Environmental risk factors have been implicated in adverse health effects. Previous epidemiological studies on environmental risk factors mainly analyzed the impact of single pollutant exposure on ...health, while in fact, humans are constantly exposed to a complex mixture consisted of multiple pollutants/chemicals. In recent years, environmental epidemiologists have sought to assess adverse health effects of exposure to multi-pollutant mixtures based on the diversity of real-world environmental pollutants. However, the statistical challenges are considerable, for instance, multicollinearity and interaction among components of the mixture complicate the statistical analysis. There is currently no consensus on appropriate statistical methods. Here we summarized the practical statistical methods used in environmental epidemiology to estimate health effects of exposure to multi-pollutant mixture, such as Bayesian kernel machine regression (BKMR), weighted quantile sum (WQS) regressions, shrinkage methods (least absolute shrinkage and selection operator, elastic network model, adaptive elastic-net model, and principal component analysis), environment-wide association study (EWAS), etc. We sought to review these statistical methods and determine the application conditions, strengths, weaknesses, and result interpretability of each method, providing crucial insight and assistance for addressing epidemiological statistical issues regarding health effects from multi-pollutant mixture.
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•Mixture analysis is challenged by high-dimensionality, multicollinearity, interaction, etc.•BKMR and WQS-based methods developed for mixture analysis are increasingly used.•Method selection should be based on its features, data traits, study purposes, etc.•Combined use of multiple statistical methods proposed in this study is recommended.•Measurement error deserves attention when assessing multi-pollutant mixture effects.
Accurate chromosome segregation during cell division relies on coordinated actions of microtubule (MT)-based motor proteins in the mitotic spindle. Kinesin-14 motors play vital roles in spindle ...assembly and maintenance by crosslinking antiparallel MTs at the spindle midzone and anchoring spindle MTs’ minus ends at the poles. In this study, we investigate the force generation and motility of the Kinesin-14 motors HSET and KlpA. Our findings reveal that both motors are non-processive, producing single load-dependent power strokes per MT encounter, with estimated load-free power strokes of ~30 and ~35 nm, respectively. Each homodimeric motor generates forces of ~0.5 pN, but when assembled in teams, they cooperate to generate forces of 1 pN or more. Notably, the cooperative activity among multiple motors leads to increased MT-sliding velocities. These results quantitatively elucidate the structure-function relationship of Kinesin-14 motors and underscore the significance of cooperative behavior in their cellular functions.This study reveals that Kinesin14 motors, HSET and KlpA, generate single load-dependent power strokes, producing forces of ~0.5 pN each. When working in teams, these motors achieve forces of 1 pN or more, enhancing MT-sliding velocities and highlighting their cooperative behaviour in cell division.
Abstract
Few study has revealed spatial transmission characteristics of COVID-19 in Wuhan, China. We aimed to analyze the spatiotemporal spread of COVID-19 in Wuhan and its influence factors. ...Information of 32,682 COVID-19 cases reported through March 18 were extracted from the national infectious disease surveillance system. Geographic information system methods were applied to analysis transmission of COVID-19 and its influence factors in different periods. We found decrease in effective reproduction number (
Rt
) and COVID-19 related indicators through taking a series of effective public health measures including restricting traffic, centralized quarantine and strict stay-at home policy. The distribution of COVID-19 cases number in Wuhan showed obvious global aggregation and local aggregation. In addition, the analysis at streets-level suggested population density and the number of hospitals were associated with COVID-19 cases number. The epidemic situation showed obvious global and local spatial aggregations. High population density with larger number of hospitals may account for the aggregations. The epidemic in Wuhan was under control in a short time after strong quarantine measures and restrictions on movement of residents were implanted.
