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Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin Long Chuanhua Ge Yueyang Zhao Yuanjie Liu Qinghua Zeng Qing Tang Zhifang Dong Guiqiong He institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina Department of Anatomy Chongqing Medical UniversityChongqingChina Department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education key laboratory of Child Development and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research Center for Child Health and Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina chongqing key laboratory of Child Neurodevelopment and Cognitive Disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase

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Multi-layer multi-pass friction rolling additive manufacturing of Al alloy:Toward complex large-scale high-performance components

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International Journal of Minerals,Metallurgy and Materials 2025年第2期32卷 425-438页

作者： Haibin Liu Run Hou Chenghao Wu Ruishan Xie Shujun Chen College of Mechanical&Energy Engineering Beijing University of TechnologyBeijing 100124China chongqing Research institute of Beijing University of Technology Chongqing 401121China

At present,the emerging solid-phase friction-based additive manufacturing technology,including friction rolling additive man-ufacturing(FRAM),can only manufacture simple single-pass *** this study,multi-layer multi-pass FRAM-deposited alumin-um alloy samples were successfully prepared using a non-shoulder tool *** material flow behavior and microstructure of the over-lapped zone between adjacent layers and passes during multi-layer multi-pass FRAM deposition were studied using the hybrid 6061 and 5052 aluminum *** results showed that a mechanical interlocking structure was formed between the adjacent layers and the adja-cent passes in the overlapped center *** friction and rolling of the tool head led to different degrees of lateral flow and plastic deformation of the materials in the overlapped zone,which made the recrystallization degree in the left and right edge zones of the over-lapped zone the highest,followed by the overlapped center zone and the non-overlapped *** tensile strength of the overlapped zone exceeded 90%of that of the single-pass deposition *** is proved that although there are uneven grooves on the surface of the over-lapping area during multi-layer and multi-pass deposition,they can be filled by the flow of materials during the deposition of the next lay-er,thus ensuring the dense microstructure and excellent mechanical properties of the overlapping *** multi-layer multi-pass FRAM deposition overcomes the limitation of deposition width and lays the foundation for the future deposition of large-scale high-performance components.

关键词： aluminum alloy additive manufacturing solid-state friction stir welding multi-layer multi-pass

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通过Knoevenagel缩合双酮吡咯和吲哚二噻吩得到乙烯基链接的非晶态共轭聚合物并应用于柔性晶体管（英文）

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Science China Materials 2025年第1期 110-116页

作者：陈雁琳陈品宇周仕弘杨志伟龙海军梁先峰陈天文黎静谭陆西张浩力董立春刘子桐 School of Chemistry and Chemical Engineering Chongqing University State key laboratory of Applied Organic Chemistry (SKLAOC) Key Laboratory of Special Function Materials and Structure Design (MOE) College of Chemistry and Chemical Engineering Lanzhou University chongqing institute of Green and Intelligent Technology Chinese Academy of Sciences

共轭聚合物在柔性薄膜晶体管器件中展现出广泛的应用潜力.然而,设计和合成具有高迁移率与优良弯曲（或拉伸）稳定性的共轭聚合物仍面临诸多挑战.本文报道了一种具有乙烯基链接的共轭聚合物PDPPVIDT,该聚合物通过双侧甲基取代的双酮吡咯...

共轭聚合物在柔性薄膜晶体管器件中展现出广泛的应用潜力.然而,设计和合成具有高迁移率与优良弯曲（或拉伸）稳定性的共轭聚合物仍面临诸多挑战.本文报道了一种具有乙烯基链接的共轭聚合物PDPPVIDT,该聚合物通过双侧甲基取代的双酮吡咯（DPP）和茚并二噻吩（IDT）二醛单体,采用环境友好的Knoevenagel缩合反应合成.该反应条件温和,且具备良好的环境友好性及规模化潜力.研究结果表明,聚合物主链的平面性得以增强,并且显示出稳定的π-π堆积特性.此外,由于乙烯基的构象异构化特性, PDPPVIDT薄膜呈现出近乎无定形的特性,从而同时确保了电荷传输效率与柔韧性.基于PDPPVIDT的柔性有机薄膜晶体管（OTFT）器件展示出高达1.70 cm2V-1s-1的优异迁移率和良好的机械弯曲恢复能力.该研究展示了乙烯基链接D-A共轭聚合物的潜力,并强调了其生产过程的工业适应性,为未来柔性电子材料的设计与合成提供了新的思路.

