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Jian-Song Ji,1,2,* Min Xu,1,* Jing-Jing Song,1,* Zhong-Wei Zhao,1,* Min-Jiang Chen,1 Wei-Qian Chen,1 Jian-Fei Tu,1 Xiao-Ming Yang2 1Department of Radiology, Affiliated Lishui Hospital of Zhejiang University, Fifth Affiliated Hospital of Wenzhou Medical University, Central Hospital of Zhejiang Lishui, Lishui, People’s Republic of China; 2Department of Radiology, Lab-Yang, University of Washington, Seattle, WA, USA *These authors contributed equally to this work Abstract: MicroRNA-126 (miR-126) has been found to promote angiogenesis, but the underlying mechanisms are still unclear. So, we conducted this study to explore the effect of miR-126 expression on angiogenesis in hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization (TACE). The expression levels of miR-126 and sprouty-related, EVH1 domain containing protein (Spred)1 in surgically resected HCC tissue, HCC tissue with TACE + operation, and tumor-adjacent tissues were determined by quantitative real-time polymerase chain reaction. The expression levels of miR-126, Spred1, and vascular endothelial growth factor were found by quantitative real-time polymerase chain reaction and Western blot. The microvessel density (MVD) of tumor tissues was determined by immunohistochemical staining. The miR-126 and Spred1 expressions in HCC tissue with TACE + operation were elevated and decreased, respectively, as compared to those in surgically resected HCC tissues and tumor-adjacent tissues (all P

The impact of early life exposure to residential greenness on childhood rhinitis and its interaction with particulate matter (PM) of different size fractions remain inconsistent. Herein, we recruited 40,486 preschool children from randomly selected daycare centers in 7 cities in China from 2019 to 2020, and estimated exposure to residential greenness by the normalized difference vegetation index (NDVI) with a 500 m buffer. Exposure to ambient PM (PM 1 , PM 2.5, and PM 10 ) was evaluated using a satellite-based prediction model (daily, at a resolution of 1 km × 1 km). By mixed-effect logistic regression, NDVI values during pregnancy, in the first (0-1 year old) and the second (1-2 years old) year of life were negatively associated with lifetime rhinitis (LR) and current rhinitis (CR) (P < 0.001). PM in the same time windows was associated with increased risks of LR and CR in children, with smaller size fraction of PM showing greater associations. The negative associations between prenatal and postnatal NDVI and LR and CR in preschool children remained robust after adjusting for concomitant exposure to PM, whereas the associations of postnatal NDVI and rhinitis showed significant interactions with PM. At lower levels of PM, postnatal NDVI remained negatively associated with rhinitis and was partly mediated by PM (10.0-40.9 %), while at higher levels of PM, the negative associations disappeared or even turned positive. The cut-off levels of PM were identified for each size fraction of PM. In conclusion, prenatal exposure to greenness had robust impacts in lowering the risk of childhood rhinitis, while postnatal exposure to greenness depended on the co-exposure levels to PM. This study revealed the complex interplay of greenness and PM on rhinitis in children. The exposure time window in prenatal or postnatal period and postnatal concomitant PM levels played important roles in influencing the associations between greenness, PM and rhinitis., Competing Interests: Declaration of competing interest None of the authors declares any conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Plant-based diets (PBDs) and planetary-health diets (PHDs) are recommended for their potential health and environmental benefits, but population-based evidence in diverse cultures is scarce., Methods: We included 9364 adults aged 45 years and older (52·3% female, 47·7% male) from the open cohort of the China Health and Nutrition Survey. Dietary intake was assessed using 3-day 24 h dietary recalls combined with weighing methods from 1997 to 2011, and mortality was documented from 1997 to 2015. We calculated the overall PBD index (PDI), healthful PBD index (hPDI), and unhealthful PBD index (uPDI; ranges 18-90), and the PHD score (range 0-140). We also estimated the related greenhouse gas emissions, land appropriation, and total water footprint and examined their associations with mortality., Findings: PBD indices were inversely related to greenhouse gas emissions, land appropriation, and total water footprint, whereas higher PHD score was related to higher environmental burdens (p<0·0001). During follow-up (mean 9·2 years), 792 (8·5%) death cases were documented. PDI (HR 1·08 [95% CI 0·88-1·32]) and hPDI (0·98 [0·80-1·21]) were not significantly associated with mortality, whereas higher uPDI was related to a higher mortality risk (1·55 [1·26-1·91]). In contrast, higher PHD score was associated with lower mortality risk (0·79 [0·63-0·99])., Interpretation: The PBDs showed environmental benefits, but are not necessarily associated with lower mortality risk. The PHD, developed mainly in western populations, was related to lower mortality risk but higher environmental burdens in the Chinese population., Funding: Fundamental Research Funds for the Central Universities, Zhejiang University Global Partnership Fund, and National Natural Science Foundation of China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

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., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Perfluoroalkyl and polyfluoroalkyl substance (PFAS) has endocrine-disrupting properties and may affect blood pressure. Endogenous hormones also play a crucial role in the progression of hypertension. However, their interaction with hypertension remains to be explored., Methods: This study included 10 794 adults aged ≥18 years from the China National Human Biomonitoring program. Weighted multiple logistic regression and linear regression were used to examine the associations of serum PFAS with hypertension, diastolic blood pressure, and systolic blood pressure. Joint effects of PFAS mixtures on hypertension, diastolic blood pressure, and systolic blood pressure were evaluated using quantile-based g-computation. Additive and multiplicative interactions were used to assess the role of PFAS with testosterone and estradiol on hypertension., Results: The prevalence of hypertension in Chinese adults was 35.50%. Comparing the fourth quartile with the first quartile, odds ratio (95% CI) of hypertension were 1.53 (1.13-2.09) for perfluorononanoic acid, 1.40 (1.03-1.91) for perfluorodecanoic acid, 1.34 (1.02-1.78) for perfluoroheptane sulfonic acid, and 1.46 (1.07-1.99) for perfluorooctane sulfonic acid. Moreover, PFAS mixtures, with perfluorononanoic acid contributing the most, were positively associated with hypertension, diastolic blood pressure, and systolic blood pressure. PFAS and endogenous hormones had an antagonistic interaction in hypertension. For example, the relative excess risk ratio, attributable proportion, and synergy index for perfluorononanoic acid and estradiol were -3.61 (-4.68 to -2.53), -1.65 (-2.59 to -0.71), and 0.25 (0.13-0.47), respectively., Conclusions: Perfluorononanoic acid, perfluorodecanoic acid, perfluoroheptane sulfonic acid, perfluorooctane sulfonic acid, and PFAS mixtures showed positive associations with hypertension, systolic blood pressure, and diastolic blood pressure. Positive associations of PFAS with hypertension might be attenuated by increased levels of endogenous sex hormones., Competing Interests: None.

