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The miR-9-5p/CXCL11 pathway is a key target of hydrogen sulfide-mediated inhibition of neuroinflammation in hypoxic ischemic brain injury

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Neural Regeneration Research 2024年第5期19卷 1084-1091页

作者： Yijing Zhao Tong Li Zige Jiang Chengcheng Gai Shuwen Yu Danqing Xin Tingting Li Dexiang Liu Zhen Wang Department of Physiology School of Basic Medical SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina Department of Neurosurgery Qingdao Municipal HospitalQingdaoShandong ProvinceChina Department of Medical Psychology and Ethics School of Basic Medicine SciencesCheeloo College of MedicineShandong UniversityJinanShandong ProvinceChina key laboratory of birth regulation and control technology of national health commission of china Maternal and Child Health Care Hospital of Shandong Province Affiliated to Qingdao UniversityJinanShandong ProvinceChina

We previously showed that hydrogen sulfide(H2S)has a neuroprotective effect in the context of hypoxic ischemic brain injury in neonatal mice.However,the precise mechanism underlying the role of H2S in this situation remains unclear.In this study,we used a neonatal mouse model of hypoxic ischemic brain injury and a lipopolysaccharide-stimulated BV2 cell model and found that treatment with L-cysteine,a H2S precursor,attenuated the cerebral infarction and cerebral atrophy induced by hypoxia and ischemia and increased the expression of miR-9-5p and cystathionineβsynthase(a major H2S synthetase in the brain)in the prefrontal cortex.We also found that an miR-9-5p inhibitor blocked the expression of cystathionineβsynthase in the prefrontal cortex in mice with brain injury caused by hypoxia and ischemia.Furthermore,miR-9-5p overexpression increased cystathionine-β-synthase and H2S expression in the injured prefrontal cortex of mice with hypoxic ischemic brain injury.L-cysteine decreased the expression of CXCL11,an miR-9-5p target gene,in the prefrontal cortex of the mouse model and in lipopolysaccharide-stimulated BV-2 cells and increased the levels of proinflammatory cytokines BNIP3,FSTL1,SOCS2 and SOCS5,while treatment with an miR-9-5p inhibitor reversed these changes.These findings suggest that H2S can reduce neuroinflammation in a neonatal mouse model of hypoxic ischemic brain injury through regulating the miR-9-5p/CXCL11 axis and restoringβ-synthase expression,thereby playing a role in reducing neuroinflammation in hypoxic ischemic brain injury.

关键词： chemokine(C-X-C motif)ligand 11 cystathionineβsynthase H2S hypoxic ischemic brain injury inflammation L-cysteine lipopolysaccharide microglia miR-9-5p neuroprotection

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Correlation between Combined Urinary Metal Exposure and Grip Strength under Three Statistical Models:A Cross-sectional Study in Rural Guangxi

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Biomedical and Environmental Sciences 2024年第1期37卷 3-18页

作者： LIANG Yu Jian RONG Jia Hui WANG Xue Xiu CAI Jian Sheng QIN Li Dong LIU Qiu Mei TANG Xu MO Xiao Ting WEI Yan Fei LIN Yin Xia HUANG Shen Xiang LUO Ting Yu GOU Ruo Yu CAO Jie Jing HUANG Chu Wu LU Yu Fu QIN Jian ZHANG Zhi Yong Department of Environmental and Occupational health School of Public HealthGuangxi Medical UniversityNanning 530021GuangxiChina key laboratory of Tumor Immunology and Microenvironmental regulation Guilin Medical UniversityGuilin 541199GuangxiChina Department of Environmental health and Occupational Medicine School of Public HealthGuilin Medical UniversityGuilin 541199GuangxiChina Guangxi Colleges and Universities key laboratory of Prevention and control of Highly Prevalent Diseases Guangxi Medical UniversityNanning 530021GuangxiChina Guangxi key laboratory of Environment and health Research Guangxi Medical UniversityNanning 530021GuangxiChina key laboratory of Longevity and Aging-related Diseases of Chinese Ministry of Education Guangxi Medical UniversityNanning 530021GuangxiChina Guangxi health commission key laboratory of Entire Lifecycle health and Care Guilin Medical UniversityGuilin 541199GuangxiChina

