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Small extracellular vesicles derived from human induced pluripotent stem cell-differentiated neural progenitor cells mitigate retinal ganglion cell degeneration in a mouse model of optic nerve injury

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Neural Regeneration Research 2025年第2期20卷 587-597页

作者： Tong li Hui-Min Xing Hai-Dong Qian Qiao Gao Sheng-lan Xu Hua Ma Zai-Long Chi State Key Laboratory of Ophthalmology Optometry and Visual ScienceEye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina National Clinical Research Center for Ocular Diseases Eye HospitalWenzhou Medical UniversityWenzhouZhejiang ProvinceChina

Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured ***,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical *** extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and *** studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye *** this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve *** results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell *** with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of *** analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve *** findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.

关键词： exosome miRNA neural progenitor cell neurodegeneration neuroinflammation neuroprotection optic nerve crush optic neuropathy retinal ganglion cell small extracellular vesicles

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核素凋亡显像评价小鼠肝细胞凋亡

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中国医学影像技术 2009年第1期25卷 29-32页

作者：兰晓莉何勇沈艳霞孙逊张永学华中科技大学同济医学院附属协和医院核医学科湖北省分子影像重点实验室湖北武汉430022

目的将凋亡显像剂99mTc-HYNIC-Annexin V用于肝细胞凋亡小鼠动物模型显像,以评价其用于显示凋亡的可行性。方法通过双功能螯合剂HYNIC偶联Annexin V后99mTc标记,鉴定99mTc-HYNIC-Annexin V标记率、放化纯和稳定性。取正常昆明小鼠随机... 详细信息

目的将凋亡显像剂99mTc-HYNIC-Annexin V用于肝细胞凋亡小鼠动物模型显像,以评价其用于显示凋亡的可行性。方法通过双功能螯合剂HYNIC偶联Annexin V后99mTc标记,鉴定99mTc-HYNIC-Annexin V标记率、放化纯和稳定性。取正常昆明小鼠随机分为正常对照组及应用anti-Fas抗体处理后肝细胞凋亡组,注射显像剂后不同时间行SPECT显像,考察显像剂在小鼠体内分布及排泄情况,应用感兴趣区(region of interest,ROI)技术比较正常组及凋亡组显像图像中肝脏/前臂比值。取两组动物肝脏组织HE染色进行病理学分析,Hoechst33258染色检测凋亡。结果99mTc-HYNIC-Annexin V标记率可达(96.32±2.08)%,放化纯度达到(96.90±2.27)%,标记物体外稳定。正常小鼠体内显像剂从肾脏排泄,肝脏仅有少量分布。凋亡组肝脏有明显显像剂浓聚,不同时间下肝脏/前臂的比值均高于正常小鼠。HE染色及Hoechst33258染色提示凋亡组有大量肝细胞凋亡。结论研究制备的凋亡显像剂99mTc-HYNIC-Annexin V可以活体显示发生凋亡的肝脏,用于在体凋亡显像,有望成为一种有良好临床应用前景的凋亡显像剂。

关键词：细胞凋亡放射性核素显像肝细胞小鼠

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转化生长因子-β_1/Smad2/3介导肾小管上皮细胞转分化与幼鼠肾间质纤维化的相关性

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中国药物与临床 2012年第8期12卷 999-1003页

作者：兰晓莉马宏李荟大同市第五人民医院儿科 037006 山西医科大学第一医院儿科

目的探讨转化生长因子β1(TGF-β1)与Smad2/3信号传导介导肾小管上皮细胞转分化(EMT)与幼鼠慢性肾间质纤维化的相关性,以及血管紧张素转换酶抑制剂(ACEI)的干预作用。方法本研究以80只幼年雌性SD大鼠为实验动物,制备7/8肾切除残肾慢性... 详细信息

