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Blocking the PD-1 signal transduction by occupying the phosphorylated ITSM recognition site of SHP-2

Science China(Life Sciences) 2025年第1期68卷 189-203页

作者： Wenjie Li Wenyi Mei Hewei Jiang Jie Wang Xiaoli Li Lina Quan Yanyan Diao Yanni Ma Sisi Fan Zhuwei Xie Mengdie Gong Huan Zhu Dewen Bi Feng Zhang Lei Ma Jian Zhang Yufeng Gao Aris Paschalidis Honghuang Lin Fangfang Liu Kangdong Liu Mingliang Ye Zhenjiang Zhao Yajun Duan Zhuo Chen Yufang Xu Weilie Xiao Shengce Tao Lili Zhu Honglin Li Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science&TechnologyShanghai 200237China Shanghai Center for Systems Biomedicine Key Laboratory of Systems Biomedicine(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200240China Key Laboratory of Medicinal Chemistry for Natural resource Ministry of EducationYunnan Characteristic Plant Extraction LaboratoryYunnan Provincial Center for Research&Development of Natural ProductsState Key Laboratory for Conservation and Utilization of Bio-Resources in YunnanSchool of Pharmacy and School of Chemical Science and TechnologyYunnan UniversityKunming650500China CAS Key Laboratory of Separation Sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China department of Cardiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China department of Infectious Diseases The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China department of Medicine University of Massachusetts Chan Medical SchoolWorcester MA 01655USA department of Pathophysiology School of Basic Medical SciencesAcademy of Medical ScienceCollege of MedicineZhengzhou UniversityZhengzhou 450001China Innovation Center for AI and Drug Discovery East China Normal UniversityShanghai 200062China Lingang Laboratory Shanghai 200031China

Targeting the PD-1/PD-L1 axis with small-molecular inhibitors is a promising approach for ***,we identify a natural pentacyclic triterpenoid,Pygenic Acid A(PA),as a PD-1 signaling *** exerts anti-tumor activity in hPD-1 knock-in C57BL/6 mice and enhances effector functions of T cells to promote immune responses by disrupting the PD-1 signaling ***,we identify SHP-2 as the direct molecular target of PA for inhibiting the PD-1 signaling ***,mechanistic studies suggest that PA binds to a new druggable site in the phosphorylated PD-1 ITSM recognition site of SHP-2,inhibiting the recruitment of SHP-2 by *** together,our findings demonstrate that PA has a potential application in cancer immunotherapy and occupying the phosphorylated ITSM recognition site of SHP-2 may serve as an alternative strategy to develop PD-1 signaling *** addition,our success in target recognition provides a paradigm of target identification and confirmation for natural products.

关键词： pygenic acid A programmed death-1 immunoreceptor tyrosine-based switch motif SH2 domain-containing protein-tyrosine phosphatase-2 target identification site recognition

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Predictions of H-mode access and edge pedestal instability in the EHL-2 spherical torus

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Plasma Science and Technology 2025年第02期 59-68页

作者：王嵎民李凯黄卓刘一良戴舒宇张洁黄艳清顾翔赵毅航徐帅王二辉郭栋石跃江谢华生梁云峰刘敏胜 the EHL-2 Team Hebei Key Laboratory of Compact Fusion ENN Science and Technology development Co. Ltd. Centre for Theoretical and Computational Physics College of Physics Qingdao University College of Computer Science South-Central Minzu University Key Laboratory of Materials Modification by Laser Ion and Electron Beams (Ministry of Education)School of Physics Dalian University of Technology department of Plasma Physics and Fusion Engineering University of Science and Technology of China College of Physics and Electronic Engineering Hengyang Normal University Forschungszentrum Jülich GmbH Institute of Fusion Energy and Nuclear Waste Management-Plasmaphysik

