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health benefits from the rapid reduction in ambient exposure to air pollutants after China's clean air actions:progress in efficacy and geographic equality

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National science Review 2024年第2期11卷 103-113页

作者： Tao Xue Ruohan Wang Meng Wang Yanying Wang Dan Tong Xia Meng Conghong Huang Siqi Ai Fangzhou Li Jingyuan Cao Mingkun Tong Xueqiu Ni Hengyi Liu Jianyu Deng Hong Lu Wei Wan Jicheng Gong Shiqiu Zhang Tong Zhu Clean Air Asia Institute of Reproductive and Child health National Health Commission Key Laboratory of Reproductive Health/Department of Epidemiology and Biostatistics Ministry of Education Key Laboratory of Epidemiology of Major Diseases(PKU) School of Public Health Peking University Health Science Centre State Environmental Protection Key Laboratory of Atmospheric Exposure and Health Risk Management and Center for Environment and Health Peking University Advanced Institute of Information Technology Peking University Department of Epidemiology and Environmental health School of Public Health and Health ProfessionsUniversity at Buffalo State Key Joint Laboratory of Environment Simulation and Pollution Control College of Environmental Sciences and EngineeringPeking University Department of Earth System science Tsinghua University School of Public health Key Laboratory of Public Health Safety of the Ministry of Education and Key Laboratory of Health Technology Assessment of the Ministry of HealthFudan University College of Land Management Nanjing Agricultural University National&Local Joint Engineering Research Center for Rural Land Resources Use and Consolidation

Clean air actions （CAAs） in China have been linked to considerable benefits in public health.However,whether the beneficial effects of CAAs are equally distributed geographically is unknown.Using high-resolution maps of the distributions of major air pollutants (fine particulate matter[PM2.5]and ozone[O3]) and population,we aimed to track spatiotemporal changes in health impacts from,and geographic inequality embedded in,the reduced exposures to PM2.5and O3from 2013 to 2020.We used a method established by the Global Burden of Diseases Study.By analyzing the changes in loss of life expectancy（LLE） attributable to PM2.5and O3,we calculated the gain of life expectancy （GLE） to quantify the health benefits of the air-quality improvement.Finally,we assessed the geographic inequality embedded in the GLE using the Gini index （GI）.Based on risk assessments of PM2.5and O3,during the first stage of CAAs（2013 to 2017）,the mean GLE was 1.87 months.Half of the sum of the GLE was disproportionally distributed in about one quarter of the population exposed （GI 0.44）.During the second stage of CAAs（2017 to 2020）,the mean GLE increased to 3.94 months and geographic inequality decreased （GI 0.18）.According to our assessments,CAAs were enhanced,from the first to second stages,in terms of not only preventing premature mortality but also ameliorating health inequalities.The enhancements were related to increased sensitivity to the health effects of air pollution and synergic control of PM2.5and O3levels.Our findings will contribute to optimizing future CAAs.

关键词： clean air action public health inequality fine particulate matter ozone

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Interaction between antigen presenting cells and autoreactive T cells derived from BXSB mice with murine lupus

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Cell Research 2007年第6期17卷 556-564页

作者： Peng Yang Bo Li Ping Lv Yan Zhang Xiao-Ming Gao, Department of Immunology, Peking University health science center, Peking University, 38 Xueyuan Rd, Beijing 100083, China Department of Immunology Peking University Health Science Center Peking University Beijing China

