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Artificial Nucleic Acid Tractor-Directed Simultaneous Depletion of Oncogenic Membrane Proteins Without Hijacking Proteolysis-Specific Actuator

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CCS Chemistry 2024年第2期6卷 439-449页

作者： Zhen Zou Songlan Pan Qian Xue Ting Chen Ziyun Huang Bei Qing Pengfei Liu Conghui zhao yunlin Sun Erhu Xiong Ronghua Yang Key Laboratory of Chemical Biology and Traditional Chinese Medicine Research Ministry of EducationCollege of Chemistry and Chemical EngineeringHunan Normal UniversityChangsha 410081 School of Chemistry and Chemical Engineering Hunan Provincial Key Laboratory of CytochemistryChangsha University of Science and TechnologyChangsha 410114 The Second Xiangya Hospital Central South UniversityChangsha 410011

Targeted protein degradation(TPD)is an emerging tool for degrading proteins of interest,which affords an attractive modality for cancer ***,the present TPD technologies must engage a proteolysis-specific actuator to initiate degradation of targeted proteins in the proteasome or ***,we report an artificial tractor that can induce endocytosis-mediated protein depletion without hijacking a proteolysis-specific *** this design,bispecific aptamer chimeras(BSACs)are established,which can bridge human epidermal growth factor receptor 2(ErbB-2),an important biomarker in a common important biomarker in cancer,with membrane proteins of *** advantage of the property of aptamer-induced endocytosis and digestion of ErbB-2,another membrane protein is translocated into the lysosome in a hitchhike-like manner,resulting in lysosomal proteolysis along with *** strategy frees the TPD from the fundamental limitation of proteolysis-specific actuator and allows simultaneous regulation of the quantity and function of two oncogenic receptors in a cell-type-specific manner,expanding the application scope of TPD-based therapeutics.

关键词： targeted protein degradation aptamer epidermal growth factor receptor 2 lysosome membrane proteins cancer therapy

Convolutional neural network for transient grating frequency-resolved optical gating trace retrieval and its algorithm optimization

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Chinese Physics B 2021年第4期30卷 586-590页

作者： Siyuan Xu Xiaoxian Zhu Ji Wang Yuanfeng Li Yitan Gao Kun zhao Jiangfeng Zhu Dacheng Zhang yunlin Chen Zhiyi Wei School of Physics and Optoelectronic Engineering Xidian UniversityXi'an 710071 China Beijing National Laboratory for Condensed Matter Physics Institute of PhysicsChinese Academy of SciencesBeijing 100190China University of Chinese Academy of Sciences Beijing 100049China Institute of Applied Micro-Nano Materials School of ScienceBeijing Jiaotong UniversityBeijing 100044China Songshan Lake Material Laboratory Dongguan 523808China

A convolutional neural network is employed to retrieve the time-domain envelop and phase of few-cycle femtosecond pulses from transient-grating frequency-resolved optical gating(TG-FROG) *** use theoretically generated TGFROG traces to complete supervised trainings of the convolutional neural networks,then use similarly generated traces not included in the training dataset to test how well the networks are *** retrieval of such traces by the neural network is *** our case,we find that networks with exponential linear unit(ELU) activation function perform better than those with leaky rectified linear unit(LRELU) and scaled exponential linear unit(SELU).Finally,the issues that need to be addressed for the retrieval of experimental data by this method are discussed.

