Projection of Mortality Burden Attributable to Nonoptimum Temperature with High Spatial Resolution in China.

The updated climate models provide projections at a fine scale, allowing us to estimate health risks due to future warming after accounting for spatial heterogeneity. Here, we utilized an ensemble of high-resolution (25 km) climate simulations and nationwide mortality data from 306 Chinese cities to estimate death anomalies attributable to future warming. Historical estimation (1986-2014) reveals that about 15.5% [95% empirical confidence interval (eCI):13.1%, 17.6%] of deaths are attributable to nonoptimal temperature, of which heat and cold corresponded to attributable fractions of 4.1% (eCI:2.4%, 5.5%) and 11.4% (eCI:10.7%, 12.1%), respectively. Under three climate scenarios (SSP126, SSP245, and SSP585), the national average temperature was projected to increase by 1.45, 2.57, and 4.98 °C by the 2090s, respectively. The corresponding mortality fractions attributable to heat would be 6.5% (eCI:5.2%, 7.7%), 7.9% (eCI:6.3%, 9.4%), and 11.4% (eCI:9.2%, 13.3%). More than half of the attributable deaths due to future warming would occur in north China and cardiovascular mortality would increase more drastically than respiratory mortality. Our study shows that the increased heat-attributable mortality burden would outweigh the decreased cold-attributable burden even under a moderate climate change scenario across China. The results are helpful for national or local policymakers to better address the challenges of future warming.

Meta-analysis of the global prevalence and risk factors of Enterocytozoon bieneusi infection in pigs from 1999 to 2021.

Enterocytozoon bieneusi (E. bieneusi), which is one of the most common microsporidia, has been identified as an important obligate intracellular pathogen that commonly colonizes in a variety of animal species and humans worldwide, including humans. In this study, the statistical analyses of E. bieneusi infection and prevalence were performed to clarify the relationship between different genotypes in different countries. The databases Chinese National Knowledge Infrastructure (CNKI), VIP Chinese Journal Database, Wanfang Data, PubMed, Web of Science and ScienceDirect were used for data collection. The research data were subjected to subgroup, univariate regression, and correlation, to reveal factors related to the high prevalence of E. bieneusi. A total of, 34 of the 498 articles published before April 2022 met the inclusion criteria. The global prevalence of E. bieneusi in pigs was 37.69% (5175/12672). The prevalence of E. bieneusi in nursery pigs was 58.87% (588/946). In developing countries and Asia, the highest prevalence of E. bieneusi in pigs were 37.62% (4752/11645) and 40.14% (4715/11345), respectively. Moreover, humans and pigs have been found to be infected with the same genotype of E. bieneusi in some cases, as evidenced by the consolidation of genotype information. The results showed that pigs are susceptible to E. bieneusi during the nursery period. The prevalence of E. bieneusi is high in developing countries, and its genotype prevalence varies in each country. Thus, it is essential to strengthen the health inspection of vulnerable groups and customs quarantine inspection.

Global prevalence and risk factors of Enterocytozoon bieneusi infection in humans: a systematic review and meta-analysis.

Enterocytozoon bieneusi is one of the most important zoonotic pathogens. In this study, we present a systematic review and meta-analysis of the prevalence of human E. bieneusi infection in endemic regions and analyze the various potential risk factors. A total of 75 studies were included. Among 31,644 individuals tested, 2,291 (6.59%) were E. bieneusi-positive. The highest prevalence of E. bieneusi in the male population was 5.50%. The prevalence of E. bieneusi in different age groups was varied, with 10.97% in teenagers. The prevalence of E. bieneusi in asymptomatic patients (6.49%) is significantly lower than that in HIV-infected patients (11.49%), and in patients with diarrheal symptoms (16.45%). Rural areas had a higher rate (7.58%) than urban ones. The prevalence of E. bieneusi in humans was the highest (6.42%) at altitudes <10 m. Moreover, the temperate zone marine climate (13.55%) had the highest prevalence. A total of 69 genotypes of E. bieneusi have been found in humans. This is the first global study regarding E. bieneusi prevalence in humans. Not only people with low immunity (such as the elderly, children, people with HIV, etc.), but also people in Europe in temperate marine climates should exercise caution to prevent infection with E. bieneusi during contact process with animals.

