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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 *** 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 ***,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 *** 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 *** 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 *** 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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基于常温机械灌注的器官医学及器官隔离保护治疗在不同研究领域中的应用

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中华器官移植杂志 2024年第3期45卷 162-166页

作者：邱江陈海威余双进中山大学附属第一医院器官移植中心广州510080 中山大学附属第三医院肾移植科广州510630

常温机械灌注(normothermic machine perfusion,NMP)目前是移植领域器官保存的研究热点,其在器官保存的安全性和有效性方面已经得到临床验证,并已应用于器官保存,尤其是边缘供器官的保存。此外,NMP在器官体外功能评估和维护、器官损伤... 详细信息

常温机械灌注(normothermic machine perfusion,NMP)目前是移植领域器官保存的研究热点,其在器官保存的安全性和有效性方面已经得到临床验证,并已应用于器官保存,尤其是边缘供器官的保存。此外,NMP在器官体外功能评估和维护、器官损伤修复等方面的潜在独特优势在未来可能会大大扩展其应用场景,尤其是在器官医学领域,即通过体外器官支持系统精准地对在体或离体器官进行临床干预或研究。借助体外器官支持系统,可以更为高效、安全地对单个或多个器官建立独立的体外循环系统,对靶器官进行生理支持治疗或其他干预治疗,包括器官基因编辑治疗、器官细胞治疗、器官化疗、器官溶瘤病毒治疗及器官生理支持治疗等,也称为器官隔离治疗。这一理论的出现为临床器官疾病治疗提供了全新的治疗思路及手段。本文现就基于NMP技术的器官医学理念及器官隔离保护治疗在器官移植及其他研究领域的应用进行评述。

关键词：常温机械灌注器官保存器官医学器官隔离保护治疗

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基于程序性移植肾穿刺活检的ABO血型不相容活体亲属肾移植中期疗效评价

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中华医学杂志 2024年第12期104卷 944-949页

作者：陈海威何宇阮和欢吴国彬余双进王奕陈国栋邱江王长希陈立中中山大学附属第一医院器官移植中心广州510080

目的依据程序性移植肾穿刺活检结果对ABO血型不相容活体亲属肾移植(ABOi-KT)的中期疗效进行评价。方法回顾性收集中山大学附属第一医院2015年7月至2021年11月实施的23对ABOi-KT的供受体临床资料,对受体进行脱敏治疗后行ABOi-KT,分析受... 详细信息

目的依据程序性移植肾穿刺活检结果对ABO血型不相容活体亲属肾移植(ABOi-KT)的中期疗效进行评价。方法回顾性收集中山大学附属第一医院2015年7月至2021年11月实施的23对ABOi-KT的供受体临床资料,对受体进行脱敏治疗后行ABOi-KT,分析受体术后1周、1个月、3个月、6个月和12个月程序性移植肾穿刺活检结果,结合血型抗体水平、肾功能恢复情况,对ABOi-KT的中期疗效进行评价。结果23例受体中,男19例,女性4例;年龄19~47(29.6±6.7)岁,均在接受脱敏治疗后顺利实施ABOi-KT。随访时间(44.6±22.4)个月,其中随访时间超过1年者22例。术后1周、1个月、3个月、6个月和12个月病理证实排斥反应的发生率分别为15.0%(3/20)、11.1%(1/9)、7.7%(1/13)、25.0%(3/12)和12.5%(1/8)。对于排斥反应的受体,结合临床症状及各项指标行针对性抗排斥治疗,临界性T细胞介导的排斥反应(TCMR)经抗排斥治疗后均可转为轻度小管炎。术后1周管周毛细血管补体C4d阳性率为95.0%(19/20),术后3和12个月时补体C4d阳性率均为100%。受体术后1、3、5和7年生存率均为100%。移植肾术后1、3、5和7年存活率分别为100%、93.3%、84.0%和84.0%,除2017年进行移植的2例受体于术后30和49个月出现移植肾失功外,其余移植肾均存活。结论程序性移植肾穿刺活检结果显示,ABOi-KT的中期疗效良好,可动态观察ABOi-KT病理改变,并对排斥反应行针对性治疗.

关键词：肾移植血型抗体排斥脱敏随访研究

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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 *** 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 *** article aims to provide readers with an updated review of three new technologies that address these ***,single-cell RNA sequencing technology is rapidly evolving and has recently been employed in settings related to *** new sequencing data indicate an unprecedented cellular heterogeneity within organ transplants,as well as exciting new molecular signatures involved in alloimmune ***,sophisticated nanotechnology platforms provide a means of therapeutically delivering immune modulating reagents to promote transplant *** 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 ***,CRISPR/Cas9 gene editing technology has the potential to precisely remove immunogenic molecules while inserting desirable regulatory *** technology is particularly useful in generating genetically modified pigs for xenotransplantation to solve the issue of the shortage of human ***,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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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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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 *** 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 ***,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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A new liquid membrane diffusion model for characterizing the adsorption kinetics of europium by using a continuous measurement of adsorption platform

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Nuclear Science and Techniques 2024年第1期35卷 59-72页

