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Neuroscience Bulletin 2024年第4期40卷 517-532页

作者： Yuhui Shen Mingting Shao Zhao-Zhe Hao Mengyao Huang Nana Xu Sheng Liu State key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou510060China guangdong province key laboratory of Brain Function and Disease Guangzhou510080China

Primates exhibit complex brain structures that augment cognitive function.The neocortex fulfills high-cognitive functions through billions of connected neurons.These neurons have distinct transcriptomic,morphological,and electrophysiological properties,and their connectivity principles vary.These features endow the primate brain atlas with a multimodal nature.The recent integration of next-generation sequencing with modified patch-clamp techniques is revolutionizing the way to census the primate neocortex,enabling a multimodal neuronal atlas to be established in great detail:(1)single-cell/single-nucleus RNA-seq technology establishes high-throughput transcriptomic references,covering all major transcriptomic cell types;(2)patch-seq links the morphological and electrophysiological features to the transcriptomic reference;(3)multicell patch-clamp delineates the principles of local connectivity.Here,we review the applications of these technologies in the primate neocortex and discuss the current advances and tentative gaps for a comprehensive understanding of the primate neocortex.

关键词： Neuron Brain atlas Patch-seq Connectivity Primate

Effect of Sonic hedgehog gene-modified bone marrow mesenchymal stem cells on graft-induced retinal gliosis and retinal ganglion cells survival in diabetic mice

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 34-41页

作者： Tong Wang Hai-Chun Li Jin Ma Xi-Ling Yu State key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060Guangdong ProvinceChina

AIM:To investigate the effects of Sonic hedgehog(Shh)gene-modified bone marrow mesenchymal stem cells(MSCs)on graft-induced retinal gliosis and retinal ganglion cells(RGCs)survival in diabetic mice.METHODS:Bone marrow-derived MSCs were genetically modified with the Shh gene to generate a stably transfected cell line of Shh-modified MSCs(MSC-Shh).Intravitreal injections of MSC-Shh and green fluorescent protein-modified MSCs(MSC-Gfp;control)were administered in diabetic mice.After 4wk,the effects of MSC-Shh on retinal gliosis were evaluated using fundus photography,and markers of gliosis were examined by immunofluorescence and Western blotting.The neurotrophic factors expression and RGCs survival in the host retina were evaluated using Western blotting and immunofluorescence.The mechanisms underlying the effects of MSC-Shh was investigated.RESULTS:A significant reduction of proliferative vitreoretinopathy(PVR)was observed after intravitreal injection of MSC-Shh compared to MSC-Gfp.Significant downregulation of glial fibrillary acidic protein(GFAP)was demonstrated in the host retina after MSC-Shh administration compared to MSC-Gfp.The extracellular signal-regulated kinase 1/2(ERK1/2),protein kinase B(AKT)and phosphatidylin-ositol-3-kinase(PI3K)pathways were significantly downregulated after MSC-Shh administration compared to MSC-Gfp.Brain-derived neurotrophic factor(BDNF)and ciliary neurotrophic factor(CNTF)levels were significantly increased in the host retina,and RGCs loss was significantly prevented after MSC-Shh administration.CONCLUSION:MSC-Shh administration reduces graft-induced reactive gliosis following intravitreal injection in diabetic mice.The ERK1/2,AKT and PI3K pathways are involved in this process.MSC-Shh also increases the levels of neurotrophic factors in the host retina and promoted RGCs survival in diabetic mice.

关键词： mesenchymal stem cells Sonic hedgehog signaling reactive gliosis diabetic retinopathy retinal ganglion cells

Interplay between microglia and environmental risk factors in Alzheimer's disease

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Neural Regeneration Research 2024年第8期19卷 1718-1727页

作者： Miaoping Zhang Chunmei Liang Xiongjin Chen Yujie Cai Lili Cui guangdong key laboratory of Age-Related Cardiac and Cerebral Diseases Affiliated Hospital of Guangdong Medical UniversityZhanjiangGuangdong ProvinceChina

Alzheimer s disease,among the most common neurodegenerative disorders,is chara cterized by progressive cognitive impairment.At present,the Alzheimer’s disease main risk remains genetic ris ks,but major environmental fa ctors are increasingly shown to impact Alzheimer’s disease development and progression.Microglia,the most important brain immune cells,play a central role in Alzheimer’s disease pathogenesis and are considered environmental and lifestyle"sensors."Factors like environmental pollution and modern lifestyles(e.g.,chronic stress,poor dietary habits,sleep,and circadian rhythm disorde rs)can cause neuroinflammato ry responses that lead to cognitive impairment via microglial functioning and phenotypic regulation.However,the specific mechanisms underlying interactions among these facto rs and microglia in Alzheimer’s disease are unclear.Herein,we:discuss the biological effects of air pollution,chronic stress,gut micro biota,sleep patterns,physical exercise,cigarette smoking,and caffeine consumption on microglia;consider how unhealthy lifestyle factors influence individual susceptibility to Alzheimer’s disease;and present the neuroprotective effects of a healthy lifestyle.Toward intervening and controlling these environmental risk fa ctors at an early Alzheimer’s disease stage,understanding the role of microglia in Alzheimer’s disease development,and to rgeting strategies to to rget microglia,co uld be essential to future Alzheimer’s disease treatments.