Title: Prévalence mondiale et facteurs de risque de l'infection à Enterocytozoon bieneusi chez l'homme : revue systématique et méta-analyse. Abstract: Enterocytozoon bieneusi est l'un des agents pathogènes zoonotiques les plus importants. Dans cette étude, nous présentons une revue systématique et une méta-analyse de la prévalence de l'infection humaine à E. bieneusi dans les régions endémiques et analysons les différents facteurs de risque potentiels. Au total, 75 études ont été incluses. Parmi 31 644 individus, 2 291 (6,59 %) étaient positifs à E. bieneusi. La prévalence la plus élevée d'E. bieneusi dans la population masculine était de 5,50 %. La prévalence d'E. bieneusi dans différents groupes d'âge variait, avec 10,97 % chez les adolescents. La prévalence d'E. bieneusi chez les patients asymptomatiques (6,49 %) était significativement inférieure à celle des patients VIH (11,49 %) et des patients présentant des symptômes de diarrhée (16,45 %). Les zones rurales avaient un taux plus élevé (7,58 %) que les zones urbaines. La prévalence d'E. bieneusi chez les humains était la plus élevée (6,42 %) à une altitude <10 m. De plus, le climat marin de la zone tempérée (13,55 %) avait la prévalence la plus élevée. Au total, 69 génotypes d'E. bieneusi ont été trouvés chez l'homme. Il s'agit de la première étude mondiale concernant la prévalence d'E. bieneusi chez l'homme. Non seulement les personnes ayant une faible immunité (telles que les personnes âgées, les enfants, les patients atteints du VIH, etc.), mais également les personnes vivant en Europe dans un climat marin tempéré doivent veiller à prévenir l'infection par E. bieneusi lors du contact avec des animaux.

Target genes regulated by CLEC16A intronic region associated with common variable immunodeficiency.

BACKGROUND: CLEC16A intron 19 has been identified as a candidate locus for common variable immunodeficiency (CVID). OBJECTIVES: This study sought to elucidate the molecular mechanism by which variants at the CLEC16A intronic locus may contribute to the pathogenesis of CVID. METHODS: The investigators performed fine-mapping of the CLEC16A locus in a CVID cohort, then deleted the candidate functional SNP in T-cell lines by the CRISPR-Cas9 technique and conducted RNA-sequencing to identify target gene(s). The interactions between the CLEC16A locus and its target genes were identified using circular chromosome conformation capture. The transcription factor complexes mediating the chromatin interactions were determined by proteomic approach. The molecular pathways regulated by the CLEC16A locus were examined by RNA-sequencing and reverse phase protein array. RESULTS: This study showed that the CLEC16A locus is an enhancer regulating expression of multiple target genes including a distant gene ATF7IP2 through chromatin interactions. Distinct transcription factor complexes mediate the chromatin interactions in an allele-specific manner. Disruption of the CLEC16A locus affects the AKT signaling pathway, as well as the molecular response of CD4+ T cells to immune stimulation. CONCLUSIONS: Through multiomics and targeted experimental approaches, this study elucidated the underlying target genes and signaling pathways involved in the genetic association of CLEC16A with CVID, and highlighted plausible molecular targets for developing novel therapeutics.

CDKL5 regulates p62-mediated selective autophagy and confers protection against neurotropic viruses.