作者： Hao-Qi yu Tao yu Jian-Hua Ye State Key Laboratory of Nuclear Resources and Environment East China University of TechnologyNanchang 330013China CGN Cangnan Nuclear Power Co. Ltd.Cangnan 325800China Jiangxi Province Key Laboratory of Polymer Micro/Nano Manufacturing and Devices East China University of TechnologyNanchang 330013China School of Nuclear Science and Engineering East China University of TechnologyNanchang 330013China

To explore the kinetic adsorption under continuous and nonequilibrium states, an integration of continuous measurement and adsorption platform kinetics method was proposed, which was initially called the ICM-AP kinetics method, and a corresponding kinetic adsorption experimental method was developed. Adsorption experiments of europium(Eu) on Ca-bentonite,Na-bentonite, and the D231 cation exchange resin were performed using the ICM-AP kinetics method and continuous measurements. Because the kinetic experimental results observed in this study were different from those of traditional batch adsorption data, pseudo-first-order or pseudo-second-order kinetic models were unsuitable for fitting the experimental ***, a liquid membrane diffusion(LMD) model was developed based on the assumption of simultaneous adsorption/desorption to discuss the mechanism of kinetic adsorption. The kinetic adsorption mechanism was also studied by using *** results indicated that the proposed adsorption model can fit the experimental data more suitably, and the adsorption/desorption behaviors of Eu on bentonite and the D231 resin were simultaneously observed, suggesting that the adsorption kinetics of Eu(Ⅲ) was mainly dominated by hydrated Eu(Ⅲ) ions on the liquid membrane.

关键词： ICM-AP method LMD model Adsorption mechanism Eu(Ⅲ)

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Device design principles and bioelectronic applications for flexible organic electrochemical transistors

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International Journal of Extreme Manufacturing 2024年第1期6卷 126-153页

作者： Lin Gao Mengge Wu Xinge yu Junsheng yu State Key Laboratory of Electronic Thin Films and Integrated Devices School of Optoelectronic Science and EngineeringUniversity of Electronic Science and Technology of China(UESTC)Chengdu 610054People’s Republic of China Department of Biomedical Engineering City University of Hong KongHong Kong Special Administrative Region of ChinaPeople’s Republic of China

Organic electrochemical transistors(OECTs) exhibit significant potential for applications in healthcare and human-machine interfaces, due to their tunable synthesis, facile deposition, and excellent biocompatibility. Expanding OECTs to the fexible devices will significantly facilitate stable contact with the skin and enable more possible bioelectronic applications. In this work,we summarize the device physics of fexible OECTs, aiming to offer a foundational understanding and guidelines for material selection and device architecture. Particular attention is paid to the advanced manufacturing approaches, including photolithography and printing techniques, which establish a robust foundation for the commercialization and large-scale fabrication. And abundantly demonstrated examples ranging from biosensors, artificial synapses/neurons, to bioinspired nervous systems are summarized to highlight the considerable prospects of smart healthcare. In the end, the challenges and opportunities are proposed for fexible OECTs. The purpose of this review is not only to elaborate on the basic design principles of fexible OECTs, but also to act as a roadmap for further exploration of wearable OECTs in advanced bio-applications.

关键词： flexible organic electrochemical transistors wearable bioelectronics manufacturing approaches device physics neuromorphic applications

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A guidance and control design with reduced information for a dual-spin stabilized projectile

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Defence Technology（防务技术） 2024年第3期33卷 494-505页

作者： yu Wang Jiyan yu Xiaoming Wang Jia Fangxiu Intelligent Ammunition Technology National Defense Key Discipline Laboratory Nanjing University of Science and TechnologyNanjingJiangsu210094China

In this paper,an integrated guidance and control method based on an adaptive path-following controller is proposed to control a spin-stabilized projectile with only translational motion information under the constraint of an actuator,uncertainties in aerodynamic parameters and measurements,and control system *** to the fairly high rotation speed,the dynamic model of this missile is strongly nonlinear,uncertain and coupled in pitch,yaw and roll channels.A theoretical equivalent resultant force and uncertainty compensation method are comprehensively used to realize decoupling of pitch and *** response to the strong nonlinear and time-varying characteristics of the dynamic system,the quasi-linear model whose parameters are obtained by interpolation of points selected as the segmentation points in the trajectory envelope,is used for calculation in each *** cope with the system uncertainty caused by model approximation,parameter uncertainty and ballistic interference,an extended state estimator is used to compensate the output feedback according to the test ballistic *** order to improve the tracking efficiency and ensure the tracking error convergence with only translational motion information,the virtual guide point,whose derivative is deduced according to the Lyapunov principle,is calculated in real time according to the projection relationship between the real-time position and the reference trajectory,and a virtual line-of-sight angle and the backstepping method are used for the design of the guidance and control *** order to avoid the influence of control input saturation on the guidance and control performance due to the actuator limitation and improve the robustness of the system,an anti-saturation compensator is designed according to the two-step *** feasibility and effectiveness of the path-following controller is verified through closed-loop flight simulations with measurement,control,and condition *** result

关键词： Spin-stabilized projectile Reduced information Path-following control Extended state observer Coupled nonlinear system Input saturation

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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 *** 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 ***,we anchor the MgPc molecules on fluorinated carbon nanotubes(MgPc@FCNT),which exhibits the single active Mg sites with axial *** 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 *** 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 *** 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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