Background: Exposure to air pollution has been associated with increased risks of cardiopulmonary diseases, cancer, and mortality, whereas residing near green spaces may reduce the risks. However, limited research explores their combined effect on oxidative stress., Methods: A total of 251 participants with multi-time measurements were included in the longitudinal-designed study. Personal gaseous air pollutants (CO, NO, NO 2 , and O 3 ,) and particulate pollution (PM 1 , PM 2.5 , and PM 10 ) were measured and followed in two 7-day windows while ambient exposure levels and urine samples were collected simultaneously. Participants' Normalized Difference Vegetation Index (NDVI) was estimated and used to represent greenness exposure. Urinary oxidative stress biomarkers include free malondialdehyde (MDA), total MDA, and 8-hydroxydeoxyguanosine (8-OHdG). Linear mixed-effects models were used to independently and jointly estimate the associations of greenness and air pollution with oxidative stress biomarkers., Results: We found consistent positive associations of personal ozone (O 3 ) exposure with 8-OHdG percent changes, and this association was modified by gender and outdoor activity frequency. Consistent positive associations of personal lag 2-day carbon monoxide (CO) exposure with the percent changes of the three oxidative stress biomarkers were significant. We additionally observed that individuals who lived in greener areas had lower levels of urinary-free and total MDA. Participants in the highest NDVI tertile had 0.38 and 0.46 lower free and total MDA levels, [95 % CI: (-0.70, -0.05) and (-0.78, -0.13)], compared to the lowest NDVI tertile. There was also evidence indicating the modification effects by area, education, and outdoor activity frequency on associations between NDVI exposure and creatinine adjusted free MDA (all P for interaction  < 0.05). Additional greenness modification effects on personal O 3 exposure with urinary 8-OHdG was observed., Conclusion: Our study provides biological evidence of the modification effect of the built environment on the impact of air pollution., Competing Interests: Declaration of competing interest The authors declare they have no conflicts of interest related to this work to disclose., (Copyright © 2024. Published by Elsevier B.V.)

Background: Mental health in the elderly has multiple determinants, and studies indicate household and family composition, economic status, and family support are key factors. However, these are difficult to modify, and better lifestyle for the elderly can be a possible intervention. The current study examined the mediating role of lifestyle in the association between these three types of the household and family composition (living alone, living with a spouse, and living with children) and mental health in older adults., Methods: We studied 5,407 participants (58.7% female, age 45 + years) from the Beijing Aging Brain Rejuvenation Initiative Project. All participants underwent a battery of examinations to measure degree loneliness, depression, and global cognitive function. We also surveyed personal lifestyles. We used a mediation analysis to determine the relative contribution of each lifestyle factor on mental health outcomes., Results: Older adults living alone rarely participated in mental and social activities and often had irregular diets; those adults living with children spent most of their time caring for grandchildren and had irregular eating and sleeping schedules; those living with a spouse often engaged in a variety of leisure activities and had the best life habits. Mediation analyses showed that dietary and sleeping irregularity partially mediated the negative effects of living alone on mental health, and were moderated by age and gender., Conclusions: Living with a spouse was associated with benefits for the mental health of middle-aged and older adults (especially older and female individuals), through modifying better lifestyles than those of individuals with the other two types of the household and family composition., (© 2024. The Author(s).)

There has been widespread concern about the health hazards of per- and polyfluoroalkyl substances (PFAS), which may be the risk factor for hyperuricemia with evidence still insufficient in the general population in China. Here, we conducted a nationwide study involving 9,580 adults aged 18 years or older from 2017 to 2018, measured serum concentrations of uric acid and PFAS (PFOA, PFOS, 6:2 Cl-PFESA, PFNA, PFHxS) in participants, to assess the associations of individual PFAS with hyperuricemia, and estimated a joint effect of PFAS mixtures. We found positive associations of higher serum PFAS with elevated odds of hyperuricemia in Chinese adults, with the greatest contribution from PFOA (69.37%). The nonmonotonic dose-response (NMDR) relationships were observed for 6:2 Cl-PFESA and PFHxS with hyperuricemia. Participants with less marine fish consumption, overweight, and obesity may be the sensitive groups to the effects of PFAS on hyperuricemia. We highlight the potential health hazards of legacy long-chain PFAS (PFOA) once again because of the higher weights of joint effects. This study also provides more evidence about the NMDR relationships in PFAS with hyperuricemia and emphasizes a theoretical basis for public health planning to reduce the health hazards of PFAS in sensitive groups.

Accumulating evidence linked extreme temperature events (ETEs) and fine particulate matter (PM 2.5 ) to cardiometabolic multimorbidity (CMM); however, it remained unknown if and how ETEs and PM 2.5 interact to trigger CMM occurrence. Merging four Chinese national cohorts with 64,140 free-CMM adults, we provided strong evidence among ETEs, PM 2.5 exposure, and CMM occurrence. Performing Cox hazards regression models along with additive interaction analyses, we found that the hazards ratio (HRs) of CMM occurrence associated with heatwave and cold spell were 1.006-1.019 and 1.063-1.091, respectively. Each 10 μg/m 3 increment of PM 2.5 concentration was associated with 17.9% (95% confidence interval: 13.9-22.0%) increased risk of CMM. Similar adverse effects were also found among PM 2.5 constituents of nitrate, organic matter, sulfate, ammonium, and black carbon. We observed a synergetic interaction of heatwave and PM 2.5 pollution on CMM occurrence with relative excess risk due to the interaction of 0.999 (0.663-1.334). Our study provides novel evidence that both ETEs and PM 2.5 exposure were positively associated with CMM occurrence, and the heatwave interacts synergistically with PM 2.5 to trigger CMM.

Inducing death receptor 5 (DR5) clustering holds particular promise in tumor-specific therapeutics because it could trigger an apoptotic cascade in cancerous cells. Herein, we present a tumor microenvironment H 2 O 2 -responsive self-illuminating nanoagonist, which could induce dual tumor cell death pathways through enhancing DR5 clustering. By conjugating DR5 ligand peptides onto the surfaces of self-illuminating nanoparticles with cross-linking capacity, this strategy not only provides scaffolds for ligands to bind receptors but also cross-links them through photo-cross-linking. This strategy allows for efficient activation of DR5 downstream signaling, initiating the extrinsic apoptosis pathway and immunogenic cell death of tumor cells, and contributes to improved tumor-specific immune responses, resulting in enhanced antitumor efficacy and minimized systemic adverse effects.