Virophagy, the selective autophagosomal engulfment and lysosomal degradation of viral components, is crucial for neuronal cell survival and antiviral immunity. However, the mechanisms leading to viral antigen recognition and capture by autophagic machinery remain poorly understood. Here, we identified cyclin-dependent kinase-like 5 (CDKL5), known to function in neurodevelopment, as an essential regulator of virophagy. Loss-of-function mutations in CDKL5 are associated with a severe neurodevelopmental encephalopathy. We found that deletion of CDKL5 or expression of a clinically relevant pathogenic mutant of CDKL5 reduced virophagy of Sindbis virus (SINV), a neurotropic RNA virus, and increased intracellular accumulation of SINV capsid protein aggregates and cellular cytotoxicity. Cdkl5-knockout mice displayed increased viral antigen accumulation and neuronal cell death after SINV infection and enhanced lethality after infection with several neurotropic viruses. Mechanistic studies demonstrated that CDKL5 directly binds the canonical selective autophagy receptor p62 and phosphorylates p62 at T269/S272 to promote its interaction with viral capsid aggregates. We found that CDKL5-mediated phosphorylation of p62 facilitated the formation of large p62 inclusion bodies that captured viral capsids to initiate capsid targeting to autophagic machinery. Overall, these findings identify a cell-autonomous innate immune mechanism for autophagy activation to clear intracellular toxic viral protein aggregates during infection.

TGF-ß Regulates m6A RNA Methylation after PM2.5 Exposure.

PM2.5 exposure leads to a variety of respiratory diseases, including pulmonary fibrosis, metastatic lung cancer, etc. Exposure to PM2.5 results in the alteration of epigenetic modification. M6A RNA methylation is an essential epigenetic modification that regulates gene expression at the post-transcriptional level. Our previous study found that PM2.5 exposure up-regulated m6A RNA methylation and TGF-ß expression level in the lung, but the mechanisms and pathways of PM2.5 regulation of m6A RNA methylation are still unclear. Moreover, a previous study reported that the TGF-ß signal pathway could regulate m6A RNA methylation. Based on this evidence, we investigate the role of the TGF-ß signaling pathway in PM2.5-induced m6A RNA methylation with the A549 cell line. Our results showed that PM2.5 could induce upregulation of m6A RNA methylation, accompanied by increased expression of TGF-ß, Smad3, methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14). Furthermore, these alterations induced by PM2.5 exposure could be reversed by treatment with TGF-ß inhibitor. Therefore, we speculated that the TGF-ß signal pathway plays an indispensable role in regulating m6A RNA methylation after PM2.5 exposure. Our study demonstrates that PM2.5 exposure influences m6A RNA methylation by inducing the alteration of the TGF-ß signal pathway, which could be an essential mechanism for lung-related diseases induced by PM2.5 exposure.

Stem cells as potential therapeutics for hearing loss.

Hearing impairment is a global health problem. Stem cell therapy has become a cutting-edge approach to tissue regeneration. In this review, the recent advances in stem cell therapy for hearing loss have been discussed. Nanomaterials can modulate the stem cell microenvironment to augment the therapeutic effects further. The potential of combining nanomaterials with stem cells for repairing and regenerating damaged inner ear hair cells (HCs) and spiral ganglion neurons (SGNs) has also been discussed. Stem cell-derived exosomes can contribute to the repair and regeneration of damaged tissue, and the research progress on exosome-based hearing loss treatment has been summarized as well. Despite stem cell therapy's technical and practical limitations, the findings reported so far are promising and warrant further investigation for eventual clinical translation.

Ambient black carbon variations and emission characteristics of typical Chinese vessels in the Yangtze River Delta, China.

Black carbon (BC) has a significant impact on air quality, climate change, and human health. Studies on BC from vessel exhaust have been focused on in recent years. To realize the contribution of BC from vessels to ambient air quality, 28 months of BC variation were observed from February 2019 to May 2022, including 3 fishing moratoriums and 2 normal periods. The results showed that the average daily concentration of BC in the fishing moratorium was significantly lower than that in the normal period. The difference proportion of the BC concentration between 370 and 880 nm was calculated over the whole period. As a result, the mean difference value in the fishing moratorium from February to May was 0.06 ± 0.07, and the normal period was -0.02 ± 0.05. The aethalometer model indicated that BC was greatly affected by fossil fuel combustion in the normal period. The effect of vessel emissions on regional BC concentrations was considerable. In addition, 16 PAHs and 21 elements in PM emitted from 24 vessels of different types were sampled and analyzed in Dianshan Lake and the Taipu River. EC accounted for the highest proportion (23.64%) in the sample of small trawlers compared to the emissions from cargo ships with large tonnages. The component profiles of vessel exhaust showed that Zn, As, phenanthrene (Phe), anthracene (Ant), fluoranthene (Fla), and pyrene (Pyr) were the dominant species, although some of these species were mainly recognized as characteristic factors of coal combustion. To improve the accuracy of identifying the vessel source, the diagnostic ratios of Ant/(Ant + Phe), BaA/(BaA + Chr), Phe/Ant, and BaA/Chr were provided, and they exhibited the obvious characteristics of fuel combustion.

