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Targeting TRMT5 suppresses hepatocellular carcinoma progression via inhibiting the HIF-1αpathways

Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2023年第1期24卷 50-63页

作者： Qiong ZHAO luwen zhang Qiufen HE Hui CHANG Zhiqiang WANG Hongcui CAO Ying ZHOU Ruolang PAN Ye CHEN Department of Genetics and Department of Genetic and Metabolic DiseaseThe Children's HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthHangzhou 310052China Zhejiang Provincial Key Laboratory of Genetic and Developmental Disorders Institute of GeneticsZhejiang UniversityHangzhou 310058China State Key Laboratory for Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious Diseasesthe First Affiliated HospitalZhejiang University School of MedicineHangzhou 310003China Xiangshan Hospital of TCM Medical and Health Group Ningbo 315700China Zhejiang Provincial Key Laboratory of Cell-Based Drug and Applied Technology Development Hangzhou 311121China

Accumulating evidence has confirmed the links between transfer RNA(tRNA)modifications and tumor *** present study is the first to explore the role of tRNA methyltransferase 5(TRMT5),which catalyzes the m1G37 modification of mitochondrial tRNAs in hepatocellular carcinoma(HCC)***,based on bioinformatics and clinical analyses,we identified that TRMT5 expression was upregulated in HCC,which correlated with poor *** TRMT5 attenuated HCC proliferation and metastasis both in vivo and in vitro,which may be partially explained by declined extracellular acidification rate(ECAR)and oxygen consumption rate(OCR).Mechanistically,we discovered that knockdown of TRMT5 inactivated the hypoxia-inducible factor-1(HIF-1)signaling pathway by preventing HIF-1αstability through the enhancement of cellular oxygen ***,our data indicated that inhibition of TRMT5 sensitized HCC to doxorubicin by adjusting HIF-1α.In conclusion,our study revealed that targeting TRMT5 could inhibit HCC progression and increase the susceptibility of tumor cells to chemotherapy ***,TRMT5 might be a carcinogenesis candidate gene that could serve as a potential target for HCC therapy.

关键词： Transfer RNA(tRNA) tRNA methyltransferase 5(TRMT5) Hepatocellular carcinoma(HCC) Hypoxia-inducible factor-1α(HIF-1α)

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N-palmitoylethanolamine modulates hippocampal neuroplasticity in rats with stress-induced depressive behavior phenotype

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EUROPEAN JOURNAL OF PHARMACOLOGY 2023年第1期957卷 176041页

作者： zhang, luwen Tang, Wenjuan Ouyang, Yinan zhang, Miao Li, Ruirui Sun, Lianping Liu, Chao Yu, Hailing Yanbian Univ Coll Med Dept Funct Sci Pk St 977 Yanji 133002 Jilin Peoples R China Yanbian Univ Coll Med Expt Teaching Ctr Morphol Pk St 977 Yanji 133002 Jilin Peoples R China Yanbian Univ Coll Pharm Pk St 977 Yanji 133002 Jilin Peoples R China Yanbian Univ Dept Neurol Affiliated Hosp St 1327 Yanji 133002 Jilin Peoples R China

Bioactive lipid mediator N-palmitoylethanolamide (PEA) is an endocannabinoid-like molecule. Based on our previous data, this study aimed to further investigate the antidepressant property of PEA via the peroxisome proliferator-activated receptor alpha (PPAR & alpha;) pathway, focusing on the intervention of PEA on hippocampal neuroplasticity. Behavioral tests were performed in rats induced by unpredictable chronic mild stress (uCMS) in the last week of the experiment, and then the brain tissue samples were retained for subsequent immunohistochemical detection and Western blot analysis. In vitro, the apoptosis of HT22 cells induced by CORT and apoptosis-related proteins were detected by Hoechst staining and Western blot, respectively. The results showed that PEA ameliorated the depression-like phenotype in rats induced by uCMS, prevented the uCMS-induced reduction in the number of BrdU-positive cells, and increased BrdU/NeuN co-localization in the hippocampus, and upregulated the levels of synapse associated protein NCAM, MAP2, SYN and PSD95 in the hippocampus. Hoechst staining results showed that PEA significantly increased the CORT-induced reduction in the number of hippocampal neurons. Western blot analysis showed that PEA decreased the expression of caspase-3 and ccaspase-3, and increased the ratio of Bcl-2/Bax in CORT-induced HT22 cells. MK886, a PPAR & alpha;antagonist, partially or completely reversed these effects. In conclusion, the therapeutic potential of PEA for depressive mood disorders may be through targeting the hippocampal neuroplasticity, including increasing adult neurogenesis and synaptic plasticity, as well as down-regulated neuronal apoptosis, to remodel hippocampal circuitries upon functional integration and PPAR & alpha;pathway may be involved in this process.

