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Protein lipidation in health and disease:molecular basis,physiological function and pathological implication

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1423-1465页

作者： yuan yuan Peiyuan Li jianghui Li qiu Zhao Ying Chang Xingxing He Department of Gastroenterology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Gastroenterology Zhongnan Hospital of Wuhan UniversityWuhanChina Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases WuhanChina

Posttranslational modifications increase the complexity and functional diversity of proteins in response to complex external stimuli and internal changes.Among these,protein lipidations which refer to lipid attachment to proteins are prominent,which primarily encompassing five types including S-palmitoylation,N-myristoylation,S-prenylation,glycosylphosphatidylinositol(GPl)anchor and cholesterylation.Lipid attachment to proteins plays an essential role in the regulation of protein trafficking,localisation,stability,conformation,interactions and signal transduction by enhancing hydrophobicity.Accumulating evidence from genetic,structural,and biomedical studies has consistently shown that protein lipidation is pivotal in the regulation of broad physiological functions and is inextricably linked to a variety of diseases.Decades of dedicated research have driven the development of a wide range of drugs targeting protein lipidation,and several agents have been developed and tested in preclinical and clinical studies,some of which,such as asciminib and lonafarnib are FDA-approved for therapeutic use,indicating that targeting protein lipidations represents a promising therapeutic strategy.Here,we comprehensively review the known regulatory enzymes and catalytic mechanisms of various protein lipidation types,outline the impact of protein lipidations on physiology and disease,and highlight potential therapeutic targets and clinical research progress,aiming to provide a comprehensive reference for future protein lipidation research.

关键词： Lipid ation primarily

The activity and immune dynamics of PD-1 inhibition on high-risk pulmonary ground glass opacity lesions:insights from a single-arm,phase II trial

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2202-2214页

作者： Bo Cheng Caichen Li Jianfu Li Longlong Gong Peng Liang Ying Chen Shuting Zhan Shan Xiong Ran Zhong Hengrui Liang Yi Feng Runchen Wang Haixuan Wang Hongbo Zheng Jun Liu Chengzhi Zhou Wenlong Shao yuan qiu Jiancong Sun Zhanhong Xie Zhu Liang Chenglin Yang Xiuyu Cai Chunxia Su Wei Wang Jianxing He Wenhua Liang Department of Thoracic Surgery and Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Medical Department Genecast Biotechnology Co.LtdWuxiChina Department of Radiation Oncology the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouChina Department of Respiratory Medicine the First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou Institute of Respiratory HealthState Key Laboratory of Respiratory DiseaseNational Clinical Research Center for Respiratory DiseaseGuangzhouChina Department of Cardiothoracic Surgery Affiliated Hospital of Guangdong Medical UniversityZhanjiangChina Department of Thoracic Surgery National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital&Shenzhen HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeShenzhenChina Department of VIP Inpatient Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaSun Yat-sen UniversityGuangzhouChina Department of Medical Oncology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Immune checkpoint inhibitors targeting the programmed cell death-1(PD-1)protein significantly improve survival in patients with advanced non-small-cell lung cancer(NSCLC),but its impact on early-stage ground-glass opacity(GGO)lesions remains unclear.This is a single-arm,phase II trial(NCT04026841)using Simon’s optimal two-stage design,of which 4 doses of sintilimab(200 mg per 3 weeks)were administrated in 36 enrolled multiple primary lung cancer(MPLC)patients with persistent high-risk(Lung-RADS category 4 or had progressed within 6 months)GGOs.The primary endpoint was objective response rate(ORR).T/B/NK-cell subpopulations,TCR-seq,cytokines,exosomal RNA,and multiplexed immunohistochemistry(mIHC)were monitored and compared between responders and non-responders.Finally,two intent-to-treat(ITT)lesions(pure-GGO or GGO-predominant)showed responses(ORR:5.6%,2/36),and no patients had progressive disease(PD).No grade 3-5 TRAEs occurred.The total response rate considering two ITT lesions and three non-intent-to-treat(NITT)lesions(pure-solid or solid-predominant)was 13.9%(5/36).The proportion of CD8^(+)T cells,the ratio of CD8^(+)/CD4^(+),and the TCR clonality value were significantly higher in the peripheral blood of responders before treatment and decreased over time.Correspondingly,the mIHC analysis showed more CD8^(+)T cells infiltrated in responders.Besides,responders’cytokine concentrations of EGF and CTLA-4 increased during treatment.The exosomal expression of fatty acid metabolism and oxidative phosphorylation gene signatures were down-regulated among responders.Collectively,PD-1 inhibitor showed certain activity on high-risk pulmonary GGO lesions without safety concerns.Such effects were associated with specific T-cell re-distribution,EGF/CTLA-4 cytokine compensation,and regulation of metabolism pathways.