Objective This study aimed to investigate the potential relationship between urinary metals copper(Cu),arsenic(As),strontium(Sr),barium(Ba),iron(Fe),lead(Pb)and manganese(Mn)and grip strength.Methods We used linear regression models,quantile g-computation and Bayesian kernel machine regression(BKMR)to assess the relationship between metals and grip strength.Results In the multimetal linear regression,Cu(β=−2.119),As(β=−1.318),Sr(β=−2.480),Ba(β=0.781),Fe(β=1.130)and Mn(β=−0.404)were significantly correlated with grip strength(P<0.05).The results of the quantile g-computation showed that the risk of occurrence of grip strength reduction was−1.007(95%confidence interval:−1.362,−0.652;P<0.001)when each quartile of the mixture of the seven metals was increased.Bayesian kernel function regression model analysis showed that mixtures of the seven metals had a negative overall effect on grip strength,with Cu,As and Sr being negatively associated with grip strength levels.In the total population,potential interactions were observed between As and Mn and between Cu and Mn(P_(interactions) of 0.003 and 0.018,respectively).Conclusion In summary,this study suggests that combined exposure to metal mixtures is negatively associated with grip strength.Cu,Sr and As were negatively correlated with grip strength levels,and there were potential interactions between As and Mn and between Cu and Mn.

关键词： Urinary metals Handgrip strength Quantile g-computation Bayesian kernel machine regression

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Versatile photonic molecule switch in multimode microresonators

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Light(Science & Applications) 2024年第3期13卷 498-509页

作者： Zihan Tao Bitao Shen Wencan Li Luwen Xing Haoyu Wang Yichen Wu Yuansheng Tao Yan Zhou Yandong He Chao Peng Haowen Shu Xingjun Wang State key laboratory of Advanced Optical Communications System and Networks School of ElectronicsPeking UniversityBeijing 100871China College of Engineering Peking UniversityBeijing 100871China School of Integrated Circuits Peking University100871 BejingChina Peking University Yangtze Delta Institute of Optoelectronics Nantong 226010China Frontiers Science Center for Nano-optoelectronics Peking UniversityBeijing 100871China Peng Cheng laboratory Shenzhen 518055China

Harnessing optical supermode interaction to construct artificial photonic molecules has uncovered a series of fundamental optical phenomena analogous to atomic physics.Previously,the distinct energy levels and interactions in such two-level systems were provided by coupled microresonators.The reconfigurability is limited,as they often require delicate external field stimuli or mechanically altering the geometric factors.These highly specific approaches also limit potential applications.Here,we propose a versatile on-chip photonic molecule in a multimode microring,utilizing a flexible regulation methodology to dynamically control the existence and interaction strength of spatial modes.The transition between single/multi-mode states enables the“switched-off/on”functionality of the photonic molecule,supporting wider generalized applications scenarios.In particular,“switched-on”state shows flexible and multidimensional mode splitting control in aspects of both coupling strength and phase difference,equivalent to the a.***.and d.c.Stark effect.“Switched-off”state allows for perfect low-loss single-mode transition(Qi~10 million)under an ultra-compact bend size(FSR~115 GHz)in a foundry-based silicon microring.It breaks the stereotyped image of the FSR-Q factor trade-off,enabling ultra-wideband and high-resolution millimeter-wave photonic operations.Our demonstration provides a flexible and portable solution for the integrated photonic molecule system,extending its research scope from fundamental physics to real-world applications such as nonlinear optical signal processing and sixth-generation wireless communication.

