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Global trends in diabetic eye disease research from 2012 to 2021

Neural Regeneration Research 2024年第10期19卷 2310-2320页

作者： Yuan Yuan Shangli Ji Yali Song Zhaodi Che Lu xiao Shibo Tang jia xiao Aier School of Ophthalmology Central South UniversityChangshaHunan ProvinceChina Changsha Aier Eye Hospital ChangshaHunan ProvinceChina Aier Eye Institute ChangshaHunan ProvinceChina Department of Metabolic and Bariatric Surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina

Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

关键词： clinical trials diabetic cataracts diabetic eye disease diabetic glaucoma diabetic macular edema diabetic retinopathy drug development global research publication research grant

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Goji berry-derived phenylpropionyl phenylethylamine derivatives protect against ethanol-induced hepatic damage

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Food Science and Human Wellness 2024年

作者： Zhengqun Zhou Zhaodi Che jiancong Mai Rui Zhang Zhihui Luo Yifang Li Kwokfai So jia xiao Xinsheng Yao Hao Gao GMH Institute of CNS Regeneration Guangdong Medical Key Laboratory of Brain Function and Diseases Jinan University Clinical Medicine Research Institute and Department of Metabolic and Bariatric Surgery the First Affiliated Hospital of Jinan University Institute of Traditional Chinese Medicine and Natural Products College of Pharmacy/Guangdong Province Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China Jinan University

Goji berry is a famous edible and medicinal substance around the world. In this research， 15 phenylpropionyl phenylethylamine derivatives (1-15)， including one new compound (1)， were separated and identified from goji berry. All isolates were elucidated via extensive NMR spectral analyses and chemical techniques. Six known isolates were first obtained from Lycium genus. Six isolates were effectively split into double chromatographic peaks accompanied by the basically identical areas， indicating they belong to racemates. The ORAC experiment indicated that all isolates displayed a capacity of scavenging free radicals， and most of them exhibited higher ORAC values than EGCG. In ethanol/palmitic acid (PA)-established in vitro hepatocyte injury model， four phenylpropionyl phenylethylamine derivatives (1， 2， 9， and 15) significantly alleviated hepatocyte injury， among which compound 1 exerted the strongest protective activity. Notably， the hepatoprotective effect of compound 1 was further confirmed in ethanol-established liver damage mouse model， reflected by the reduction of lipid accumulation and the attenuation of pathological alteration. Combined with the in vitro results， the in vivo observations suggested that compound 1 suppressed cell apoptosis and the outburst of inflammation. Our findings provided first-hand evidence proving that goji berry-derived phenylpropionyl phenylethylamine derivatives hold a potential in treating alcoholic liver disease.

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Data augmentation method for insulators based on Cycle-GAN

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Journal of Electronic Science and Technology 2024年第2期22卷 36-47页

作者： Run Ye Azzedine Boukerche xiao-Song Yu Cheng Zhang Bin Yan xiao-jia Zhou School of Automation Engineering University of Electronic Science and Technology of ChinaChengdu611731China School of Electrical Engineering and Computer Science University of OttawaOttawaK1N6N5Canada Yangtze River Delta Research Institute(Huzhou) University of Electronic Science and Technology of ChinaHuzhou313001China

Data augmentation is an important task of using existing data to expand data sets.Using generative countermeasure network technology to realize data augmentation has the advantages of high-quality generated samples,simple training,and fewer restrictions on the number of generated samples.However,in the field of transmission line insulator images,the freely synthesized samples are prone to produce fuzzy backgrounds and disordered samples of the main insulator features.To solve the above problems,this paper uses the cycle generative adversarial network(Cycle-GAN)used for domain conversion in the generation countermeasure network as the initial framework and uses the self-attention mechanism and channel attention mechanism to assist the conversion to realize the mutual conversion of different insulator samples.The attention module with prior knowledge is used to build the generation countermeasure network,and the generative adversarial network(GAN)model with local controllable generation is built to realize the directional generation of insulator belt defect samples.The experimental results show that the samples obtained by this method are improved in a number of quality indicators,and the quality effect of the samples obtained is excellent,which has a reference value for the data expansion of insulator images.