Ambient Volatile Organic Compound Characterization, Source Apportionment, and Risk Assessment in Three Megacities of China in 2019.

In order to illustrate pollution characterization, source apportionment, and risk assessment of VOCs in Beijing, Baoding, and Shanghai, field observations of CO, NO, NO2, O3, and volatile organic compounds (VOCs) were conducted in 2019. Concentrations of VOCs were the highest in Beijing (105.4 ± 52.1 ppb), followed by Baoding (97.1 ± 47.5 ppb) and Shanghai (91.1 ± 41.3 ppb). Concentrations of VOCs were the highest in winter (120.3 ± 61.5 ppb) among the three seasons tested, followed by summer (98.1 + 50.8 ppb) and autumn (75.5 + 33.4 ppb). Alkenes were the most reactive VOC species in all cities, accounting for 56.0%, 53.7%, and 39.4% of ozone formation potential in Beijing, Baoding, and Shanghai, respectively. Alkenes and aromatics were the reactive species, particularly ethene, propene, 1,3,5-trimethylbenzene, and m/p-xylene. Vehicular exhaust was the principal source in all three cities, accounting for 27.0%, 30.4%, and 23.3% of VOCs in Beijing, Baoding, and Shanghai, respectively. Industrial manufacturing was the second largest source in Baoding (23.6%) and Shanghai (21.3%), and solvent utilization was the second largest source in Beijing (25.1%). The empirical kinetic modeling approach showed that O3 formation was limited by both VOCs and nitric oxides at Fangshan (the suburban site) and by VOCs at Xuhui (the urban site). Acrolein was the only substance with an average hazard quotient greater than 1, indicating significant non-carcinogenic risk. In Beijing, 1,2-dibromoethane had an R-value of 1.1 × 10-4 and posed a definite carcinogenic risk.

Personal PM2.5-bound PAH exposure and lung function in healthy office workers: A pilot study in Beijing and Baoding, China.

The effect of short-term exposure to polycyclic aromatic hydrocarbons (PAHs) on the respiratory system among healthy residents is unclear. Beijing and Baoding are typical polluted cities in China, and there is little research on PAH exposure and its health effects at the individual level. Fourteen healthy female office workers were recruited in urban Beijing and Baoding, China, in 2019. The personal exposure to fine particulate matter (PM2.5)-bound PAHs and lung function were seasonally monitored. The relationships between PAH exposure and lung function were determined by a generalized mixed linear model. Subjects were exposed to high levels of PAH, in which the benzo[a]pyrene (BaP) level (1.26 ng/m3) was over than Chinese national indoor standard (1 ng/m3). All PAHs concentration was higher in winter than that in summer and autumn. Only benz[a]anthracene (BaA) and chrysene (Chr) exposure showed weak relations with decreased lung function, i.e., a 0.58% and 0.73% decrease in peak expiratory flow at lag 2 day, respectively (p < 0.05). PAHs may not be suitable exposure indicators for short-term change in lung function. Our findings highlight the importance of reducing PAH pollution for public respiratory health protection in heavy-polluted cities of China. This pilot study also provides experience on personal PAH assessment such as estimation of the number of repeated measurements required, which is helpful to determine the relationship between PAH exposure and health effect.

Influence of temperature on the risk of gestational diabetes mellitus and hypertension in different pregnancy trimesters.