关键词： switched multimode millimeter

ALKBH5 gene polymorphisms and risk of neuroblastoma in Chinese children from Jiangsu Province

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Cancer Innovation 2024年第2期3卷 72-79页

作者： Qian Guan Xinxin Zhang Jiabin Liu Chunlei Zhou Jinhong Zhu Haiyan Wu Zhenjian Zhuo Jing He Department of Pediatric Surgery Guangzhou Institute of PediatricsGuangdong Provincial Key Laboratory of Research in Structural Birth Defect DiseaseGuangdong Provincial Clinical Research Center for Child HealthGuangzhou Women and Children's Medical CenterGuangzhou Medical UniversityGuangzhouGuangdongChina Department of Pathology Children's Hospital of Nanjing Medical UniversityNanjingJiangsuChina Department of Clinical laboratory BiobankHarbin Medical University Cancer HospitalHarbinHeilongjiangChina laboratory Animal Center School of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate SchoolShenzhenGuangdongChina

Background:Neuroblastoma is one of the most common extracranial malignant solid tumors in children.AlkB homolog 5(ALKBH5)is an RNA N6-methyladenosine(m6A)demethylase that plays a critical role in tumorigenesis and development.We assessed the association between single nucleotide polymorphisms(SNPs)in ALKBH5 and the risk of neuroblastoma in a case-control study including 402 patients and 473 non-cancer controls.Methods:Genotyping was determined by the TaqMan method.The association between ALKBH5 polymorphisms(rs1378602 and rs8400)and the risk of neuroblastoma was evaluated using the odds ratio(OR)and 95%confidence interval(CI).Results:We found no strong association of ALKBH5 rs1378602 and rs8400 with neuroblastoma risk.Further stratification analysis by age,sex,primary site,and clinical stage showed that the rs1378602 AG/AA genotype was associated with a lower risk of neuroblastoma in males(adjusted OR=0.58,95%CI=0.35–0.97,p=0.036)and children with retroperitoneal neuroblastoma(adjusted OR=0.58,95%CI=0.34–0.98,p=0.040).Conclusions:ALKBH5 SNPs do not seem to be associated with neuroblastoma risk.More studies are required to confirm this negative result and reveal the relationship between gene polymorphisms of the m6A modifier ALKBH5 and neuroblastoma.

关键词： ALKBH5 neuroblastoma polymorphism susceptibility

A STAMP-Game model for accident analysis in oil and gas industry

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Petroleum Science 2024年第3期21卷 2154-2167页

作者： Huixing Meng Xu An Daiwei Li Shijun Zhao Enrico Zio Xuan Liu Jinduo Xing State key laboratory of Explosion Science and Safety Protection Beijing Institute of Technology School of Emergency Management and Safety Engineering China University of Mining and Technology (Beijing) Energy Department Politecnico di Milano Mines Paris PSL Centre de Recherche sur les Risques et les Crises School of Mechanical-Electronic and Vehicle Engineering Beijing University of Civil Engineering and Architecture

Accidents in engineered systems are usually generated by complex socio-technical factors. It is beneficial to investigate the increasing complexity and coupling of these factors from the perspective of system safety. Based on system and control theories, System-Theoretic Accident Model and Processes(STAMP) is a widely recognized approach for accident analysis. In this paper, we propose a STAMP-Game model to analyze accidents in oil and gas storage and transportation systems. Stakeholders in accident analysis by STAMP can be regarded as players of a game. Game theory can, thus, be adopted in accident analysis to depict the competition and cooperation between stakeholders. Subsequently, we established a game model to study the strategies of both supervisory and supervised entities. The obtained results demonstrate that the proposed game model allows for identifying the effectiveness deficiency of the supervisory entity, and the safety and protection altitudes of the supervised entity. The STAMP-Game model can generate quantitative parameters for supporting the behavior and strategy selections of the supervisory and supervised entities. The quantitative data obtained can be used to guide the safety improvement, to reduce the costs of safety regulation violation and accident risk.