Systemic lupus erythematosus (SLE) is a typical autoimmune disease involving multiple systems and organs. Ampleevidence suggests that autoreactive T cells play a pivotal role in the development of this autoimmune disorder. This studywas undertaken to investigate the mechanisms of interaction between antigen presenting cells (APCs) and an autoreactiveT cell (ATL1) clone obtained from lupus-prone BXSB mice. ATL1 cells, either before or after γ-ray irradiation, wereable to activate naive B cells, as determined by B cell proliferation assays. Macrophages from BXSB mice were able tostimulate the proliferation of resting ATL1 cells at a responder/stimulator (R/S) ratio of 1/2.5. Dendritic cells (DCs) weremuch more powerful stimulators for ATL1 cells on a per cell basis. The T cell stimulating ability of macrophages and Bcells, but not DCs, was sensitive to γ-ray irradiation. Monoclonal antibodies against mouse MHC-Ⅱ and CD4 were ableto block DC-mediated stimulation of ATL1 proliferation, indicating cognate recognition between ATL1 and APCs. Ourdata suggest that positive feedback loops involving macrophages, B cells and autoreactive T cells may play a pivotalrole in keeping the momentum of autoimmune responses leading to autoimmune diseases.

关键词： SLE T cells antigen presenting cells

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CircPTEN-MT from PTEN regulates mitochondrial energy metabolism

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Journal of Genetics and Genomics 2024年第5期51卷 531-542页

作者： Danhui Ruan Jiancheng Xu Yang Liu Juan Luo Xuyang Zhao Yuhua Li Guangxi Wang Jiawen Feng Hui Liang Yue Yin Jianyuan Luo Yuxin Yin Institute of Systems Biomedicine Department of PathologySchool of Basic Medical SciencesBeijing Key Laboratory of Tumor Systems BiologyPeking University International Cancer InstitutePeking-Tsinghua Center of Life SciencesPeking University Health Science CenterBeijing 100191China Institute of Precision Medicine Peking University Shenzhen HospitalShenzhenGuangdong 518036China Department of Pharmacology School of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Department of Medical Genetics Center for Medical GeneticsSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Soochow University Cancer Institute SuzhouJiangsu 215127China

Phosphatase and tensin homolog(PTEN)is a multifunctional gene involved in a variety of physiological and pathological processes.Circular RNAs(circRNAs)are generated from back-splicing events during mRNA processing and participate in cell biological processes through binding to RNAs or proteins.However,PTEN-related circRNAs are largely unknown.Here,we report that circPTEN-mitochondria(MT)(hsa_circ_0002934)is a circular RNA encoded by exons 3,4,and 5 of PTEN and is a critical regulator of mitochondrial energy metabolism.CircPTEN-MT is localized to mitochondria and physically associated with leucine-rich pentatricopeptide repeat-containing protein(LRPPRC),which regulates posttranscriptional gene expression in mitochondria.Knocking down circPTEN-MT reduces the interaction of LRPPRC and steroid receptor RNA activator(SRA)stem-loop interacting RNA binding protein(SLIRP)and inhibits the polyadenylation of mitochondrial mRNA,which decreases the mRNA level of the mitochondrial complex I subunit and reduces mitochondrial membrane potential and adenosine triphosphate production.Our data demonstrate that circPTEN-MT is an important regulator of cellular energy metabolism.This study expands our understanding of the role of PTEN,which produces both linear and circular RNAs with different and independent functions.

关键词： Circular RNA LRPPRC Mitochondrial energy metabolism mtDNApost-transcriptional regulation

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Lactobacillus plantarum AR495 improves stress-induced irritable bowel syndrome in rats by targeting gut microbiota and Mast cell-PAR2-TRPV1 signaling pathway

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Food science and Human Wellness 2024年第2期13卷 698-708页

作者： Hongyun Zhang Guangqiang Wang Zhiqiang Xiong Zhuan Liao Yangyan Qian Xin Song Li Sui Lianzhong Ai Yongjun Xia Shanghai Engineering Research center of Food Microbiology School of Health Science and EngineeringUniversity of Shanghai for Science and TechnologyShanghai 200093China Department of Gastroenterol Digestive Endoscopy CenterShanghai HospitalShanghai 200093China

