. Effect estimates also suggested associations for higher maternal 6 m-PFOS and PFDA concentrations with ventricular septal defect. However, we did not observe these associations in cord blood. Conclusion: These exploratory findings suggested that gestational exposure to most PFAS, especially linear PFOS, 6 m-PFOS, PFDA, and PFDoA, was associated with greater risks for septal and conotruncal defects. However, a larger, adequately powered study is needed to confirm our findings, and to more comprehensively investigate the potential teratogenic effects of other more recently introduced PFAS, and on associations with individual CHD subtypes.

Natural and social environment changes have played important roles in social evolution in different times and spaces. Geopolitical change, in particular, might play a decisive role in social evolution during historical periods. The eastern Tienshan Mountains was a transportation hub for communication between the East and the West, where the natural environment is fragile and the social environment has been complex during the historical period. However, geopolitical change and its impact on local social development remain unclear due to fragmented historical records and limited studies. This study investigates the spatiotemporal variations of military facilities in the Hami region, and compares historical documents and archaeological and paleoclimate records to discuss geopolitical changes and social evolution during the historical period in the eastern Tienshan Mountains. A total of 84 visible organic remains from 38 historic beacon towers and 8 dak sites in the Hami region of the eastern Xinjiang Uygur Autonomous Region, northwestern China, were collected and the radiocarbon (14C) dates of these ruins were systematically determined with accelerator mass spectrometry. The dating results show that these sites were mainly built during two major periods: ca. 600–900 cal AD and ca. 1600–1950 cal AD, which roughly correspond to the Tang Dynasty (618–907 AD) and the Qing Dynasty (1636–1912 AD) in ancient China. Human settlement intensity was high during the Han, Tang, and Qing dynasties, and relatively low when the area was controlled by nomadic or local regimes. This suggests that agricultural empires and nomadic/local regimes adopted different strategies for regional management. Climate change might have affected geopolitical patterns, which, in turn, profoundly influenced human activities and social evolution in the eastern Tienshan Mountains over the last two millennia. This study systematically reveals the spatiotemporal variations of beacon towers and dak ruins in the region through a large number of reliable direct 14C dating, it reveals the remarkable differences in human activities in the eastern Tienshan Mountains under different administrations, and it explores the influence of geopolitics and climate change on social evolution in the eastern Tienshan Mountains from a multidisciplinary perspective.

Evidence is still limited for the role of long-term PM2.5 exposure in cerebrovascular diseases among residents in high pollution regions. The study is aimed to investigate the long-term effects of PM2.5 exposure on stroke mortality, and further explore the effect modification of temperature variation on the PM2.5-mortality association in northern China. Based on a cohort data with an average follow-up of 9.8 years among 38,435 urban adults, high-resolution estimates of PM2.5 derived from a satellite-based model were assigned to each participant. A Cox regression model with time-varying exposures and strata of geographic regions was employed to assess the risks of stroke mortality associated with PM2.5, after adjusting for individual risk factors. The cross-product term of PM2.5 exposure and annual temperature range was further added into the regression model to test whether the long-term temperature variation would modify the association of PM2.5 with stroke mortality. Among the study participants, the annual mean level of PM2.5 concentration was 66.3 μg/m3 ranging from 39.0 μg/m3 to 100.6 μg/m3. For each 10 μg/m3 increment in PM2.5, the hazard ratio (HR) was 1.31 (95% CI: 1.04–1.65) for stroke mortality after multivariable adjustment. In addition, the HRs of PM2.5 decreased gradually as the increase of annual temperature range with the HRs of 1.95 (95% CI: 1.36–2.81), 1.53 (95% CI: 1.06–2.22), and 1.11 (95% CI: 0.75–1.63) in the low, middle, and high group of annual temperature range, respectively. The findings provided further evidence of long-term PM2.5 exposure on stroke mortality in high-exposure settings such as northern China, and also highlighted the view that assessing the adverse health effects of air pollution might not ignore the role of temperature variations in the context of climate change.