Adverse health effects of ambient ozone are getting widespread attention, but the evidence on the relationship between ozone levels and circulatory system diseases are limited and inconsistent. Daily ...data for ambient ozone levels and hospitalizations for total circulatory diseases and five subtypes in Ganzhou, China from January 1, 2016 to December 31, 2020 were collected. We constructed a generalized additive model with quasi-Poisson regression accounting for lag effects to estimate the associations between ambient ozone levels and the number of hospitalized cases of total circulatory diseases and five subtypes. The differences among gender, age, and season subgroups were furtherly assessed through stratified analysis. A total of 201,799 hospitalized cases of total circulatory diseases were included in the present study, including 94,844 hypertension (HBP), 28,597 coronary heart disease (CHD), 42,120 cerebrovascular disease (CEVD), 21,636 heart failure (HF), and 14,602 arrhythmia. Significantly positive associations were observed between ambient ozone levels and daily hospitalizations for total circulatory diseases and all subtypes except arrhythmia. Each 10 μg/m3 increase in ozone concentration, the risk of hospitalizations for total circulatory diseases, HBP, CHD, CEVD, and HF increased by 0.718% (95% confidence interval, 0.156%–1.284%), 0.956% (0.346%–1.570%), 0.499% (0.057%–0.943%), 0.386% (0.025%–0.748%), and 0.907% (0.118%–1.702%), respectively. The above associations remained significant after adjusting for other air pollutants. The risk of hospitalization for circulatory diseases was higher in warm season (May to October) and varied in gender and age subgroups. This study suggested that short-term exposure to ambient ozone may increase the risk of hospitalizations for circulatory diseases. Our findings reinforce the importance of reducing ambient ozone pollution levels for protecting public health.
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•Ambient ozone levels were positively associated with daily hospitalizations for circulatory diseases.•The associations between ozone and hospitalizations for circulatory diseases were still significant after the adjustment of other air pollutants.•The risk of hospitalizations for circulatory diseases associated with ambient ozone was higher in warm season.
In dryland cropping ecosystems, nitrogen (N) fertilization causes changes in soil biochemical cycling and influences the crop biomass and grain yield. Based on a long-term field experiment involving ...three N rates (0 (N0), 160 (N160), and 320 (N320) kg N ha
−1
year
−1
), we measured nitrous oxide (N
2
O) and carbon dioxide (CO
2
) emissions from wheat fields and determined the soil organic carbon (SOC), total N, microbial biomass C (MBC), and N (MBN), mineralized C (C
min
) and N (N
min
) concentrations and the bacterial community composition. The results showed that N fertilization significantly (
P
< 0.05) increased N
2
O and CO
2
emissions. N fertilization also significantly (
P
< 0.05) increased SOC by 13.2%, total N by 7.4%, MBN by 34.3%, C
min
by 15.5%, and N
min
by 27.8%, as well as the soil bacterial diversity and abundances of N cycling functional groups (by 149%). Additionally, N
2
O and CO
2
emissions were positively and linearly correlated with NH
4
-N and NO
3
-N concentrations and positively correlated with SOC, total N, MBN, and the number of bacterial species, as well as most of the bacterial phyla and functional groups. These results suggest that N fertilizer applied to the dryland soils improved soil fertility and changed the soil bacterial community composition and function, thus increased N
2
O and CO
2
emissions. Therefore, to mitigate greenhouse gas emissions and maintain soil fertility for wheat production, an optimized N fertilizer rate should be applied in the southern region of the Loess Plateau in China.
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•Urinary acrolein metabolites (UAMs) were repeatedly measured over a period of 3 years.•UAMs were cross-sectionally associated with pulmonary function (PF) reduction.•UAMs were ...longitudinally associated with PF decline in 3 years.•8-OHdG, CRP, and CC16 aggravated and/or mediated acrolein-associated PF reduction.•This is the first study to report the associations of UAMs with PF.
Acrolein is a significant high priority hazardous air pollutant with pulmonary toxicity and the leading cause of most noncancer adverse respiratory effects among air toxics that draws great attention. Whether and how acrolein exposure impacts pulmonary function remain inconclusive.
To assess the association of acrolein exposure with pulmonary function and the underlying roles of oxidative DNA damage, inflammation, and pulmonary epithelium integrity.
Among 3,279 Chinese adults from the Wuhan-Zhuhai cohort, associations of urinary acrolein metabolites (N-Acetyl-S-(2-carboxyethyl)-L-cysteine, CEMA; N-Acetyl-S-(3-hydroxypropyl)-L-cysteine, 3HPMA) as credible biomarkers of acrolein exposure with pulmonary function were analyzed by linear mixed models. Joint effects of biomarkers of oxidative DNA damage (8-hydroxy-deoxyguanosine), inflammation (C-reactive protein, CRP), and pulmonary epithelium integrity (Club cell secretory protein, CC16) with acrolein metabolites on pulmonary function and the mediating roles of these biomarkers were assessed. Besides, a subgroup (N = 138) was randomly recruited from the cohort to assess the stabilities of acrolein metabolites and their longitudinal associations with pulmonary function change in three years.