目的探讨转化生长因子β1(TGF-β1)与Smad2/3信号传导介导肾小管上皮细胞转分化(EMT)与幼鼠慢性肾间质纤维化的相关性,以及血管紧张素转换酶抑制剂(ACEI)的干预作用。方法本研究以80只幼年雌性SD大鼠为实验动物,制备7/8肾切除残肾慢性进展性肾功能衰竭模型。模型成功后随机将动物分为假手术组、7/8肾切除未治疗组和7/8肾切除干预治疗组。以模型制备后第2、4、8、12周为不同时间点。检测各时间点大鼠肾组织常规病理;采用免疫组织化学染色检测残肾组织中TGF-β1、Smad2/3:α-平滑肌肌动蛋白(α-SMA)、E-钙黏连蛋白及纤维连接蛋白(FN)在肾组织表达趋势。结果实验第2周时未治疗组肾小管间质大量炎性细胞浸润、肾小管上皮细胞肿胀、肾小管间隙加宽。至第12周未治疗组肾小管广泛扩张、基底膜增厚、皱缩或断裂,间质纤维化明显。而治疗组残肾组织病理变化较未治疗组有明显改善。免疫组织化学半定量分析显示未治疗组TGF-β1阳性细胞或阳性小管染色积分值呈逐渐升高趋势。对照组与未治疗组各时间点相比较差异有统计学意义(P<0.05)。Smad2/3表达趋势与TGF-β1相似。α-SMA蛋白表达趋势同步上调,E-钙黏连蛋白同步下调,未治疗组各时间点FN均呈现逐渐升高趋势(P<0.05)。未治疗组TGF-β1、Smad2/3、α-SMA、FN各指标不同时间点免疫组织化学蛋白染色积分值呈正相关,而与E-钙黏连蛋白表达趋势呈负相关(P<0.01)。干预组不同时间点TGF-β1、Smad2/3、α-SMA和FN蛋白表达趋势明显弱于未治疗组,但强于对照组,而E-钙黏连蛋白表达下调(P<0.01)。结论在幼年期肾损伤过程中,TGF-β1高表达与Smad2/3分子使其高表达,可能通过介导EMT导致肾小管间质区细胞外基质(ECM)异常合成与沉积,最终引起肾小管间质纤维化形成。早期给予ACEI干预可改善这种病理变化。

关键词：转化生长因子β1 纤维化细胞外基质

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^(18)F-FDG PET/CT显像在鼻咽癌综合治疗后随访中的诊断及预后评估效能

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中国医学影像技术 2013年第3期29卷 349-353页

作者：田月丽兰晓莉吴志坚贾清何勇张永学华中科技大学同济医学院附属协和医院核医学科湖北省分子影像重点实验室湖北武汉430022

目的评价18F-FDG PET/CT显像对鼻咽癌患者综合治疗后随访的诊断效能及其预后评估价值。方法收集鼻咽癌综合治疗后患者89例,回顾18F-FDG PET/CT和常规影像学诊断结果,并与组织病理学诊断和(或)长期临床随访资料进行比较,计算18F-FDG PET... 详细信息