Previous studies have proved that exposure to extreme temperature in specific windows of pregnancy could cause some complications, such as pregnancy induced hypertension (PIH) and gestational diabetes mellitus (GDM), but differences in the effect of extreme temperature on the 2 complications are rarely studied. We carried a retrospective study on the impact of temperature on GDM/PIH in different trimesters based on data from a maternal and child health center in Beijing, China. Ambient temperatures (°C) were obtained from the China Meteorological Administration from January 1st, 2013 to May 15th, 2018. We use distributed lag non-linear models (DLNMs) combined with logistic regression to calculate the lag exposure-response relationships between the temperature and GDM/PIH from 1st to 24th/20th weeks of pregnancy. In both first and second trimesters, the risk of GDM was increased in summer with high temperatures; in second trimester, the risk of GDM increased in winter with low temperatures. In first half of pregnancy, risk of PIH was decreased in winter with low temperatures. These findings can provide the guideline for preventing the GDM and PIH induced by extreme temperature during pregnancy.

Effect of acute PM2.5 exposure on PTGS2 and RNA m6A modification.

Particulate matter 2.5 (PM2.5) is a prevalent risk factor in many diseases, but its molecular mechanism remains ambiguous and may be diverse. RNA m6A is an important epigenetic modification that regulates gene expression at the post-transcriptional level. Some previous animal exposure studies found that PM2.5 exposure up-regulated m6A RNA methylation in the lung, but there is no research on m6A RNA methylation in humans from PM2.5 exposure now. Here, in the present experiment, we performed a panel study of 65 students at the Chinese research academy of environmental sciences (CRAES) with 3 rounds of follow-up visits from August 2021 to January 2022. We examined m6A RNA modification profiles of peripheral blood mononuclear cells (PBMCs) from subjects after low and high concentrations of ambient PM2.5 exposure. We applied a linear mixed-effect (LME) model to investigate the association between PM2.5 exposure and global m6A RNA methylation and PTGS2 level in peripheral blood. We found that increased levels of global m6A RNA methylation and PTGS2 level were associated with higher PM2.5 exposure. Among the methylated mRNAs, PTGS2 was hyper-methylated after high concentrations of PM2.5 exposure, which coincided with the increased expression of PTGS2 mRNA. In the present study, we determined that PM2.5 exposure promoted RNA m6A modification, and PTGS2 in peripheral blood could serve as a novel regulatory factor of inflammation induced by PM2.5 exposure. Furthermore, RNA m6A modification may contribute to the altered expression of PTGS2 induced by PM2.5 exposure. Our finding provided a new perspective for the prevention and treatment of PM2.5 exposure-induced adverse health effects.

Associations between exposure to ambient air pollution and changes in blood telomeres in young people: A repeated-measure study.

Telomere length (TL) is one of the early biomarkers of aging. Air pollutants play an important role in promoting the aging process. However, few studies have explored how they adversely affect human health by altering telomeres. This study aims to investigate the associations between telomere alterations and exposure to ambient air pollutants, thereby shedding light on the intrinsic and profound link between these pollutants and aging. We recruited 26 healthy young people and conducted 7 repeated measure studies from 2019 to 2021, and TL and telomerase (TA) in the blood samples. We analyzed the associations between air pollutants, including ozone (O3), particulate matter in diameter smaller than 2.5 µm (PM2.5) and 10 µm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and carbon monoxide (CO) and telomere variability, and explored the lagged effects by linear mixed-effects model. The result showed that short-term exposure to O3 was negatively associated with TL, and this effect in the lag days went up to around 0. In contrast, the associations between O3 and TA presented positive tendency and gradually decreased to around 0 in the lag days. The association between PM2.5 and TL showed positive tendency and gradually decreased to negative. There was no statistically significant association between PM2.5 and TA. Other pollutants (PM10, NO2, SO2, CO) showed similar patterns of variation to that of PM2.5. Our findings suggest that short-term exposure to O3 shortens TL, which can be gradually recovered through activating TA activity, while exposure to PM2.5, PM10, NO2, SO2 and CO lengthens TL and then becomes shorter over time. This implies that the human body has some ability to self-repair telomere changes after exposure to air pollutants, and predictably, when this exposure exceeds a certain threshold, it cannot be repaired, leading to aging of the body.