关键词： Data expansion Deep learning Generate confrontation network Insulator

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miRNA-21-5p is an important contributor to the promotion of injured peripheral nerve regeneration using hypoxia-pretreated bone marrow-derived neural crest cells

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Neural Regeneration Research 2025年第1期20卷 277-290页

作者： Meng Cong Jing-Jing Hu Yan Yu xiao-Li Li xiao-Ting Sun Li-Ting Wang Xia Wu Ling-Jie Zhu xiao-jia Yang Qian-Ru He Fei Ding Hai-Yan Shi School of Medicine Nantong UniversityNantongJiangsu ProvinceChina Key Laboratory of Neuroregeneration of jiangsu and Ministry of Education and Coinnovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Physiology Jiangsu Health Vocational CollegeNanjingJiangsu ProvinceChina Department of Pathology Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina jiangsu Clinical Medicine Center of Tissue Engineering and Nerve Injury Repair Affiliated Hospital of Nantong UniversityNantongJiangsu ProvinceChina

Our previous study found that rat bone marrow–derived neural crest cells(acting as Schwann cell progenitors)have the potential to promote long-distance nerve repair.Cell-based therapy can enhance peripheral nerve repair and regeneration through paracrine bioactive factors and intercellular communication.Nevertheless,the complex contributions of various types of soluble cytokines and extracellular vesicle cargos to the secretome remain unclear.To investigate the role of the secretome and extracellular vesicles in repairing damaged peripheral nerves,we collected conditioned culture medium from hypoxia-pretreated neural crest cells,and found that it significantly promoted the repair of sensory neurons damaged by oxygen-glucose deprivation.The mRNA expression of trophic factors was highly expressed in hypoxia-pretreated neural crest cells.We performed RNA sequencing and bioinformatics analysis and found that miR-21-5p was enriched in hypoxia-pretreated extracellular vesicles of neural crest cells.Subsequently,to further clarify the role of hypoxia-pretreated neural crest cell extracellular vesicles rich in miR-21-5p in axonal growth and regeneration of sensory neurons,we used a microfluidic axonal dissociation model of sensory neurons in vitro,and found that hypoxia-pretreated neural crest cell extracellular vesicles promoted axonal growth and regeneration of sensory neurons,which was greatly dependent on loaded miR-21-5p.Finally,we constructed a miR-21-5p-loaded neural conduit to repair the sciatic nerve defect in rats and found that the motor and sensory functions of injured rat hind limb,as well as muscle tissue morphology of the hind limbs,were obviously restored.These findings suggest that hypoxia-pretreated neural crest extracellular vesicles are natural nanoparticles rich in miRNA-21-5p.miRNA-21-5p is one of the main contributors to promoting nerve regeneration by the neural crest cell secretome.This helps to explain the mechanism of action of the secretome and extracellular vesicles of neural crest cells in r

关键词： axotomy cell-free therapy conditioned medium extracellular vesicles hypoxic preconditioning microRNA oxygen-glucose deprivation peripheral nerve injury Schwann cell precursors

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Exosome-Transmitted miR-224-5p Promotes Colorectal Cancer Cell Proliferation via Targeting ULK2 in p53-Dependent Manner

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Biomedical and Environmental Sciences 2024年第1期37卷 71-84页

作者： YANG Le Mei ZHENG Qi LIU xiao jia LI Xian Xian Veronica Lim CHEN Qi ZHAO Zhong Hua WANG Shu Yang Department of Pathology School of Basic MedicineFudan UniversityShanghai 200032China Department of Pathology Dunedin School of MedicineUniversity of OtagoDunedin 9054New Zealand Department of Pathology Huashan HospitalFudan UniversityShanghai 200040China Shanghai Cancer Institute Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200127China Teladoc Health Inc Shanghai 200335China Shanghai Medical College Fudan UniversityShanghai 200032China Shanghai Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention Shanghai 200032China