关键词： N-Palmitoylethanolamide Hippocampus Neurogenesis Neuroplasticity Apoptosis Rats

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基于态基近场动力学的多重失效弹性模型及其在船-冰碰撞中的应用

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哈尔滨工程大学学报（英文版） 2023年第3期22卷 395-410页

作者：宋莹张律文李少凡李云波 College of Ocean Science and Engineering Shanghai Maritime UniversityShanghai 201306China Department of Civil and Environmental Engineering University of CaliforniaBerkeley CA 94720USA

Due to complex mesoscopic and the distinct macroscopic evolution characteristics of ice,especially for its brittle-to-ductile transition in dynamic response,it is still a challenging task to build an accurate ice constitutive model to predict ice loads during ship-ice *** address this,we incorporate the conventional multi-yield-surface plasticity model with the state-based peridynamics to simulate the stress and crack formation of ice under ***,we take into account of the effects of inhomogeneous temperature distribution,strain rate,and pressure *** doing so,we can successfully predict material failure of isotropic freshwater ice,iceberg ice,and columnar saline ***,the proposed ice constitutive model is validated through several benchmark tests,and proved its applicability to model ice fragmentation under impacts,including drop tower tests and ballistic *** results show that the proposed approach provides good computational performance to simulate ship-ice collision.

关键词： Ice loads Multi-yield-surface Constitutive model Peridynamics Ice-structure interaction

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Co-occurrence patterns and related risk factors of ischaemic heart disease and ischaemic stroke across 203 countries and territories: a spatial correspondence and systematic analysis

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The Lancet Global Health 2025年第5期13卷 e808-e819页

作者： An, Xuanqi Liu, Zeye zhang, luwen Zhao, Jing Gu, Qing Han, Wei Hu, Yaoda Xue, Fang zhang, Fengwen Wang, Shouzheng Ouyang, Wenbin Yang, Yanmin Fu, Rui Yang, Weixian Leng, Sean X Liu, Jue Jiang, Jingmei Pan, Xiangbin Emergency Department National Clinical Research Center of Cardiovascular Diseases Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China Department of Structural Heart Disease National Clinical Research Center of Cardiovascular Diseases Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China State Key Laboratory of Cardiovascular Disease National Clinical Research Center of Cardiovascular Diseases Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China National Clinical Research Center of Cardiovascular Diseases Fuwai Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China National Health Commission Key Laboratory of Cardiovascular Regeneration Medicine Beijing China Key Laboratory of Innovative Cardiovascular Devices Chinese Academy of Medical Sciences Beijing China Department of Epidemiology and Biostatistics Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Beijing China Johns Hopkins Center on Aging and Immune Remodeling Division of Geriatric Medicine and Gerontology Department of Medicine Johns Hopkins University School of Medicine and Bloomberg School of Public Health Baltimore MD United States Department of Health Policy and Management and W Harry Feinstone Department of Molecular Microbiology and Immunology Johns Hopkins University School of Medicine and Bloomberg School of Public Health Baltimore MD United States Department of Epidemiology and Biostatistics School of Public Health Peking University Beijing China

Background: Ischaemic heart disease (IHD) and ischaemic stroke are leading causes of death worldwide. Although extensively studied, previous research has predominantly addressed these two diseases in isolation. Comorbidity research faces challenges both at the patient level and in terms of study methods. We aimed to characterise the global co-occurrence pattern of IHD and ischaemic stroke from a spatial perspective and to identify the corresponding risk factors of the comorbidity. Methods: Using data from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 database, we extracted incidence rates of IHD and ischaemic stroke and exposure rates of the 68 most detailed risk factors among individuals aged 25 years or older from 203 countries and territories. Based on the four quartiles of global incidence rates for both diseases, we proposed the comorbidity's co-occurrence patterns and classified the 203 countries or territories into three distinct regions (consistent, IHD-dominant, and ischaemic stroke-dominant areas). We used machine learning and negative binomial regression to screen and quantify the effects of corresponding risk factors and computed the population-attributable fraction and composite risk index to evaluate the global disease burden of IHD and ischaemic stroke. Findings: 89 countries were classified as consistent, 59 as IHD-dominant, and 55 as ischaemic stroke-dominant. The spatial distribution of the three co-occurrence patterns overlapped with exposure to environmental, dietary, and behavioural risk factors. Nine risk factors were identified and functionally classified into common and specific features. Most countries are simultaneously exposed to the combined effects of multiple risk factors. Overall, 45·43% of IHD incidence and 38·53% of ischaemic stroke incidence is attributable to cumulative exposure to the respective risk factors, with specific combinations and variations of these factors greatly influencing the global disp