Specific mating behavior of Malayan pangolin (Manis javanica) in captivity.

Pangolin is a mysterious animal in the Family Pholidota, Mammalia. Malayan pangolin (Manis javanica) is one of eight existing species and is listed in Manis. With the number of wild pangolins (Manis spp.) rapidly decreasing, captive breeding has become an important way to protect them from extinction. The research on mating behavior of pangolins is an important content to understand its reproductive characteristics and develop breeding management. From 2016 to 2022, a total of 360 mating events were observed in six males and 24 females through closed circuit television (CCTV) surveillance. The results show that males do not engage in complex courtship behavior before mating. In addition, we found that male pangolins adopted a ventrolateral mating position. Once males selected the side (left/right) of the female pangolin from which to approach to mate, they usually remained on the same side for subsequent mating, suggesting that male pangolins may have a preference in mating position. Finally, all mating events were observed at 1.72 ± 1.47 (n = 83, Mean ± SD) days after cohabitation and adjustment time before mating (from the male touching the female to intromission) took 4.98 ± 3.86 mins (n = 323). During mating, males hugged females and remained still for 47.37 ± 10.08 seconds (n = 323), which is the ejaculation and post-ejaculation quiescent time. Remarkably, we observed for the first time two peak mating times, 19:00 to 22:00 and 1:00 to 3:00, suggesting that they may have a preference for mating times. This study provides new insight into the mating behavior of M. javanica and contributes to the development of scientific conservation measures to improve the reproductive capacity of M. javanica.

Respiratory Effects of Traffic-Related Air Pollution: A Randomized, Crossover Analysis of Lung Function, Airway Metabolome, and Biomarkers of Airway Injury.

BACKGROUND: Exposure to traffic-related air pollution (TRAP) has been associated with increased risks of respiratory diseases, but the biological mechanisms are not yet fully elucidated. OBJECTIVES: Our aim was to evaluate the respiratory responses and explore potential biological mechanisms of TRAP exposure in a randomized crossover trial. METHODS: We conducted a randomized crossover trial in 56 healthy adults. Each participant was exposed to high- and low-TRAP exposure sessions by walking in a park and down a road with high traffic volume for 4 h in random order. Respiratory symptoms and lung function, including forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), the ratio of FEV1 to FVC, and maximal mid-expiratory flow (MMEF), were measured before and after each exposure session. Markers of 8-isoprostane, tumor necrosis factor-α (TNF-α), and ezrin in exhaled breath condensate (EBC), and surfactant proteins D (SP-D) in serum were also measured. We used linear mixed-effects models to estimate the associations, adjusted for age, sex, body mass index, meteorological condition, and batch (only for biomarkers). Liquid chromatography-mass spectrometry was used to profile the EBC metabolome. Untargeted metabolome-wide association study (MWAS) analysis and pathway enrichment analysis using mummichog were performed to identify critical metabolomic features and pathways associated with TRAP exposure. RESULTS: Participants had two to three times higher exposure to traffic-related air pollutants except for fine particulate matter while walking along the road compared with in the park. Compared with the low-TRAP exposure at the park, high-TRAP exposure at the road was associated with a higher score of respiratory symptoms [2.615 (95% CI: 0.605, 4.626), p=1.2×10-2] and relatively lower lung function indicators [-0.075L (95% CI: -0.138, -0.012), p=2.1×10-2] for FEV1 and -0.190L/s (95% CI: -0.351, -0.029; p=2.4×10-2) for MMEF]. Exposure to TRAP was significantly associated with changes in some, but not all, biomarkers, particularly with a 0.494-ng/mL (95% CI: 0.297, 0.691; p=9.5×10-6) increase for serum SP-D and a 0.123-ng/mL (95% CI: -0.208, -0.037; p=7.2×10-3) decrease for EBC ezrin. Untargeted MWAS analysis revealed that elevated TRAP exposure was significantly associated with perturbations in 23 and 32 metabolic pathways under positive- and negative-ion modes, respectively. These pathways were most related to inflammatory response, oxidative stress, and energy use metabolism. CONCLUSIONS: This study suggests that TRAP exposure might lead to lung function impairment and respiratory symptoms. Possible underlying mechanisms include lung epithelial injury, inflammation, oxidative stress, and energy metabolism disorders. https://doi.org/10.1289/EHP11139.

