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Design and discovery of a highly potent ultralong-acting GLP-1 and glucagon co-agonist for attenuating renal fibrosis

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1283-1301页

作者： Qian Zhao Jiale Dong Han Liu Hui Chen Huan yu Shuyin Ye shuangjin yu yu Li Longhui Qiu Nazi Song Hongjiao Xu Qi Liu Zhiteng Luo yuyi Li Rui Wang Guodong Chen Xianxing Jiang School of Pharmaceutical Sciences Guangdong Provincial Key Laboratory of Chiral Molecule and Drug DiscoverySun Yat-sen UniversityGuangzhou 510006China Organ Transplant Center the First Affiliated HospitalSun Yat-sen UniversityGuangzhou 510006China Zhongshan School of Medicine Sun Yat-sen UniversityGuangzhou 510006China Shenzhen Turier Biotech.Co. Ltd.Shenzhen 518118China School of Life Sciences Key Laboratory of Preclinical Study for New Drugs of Gansu ProvinceSchool of Basic Medical Sciences&Research Unit of Peptide ScienceChinese Academy of Medical SciencesLanzhou UniversityLanzhou 730000China

The role of co-agonists of glucagon-like peptide-1 receptor(GLP-1R)and glucagon receptor(GCGR)in chronic kidney disease(CKD)remains unclear.Herein we found that GLP-1R and GCGR expression levels were lower in the kidneys of mice with CKD compared to healthy mice and were correlated with disease severity.Interestingly,GLP-1R or GCGR knockdown aggravated the progression of kidney injury in both diabetic db/db mice and non-diabetic mice undergoing unilateral ureteral obstruction(UUO).Based on the importance of GLP-1R and GCGR in CKD,we reported a novel monomeric peptide,1907-B,with dual-agonism on both GLP-1R and GCGR.The data confirmed that 1907-B had a longer half-life than long-acting semaglutide in rats or cynomolgus monkeys(~2-3 fold)and exhibited better therapeutic contribution to CKD than best-in-class monoagonists,semaglutide,or glucagon,in db/db mice and UUO mice.Various lock-of-function models,including selective pharmacological activation and genetic knockdown,confirmed that 1907-B’s effects on ameliorating diabetic nephropathy in db/db mice,as well as inhibiting kidney fibrosis in UUO mice,were mediated through GLP-1 and glucagon signaling.These findings highlight that 1907-B,a novel GLP-1R and GCGR co-agonist,exerts multifactorial improvement in kidney injuries and is an effective and promising therapeutic option for CKD treatment.

关键词： GLP-1 receptor Glucagon receptor Chronic kidney disease Diabetic nephropathy Kidney fibrosis Dual-agonism

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Emerging approaches and technologies in transplantation:the potential game changers

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Cellular & Molecular Immunology 2019年第4期16卷 334-342页

作者： Anil Dangi shuangjin yu Xunrong Luo Division of Nephrology Department of MedicineDuke University Medical CenterDurhamNCUSA Duke Transplant Center Duke University Medical CenterDurhamNCUSA

Newly emerging technologies are rapidly changing conventional approaches to organ transplantation.In the modern era,the key challenges to transplantation include(1)how to best individualize and possibly eliminate the need for life-long immunosuppression and(2)how to expand the donor pool suitable for human transplantation.This article aims to provide readers with an updated review of three new technologies that address these challenges.First,single-cell RNA sequencing technology is rapidly evolving and has recently been employed in settings related to transplantation.The new sequencing data indicate an unprecedented cellular heterogeneity within organ transplants,as well as exciting new molecular signatures involved in alloimmune responses.Second,sophisticated nanotechnology platforms provide a means of therapeutically delivering immune modulating reagents to promote transplant tolerance.Tolerogenic nanoparticles with regulatory molecules and donor antigens are capable of targeting host immune responses with tremendous precision,which,in some cases,results in donor-specific tolerance.Third,CRISPR/Cas9 gene editing technology has the potential to precisely remove immunogenic molecules while inserting desirable regulatory molecules.This technology is particularly useful in generating genetically modified pigs for xenotransplantation to solve the issue of the shortage of human organs.Collectively,these new technologies are positioning the transplant community for major breakthroughs that will significantly advance transplant medicine.