目的评价18F-FDG PET/CT显像对鼻咽癌患者综合治疗后随访的诊断效能及其预后评估价值。方法收集鼻咽癌综合治疗后患者89例,回顾18F-FDG PET/CT和常规影像学诊断结果,并与组织病理学诊断和(或)长期临床随访资料进行比较,计算18F-FDG PET/CT与常规影像学在鼻咽癌综合治疗后对残留、复发或转移诊断的灵敏度、特异度、准确性、阳性预测值(PPV)及阴性预测值(NPV)。结合18 F-FDG PET/CT图像及患者临床表现做定性诊断,勾画鼻咽部局部病灶并测量最大标准摄取值(SUVmax)。以ROC曲线确定18F-FDG PET/CT诊断最佳SUVmax,以定性诊断结果和ROC曲线最佳SUVmax为界点行生存分析,以性别、年龄、鼻咽部SUVmax、治疗方法、病灶数目进行COX比例风险回归模型分析,观察影响整体生存率(OS)及无病生存率(DFS)的因素。结果 89例患者平均生存(69.22±4.46)个月,5年OS为73.00%。18F-FDG PET/CT诊断灵敏度、特异度、准确率、PPV及NPV分别为100%(59/59)、90.20%(46/51)、95.45%(105/110)、92.19%(59/64)和100%(46/46);传统影像学分别为75.86%(44/58)、78.85%(41/52)、77.27%(85/110)、80.00%(44/55)和72.73%(40/55),18F-FDG PET/CT灵敏度和准确率高于传统影像学(P均<0.01)。鼻咽部SUVmax=2.5时18F-FDG PET/CT诊断效能最佳,SUVmax<2.5患者5年OS为81.90%,高于SUVmax≥2.5者为62.00%(P=0.036)。18F-FDG PET/CT阴性患者5年OS为100%,阳性者59.90%(P=0.006)。COX比例风险回归模型分析显示,根据SUVmax[相对危险度(RR)=1.205;P=0.014]和病灶数目(RR=2.734;P=0.005)可预测OS,病灶数目是影响DFS(RR=2.105;P=0.008)的主要因素。结论 18F-FDG PET/CT诊断鼻咽癌患者综合治疗后复发和(或)转移具有较高灵敏度和准确率;鼻咽部SUVmax=2.5可能是18F-FDG PET/CT诊断的最佳界值点;18 F-FDG PET/CT定性诊断为阳性以及鼻咽部SUVmax≥2.5患者的远期生存预后不佳。根据鼻咽部SUVmax和病灶数目可以预测OS,病灶数目同时是影响DFS的主要因素。

关键词：鼻咽肿瘤正电子发射型体层摄影术体层摄影术,X线计算机 18F氟脱氧葡萄糖预后

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Reduced mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor contributes to neurodegeneration in a model of spinal and bulbar muscular atrophy pathology

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Neural Regeneration Research 2025年第9期20卷 2655-2666页

作者： Yiyang Qin Wenzhen Zhu Tingting Guo Yiran Zhang Tingting Xing Peng Yin Shihua li xiao-Jiang li Su Yang Guangdong Key Laboratory of Non-human Primate Research Key Laboratory of CNS Regeneration(Ministry of Education)Guangdong–HongKong–Macao Institute of CNS RegenerationJinan UniversityGuangzhouGuangdong ProvinceChina

Spinal and bulbar muscular atrophy is a neurodegenerative disease caused by extended CAG trinucleotide repeats in the androgen receptor gene,which encodes a ligand-dependent transcription facto *** mutant androgen receptor protein,characterized by polyglutamine expansion,is prone to misfolding and forms aggregates in both the nucleus and cytoplasm in the brain in spinal and bulbar muscular atrophy *** aggregates alter protein-protein interactions and compromise transcriptional *** this study,we reported that in both cultured N2a cells and mouse brain,mutant androgen receptor with polyglutamine expansion causes reduced expression of mesencephalic astrocyte-de rived neurotrophic *** n of mesencephalic astrocyte-derived neurotrophic factor amelio rated the neurotoxicity of mutant androgen receptor through the inhibition of mutant androgen receptor *** down endogenous mesencephalic astrocyte-derived neurotrophic factor in the mouse brain exacerbated neuronal damage and mutant androgen receptor *** findings suggest that inhibition of mesencephalic astrocyte-derived neurotrophic factor expression by mutant androgen receptor is a potential mechanism underlying neurodegeneration in spinal and bulbar muscular atrophy.

关键词： androgen receptor mesencephalic astrocyte-derived neurotrophic factor mouse model neurodegeneration neuronal loss neurotrophic factor polyglutamine disease protein misfolding spinal and bulbar muscular atrophy transcription factor

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Carbon-supported CeNCl as an efficient catalyst for CO_(2)cycloaddition

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Nano Research 2025年第1期18卷 157-163页

作者： li liu lingling Zhang Xiang Chu Baokang Geng Huilin Wang Zongxiang li xiao Wang Shuyan Song Hongjie Zhang School of Applied Chemistry and Engineering University of Science and Technology of ChinaHefei 230026China State Key Laboratory of Rare Earth Resource Utilization Changchun Institute of Applied ChemistryChinese Academy of SciencesChangchun 130022China Sinocare Incorporation Changsha 410221China Department of Chemistry Tsinghua UniversityBeijing 100084China