Exposure to ambient air pollution from the preconceptional period and risk of gestational hypertension.

Although accumulative studies have revealed the associations between air pollutants and elevated risk of gestational hypertension (GH), evidence from developing countries with relatively higher levels of air pollutants remains limited. In this retrospective study, a total of 45,439 birth records were collected in Beijing, China from 2013 to 2018. For PM2.5, SO2, NO2, and O3, exposure windows from the 3rd month of preconception to the 6th month of conception and the averages of 3 months of preconception, trimester 1 and trimester 2 periods were all calculated for assessment of GH risks. The correlations between air pollutants and the risk of GH were analyzed by logistic regression model. Our results showed that exposure to PM2.5 and SO2 in the preconceptional and early pregnancy periods was related to the elevated risk of GH. Furthermore, 3 months preconceptional exposure to PM2.5 (PCPM2.5: OR = 1.134 (1.114, 1.155)) and SO2 (PCSO2: OR = 1.158 (1.135, 1.181)) showed a higher risk of GH than the results of the trimester 1 (T1PM2.5: OR = 1.131 (1.104, 1.159); T1SO2: OR = 1.164 (1.141, 1.187)) and the trimester 2 (T2PM2.5: OR = 1.154 (1.126, 1.182); T2SO2: OR = 1.121 (1.098, 1.144)). The study also found significant and higher OR values for PCPM2.5, and PCSO2 from 2013 to 2016 when air pollution was serious in Beijing compared with 2017 to 2018 when the air pollution was obviously improved. Subgroup analysis also found that during 3 months of preconception women with higher age and who exposure to higher temperatures showed higher GH risk from PM2.5 and SO2 than that of the younger group and who exposure to lower temperature, respectively. Collectively, our findings suggest that air pollution exposure was adversely associated with GH in pregnant women and the preconceptional period is a critical air pollution exposure window for GH. Improving air quality can benefit public health, especially for sensitive populations like pregnant women.

Advances in Drug Discovery Targeting Lysosomal Membrane Proteins.

Lysosomes are essential organelles of eukaryotic cells and are responsible for various cellular functions, including endocytic degradation, extracellular secretion, and signal transduction. There are dozens of proteins localized to the lysosomal membrane that control the transport of ions and substances across the membrane and are integral to lysosomal function. Mutations or aberrant expression of these proteins trigger a variety of disorders, making them attractive targets for drug development for lysosomal disorder-related diseases. However, breakthroughs in R&D still await a deeper understanding of the underlying mechanisms and processes of how abnormalities in these membrane proteins induce related diseases. In this article, we summarize the current progress, challenges, and prospects for developing therapeutics targeting lysosomal membrane proteins for the treatment of lysosomal-associated diseases.

Influence of different concentrations of ozone on the alteration of mitochondrial DNA copy numbers in human peripheral blood.

By now, O3 pollution has become a main environmental problem. O3 is a prevalent risk factor for many diseases, but the regulatory factors linking O3 and diseases remain ambiguous. Mitochondrial DNA (mtDNA) is the genetic material in mitochondria, which plays a key role in the production of respiratory ATP. Due to a lack of histone protection, mtDNA is easily damaged by ROS, and O3 is an important source to stimulate the production of endogenous ROS in vivo. Therefore, we logically speculate that O3 exposure can alter mtDNA copy number by the induction of ROS. In the present study, we performed a panel study of 65 MSc students at the Chinese research academy of environmental sciences (CRAES) with 3 rounds of follow-up visits from August 2021 to January 2022. We examined the mtDNA copy numbers in the peripheral blood of subjects using quantitative polymerase chain reaction. Linear mixed-effect (LME) model and stratified analysis were used to investigate the association between O3 exposure and mtDNA copy numbers. We found a dynamic process of the association between the concentration of O3 exposure and the mtDNA copy number in the peripheral blood. The lower concentration of O3 exposure did not affect the mtDNA copy number. As the concentration of O3 exposure increased, the mtDNA copy number also increased. While, when O3 exposure reached a certain concentration, a decrease in mtDNA copy number was found. This correlation between the concentration of O3 and the mtDNA copy number could be ascribed to the severity of cellular damage induced by O3 exposure. Our results provide a new perspective for the discovery of a biomarker of O3 exposure and health response, as well as for the prevention and treatment of adverse health effects caused by different concentrations of O3.