关键词： Accident analysis STAMP System engineering Game theory Oil and gas storage and transportation systems

Deamidation enables pathogenic SMAD6 variants to activate the BMP signaling pathway

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Science china Life Sciences 2024年

作者： Ling Li Lei Lu Ziqi Xiao Jingyi Lv Hefeng Huang Bo Wu Tongjin Zhao Chengtao Li Weimin Wang Hongyan Wang Obstetrics and Gynecology Hospital State Key Laboratory of Genetic Engineering Institute of Reproduction and Development and Children's Hospital Fudan University Shanghai key laboratory of Metabolic Remodeling and health Institute of Metabolism and Integrative Biology Fudan University Prenatal Diagnosis Center of Shenzhen Maternity & Child healthcare Hospital Shanghai Medical College Fudan University Department of Pharmacy College of Life Sciences China Jiliang University

The BMP signaling pathway plays a crucial role in regulating early embryonic development and tissue homeostasis. SMAD6 encodes a negative regulator of BMP, and rare variants of SMAD6 are recurrently found in individuals with birth defects. However, we observed that a subset of rare pathogenic variants of SMAD6 consistently exhibited positive regulatory effects instead of the initial negative effects on the BMP signaling pathway. We sought to determine whether these SMAD6 variants have common pathogenic mechanisms. Here, we showed that pathogenic SMAD6 variants accompanying this functional reversal exhibit similar increases in deamidation. Mechanistically, increased deamidation of SMAD6 variants promotes the accumulation of the BMP receptor BMPR1A and the formation of new complexes, both of which lead to BMP signaling pathway activation. Specifically, two residues, N262 and N404, in SMAD6 were identified as the crucial sites of deamidation, which was catalyzed primarily by glutamine-fructose-6-phosphate transaminase 2(GFPT2). Additionally, treatment of cells harboring SMAD6 variants with a deamidase inhibitor restored the inhibitory effect of SMAD6 on the BMP signaling pathway. Conversely,when wild-type SMAD6 was manually simulated to mimic the deamidated state, the reversed function of activating BMP signaling was reproduced. Taken together, these findings show that deamidation of SMAD6 plays a crucial role in the functional reversal of BMP signaling activity, which can be induced by a subset of various SMAD6 variants. Our study reveals a common pathogenic mechanism shared by these variants and provides a potential strategy for preventing birth defects through deamidation regulation, which might prevent the off-target effects of gene editing.

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Male reproductive system and simulated high-altitude environment:preliminary results in rats

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Asian Journal of Andrology 2023年第3期25卷 426-432页

作者： Xiu-Yun Li Mei-Hua Zhang Zhao-Wen Chen Bin Zhang Gang Bai He-Feng Wang key laboratory of birth regulation and control technology of national health commission of china Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao UniversityJinan 250014China Department of Obstetrics Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao UniversityJinan 250014China Department of Ophthalmology Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao UniversityJinan 250014China Center for Reproductive Medicine Shandong UniversityJinan 250012China Department of Pediatric Surgery Shandong Provincial Maternal and Child Health Care Hospital Affiliated to Qingdao UniversityJinan 250014China

This study assessed the effects of a simulated high-altitude environment on the reproductive system of prepubertal male rats and the reversibility of these effects upon return to a normal environment.Three-week-old male Wistar rats were randomly allocated to 4 groups that were exposed to different conditions:a normal environment for 6 weeks and 12 weeks,respectively,hypobaric hypoxia for 6 weeks,and hypobaric hypoxia for 6 weeks followed by a normal environment for 6 weeks.Multiple pathophysiological parameters were evaluated at the histological,endocrine,and molecular levels.Hypobaric hypoxia exposure for 6 weeks during the prepubertal phase significantly altered physiological parameters,body functions,blood indices,and reproductive potential.Six weeks after returning to a normal environment,the damaged reproductive functions partially recovered due to compensatory mechanisms.However,several changes were not reversed after returning to a normal environment for 6 weeks,including disorders of body development and metabolism,increased red blood cells,increased fasting blood glucose,abnormal blood lipid metabolism,decreased testicular and epididymis weights,abnormal reproductive hormone levels,excessive apoptosis of reproductive cells,and decreased sperm concentration.In summary,a hypobaric hypoxic environment significantly impaired the reproductive function of prepubertal male rats,and a return to normal conditions during the postpubertal phase did not fully recover these impairments.

