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A promising small molecule binding pocket in class B GPCRs: expanding potential for drug development

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Signal Transduction and Targeted Therapy 2023年第9期8卷 3888-3889页

作者： Huan Xiao Qian Sun Qiu sun Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan University/West China School of NursingSichuan UniversityChengdu 610041China West China Medical Publishers West China HospitalSichuan UniversityChengdu 610041China

Recently,Xu et al.1 have published in Nature,solved the high-resolution structure of a small molecule agonist PCO371 and Gs bound human parathyroid hormone receptor 1(PTH1R)by cryo-electron microscopy.This study reveals a novel conserved small molecule agonist binding pocket of class B G protein-coupled receptors(GPCRs)and provides new insights into drug develop-ment for various therapeutic indications.GPCRs are a family of receptors with a seven transmembrane(7TM)domains that mediate various downstream signals by activating G proteins or recruitingβ-arrestins.As the largest family of cell membrane receptors encoded by the human genome,GPCRs are widely involved in human physiological and patholo-gical processes and have become the most important therapeutic targets.

关键词： expanding insight class

Soft overcomes the hard:Flexible materials adapt to cell adhesion to promote cell mechanotransduction

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Bioactive Materials 2022年第4期7卷 397-404页

作者： Qian Sun Yong Hou Zhiqin Chu qiang Wei College of Polymer Science and Engineering State Key Laboratory of Polymer Materials and EngineeringSichuan UniversityChengdu610065China Department of Electrical and Electronic Engineering The University of Hong KongHong KongChina Joint Appointment with School of Biomedical Sciences The University of Hong KongHong KongChina College of Biomedical Engineering Sichuan UniversityChengdu610065China

Cell behaviors and functions show distinct contrast in different mechanical microenvironment.Numerous materials with varied rigidity have been developed to mimic the interactions between cells and their surroundings.However,the conventional static materials cannot fully capture the dynamic alterations at the bio-interface,especially for the molecular motion and the local mechanical changes in nanoscale.As an alternative,flexible materials have great potential to sense and adapt to mechanical changes in such complex microenvironment.The flexible materials could promote the cellular mechanosensing by dynamically adjusting their local mechanics,topography and ligand presentation to adapt to intracellular force generation.This process enables the cells to exhibit comparable or even higher level of mechanotransduction and the downstream‘hard’phenotypes compared to the conventional stiff or rigid ones.Here,we highlight the relevant studies regarding the development of such adaptive materials to mediate cell behaviors across the rigidity limitation on soft substrates.The concept of‘soft overcomes the hard’will guide the future development and application of biological materials.

关键词： Cell Mechanotransduction Intracellular force Biomaterials Soft materials

Explaining the state-owned enterprise wage premium in China:is it unobserved heterogeneity?

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Economic and Political Studies 2018年第2期6卷 135-157页

作者： Qian Sun Department of Economics McGill UniversityMontrealQuebecCanada

State-owned enterprises(SOEs)in China pay higher wages thanprivate firms.Is it because SOEs pay their workers wage premiumor because they employ high-quality workforce?Using the latestmethods and data,this paper accounts for the unobserved heterogeneity and estimates the SOE wage premium for the period1995–2013.It is found that the wage premium has diminishedsince 1995 and has become insignificant since 2000.The significant wage gap between SOEs and non-SOEs can be explained bythe fact that SOEs recruit high-quality workforce in correlationwith SOEs’industrial composition.This paper also evaluates theinstruments used in the previous studies and rejects themthrough validity tests.The evidence suggests that the labour market in China is not segmented by ownership.

关键词： SOE wage premium unobserved heterogeneity instrument validity implied ratio

Laser Oscillating of Nickel Alloyed Welds on Press‑Hardened Steel

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Chinese Journal of Mechanical Engineering 2022年第6期35卷 247-256页

作者： Qian Sun Zhenghui Zhang Xiaonan Wang Qingyu Zhang Zhenguang Liu School of Mechanical and Electrical Engineering Soochow UniversitySuzhou 215137China Shagang School of Iron and Steel Soochow UniversitySuzhou 215137China School of Materials Science and Engineering Jiangsu University of Science and TechnologyZhenjiang 212000China