The cycloaddition reaction of CO_(2)with epoxide not only effectively reduces the concentration of CO_(2)in the atmosphere,but also has excellent industrial application value and up to 100%atom utilization,but there are difficulties in separation and recovery of traditional homogeneous catalysts,harsh reaction conditions of traditional heterogeneous catalysts,and activation of CO_(2)*** this paper,an easily synthesized heterogeneous catalyst CeNCl/C was used to catalyze the cycloaddition reaction of CO_(2)with styrene oxide,with a high yield of 92.7%,a high selectivity of 96.7%,a turnover numbers(TON)value of 349,and a good stability demonstrated in six cycle tests(equivalent to 216 h of testing).Through comprehensive studies,it was shown that CeNCl/C contains Lewis acid-base centers as active centers,which can effectively reduce the energy barrier required for ring opening of the reaction substrate,enhance the adsorption and activation of CO_(2),and promote the formation of intermediates,which led to the acquisition of excellent catalytic activity.

关键词： CO_(2)cycloaddition heterogeneous catalysis CeNCl Lewis acid/base

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Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

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Neural Regeneration Research 2025年第5期20卷 1455-1466页

作者： Ju Zheng Yixin li Ting Zhang Yanlin Fu Peiyan Long xiao Gao Zhengwei Wang Zhizhong Guan xiaolan Qi Wei Hong Yan xiao Key Laboratory of Endemic and Ethnic Diseases Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou ProvinceGuizhou Medical UniversityGuiyangGuizhou ProvinceChina Guizhou Center for Disease Control and Prevention GuiyangGuizhou ProvinceChina Department of Histology and Embryology Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional Diseases Co-constructed by the Province and Ministry GuiyangGuizhou ProvinceChina

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion *** occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains *** this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion *** found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced ***,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating *** autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion *** from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关键词： apoptosis ATF4 autophagy C/EBP homologous protein cerebral ischemia/reperfusion injury eIF2α endoplasmic reticulum stress PERK

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Effects of the extrusion parameters on microstructure,texture and room temperature mechanical properties of extruded Mg-2.49Nd-1.82Gd-0.2Zn-0.2Zr alloy

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International Journal of Minerals,Metallurgy and Materials 2025年第1期32卷 136-146页

作者： Chenjin Zhang Guangyu Yang Lei xiao Zhiyong Kan Jing Guo Qiang li Wanqi Jie State Key Laboratory of Solidification Processing Northwestern Polytechnical UniversityXi’an 710072China College of Materials Science and Engineering Fuzhou UniversityFuzhou 350108China College of Chemistry and Environmental Science Qujing Normal UniversityQujing 655011China

Microstructure,texture,and mechanical properties of the extruded Mg-2.49Nd-1.82Gd-0.2Zn-0.2Zr alloy were investigated at different extrusion temperatures(260 and 320℃),extrusion ratios(10:1,15:1,and 30:1),and extrusion speeds(3 and 6 mm/s).The experimental results exhibited that the grain sizes after extrusion were much finer than that of the homogenized alloy,and the second phase showed streamline distribution along the extrusion direction(ED).With extrusion temperature increased from 260 to 320℃,the microstructure,texture,and mechanical properties of alloys changed *** dynamic recrystallization(DRX)degree and grain sizes enhanced as the extrusion ratio increased from 10:1 to 30:1,and the strength gradually decreased but elongation(EL)*** the extrusion speed increased from 3 to 6 mm/s,the grain sizes and DRX degree increased significantly,and the samples presented the typical-rare-earth(RE)*** alloy extruded at 260℃ with extrusion ratio of 10:1 and extrusion speed of 3 mm/s showed the tensile yield strength(TYS)of 213 MPa and EL of 30.6%.After quantitatively analyzing the contribution of strengthening mechanisms,it was found that the grain boundary strengthening and dislocation strengthening played major roles among strengthening *** results provide some guidelines for enlarging the industrial application of extruded Mg-RE alloy.