Background: Epidemiological studies on the association of residential greenness with sleep quality are limited in China. Objective: This study aims to investigate the association of long-term exposure to residential greenness with sleep quality in rural China. Methods: In our study, 27,654 rural residents were selected from 4 counties of Henan Province by a multi-stage stratified cluster sampling method. Participants’ sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). The Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI), two satellite-derived vegetation indexes, were used to assess the level of residential greenness. Long-term greenness exposure was defined as the averages of NDVI and EVI during the three years prior to the baseline survey. The relationship between sleep quality and greenness was assessed using the mixed-effect linear regression models. Results: Among 27,654 rural residents, the mean age was 55.89 years (standard deviation, SD = 12.22) and 60.18% of them were female. In the crude model, the PSQI score decreased with per interquartile range (IQR) increase in EVI and NDVI [ΔPSQI score (95% confidence interval, 95%CI): −0.073 (−0.115, −0.030) and −0.047 (−0.089, −0.002)]. After controlling potential confounders, ΔPSQI scores and 95%CIs were −0.055 (−0.095, −0.012) and −0.090 (−0.151, −0.025) associated with per IQR increment in EVI and NDVI. The results of stratified analyses showed the effect of residential greenness on sleep was stronger among males and individuals with higher household income and educational attainment than females and those with lower household income and educational attainment. Moreover, the modification effect of air pollution was observed in the greenness-sleep association. Conclusions: Our study indicated that higher residential greenness was significantly associated with better sleep quality in Chinese rural population, which highlights the significant effect of green space on human health.

Summary: Background: Depression and anxiety are top contributors to non-fatal health loss globally. Several studies have indicated the association between residential greenness and mental health. Method: The participants (n = 27,366) were recruited from four counties in Henan Province, China during 2015–2017. Symptoms of depression and anxiety were evaluated using the Patient Health Questionnaire-2 (PHQ-2) and the Generalized Anxiety Disorder-2 (GAD-2) in the baseline survey. The level of residential greenness during the 3-year period before the baseline survey was assessed using the Moderate Resolution Imaging Spectroradiometer (MODIS) Normalized Difference Vegetation Index (NDVI) and Enhanced Vegetation Index (EVI). The mixed-effect linear regression model was applied to examine the associations of residential greenness with depression and anxiety. Results: The results of adjusted models showed that the score of PHQ-2 (Δscore and 95% confidence interval [CI]) decreased by −0.024 (−0.041, −0.006) and −0.022 (−0.038, −0.004) with an interquartile range (IQR) increase in NDVI and EVI within a 1,000-m buffer radius, respectively. The score of GAD-2 (Δscore and 95% CI) decreased by −0.024 (−0.040, −0.006) and −0.028 (−0.044, −0.011), in relation to an IQR increase in NDVI and EVI within a 1,000-m buffer radius, respectively. Conclusions: A higher level of residential greenness was significantly associated with lower risk of depression and anxiety in rural areas of Henan Province. Improving residential greenness accessibility may help to promote the mental health of rural populations.

Background: Proximity to greenness has shown protective effects on coronary heart diseases by limiting exposure to environmental hazards, encouraging physical activity, and reducing mental stress. However, no studies have previously evaluated the impacts of greenness on congenital heart defects (CHDs). We examined the association between maternal residential greenness and the risks of CHDs. Methods: We conducted a case-control study (8042 children with major CHDs and 6887 controls without malformations) in 21 cities in Southern China, 2004 – 2016. CHDs cases were diagnosed and verified by obstetrician, pediatrician, or pediatric cardiologists, within one year. We estimated maternal residential greenness using satellite-derived normalized difference vegetation index (NDVI) in zones of 500 meters (m) and 1000 m surrounding participants’ residences. Logistic regression models were used to assess NDVI-CHD relationships adjusting for confounders. Results: Interquartile range NDVI increases within 500 m or 1000 m were associated with odds ratios (OR) of 0.95 (95% confidence interval (CI): 0.92, 0.98) and 0.94 (95%CI: 0.91, 0.97) for total CHDs respectively. Air pollutants mediated 52.1% of the association. We also identified a protective threshold at 0.21 NDVI on CHD. Similar protective effects from greenness were found in most CHDs subtypes. The protective associations were stronger for fall, urban or permanent residents, higher household income maternal age ≤35 years of age, and high maternal education (ORs: ranged from 0.85 to 0.96). Conclusion: Our findings suggest a beneficial effect of maternal residential greenness on CHDs. Further studies are needed to confirm our findings, which will help to refine preventive health and urban design strategies.

