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Glucagon-like peptide-1 receptor agonists rescued diabetic vascular endothelial damage through suppression of aberrant STING signaling

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2613-2630页

作者： Xuemin He Siying Wen Xixiang Tang Zheyao Wen rui Zhang Shasha Li rong Gao Jin Wang Yanhua Zhu dong Fang Ting Li ruiping Peng Zhaotian Zhang Shiyi Wen Li Zhou Heying Ai Yan Lu Shaochong Zhang Guojun Shi Yanming Chen department of Endocrinology and Metabolic diseases the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China guangdong Provincial key Laboratory of diabetology&Guangzhou Municipal key Laboratory of Mechanistic and Translational Obesity research the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China VIP Medical Service Center the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China department of Clinical Immunology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China department of Ophthalmology the Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630China State key Laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhou 510060China department of Fundus Shenzhen Eye Hospital of Jinan UniversityShenzhen 518048China

Glucagon-like peptide-1 receptor agonists(GLP-1 rAs)protect against diabetic cardiovascular diseases and ***,their activity in diabetic retinopathy(dr)remains *** retrospective cohort study involving 1626 T2dM patients revealed superior efficacy of GLP-1 rAs in controlling dr compared to other glucose-lowering medications,suggesting their advantage in dr *** single-cell rNA-sequencing analysis and immunostaining,we observed a high expression of GLP-1r in retinal endothelial cells,which was down-regulated under diabetic *** of GLP-1 rAs significantly restored the receptor expression,resulting in an improvement in retinal degeneration,vascular tortuosity,avascular vessels,and vascular integrity in diabetic *** and GSEA analyses further implicated enhanced mitochondrial gene translation and mitochondrial functions by GLP-1 ***,the treatment attenuated STING signaling activation in retinal endothelial cells,which is typically activated by leaked mitochondrial *** of STING mrNA was positively correlated to the levels of angiogenic and inflammatory factors in the endothelial cells of human fibrovascular *** investigation revealed that the cAMP-responsive element binding protein played a role in the GLP-1r signaling pathway on suppression of STING *** study demonstrates a novel role of GLP-1 rAs in the protection of diabetic retinal vasculature by inhibiting STING-elicited inflammatory signals.

关键词： GLP-1 rAs STING signaling retinal endothelial cells Mitochondrial leakage retinal vascular dysfunction diabetic retinopathy CrEB Inflammation

Parameter Estimation of a Valve-Controlled Cylinder System Model Based on Bench Test and Operating data Fusion

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Chinese Journal of Mechanical Engineering 2024年第2期37卷 247-263页

作者： deying Su Shaojie Wang Haojing Lin Xiaosong Xia Yubing Xu Liang Hou Pen-Tung Sah Institute of Micro-Nano Science and Technology Xiamen UniversityXiamen 361102China Xuzhou XCMG Excavation Machinery Co. LtdXuzhou 221000China

The accurate estimation of parameters is the premise for establishing a high-fidelity simulation model of a valve-controlled cylinder *** test data are easily obtained,but it is challenging to emulate actual loads in the research on parameter estimation of valve-controlled cylinder *** the actual load information contained in the operating data of the control valve,its acquisition remains *** paper proposes a method that fuses bench test and operating data for parameter estimation to address the aforementioned *** proposed method is based on Bayesian theory,and its core is a pool fusion of prior information from bench test and operating ***,a system model is established,and the parameters in the model are ***,the bench and operating data of the system are ***,the model parameters and weight coefficients are estimated using the data fusion ***,the estimated effects of the data fusion method,Bayesian method,and particle swarm optimisation(PSO)algorithm on system model parameters are *** research shows that the weight coefficient represents the contribution of different prior information to the parameter estimation *** effect of parameter estimation based on the data fusion method is better than that of the Bayesian method and the PSO *** load complexity leads to a decrease in model accuracy,highlighting the crucial role of the data fusion method in parameter estimation studies.