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Increased serum levels of soluble CD146 and vascular endothelial growth factor receptor 2 in patients with exudative age-related macular degeneration

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International Journal of ophthalmology(English edition) 2019年第3期12卷 457-463页

作者： Yan-Yao Liu Yue Bin Xing Wang Hui Peng Department of ophthalmology the First Affiliated Hospital of Chongqing Medical University chongqing key laboratory of ophthalmology Chongqing Eye Institute

AIM: To investigate serum levels of soluble CD146(s CD146) and vascular endothelial growth factor receptor 2(VEGFR2) in patients with age-related macular degeneration(AMD). METHODS: Eighty-eight patients with exudative AMD and 45 sex-and age-matched healthy controls were enrolled in this study conducted in China. Serum samples was obtained from the patients with exudative AMD and from the controls. Serum sCD146 and VEGFR2 protein levels were measured using an enzyme-linked immunosorbent ***: We found that serum sCD146 and VEGFR2 protein levels were significantly higher in the patients with exudative AMD group than in the controls(t=3.859, P<0.001 and t=3.829, P<0.001, respectively). Serum sCD146 levels were significantly higher in patients with classic choroidal neovascularization(CNV) than in those with occult CNV(t=9.899, P<0.001). There was a significant difference in the trend for exudative AMD in the highest versus lowest quartile of circulating sCD146 levels(χ2=10.29, P=0.001). The receiver operating characteristic curve analysis showed that the area under the curve was 0.696 for s CD146(95%CI: 0.601-0.791) with an optimum diagnostic cut-off value of 157.16 ng/mL, a sensitivity of 55.7%, and a specificity of 82.2%.CONCLUSION: The serum sCD146 level increases and may be a biomarker for exudative AMD.

关键词： age-related macular degeneration soluble CD146 vascular endothelial growth factor receptor 2 serum

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Increased interleukin-26 expression in proliferative diabetic retinopathy

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International Journal of ophthalmology(English edition) 2019年第11期12卷 1688-1692页

作者： Peng Wang Wen-Yan Wang Xue-Dong Zhang Department of ophthalmology the First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ophthalmology Chongqing Eye Institute

AIM: To detect the possible role of interleukin(IL)-26 in diabetic retinopathy(DR) ***: Subjects were divided into diabetes without retinopathy(DWR) group(n=20), non-proliferative diabetic retinopathy(NPDR) group(n=20), proliferative diabetic retinopathy(PDR) group(n=20) and normal control group(n=20). The protein expression of IL-26 in the serum and vitreous fluid were measured by enzyme-linked immunosorbent assay(ELISA). The m RNA change of IL-26 in peripheral blood mononuclear cells(PBMCs) was assessed by real-time polymerase chain ***: The serum expression of IL-26 in PDR group was significantly elevated compared with the normal control group, DWR group and NPDR group. The vitreous fluid concentration of IL-26 in PDR patients(without antiVEGF therapy) was also higher compared to normal controls. However, no obvious significance was found concerning the expression of IL-26 in vitreous fluid between PDR after anti-VEGF therapy and normal controls. In PDR group, the m RNA level of IL-26 significantly increased compared with the normal controls and DWR patients in the ***: Protein and m RNA expression of IL-26 are increased in serum, vitreous fluid and PBMCs in PDR patients, suggesting that IL-26 may be associated with the pathogenesis of PDR.

关键词： interleukin-26 serum vitreous fluid peripheral blood mononuclear cells proliferative diabetic retinopathy

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Activated complement classical pathway in a murine model of oxygen-induced retinopathy

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International Journal of ophthalmology(English edition) 2015年第1期8卷 17-22页

作者： Xue-Ying Tao Shi-Jie Zheng Bo Lei Department of ophthalmology the First Affiliated Hospital of Chongqing Medical UniversityChongqing Key Laboratory of OphthalmologyChongqing Eye Institute Department of ophthalmology Chongqing Maternal and Child Health-Care Hospital

AIM: To investigate whether the complement system is involved in a murine model of oxygen-induced retinopathy(OIR).METHODS: Forty C57BL/6J newborn mice were divided randomly into OIR group and control group. OIR was induced by exposing mice to 75% ±2% oxygen from postnatal 7d(P7) to P12 and then recovered in room *** the control group, the litters were raised in room *** the postnatal 17d(P17), gene expressions of the complement components of the classical pathway(CP),the mannose-binding lectin(MBL) pathway and the alternative pathway(AP) in the retina were determined by quantitative real-time polymerase chain reaction(RT-PCR). Retinal protein expressions of the key components in the CP were examined by Western blotting.· RESULTS: Whole mounted retina in the OIR mice showed area of central hypoperfusion in both superficial and deep layers and neovascular tufts in the *** expressions of C1 qb and C4 b genes in the OIR retina were significantly higher than those of the controls. The expression of retinal complement factor B(CFB) gene in OIR mice was significantly lower than those of the controls. However, the expressions of C3 and complement factor H(CFH) genes were higher. The protein synthesis of the key components involved in the CP(C1q, C4 and C3) were also significantly higher in OIR mouse retina. Although MBL-associated serine protease 1(MASP1) and MASP2 were detected in both the OIR and the control groups, the expressions were weak and the difference between the two groups was not ***: Our data suggest that the complement system CP is activated during the pathogenesis of murine model of OIR.