Heat exposure is associated with an increased risk of preterm birth (PTB), with previous work suggesting that maternal blood pressure may play a role in these associations. Here we conducted a cohort study of 197,080 singleton live births across 8 provinces in China from 2015 to 2018. The study first estimated the associations between heat exposure, maternal hypertension and clinical subtypes of PTB, and then quantified the role of maternal hypertension in heat and PTB using mediation analyses. We show that heat exposure (>85th, 90th and 95th percentiles of local temperature distributions) spanning from conception to the 20th gestational week was associated with a 15-21% increase in PTB, and a 20-22% increase in medically indicated PTB. Heat exposure is likely to increase the risk of maternal hypertension and elevated blood pressure. Maternal hypertension mediated 15.7% and 33.9% of the effects of heat exposure (>90th percentile) on PTB and medically indicated PTB, respectively. Based on this large-population study, we found that exposure to heat in early pregnancy can increase the risk of maternal hypertension, thereby affecting the incidence of PTB., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Wastewater-based epidemiology (WBE) has emerged as a promising tool for monitoring the spread of COVID-19, as SARS-CoV-2 can be shed in the faeces of infected individuals, even in the absence of symptoms. This study aimed to optimize a prediction model for estimating COVID-19 infection rates based on SARS-CoV-2 RNA concentrations in wastewater, and reveal the infection trends and variant diversification in Shenzhen, China following the lifting of a strict COVID-19 strategy. Faecal samples (n = 4337) from 1204 SARS-CoV-2 infected individuals hospitalized in a designated hospital were analysed to obtain Omicron variant-specific faecal shedding dynamics. Wastewater samples from 6 wastewater treatment plants (WWTPs) and 9 pump stations, covering 3.55 million people, were monitored for SARS-CoV-2 RNA concentrations and variant abundance. We found that the viral load in wastewater increased rapidly in December 2022 in the two districts, demonstrating a sharp peak in COVID-19 infections in late-December 2022, mainly caused by Omicron subvariants BA.5.2.48 and BF.7.14. The prediction model, based on the mass balance between total viral load in wastewater and individual faecal viral shedding, revealed a surge in the cumulative infection rate from <0.1 % to over 70 % within three weeks after the strict COVID-19 strategy was lifted. Additionally, 39 cryptic SARS-CoV-2 variants were identified in wastewater, in addition to those detected through clinical surveillance. These findings demonstrate the effectiveness of WBE in providing comprehensive and efficient assessments of COVID-19 infection rates and identifying cryptic variants, highlighting its potential for monitoring emerging pathogens with faecal shedding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Heat exposure during pregnancy can increase the risk of preterm birth (PTB) through a range of potential mechanisms including pregnancy complications, hormone secretion and infections. However, current research mainly focuses on the effect of heat exposure on pathophysiological pathways of pregnant women, but ignore that maternal heat exposure can also cause physiological changes to the fetus, which will affect the risk of PTB., Objective: In this study, we aimed to explore the mediating role of fetal heart rate (FHR) in the relationship between maternal heat exposure and PTB incidence., Methods: We assigned heat exposure to a multi-center birth cohort in China during 2015-2018, which included all 162,407 singleton live births with several times FHR measurements during the second and third trimesters. We examined the associations between heat exposure, FHR and PTB in the entire pregnancy, each trimester and the last gestational month. The inverse odds ratio-weighted approach applied to the Cox regression was used to identify the mediation effect of heat exposure on PTB and its clinical subtypes via FHR., Findings: Exposure to heat significantly increased the risk of PTB during the third trimester and the entire pregnancy, hazard ratios and 95 % CIs were 1.266 (1.161, 1.379) and 1.328 (1.218, 1.447). Heat exposure during the third trimester and entire pregnancy increased FHR in the third trimester by 0.24 bpm and 0.14 bpm. The proportion of heat exposure mediated by FHR elevation on PTB and its subtype ranged from 3.68 % to 24.06 %, with the significant mediation effect found for both medically indicated PTB and spontaneous PTB., Conclusions: This study suggests that heat exposure during pregnancy has an important impact on fetal health, and FHR, as a surrogate marker of fetal physiology, may mediate the increased risk of PTB caused by extreme heat. Monitoring and managing physiological changes in the fetus would constitute a promising avenue to reduce adverse birth outcomes associated with maternal heat exposure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Urban living is linked to better health outcomes due to a combination of enhanced access to healthcare, transportation, and human development opportunities. However, spatial inequalities lead to disparities, resulting in urban health advantages and penalties. Understanding the relationship between health and urban development is needed to generate empirical evidence in promoting healthy aging populations. This study provides a comparative analysis using epidemiological evidence across diverse major Chinese cities, examining how their unique urban development trajectories over time have impacted the health of their aging residents., Methods: We tracked changes in air pollution (NO 2 , PM 2.5 , O 3 ), green space (measured by NDVI), road infrastructure (ring road areas), and nighttime lighting over 20 years in six major cities in China. We followed a longitudinal cohort of 4992 elderly participants (average age 87.8 years) over 16,824 person-years. We employed Cox proportional hazard regression to assess longevity, assessing 14 variables, including age, sex, ethnicity, marital status, residence, household income, occupation, education, smoking, alcohol consumption, exercise, and points of interest (POI) count of medicine-related facilities, sports, and leisure service-related places, and scenic spots within a 5 km-radius buffer., Findings: Geographic proximity to points of interest significantly improves survival. Elderly living in proximity of the POI-rich areas had a 34.6%-35.6% lower mortality risk compared to those in POI-poor areas, for the highest compared to the lowest quartile. However, POI-rich areas had higher air pollution levels, including PM 2.5 and NO 2 , which was associated with a 21% and 10% increase in mortality risk for increase of 10 μg/m 3 , respectively. The benefits of urban living had higher effect estimates in monocentric cities, with clearly defined central areas, compared to polycentric layouts, with multiple satellite city centers., Interpretation: Spatial inequalities create urban health advantages for some and penalties for others. Proximity to public facilities and economic activities is associated with health benefits, and may counterbalance the negative health impacts of lower green space and higher air pollution. Our empirical evidence show optimal health gains for age-friendly urban environments come from a balance of infrastructure, points of interest, green spaces, and low air pollution., Funding: Natural Science Foundation of Beijing (IS23105), National Natural Science Foundation of China (82250610230, 72061137004), World Health Organization (2024/1463606-0), Research Fund Vanke School of Public Health Tsinghua University (2024JC002), Beijing TaiKang YiCai Public Welfare Foundation, National Key R&D Program of China (2018YFC2000400)., Competing Interests: We declare no competing interests., (© 2024 The Author(s).)

What Is Already Known About This Topic?: Antimony (Sb) has been identified as a new neurotoxicant that impacts neurological functions in animal studies. However, its effects on the human population remain unknown., What Is Added by This Report?: The study reveals that there is an association between exposure to Sb and a higher incidence of cognitive impairment in older adults. The dose-response curve demonstrates that the risk of cognitive impairment consistently increased with higher levels of Sb exposure without a discernible threshold., What Are the Implications for Public Health Practice?: Reducing exposure to Sb may have a beneficial effect in delaying or preventing the onset of cognitive impairment. This intervention has the potential to significantly decrease the disease burden associated with cognitive impairment, ultimately contributing to social development., Competing Interests: Xiaoming Shi is a editorial board member of the journal China CDC Weekly. He was not involved in the peer-review or handling of the manuscript. The authors have no other competing interests to disclose., (Copyright and License information: Editorial Office of CCDCW, Chinese Center for Disease Control and Prevention 2024.)

Neuroendocrine neoplasms (NENs) are highly heterogeneous and potentially malignant tumors arising from secretory cells of the neuroendocrine system. Gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs) are the most common subtype of NENs. Historically, GEP-NENs have been regarded as infrequent and slow-growing malignancies; however, recent data have demonstrated that the worldwide prevalence and incidence of GEP-NENs have increased exponentially over the last three decades. In addition, an increasing number of studies have proven that GEP-NENs result in a limited life expectancy. These findings suggested that the natural biology of GEP-NENs is more aggressive than commonly assumed. Therefore, there is an urgent need for advanced researches focusing on the diagnosis and management of patients with GEP-NENs. In this review, we have summarized the limitations and recent advancements in our comprehension of the epidemiology, clinical presentations, pathology, molecular biology, diagnosis, and treatment of GEP-NETs to identify factors contributing to delays in diagnosis and timely treatment of these patients., (© 2024. The Author(s).)

