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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11卷 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 SciencesTianjin Medical UniversityTianjin 300070China Department of hepatology and Gastroenterology Tianjin Union Medical CenterTianjin Medical UniversityTianjin Union Medical Center Affiliated to Nankai UniversityTianjin 300000China

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug ***,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver ***,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 ***,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 ***,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 ***,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 Gpr65knockout 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-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of

关键词： GPR65 hepatic fibrosis hepatic macrophages Inflammation c-Jun N-terminal kinase Nuclear factorκB

Ischemic colitis induced by a platelet-raising capsule: A case report

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World Journal of Clinical Cases 2024年第3期12卷 607-615页

作者： Chen-Lu wang Ze-kun si Guo-Hong Liu Chen Chen Hui Zhao Lei Li The Affiliated Hospital of Shandong Second Medical University School of Clinical MedicineShandong Second Medical UniversityWeifang 261000Shandong ProvinceChina Department of Gastroenterology The Affiliated Hospital of Shandong Second Medical UniversityWeifang 261000Shandong ProvinceChina

BACKGROUND Ischemic colitis(IC)is also known as colon ischemia and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon and is not significant enough to maintain the metabolic function of cells,leading to intestinal wall *** main symptoms include abdominal pain,diarrhea,and bloody *** severe cases,intestinal gangrene,peritonitis,intestinal stenosis and even intestinal obstruction may *** induced by long-term use of certain special drugs is relatively rare in clinical *** article describes the clinical diagnosis and treatment of a typical case and provides a new treatment idea for the treatment of *** SUMMARY The patient was admitted to the hospital with"abdominal pain for half a month and bloody stool with mucous and pus for 3 d"and was diagnosed with"IC".Symptomatic and supportive treatment,such as antibiotics(levofloxacin),acid inhibition and stomach protection,fluid replenishment,and intravenous nutrition,was *** patient's colonic ulcers were considered to be related to the oral administration of platelet(PLT)-raising capsules;the patient was asked to stop PLT-raising drugs for selective review via colonoscopy,and antibiotics and mesalazine enteric-coated tablets were *** the guidance of hematology consultation,60 mg of methylprednisolone was given in combination with PLT infusion to increase the *** treatment,the patient's condition stabilized,the patient’s stool turned yellow,the patient’s symptoms improved,and the patient was allowed to leave the *** PLT-raising capsules can lead to IC,so clinicians should have a full understanding of the application of these drugs in the treatment of various causes of thrombocyt-INTRODUCTION Ischemic colitis(IC)is also known as colon ischemia(CI)and is caused by colon vascular occlusion or nonocclusion,which results in a reduced blood supply to the colon;this process is not significant enough to maintai

关键词： Platelet-raising capsule Ischemic colitis Drug-related Colonic ulcer Case report

Genome mining of sulfonated lanthipeptides reveals unique cyclic peptide sulfotransferases

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Acta Pharmaceutica sinica B 2024年第6期14卷 2773-2785页

作者： Meng wang Wen-Wei Li Zhe Cao Jianong Sun Jiang Xiong si-Qin Tao Tinghong Lv kun Gao Shangwen Luo Shi-Hui Dong State Key Laboratory of Applied Organic Chemistry College of Chemistry and Chemical EngineeringLanzhou UniversityLanzhou 730000China

Although sulfonation plays crucial roles in various biological processes and is frequently utilized in medicinal chemistry to improve water solubility and chemical diversity of drug leads,it is rare and underexplored in ribosomally synthesized and post-translationally modified peptides(RiPPs).Biosynthesis of RiPPs typically entails modification of hydrophilic residues,which substantially increases their chemical stability and bioactivity,albeit at the expense of reducing water *** explore sulfonated RiPPs that may have improved solubility,we conducted co-occurrence analysis of RiPP class-defining enzymes and sulfotransferase(ST),and discovered two distinctive biosynthetic gene clusters(BGCs)encoding both lanthipeptide synthetase(LanM)and *** expressing these BGCs,we characterized the structures of novel sulfonated lanthipeptides and determined the catalytic details of LanM and *** demonstrate that SslST-catalyzed sulfonation is leader-independent but relies on the presence of A ring formed by *** LanM and ST are promiscuous towards residues in the A ring,but ST displays strict regioselectivity toward *** recognition of cyclic peptide by ST was further *** evaluation underscores the significance of the ST-catalyzed *** study sets up the starting point to engineering the novel lanthipeptide STs as biocatalysts for hydrophobic lanthipeptides improvement.

关键词： Lanthipeptides Sulfotransferases Sulfonation Biosynthesis Genome mining

A defect-correction method for unsteady conduction convection problems Ⅰ:spatial discretization

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Science China Mathematics 2011年第1期54卷 185-204页

作者： si zhiyong he yinnian wang kun Faculty of Science Xi'an Jiaotong University Xi'an 710049 China

In this paper, a semi-discrete defect-correction mixed finite element method (MFEM) for solving the non-stationary conduction-convection problems in two dimension is presented. In this method, we solve the nonlinear equations with an added artificial viscosity term on a finite element grid and correct this solutions on the same grid using a linearized defect-correction technique. The stability and the error analysis are derived. The theory analysis shows that our method is stable and has a good convergence property.