关键词： transient-grating frequency-resolved optical gating convolutional neural network activation function phase retrieval algorithm

Efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus: a randomized controlled trial

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Journal of Traditional Chinese Medicine 2016年第5期36卷 640-648页

作者： Guo Qiang Zhang Hengyao Li Mindian zhao Ziyi Luo yunlin Luo Yulei Cao Wenzhai zhao Huan Zhu Ranran Lei Xingxing Chen Huizhen Gan Huakui Zuo Zhihuang Chen Qi Shi Cuimei Zhang Xinli Guo Jian Zhong Sen Chen Qiu School of Clinical Medicine Chengdu University of Traditional Chinese Medicine Department of Endocrinology Ningxia Chinese Medicine Research Center Department of Cellular and Molecular Physiology Section of Comparative Medicine and Program in Integrative Cell Signaling and Neurobiology of Metabolism Yale University School of Medicine Department of Central Laboratory Teaching Hospital of Chengdu University of Traditional Chinese Medicine Department of Traditional Chinese Medicine Dujiangyan Traditional Chinese Medicine Hospital Diabetes Center The third Teaching Hospital of Chengdu University of Traditional Chinese Medicine Medical Department of Cardiology Zigong First People's Hospital Medical Department of Neurology Teaching Hospital of Chengdu University of Traditional Chinese Medicine Department of Endocrinology The First People's Hospital of Neijiang Department of Endocrinology The Central Hospital of Guangyuan Department of Endocrinology Zizhong County Hospital of Traditional Chinese Medicine Department of Endocrinology Hospital of traditional Chinese Medicine of Xichang Department of Endocrinology Liangshan Hospital of Integrated Traditional and Western Medicine Department of Endocrinology The Second People's Hospital of Leshan Medical Department of Infections Teaching Hospital of Chengdu University of Traditional Chinese Medicine Medical Department of Endocrinology Teaching Hospital of Chengdu University of Traditional Chinese Medicine

OBJECTIVE: To assess the efficacy and safety of Sancai powder in patients with type 2 diabetes mellitus(T2DM) inadequately controlled with single oral metformin in a randomized controlled trial(RCT).METHODS: A total of 132 patients with T2 DM were enrolled in the study, who only took metformin(500-1000 mg/day) for at least three months and with inadequate glycemic control(7.0% ≤ hemoglobin A1 c ≤ 9.0%) in the past three *** patients stopped taking metformin with lifestyle interventions for three weeks, and 105 patients qualified for the program. They were randomly divided into the Sancai powder group and the metformin group(1500 mg/day). The follow-up period was for 12 weeks. Comparisons of several variables were ***: No significant differences were found between the two groups in hemoglobin A1c(Hb A1c),fasting plasma glucose(FPG) and 2 h post-meal glucose(2h PG), although they had decreased significantly(P < 0.01). Homeostasis model assessment of beta cell function index was significantly improved in Sancai powder group(P < 0.01), and there were significant differences in the changes of homeostasis model assessment of insulin resistance and insulin sensitivity index in the two groups(P < 0.05). Sancai powder significantly reduced triglyceride level(P < 0.05), although there was no significant difference in the body weight and body mass index in the two ***: In this 12-week study, Sancai powder could significantly reduce hemoglobin A1 c,FPG and 2h PG levels, improved beta-cell function and insulin resistance of the T2 DM inadequately controlled with metformin.

关键词： Diabetes Mellitus Type 2 Sancai powder Metformin Treatment outcome Randomized controlled trial

Comparative metabolomics analysis of unique yellow hawthorn(Crataegus pinnatifida)and red-skinned cultivars reveals a different polyphenol biosynthesis flux and antioxidative and antidiabetic potential

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Food Quality and Safety 2024年第3期8卷 520-533页

作者： Yilong Liu Wenwen You Ruoqi Wang Tao Zeng Xiaoyong zhao yunlin Cao Wenna Zhang Zongxing Nie Xiaochun Yang Xian Li Zhejiang Provincial Key Laboratory of Horticultural Plant Integrative Biology Zhejiang UniversityHangzhouChina Shandong(Linyi)Institute of Modern Agriculture Zhejiang UniversityLinyiChina Center for Drug Safety Evaluation and Research College of Pharmaceutical SciencesZhejiang UniversityHangzhouChina Damenshan Hawthorn Research Institute in Fei County LinyiChina

