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

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Science China Life sciences 2024年

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 Innovation Center for AI and Drug Discovery East China Normal University Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science&Technology Shanghai Center for Systems Biomedicine Key Laboratory of Systems Biomedicine (Ministry of Education)Shanghai Jiao Tong University Lingang Laboratory 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 University CAS Key Laboratory of Separation sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of Sciences Department of Cardiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of China Department of Infectious Diseases The First Affiliated Hospital of Anhui Medical University Department of Medicine University of Massachusetts Chan Medical School Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical ScienceCollege of MedicineZhengzhou University

Targeting the PD-1/PD-L1 axis with small-molecular inhibitors is a promising approach for immunotherapy. Here, we identify a natural pentacyclic triterpenoid, Pygenic Acid A(PA), as a PD-1 signaling inhibitor. PA 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 transduction. Furthermore, we identify SHP-2 as the direct molecular target of PA for inhibiting the PD-1 signaling transduction. Subsequently, 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 PD-1. Taken 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 inhibitors. In addition, our success in target recognition provides a paradigm of target identification and confirmation for natural products.

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Fermi level tuning in SnPbTe/Pb heterostructure via changing interface roughness

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Science China(Physics,Mechanics & Astronomy) 2024年

作者： Tengteng Liu Zhaoxia Yi Bangjin Xie Weiyan Zheng Dandan Guan Shiyong Wang Hao Zheng Canhua Liu Hao Yang Yaoyi Li Jinfeng Jia Key Laboratory of Artificial Structures and Quantum Control (Ministry of Education) Tsung-Dao Lee InstituteSchool of Physics and AstronomyShanghai Jiao Tong University Shanghai Research Center for Quantum sciences Hefei National Laboratory

Superconducting SnTe-type topological crystalline insulators （TCIs） are predicted to host multiple Majorana zero modes（MZMs） which can coexist in a single vortex. Fermi level （FL） close to the Dirac points of topological surface states is helpful for detecting MZMs. However, the TCI SnTe is a heavily p-type semiconductor which is very difficult to modify to n-type via doping or alloying. In this work, we fabricate the atomically flat Sn1-xPbxTe/Pb heterostructure by molecular beam epitaxy, and make the p-type Sn1-xPbxTe become n-type through changing the interface roughness. Using scanning tunnelling microscope, we find the Dirac points of Sn1-xPbxTe/Pb heterostructure are always above the FL due to the Fermi level pinning （FLP） induced by topological surface states at atomically flat interface. After increasing the interface roughness, the FLP effect is suppressed and then the Dirac points of p-type Sn1-xPbxTe can be tuned very close to or even below the FL. Our work provides a new method for tuning the FL of SnTe-type TCI which has potential application in novel topological superconductor device.

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Synthesis of hierarchically porous carbon materials by zinc salts-assisted carbonization of biomass and organic solid wastes

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Particuology 2024年第1期84卷 45-52页

作者： Le-Le Zhang Lei Tong Yanwei Ding Wanqun Zhang Hai-Wei Liang Hefei National Research Center for Physical sciences at the Microscale Department of ChemistryUniversity of Science and Technology of ChinaHefei230026China

Hierarchically porous carbons(HPCs)with multimodal pores have attracted considerable attention due to their unique physical and chemical properties and various application potentials in heterogeneous catalysis,environmental treatment,and energy storage and ***,we report a general and simple zinc salts-assisted method for the synthesis of HPCs with varied porosity and chemical func-tionalities by the direct carbonization of diverse biomass and *** the carbonization,zinc salts are thermally decomposed into nanoparticles that serve as in-situ templates to introduce nanopores in *** prepared HPCs exhibit high specific surface areas(up to 2432 m2 g-1),large pore volumes(up to 4.30 cm^(3)g^(-1)),and broad pore size ***,the zinc salts can be recovered and recycled,supporting the sustainable production of HPCs on large *** prepared HPCs-supported catalysts with atomically dispersed metal sites exhibit promising electrocatalytic performance for the oxygen reduction reaction.

关键词： Hierarchical porous carbon Zinc salts Biomass Wastes Electrocatalysis

Provenance and paleogeographic evolution of the Upper Paleozoic–Lower Mesozoic strata in northern Laos

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Journal of Earth Science 2024年

作者： Jingjie Jin Xin Qian Vongpaseuth Senebouttalath Yuzhi Zhang Yuejun Wang Guangdong Provincial Key Lab of Geodynamics and Geohazards school of Earth sciences and Engineering Sun Yat-sen University and Southern Marine Science and Engineering Guangdong Laboratory (Zhuhai) Ministry of Energy and Mines Department of Geology and Minerals