关键词： high altitude hypobaric hypoxia male rats reproductive potential testis

Air Pollution health Impact Monitoring and health Risk Assessment technology and Its Application-china,2006-2019

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china CDC weekly 2022年第26期4卷 577-581页

作者： Jingxiu Han Dongqun Xu Donggang Xu Xu Yang Qin Wang Mingqing Chen Wenrong Xia Weiwei Xing Chunyu Xu Yue Liu Junrui Chang Wenliang Fu Shuxin Hao Na Li Xiaoyan Dong Yunpu Li Congshen Meng Jingyi Liu china CDC key laboratory of Environment and Population health National Institute of Environmental HealthChinese Center for Disease Control and PreventionBeijingChina Academy of Military Medical Sciences Academy of Military SciencesBeijingChina Hubei key laboratory of Genetic regulation and Integrative Biology College of Life SciencesCentral China Normal UniversityWuhan CityHubei ProvinceChina

Air pollution is a significant risk factor contributing to the burden of disease in china.health risk assessment and management are important to reduce the impact of air pollution on public health.To help formulate standardized health risk assessment techniques,a series of studies were conducted from 2006 to 2019.Through systematic review,study of molecular mechanisms,epidemiological investigation,and health effect monitoring,the overall project established a monitoring and evaluation indicator system,a comprehensive information platform,software for automatic data cleaning,and standardized health risk assessment techniques.Technical specifications have been issued by the national health commission for promoting health risk assessments across china.This paper introduces the project,the research approach,its main research accomplishments,innovations,and public health significance,and describes directions for further research.

关键词： pollution Impact accomplishment

p53 positively regulates the proliferation of hepatic progenitor cells promoted by laminin-521

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Signal Transduction and Targeted Therapy 2022年第9期7卷 3592-3608页

作者： Mingyang Ma Shuyao Hua Xiangde Min Liang Wang Jun Li Ping Wu Huifang Liang Bixiang Zhang Xiaoping Chen Shuai Xiang Department of General Surgery Tianjin Medical University General HospitalTianjinChina Hepatic Surgery Center Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Clinical Nutrition Shanghai Jiao Tong University Affliated Sixth People's HospitalShanghaiChina Department of Radiology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Wuhan Pulmonary Hospital Wuhan Institute for Tuberculosis ControlWuhanChina Department of Pathophysiology Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Hubei key laboratory of Hepato-Pancreato-Biliary Disease WuhanChina key laboratory of Organ Transplantation Ministry of EducationWuhanChina key laboratory of Organ Transplantation National Health CommissionWuhanChina key laboratory of Organ Transplantation Chinese Academy of Medical SciencesWuhanChina

Hepatic progenitor cells(HPCs)hold tremendous potential for liver regeneration,but their well-known limitation of proliferation hampers their broader use.There is evidence that laminin is required for the proliferation of HPCs,but the laminin isoform that plays the dominant role and the key intracellular downstream targets that mediate the regulation of HPC proliferation have yet to be determined.Here we showed that p53 expression increased gradually and reached maximal levels around 8 days when lamininα4,α5,β2,β1,andγ1 subunit levels also reached a maximum during HPC activation and expansion.Laminin-521(LN-521)promoted greater proliferation of HPCs than do laminin,matrigel or other laminin isoforms.Inactivation of p53 by PFT-αor Ad-p53^(V143A) inhibited the promotion of proliferation by LN-521.Further complementary MRI and bioluminescence imaging analysis showed that p53 inactivation decreased the proliferation of transplanted HPCs in vivo.p53 was activated by LN-521 through the Integrinα6β1/FAK-Src-Paxillin/Akt axis.Activated p53 was involved in the nuclear translocation of CDK4 and inactivation of Rb by inducing p27^(Kip1).Taken together,this study identifies LN-521 as an ideal candidate substrate for HPC culture and uncovers an unexpected positive role for p53 in regulating proliferation of HPCs,which makes it a potential target for HPC-based regenerative medicine.

关键词： laminin progenitor inhibited