关键词： lesions metabolism doses

Research on Credit Regulation Mechanism of E-commerce Platform Based on Evolutionary Game Theory

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Journal of Systems Science and Systems Engineering 2024年第3期33卷 330-359页

作者： Zeguo qiu Yuchen Yin Yao yuan Yunhao Chen School of Computer and Information Engineering Harbin University of CommerceHarbin150028China School of Management Harbin University of CommerceHarbin150028China

In the growing e-commerce industry,the problem of malicious business operations has become increasingly prominent,exposing many problems such as weak supervision of e-commerce platforms and no way for consumers to complain.In order to solve the problems of counterfeit and shoddy products on e-commerce platforms and promote the sustainable development of the e-commerce industry in China,this paper constructs a three-party evolutionary game model of e-commerce platforms,merchants,and consumers,investigates the influence of each influencing factor on each party’s strategy choice,and provides targeted suggestions to e-commerce platforms based on relevant factors.Finally,the impact of several important parameters on the equilibrium solution is discussed through sensitivity analysis.The results show that:1)the smaller the cost difference between active and negative regulation,the more the e-commerce platform tends to active regulation strategy,but increasing fines for dishonest merchants and consumer complaints have little impact on the e-commerce platform;2)increasing consumer compensation,creating an honest business environment,and reducing the cost of honest business all help companies tend to operate in good faith;3)the only factor that affects the tendency of consumer complaint strategies is the cost of complaints.The loss suffered by silence and the compensation given to consumers have little effect on consumers’tendency to complain strategy.The results can provide theoretical guidance for participants to make useful strategic decisions in the e-commerce market.

关键词： Evolutionary game e-commerce data simulation

A novel AMH variant at the prehelix loop impairs the binding to AMHR2 and causes persistent Mullerian duct syndrome

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Asian Journal of Andrology 2024年第2期26卷 222-224页

作者： Qiang Du Chuang qiu yuan-yuan Zhang Xue-Jun Shang Xiao-Liang Liu Center of Reproductive Medicine Shengjing Hospital of China Medical UniversityShenyang 110004China Department of Orthopedics Shengjing Hospital of China Medical UniversityShenyang 110004China Department of Clinical Genetics Shengjing Hospital of China Medical UniversityShenyang 110004China Department of Urology Jinling HospitalSchool of MedicineNanjing UniversityNanjing 210012China

Dear Editor,Persistent Mullerian duct syndrome(PMDS;Online Mendelian Inheritance in Man[OMIM]:#261550)is a rare autosomal recessive inherent difference in sex development in males with Mullerian duct derivatives,including the uterus,fallopian tubes,and upper part of the vagina.'Approximately 88%of PMDS patients were found to have biallelic variants in the anti-Mullerian hormone(AMH;OMIM:*600957)or AMH type 2 receptor(AMHR2;OMIM:*600956)genes,and the rest were referred as idiopathic.I The serum AMH levels are usually very low or undetectable in PMDS patients with AMH gene mutations but normal or elevated in those with AMHR2 gene mutations.Here,an adult Chinese patient with PMDS carrying biallelic variants of the AMH gene was reported to have unexpectedly normal serum AMH level.Please refer to Supplementary Information of Patient and Methods for methodologies.