关键词： Valve-controlled cylinder system Parameter estimation The Bayesian theory data fusion method Weight coefficients

High-timing-precision detection of single X-ray photons by superconducting nanowires

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National Science review 2024年第1期11卷 194-203页

作者： Shuya Guo Jingrou Tan Hengbin Zhang Jinguang Wang Tianhao Ji Labao Zhang Xiaolong Hu Jian Chen Jun Xie Kai Zou Yun Meng Xiaomin Bei Ling-An Wu Qi Chen Hao Wang Xuecou Tu Xiaoqing Jia Qing-Yuan Zhao Lin Kang Peiheng Wu research Institute of Superconductor Electronics Nanjing University Qian Xuesen Laboratory of Space Technology Beijing National Laboratory of Condensed Matter Physics Institute of Physics Chinese Academy of Sciences Hefei National Laboratory School of Precision Instrument and Optoelectronic Engineering Tianjin University key Laboratory of Optoelectronic Information Science and Technology Ministry of Education

Precisely acquiring the timing information of individual X-ray photons is important in both fundamental research and practical applications. The timing precision of commonly used X-ray single-photon detectors remains in the range of one hundred picoseconds to microseconds. In this work, we report on high-timing-precision detection of single X-ray photons through the fast transition to the normal state from the superconductive state of superconducting nanowires. We successfully demonstrate a free-running X-ray single-photon detector with a timing resolution of 20.1 ps made of 100-nm-thick niobium nitride film with an active area of 50 μm by 50 μm. By using a repeated differential timing measurement on two adjacent X-ray single-photon detectors, we demonstrate a precision of 0.87 ps in the arrival-time difference of X-ray photon measurements. Therefore, our work significantly enhances the timing precision in X-ray photon counting, opening a new niche for ultrafast X-ray photonics and many associated applications.

关键词： single-photon detection timing precision superconductor ultrafast phenomenon pulsar X-ray navigation

redox responsive polymeric nanoparticles enhance the efficacy of cyclin dependent kinase 7 inhibitor for enhanced treatment of prostate cancer

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Chinese Chemical Letters 2024年第8期35卷 443-448页

作者： Yiran Tao Chunlei dai Zhaoxiang Xie Xinru You Kaiwen Li Jun Wu Hai Huang department of Urology Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China department of Urology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510120China Biomedical Innovation Center The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510120China School of Biomedical Engineering Sun Yat-sen UniversityShenzhen 518107China Center for Nanomedicine and department of Anesthesiology Brigham and Women’s HospitalHarvard Medical SchoolBostonMA 02115United States guangdong Provincial key Laboratory of Malignant Tumor Epigenetics and Gene regulation Sun Yat-sen Memorial HospitalSun Yat-Sen UniversityGuangzhou 510120China department of Urology The Sixth Affiliated Hospital of Guangzhou Medical UniversityQingyuan People’s HospitalQingyuan 511518China Bioscience and Biomedical Engineering Thrust The Hong Kong University of Science and Technology(Guangzhou)Guangzhou 511400China division of Life Science The Hong Kong University of Science and TechnologyHong KongChina guangdong Provincial Clinical research Center for Urological diseases Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhou 510120China

Traditional therapies such as surgery and endocrine therapy no longer meet the clinical needs in prostate cancer treatment,and more effective treatments are urgently *** studies have reported that targeted inhibition of the transcription factor cyclin dependent kinase 7(CdK7)could effectively suppress prostate cancer ***,the toxicity of CdK7 inhibitors such as THZ1 is the main limitation of the clinical *** this work,we synthesized Cys8E(C8E)nanoparticles(NPs)loaded with THZ1(C8E@THZ1),a novel GSH-targeting and stimuli-responsive nano-delivery platform,and investigated its anti-tumor potential and biosafety *** vitro,C8E@THZ1 potently inhibited the proliferation and promoted the apoptosis of prostate cancer *** tumor-bearing mice,C8E@THZ1 inhibited tumors by up to 85%,while the damage of THZ1 to liver function was effectively *** results confirmed that inhibition of CdK7 can effectively block the progression of prostate cancer,and that Cys8E NPs is a highly prospective delivery platform to promote the clinical application of CdK7 inhibitors.