Laser oscillating welding was employed to fabricate Al-Si coated press-hardened steel(PHS)to improve the element homogeneity in the fusion zone.Laser oscillating welding was employed with various oscillation amplitudes(0 mm,0.5 mm and 1.3 mm)in this present.Ni foil of 0.06 mm thickness was used as an interlayer between two tailored PHS welded.The weld morphology,elemental profile,microstructure and tensile strength of welded joints were studied.The results showed that full penetration weld without any weld defects were achieved for any oscillation amplitudes,and weld width increased with increasing oscillation amplitudes.With the oscillation amplitudes increased,Ni and Al had an uneven elemental profile due to strong stirring force,but the Ni and Al content in the weld was decreased and Ni had a sharp descent compared to Al element.Only fewδ-ferrite was presented in fusion line with the oscillation amplitudes increased to 1.3 mm.The oscillation amplitudes did not have an effect on the tensile properties,which was similar to that of base metal.But if keeping increasing the oscillation amplitudes or reducing the thickness of Ni interlayer,it has a potential risk to form more and moreδferrite such that deteriorate the mechnical properties of welded joints.

关键词： Laser oscillating welding Al-Si coating Press-hardened steel Nickel alloyed Microstructure and properties

Migration and transformation of Sb are affected by Mn(Ⅲ/Ⅳ)associated with lepidocrocite originating from Fe(Ⅱ)oxidation

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Journal of Environmental Sciences 2022年第5期34卷 308-318页

作者： Yalu Shao Qian Sun Liangkai Wang Weiyong Zhan Hongwei Zhang Hua Zhong State Key Laboratory of Water Resources and Hydropower Engineering Science Wuhan UniversityWuhan 430072China School of Agriculture and Food The University of MelbourneVictoria 3010Australia College of Agricultural Sciences and Engineering Hohai UniversityNanjing 210098China

Antimony(Sb)is a recognized priority pollutant with toxicity that is influenced by its mi-gration and transformation processes.Oxidation of Fe(Ⅱ)to Fe(Ⅲ)oxides,which is a com-mon phenomenon in the environment,is often accompanied by the formation of Mn(Ⅲ/Ⅳ)and might affect the fate of Sb.In this study,incorporated Mn(Ⅲ)and sorbed/precipitated Mn(Ⅲ/Ⅳ)associated with lepidocrocite were prepared by adding Mn(Ⅱ)during and after Fe(Ⅱ)oxidation,respectively,and the effects of these Mn species on Sb fate were inves-tigated.Our results indicated that the association of these Mn species with lepidocrocite obviously enhanced Sb(Ⅲ)oxidation to Sb(V),while concomitantly inhibiting Sb sorption due to the lower sorption capacity of lepidocrocite for Sb(V)than Sb(Ⅲ).Additionally,Mn oxide equivalents increased in the presence of Sb,indicating that Sb oxidation by Mn(Ⅲ/Ⅳ)associated with lepidocrocite was a continuous recycling process in which Mn(Ⅱ)released from Mn(Ⅲ/Ⅳ)reduction by Sb(Ⅲ)could be oxidized to Mn(Ⅲ/Ⅳ)again.This recycling pro-cess was favorable for effective Sb(Ⅲ)oxidation.Moreover,Sb(Ⅴ)generated from Sb(Ⅲ)ox-idation by Mn(Ⅲ/Ⅳ)enhanced Mn(Ⅱ)sorption at the beginning of the process,and thus favored Mn(Ⅲ/Ⅳ)formation,which could further promote Sb(Ⅲ)oxidation to Sb(V).Over-all,this study elucidated the effects of Mn(Ⅲ/Ⅳ)associated with lepidocrocite arisen from Fe(Ⅱ)oxidation on Sb migration and transformation and revealed the underlying reaction mechanisms,contributing to a better understanding of the geochemical dynamics of Sb.

关键词： Antimony Manganese Lepidocrocite Sorption Oxidation

Solving the transient response of the randomly excited dry friction system via piecewise RBF neural networks

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Science China(Technological Sciences) 2023年第5期66卷 1408-1416页

作者： qian JiaMin CHEN LinCong sun JianQiao College of Civil Engineering Huaqiao UniversityXiamen361021China Key Laboratory for Intelligent Infrastructure and Monitoring of Fujian Province Huaqiao UniversityXiamen361021China Department of Mechanical Engineering School of EngineeringUniversity of CaliforniaMercedCA95343USA