Probiotics have great potential in regulating intestinal pain.In this study,the effects of Lactobacillus plantarum AR495 on the visceral sensitivity and gut microbiota of irritable bowel syndrome(IBS)rats were studied.The results showed that tryptase released after mast cell activation and degranulation plays a key role in visceral pain,and L.plantarum AR495 reduced the stimulation of colonic mast cells and the expression of protease-activated receptor 2(PAR2)and TRPV1 in dorsal root ganglia.Research further showed that supplementation with L.plantarum AR495 increased the level of short-chain fatty acids(SCFAs)and enhanced the barrier function of the colon.In addition,the microbiota analysis of the colon indicated that L.plantarum AR495 promoted the proliferation of Bifidobacterium and inhibited the proliferation of Lachnospiraceae,which alleviated the imbalance of the intestinal microbiota caused by IBS to a certain extent.In total,L.plantarum AR495 might reduce visceral sensitivity through the Mast cell-PAR2-TRPV1 signaling pathway by maintaining the homeostasis of the intestinal barrier.

关键词： Lactobacillus plantarum Irritable bowel syndrome Visceral sensitivity Dorsal root ganglia Tryptase Microbiota

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Establishment of liver specific glucokinase gene knockout mice: a new animal model for screening anti-diabetic drugs

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Acta Pharmacologica Sinica 2004年第12期25卷 93-99页

作者： Ya-li ZHANG, Xiao-hong TAN2, Mei-fang XIAO, Hui LI, Yi-qing Mao, Xiao YANG2, Huan-ran TAN3 Department of Pharmacology, School of Basic Medical science, Peking University health science center, Beijing 100083 2Institute of Biotechnology Academy ofMilitary Medical science, Beijing 100071, China Department of Pharmacology School of Basic Medical Science Peking University Health Science Center 北京 100083 Institute of Biotechnology Academy of Military Medical science 北京 100071

AIM: To characterize the liver-specific role of glucokinase in maintaining glucose homeostasis and to create an animal model for diabetes. METHODS: We performed hepatocyte-specific gene knockout of glucokinase in mice using Cre-loxP gene targeting strategy. First, two directly repeated loxP sequences were inserted to flank the exon 9 and exon 10 of glucokinase in genomic DNA. To achieve this, linearized targeting vector was electroporated into ES cells. Then G418- and Gancyclovir-double-resistant clones were picked and screened by PCR analysis and the positives identified by PCR were confirmed by Southern blot. A targeted clone was selected for microinjection into C57BL/6J blastocysts and implanted into pseudopregnant FVB recipient. Chimeric mice and their offspring were analyzed by Southern blot. Then by intercrossing the Alb-Cre transgenic mice with mice containing a conditional gk allele, we obtained mice with liver-specific glucokinase gene knockout. RESULTS: Among 161 double resistant clones 4 were positive to PCR and Southern blot and only one was used for further experiments. Eventually we generated the liver specific glucokinase knockout mice. These mice showed increased glucose level with age and at the age of 6 weeks fasting blood glucose level was significantly higher than control and they also displayed impaired glucose tolerance. CONCLUSION: Our studies indicate that hepatic glucokinase plays an important role in glucose homeostasis and its deficiencies contribute to the development of diabetes. The liver glucokinase knock- out mouse is an ideal animal model for MODY2, and it also can be applied for screening anti-diabetic drugs.

关键词： animal disease model non insulin dependent diabetes mellitus type 2 diabetes mellitus glucokinase knockout mice

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Exosome-encapsulated lncRNA HOTAIRM1 contributes to PM_(2.5)-aggravated COPD airway remodeling by enhancing myofibroblast differentiation

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science China(Life sciences) 2024年第5期67卷 970-985页

作者： Huaqi Guo Luo Fei Hengyi Yu Yan Li Yan Feng Shaowei Wu Yan Wang The Ninth People’s Hospital of Shanghai Jiao Tong University School of Medicine Shanghai 200011China School of Public health Shanghai Jiao Tong University School of MedicineShanghai 200020China Department of Occupational and Environmental health sciences School of Public HealthXi’an Jiao Tong University Health Science CenterXi’an 710049China