From the onset of coronavirus disease (COVID-19) pandemic, there are concerns regarding the disease spread and environmental pollution of biohazard since studies on genetic engineering flourish and numerous genetic materials were used such as the nucleic acid test of the severe acute respiratory syndrome coronavirus (SARS-CoV-2). In this work, we studied genetic material pollution in an institute during a development cycle of plasmid, one of typical genetic materials, with typical laboratory settings. The pollution source, transmission routes, and pollution levels in laboratory environment were examined. The Real-Time quantitative- Polymerase Chain Reaction results of all environmental mediums (surface, aerosol, and liquid) showed that a targeted DNA segment occurred along with routine experimental operations. Among the 79 surface and air samples collected in the genetic material operation, half of the environment samples (38 of 79) are positive for nucleic acid pollution. Persistent nucleic acid contaminations were observed in all tested laboratories and spread in the public area (hallway). The highest concentration for liquid and surface samples were 1.92 × 10 8 copies/uL and 5.22 × 10 7 copies/cm 2 , respectively. Significant amounts of the targeted gene (with a mean value of 74 copies/L) were detected in the indoor air of laboratories utilizing centrifuge devices, shaking tables, and cell homogenizers. Spills and improper disposal of plasmid products were primary sources of pollution. The importance of establishing designated experimental zones, employing advanced biosafety cabinets, and implementing highly efficient cleaning systems in laboratories with lower biosafety levels is underscored. SYNOPSIS: STATEMENT. Persistent environmental pollutions of genetic materials are introduced by typical experiments in laboratories with low biosafety level., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The role of transarterial chemoembolization (TACE) in the treatment of advanced hepatocellular carcinoma (HCC) is unconfirmed. This study aimed to assess the efficacy and safety of immune checkpoint inhibitors (ICIs) plus anti-vascular endothelial growth factor (anti-VEGF) antibody/tyrosine kinase inhibitors (TKIs) with or without TACE as first-line treatment for advanced HCC., Methods: This nationwide, multicenter, retrospective cohort study included advanced HCC patients receiving either TACE with ICIs plus anti-VEGF antibody/TKIs (TACE-ICI-VEGF) or only ICIs plus anti-VEGF antibody/TKIs (ICI-VEGF) from January 2018 to December 2022. The study design followed the target trial emulation framework with stabilized inverse probability of treatment weighting (sIPTW) to minimize biases. The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), and safety. The study is registered with ClinicalTrials.gov, NCT05332821., Findings: Among 1244 patients included in the analysis, 802 (64.5%) patients received TACE-ICI-VEGF treatment, and 442 (35.5%) patients received ICI-VEGF treatment. The median follow-up time was 21.1 months and 20.6 months, respectively. Post-application of sIPTW, baseline characteristics were well-balanced between the two groups. TACE-ICI-VEGF group exhibited a significantly improved median OS (22.6 months [95% CI: 21.2-23.9] vs 15.9 months [14.9-17.8]; P < 0.0001; adjusted hazard ratio [aHR] 0.63 [95% CI: 0.53-0.75]). Median PFS was also longer in TACE-ICI-VEGF group (9.9 months [9.1-10.6] vs 7.4 months [6.7-8.5]; P < 0.0001; aHR 0.74 [0.65-0.85]) per Response Evaluation Criteria in Solid Tumours (RECIST) version 1.1. A higher ORR was observed in TACE-ICI-VEGF group, by either RECIST v1.1 or modified RECIST (41.2% vs 22.9%, P < 0.0001; 47.3% vs 29.7%, P < 0.0001). Grade ≥3 adverse events occurred in 178 patients (22.2%) in TACE-ICI-VEGF group and 80 patients (18.1%) in ICI-VEGF group., Interpretation: This multicenter study supports the use of TACE combined with ICIs and anti-VEGF antibody/TKIs as first-line treatment for advanced HCC, demonstrating an acceptable safety profile., Funding: National Natural Science Foundation of China, National Key Research and Development Program of China, Jiangsu Provincial Medical Innovation Center, Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions, and Nanjing Life Health Science and Technology Project., Competing Interests: We declare no competing interests., (© 2024 Published by Elsevier Ltd.)

Aging populations are susceptible to heat-related mortality because of physiological factors and comorbidities. However, the understanding of individual vulnerabilities in the aging population is incomplete. In the Chinese Longitudinal Healthy Longevity Survey, we assessed daily heatwave exposure individually for 13,527 participants (median age = 89 years) and 3,249 summer mortalities during follow-up from 2008 to 2018. The mortality risk during heatwave days according to relative temperature is approximately doubled (hazard ratio (HR) range = 1.78-1.98). We found that heatwave mortality risks were increased for individuals with functional declines in mobility (HR range = 2.32-3.20), dependency in activities of daily living (HR range = 2.22-3.27), cognitive impairment (HR = 2.22) and social isolation reflected by having nobody to ask for help during difficulties (HR range = 2.14-10.21). Contrary to current understanding, older age was not predictive of heatwave mortality risk after accounting for individual functional declines; no statistical differences were detected according to sex. Beyond age as a risk factor, our findings emphasize that functional aging is an underlying factor in enhancing heatwave resilience. Assessment of functional decline and implementing care strategies are crucial for targeted prevention of mortality during heatwaves., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

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.

Immunotherapy is the most promising systemic therapy for hepatocellular carcinoma. However, the outcome remains poor. Proprotein convertase subtilisin/kexin type 9 (PCSK9) plays a role in altering cell-surface protein levels, potentially undermining the efficacy of immunotherapy against tumors. This highlights its potential as a target for antitumor therapy. Herein, CaCO 3 -based nanoparticles coencapsulated with DOX, an immunogenic cell death (ICD) inducer, and evolocumab was developed to enhanced the efficacy of immunotherapy. The obtained DOX/evolocumab-loaded CaCO 3 nanoparticle (named DECP) exhibits a good capacity of acid neutralization and causes ICD of cancer cells. In addition, DECP is able to evaluate the cell-surface level of MHC-I, a biomarker that correlates positively with patients' overall survival. Upon intravenous injection, DECP accumulates within the tumor site, leading to growth inhibition of hepa1-6 bearing subcutaneous tumors. Specifically, DECP treatment causes augmented ratios of matured dendritic cells, tumor-infiltrating CD8 + T cells and natural killing cells, while concurrently depleting Foxp3 + regulatory T cells. Peritumoral delivery of DECP enhances the immune response of distant tumors and exhibits antitumor effects when combined with intravenous αPD-L1 therapy in a bilateral tumor model. This study presents CaCO 3 -based nanoparticles with multiple immunomodulatory strategies against hepatocellular carcinoma by targeting PCSK9 inhibition and modulating immune homeostasis in the unfavorable TME.

Background: Sarcopenic obesity, a clinical and functional condition characterized by the coexistence of obesity and sarcopenia, has not been investigated in relation to dementia risk and its onset., Methods: We included 208,867 participants from UK biobank, who aged 60 to 69 years at baseline. Dementia diagnoses were identified using hospital records and death register data. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models to evaluate the associations of obesity, sarcopenia, and sarcopenic obesity with dementia risk, stratified by sex. Stratified analyses were performed across dementia-related polygenic risk score (PRS). Restricted mean survival time models were established to estimate the difference and 95%CIs of dementia onset across different status. Additionally, linear regression models were employed to estimate associations of different status with brain imaging parameters. The mediation effects of chronic diseases were also examined., Results: Obese women with high PRS had a decreased risk (HR = 0.855 [0.761-0.961]), but obese men with low PRS had an increased risk (HR = 1.223 [1.045-1.431]). Additionally, sarcopenia was associated with elevated dementia risk (HR women = 1.323 [1.064-1.644]; HR men = 2.144 [1.753-2.621]) in those with low PRS. Among those with high PRS, however, the association was only significant in early-life (HR women = 1.679 [1.355-2.081]; HR men = 2.069 [1.656-2.585]). Of note, sarcopenic obesity was associated with higher dementia risk (HR women = 1.424 [1.227-1.653]; HR men = 1.989 [1.702-2.323]), and results remained similar stratified by PRS. Considering dementia onset, obesity was associated with dementia by 1.114 years delayed in women, however, 0.170 years advanced in men. Sarcopenia (women: 0.080 years; men: 0.192 years) and sarcopenic obesity (women: 0.109 years; men: 0.511 years) respectively advanced dementia onset. Obesity, sarcopenia, and sarcopenic obesity were respectively related to alterations in different brain regions. Association between sarcopenic obesity and dementia was mediated by chronic diseases., Conclusions: Sarcopenic obesity and sarcopenia were respectively associated with increased dementia risk and advanced dementia onset to vary degree. The role of obesity in dementia may differ by sex and genetic background., (© 2024. The Author(s).)