关键词： Mg-rare earth alloys extrusion temperature extrusion ratio extrusion speed strengthening mechanisms

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Return to work in young and middle-aged colorectal cancer survivors:Factors influencing self-efficacy,fear,resilience,and financial toxicity

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World Journal of Gastroenterology 2025年第1期31卷 79-92页

作者： Dan Hu Yue li Hua Zhang lian-lian Wang Wen-Wen liu Xin Yang Ming-Zhao xiao Hao-ling Zhang Juan li Department of Nursing The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Nursing National Clinical Research Center for Child Health and DisordersMinistry of Education Key Laboratory of Child Development and DisordersChildren’s Hospital of Chongqing Medical UniversityChongqing 400014China Department of Gastrointestinal Surgery The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Biomedical Science Advanced Medical and Dental InstituteUniversity Sains MalaysiaPenang 13200Malaysia Academic Affairs Office The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China

BACKGROUND Return to work(RTW)serves as an indication for young and middle-aged colorectal cancer(CRC)survivors to resume their normal social ***,these survivors encounter significant challenges during their RTW ***,scientific research is necessary to explore the barriers and facilitating factors of returning to work for young and middle-aged CRC *** To examine the current RTW status among young and middle-aged CRC survivors and to analyze the impact of RTW self-efficacy(RTW-SE),fear of progression(FoP),eHealth literacy(eHL),family resilience(FR),and financial toxicity(FT)on their RTW *** A cross-sectional investigation was adopted in this *** September 2022 to February 2023,a total of 209 participants were recruited through a convenience sampling method from the gastrointestinal surgery department of a class A tertiary hospital in *** investigation utilized a general information questionnaire alongside scales assessing RTW-SE,FoP,eHL,FR,and *** analyze the factors that influence RTW outcomes among young and middle-aged CRC survivors,Cox regression modeling and Kaplan-Meier survival analysis were *** A total of 43.54%of the participants successfully returned to work,with an average RTW time of 100 *** regression univariate analysis revealed that RTW-SE,FoP,eHL,FR,and FT were significantly different between the non-RTW and RTW groups(Plitating their timely reintegration into mainstream society.

关键词： Return to work Colorectal neoplasms Return-to-work self-efficacy Fear of progression Family resilience Financial toxicity

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Biomass materials for zinc-based sustainable and green energy storage devices:Strategy and mechanism

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Nano Research 2025年第1期18卷 294-314页

作者： xiaotong Yang xiaoxin Nie Chenke Tang Yiyang xiao Qiongguang li Du Yuan Meng Yao College of Materials Science and Engineering Changsha University of Science and TechnologyChangsha 410004China College of Materials Science and Engineering Sichuan UniversityChengdu 610065China Anhui Province International Research Center on Advanced Building Materials School of Materials and Chemical EngineeringAnhui Jianzhu UniversityHefei 230601China

As next-generation rechargeable alternatives,zincbased energy storage devices(ZESs)are being intensely explored due to their merits of abundant resource,low cost,safety and environmental ***,ZESs face a succession of critical challenges on pursuing advancing performance,including the stability and kinetics of cathode,stability and transport of zinc electrolyte,reversibility and deep utilization of metallic Zn ***,possessing unique molecular structures with abundant functionals groups,motivates the interdisciplinary field emerging from biomass and aqueous rechargeable *** its high compatibility with ZES design,we here summarize the application of biomass materials in ZESs from the aspects of cathode,electrolyte,membrane/separator and Zn anode,with their corresponding operational mechanisms and attractive functionalities from polymeric ***,the outlooks and perspectives are provided,regarding current challenges and future *** anticipate our minireview paves way on exploring the roles of biomass in aqueous rechargeable batteries.

关键词： zinc biomass materials skeleton/host coating solid-electrolyte interphase(SEI)

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