Objectives:This paper aims to investigate the polyphenol metabolite variation and bioactivities of different-colored hawthorn berries(Crataegus pinnatifida).Materials and Methods:Comparative metabolomics analysis between peel and flesh of yellow hawthorn'Jinruyi'(JRY)and red-skinned ones was carried out by UPLC-MS/*** activities andα-glucosidase inhibition capacity were also tested among different colored hawthorn ***:A total of 453 polyphenols was characterized,among which phenolic acids and flavonoids were abundant,and were closely relevant to the antioxidant capacity of hawthorn *** profile showed accession-specific accumulation in peel or flesh of different colored *** unique yellow hawthorn was found to have few anthocyanins but showed enhanced flux to synthesize flavones and flavonols,especially flavone C-glycosides and acylated flavonol *** specific acylation decoration included acetylation,p-coumaroylation,and *** addition,yellow hawthorn showed excellentα-glucosidase inhibitory effect,which might be associated with the high concentration of 8 polyphenols including 5 phenolic acids,2 flavone C-glycosides,and an acylated flavonol glycoside,namely,quercetin-7-O-(6ʹʹ-malonyl)*** acylated flavonol showed the strongest correlation with the inhibition effect of hawthorn fruits onα-glucosidase,and was predicted to have the lowest binding energy with the enzyme according to molecular docking analysis,indicating its great potential as a strongα-glucosidase inhibitor and an important antidiabetic ingredient in yellow ***:The acylated flavonol glycosides and C-glycosyl flavones might be chemotaxonomic markers differentiating varieties and bioactivities of yellow hawthorn from the traditional red-skinned *** findings complement the existing knowledge on the metabolite composition and nutritional properties of hawthorn fruits.

关键词： Hawthorn fruit comparative metabolomics analysis antioxidant activity α-glucosidase inhibitory effect polyphenol biosynthesis

二氧化硅/木材复合材料的微观结构与物理性能

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复合材料学报 2006年第4期23卷 52-59页

作者：符韵林赵广杰全寿京广西大学林学院南宁530004 北京林业大学材料科学与技术学院北京100083 江原大学山林科学学院春川韩国200701

为了明确二氧化硅/木材复合材料的微观结构与物理性能,通过EDAX及XRD的测定分析了溶胶-凝胶法制备的二氧化硅/木材复合材料的微观结构,通过应力松弛、介电性质、热重、表面显微硬度的测定分析了该材料的物理性能。结果表明:生成的二氧... 详细信息

为了明确二氧化硅/木材复合材料的微观结构与物理性能,通过EDAX及XRD的测定分析了溶胶-凝胶法制备的二氧化硅/木材复合材料的微观结构,通过应力松弛、介电性质、热重、表面显微硬度的测定分析了该材料的物理性能。结果表明:生成的二氧化硅与增重率呈正相关,在纤维饱和点以下,生成的二氧化硅存在于细胞壁中。XRD衍射峰位置没有改变,增重率增大,峰强减弱,结晶度减小。应力松弛量变小,材料内部的结合力增强,分子间产生了交联结合。介电常数值增大,介电损耗随着频率的增加呈先增加后减小的趋势,室温下,出现最大峰值的频率均在logf=6.5 Hz附近。热失重过程中,快速失重的起始温度提高,残余质量增加,表面显微硬度提高。

关键词：溶胶-凝胶法二氧化硅/木材复合材料微观结构物理性能

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太湖梅梁湾水下光场扰动的特征分析

光学学报 2007年第5期27卷 760-765页

作者：赵巧华秦伯强张运林中国科学院南京地理与湖泊研究所

在水体表面波的扰动作用下,水下光场随深度呈现较为明显的波动现象,且水中光合作用会对水下光场波动作出响应,因而此现象引起了广泛的关注。基于太湖梅梁湾观测的水下光场数据,计算了水下光场随深度的变化,并分析了其波动特征。结果表明... 详细信息