Significant inverse dose–response relationships between acrolein metabolites and pulmonary function were found. Each 10-fold increment in CEMA, 3HPMA, or ΣUACLM (CEMA + 3HPMA) was cross-sectionally related to a 68.56-, 40.98-, or 46.02-ml reduction in FVC and a 61.54-, 43.10-, or 50.14-ml reduction in FEV1, respectively (P < 0.05). Furthermore, acrolein metabolites with fair to excellent stabilities were found to be longitudinally associated with pulmonary function decline in three years. Joint effects of acrolein metabolites with 8-hydroxy-deoxyguanosine, CRP, and CC16 on pulmonary function were identified. CRP significantly mediated 5.97% and 5.51% of CEMA-associated FVC and FEV1 reductions, respectively. 8-hydroxy-deoxyguanosine significantly mediated 6.78%, 6.88%, and 7.61% of CEMA-, 3HPMA-, and ΣUACLM-associated FVC reductions, respectively.
Acrolein exposure of general adults was cross-sectionally and longitudinally related to pulmonary function decline, which was aggravated and/or partly mediated by oxidative DNA damage, inflammation, and pulmonary epithelium injury.
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•Acrylamide (ACR) exposure was associated with increased cardiovascular (CV) risk.•Long-term daily ACR exposure could longitudinally increase CV risk over 3 years.•ACR exposure was ...related to oxidative stress, inflammation, and TGF-β1 induction.•Oxidative stress, inflammation, and TGF-β1 mediated ACR-associated CV risk increase.
Acrylamide (ACR) exposure and consequent health hazards are alarming public health issues that attract worldwide concern. The World Health Organization urges more researches into health hazards from ACR exposure. However, whether and how ACR exposure increases cardiovascular risk remain unclear, and we sought to address these issues in this prospective cohort study conducted on 3024 general adults with 3-year follow-up (N = 871 at follow-up). Individual urinary ACR metabolites (N-Acetyl-S-(2-carbamoylethyl)-L-cysteine AAMA and N-Acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine GAMA) as credible biomarkers of ACR exposure were detected to assess their cross-sectional and longitudinal relationships with 10-year cardiovascular disease (CVD) risk, a well measure of overall cardiovascular risk. Besides, biomarkers of oxidative stress (urinary 8-hydroxy-deoxyguanosine 8-OHdG and 8-iso-prostaglandin-F2α 8-iso-PGF2α) and inflammation (circulating mean platelet volume MPV and plasma C-reactive protein CRP) as well as plasma transforming growth factor-β1 (TGF-β1) were measured to assess their mediating/mechanistic roles in the relationships of ACR metabolites with 10-year CVD risk. We found AAMA, GAMA, and ΣUAAM (AAMA + GAMA) were cross-sectionally and longitudinally related to increased 10-year CVD risk with odds ratios (95% confidence intervals CIs) of 1.32 (1.04, 1.70), 1.81 (1.36, 2.40), and 1.40 (1.07, 1.82), respectively, and risk ratios (95% CIs) of 1.99 (1.10, 3.60), 2.48 (1.27, 4.86), and 2.13 (1.15, 3.94), respectively. Furthermore, 8-OHdG, 8-iso-PGF2α, MPV, CRP, and TGF-β1 were found to significantly mediate 8.06–48.92% of the ACR metabolites-associated 10-year CVD risk increment. In summary, daily ACR exposure of general adults was cross-sectionally and longitudinally associated with increased cardiovascular risk, which was partly mediated by oxidative stress, inflammation, and TGF-β1, suggesting for the first time that ACR exposure may well increase cardiovascular risk of general adult population partly by mechanisms of inducing oxidative stress, inflammation, and TGF-β1. Our findings have important public health implications that provide potent epidemiological evidence and vital mechanistic insight into cardiovascular risk increment from ACR exposure.