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Predictions of mortality related to four major cancers in China,2020 to 2030

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Cancer Communications 2021年第5期41卷 404-413页

作者： Ning Li Peng Wu Yubing Shen Cuihong Yang luwen zhang Yali Chen Zixing Wang Jingmei Jiang Department of Epidemiology and Biostatistics Institute of Basic Medicine SciencesChinese Academy of Medical Sciences/School of Basic MedicinePeking Union Medical CollegeBeijing 100005P.R.China

Background:Cancer has become a global health problem,and assessments of cancer mortality are important for effective public health policy-making and adequate resource *** this study,we aimed to predict the mortality rates and numbers of deaths related to four common cancers(lung,liver,stomach,and esophagus)in China from 2020 to 2030 and to estimate the corresponding cancer burden caused by population aging and tobacco ***:Cancer mortality data(2004-2017)were extracted from China’s death surveillance datasets,and China’s population figures(2020-2030)were obtained from the United Nations population *** prevalence data were retrieved from a World Health Organization global report,and relative risks of smoking and cancers were derived from large-scale Asian *** predicted the deaths related to the four major cancers and age-standardized mortality rates using joinpoint regression and linear regression *** tobacco smoking related burden of these four major cancers was estimated using the population attributable ***:Unlike lung cancer mortality which was predicted to continue to increase,the age-standardized mortality rates for digestive cancers(liver,stomach,and esophageal cancers)are predicted to decline over the next *** number of deaths caused by the four major cancers is predicted to increase from 1,490,304 in 2020 to 1,823,960 in *** age-specific mortality rates of the four major cancers are predicted to increase with age after 40-45 years,peaking in the age groups of 80-84 and ≥85 *** 2030,the combined number of deaths from the four examined cancers among adults aged ≥65 years is predicted to be 1,167,153,accounting for 64% of all deaths from these *** smoking is predicted to contribute to nearly 29% of deaths fromthese cancers,corresponding to 527,577 ***:The overall trend in the combined total mortality from four major cancers is predicted to decline over th

关键词： cancer mortality China esophageal cancer liver cancer lung cancer population aging prediction smoking stomach cancer

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Assessment of the spatial association between multiple pollutants of surface water and digestive cancer incidence in China: A novel application of spatial machine learning

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ECOLOGICAL INDICATORS 2023年第1期154卷

作者： Gu, Wentao Xue, Fang Han, Wei Wang, Zixing Zhao, Jing zhang, luwen Yang, Cuihong Jiang, Jingmei Chinese Acad Med Sci Inst Basic Med Sci Dept Epidemiol & Biostat Beijing Peoples R China Peking Union Med Coll Sch Basic Med Beijing Peoples R China

Surface water pollution and digestive cancers are concerning environmental health issues. Multiple pollutants of surface water coexist within unique geospatial heterogeneous contexts of surface water flow, which can lead to complex patterns of impact on cancer incidence. This complexity has posed challenges to comprehensive assessment. In this study, we integrated nationwide surface water data of 21 pollutants collected from 3632 sections of nine large river basins and cancer incidence data for six digestive cancers covering 381.6 million people in China. Local Moran's I method was used to assess the patterns of spatial aggregation of each surface water pollutant separately to observe the local spatial nonstationarity and heterogeneity of the pollutant con-centrations in different spatial areas. A geographically weighted random forest (GWRF) model, a spatial machine learning approach, was applied to address the spatial heterogeneity of the pollutants and assess their association with cancer incidence. Goodness-of-fit and overall performance of the GWRF model were assessed by the local statistics in the out-of-bag set, such as the mean local pseudo-R2, increase in mean squared error, and local re-siduals in each local model. Compared with the aspatial random forest model, the GWRF model had better performance (mean local pseudo-R2 ranged from 0.16 (gallbladder cancer) to 0.60 (pancreatic cancer)). Surface water pollution was associated with digestive cancer incidence mainly in the Songhua and Liaohe, Haihe, and Huaihe River Basins. By focusing on these areas, we identified key pollutants specific to different cancer types. Incidence of oesophageal, stomach, colorectal, gallbladder, and pancreatic cancer was associated with common pollutants such as fluoride and arsenic. Our assessment provides targets for the government and environmental health specialists to take tailored actions to control pollution and effectively prevent cancer incidence.