Emphysema,myofibroblast accumulation and airway remodeling can occur in the lungs due to exposure to atmospheric pollution,especially fine particulate matter(PM_(2.5)),leading to chronic obstructive pulmonary disease(COPD).Specifically,bronchial epithelium-fibroblast communication participates in airway remodeling,which results in COPD.An increasing number of studies are now being conducted on the role of exosome-mediated cell-cell communication in disease pathogenesis.Here,we investigated whether exosomes generated from bronchial epithelial cells could deliver information to normal stromal fibroblasts and provoke cellular responses,resulting in airway obstruction in COPD.We studied the mechanism of exosome-mediated intercellular communication between human bronchial epithelial(HBE) cells and primary lung fibroblasts(pLFs).We found that PM_(2.5)-induced HBE-derived exosomes promoted myofibroblast differentiation in pLFs.Then,the exosomal lncRNA expression profiles derived from PM_(2.5)-treated HBE cells and nontreated HBE cells were investigated using an Agilent Human LncRNA Array.Combining coculture assays and direct exosome treatment,we found that HBE cell-derived exosomal HOTAIRM1 facilitated the myofibroblast differentiation of pLFs.Surprisingly,we discovered that exosomal HOTAIRM1 enhanced p LF proliferation to secrete excessive collagen secretion,leading to airway obstruction by stimulating the TGF-β/SMAD3 signaling pathway.Significantly,PM_(2.5)reduced FEV1/FVC and FEV1 and increased the level of serum exosomal HOTAIRM1 in healthy people;moreover,serum exosomal HOTAIRM1 was associated with PM_(2.5)-related reductions in FEV1/FVC and FVC.These findings show that PM_(2.5)triggers alterations in exosome components and clarify that one of the paracrine mediators of myofibroblast differentiation is bronchial epithelial cell-derived HOTAIRM1,which has the potential to be an effective prevention and therapeutic target for PM_(2.5)-induced COPD.

关键词： PM2.5 exosomal lncRNAs HOTAIRM1 chronic obstructive pulmonary disease

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The Role of Childhood Circumstances in healthy Aging Inequalities Among Older Adults—China,2011–2020

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China CDC weekly 2024年第11期6卷 208-212,I0004-I0007页

作者： Peng Nie Xili Lin Lanlin Ding School of Economics and Finance Xi’an Jiaotong UniversityXi’an CityShaanxi ProvinceChina Global health Institute Xi’an Jiaotong University Health Science CenterXi’an CityShaanxi ProvinceChina National School of Development Peking UniversityBeijingChina

What is already known about this topic?Addressing health disparities is a worldwide priority,with a well-established acknowledgment of the influence of childhood circumstances on these discrepancies.In China,particularly among the elderly,health inequalities are a notable concern.What is added by this report?The inequality in healthy aging has increased from 2011 to 2020,both in general and concerning childhood factors.Nevertheless,the impact of early-life healthcare access and parental health behaviors on healthy aging gaps has reduced among older adults in better health within the top segment of healthy aging.What are the implications for public health practice?Efforts towards reducing regional health disparities and improving healthcare access for children,along with promoting the health and well-being of parents,especially in economically disadvantaged households,are crucial policy considerations.

关键词： ledgment inequalities circumstances

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TDP-43 is a key molecule accelerating development of Alzheimer’s disease following traumatic brain injury

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Neural Regeneration Research 2024年第5期19卷 955-956页

作者： Chu Chen Department of Cellular and Integrative Physiology Long School of MedicineUniversity of Texas Health Science Center at San AntonioSan AntonioTXUSA

Currently,more than 55 million people have dementia worldwide and Alzheimer’s disease(AD)is one of the most common causes of dementia in aging.However,no effective therapies are currently available for the prevention and treatment of AD.This is largely due to our limited understanding of the mechanisms underlying the neuropathogenesis of AD.It has widely been recognized that AD is heterogeneous and that multi-factors are contributing to the pathogenesis of AD.Accumulated evidence suggests that traumatic brain injury(TBI)is an important risk factor for the development of AD and dementia later in life(Guo et al.,2000;Johnson et al.,2010).However,the precise mechanism by which TBI contributes to developing AD has yet to be elucidated.