The EHL-2 spherical torus is designed to demonstrate proton-boron(p-11B) fusion within a compact spherical *** planned heating system includes a negative ion-based neutral beam injection（N-NBI）,two positive ion-based NBI systems（P-NBI）,electron cyclotron resonance heating（ECRH）,ion cyclotron resonance heating（ICRH）,and high harmonic fast wave（HHFW）,with a total power output of 31 *** to scaling law estimates,the device is capable of achieving H-mode *** plasma density,ne,min,at the minimum LH power threshold,PLH,is estimated to be 4.4× *** pedestal parameters were calculated using the REPED *** B as the primary impurity ion,the predicted pedestal width and height are lower compared to the typical case with carbon *** pedestal collisionality for EHL-2 is estimated to range between 0.06 and 0.17,indicating the potential for significant energy loss due to edge localized modes（ELMs）.The heat flux on the divertor plate has been calculated using the JOREK *** peak heat fluxes during ELM bursts are approximately 31.0 MW/m2at the lower inboard target and 39.5 MW/m2at the lower outboard target.A preliminary design of the resonant magnetic perturbation（RMP） coils has been completed to both control type-Ⅰ ELMs and correct error *** system comprises 16coils arranged into 2×4 *** ELM control mode,a 14/2 component is generated at 1.7 G/kAt,with a current of 4.9 kA required to achieve σChirikov=1 at the resonant surface,where the normalized poloidal magnetic flux is *** error field（EF） modulation mode,2/1 and 3/1components are generated at 3.5 G/kAt and 2.8 G/kAt,respectively.

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Hydrogen Energy Demand management in China:A department Scenario Analysis Method

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Energy Engineering 2025年第3期122卷 971-983页

作者： Zhongxun Li Bing Wang Xiaolin Liu Center for Sustainable development and Energy Policy Research School of Energy and Mining EngineeringChina University of Mining and Technology-BeijingBeijing100083China Research Institute of Decision-Making Science and Big Data School of ManagementChina University of Mining and Technology-BeijingBeijing100083China

The proposal of carbon neutrality target makes decarbonization and hydrogenation typical features of future energy development in *** a wide range of application scenarios,hydrogen energy will experience rapid growth in production and *** formulate an effective hydrogen energy development strategy for the future of China,this study employs the departmental scenario analysis method to calculate and evaluate the future consumption of hydrogen energy in China’s heavy industry,transportation,electricity,and other related *** technical parameters are selected and predicted accurately and reliably in combination with different development *** findings indicate that the period from 2030 to 2050 will enjoy rapid development of hydrogen energy,having an average annual growth rate of 2%to 4%.The technological progress and breakthroughs scenario has the greatest potential for hydrogen demand scale among the four development *** this scenario,the total demand for hydrogen energy is expected to reach 446.37Mt in *** sector will be the sector with the greatest potential for hydrogen deployment growth from 2023 to 2060,which is expected to rise from 0.038Mt to about 163.18Mt,with the ambitious growth in the ***,hydrogen energy has a considerable development potential in the steel sector,and the trend of de-refueling coke by hydrogenation in this sector will be imperative for this energy-intensive industries.

关键词： Hydrogen demand management department scenario analysis carbon neutrality

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Anti Toxoplasma antibodies prevalence and associated risk factors among HIV patients

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Asian Pacific Journal of Tropical Medicine 2016年第5期9卷 446-451页

作者： Dechassa Tegegne Mukarim Abdurahaman Tadesse Mosissa Moti Yohannes department of Microbiology and Veterinary Public Health Jimma University department of Natural resource management Jimma University

Objective: To assess the seroprevalence and associated risk factors of toxoplasmosis among HIV patients in Agaro Town Health Center of Jimma zone. Methods: Convenient sampling was used to collect blood samples from 135 patients attending anti retroviral therapy from February to March 2015. Serum samples were tested for anti-Toxoplasma gondii(T. gondii) antibody by using latex agglutination test. Structured questionnaire was used to collect data on socio-demographic and risk factors associated with toxoplasmosis. Results: Overall seroprevalence of toxoplasmosis was 80.7%(109/135, CI: 74.04-87.36). In multivariate analysis significant association was observed between anti T. gondii seropositivity and raw meat consumption(OR: 3.514, CI: 1.167 10.581, P=0.025), knowledge about toxoplasmosis(OR: 5.225, CI: 1.382, P=0.015) and sex(OR: 4.023, CI: 1.382-19.762, P=0.015). Conclusions: Immuno compromised patients showed high rate of seropositivity and thus, it is highly advisable to introduce routine anti-T. gondii antibodies serological screening test prior to ART commencement.