关键词： Transplantation Single cell sequencing Crisper Cas9 Nanotechnology

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Quantum Spin Exchange Interactions to Accelerate the Redox Kinetics in Li–S Batteries

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Nano-Micro Letters 2024年第5期16卷 370-383页

作者： yu Du Weijie Chen yu Wang yue yu Kai Guo Gan Qu Jianan Zhang Key Laboratory of Advanced Energy Catalytic and Functional Materials Preparation of Zhengzhou City College of Materials Science and EngineeringZhengzhou UniversityZhengzhou 450001People’s Republic of China

Spin-engineering with electrocatalysts have been exploited to suppress the“shuttle effect”in Li–S batteries.Spin selec-tion,spin-dependent electron mobility and spin potentials in activation barriers can be optimized as quantum spin exchange interactions lead-ing to a significant reduction of the electronic repulsions in the orbitals of catalysts.Herein,we anchor the MgPc molecules on fluorinated carbon nanotubes(MgPc@FCNT),which exhibits the single active Mg sites with axial displacement.According to the density functional theory calculations,the electronic spin polarization in MgPc@FCNT not only increases the adsorption energy toward LiPSs intermediates but also facilitates the tunneling process of electron in Li–S batter-ies.As a result,the MgPc@FCNT provides an initial capacity of 6.1 mAh cm^(-2) even when the high sulfur loading is 4.5 mg cm^(-2),and still maintains 5.1 mAh cm^(-2) after 100 cycles.This work provides a new perspective to extend the main group single-atom catalysts enabling high-performance Li–S batteries.

关键词： Metal phthalocyanines Spin polarization Electrocatalysis Li–S batteries

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Light People:Professor Laura Na Liu

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Light(Science & Applications) 2024年第2期13卷 184-189页

作者： Hui Wang Cun yu Changchun Institute of Optics Fine Mechanics and PhysicsChinese Academy of Sciences130033ChangchunChina

Editorial The DNA nanotechnology outlines a new chapter in biological sciences,opening a new era of scientific and technological advancements.A pioneer of DNA nanotechnology,Professor Liu from the University of Stuttgart in Germany,our latest Light People,has been working at the interface,where nanophotonics meets biology and chemistry.On the path of scientific explorations.

关键词： chemistry. advancement pioneer

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Macroporous Directed and Interconnected Carbon Architectures Endow Amorphous Silicon Nanodots as Low‑Strain and Fast‑Charging Anode for Lithium‑Ion Batteries

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Nano-Micro Letters 2024年第5期16卷 333-351页

作者： Zhenwei Li Meisheng Han Peilun yu Junsheng Lin Jie yu Guangdong Provincial Key Laboratory of Semiconductor Optoelectronic Materials and Intelligent Photonic Systems Shenzhen Engineering Lab for Supercapacitor MaterialsSchool of Material Science and EngineeringHarbin Institute of TechnologyShenzhenUniversity TownShenzhen 518055People’s Republic of China Songshan Lake Materials Laboratory Dongguan Dongguan 523808GuangdongPeople’s Republic of China Department of Mechanical and Energy Engineering Southern University of Science and TechnologyShenzhen 518055People’s Republic of China

Fabricating low-strain and fast-charging silicon-carbon composite anodes is highly desired but remains a huge challenge for lithium-ion batteries.Herein,we report a unique silicon-carbon composite fabricated by uniformly dis-persing amorphous Si nanodots(SiNDs)in carbon nanospheres(SiNDs/C)that are welded on the wall of the macroporous carbon framework(MPCF)by vertical graphene(VG),labeled as MPCF@VG@SiNDs/C.The high dispersity and amor-phous features of ultrasmall SiNDs(~0.7 nm),the flexible and directed electron/Li+transport channels of VG,and the MPCF impart the MPCF@VG@SiNDs/C more lithium storage sites,rapid Li+transport path,and unique low-strain property during Li+storage.Consequently,the MPCF@VG@SiNDs/C exhibits high cycle stability(1301.4 mAh g^(-1) at 1 A g^(-1) after 1000 cycles without apparent decay)and high rate capacity(910.3 mAh g^(-1),20 A g^(-1))in half cells based on industrial electrode standards.The assembled pouch full cell delivers a high energy density(1694.0 Wh L^(-1);602.8 Wh kg^(-1))and an excellent fast-charging capability(498.5 Wh kg^(-1),charging for 16.8 min at 3 C).This study opens new possibilities for preparing advanced silicon-carbon com-posite anodes for practical applications.