Purpose: Acknowledging the associated risk factors may have a positive impact on reducing the incidence of ectopic pregnancy (EP). In recent years, body mass index (BMI) has been mentioned in research. However, few studies are available and controversial on the relationship between EP and BMI., Methods: We retrospectively studied the EP women as a case group and the deliveries as a control group in the central hospital of Wuhan during 2017 ~ 2021. χ 2 test of variables associated with ectopic pregnancy was performed to find differences. Univariate and multivariate binary logistic regression analysis was conducted to analyze the association of the variables of age, parity, history of induced abortion, history of ectopic pregnancy, history of spontaneous abortion, history of appendectomy surgery and BMI (< 18.5 kg/m 2 , 18.5 ~ 24.9 kg/m 2 , 25 kg/m 2  ~ 29.9 kg/m 2 , ≥ 30 kg /m 2 ) with EP., Results: They were 659 EP and 1460 deliveries. The variables of age, parity, history of induced abortion, history of ectopic pregnancy and BMI were different significantly(P < 0.05). Multivariate analysis showed that the variables of age > 35 years old [(OR (Odds Ratio), 5.415; 95%CI (Confidence Interval), 4.006 ~ 7.320, P < 0.001], history of ectopic pregnancy (OR, 3.944; 95%CI, 2.405 ~ 6.467; P < 0.001), history of induced abortion(OR, 3.365; 95%CI, 2.724 ~ 4.158, P < 0.001) and low BMI (< 18.5 kg/m 2 ) (OR, 1.929; 95%CI, 1.416 ~ 2.628, P < 0.001])increased the risk of EP., Conclusion: The history of ectopic pregnancy, history of induced abortion and age > 35 years old were the risk factors with EP. In addition to these traditional factors, we found low BMI (< 18.5 kg/m 2 ) with women may increase the risk to EP., (© 2024. The Author(s).)

Importance: In China, parental labor migration often leaves children behind and is potentially adversely associated with children's health. However, the association between parental migration and aggression among their offspring remains largely underexplored., Objective: To investigate the associations of parental labor migration with total and subtypes of aggression among their offspring as well as potential sex differences therein., Design, Setting, and Participants: This cross-sectional study was conducted from February to October 2015 among students aged 11 to 20 years from 45 public middle and high schools across 5 provinces of China. Data analysis was performed from December 1, 2022, to August 1, 2023., Exposures: Parental migration, including migration status (yes or no), pattern (father, mother, or both), and the child's age at the initial parent-child separation., Main Outcomes and Measures: Total and subtypes of aggression (including physical aggression [PA], verbal aggression [VA], indirect aggression [IA], anger, and hostility) were measured using the Chinese version of the Buss-Warren Aggression Questionnaire. Binomial logistic regression analyses were used separately to estimate adjusted odds ratios (aORs) and 95% CIs of parental migration by total and subtypes of aggression., Results: A total of 15 301 participants (7900 [51.6%] male and 7401 [48.4%] female) aged 11 to 20 years (mean [SD] age, 15.1 [1.8] years) were included. Of these participants, 5961 (39.0%) experienced parental migration; 2451 (16.0%) met the criteria for total aggression, 2407 (15.7%) for PA, 2283 (14.9%) for VA, 2899 (18.9%) for IA, 2307 (15.1%) for anger, and 2564 (16.8%) for hostility. Parental migration was associated with total aggression (aOR, 1.11; 95% CI, 1.01-1.22); no significant association between parental migration and subtypes of aggression was found except for PA (aOR, 1.14; 95% CI, 1.03-1.25). Compared with children whose parents did not migrate, the aORs for total aggression and PA for participants whose father migrated were 1.12 (95% CI, 1.01-1.28) and 1.15 (95% CI, 1.03-1.29), respectively; for participants with both parents having migrated, the aORs were 1.16 (95% CI, 1.02-1.31) and 1.12 (95% CI, 1.04-1.24), respectively. Compared with children whose parents did not migrate, children who experienced initial separation from 1 or both parents at adolescence had an aOR for total aggression of 1.20 (95% CI, 1.04-1.36), children who experienced initial separation from 1 or both parents at school age or adolescence had an aOR for PA of 1.15 (95% CI, 1.01-1.32) and 1.26 (95% CI, 1.04-1.51), respectively. No sex differences were found in these associations., Conclusions and Relevance: In this cross-sectional study of Chinese children and adolescents, we found that parental migration, mainly of the father or both parents or an initial separation at adolescence or school age from 1 or both parents, was associated with higher odds of total aggression and PA among offspring. These associations were similar between male and female participants.

Objective: The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach. Methods: Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis. Results: A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score ( r = 0.47, P = 0.002), albumin-bilirubin score ( r = 0.37, P = 0.001), Lok index ( r = 0.36, P = 0.02), liver stiffness ( r = 0.58, P = 0.01), and spleen stiffness ( r = 0.77, P = 0.01), while negatively correlated with albumin ( r = -0.42, P = 0.006). Conclusion: The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

Competing Interests: Declaration of interests We declare no competing interests.

Climate change is expected to increase occupational heat stress, which will lead to diminished work performance and labor losses worldwide. However, sub-regional analyses remain insufficient, especially for countries with a heterogeneous spatial distribution of working populations, industries and climates. Here, we projected heat-induced labor losses in China, by considering local climate simulations, working population characteristics and developing an exposure-response function suitable for Chinese workers. We showed that the annual heat-induced work hours lost (WHL), compared to the baseline of 21.3 billion hours, will increase by 121.1% (111.2%-131.1%), 10.8% (8.3%-15.3%), and -17.8% (-15.3%--20.3%) by the end of the century under RCP(Representative Concentration Pathways)8.5, RCP4.5, and RCP2.6, respectively. We observed an approximately linear upward trend of WHL under RCP8.5, despite the decrease in future working population. Notably, WHL will be most prominent in the southern, eastern and central regions, with Guangdong and Henan accounting for a quarter of national total losses; this is largely due to their higher temperature exposure, larger population size, and higher shares of vulnerable population in total employment. In addition, limiting global warming to 1.5 °C would yield substantial gains. Compared to RCP2.6, RCP4.5, and RCP8.5, all provinces can avoid an average of 11.8%, 33.7%, and 53.9% of annual WHL if the 1.5 °C target is achieved, which is equivalent to avoiding 0.1%, 0.6%, and 1.4% of annual GDP losses in China, respectively. This study revealed climate change will exacerbate future labor losses, and adverse impacts can be minimized by adopting stringent mitigation policies coupled with effective adaptation measures. Policymakers in each province should tailor occupation health protection measures to their circumstances., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest., (Copyright © 2023 Science China Press. Published by Elsevier B.V. All rights reserved.)