关键词： Digestive cancer Surface water pollutant Spatial machine learning Spatial association China

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Enhanced room temperature ammonia response of 2D-Ti3C2Tx MXene decorated with Ni(OH)2 nanoparticles

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CERAMICS INTERNATIONAL 2021年第14期47卷 19471-19480页

作者： Kuang, Delin Guo, Xuezheng Zhu, ZeTao Ding, Yanqiao Sun, Xia Wu, Zhilin zhang, luwen Zhou, Yangyang He, Yong Chongqing Univ Coll Optoelect Engn Educ Minist China Key Lab Optoelect Technol & Syst Chongqing 400044 Peoples R China Chongqing Univ State Key Lab Coal Mine Disaster Dynam & Control Chongqing 400044 Peoples R China Nagoya Univ Grad Sch Engn Dept Biomol Engn Nagoya 4648603 Japan

Due to the expansion of human production activities, toxic ammonia (NH3) is excessively released into the atmosphere, being a huge threat to human health and the natural environment. Therefore, it is of great significance to design an easy-synthesized gas-sensing material with both good room temperature sensitivity and selectivity for trace-level NH3 detection. Herein, we fabricate a chemiresistive NH3 gas sensor with enhanced performance based on Ni(OH)2/Ti3C2Tx hybrid materials. The Ni(OH)2/Ti3C2Tx hybrid materials are synthesized by an in-situ electrostatic self-assembly method. Attributed to the formation of interfacial heterojunctions and the modulation of carrier density, the Ni(OH)2/Ti3C2Tx hybrid sensor exhibits high response, outstanding repeatability, good selectivity and stability in low concentrations of NH3. Moreover, the Ni(OH)2/Ti3C2Tx hybrid sensor has a higher response to 10 ppm NH3 at the relative humidity of 40% and 60%, which makes it promising for applications in real complex environments with high humidity. Benefitting from the low power consumption and easy fabrication process, the Ni(OH)2/Ti3C2Tx hybrid sensor possesses a broad application prospect in the internet of things (IoT) environmental monitoring.

关键词： MXene Nickel hydroxide Hybrid materials Environmental monitoring Ammonia sensor

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Prediction of complications associated with general surgery using a Bayesian network

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SURGERY 2023年第5期174卷 1227-1234页

作者： Yu, Xiaochu Chen, Wangyue Han, Wei Wu, Peng Shen, Yubing Huang, Yuguang Xin, Shijie Wu, Shizheng Zhao, Shengxiu Sun, Hong Lei, Guanghua Wang, Zixing Xue, Fang zhang, luwen Gu, Wentao Jiang, Jingmei Chinese Acad Med Sci Peking Union Med Coll Hosp Dept Nephrol Beijing Peoples R China Chinese Acad Med Sci Peking Union Med Coll Sch Basic Med Inst Basic Med SciDept Epidemiol & Biostat Beijing Peoples R China Chinese Acad Med Sci Peking Union Med Coll Hosp Dept Anaesthesiol Beijing Peoples R China China Med Univ Hosp 1 Dept Vasc & Thyroid Surg Shenyang Liaoning Peoples R China Qinghai Prov Peoples Hosp Inst Geriatr Xining Peoples R China Qinghai Prov Peoples Hosp Dept Nursing Xining Peoples R China Cent South Univ Xiangya Hosp Dept Otolaryngol Skull Base Surg Changsha Hunan Peoples R China Cent South Univ Xiangya Hosp Dept Orthopaed Changsha Hunan Peoples R China Chinese Acad Med Sci Peking Union Med Coll Sch Basic Med Inst Basic Med SciDept Epidemiol & Biostat 5 Dongdan Santiao St Beijing 100005 Peoples R China