关键词： Amorphous Si nanodots Low-strain Fast-charging Lithium-ion batteries

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Linear-Quadratic Pareto Cooperative Game for Mean-Field Backward Stochastic System

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Journal of Systems Science & Complexity 2024年第3期37卷 947-964页

作者： WANG yu School of Control Science and Engineering Shandong UniversityJinan 250061China

This paper focuses on a Pareto cooperative differential game with a linear mean-field backward stochastic system and a quadratic form cost functional. Based on a weighted sum optimality method, the Pareto game is equivalently converted to an optimal control problem. In the first place,the feedback form of Pareto optimal strategy is derived by virtue of decoupling technology, which is represented by four Riccati equations, a mean-field forward stochastic differential equation(MF-FSDE),and a mean-field backward stochastic differential equation(MF-BSDE). In addition, the corresponding Pareto optimal solution is further obtained. Finally, the author solves a problem in mathematical finance to illustrate the application of the theoretical results.

关键词： Backward stochastic differential equation linear-quadratic control mean-field Pareto optimality

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Effect of relative humidity on the desulfurization performance of calcium-based desulfurizer

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Journal of Environmental Sciences 2024年第4期138卷 179-188页

作者： Juan Lǖ yu Fu Haiyan yu HuanWang Zhe Wang Haiyan Chen School of Environment and Resource Southwest University of Science and TechnologyMianyang 621010China Guangyuan Emergency Management bureau Guangyuan 628000China

Low desulfurization efficiency impedes the wide application of dry desulfurization technology,which is a low-cost and simple process,and one significant solution is the development and manufacture of high-performance desulfurizers.In this study,firstly,a steam jet mill was used to digest quicklime;then,we utilized numerical simulation to study the flow field distribution and analyze the driving factors of quicklime digestion;and lastly,the desulfurization performance of the desulfurizer was evaluated under different relative humidities.The results show that the desulfurizer prepared via the steam jet mill had better apparent activity than traditional desulfurizers.Also,the entire jet flow field of the steam jet mill is in a supersonic and highly turbulent flow state,with high crushing intensity and good particle acceleration performance.Sufficient contact with the nascent surface maximizes the formation of slaked lime.The experiments demonstrated that the operating time with 100%desulfurization efficiency and the“break-through”time for the desulfurizer prepared via the steam jet mill is longer than that of traditional desulfurizers,and has significant advantages,especially at low flue gas relative humidity.Compared with traditional desulfurizers,the desulfurizer prepared via steam jet mill expands the range of acceptable flue gas temperature,and the failure temperature is 1.625 times that of traditional desulfurizers.This work breaks through the technical bottleneck of low dry desulfurization efficiency,which is an important step in pushing forward the application of dry desulfurization.

关键词： Dry desulfurization Relative humidity Desulfurization efficiency High-efficiency desulfurizer Quicklime digestion

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Visible Light-Induced[3+2]Annulation Reaction of Alkenes with Vinyl Azides:Direct Synthesis of Functionalized Pyrroles

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Chinese Journal of Chemistry 2024年第2期42卷 151-156页

作者： Ming Yang Xin-yu Wang Jie Wang yu-Long Zhao Jilin Province Key Laboratory of Organic Functional Molecular Design&Synthesis Faculty of ChemistryNortheast Normal UniversityChangchunJilin 130024China

A photocatalytic[3+2]annulation of alkenes with vinyl azides was developed under irradiation by visible light in the presence of organic dye photocatalysts.Broad substrate scope and high functional group tolerance were demonstrated by more than 50 examples.The reaction provides a novel and efficient method for the synthesis of polyfunctionalized pyrroles under very mild metal-free conditions without other additives.