Background: Dyslipidemia is a major risk factor for cardiovascular disease. Several studies have explored the associations of greenness with blood lipids. However, the evidence is still limited and mixed, especially in rural areas. Methods: From May to September 2016, we recruited 4735 Uyghur adults from rural areas of northwestern China. We measured levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). Two satellite-derived vegetation indices — Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI) — were used to estimate residential greenness levels. The associations between exposure to residential greenness and blood lipids levels and dyslipidemia prevalence were examined using the Generalized Linear Mixed Models. Results: Living in greener areas was associated with lower TG levels, higher HDL-C levels, and lower odds of hypoalphalipoproteinemia (e.g., per 0.20-unit increase in NDVI100 m was associated with 0.02 mmol/L (95% CI: 0.001, 0.03) higher levels of HDL-C and 0.87-fold (95% CI: 0.77, 0.98) lower odds of hypoalphalipoproteinemia). These associations remained in a series of sensitivity analyses. Stratified analyses showed that the associations of NDVI100 m with LDL-C and HDL-C levels were stronger in women and in participants with higher education level. Conclusions: Higher greenness exposure was beneficially associated with blood lipids among rural Uyghur population in China, especially among women or those with higher education level.

The mid-late Holocene witnessed the rapid development of Neolithic and Bronze cultures in the Yellow River Valley (YRV) of northern China. Spatio-temporal patterns of plant utilization during this period and its influencing factors have been intensively discussed, whereas the variation in animal exploitation in relation to climate change and human activities has not been adequately studied. In this paper, we reviewed zooarchaeological data obtained from 38 Neolithic and Bronze sites in YRV, and compared them with paleoclimate and archaeological records, to reconstruct the trajectory of animal utilization in this area between 7500 and 2000 BP and discern the influencing factors driving it. The results revealed that animal exploitation was mainly sourced from wildlife between 7500 and 6000 BP, shifting to omnivorous livestock sources in the period of 6000–4000 BP except in the northeast Tibetan Plateau. During 4000–2000 BP, however, omnivorous and herbivorous livestock had come to dominate humans' subsistence on animals, which nonetheless showed substantial spatio-temporal variation in the YRV. Further analysis suggests that animal exploitation in the Neolithic and Bronze YRV were both directly affected by human activities, while climate change might have influenced the environment surrounding human settlements and, indirectly, their choice of animals to exploit. This work provides new perspectives for exploring the changing patterns of human-environment interactions in the YRV during the mid-late Holocene.

Background: While previous studies uncovered individual vulnerabilities to health risks during catastrophic storms, few evaluated the population vulnerability which is more important for identifying areas in greatest need of intervention. Objectives: We assessed the association between community factors and multiple health outcomes, and developed a community vulnerability index. Methods: We retained emergency department visits for several health conditions from the 2005–2014 New York Statewide Planning and Research Cooperative System. We developed distributed lag nonlinear models at each spatial cluster across eight counties in downstate New York to evaluate the health risk associated with Superstorm Sandy (10/28/2012–11/9/2012) compared to the same period in other years, then defined census tracts in clusters with an elevated risk as “risk-elevated communities”, and all others as “unelevated”. We used machine-learning techniques to regress the risk elevation status against community factors to determine the contribution of each factor on population vulnerability, and developed a community vulnerability index (CVI). Results: Overall, community factors had positive contributions to increased community vulnerabilities to Sandy-related substance abuse (91.35%), injuries (70.51%), cardiovascular diseases (8.01%), and mental disorders (2.71%) but reversely contributed to respiratory diseases (−34.73%). The contribution of low per capita income (max: 22.08%), the percentage of residents living in group quarters (max: 31.39%), the percentage of areas prone to flooding (max: 38.45%), and the percentage of green coverage (max: 29.73%) tended to be larger than other factors. The CVI based on these factors achieved an accuracy of 0.73–0.90 across outcomes. Conclusions: Our findings suggested that substance abuse was the most sensitive disease susceptible to less optimal community indicators, whereas respiratory diseases were higher in communities with better social environment. The percentage of residents in group quarters and areas prone to flooding were among dominant predictors for community vulnerabilities. The CVI based on these factors has an appropriate predictive performance. Keywords: Catastrophic storms, Multiple health outcomes, Community vulnerability index, ROC