关键词： Toxoplasma gondii HIV LAT Seroprevalence

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Improve access to the EU market by identifying French consumer preference for fresh fruit from China

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Journal of Integrative Agriculture 2018年第6期17卷 1463-1474页

作者： WANG Er-peng Zhifeng Gao Yan Heng School of Economics and management Nanjing Tech University College of Economics and management Jilin Agricultural University Food and resource Economics department University of Florida

Most previous studies have investigated country-of-origin effect for agricultural products from the economically developed country, but few have focused on the impact of country-of-origin on agricultural products from economically developing countries. Using a national online survey in France, we determine French consumers＇ perceptions and preferences for fresh fruit from China. Results of ordered logit models show that fresh fruit from China was perceived as low quality and unsafe. Respondents who care about country-of-origin were less likely to purchase fresh fruit from China, while those who care about brand were more likely to buy Chinese fresh fruit. Risk perception and quality perception both had a significant impact on the purchase of Chinese fresh fruit. Results of latent class models obtained with key consumer demographics show that heterogeneous preferences exist among different consumer groups. The results provide critical information to both China and other economically developing countries in their efforts to improve market penetration in economically developed countries.

关键词： country of origin perception consumer preference fresh fruit China

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Bacterial succession in epiphytic biofilms and deciduous layer sediments during Hydrilla verticillata decay: A field investigation

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Journal of Environmental Sciences 2020年第7期32卷 193-201页

作者： Tingting Si Hezhou Chen Zheng Qiu Lisha Zhang Okugbe Ebiotubo Ohore Songhe Zhang Ministry of Education Key Laboratory of Integrated Regulation and resource development on Shallow Lakes College

Submersed macrophytes decay is an important natural process and has important role in mass and energy flow in aquatic ***,little is known about the dynamical changes in nutrients release and bacterial community during submersed macrophyte decay in natural *** this study,a field observation was conducted in a wetland dominated with Hydrilla verticillata for 36 *** of H2O2 and malondialdehyde(MDA)content and decrease of soluble proteins concentration were detected in leaves during *** ***,ammonium-N,soluble microbial products(SMP)and TOC concentration increased in overlying *** to bacterial 16 S r RNA Illumina sequencing analysis,the Shannon values were lower in epiphytic biofilms than deciduous layer *** relative abundances of Proteobacteria,Cyanobacteria and Actinobacteria were higher in epiphytic biofilms than in deciduous layer sediments(P0.6)were identified from 122 and 112 genera in epiphytic biofilms and deciduous layer sediments,*** to co-occurrence patterns,eight hubs were mainly from phyla Proteobacteria,Acidobacteria and Parcubacteria in epiphytic biofilms;while 37 hubs from the 14 phyla(Proteobacteria,Bacteroidetes,Acidobacteria,Chloroflexi,et al.)were detected in deciduous layer *** results indicate that bacterial community in deciduous layer sediments was more susceptible than in epiphytic biofilms during decay *** data highlight the role of microbial community in deciduous layer sediments on nutrients removal during *** decay and will provide useful information for wetland management.

关键词： Submersed macrophyte Decay Biofilm Bacterial community Co-occurrence network

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Amoenucles A-F,novel nucleoside derivatives with TNF-α inhibitory activities from Aspergillus amoenus TJ507

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Chinese Journal of Natural Medicines 2025年第1期23卷 111-118页