China's health gains over the past decades face potential reversals if climate change adaptation is not prioritized. China's temperature rise surpasses the global average due to urban heat islands and ecological changes, and demands urgent actions to safeguard public health. Effective adaptation need to consider China's urbanization trends, underlying non-communicable diseases, an aging population, and future pandemic threats. Climate change adaptation initiatives and strategies include urban green space, healthy indoor environments, spatial planning for cities, advance location-specific early warning systems for extreme weather events, and a holistic approach for linking carbon neutrality to health co-benefits. Innovation and technology uptake is a crucial opportunity. China's successful climate adaptation can foster international collaboration regionally and beyond., Competing Interests: Authors declare no competing interests., (© 2023 The Authors.)

The winter heating policy in northern China was designed to safeguard households from the harsh subfreezing temperatures. However, it has inadvertently resulted in seasonal spikes in air pollution levels because of the reliance on coal as an energy source. While the loss of life years attributable to mortality from air pollution caused by winter heating has been estimated, the beneficial effect of protection from cold temperatures has not been assessed, primarily due to a lack of individual-level data linking these variables. Our study aims to address this research gap. We provide individual-level empirical evidence that quantifies the impact of protection from cold temperatures and air pollution on mortality, studying 5,334 older adults living around the Huai River during the period between 2000 and 2018. Our adjusted Cox-proportional hazard models show that winter heating was associated with a 22% lower mortality rate (95% CI: 16-28%). Individuals residing in areas without access to winter heating are subjected to heightened mortality risks during periods of cold temperatures. The protective effect is offset by a 27.8% rise attributed to elevated PM 2.5 levels. Our results imply that the equilibrium between the effects of these two factors is achieved when PM 2.5 concentration exceeds 24.3 µg/m 3 (95% CI: 18.4-30.2). Our research suggests that while the existing winter heating policy significantly mitigates winter mortality by lessening the detrimental effects of cold temperatures, future air pollution reduction could provide further health benefits., (© The Author(s) 2023. Published by Oxford University Press on behalf of National Academy of Sciences.)

We aimed to report real-world longitudinal ambient air pollutants levels compared to WHO Air Quality Guidelines (AQG) and analyze multiple air pollutants' joint effect on longevity, and the modification and confounding from the climate and urbanization with a focus on the oldest-old. This study included 13,207 old participants with 73.3% aged 80 and beyond, followed up from 2008 to 2018 in 23 Chinese provinces. We used the Cox-proportional hazards model and quantile-based g-computation model to measure separate and joint effects of the multiple pollutants. We adjusted for climate and area economic factors based on a directed acyclic graph. In 2018, no participants met the WHO AQG for PM 2.5 and O 3 , and about one-third met the AQG for NO 2 . The hazard ratio (HR) for mortality was 1.07 (95% confidence interval-CI: 1.05, 1.09) per decile increase in all three pollutants, with PM 2.5 being the dominant contributor according to the quantile-based g-computation model. In the three-pollutant model, the HRs (95% CI) for PM 2.5 and NO 2 were 1.27 (1.25, 1.3) and 1.08 (1.05, 1.12) per 10 μg/m 3 increase, respectively. The oldest-old experienced a much lower mortality risk from air pollution compared to the young-old. The mortality risk of PM 2.5 was higher in areas with higher annual average temperatures. The adjustment of road density considerably intensified the association between NO 2 and mortality. The ambient PM 2.5 and O 3 levels in China exceeded the WHO AQG target substantially. Multiple pollutants coexposure, confounding, and modification of the district economic and climate factors should not be ignored in the association between air pollution and mortality., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Co-published by Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, and American Chemical Society.)

Background: High-level exposure to indoor air pollutants (IAPs) and their corresponding adverse health effects have become a public concern in China in the past 10 years. However, neither national nor provincial level burden of disease attributable to multiple IAPs has been reported for China. This is the first study to estimate and rank the annual burden of disease and the financial costs attributable to targeted residential IAPs at the national and provincial level in China from 2000 to 2017., Methods: We first did a systematic review and meta-analysis of 117 articles from 37 231 articles identified in major databases, and obtained exposure-response relationships for the candidate IAPs. The exposure levels to these IAPs were then collected by another systematic review of 1864 articles selected from 52 351 articles. After the systematic review, ten IAPs with significant and robust exposure-response relationships and sufficient exposure data were finally targeted: PM 2·5 , nitrogen dioxide, sulphur dioxide, ozone, carbon monoxide, radon, formaldehyde, benzene, toluene, and p-dichlorobenzene. The annual exposure levels in residences were then evaluated in all 31 provinces in mainland China continuously from 2000 to 2017, using the spatiotemporal Gaussian process regression model to analyse indoor originating IAPs, and the infiltration factor method to analyse outdoor originating IAPs. The disability-adjusted life-years (DALYs) attributable to the targeted IAPs were estimated at both national and provincial levels in China, using the population attributable fraction method. Financial costs were estimated by an adapted human capital approach., Findings: From 2000 to 2017, annual DALYs attributable to the ten IAPs in mainland China decreased from 4620 (95% CI 4070-5040) to 3700 (3210-4090) per 100 000. Nevertheless, in 2017, IAPs still ranked third among all risk factors, and their DALYs and financial costs accounted for 14·1% (95% CI 12·3-15·6) of total DALYs and 3·45% (3·01-3·82) of the gross domestic product. Specifically, the rank of ten targeted IAPs in order of their contribution to DALYs in 2017 was PM 2·5 , carbon monoxide, radon, benzene, nitrogen dioxide, ozone, sulphur dioxide, formaldehyde, toluene, and p-dichlorobenzene. The DALYs attributable to IAPs were 9·50% higher than those attributable to outdoor air pollution in 2017. For the leading IAP, PM 2·5 , the DALYs attributable to indoor origins are 18·3% higher than those of outdoor origins., Interpretation: DALYs attributed to IAPs in China have decreased by 20·0% over the past two decades. Even so, they are still much higher than those in the USA and European countries. This study can provide a basis for determining which IAPs to target in various indoor air quality standards and for estimating the health and economic benefits of various indoor air quality control approaches, which will help to reduce the adverse health effects of IAPs in China., Funding: The National Key Research and Development Program of China and the National Natural Science Foundation of China., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