Objective To investigate the role and molecular mechanism of exosomal miR-224-5p in colorectal cancer(CRC).Methods The miR-224-5p expression in CRC patient tissues and cell-derived exosomes was measured by laser capture microdissection and qRT-PCR,respectively.Dual-luciferase reporter gene assay was used to determine the target gene of miR-224-5p.The protein expressions of p53 and unc-51 like kinase 2(ULK2)in CRC cells were detected by western blot.Flow cytometry was used to detect cell cycle and apoptosis.Cell proliferation was measured by CCK8 and EdU assay.Results The miR-224-5p expression was upregulated in CRC tissues and increased progressively with the rise of CRC stage.CRC cells secreted extracellular miR-224-5p mainly in an exosome-dependent manner,and then miR-224-5p could be transferred to surrounding tumor cells to regulate cell proliferation in the form of autocrine or paracrine.Moreover,ULK2 was characterized as a direct target of miR-224-5p and was downregulated in CRC tissues.Interestingly,ULK2 inhibited CRC cell proliferation in a p53-dependent manner.Furthermore,exosome-derived miR-224-5p partially reversed the proliferation regulation of ULK2 on CRC cells.Conclusion Our findings demonstrate that exosome-transmitted miR-224-5p promotes p53-dependent cell proliferation by targeting ULK2 in CRC,which may offer promising targets for CRC prevention and therapy.

关键词： miR-224-5p Exosome ULK2 p53 Cell proliferation Colorectal cancer

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Optimization of Thermal Conductivity of Alumina-Filled Composites by Numerical Simulations

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Journal of Thermal Science 2023年第4期32卷 1569-1582页

作者： LI Shikun LIU Bin jia xiao XU Min ZONG Ruoyu LIU Guohua HUAI Xiulan Beijing Key Laboratory of Multiphase Flow and Heat Transfer for Low Grade Energy Utilization North China Electric Power UniversityBeijing102206China Institute of Engineering Thermophysics Chinese Academy of SciencesBeijing100190China Nanjing Institute of Future Energy System Nanjing211135China

Understanding the correlation between the physical features of composite components and thermal conductive pathway is beneficial to optimizing the overall heat-transfer performance.Herein,we conduct numerical simulation to investigate the thermal conductivity and heat flux distributions of alumina(Al_(2)O_(3))-filled composites.The finite element model was verified by both experimental data and theoretical models.The crucial factors include the influence of the interface thermal resistance,the intrinsic thermal conductivity of the matrix and Al_(2)O_(3)filler,and the size effect of Al_(2)O_(3)fillers were investigated.For single Al_(2)O_(3)-filled composites,the results indicate that increasing the intrinsic thermal conductivity of the matrix is conductive to bridge the Al_(2)O_(3)pathway along heat-transfer direction,but there are very limited contributions by enhancing the intrinsic thermal conductivity of Al_(2)O_(3)filler,tuning the size of Al_(2)O_(3)filler,and reducing the interface thermal resistance.After introducing the multiscale fillers,it is found that the high thermal conductivity can be achieved by regulating their size matching effect.At the optimal binary ratio of 70:30(40µm:15µm)and ternary ratio of 55:35:10(40µm:15µm:10µm),the heat-conduction network presents the dominant skeleton of large-sized filler and the bridging branch of small-sized fillers features,which facilitates the formation of a complete and continuous thermal conductive network.This study gives a practical guidance for the thermal conductive design of Al_(2)O_(3)-filled composites.

关键词： optimization size matching effect thermal conductivity numerical simulation multiscale Al_(2)O_(3)filler

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Hepatitis B virus X protein induces ALDH2 ubiquitin-dependent degradation to enhance alcoholic steatohepatitis

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Gastroenterology Report 2023年第1期11卷 230-246页

作者： Haoxiong Zhou Sizhe Wan Yujun Luo Huiling Liu Jie jiang Yunwei Guo jia xiao Bin Wu Department of Gastroenterology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Alcoholic Liver Disease Center The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongP.R.China Guangdong Provincial Key Laboratory of Liver Disease Research GuangzhouGuangdongP.R.China Clinial Medical Research Institute The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdongP.R.China Department of Metabolic and Bariatric Surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdongP.R.China