关键词： Prostate cancer Nanoparticles CdK7 THZ1 THZ1@Cys8E NPs

Structure–performance relationship of Au nanoclusters in electrocatalysis:Metal core and ligand structure

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Carbon Energy 2024年第8期6卷 63-89页

作者： Bowen Li Lianmei Kang Yongfeng Lun Jinli Yu Shuqin Song Yi Wang The key Lab of Low‐Carbon Chemistry&Energy Conservation of guangdong Province PCFM LabSchool of Chemical Engineering and TechnologySchool of Materials Science and EngineeringSun Yat‐sen UniversityGuangzhouChina department of Chemistry City University of Hong KongHong KongChina

remarkable progress has characterized the field of electrocatalysis in recent decades,driven in part by an enhanced comprehension of catalyst structures and mechanisms at the *** precise metal nanoclusters,serving as exemplary models,significantly expand the range of accessible structures through diverse cores and ligands,creating an exceptional platform for the investigation of catalytic ***,ligand‐protected Au nanoclusters(NCs)with precisely defined core numbers offer a distinct advantage in elucidating the correlation between their specific structures and the reaction mechanisms in *** strategic modulation of the fine microstructures of Au NCs presents crucial opportunities for tailoring their electrocatalytic performance across various *** review delves into the profound structural effects of Au NC cores and ligands in electrocatalysis,elucidating their underlying mechanisms.A detailed exploration of the fundamentals of Au NCs,considering core and ligand structures,***,the interaction between the core and ligand structures of Au NCs and their impact on electrocatalytic performance in diverse reactions are *** the discourse,challenges and personal prospects are presented to guide the rational design of efficient electrocatalysts and advance electrocatalytic reactions.

关键词： Au nanoclusters core electrocatalytic performance ligand structures

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铁浴条件下电炉粉尘球团的熔融与分离行为

Transactions of Nonferrous Metals Society of China 2024年第1期34卷 347-360页

作者：杨超佘雪峰王如意王静松薛庆国北京科技大学钢铁冶金新技术国家重点实验室北京100083 宝山钢铁股份有限公司技术中心上海201900

为了提高对含锌电弧炉粉尘(EAFd)的利用效率,实验研究EAFd球团在铁浴条件下的还原熔化行为。定义铁液滴球形度作为判断其凝聚的标准,然后探讨铁液滴直径和球形度之间随时间变化的关系。根据实验最终建立EAFd颗粒的熔化和分离行为。结果... 详细信息

为了提高对含锌电弧炉粉尘(EAFd)的利用效率,实验研究EAFd球团在铁浴条件下的还原熔化行为。定义铁液滴球形度作为判断其凝聚的标准,然后探讨铁液滴直径和球形度之间随时间变化的关系。根据实验最终建立EAFd颗粒的熔化和分离行为。结果表明,在铁浴条件下,EAFd球团的Zn去除率在5.0 min时达到99%以上,但在15.0 min时金属渣分离还没有完成。由于成分的波动,在EAFd球团中形成几个区域的液态渣,然后液态渣不断增加,直到球团完全熔化。球形度>65%、直径>500μm的Fe液滴的数量随着时间的推移而减少,大直径的Fe液滴先完成分离。渣铁分离过程如下:在布朗运动下Fe液滴在渣中形成,之后Fe液滴直径在马兰戈尼效应下增加,Fe液滴在渣中下降速度符合斯托克斯定律。

关键词：电炉粉尘铁浴球团融化渣铁分离

Isolation and characterization of mpox virus from the first mpox case in Shenzhen,China

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Virologica Sinica 2024年第2期39卷 335-337页

作者： Lin Cheng Liuqing Yang Miao Wang Yabo Peng Haiyan Wang Xiaoxiang Yang Juanjuan Zhao Mingxia Zhang Fuxiang Wang Zheng Zhang Institute for Hepatology National Clinical Research Center for Infectious DiseaseShenzhen Third People's HospitalShenzhen518112China department of Infectious diseases Shenzhen Third People's HospitalShenzhen 518112China The Second Affiliated Hospital School of MedicineSouthern University of Science and TechnologyShenzhen 518112China

dear Editor,Unlike previous outbreaks of the mpox(previously known as monkeypox),which were localized in Africa and resulted in small numbers of infections due to limited human-to-human transmission,the current outbreak beginning in May 2022,has spread rapidly primarily through human-to-human transmission in non-endemic countries(Gong et al.,2022).As of 27 Sep 2023,115 countries and regions have reported cases of mpox to the World Health Organization(WHO),bringing the total number of confirmed cases to 90,618 including 125 *** the number of new cases has decreased in most WHO regions in the second half of 2022,the curves reveal a long outbreak tail in different subregions of the *** worrying,106 mpox cases were reported in the mainland of China in June 2023.