Fine particulate matter (PM
2.5
) is still the primary air pollutant in most Chinese cities and its adverse effects on lung function have been widely reported. However, short-term effects of ...individual exposure to PM
2.5
on pulmonary expiration flow indices remain largely unknown. In this study, we examined the short-term effects of real-time individual exposure to PM
2.5
on lung function in a panel of 115 healthy adults. We measured individual real-time PM
2.5
exposure and lung function. Environmental PM
2.5
concentrations in the same period were collected from the nearest monitoring station. Generalized linear model was used to assess the effects of individual PM
2.5
exposure on lung function after adjusting for potential confounders. Individual PM
2.5
exposure ranged from 18.5 to 42.4 μg/m
3
with fluctuations over time and ambient PM
2.5
concentrations presented a moderate trend of fluctuation at the same day. Except forced expiratory volume in 1 s (FEV
1
) decline related to 2-h moving average PM
2.5
exposure, no significant associations between individual PM
2.5
exposure and other volume indices including forced vital capacity (FVC) and FEV
1
/FVC ratio were observed. The adverse effects of individual PM
2.5
exposure on pulmonary expiration flow indices including peak expiratory flow (PEF), maximal mid-expiratory flow (MMF) and forced expiratory flow at 50%, and 75% of vital capacity (FEF
50%
and FEF
75%
) were observed to be strongest at 2 moving average hours and could last for 24 h. Stratified analysis showed greater and longer effects among participants who were aged over 40 years, males, or smokers. These findings suggested that individual PM
2.5
exposure was significantly associated with altered lung function, especially with pulmonary expiration flow indices decline, which was strongest at 2 moving average hours and could last for 24 h.
Sensory hair cells rely on otoferlin as the calcium sensor for exocytosis and encoding of sound preferentially over the neuronal calcium sensor synaptotagmin. Although it is established that ...synaptotagmin cannot rescue the otoferlin KO phenotype, the large size and low solubility of otoferlin have prohibited direct biochemical comparisons that could establish functional differences between these two proteins. To address this challenge, we have developed a single-molecule colocalization binding titration assay (smCoBRA) that can quantitatively characterize full-length otoferlin from mammalian cell lysate. Using smCoBRA, we found that, although both otoferlin and synaptotagmin bind membrane fusion SNARE proteins, only otoferlin interacts with the L-type calcium channel Cav1.3, showing a significant difference between the synaptic proteins. Furthermore, otoferlin was found capable of interacting with multiple SNARE and Cav1.3 proteins simultaneously, forming a heterooligomer complex. We also found that a deafness-causing missense mutation in otoferlin attenuates binding between otoferlin and Cav1.3, suggesting that deficiencies in this interaction may form the basis for otoferlin-related hearing loss. Based on our results, we propose a model in which otoferlin acts as a calcium-sensitive scaffolding protein, localizing SNARE proteins proximal to the calcium channel so as to synchronize calcium influx with membrane fusion. Our findings also provide a molecular-level explanation for the observation that synaptotagmin and otoferlin are not functionally redundant. This study also validates a generally applicable methodology for quantitatively characterizing large, multivalent membrane proteins.
In drylands, optimized management of fertilization based on precipitation is very important to reduce fertilizer inputs and environmental risks and improve crop yield and benefits. Based on a ...four-year winter wheat experiment with two treatments (FP, farmers’ practices; NE, Nutrient Expert system recommendation) at nine counties of the Chinese Loess Plateau, we determined the effects of NE on wheat yield, environmental risks, and economic benefits under three precipitation year types (dry, normal, and wet) and recommended optimized N fertilization. The results showed that the NE treatment reduced N and P fertilizer input rates by 21.7% and 50.0%, respectively, Nr losses by 30.1% and GHG emissions by 21.6%, but it did not affect wheat grain yield compared to the FP treatment. There were no significant differences in N and P input rates among the three precipitation year types, but higher grain yield and partial factor productivity of N and P fertilizers were found in wet years in the NE treatment. Additionally, soil nitrate N residues in the 0–100 cm soil layers were ordered in wet years < normal years < dry years. Based on the NE system, the optimized N fertilization method could further reduce the N fertilizer rate by 16.6% and 62.5%, Nr losses by 20% and 68%, and GHG emissions by 1.7% and 47.8% in normal and dry years, respectively, but could increase economic benefits by 3.3% and 5.6%, suggesting that optimized fertilization based on fallow season precipitation can result in multiple benefits for agriculture and the environment.
•Wheat yield and soil nitrate N residues were affected by rainfall in fallow season.•NE reduced N and P fertilizer input rates by 21.7% and 50.0% but not wheat yield.•NE increased the use efficiency of N and P by 27.3% and 106.2% and had higher values in the wet years.•A recommendation method for NE based on precipitation in summer fallow season.•New method can further reduce N inputs and increase economic benefits in normal and dry years.
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