To assess the carcinogenic potential of PM2.5 exposure, we developed a cell-based experimental protocol to examine the cell transformation activity of PM2.5 samples from different regions in China. The seasonal ambient PM2.5 samples were collected from three megacities, Beijing (BJ), Wuhan (WH), and Guangzhou (GZ), from November 2016 to October 2017. The mean concentrations of PM2.5 were much higher in the winter season (BJ: 109.64 μg/m3, WH: 79.99 μg/m3, GZ: 49.99 μg/m3) than that in summer season (BJ: 42.40 μg/m3, WH: 25.82 μg/m3, GZ: 19.82 μg/m3). The organic extracts (OE) of PM2.5 samples from combined summer (S) (June, July, August) or winter (W) (November, December, January) seasons were subjected to characterization of chemical components. We treated human bronchial epithelial (HBE) cells expressing CYP1A1 (HBE-1A1) with PM2.5 samples at doses ranging from 0 to 100 μg/mL (0, 1.563, 3.125, 6.25, 12.5, 25, 50, 100 μg/mL) and determined the phenotype of malignant cell transformation. A dose-response relationship was analyzed by benchmark dose (BMD) modeling, and the potential were indicated by BMDL10. The order of the carcinogenic risk of seasonal PM2.5 samples from high to low was BJ-W, WH-W, GZ-W, WH-S, BJ-S, and GZ-S. Notably, we found that the alteration in the lung cancer-related biomarkers, KRAS, PTEN, p53, c-Myc, PCNA, pAKT/AKT, and pERK/ERK was congruent with the activity of cell transformation and the content of specific components of polycyclic aromatic hydrocarbon (PAHs) bound to PM2.5. Taken together, we have successfully developed a cell-based alternative model for the evaluation of potent carcinogenicity upon long-term PM2.5 exposure. Keywords: Particulate matter, Human bronchial epithelial cells, P450 CYP1A1, Cell transformation, BMDL10, Carcinogenic potential

Aflatoxin B1 (AFB1) is a common toxic mycotoxin and is detectable in pregnant women. Animal studies have revealed that AFB1 caused the lysis of erythrocytes and a decrease in hemoglobin. We conducted a prospective cohort study in Guangxi, China, in order to evaluate the association between AFB1 exposure and anemia in pregnant women during the entire pregnancy. A total of 616 pregnant women from the Guangxi Zhuang Birth Cohort were included in the study. Serum AFB1-albumin (AFB1-ALB) adduct levels were measured. The effect of AFB1-ALB adducts on hemoglobin (Hb), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), and mean corpuscular hemoglobin concentration (MCHC) were analyzed by using multivariable linear regression. The risks of anemia from AFB1-ALB adduct exposure were assessed by multivariable logistic regression. We found that the AFB1-ALB adduct was significantly associated with a decrease in Hb (β = −4.99, 95% CI: −8.42, −1.30), MCV (β = −4.58, 95% CI: −7.23, −1.94), MCH (β = −1.86, 95% CI: −2.87, −0.85), and MCHC (β = −5.23, 95% CI: −8.28, −2.17) in the first trimester with the third tertile of AFB1-ALB adducts when compared with the first tertile. Furthermore, the third tertile of the AFB1-ALB adduct significantly increased the risk of anemia by 2.90 times than compared to the first tertile in the first trimester (OR = 3.90, 95% CI: 1.67, 9.14). A significant positive does–response relationship existed between AFB1-ALB adduct levels and anemia risk (Ptrend = 0.001). When dividing anemia types, we only found that the third tertile of AFB1-ALB adduct increased the risk of microcytic hypochromic anemia (MHA) in the first trimester (OR = 14.37, 95% CI: 3.08, 67.02) and second trimester (OR = 4.75, 95% CI: 1.96, 11.51). These findings demonstrate the correlation between maternal AFB1 exposure during early pregnancy and risk of anemia, especially MHA, and during different trimesters in Southern China. More efforts should be made to diminish AFB1 exposure for pregnant women.

To explore whether the alteration of lncRNA expression is correlated with polycyclic aromatic hydrocarbons (PAHs) exposure and DNA damage, we examined PAHs external and internal exposure, DNA damage and lncRNAs (HOTAIR, MALAT1, TUG1 and GAS5) expression in peripheral blood lymphocytes (PBLCs) of 150 male coke oven workers and 60 non-PAHs exposure workers. We found the expression of HOTAIR, MALAT1, and TUG1 were enhanced in PBLCs of coke oven workers and positively correlated with the levels of external PAHs exposure (adjusted Ptrend