关键词： oxygen-induced retinopathy complement activation classical pathway retina mouse

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Hemoglobin integrated red blood cell membrane-coated metalorganic framework nano-platform for improving the self-adaptive blood glucose management

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Nano Research 2025年第1期18卷 618-627页

作者： Shuai Wu Li Zhu Sheng Ni Xiong Zhao Meng Yan Yuan Zhong Karissa Kusuma Yi Liang Kaiwen Bao Kai Qu Xian Qin Kun Zhang Wuquan Deng Da Sun Wei Wu key laboratory of Biorheological Science and Technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400044China chongqing University Three Gorges Hospital Chongqing Municipality Clinical Research Center for Endocrinology and Metabolic DiseasesChongqing 404000China institute of Life Sciences&Biomedical Collaborative Innovation Center of Zhejiang Province Wenzhou UniversityWenzhou 325035China Department of Endocrinology School of MedicineChongqing Emergency Medical CenterChongqing University Central HospitalChongqing 400014China

Diabetes,a prevalent chronic metabolic disorder,often leads to severe ***,existing treatment methods may pose life-threatening risks due to poor patient compliance and inaccurate dosing of subcutaneous insulin ***,a biomimetic red blood cell(RBC)membrane-coated glucose-responsive nanoplatform is developed for controlling insulin *** nanoplatforms with RBC membrane can prolong the half-life of nano-formulation in vivo mediated by the biomimetic immune ***,the cascade catalytic effect of glucose oxidase(GOx)encapsulated in metal-organic frameworks(MOFs)and hemoglobin(Hb)in the RBC membrane are able to not only facilitate glucose-responsive insulin release,but also eliminate the detrimental by-product hydrogen peroxide(H_(2)O_(2))resulting from the Hb mediated H_(2)O_(2)*** in vitro and in vivo studies have demonstrated the favorable glucose-responsive performances of this advanced nano-platform with a single intravenous injection maintaining blood glucose balance in Type 1 Diabetes(T1D)mice for an extended duration without the hypoglycemia ***,this biomimetic insulin delivery system is poised to function as a strategy for the intravenous insulin administration,offering a promising drug candidate for the self-adaptive long-term T1D treatment.

关键词： glucose-responsive metal-organic frameworks red blood cell membrane insulin delivery glucose oxidase hemoglobin

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Th lymphocyte subsets in patients with Vogt-KoyanagiHarada disease

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International Journal of ophthalmology(English edition) 2019年第2期12卷 207-211页

作者： Liang Liang Xiao-Yan Peng Hong Wang The First Affiliated Hospital of chongqing Medical University Chongqing Key Laboratory of Ophthalmology and Chongqing Eye Institute Beijing Tongren eye Center Beijing Key Laboratory of Ophthalmology and Visual Science Beijing Tongren HospitalCapital Medical University

AIM: To assess helper T(Th) lymphocyte subset balance in patients with Vogt-Koyanagi-Harada(VKH) disease. METHODS: Sixty-eight active VKH patients and seventytwo inactive VKH patients were included in this study. One hundred healthy individuals served as controls. Peripheral blood was obtained from VKH patients and healthy controls. Th lymphocyte subsets were analyzed by flow cytometry. Plasma concentration of interleukin(IL)-17, IL-10, transforming growth factor(TGF)-β, IL-23 and IL-6 was examined by enzyme-linked immunosorbent assay(ELISA). RESULTS: VKH patients with active uveitis had significantly higher percentages of both Th1 and Th17 cells and lower percentages of regulatory T(Treg) cells as compared with inactive VKH patients and healthy controls. Th1/Th2 and Th17/Treg ratios were also significantly elevated in active VKH patients. The percentages of Th1, Th17 and Treg cells and the Th1/Th2, Th17/Treg ratio did not differ between inactive VKH patients and healthy controls. There was no difference concerning the percentage of Th2 cells among all the groups. VKH patients with active uveitis showed an elevated level of peripheral Th17 related cytokines levels(TGF-β, IL-6, IL-23, and IL-17) and a decreased level of Treg related cytokines(IL-10) compared with inactive VKH patients and healthy controls. Inactive VKH patients showed no differences in peripheral Th17 related cytokines(TGF-β, IL-6, IL-23, and IL-17) and Treg related cytokines(IL-10) levels compared with healthy controls. CONCLUSION: Th1 and Th17 cells are significantly increased and Treg cells significantly decreased in active VKH compared with inactive VKH or healthy controls. Therefore, Th lymphocyte subset analysis may serve as a disease biomarker for VKH.