关键词： mainland bringing

development of LAG-3/FGL1 blocking peptide and combination with radiotherapy for cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1150-1165页

作者： Yuzhen Qian Yixuan Sun Peishang Shi Xiuman Zhou Qiongqiong Zhang Qingyu dong Shengzhe Jin Lu Qiu Xiaoshuang Niu Xiaowen Zhou Wenshan Zhao Yahong Wu Wenjie Zhai Yanfeng Gao School of Life Sciences Zhengzhou UniversityZhengzhou 450001China School of Pharmaceutical Sciences(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107China International Joint Laboratory for Protein and Peptide drugs of Henan Province Zhengzhou UniversityZhengzhou 450001China

Aside from antibodies,peptides show great potential as immune checkpoint inhibitors(ICIs)due to several advantages,such as better tumor penetration and lower ***-activation gene 3(LAG-3)is an immune checkpoint which can induce T cell dysfunction through interaction with its soluble ligand fibrinogen like protein-1(FGL1).Here,we found that LAG-3 expression was higher than programmed cell death protein 1(Pd-1)in multiple human cancers by TCGA databases,and successfully identified a LAG-3 binding peptide LFP-6 by phage display bio-panning,which specifically blocks the interaction of LAG-3/FGL1 but not LAG-3/***,d-amino acids were introduced to substitute the N-and C-terminus of LFP-6 to obtain the proteolysis-resistant peptide LFP-d1,which restores T cell function in vitro and inhibits tumor growth in ***,a bispecific peptide LFOP targeting both Pd-1/Pd-L1 and LAG-3/FGL1 was designed by conjugating LFP-d1 with Pd-1/Pd-L1blocking peptide OPBP-1(8-12),which activates T cell with enhanced proliferation and IFN-γ *** importantly,LFOP combined with radiotherapy significantly improve the T cell infiltration in tumor and elevate systemic antitumor immune *** conclusion,we developed a novel peptide blocking LAG-3/FGL1 which can restore T cell function,and the bispecific peptide synergizes with radiotherapy to further enhance the antitumor immune response.

关键词： LAG-3 FGL1 Pd-1 Pd-L1 Peptide Immune checkpoint radiotherapy Cancer immunotherapy

design of Low-Power Turbo Encoder and decoder for NB-IoT

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Chinese Journal of Electronics 2024年第2期33卷 403-414页

作者： Chong ZHANG Yuhang LIN deming WANG Jianguo HU School of Microelectronics Science and Technology Sun Yat-sen University School of Physics and Telecommunication Engineering South China Normal University School of Electronics and Information Engineering South China Normal University development research Institute of Guangzhou Smart City Shenzhen research Institute of Sun Yat-sen University

Turbo code is an error correction coding scheme close to the Shannon limit, usually used in wireless data transmission. Based on the parallel Turbo code algorithm, a parallel Turbo code circuit design scheme is *** the encoder, the recursive systematic convolutional encoder is multiplexed. The decoder is divided into branch metric, recursive, maximum likelihood ratio, and external information calculation modules. The decoding algorithm is based on Max-Log-MAP, controlling the component decoder in parallel. And the state metric calculation in the decoding circuit is combined to reduce the overall power consumption effectively, enabling the encoder and decoder to be used in narrowband Internet of things(NB-IoT). Finally, the hardware scheme of the main functional modules of Turbo code encoding and decoding is designed and implemented. The results show that the dynamic power consumption is less than 50 m W. The overall on-chip power consumption is reduced by 40% at the frequency of 125 MHz compared with previous jobs.

关键词： Measurement Wireless communication Power demand Systematics Turbo codes System-on-chip Power dissipation