作者： Yeting Zhang Zhengyi Shi Chunhua Zhao Lanqin Li Ming Chen Yunfang Cao Fengqing Wang Bo Tao Xinye Huang Jieru Guo Changxing Qi Weiguang Sun Yonghui Zhang Hubei Key Laboratory of Natural Medicinal Chemistry and resource Evaluation School of Pharmacy Tongji Medical College Huazhong University of Science and Technology department of Pharmacy Tongji Hospital Tongji Medical college Huazhong University of Science and Technology Institute of Organ Transplantation Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Key Laboratory of Organ Transplantation Ministry of Education NHC Key Laboratory of Organ Transplantation Chinese Academy of Medical Sciences

Amoenucles A-F(1-6), six previously undescribed nucleoside derivatives, and two known analogs(7 and 8) were isolated from the culture of Aspergillus amoenus TJ507. Their structures were elucidated through spectroscopic analysis, single-crystal X-ray crystallography,and chemical reactions. Notably, 3 and 4 represent the first reported instances of nucleosides with an attached pyrrole moiety. Of particular significance, the absolute configuration of the sugar moiety of 1-4 was determined using nuclear magnetic resonance(NMR), electric circular dichroism(ECD) calculations, and a hydrolysis reaction, presenting a potentially valuable method for confirming nucleoside structures. Furthermore, 1, 2, and 5-8 exhibited potential tumor necrosis factor α(TNF-α) inhibitory activities, which may provide a novel chemical template for the development of agents targeting autoimmune and inflammatory diseases.

关键词： Aspergillus amoenus TJ507 Intramolecular transesterification Nucleoside derivatives Tumor necrosis factor α (TNF-α)

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A methodological framework for analyzing PPGIS data collected in 3D

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International Journal of Digital Earth 2023年第1期16卷 3435-3455页

作者： Kamyar Hasanzadeh Nora Fagerholm Hans Skov-Petersen Anton Stahl Olafsson department of Geography and Geology University of TurkuTurkuFinland department of Geosciences and Natural resource management University of CopenhagenCopenhagenDenmark

Public participation geographic information system(PPGIS)is a facilitated Volunteered Geographic Information approach and data collection method that aims to capture the spatial experiences of *** we experience the space around us three-dimensionally,altitude,as the third dimension,has been often absent from PPGis research and *** is largely because of the complexity of implementing surveys in 3D but can also be attributed to a lack of analytical preparedness for using such *** study complements 3D PPGIS data collected from a pilot study of the Aninkainen block in Turku,Finland with synthetic,*** manufactured,data to propose an analytical framework for the study of 3D PPGIS *** analytical framework divides methods based on the geographical scale into two groups:micro-and macro-scale *** this framework,we propose the use of geospatial metrics to analyze 3D PPGIS *** argue that while this multidisciplinary area of research is in its infancy,use of intuitive 3D adapted geometric and landscape metrics can help overcome some of complexities associated with use of this emerging participatory *** conclude by outlining the limitations and envisioning areas for future research.

关键词： 3D GIS landscape metrics PPGIS

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Stir-Fried Semen Armeniacae Amarum Suppresses Aristolochic AcidⅠ-Induced Nephrotoxicity and DNA Adducts

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Chinese Journal of Integrative Medicine 2025年第2期31卷 142-152页

作者： LI Cheng-xian XIAO Xiao-he LI Xin-yu XIAO Da-ke WANG Yin-kang WANG Xian-ling ZHANG Ping LI Yu-rong NIU Ming BAI Zhao-fang School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing(100102)China department of Hepatology Military Institute of Chinese Materiathe Fifth Medical CentreGeneral Hospital of PLABeijing(100039)China National Key Laboratory of Kidney Beijing(100039)China School of Pharmacy Chengdu University of Traditional Chinese MedicineChengdu(610075)China School of Traditional Chinese Medicine Capital Medical UniversityBeijing(100069)China School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou(510515)China department of Pharmacy Medical Supplies Center of PLA General HospitalBeijing(100039)China department of Military Patient management the Fifth Medical Center of PLA General HospitalBeijing(100039)China department of Hematology the Fifth Medical Center of Chinese PLA General HospitalBeijing(100071)China