关键词： unsteady conduction-convection problems mixed finite element method defect-correction stability analysis error estimates

A highly sensitive ratiometric near-infrared nanosensor based on erbium-hyperdoped silicon quantum dots for iron(Ⅲ) detection

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Journal of Semiconductors 2024年第8期45卷 49-58页

作者： kun wang Wenxuan Lai Zhenyi Ni Deren Yang Xiaodong Pi State Key Laboratory of silicon and Advanced Semiconductor Materials&School of Materials Science and Engineering Zhejiang UniversityHangzhou 310027China Institute of Advanced Semiconductors&Zhejiang Provincial Key Laboratory of Power Semiconductor Materials and Devices ZJ-UHangzhou Global Scientific and Technological Innovation CenterZhejiang UniversityHangzhou 311215China

Ratiometric fluorescent detection of iron(Ⅲ)(Fe^(3+))offers inherent self-calibration and contactless analytic ***,realizing a dual-emission near-infrared(NIR)nanosensor with a low limit of detection(LOD)is rather *** this work,we report the synthesis of water-dispersible erbium-hyperdoped silicon quantum dots(si QDs:Er),which emit NIR light at the wavelengths of 810 and 1540 nm.A dual-emission NIR nanosensor based on water-dispersible si QDs:Er enables ratiometric Fe^(3+)detection with a very low LOD(0.06μM).The effects of pH,recyclability,and the interplay between static and dynamic quenching mechanisms for Fe^(3+)detection have been systematically *** addition,we demonstrate that the nanosensor may be used to construct a sequential logic circuit with memory functions.

关键词： erbium-hyperdoped silicon quantum dots dual-emission near-infrared nanosensor Fe^(3+)detection sequential logic circuit

Design of hadronic calorimeter for DarkSHINE experiment

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Nuclear Science and Techniques 2024年第9期35卷 155-167页

作者： Zhen wang Rui Yuan Han-Qing Liu Jing Chen Xiang Chen Kim siang Khaw Liang Li Shu Li kun Liu Qi-Bin Liu si-Yuan Song Tong Sun Xiao-Long wang Yu-Feng wang Hai-Jun Yang Jun-Hua Zhang Yu-Lei Zhang Zhi-Yu Zhao Chun-Xiang Zhu Xu-Liang Zhu Yi-Fan Zhu Tsung-Dao Lee Institute Shanghai Jiao Tong University1 Lisuo RoadShanghai 201210China Institute of Nuclear and Particle Physics School of Physics and Astronomy800 Dongchuan RoadShanghai 200240China Key Laboratory for Particle Astrophysics and Cosmology(MOE) Shanghai Key Laboratory for Particle Physics and Cosmology(SKLPPC)Shanghai Jiao Tong University800 Dongchuan RoadShanghai 200240China Key Laboratory of Nuclear Physics and Ion-beam Application(MOE) Fudan UniversityShanghai 200443China Institute of Modern Physics Fudan UniversityShanghai 200443China

The sensitivity of the dark photon search through invisible decay final states in low-background experiments relies sig-nificantly on the neutron and muon veto efficiencies,which depend on the amount of material used and the design of the detector *** paper presents the optimized design of the hadronic calorimeter(HCAL)used in the DarkSHINE experiment,which is studied using a GEANT4-based simulation *** geometry is optimized by comparing a traditional design with uniform absorbers to one that uses different thicknesses at different locations on the detector,which enhances the efficiency of vetoing low-energy neutrons at the sub-GeV *** overall size and total amount of material used in the HCAL are optimized to be lower,owing to the load and budget requirements,whereas the overall performance is studied to satisfy the physical objectives.

关键词： Hadronic calorimeter GEANT4 simulation Neutron background Scintillation detector Dark photon

Dielectric ultracapacitors based on columnar nano-grained ferroelectric oxide films with gradient phases along the growth direction

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Journal of Advanced Ceramics 2024年第7期13卷 1072-1079页

作者： Chuanqi Song Feifan Zheng Yuan Zhang Hongbo Cheng Long Teng kun wang Hanfei Zhu Chao Liu Li wang Zhengyan Liang Jun Ouyang Institute of Advanced Energy Materials and Chemistry School of Chemistry and Chemical EngineeringQilu University of Technology(Shandong Academy of Sciences)Jinan 250353China Department of Materials Science and Engineering Southern University of Science and TechnologyShenzhen 518055China Key Laboratory of Key Film Materials&Application for Equipment(Hunan Province) School of Materials Science and EngineeringXiangtan UniversityXiangtan 411105China China Tobacco Shandong Industrial Co. Ltd.Jinan 250104China