关键词： elevated AMH Muller

Unravelling the anisotropic light-matter interaction in strainengineered trihalide MoCl_(3)

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Nano Research 2024年第4期17卷 2981-2987页

作者： Yuxuan Sun Ziang Liu Zeya Li Feng Qin Junwei Huang Caiyu qiu Hongtao yuan National Laboratory of Solid State Microstructures Jiangsu Key Laboratory of Artificial Functional MaterialsCollege of Engineering and Applied Sciencesand Collaborative Innovation Center of Advanced MicrostructuresNanjing UniversityNanjing 210000China

Layered trihalides exhibit distinctive band structures and physical properties due to the sixfold coordinated 3d or 4d transition metal site and partially occupied d orbitals,holding great potential in condensed matter physics and advanced electronic applications.Prior research focused on trihalides with highly symmetric honeycomb-like structures,such as CrI3 andα-RuCl_(3),while the role of crystal anisotropy in trihalides remains elusive.In particular,the trihalide MoCl_(3) manifests strong in-plane crystal anisotropy with the largest difference in Mo–Mo interatomic distances.Research on such material is imperative to address the lack of investigations on the effect of anisotropy on the properties of trihalides.Herein,we demonstrated the anisotropy of MoCl_(3) through polarized Raman spectroscopy and further tuned the phonon frequency via strain engineering.We showed the Raman intensity exhibits twofold symmetry under parallel configuration and fourfold symmetry under perpendicular configuration with changing the polarization angle of incident light.Furthermore,we found that the phonon frequencies of MoCl_(3) decrease gradually and linearly with applying uniaxial tensile strain along the axis of symmetry in the MoCl_(3) crystal,while those frequencies increase with uniaxial tensile strain applied perpendicularly.Our results shed light on the manipulation of anisotropic light-matter interactions via strain engineering,and lay a foundation for further exploration of the anisotropy of trihalides and the modulation of their electronic,optical,and magnetic properties.

关键词： layered trihalide MoCl_(3) polarized Raman spectroscopy strain engineering anisotropy

Effect of Mn content on microstructure and properties of AlCrCuFeMnx high-entropy alloy

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China Foundry 2024年第2期21卷 147-158页

作者： Ning Wang Kai Ma qiu-da Li Yu-dong yuan Yan-chun Zhao Li Feng School of Materials Science and Engineering Lanzhou University of TechnologyLanzhou 730050China State Key Laboratory of Advanced Processing and Reuse of Nonferrous Metals Lanzhou 730050China CNNC Nuclear Power Operation and Management Co. Ltd.Haiyan 314300ZhejiangChina

AlCrCuFeMnx(x=0,0.5,1,1.5,and 2)high-entropy alloys were prepared using the vacuum arc melting technology.The microstructure and mechanical properties of AlCrCuFeMnxwere analyzed and tested by XRD,SEM,TEM,nanoindentation,and electronic universal testing.The results indicate that the AlCrCuFeMnxhigh-entropy alloy exhibits a dendritic structure,consisting of dendrites with a BCC structure,interdendrite regions with an FCC structure,and precipitates with an ordered BCC structure that form within the dendrite.Manganese(Mn)has a strong affinity for dendritic,interdendritic,and precipitate structures,allowing it to easily enter these areas.With an increase in Mn content,the size of the precipitated nanoparticles in the dendritic region initially increases and then decreases.Similarly,the area fraction initially decreases and then increases.Additionally,the alloy’s strength and wear resistance decrease,while its plasticity increases.The Al Cr Cu Fe Mn1.5alloy boasts excellent mechanical properties,including a hardness of 360 HV and a wear rate of 2.4×10^(-5)mm^(3)·N^(-1)·mm^(-1).It also exhibits impressive yield strength,compressive strength,and deformation rates of 960 MPa,1,700 MPa,and 27.5%,respectively.

关键词： high-entropy alloys microstructure mechanical properties wear resistance strengthening mechanisms

Highly Stable sp^(2) Carbon-Conjugated Porous Organic Cages

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CCS Chemistry 2024年第1期6卷 149-156页

作者： Fenglei qiu Xun Chen Wenjing Wang Kongzhao Su Daqiang yuan State Key Laboratory of Structural Chemistry Fujian Institute of Research on the Structure of MatterChinese Academy of SciencesFuzhouFujian 350002 College of Chemistry Fuzhou UniversityFuzhouFujian 350116 University of the Chinese Academy of Sciences Beijing 100049

The high-yield synthesis of ultrastable porous organic cages(POCs)by facile methods is highly desirable but challenging.Inspired by highly stable sp^(2) carbon-conjugated(C=C)covalent organic frameworks,we used rational design and synthesized the first family of sp^(2) carbon-linked POCs(sp^(2)c-POCs)with triangular prism shapes by a one-step Knoevenagel reaction that is a high yield[2+3]condensation reaction.The stability of sp^(2)c-POC was demonstrated under strenuous conditions involving for example concentrated HCl or saturated NaOH solution.sp^(2)c-POC was used as a robust adsorbent for efficient separation of CO_(2)/CH_(4) or CO_(2)/N_(2) mixtures.In view of their facile synthesis and unique properties,we expect widespread use of these sp^(2) C=C linkages in the development of POC materials.