Background:Excessive alcohol intake with hepatitis B virus(HBV)infection accelerates chronic liver disease progression and patients with HBV infection are more susceptible to alcohol-induced liver disease.Hepatitis B virus X protein(HBx)plays a crucial role in disease pathogenesis,while its specific role in alcoholic liver disease(ALD)progression has not yet been elucidated.Here,we studied the role of HBx on the development of ALD.Methods:HBx-transgenic(HBx-Tg)mice and their wild-type littermates were exposed to chronic plus binge alcohol feeding.Primary hepatocytes,cell lines,and human samples were used to investigate the interaction between HBx and acetaldehyde dehydrogenase 2(ALDH2).Lipid profiles in mouse livers and cells were assessed by using liquid chromatography–mass spectrometry.Results:We identified that HBx significantly aggravated alcohol-induced steatohepatitis,oxidative stress,and lipid peroxidation in mice.In addition,HBx induced worse lipid profiles with high lysophospholipids generation in alcoholic steatohepatitis,as shown by using lipidomic analysis.Importantly,serum and liver acetaldehyde were markedly higher in alcoholfed HBx-Tg mice.Acetaldehyde induced lysophospholipids generation through oxidative stress in hepatocytes.Mechanistically,HBx directly bound to mitochondrial ALDH2 to induce its ubiquitin–proteasome degradation,resulting in acetaldehyde accumulation.More importantly,we also identified that patients with HBV infection reduced ALDH2 protein levels in the liver.Conclusions:Our study demonstrated that HBx-induced ubiquitin-dependent degradation of mitochondrial ALDH2 aggravates alcoholic steatohepatitis.

关键词： hepatitis B virus X protein alcoholic steatohepatitis acetaldehyde dehydrogenase 2 ubiquitination lysophos-pholipids reactive oxygen species

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基于黏液和黏膜屏障探究楹树皂苷对乙醇致大鼠急性胃溃疡的保护作用机制

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中国中药杂志 2024年第12期49卷 3340-3347页

作者：贾晓雨张建军中国医学科学院北京协和医学院药物研究所消化健康全国重点实验室

探究楹树皂苷对乙醇致大鼠急性胃溃疡的保护作用及其机制。SD大鼠实验前24 h禁食不禁水，正常对照组和模型组灌胃水，阳性药组灌胃雷贝拉唑钠溶液(40 mg·kg-1),受试物组灌胃不同剂量的楹树皂苷溶液(3、10、30 mg·kg-1),30 min后正常... 详细信息

探究楹树皂苷对乙醇致大鼠急性胃溃疡的保护作用及其机制。SD大鼠实验前24 h禁食不禁水，正常对照组和模型组灌胃水，阳性药组灌胃雷贝拉唑钠溶液(40 mg·kg-1),受试物组灌胃不同剂量的楹树皂苷溶液(3、10、30 mg·kg-1),30 min后正常对照组灌胃1.5 mL水，其余各组均灌胃等体积95%乙醇造模，6 h后颈椎脱臼法处死大鼠取胃。统计出血面积，计算溃疡指数；苏木素-伊红（HE）染色检测胃组织病理改变；高碘酸-席夫（PAS）染色检测胃黏膜表面黏液分布；酶联免疫吸附法（ELISA）检测胃黏膜磷脂和氨基己糖含量；Western blot检测胃组织碳酸氢根转运体、基质金属蛋白酶和细胞间紧密连接相关蛋白表达量；免疫组织化学（immunohistochemistry, IHC）染色检测分泌型黏蛋白和紧密连接相关蛋白阳性细胞。结果显示正常对照组大鼠胃组织表面光滑无出血点，模型组大鼠胃溃疡指数为35±11,楹树皂苷在3、10、30 mg·kg-1剂量下对大鼠胃溃疡的抑制率分别为46%（P<0.01）、85%（P<0.001）、100%（P<0.001）。模型组大鼠胃黏膜结构破坏严重，无法观察到黏液层。与模型组相比，楹树皂苷组大鼠胃黏膜表面黏液层完整，黏液中磷脂和氨基己糖含量显著增加，分泌型黏蛋白MUC5AC阳性细胞数明显增多，碳酸氢根转运体SLC26A3和CFTR的表达水平显著提高，应激活化蛋白激酶c-Jun氨基末端激酶（JNK）和核转录因子c-Jun磷酸化显著减少，基质金属蛋白酶（MMP）-8表达量明显降低，同时检测到MMP-8内源性抑制剂（TIMP-1）表达升高，紧密连接蛋白Occludin和ZO-1表达量明显增加。结果表明楹树皂苷一方面通过上调分泌型黏蛋白MUC5AC以及磷脂和氨基己糖含量，同时提高碳酸氢根转运体SLC26A3和CFTR的表达水平来增强黏液-碳酸氢盐屏障功能；另一方面通过抑制JNK信号通路，阻止MMP-8过度活化，从而减少Occludin和ZO-1的降解来增强黏膜屏障功能。即楹树皂苷在黏液屏障和黏膜屏障2个方面共同发挥抗胃溃疡的作用。