关键词： Vogt-Koyanagi-Harada disease Th lymphocyte Th17 cell Treg cell cytokines

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Upregulated inflammatory associated factors and blood-retinal barrier changes in the retina of type 2diabetes mellitus model

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International Journal of ophthalmology(English edition) 2016年第11期9卷 1591-1597页

作者： Rui-Jin Ran Xiao-Ying Zheng Li-Ping Du Xue-Dong Zhang Xiao-Li Chen Shen-Yin Zhu Department of ophthalmology the First Affiliated Hospital of Chongqing Medical University Chongqing Key Laboratory of Ophthalmology Chongqing Eye InstituteChongqing 400016 China University Hospital of Hubei University for Nationalities Enshi 445000 Hubei Province China

AIM： To examine the expression of high mobility group box-1（HMGB-1） and intercellular adhesion molecule-1（ICAM-1） in the retina and the hippocampal tissues; and further to evaluate the association of these two molecules with the alterations of blood-retinal barrier（BRB） and blood-brain barrier（BBB） in a rat model of type 2 ***： The type-2 diabetes mellitus（DM） model was established with a high-fat and high-glucose diet combined with streptozotocin（STZ）. Sixteen weeks after DM induction, morphological changes of retina and hippocampus were observed with hematoxylin-eosin staining, and alternations of BRB and BBB permeability were measured using Evans blue method. Levels of HMGB-1 and ICAM-1 in retina and hippocampus were detected by Western blot. Serum HMGB-1 levels were determined by enzyme-linked immunosorbent assay（ELISA）.RESULTS： A significantly higher serum fasting blood glucose level in DM rats was observed 2wk after STZ injection（P 〈0.01）. The serum levels of fasting insulin,Insulin resistance homeostatic model assessment（IRHOMA）,total cholesterol（TC）, total triglycerides（TG） and low density lipoprotein cholesterol（LDL-C） in the DM rats significantly higher than those in the controls（all P 〈0.01）.HMGB-1（0.96±0.03, P 〈0.01） and ICAM-1（0.76±0.12, P 〈0.05） levels in the retina in the DM rats were significantly higher than those in the controls. HMGB-1（0.83±0.13, P 〈0.01） and ICAM-1（1.15 ±0.08, P 〈0.01） levels in the hippocampal tissues in the DM rats were alsosignificantly higher than those in the controls. Sixteen weeks after induction of DM, the BRB permeability to albumin-bound Evans blue dye in the DM rats was significantly higher than that in the controls（P 〈0.01）.However, there was no difference of BBB permeability between the DM rats and controls. When compared to the controls, hematoxylin and eosin staining showed obvious irregularities in the DM ***： BRB permeability increases significantly in rats with type-2 DM, which may be as

关键词： blood-retinal barrier blood-brain barrier diabetes mellitus permeability: high mobility group box-1protein rats

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The genetics of Behcet’s disease in a Chinese population

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Frontiers of Medicine 2012年第4期6卷 354-359页

作者： Shengping Hou Aize Kijlstra Peizeng Yang The First Affiliated Hospital of chongqing Medical University Chongqing 400016China chongqing eye institute and chongqing key laboratory of ophthalmology Chongqing 400016China University eye Clinic Maastricht MaastrichtLimburgthe Netherlands

Behcet’s disease is defined as a multisystemic inflammatory *** the precise pathogenesis and etiology is still a mystery,accumulating evidence shows that genetic variants of immune-related genes have a profound influence on the development of Behcet’s *** explore the genetic factors for Behcet’s disease,our group investigated the association of Behcet’s disease with multiple immune response genes and has identified multiple Behcet’s disease-related immunoregulatory pathways in the Chinese Han population.A large number of gene polymorphisms were studied including STAT4,IL23R,CD40,CCR1/CCR3,STAT3,OPN,IL17,JAK2,MCP-1,CTLA4,PD-1,PD-L1,PD-L2,TGRBR3,CCR6,PTPN22,FCRL3,IRF5,SUMO4 and *** associations were found between Behcet’s disease and STAT4,IL23R,CD40,CCR1/CCR3,STAT3,MCP-1,TGFBR3,FCRL3,SUMO4,*** genetic predisposition studies support an important role for both lymphocyte differentiation as well as ubiquitination *** findings are helpful in elucidating the pathogenesis of Behcet’s disease and hopefully will allow the development of novel treatment regimes.

关键词： Behcet’s disease SNPs immune gene genetic study

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