Over the years,practical importance and interesting dynamical features have caused a growing interest in dry friction systems.Nevertheless,an effective approach to capture the non-smooth transition behavior of such systems is still lacking.Accordingly,we propose a piecewise radial basis function neural network(RBFNN)strategy to solve the transient response of the randomly excited dry friction system.Within the established framework,the transient probability density function of the dry friction system is expressed in a piecewise form.Each segment of the solution is expressed by the sum of a series of Gaussian activation functions with time-dependent weights.These time dependent weights are solved by minimizing the loss function,which involves the residual of the Fokker-Planck-Kolmogorov equations and constraint conditions.To avoid the singularity of the initial condition being a Dirac delta function,a short-time Gaussian approximation strategy is presented to solve the initiating time-dependent weights.Based on some numerical results,the proposed scheme effectively performs.Moreover,a comparison with other existing methods reveals that the proposed scheme can completely capture the nonlinear characteristic of the dry friction system stochastic response more closely.Noteworthy,we can easily extend the proposed method to other types of non-smooth systems with piecewise response characteristics.Moreover,the semi-analytical solution provides a valuable reference for system optimization.

关键词： dry friction system transient response semi-analytical solution piecewise RBF neural networks

Autocrine motility factor receptor as a therapeutic target for asthma:comments on‘AMFR drives allergic asthma development by promoting alveolar macrophage-derived GM-CSF production’

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Journal of Molecular Cell Biology 2022年第5期14卷 57-59页

作者： Huihui Zhang Feng qian Lei sun Engineering Research Center of Cell&Therapeutic Antibody Ministry of EducationPharm-X CenterSchool of PharmacyShanghai Jiao Tong UniversityShanghai 200240China

Asthma is a chronic inflammatory disease characterized by airway hyper-responsiveness and tissue remodeling(Nobsetal.,2021).Although explorations into the pathogenesis of asthma are increasing,the underlying molecular and cellular mechanisms of asthma remain indistinct,and existing targeted therapy strategies are still limited and ineffective.

关键词： asthma allergic

Comprehensive insights into the effects and regulatory mechanisms of immune cells expressing programmed death-1/programmed death ligand 1 in solid tumors

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Cancer Biology & Medicine 2020年第3期17卷 626-639页

作者： Min Liu Qian Sun Feng Wei Xiubao Ren Department of Immunology Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinKey Laboratory of Cancer Immunology and BiotherapyTianjin's Clinical Research Center for CancerTianjin 300060China

The programmed cell death-1(PD-1)/programmed cell death ligand 1(PD-L1)signaling pathway is an important mechanism in tumor immune escape,and expression of PD-L1 on tumor cells has been reported more frequently.However,accumulating evidence suggests that PD-1/PD-L1 is also widely expressed on immune cells,and that regulation is also critical for tumor immune responses.In this review,we emphasized that under solid tumor conditions,the immunoregulatory effects of immune cells expressing PD-1 or PD-L1,affected the prognoses of cancer patients.Therefore,a better understanding of the mechanisms that regulate PD-1 or PD-L1 expression on immune cells would provide clear insights into the increased efficacy of anti-PD antibodies and the development of novel tumor immunotherapy strategies.

关键词： Immune cell immunotherapy programmed cell death ligand 1 programmed cell death-1 solid tumor

A visualization pipeline for in vivo two-photon volumetric astrocytic calcium imaging

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The Journal of Biomedical Research 2022年第5期36卷 358-367页

作者： Qian Sun Yusi Hu Saiyue Deng Yanyu Xiong Zhili Huang Department of Pharmacology School of Basic Medical ScienceFudan UniversityShanghai 200032China State Key Laboratory of Medical Neurobiology Institutes of Brain Science and Collaborative Innovation Center for Brain ScienceFudan UniversityShanghai 200032China Department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430030China

Astrocytes,the multi-functional glial cells with the most abundant population in the brain,integrate information across their territories to regulate neuronal synaptic and cerebrovascular activities.Astrocytic calcium(Ca^(2+))signaling is the major readout of cellular functional state of astrocytes.The conventional two-photon in vivo imaging usually focuses on a single horizontal focal plane to capture the astrocytic Ca^(2+)signals,which leaves>80%spatial information undetected.To fully probe the Ca^(2+)activity across the whole astrocytic territory,we developed a pipeline for imaging and visualizing volumetric astrocytic Ca^(2+)time-lapse images.With the pipeline,we discovered a new signal distribution pattern from three-dimensional(3D)astrocytic Ca^(2+)imaging data of mice under isoflurane anesthetic states.The tools developed in this study enable a better understanding of the spatiotemporal patterns of astrocytic activity in 3D space.

关键词： astrocyte calcium imaging three-dimensional visualization