关键词： Alzheimer traumatic

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Kinetics of thymocyte developmental process in fetal and neonatal mice

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Cell Research 2003年第4期13卷 265-273页

作者： SHI YUN XIAO, YAN LI, WEI FENG CHENDepartment of Immunology, School of Basic Medical sciences, Peking University health science center, 38 Xueyuan Road, Beijing 100083, China Department of Immunology School of Basic Medical Sciences Peking University Health Science Center Beijing China

Kinetics of thymocyte development in vivo during embryogenesis was pursued. The early development of thymocytes in the fetal and neonatal BALB/c mice was discontinuous, with four waves of cell proliferation occurring at fetal day (Fd) 14 to 17, Fd 18 to day (D) 1 after birth, D 2 to D 5 and D6 thereafter. The first three proliferation waves coincided with the generation of CD4/"CD8/" (DP), TCR+CD4/hiCD8-/lo (CD4 SP), and TCR+CD4-/loCD8int/hi (CD8 SP) thymocytes, respectively. The transition from DN to DP cells was further investigated and it was found out that there were two differential pathways via immature single positive (ISP) cells in the BALB/c mice, each functioning at different fetal ages. One is via TCR-CD4-CD8+ cells, occurring between Fd 15 and Fd 17 and the other is via TCR-CD4+CD8- cells, occurring from Fd 17 until birth. In contrast, the TCR-CD4-CD8+ pathway dominated overwhelmingly in the C57BL/6 mice. These findings shed new light on the hypothesis that the differential pathway preferenc

关键词： fetal thymus neonatal mice thymocyte ontogeny.

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Relationship of Body Mass Index, Waist Circumference and Cardiovascular Risk Factors in Chinese Adult

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Biomedical and Environmental sciences 2010年第2期23卷 92-101页

作者： SONG-MING DU GUAN-SHENG MA YAN-PING LI HONG-YUN FANG XIAO-QI HU XIAO-GUANG YANG YONG-HUA HU School of Public health Peking University Health Science Center Beijing 100083 China National Institute for Nutrition and Food Safety Chinese Center for Disease Control and Prevention Beijing 100021 China

Objective To compare the relative risk of waist circumference （WC） and/or BMI on cardiovascular risk factors. Methods A cross-sectional data of 41 087 adults （19 567 male and 21 520 female） from the 2002 China National Nutrition and health Survey were examined. According to the obesity definition of WGOC （BMI, 24 kg/m^2 and 28 kg/m^2; WC, male 85 cm and 95 cm for male, 80 cm and 90 cm for female）, the study population were divided into 9 groups. The prevalence and odds ratio （ORs） of cardiovascular disease （CVD） risk factors （hypertension, high fasting plasma glucose and dyslipidemia） were compared among these 9 groups. Stepwise linear regression analyses were used to compare the likelihood of BMI and/or WC on CVD risk factors. Results Both the indexes levels and the odds ratios of CVD risk factors were significantly increased （decreased for HDL-C levels） along with the increase of WC and/or BMI, even when the effect of age, sex, income, education, sedentary activity and dietary factors were adjusted. The variances （R2） in CVD risk factors explained by WC only and BMI only were quite similar, but a little bit larger when WC and BMI were combined. The standard fl was higher of BMI when predicting systolic BP and was higher of WC when predicting TG, TC and HDL. Conclusions BMI and WC had independent effects on CVD risk factors and combination of BMI and WC would be more predictive. Findings from the present study provided substantive evidence for the WGOC recommendation of a combined use of BMI and WC classifications.

关键词： obesity central obesity cardiovascular disease risk factors multivariate regression

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