在水体表面波的扰动作用下,水下光场随深度呈现较为明显的波动现象,且水中光合作用会对水下光场波动作出响应,因而此现象引起了广泛的关注。基于太湖梅梁湾观测的水下光场数据,计算了水下光场随深度的变化,并分析了其波动特征。结果表明:表面波引起了水下光场较为明显的波动现象,波动振幅最大的深度基本小于20 cm,远小于海洋中对应的深度;水下光场波动的振幅随深度呈e的负指数衰减,漫射消光系数越大,水下光场的波动衰减得也越快;当深度大于30 cm时,水下光场的扰动现象基本消失。还计算了船舶对水下光场观测的影响,发现直射光未被遮挡的情况下,漫射比例越高,其相对误差越大。

关键词：海洋光学表面波水下光场波动

Infection with SARS-CoV-2 can cause pancreatic impairment

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2143-2160页

作者： Wei Deng Linlin Bao Zhiqi Song Ling Zhang Pin Yu Yanfeng Xu Jue Wang Wenjie zhao Xiuqin Zhang yunlin Han Yanhong Li Jiangning Liu Qi Lv Xujian Liang Fengdi Li Feifei Qi Ran Deng Siyuan Wang Yibai Xiong Ruiping Xiao Hongyang Wang Chuan Qin NHC Key Laboratory of Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijing 100021China Institute of Molecular Medicine College of Future TechnologyPeking UniversityBeijing 100871China Beijing Key Laboratory of Cardiometabolic Molecular Medicine Peking UniversityBeijing 100871China State Key Laboratory of Biomembrane and Membrane Biotechnology Peking-Tsinghua Center for Life SciencesBeijing 100871China Chinese Academy of Engineering Eastern Hepatobiliary Surgery Hospital225 Changhai RoadYangpu DistrictShanghai 200438China International Co-operation Laboratory on Signal Transduction Eastern Hepatobiliary Surgery InstituteSecond Military Medical UniversityShanghai 200438PR China National Laboratory for Oncogenes and Related Genes Cancer Institute of Shanghai Jiao Tong UniversityShanghai 200441PR China Changping National laboratory(CPNL) Beijing 102206China State Key Laboratory of Respiratory Health and Multimorbidity National Health Commission of the People’s Republic of ChinaBeijingPR China

Evidence suggests associations between COVID-19 patients or vaccines and glycometabolic dysfunction and an even higher risk of the occurrence of ***,we retrospectively analyzed pancreatic lesions in autopsy tissues from 67 SARS-CoV-2 infected non-human primates(NHPs)models and 121 vaccinated and infected NHPs from 2020 to 2023 and COVID-19 ***-label immunofluorescence revealed direct infection of both exocrine and endocrine pancreatic cells by the virus in NHPs and *** and limited phenotypic and histopathological changes were observed in adult *** proteomics and metabolomics results indicated metabolic disorders,mainly enriched in insulin resistance pathways,in infected adult NHPs,along with elevated fasting C-peptide and C-peptide/glucose ratio ***,in elder COVID-19 NHPs,SARS-CoV-2 infection causes loss of beta(β)cells and lower expressed-insulin in situ characterized by islet amyloidosis and necrosis,activation ofα-SMA and aggravated fibrosis consisting of lower collagen in serum,an increase of pancreatic inflammation and stress markers,ICAM-1 and G3BP1,along with more severe glycometabolic *** contrast,vaccination maintained glucose homeostasis by activating insulin receptorαand insulin receptorβ.Overall,the cumulative risk of diabetes post-COVID-19 is closely tied to age,suggesting more attention should be paid to blood sugar management in elderly COVID-19 patients.