The emerging Metaverse will likely increase time expenditure in indoor virtual environments, which could impact human health and well-being. The biophilia hypothesis suggests that humans have an innate tendency to seek connections with the natural world and there is increasing evidence that biophilic design such as the incorporation of green plants can yield health benefits. Recently, virtual reality (VR) has been used to regulate stress and improve overall wellness, particularly by incorporating natural settings. In this randomized crossover study, we designed five virtual classroom scenes with different biophilic elements and turbidity in VR and investigated whether the visual stimulations can affect the stress levels and cognitive functions of 30 young adults from a university in China. We measured their physiological indicators of stress reaction by wearable biomonitoring sensors (blood pressure (BP), heart rate (HR), heart rate variability (HRV), and skin conductance level (SCL)), conducted verbal cognitive tests on attention and creativity, and evaluated subjective/perceived (self-reported) stress levels and connection with nature. Albeit our results suggested no significant change in physiological stress reactions or cognitive functions induced by the biophilic and turbid interventions in VR, the addition of biophilic elements in the Metaverse could benefit students' health due to significantly decreased perceived stress levels and increased connections with nature., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 You et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Atmospheric chemistry studies suggest air pollution impedes ultraviolet B photons and thus reduces cutaneous vitamin D 3 synthesis. Biological evidence shows that inhaled pollutants disrupt circulating 25-hydroxyvitamin D (25[OH]D) metabolism and ultimately impact bone health. The hypothesis is that higher air pollution concentrations are associated with a higher risk of fractures, mediated by lower circulating 25(OH)D. The study included participants of the UK Biobank who were free of fracture history at enrollment (2006 to 2010) and analyzed their environmental exposure data (2007 to 2010). Air pollution measurements included the annual averages of air particulate matter (PM 2.5 , PM 2.5-10 , and PM 10 ), nitrogen oxides (NO 2 and NO x ), and a composite air pollution score. Multivariable Cox proportional hazard models were used to assess the associations of the individual pollutants and the score with fracture risks. Mediation analyses were conducted to assess the underlying role of serum 25(OH)D in such associations. Among 446,395 participants with a median of 8-year follow-up, 12,288 incident fractures were documented. Participants living in places with the highest quintile of air pollution score had a 15.3% increased risk of fractures (hazard ratio [95%CI]: 1.15[1.09,1.22]) compared to those in the lowest, and 5.49% of this association was mediated through serum 25(OH)D (p mediation  < 0.05). Pollutant-specific hazard of top-to-bottom quintiles was 16% for PM 2.5 , 4% for PM 2.5-10 , 5% for PM 10 , 20% for NO 2 , and 17% for NO x , with a 4% to 6% mediation effect of serum 25(OH)D concentrations. The associations of the air pollution score with fracture risks were weaker among female participants, those who drank less alcohol, and consumed more fresh fruit than their counterparts (p interaction  < 0.05). © 2023 American Society for Bone and Mineral Research (ASBMR)., (© 2023 American Society for Bone and Mineral Research (ASBMR).)

Association of greenness surrounding school with aggression among adolescents was not well understood. This study aimed to investigate the associations of greenness surrounding school with adolescents' total and sub-types of aggression and explore potential mediators underlying these associations. A multi-site study of 15,301 adolescents aged 11-20 years were recruited through a multistage, random cluster sampling across 5 representative provinces in mainland China. Satellite-derived Normalized Difference Vegetation Index (NDVI) values within circular buffers of 100 m, 500 m, and 1000 m surrounding school were used to indicate the adolescents' greenness exposure. We used the Chinese version of Buss and Warren's Aggression Questionnaire to assess total and sub-types of aggression. Daily concentrations of PM 2.5, and NO 2 were obtained from the China High Air Pollutants datasets. Per IQR increment of NDVI 100 m and 500 m surrounding school was associated with lower odds of total aggression; odds ratio [OR] with 95% CI was 0.958 (0.926-0.990) for the 100 m buffer and 0.963 (0.932-0.996) for the 500 m buffer, respectively. Similar associations can be observed in two sub-types of aggression, including verbal (NDVI 100 m: 0.960 (0.925-0.995); NDVI500m: 0.964 (0.930-0.999)) and indirect aggression (NDVI 100 m: 0.956 (0.924-0.990); NDVI500m: 0.953 (0.921-0.986)). There were no sex and age differences in the associations of school surrounding greenness with aggression, except that the beneficial associations of greenness exposure with total aggression (0.933(0.895-0.975) vs.1.005(0.956-1.056)), physical aggression (0.971(0.925-1.019) vs.1.098(1.043-1.156)), and hostility (0.942(0.901-0.986) vs.1.016(0.965-1.069)) were greater among participants aged ≥16 years than those aged<16 years. PM 2.5 (proportion mediated estimates: 0.21; 95% CI: 0.08, 0.94) and NO 2 (-0.78, 95% CI: -3.22, -0.37) mediated the association of NDVI 500 m surrounding school with total aggression. Our data indicated that exposure to greenness in school surroundings was associated with reduced aggression, particularly in verbal and indirect aggression. The presence of PM 2.5 and NO 2 partially mediated these associations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The two-signal model of T cell activation has helped shape our understanding of the adaptive immune response for over four decades. According to the model, activation of T cells requires a stimulus through the T cell receptor/CD3 complex (signal 1) and a costimulatory signal 2. Stimulation of activatory signals via T cell agonists has thus emerged. However, for a robust T cell activation, it necessitates not only the presence of both signal 1 and signal 2, but also a high signaling strength. Herein, we report a photo-activable nano-agonist for the two-signal model of T cell in vivo activation. A UV-crosslinkable polymer is coated onto upconversion nanoparticles with satisfactory NIR-to-UV light conversion efficiency. Then dual signal molecules, i.e., signal 1 and signal 2, are conjugated to the polymer end to yield the photo-activable T cell nano-agonist. In melanoma and breast cancer models, photo-activable nano-agonist could bind onto corresponding activatory receptors on the surface of T cells, but has limited activity without the application of NIR light (absence of photo-crosslinking of receptors and consequently a poor signaling strength). While when the NIR light is switched on locally, T cells in tumor are remarkably activated and kill tumor cells effectively. Moreover, we do not observe any detectable toxicities related to the photo-activable nano-agonist. We believe with two activatory signals being simultaneously strengthened by local photo-switched crosslinking, T cells realize a robust and selective activation in tumor and, consequently contribute to an enhanced and safe tumor immunotherapy., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Current guidelines recommend hepatocellular carcinoma (HCC) surveillance for at-risk individuals, including individuals with hepatitis B virus infection. However, the performance and survival benefits of annual screening have not been evaluated through multicenter prospective studies in a Chinese population. Between 2017 and 2021, we included 14,426 participants with hepatitis B surface antigen seropositivity in an annual HCC screening study in China using a multicenter prospective design with ultrasonography and serum alpha-fetoprotein. After four rounds of screening and follow-up, the adjusted hazard ratios of death after correction for lead-time and length-time biases for screen-detected cancers at the prevalent and incident rounds were 0.74 (95% confidence interval = 0.60-0.91) and 0.52 (95% confidence interval = 0.40-0.68), respectively. A meta-analysis demonstrated that HCC screening was associated with improved survival after adjusting for lead-time bias. Our findings highlight the 'real-world' feasibility and effectiveness of annual HCC screening in community settings for the early detection of HCC and to improve survival., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Skin wounds are characterized by injury to the skin due to trauma, tearing, cuts, or contusions. As such injuries are common to all human groups, they may at times represent a serious socioeconomic burden. Currently, increasing numbers of studies have focused on the role of mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) in skin wound repair. As a cell-free therapy, MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy. Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures, including the regeneration of vessels, nerves, and hair follicles. In addition, MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization, wound angiogenesis, cell proliferation, and cell migration, and by inhibiting excessive extracellular matrix production. Additionally, these structures can serve as a scaffold for components used in wound repair, and they can be developed into bioengineered EVs to support trauma repair. Through the formulation of standardized culture, isolation, purification, and drug delivery strategies, exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair. In conclusion, MSC-derived EVs-based therapies have important application prospects in wound repair. Here we provide a comprehensive overview of their current status, application potential, and associated drawbacks., (© 2023. People´s Military Medical Press.)