关键词： Photocatalysis Vinyl azides Alkenes Pyrroles Annulation Radical reactions

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Efficient degradation of aqueous dichloromethane by an enhanced microbial electrolysis cell:Degradation kinetics,microbial community and metabolic mechanisms

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Journal of Environmental Sciences 2024年第5期139卷 150-159页

作者： Meng Wu Di Zhao Bing Gu ZiruWang Jun Hu Zhiliang yu Jianming yu College of Environment College of Biotechnology and BioengineeringCollaborative Innovation Center of Yangtze River Delta Region Green PharmaceuticalsZhejiang University of TechnologyHangzhou 310014China Shentuo Environment(Hangzhou)Co.Ltd. Hangzhou 311121China Zhejiang Tianyi Environmental Co.Ltd. Hangzhou 310000China

Dichloromethane(DCM)has been listed as a toxic and harmful water pollutant,and its re moval needs attention.Microbial electrolysis cells(MECs)are viewed as a promising alterna tive for pollutant removal,which can be strengthened from two aspects:microbial inocula tion and acclimation.In this study,the MEC for DCM degradation was inoculated with the ac tive sludge enhanced by Methylobacterium rhodesianum H13(strain H13)and then acclimated in the form of a microbial fuel cell(MFC).Both the introduction of strain H13 and the initi ation in MFC form significantly promoted DCM degradation.The degradation kinetics were fitted by the Haldane model,with V_(max),K_(h),K_(i)and v_(max)values of 103.2 mg/L/hr,97.8 mg/L268.3 mg/L and 44.7 mg/L/hr/cm^(2),respectively.The cyclic voltammogram implies that DCM redox reactions became easier with the setup of MEC,and the electrochemical impedance spectrogram shows that the acclimated and enriched microbes reduced the charge transfe resistance from the electrode to the electrolyte.In the biofilm,the dominant genera shifted from Geobacter to Hyphomicrobium in acclimation stages.Moreover,Methylobacterium played an increasingly important role.DCM metabolism mainly occurred through the hydrolytic glutathione S-transferase pathway,given that the gene dcmA was identified rather than the dhlA and P450/MO.The exogenous electrons facilitated the reduction of GSSG,directly o indirectly accelerating the GSH-catalyzed dehalogenation.This study provides support fo the construction of an efficient and stable MEC for DCM removal in water environment.

关键词： Dichloromethane Microbial electrolysis cells Metabolic pathways Electron transfer Degradation kinetics

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Topological Stability and Entropy for Certain Set-valued Maps

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Acta Mathematica Sinica,English Series 2024年第4期40卷 962-984页

作者： yu ZHANG yu Jun ZHU School of Mathematical Sciences Xiamen UniversityXiamen 361005P.R.China

In this paper,the dynamics(including shadowing property,expansiveness,topological stability and entropy)of several types of upper semi-continuous set-valued maps are mainly considered from differentiable dynamical systems points of view.It is shown that(1)if f is a hyperbolic endomorphism then for eachε>0 there exists a C^(1)-neighborhood U of f such that the induced set-valued map F_(f,U)has theε-shadowing property,and moreover,if f is an expanding endomorphism then there exists a C^(1)-neighborhood U of f such that the induced set-valued map F_(f,U)has the Lipschitz shadowing property;(2)when a set-valued map F is generated by finite expanding endomorphisms,it has the shadowing property,and moreover,if the collection of the generators has no coincidence point then F is expansive and hence is topologically stable;(3)if f is an expanding endomorphism then for eachε>0 there exists a C^(1)-neighborhood U of f such that h(F_(f,U,ε))=h(f);(4)when F is generated by finite expanding endomorphisms with no coincidence point,the entropy formula of F is given.Furthermore,the dynamics of the set-valued maps based on discontinuous maps on the interval are also considered.

关键词： Set-valued map orbit space hyperbolic endomorphism perturbation shadowing expansiveness topological stability entropy

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