关键词： infected elevated homeostasis

Integrated histopathological,lipidomic,and metabolomic profiles reveal mink is a useful animal model to mimic the pathogenicity of severe COVID-19 patients

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Signal Transduction and Targeted Therapy 2022年第2期7卷 560-572页

作者： Zhiqi Song Linlin Bao Wei Deng Jiangning Liu Erjun Ren Qi Lv Mingya Liu Feifei Qi Ting Chen Ran Deng Fengdi Li Yunpeng Liu Qiang Wei Hong Gao Pin Yu yunlin Han Wenjie zhao Junjun Zheng Xujian Liang Fuhe Yang Chuan Qin NHC Key Laboratory of Human Disease Comparative Medicine Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious DiseasesInstitute of Laboratory Animal ScienceChinese Academy of Medical Sciences and Comparative Medicine CenterPeking Union Medical CollegeBeijingChina Shi Jia Zhuang Academy Of Agricultural And Forestry Sciences ShijiazhuangChina Institute of Special Animal and Plant Sciences of CAAS ChangchunChina Chinese Academy of Agricultural Sciences(CAAS) BeijingChina

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is transmitted on mink farms between minks and humans in many ***,the systemic pathological features of SARS-CoV-2-infected minks are mostly ***,we demonstrated that minks were largely permissive to SARS-CoV-2,characterized by severe and diffuse alveolar damage,and lasted at least 14 days post inoculation(dpi).We first reported that infected minks displayed multiple organ-system lesions accompanied by an increased inflammatory response and widespread viral distribution in the cardiovascular,hepatobiliary,urinary,endocrine,digestive,and immune *** viral protein partially co-localized with activated Mac-2+macrophages throughout the ***,we first found that the alterations in lipids and metabolites were correlated with the histological lesions in infected minks,especially at 6 dpi,and were similar to that of patients with severe and fatal ***,altered metabolic pathways,abnormal digestion,and absorption of vitamins,lipids,cholesterol,steroids,amino acids,and proteins,consistent with hepatic dysfunction,highlight metabolic and immune *** kynurenine in infected minks contributed to significant activation of the kynurenine pathway and was related to macrophage ***,which has significant anti-inflammatory and immunomodulating effects,was significantly downregulated at 6 dpi and displayed potential as a targeted *** data first illustrate systematic analyses of infected minks to recapitulate those observations in severe and fetal COVID-19 patients,delineating a useful animal model to mimic SARS-CoV-2-induced systematic and severe pathophysiological features and provide a reliable tool for the development of effective and targeted treatment strategies,vaccine research,and potential biomarkers.

关键词： patients alterations vitamin

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二氧化硅/木材复合材料的动态黏弹性

林业科学 2009年第3期45卷 101-104页

作者：符韵林赵广杰东北林业大学材料科学与工程学院哈尔滨150040 广西大学林学院南宁530004 北京林业大学材料科学与技术学院北京100083

为弄清二氧化硅/木材复合材料的动态黏弹性,通过动态热机械分析仪研究不同增重率的二氧化硅/木材复合材料松弛过程的转变温度及力学损耗角正切的变化。结果表明:二氧化硅/木材复合材料的松弛过程数量减少,直接溶胶-凝胶法制备的二氧化硅... 详细信息

为弄清二氧化硅/木材复合材料的动态黏弹性,通过动态热机械分析仪研究不同增重率的二氧化硅/木材复合材料松弛过程的转变温度及力学损耗角正切的变化。结果表明:二氧化硅/木材复合材料的松弛过程数量减少,直接溶胶-凝胶法制备的二氧化硅/木材复合材料,α松弛过程的转变温度随着增重率的增加而向高温方向移动,增重率为0,5.10%和28.00%的α松弛过程的转变温度分别为75.2,76.8和93.6℃;α松弛峰的峰值减小,增重率为0,5.10%,12.63%和28.00%的α松弛过程的损耗角正切值分别为0.043,0.041,0.033和0.03。加硅烷偶联剂法制备的二氧化硅/木材复合材料,随着增重率的增加,α松弛过程的起始温度向低温方向移动,增重率为6.61%,8.08%和10.58%的α松弛过程的起始温度分别为44.9,41.0和32.2℃。

关键词：二氧化硅/木材复合材料动态黏弹性松弛过程损耗角正切