Objective:To investigate the protective effects of stir-fried Semen Armeniacae Amarum(SAA)against aristolochic acidⅠ(AAⅠ)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et ***:In vitro,HEK293T cells overexpressing Flag-tagged multidrug resistance-associated protein 3(MRP3)were constructed by Lentiviral transduction,and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening *** m RNA,protein expressions,and enzyme activity levels of NAD(P)H quinone dehydrogenase 1(NQO1)and cytochrome P4501A2(CYP1A2)were measured in differentiated Hepa RG *** toxicity after inhibition of AAⅠmetabolite transport was detected using cell counting kit-8 *** vivo,C57BL/6 mice were randomly divided into 5 groups according to a random number table,including:control(1%sodium bicarbonate),AAⅠ(10 mg/kg),stir-fried SAA(1.75 g/kg)and AAⅠ+stir-fried SAA(1.75 and 8.75 g/kg)groups,6 mice in each *** 7 days of continuous gavage administration,liver and kidney damages were assessed,and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined ***:In vivo,combination of 1.75 g/kg SAA and 10 mg/kg AAⅠsuppressed AAⅠ-induced nephrotoxicity and reduced d A-ALI formation by 26.7%,and these detoxification effects in a dose-dependent manner(P<0.01).Mechanistically,SAA inhibited MRP3 transport in vitro,downregulated NQO1 expression in vivo,increased CYP1A2 expression and enzymatic activity in vitro and in vivo,respectively(P<0.05 or P<0.01).Notably,SAA also reduced AAⅠ-induced hepatotoxicity throughout the detoxification process,as indicated by a 41.3%reduction in the number of liver adducts(P<0.01).Conclusions:Stirfried SAA is a novel drug candidate for the suppression of AAⅠ-induced liver and kidney dam

关键词： aristolochic acidⅠ stir-fried Semen Armeniacae Amarum detoxification principles of compatibility metabolic enzymes transporters

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The PtobZIP55–PtoMYB170 module regulates the wood anatomical and chemical properties of Populus tomentosa in acclimation to low nitrogen availability

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Journal of Integrative Plant Biology 2025年第1期67卷 117-134页

作者： Jiangting Wu Shurong Deng Yang Wang Chenlin Jia Jia Wei Mengyan Zhou Dongyue Zhu Zhuorong Li Payam Fayyaz Zhi-Bin Luo Jing Zhou Wenguang Shi State Key Laboratory of Tree Genetics and Breeding Research Institute of ForestryChinese Academy of ForestryBeijing 100091China Forest Range and Watershed Management DepartmentAgriculture and Natural Resources FacultyYasouj UniversityYasuj ***Iran Instituteof Ecological Conservation and Restoration Chinese Academy of ForestryBeijing 100091China Comprehensive Experimental Center of Chinese Academy of Forestry in Yellow River Delta DongyingShandong 257000China

Poplar plantations are often established on nitrogen-poor land,and poplar growth and wood formation are constrained by low nitrogen(LN)***,the molecular mechanisms by which specific genes regulate wood formation in acclimation to LN availability remain ***,we report a previously unrecognized module,basic region/leucine zipper 55(PtobZIP55)–PtoMYB170,which regulates the wood formation of Populus tomentosa in acclimation to LN ***55 was highly expressed in poplar wood and induced by *** wood anatomical properties and increased lignification were detected in PtobZIP55-overexpressing poplars,whereas the opposite results were detected in PtobZIP55-knockout *** and transgenic analyses revealed that PtobZIP55 directly binds to the promoter sequence of PtoMYB170to activate its *** phenotypes of PtoMYB170 transgenic poplars were similar to those of PtobZIP55 transgenic poplars under LN *** molecular analyses revealed that PtoMYB170 directly bound the promoter sequences of lignin biosynthetic genes to activate their transcription to increase lignin concentrations in LN-treated poplar *** results suggest that PtobZIP55 activates PtoMYB170 transcription,which in turn positively regulates lignin biosynthetic genes,increasing lignin deposition in the wood of *** in the context of acclimation to LN availability.

关键词： lignin biosynthesis nitrogen deficiency Populus secondary xylem transcriptional regulation wood formation

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