The Late Paleozoic–Early Mesozoic sedimentary system of the Luang Prabang Paleotethyan back-arc basin in northern Laos is important for investigating sedimentary provenance， paleogeographic patterns， and the tectonic evolution of the Eastern Paleotethyan Ocean. This study presents systematic stratigraphy， petrology， geochemistry， and detrital zircon U–Pb–Hf isotopic analyses for the Late Carboniferous–Jurassic sedimentary strata on both sides of the Luang Prabang basin. Based on distinct stratigraphic ages and provenance characteristics， the clastic rock samples can be divided into four groups. The Group 1 Late Carboniferous–Early Permian samples from the western part of the basin yield detrital zircon age-peaks of ～348 and ～1425 Ma， with corresponding εHf(t) values ranging from -2.0 to +15.5 and +1.5 to +14， respectively. The age spectrum of Group 2 Late Carboniferous–Early Permian samples from the eastern part of the basin shows major age-peaks of ～287 and ～1860 Ma， with εHf(t) values of -5.9–-0.9 and -3.6–+4.2， respectively. Group 3 Late Permian–Triassic samples exhibit age-peaks of ～242 and ～1853 Ma， along with εHf(t) values of -0.7–+14.4 and -5.4–-1.8， respectively. Group 4 Middle–Late Jurassic samples yield age-peaks of ～237，～431，～813，～1833， and ～2460 Ma， lacking Late Devonian (413–345 Ma) detrital zircons. All these data collectively suggest that the Group 1 sample primarily originated from the Sukhothai Arc in western Indochina， Group 2 was from the Kontum and Truong Son in eastern Indochina， and Group 3 has a combined provenance of the Sukhothai， Kontum， and Truong Son. Regional comparisons suggest that the Jurassic provenance was mainly derived from South China， which was imported through the northern river system. Our data， combined with the regional angular unconformities between Jurassic continental strata and pre-Jurassic marine strata， suggest that the Luang Prabang basin transformed into a superimposed collisional retroforeland basin during the Ju

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Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

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Military Medical Research 2024年第4期 500-520页

作者： Kun Zhang Meng-Xia Zhang Xiao-Xiang Meng Jing Zhu Jia-Jun Wang Yi-Fan He Ye-Hua Li Si-Cong Zhao Zhe-Min Shi Li-Na Zheng Tao Han Wei Hong Department of Histology and Embryology School of Basic Medical Sciences Tianjin Medical University Department of Hepatology and Gastroenterology Tianjin Union Medical Center Tianjin Medical University Tianjin Union Medical Center Affiliated to Nankai University

Background: G-protein coupled receptors（GPCRs） are recognized as attractive targets for drug therapy. However, it remains poorly understood how GPCRs, except for a few chemokine receptors, regulate the progression of liver fibrosis. Here, we aimed to reveal the role of GPR65, a proton-sensing receptor, in liver fibrosis and to elucidate the underlying ***: The expression level of GPR65 was evaluated in both human and mouse fibrotic livers. Furthermore, Gpr65-deficient mice were treated with either bile duct ligation（BDL） for 21 d or carbon tetrachloride（CCl4） for 8 weeks to investigate the role of GPR65 in liver fibrosis. A combination of experimental approaches, including Western blotting, quantitative real-time reverse transcription-polymerase chain reaction（qRT-PCR）, and enzyme-linked immunosorbent assay（ELISA）, confocal microscopy and rescue studies, were used to explore the underlying mechanisms of GPR65's action in liver fibrosis. Additionally, the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was ***: We found that hepatic macrophage（HM）-enriched GPR65 was upregulated in both human and mouse fibrotic livers. Moreover, knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation, injury and fibrosis in vivo, and mouse bone marrow transplantation（BMT） experiments further demonstrated that the protective effect of Gpr65 knockout is primarily mediated by bone marrow-derived macrophages（BMMs）. Additionally, in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited, while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α（TNF-ivationα）, interleukin-6（IL-6） and transforming growth factor-of hepatic stellate cells（HSCs） and the damage of hepaβ（TGF-tocytes β）, all of which subsequently promoted the act（HCs）. Mechanistically, GPR65 overexpression, the acidic pH and GPR65 exo

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Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions

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World Journal of Gastroenterology 2024年第14期30卷 1968-1981页

作者： Hong-Ju Sun Bo Jiao Yan Wang Yue-Hua Zhang Ge Chen Zi-Xuan Wang Hong Zhao Qing Xie Xiao-Hua Song Department of General Medicine Qingdao Central HospitalUniversity of Health and Rehabilitation Sciences(Qingdao Central Medical Group)Qingdao 266042Shandong ProvinceChina Department of Gastroenterology Qingdao Central HospitalUniversity of Health and Rehabilitation Sciences(Qingdao Central Medical Group)Qingdao 266042Shandong ProvinceChina Department of Medical Administration Qingdao Central HospitalUniversity of Health and Rehabilitation Sciences(Qingdao Central Medical Group)Qingdao 266042Shandong ProvinceChina Qingdao Medical College Qingdao UniversityQingdao 266042Shandong ProvinceChina Department of Infectious Diseases Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China

Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver ***,the disease is underappreciated as a remarkable chronic disorder as there are rare managing *** studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic ***,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular *** the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the *** study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic ***,further studies are necessary.