Background: Racial/ethnic disparities in prostate cancer are reported in the United States (US). However, long-term trends and contributors of racial/ethnic disparities in all-cause and cause-specific death among patients with prostate cancer remain unclear. We analysed the trends and contributors of racial/ethnic disparities in prostate cancer survivors according to the cause of death in the US over 25 years., Methods: In this retrospective, population-based longitudinal cohort study, we identified patients diagnosed with first primary prostate cancer between 1995 and 2019, with follow-up until Dec 31, 2019, using population-based cancer registries' data from the Surveillance, Epidemiology, and End Results (SEER) Program. We calculated the cumulative incidence of death for each racial/ethnic group (Black, white, Hispanic, Asian or Pacific Islander [API], and American Indian or Alaska Native [AI/AN] people), by diagnostic period and cause of death. We quantified absolute disparities using rate changes for the 5-year cumulative incidence of death between racial/ethnic groups and diagnostic periods. We estimated relative (Hazard ratios [HR]) racial/ethnic disparities and the percentage of potential factors contributed to racial/ethnic disparities using Cox regression models., Findings: Despite a decreasing trend in the cumulative risk of death across five racial/ethnic groups, AI/AN and Black patients consistently had the highest rate of death between 1995 and 2019 with an adjusted HR of 1.48 (1.40-1.58) and 1.40 (1.38-1.42) respectively. The disparities in all-cause mortality between AI/AN and white patients increased over time, with adjusted HR 1.32 (1.17-1.49) in 1995-1999 and 1.95 (1.53-2.49) in 2015-2019. Adjustment of stage at diagnosis, initial treatment, tumor grade, and household income explained 33% and 24% of the AI/AN-white and Black-white disparities in all-cause death among patients with prostate cancer., Interpretation: The enduring racial/ethnic disparities in patients with prostate cancer, call for new interventions to eliminate health disparities. Our study provides important evidence and ways to address racial/ethnic inequality., Funding: National Key R&D Program of China, National Natural Science Foundation of China, Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support, the Open Research Fund from Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Key Projects of Philosophy and Social Sciences Research, Ministry of Education of China., Competing Interests: We declare no competing interests., (© 2023 The Author(s).)

Due to a combination of lifestyle risk factors, the burden of cardiovascular disease (CVD) has been increasing in China, affecting an estimated 330 million people. Environmental risk factors can exacerbate these risks or independently contribute to CVD. Ozone is an overlooked and invisible risk factor, and it plays a significant role in the development of CVD. Our study provides a novel quantification of the ozone-attributable CVD mortality burden based on daily maximum 8-h average ozone concentration during May to October (6mDMA8) in Chinese adults in 2050, projected under Shared Socioeconomic Pathways 585 and 126, and using the updated WHO air quality guideline level. The study also considers the contributions made by changes in ozone exposure, population aging, population size, and baseline death rates of CVD between 2019 and 2050. While adopting a sustainable and green pathway (SSP 126) can reduce the projected magnitude of premature CVD deaths to 359,200 in 2050, it may not be sufficient to reduce the CVD mortality burden significantly. Therefore, it is crucial to implement strategies for stricter ozone control and reducing the baseline death rate of CVD to mitigate the impacts of ozone on Chinese adults.

Background: Future climate change is likely to alter cold spell-related disease burden. Few projection studies have considered the potential impact of the aging population with changing population size on cold spell-related disease burdens., Methods: We derived the association between cold spells and daily mortality for 272 main cities in mainland China. We combined these associations with modeled daily temperatures from three different climate models under two climate change scenarios and three population scenarios to project excess deaths related to cold spells. Furthermore, we used the factor separation method to calculate the independent contribution of future population size, age structure, and climate change on projected deaths attributable to cold spells., Findings: Compared to the baseline period, future excess deaths related to cold spells are expected to increase over most of the decades under RCP 2.6 (81.5% in 2050 s and 37% in 2090 s) and RCP 4.5 (55.5% in 2050 s and -19% in 2090 s). The factor analysis indicated that the rise of the aged population (≥65) substantially would amplify the excess deaths related to cold spells (increase by 101.1% in the 2050 s and 146.2% in the 2090 s). For the near future (2021-2040), population aging could fully offset the influence of decreased cold-spell days. In the middle of this century (2051-2070), the total excess deaths will exhibit significant variation across three scenarios. By the end of 21 century (2081-2100), the population shrinking would reduce the total excess deaths., Interpretation: Excess deaths related to cold spells may still increase in a warming climate and future demographic shifts would produce considerable influences in this increase for different periods., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Subjective well-being (SWB) measures mental health and happiness. Greenspace can have a positive impact on mental health, and higher SWB is associated with lower all-cause mortality. We conducted a mediation analysis on greenspace and all-cause mortality through improving SWB, in a prospective cohort of Chinese older adults., Methods: We included older adults over 65 from the 2008-2014 Chinese Longitudinal Healthy Longevity Survey (CLHLS). We used satellite-derived normalized difference vegetation index (NDVI) to measure greenspaces and calculated SWB measured by eight items. Three main statistical approaches were used. First, we used generalized estimating equations (GEE) and Cox proportional hazard models to examine NDVI-SWB and SWB-mortality relationships. Second, we conducted a causal mediation analysis to investigate the mediating effect of greenspace on all-cause mortality through SWB. Third, we conducted subgroup analyses to discover effect modification., Findings: Among 13,133 participants, the mean SWB score and NDVI in 2008 were 28·9 (SD 4·34) and 0·41 (SD 0·14), respectively. We found SWB partially mediated the relationship between residential greenspace and mortality in the adjusted model (average causal mediation effect = 0·11, p = 0·04; average direct effect = 1·96, p < 0·001; total effect = 2·07, p < 0·001) with varying proportions in subgroups. The protective influence was more evident for people with impaired cognitive function, living in rural areas and towns, and with lower income., Interpretation: We found a positive association between greenspace, SWB, and mortality. Greenness in the living environment confers better mental health and promotes longevity in the elderly population., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Heat events increase the risk of preterm birth (PTB), and identifying the risk-related event thresholds contributes to developing early warning system for pregnant women and guiding their public health response. However, the event thresholds that cause the risk remain unclear. We aimed to investigate the effects of heat events defined with different intensities and durations on PTB throughout pregnancy, and to determine thresholds for the high-risk heat events., Methods: Using a population-based birth cohort data, we included 210,798 singleton live births in eight provinces in China during 2014-2018. Daily meteorological variables and inverse distance weighted methods were used to estimate exposures at a resolution of 1 km × 1 km. A series of cut off temperature intensities (50th-97.5th percentiles, or 18 °C-35 °C) and durations (at least 1, 2, 3, 4 or 5 consecutive days) were used to define the heat events. Cox regression models were used to estimate the effects of heat events on PTB in various gestational weeks during the entire pregnancy, and event thresholds were determined by calculating population attributable fractions., Findings: The hazard ratios of heat event exposure on PTB ranged from 1.07 (95% CI: 1.00, 1.13) to 1.43 (1.15, 1.77). Adverse effects of heat event exposure were prominently detected in gestational week 1-4, week 21-32 and the four weeks before delivery. The heat event thresholds were determined to be daily maximum temperature at the 90th percentile of the distribution or 30 °C lasting for at least one day. If pregnant women were able to avoid the heat exposures from the early warning systems triggered by these thresholds, approximately 15% or 17% of the number of total PTB cases could have been avoided., Interpretation: Exposure to heat event can increase the risk of PTB when thermal event exceeds a specific intensity and duration threshold, particularly in the first four gestational weeks, and between week 21 and the last four weeks. This study provides compelling evidence for the development of heat-health early warning systems for pregnant women that could substantially mitigate the risk of PTB., Funding: National Key R&D Program of China (No. 2018YFA0606200), National Natural Science Foundation of China (No. 42175183), Sanming Project of Medicine in Shenzhen (No. SZSM202111001)., Competing Interests: The authors declare no competing interests., (© 2023 The Author(s).)