In this work,dielectric ultracapacitors were designed and fabricated using a combination of phase boundary and nanograin *** ultracapacitors are based on submicron-thick Ba(Zr_(0.2)Ti_(0.8))O_(3) ferroelectric films sputterdeposited on si at 500℃.With a composition near a polymorphic phase boundary(PPB),a compressive strain,and a high nucleation rate due to the lowered deposition temperature,these films exhibit a columnar nanograined microstructure with gradient phases along the growth *** a microstructure presents three-dimensional polarization inhomogeneities on the nanoscale,thereby significantly delaying the saturation of the overall electric ***,a pseudolinear,ultraslim polarization(P)-electric field(E)hysteresis loop was obtained,featuring a high maximum applicable electric field(~5.7 MV/cm),low remnant polarization(~5.2μC/cm^(2))and high maximum polarization(~92.1μC/cm^(2)).This P-E loop corresponds to a high recyclable energy density(W_(rec)~208 J/cm^(3))and charge‒discharge efficiency(~88%).An indepth electron microscopy study revealed that the gradient ferroelectric phases consisted of tetragonal(T)and rhombohedral(R)polymorphs along the growth direction of the *** T-rich phase is abundant near the bottom of the film and gradually transforms into the R-rich phase near the *** films also exhibited a high Curie temperature of~460℃and stable capacitive energy storage up to 200℃.These results suggest a feasible pathway for the design and fabrication of high-performance dielectric film capacitors.

关键词： ferroelectric thin films energy storage phase coexistence nanograin silicon

simultaneously achieving high energy density and responsivity in submicron BaTiO_(3) film capacitors integrated on si

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Journal of Advanced Ceramics 2024年第2期13卷 198-206页

作者： Jun Ouyang Yinxiu Xue Chuanqi Song Meiling Yuan kun wang Yuyao Zhao Hongbo Cheng Hanfei Zhu Chao Liu Institute of Advanced Energy Materials and Chemistry School of Chemistry and Chemical EngineeringQilu University of Technology(Shandong Academy of Sciences)Jinan 250353China Key Laboratory of Key Film Materials&Application for Equipment School of Material Sciences and EngineeringXiangtan UniversityXiangtan 411105China School of Materials Science and Engineering Shandong UniversityJinan 250061China Academic Affairs Office Civil Aviation University of ChinaTianjin 300300China China Tobacco Shandong Industrial Co. Ltd.Jinan 250014China

In the research field of energy storage dielectrics,the“responsivity”parameter,defined as the recyclable/recoverable energy density per unit electric field,has become critically important for a comprehensive evaluation of the energy storage capability of a *** this work,high recyclable energy density and responsivity,i.e.,W_(rec)=161.1 J·cm^(-3) and ξ=373.8 J·(kV·m^(2))^(-1),have been simultaneously achieved in a prototype perovskite dielectric,BaTiO_(3),which is integrated on si at 500℃ in the form of a submicron thick *** ferroelectric film features a multi-scale polar structure consisting of ferroelectric grains with different orientations and inner-grain ferroelastic domains.A LaNiO_(3) buffer layer is used to induce a{001}textured,columnar nanograin microstructure,while an elevated deposition temperature promotes lateral growth of the nanograins(in-plane diameter increases from~10-20 nm at lower temperatures to~30 nm).These preferably oriented and periodically regulated nanograins have resulted in a small remnant polarization and a delayed polarization saturation in the film’s P-E behavior,leading to a high recyclable energy ***,an improved polarizability/dielectric constant of the BaTiO_(3) film has produced a much larger maximum polarization than those deposited at lower temperatures at the same electric field,leading to a record-breaking responsivity for this simple perovskite.

关键词： energy storage energy density responsivity BaTiO_(3) dielectric capacitor si

Bias distribution and regulation in photoelectrochemical overall water-splitting cells

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National Science Review 2024年第4期11卷 141-150页

作者： kun Dang siqin Liu Lei Wu Daojian Tang Jing Xue Jiaming wang Hongwei Ji Chuncheng Chen Yuchao Zhang Jincai Zhao Key Laboratory of Photochemistry CAS ResearchEducation Center for Excellence in Molecular Sciences Institute of Chemistry Chinese Academy of Sciences University of Chinese Academy of Sciences

The water oxidation half-reaction at anodes is always considered the rate-limiting step of overall water splitting（OWS）,but the actual bias distribution between photoanodes and cathodes of photoelectro chemical（PEC） OWS cells has not been investigated *** this work,we find that,for PEC cells consisting of photoanodes（nickel-modified n-si [Ni/n-si] and α-Fe2O3） with low photovoltage(Vphhe Pt cathode for satisfying the hydrogen evolution thermodynamics,showing a thermodynamics-controlled *** contrast,for photoanodes（TiO2and BiVO4） with Vph> 1V,the bias required for cathode activation can be significantly reduced,exhibiting a kinetics-controlled *** investigations show that the bias distribution can be regulated by tuning the electrolyte pH and using alternative half-reaction ***,a volcano plot is presented for the rational design of the overall reactions and unbiased PEC *** by this,an unbiased PEC cell consisting of a simple Ni/n-si photoanode and Pt cathode is assembled,delivering a photo current density of 5.3±0.2 mA cm-2.

关键词： photoelectrochemistry overall reaction cell bias distribution photoanode water splitting