关键词： Nonalcoholic fatty liver disease Apoptosis Necroptosis Cell death Diagnosis Treatment

柔性纳米压印技术在翘曲衬底上制造仿生微结构及其在Ⅲ族氮化物半导体光电器件中的应用（英文）

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Science Bulletin 2024年第13期 2080-2088页

作者：崔思远孙珂廖喆夫周千禧 Leonard Jin 金从龙胡加辉文国昇刘胜周圣军 Center for Photonics and Semiconductors School of Power and Mechanical Engineering Wuhan University Department of Mechanical and Mechatronics Engineering University of Waterloo Jiangxi SMTC Semiconductor Co. Ltd. The Institute of Technological sciences Wuhan University

Ⅲ-nitride materials are of great importance in the development of modern optoelectronics, but they have been limited over years by low light utilization rate and high dislocation densities in heteroepitaxial films grown on foreign substrate with limited refractive index contrast and large lattice mismatches. Here, we demonstrate a paradigm of high-throughput manufacturing bioinspired microstructures on warped substrates by flexible nanoimprint lithography for promoting the light extraction capability. We design a flexible nanoimprinting mold of copolymer and a two-step etching process that enable high-efficiency fabrication of nanoimprinted compound-eye-like Al2O3microstructure（NCAM） and nanoimprinted compound-eye-like SiO2microstructure（NCSM） template, achieving a 6.4-fold increase in throughput and 25% savings in economic costs over stepper projection lithography. Compared to NCAM template,we find that the NCSM template can not only improve the light extraction capability, but also modulate the morphology of AlN nucleation layer and reduce the formation of misoriented GaN grains on the inclined sidewall of microstructures, which suppresses the dislocations generated during coalescence, resulting in40% reduction in dislocation density. This study provides a low-cost, high-quality, and high-throughput solution for manufacturing microstructures on warped surfaces of Ⅲ-nitride optoelectronic devices.

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具有高阶范霍夫奇点的自选轨道耦合体系中的鲁棒拓扑超导（英文）

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Science Bulletin 2024年第3期 319-324页

作者：韩欣龙占俊张富春胡江平吴贤新 Kavli Institute for Theoretical sciences University of Chinese Academy of Sciences Beijing National Laboratory for Condensed Matter Physics and Institute of Physics Chinese Academy of Sciences school of Physical sciences University of Chinese Academy of Sciences CAS Key Laboratory of Theoretical Physics Institute of Theoretical Physics Chinese Academy of Sciences

Van Hove singularities in proximity to the Fermi level promote electronic interactions and generate diverse competing instabilities. It is also known that a nontrivial Berry phase derived from spin–orbit coupling can introduce an intriguing decoration into the interactions and thus alter correlated phenomena. However, it is unclear how and what type of new physics can emerge in a system featured by the interplay between van Hove singularities(VHSs) and the Berry phase. Here, based on a general Rashba model on the square lattice, we comprehensively explore such an interplay and its significant influence on the competing electronic instabilities by performing a parquet renormalization group analysis. Despite the existence of a variety of comparable fluctuations in the particle–particle and particle-hole channels associated with higher-order VHSs, we find that the chiral p ± ip pairings emerge as two stable fixed trajectories within the generic interaction parameter space, namely the system becomes a robust topological superconductor. The chiral pairings stem from the hopping interaction induced by the nontrivial Berry phase. The possible experimental realization and implications are discussed. Our work sheds new light on the correlated states in quantum materials with strong spin–orbit coupling(SOC) and offers fresh insights into the exploration of topological superconductivity.

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RNF6 promotes chronic myelogenous leukemia cell proliferation and migration by stabilizing vimentin via multiple atypical ubiquitinations

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Genes & Diseases 2024年第1期11卷 87-90页

作者： Hongxia Zhang Yueya Zhong Yuanming He Yujia Xu Ying Ren Haixia Zhuang Tong Sun Zhigang Zhu Xinliang Mao Institute of Clinical Pharmacology Science and Technology Innovation CenterGuangzhou University of Chinese MedicineGuangzhouGuangdong 510403China Guangdong Provincial Key Laboratory of Protein Modification and Degradation School of Basic Medical SciencesGuangzhou Medical UniversityGuangzhouGuangdong 511436China Department of Pharmacology College of Pharmaceutical SciencesSoochow UniversitySuzhouJiangsu 215123China Division of Hematology&Oncology Department of GeriatricsGuangzhou First People's HospitalCollege of MedicineSouth China University of TechnologyGuangzhouGuangdong 510180China

Chronic myelogenous leukemia(CML)is a malignancy from bone marrow myeloid stem cells mainly driven by the fusion gene *** addition to BCR-ABL,other genes including RNF6 are also dysregulated in CML cells.1 RNF6,a ubiquitin ligase of the RING family,promotes various cancer cell proliferation,chemoresistance,and tumor growth in vivo by targeting various proteins for ubiquitination and degradation,including SHP1,TLE3,FOXA1,and MAD1.^(2) However,its specific mechanism in CML is not known.

关键词： ubiquitin myelogenous leukemia