关键词： porous organic cages Knoevenagel condensation sp^(2)C=C linkage exceptional chemical stability gas adsorption and separation properties

Multi-process production occurs in the iron and steel industry,supporting‘dual carbon'target:An in-depth study of CO_(2)emissions from different processes

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Journal of Environmental Sciences 2024年第6期140卷 46-58页

作者： Hongming Na Yuxing yuan Tao Du Tianbao Zhang Xi Zhao Jingchao Sun Ziyang qiu Lei Zhang SEP Key Laboratory of Eco-Industry Northeastern UniversityShenyang 110819China School of Metallurgy Northeastern UniversityShenyang 110819China

Reducing CO_(2)emissions of the iron and steel industry,a typical heavy CO_(2)-emitting sector is the only way that must be passed to achieve the‘dual-carbon’goal,especially in China.In previous studies,however,it is still unknown what is the difference between blast furnace basic oxygen furnace(BF-BOF),scrap-electric furnace(scrap-EF)and hydrogen metallurgy process.The quantitative research on the key factors affecting CO_(2)emissions is insufficient There is also a lack of research on the prediction of CO_(2)emissions by adjusting industria structure.Based on material flow analysis,this study establishes carbon flow diagrams o three processes,and then analyze the key factors affecting CO_(2)emissions.CO_(2)emissions of the iron and steel industry in the future is predicted by adjusting industrial structure The results show that:(1)The CO_(2)emissions of BF-BOF,scrap-EF and hydrogen metallurgy process in a site are 1417.26,542.93 and 1166.52 kg,respectively.(2)By increasing pellet ratio in blast furnace,scrap ratio in electric furnace,etc.,can effectively reduce CO_(2)emissions(3)Reducing the crude steel output is the most effective CO_(2)reduction measure.There is still 5.15×10^(8)-6.17×10^(8) tons of CO_(2)that needs to be reduced by additional measures.

关键词： Blast furnace-basic oxygen furnace process Scrap-electric furnace process Hydrogen metallurgy process Carbon flow diagram Influencing factors CO_(2)emission prediction

Understanding the Thermal Impedance of Silicone Rubber/Hexagonal Boron Nitride Composites as Thermal Interface Materials

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Chinese Journal of Polymer Science 2024年第3期42卷 352-363,I0008页

作者： yuan Ji Shi-Da Han Hong Wu Shao-Yun Guo Feng-Shun Zhang Jian-Hui qiu The State Key Laboratory of Polymer Materials Engineering Sichuan Provincial Engineering Laboratory of Plastic/Rubber Complex Processing TechnologyPolymer Research InstituteSichuan UniversityChengdu 610065China Institute of Chemical Materials China Academy of Engineering PhysicsMianyang 621900China Department of Mechanical Engineering Faculty of Systems Science and TechnologyAkita Prefectural UniversityAkita 015-0055Japan

Silicone rubber(SR) composites are most widely used as thermal interface materials(TIMs) for electronics heat dissipation. Thermal impedance as the main bottleneck limiting the performance of TIMs is usually neglected. Herein, the thermal impedance of SR composites loaded with different levels of hexagonal boron nitride(h-BN) as TIMs was elaborated for the first time by the ASTM D 5470 standard test and finite element analysis. It was found that elastic modulus and surface roughness of SR composites increased with the increase of h-BN content, indicating that the conformity was reduced. When the assembly pressure was 0.69 MPa, there existed an optimal h-BN content at which the contact resistance was minimum(0.39 K·cm^(2)·W^(-1)). Although the decreased bond line thickness(BLT) by increasing the assembly pressure was beneficial to reduce the thermal impedance, the proper assembly pressure should be selected to prevent the warpage of the contact surfaces and the increase in contact resistance, according to the compression properties of the SR composites. This study provides valuable insights into fabrication of high-performance TIMs for modern electronic device applications.

关键词： Thermal interface materials Hexagonal boron nitride Thermal impedance Surfaces