Short and long-term association of exposure to ambient black carbon with all-cause and cause-specific mortality: A systematic review and meta-analysis.

Black carbon (BC) is a product of incomplete or inefficient combustion and may be associated with a variety of adverse effects on human health. The objective of this study was to analyze the association between various mortalities and long-/short-term exposure to BC as an independent pollutant. In this systematic review, we searched 4 databases for original research in English up to 6th October 2022, that investigated population-wide mortality due to BC exposure. We pooled mortality estimates and expressed them as relative risk (RR) per 10 µg/m3 increase in BC. We used a random-effect model to derive the pooled RRs. Of the 3186 studies identified, 29 articles met the eligibility criteria, including 18 long-term exposure studies and 11 short-term exposure studies. In the major meta-analysis and sensitivity analysis, positive associations were found between BC and total mortality and cause-specific disease mortalities. Among them, the short-term effects of BC on total mortality, cardiovascular disease mortality, respiratory disease mortality, and the long-term effects of BC on total mortality, ischemic heart disease mortality, respiratory disease mortality and lung cancer mortality were found to be statistically significant. The heterogeneity of the meta-analysis results was much lower for short-term studies than for long-term. Few studies were at a high risk of bias in any domain. The certainty of the evidence for most of the exposure-outcome pairs was moderate. Our study showed a significantly positive association between short-/long-term BC exposure and various mortalities. We speculate that BC has a higher adverse health effect on the respiratory system than on the cardiovascular system. This is different from the effect of PM2.5. Therefore, more studies are needed to consider BC as a separate pollutant, and not just as a component of PM2.5.

Air pollution exposure and the risk of macrosomia: Identifying specific susceptible months.

Birth weight is an important indicator of future growth and development for newborns. Few studies investigated the potential effects of air pollutants on macrosomia and their susceptible windows. We included 38,971 singleton full-term births from Beijing HaiDian Maternal and Child Health Hospital between 2014 and 2018, and assessed the associations of air pollutants exposure during preconception and pregnancy with macrosomia as well as the corresponding susceptible windows. The concentrations of air pollutants (PM2.5, PM10, SO2, NO2, CO and O3) for participants were calculated by the data from the nearest monitoring stations. Distributed lag models (DLM) incorporating logistic regression models were used to estimate the associations between air pollutants exposure during the 3 months before conception and pregnancy period and the risk of macrosomia, identifying susceptible windows of air pollutants. Weighted quantile sum (WQS) regression was applied to estimate the joint effect of air pollutants. A 10 µg/m3 increase in PM2.5 exposure from 3rd to 8th gestational month was positively associated with the risk of macrosomia, with the strongest effect in the 6th month (OR = 1.010, 95 % CI: 1.002-1.019). For a 10 µg/m3 increase in SO2, the windows of significant exposure were from the 1st preconception month to the 3rd gestational month, with the strongest effect in the 2nd month (OR = 1.030, 95 % CI: 1.010-1.049). We also observed the significant positive associations were in the 5th-8th gestational months for PM10, the 8th-9th gestational months for NO2 and the 3rd-7th gestational months for CO respectively. WQS regression also indicated a positive association between co-exposure to air pollutants and macrosomia. Our results suggest air pollution exposure is associated with increased risk of macrosomia. The windows of exposure for susceptibility to the risk of macrosomia vary between air pollutants. The susceptible exposure windows were middle and late pregnancy for PM, CO and NO2, while for SO2, early pregnancy is the window of vulnerability. Our findings provide the evidence that air pollution exposure is an independent risk factor for macrosomia and a basis for targeted environment policy.