Background: Numerous attempts have been made to identify risk factors for surgery complications, but few studies have identified accurate methods of predicting complex outcomes involving multiple complications. Methods: We performed a prospective cohort study of general surgical inpatients who attended 4 regionally representative hospitals in China from January to June 2015 and January to June 2016. The risk factors were identified using logistic regression. A Bayesian network model, consisting of directed arcs and nodes, was used to analyze the relationships between risk factors and complications. Probability ratios for complications for a given node state relative to the baseline probability were calculated to quantify the potential effects of risk factors on complications or of complications on other complications. Results: We recruited 19,223 participants and identified 21 nodes, representing 9 risk factors and 12 complications, and 55 direct relationships between these. Respiratory failure was at the center of the network, directly affected by 5 risk factors, and directly affected 7 complications. Cardiopulmonary resuscitation and sepsis or septic shock also directly affected death. The area under the receiver operating characteristic curve for the ability of the network to predict complications was >0.7. Notably, the probability of other severe complications or death significantly increased when a severe complication occurred. Most importantly, there was a 141-fold higher risk of death when cardiopulmonary resuscitation was required. Conclusion: We have created a Bayesian network that displays how risk factors affect complications and their interrelationships and permits the accurate prediction of complications and the creation of appropriate preventive guidelines.

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Immunogenic and diagnostic potential of recombinant apical membrane antigen-1 from Plasmodium malariae

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DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE 2024年第3期110卷 116480-116480页

作者： Li, Moyan Liu, Tingting Wang, Yuerong zhang, luwen Lu, Fanbo Xia, Jinxing Zheng, Meijuan zhang, Min Wang, Bo Xu, Yuanhong Anhui Med Univ Affiliated Hosp 1 Dept Clin Lab Hefei 230022 Anhui Peoples R China Nanjing Med Univ Childrens Hosp Inst Pediat Nanjing Jiangsu Peoples R China Anhui Univ Tradit Chinese Med Affiliated Hosp 2 Dept Clin Lab Hefei Anhui Peoples R China Anhui Med Univ Affiliated Hosp 2 Dept Clin Lab Hefei Anhui Peoples R China

The apical membrane antigen-1 (AMA-1) is a crucial target for malaria management and prevention strategies. While the immunogenicity of AMA-1 has been extensively studied for Plasmodium falciparum and Plasmodium vivax, there is a notable scarcity of information for Plasmodium malariae. In this study, recombinant PmAMA-1 was expressed in Escherichia coli, and its integrity was confirmed via western blotting and indirect immunofluorescence assays. Immunization of BALB/c mice with rPmAMA-1 emulsified in Freund's adjuvant resulted in significantly elevated specific IgG antibodies, predominantly IgG1. The immune response exhibited Th1, Th2, and Th17 phenotypes, with a notable Th1 bias. Antisera from immunized mice effectively recognized native PmAMA-1 on P. malariae. These results suggest that PmAMA-1 is a promising target for both vaccine development and diagnostic applications for P. malariae infections, offering dual preventive and diagnostic benefits in malaria control.

关键词： Plasmodium malariae AMA-1 Immunogenicity IgG subclasses Cytokines

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人民币汇率波动与企业根本性创新:立竿见影还是润物无声?

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金融市场研究 2025年第1期 16-28页

作者：张晓莉韦啸张露文上海对外经贸大学国际经贸学院上海对外经贸大学世界经济研究所上海对外经贸大学金融管理学院南开大学经济学院

党的二十大报告指出,我国未来发展的总体目标之一是实现高水平科技自立自强,进入创新型国家前列,而取得根本性创新是实现该目标的重要途径。本文从汇率升值的视角出发,实证检验了其对企业创新质量和根本性创新的影响。结果表明人民币升... 详细信息

党的二十大报告指出,我国未来发展的总体目标之一是实现高水平科技自立自强,进入创新型国家前列,而取得根本性创新是实现该目标的重要途径。本文从汇率升值的视角出发,实证检验了其对企业创新质量和根本性创新的影响。结果表明人民币升值提升企业创新质量的渠道是进口中间品种类的增加和质量的提高,但由于“卡脖子”等问题的存在使得从整体上看汇率升值对根本性创新的推动不显著,然而渠道检验表明人民币升值时进口中间品种类的增加和质量的提高有助于促进企业的根本性创新。异质性分析表明在人民币升值时,原本融资约束更强的企业对创新的推动更明显,而原本行业竞争力更强的企业却缺乏创新的动力。本文创新之处在于发现了虽然人民币升值能从整体上提高企业的创新质量,但对于根本性创新的推动不是立竿见影的而是渐进的。该结论有助于政策制定者针对特定的企业类型制定相应的汇率政策更好地促进根本性创新,为我国进入创新型国家赋能。

关键词：汇率企业创新质量根本性创新

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