关键词：楹树皂苷胃溃疡黏液-碳酸氢盐屏障黏膜屏障细胞间紧密连接基质金属蛋白酶

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SiC/SiC_(f)复合材料包壳管在高温高压水中的应力腐蚀开裂行为

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腐蚀与防护 2024年第6期45卷 75-80页

作者：汪峰肖嘉国家电投集团科学技术研究院核能与核技术研究所北京102209

针对SiC/SiC_(f)复合材料包壳管,采用三点弯加载方法,在模拟压水堆一回路水化学工况的高温高压水中开展了应力腐蚀开裂(SCC)试验,通过腐蚀形貌分析了该材料的抗SCC能力。结果表明:在三点弯加载和高温高压水环境的作用下,该复合材料包壳... 详细信息

针对SiC/SiC_(f)复合材料包壳管,采用三点弯加载方法,在模拟压水堆一回路水化学工况的高温高压水中开展了应力腐蚀开裂(SCC)试验,通过腐蚀形貌分析了该材料的抗SCC能力。结果表明:在三点弯加载和高温高压水环境的作用下,该复合材料包壳管外涂层发生氧化及腐蚀溶解,部分区域出现裂纹扩展和涂层剥落现象,而涂层剥落又进一步加剧了外涂层的腐蚀溶解,导致外涂层过早失效和SiC纤维层暴露;在应力和水化学环境的耦合作用下,中间层SiC纤维出现腐蚀溶解和裂纹扩展现象,SiC纤维层表面的裂纹扩展没有明显的取向性,交叉裂纹的不断产生最终导致纤维层的断裂和整体失效。在涂层表面的孔隙缺陷处易产生应力集中,从而成为裂纹萌生位置,需优化涂层制备工艺。

关键词： SiC/SiC_(f)复合材料包壳管高温高压水应力腐蚀开裂(SCC)

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SiC/SiC_(f)复合材料包壳管在高温高压水中的腐蚀行为

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腐蚀与防护 2024年第5期45卷 26-31页

作者：汪峰肖嘉国家电投集团科学技术研究院核能与核技术研究所北京102209

采用循环高温高压水腐蚀系统模拟压水堆一回路水化学工况对SiC/SiC_(f)复合材料包壳管进行腐蚀试验。通过腐蚀后质量损失和微观形貌分析了SiC/SiC_(f)复合材料包壳管的腐蚀行为。结果表明:腐蚀过程中SiC/SiC_(f)复合材料包壳管依次经历... 详细信息

采用循环高温高压水腐蚀系统模拟压水堆一回路水化学工况对SiC/SiC_(f)复合材料包壳管进行腐蚀试验。通过腐蚀后质量损失和微观形貌分析了SiC/SiC_(f)复合材料包壳管的腐蚀行为。结果表明:腐蚀过程中SiC/SiC_(f)复合材料包壳管依次经历了质量增加、质量加速损失、质量稳定损失和质量损失趋缓等阶段;在腐蚀初期的质量增加阶段,富硅的氧化物薄膜覆盖在胞状晶表面从而减缓了包壳管腐蚀溶解;在质量加速损失阶段,腐蚀溶解以及氧化物脱落导致包壳管加速腐蚀;在质量稳定损失阶段,表面腐蚀溶解和氧化物的生成起到了互相平衡作用;在质量损失趋缓阶段,试样表面出现的密集氧化物,显著缓解了腐蚀溶解,使腐蚀后质量损失速率降低。

关键词： SiC/SiC_(f)复合材料包壳管高温高压水腐蚀

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