关键词： Alzheimer’s disease chronic stress environmental factor gut microbiota microglia particulate matter with diameter<2.5μm

Topological magnetoelectric response in ferromagnetic axion insulators

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National science Review 2024年第2期11卷 8-14页

作者： Yuhao Wan Jiayu Li Qihang Liu Department of Physics and Shenzhen Institute for Quantum science and Engineering(SIQSE) Southern University of Science and Technology Shenzhen key laboratory of Advanced Quantum Functional Materials and Devices Southern University of Science and Technology guangdong Provincial key laboratory for computational science and Material Design Southern University of Science and Technology

The topological magnetoelectric effect （TME） is a hallmark response of the topological field theory,which provides a paradigm shift in the study of emergent topological phenomena.However,its direct observation is yet to be realized due to the demanding magnetic configuration required to gap all surface states.Here,we theoretically propose that axion insulators with a simple ferromagnetic configuration,such as the MnBi2Te4/（Bi2Te3）nfamily,provide an ideal playground to realize the TME.In the designed triangular prism geometry,all the surface states are magnetically gapped.Under a vertical electric field,the surface Hall currents give rise to a nearly half-quantized orbital moment,accompanied by a gapless chiral hinge mode circulating in parallel.Thus,the orbital magnetization from the two topological origins can be easily distinguished by reversing the electric field.Our work paves the way for direct observation of the TME in realistic axion-insulator materials.

关键词： topological magnetoelectric effect axion insulator magnetic topological materials

Rhegmatogenous retinal detachment in highly myopic eyes with implantable collamer lens

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International Journal of Ophthalmology(English edition) 2024年第2期17卷 392-396页

作者： Jun Li Chong-Lin Chen Jia-Qing Li Xiao-Ling Liang Chun Zhang State key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangzhou 510060Guangdong ProvinceChina

AIM:To investigate the clinical characteristics,treatment methods and outcomes of rhegmatogenous retinal detachment(RRD)in highly myopic eyes with implantable collamer lens(ICL).METHODS:High myopia patients who received treatment for nontraumatic RRD after ICL implantation surgery at the Retinal Department of Zhongshan Ophthalmic Center from Jan 2018 to Dec 2022 were reviewed.Comprehensive ophthalmologic examinations including visual acuity measurement and digital fundus photography were performed in each patient.RESULTS:A total of nine RRD eyes from nine patients who received V4c-ICL implantation were included.The mean time from ICL implantation surgery to the diagnosis of RRD was 32.44±22.56mo(range,1-60mo).At the initial visit for RRD,giant retinal tear(GRT),horseshoe tear,simple round hole,and horseshoe tear combined with round hole were detected in 3,3,2,and 1 eye(s),respectively,with maculaoff in eyes.Eight patients received surgical treatment,and one patient was treated by retinal laser photocoagulation alone.The ICL was preserved in 7 eyes.At the last followup,the mean best corrected visual acuity(BCVA)improved significantly from 1.76±1.06 logMAR at presentation to 0.81±1.01 logMAR(P=0.035),and no case of recurrent retinal detachment was found.CONCLUSION:The morphological presentation of retinal breaks is diverse in this study.The ICL can be preserved in most cases during the course of retinal detachment repair surgery in our data,companied with acceptable visual and anatomical outcomes.

关键词： high myopia implantable collamer lens rhegmatogenous retinal detachment

Effect of lens surgery on health-related quality of life in preschool children with congenital ectopia lentis

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 66-72页

作者： Yan-Qiao Huang Qian-Zhong Cao Yi-Yao Wang Yi-Jing Zhou Dan-Ying Zheng State key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangdong Provincial Clinical Research Center for Ocular DiseasesGuangzhou 510060Guangdong ProvinceChina

AIM:To evaluate the effect of lens surgery on health-related quality of life(HRQoL)of preschool children with congenital ectopia lentis(CEL).METHODS:A prospective self-controlled study was conducted in Zhongshan Ophthalmic Center.Children aged from 5 to 7y whom were diagnosed with CEL and underwent phacoemulsification with scleral-fixated posterior chamber intraocular lens implantation and their parents were enrolled in this study.All of them completed the child and proxy(parental)PedsQL™4.0 before and after the surgery.Their preoperative scores were compared to their postoperative ones.Subgroup analyses were performed based on gender and preoperative bilateral presenting visual acuity of the children.RESULTS:Thirty-two children with CEL successfully underwent surgery without any complications,among whom 8 had monocular surgery and 24 had binocular surgery.Preoperative and postoperative questionnaires were completed by 32 child-parent pairs.Surgical intervention could significantly improve the vision of affected children(P<0.001).The medians of physical,psychosocial and total health scores self-reported by the children were 68.75(62.50,81.25),65.00(60.00,80.00)and 67.39(60.87,78.26)preoperatively and were 93.75(87.50,100.00),90.00(83.33,96.67)and 89.13(85.32,95.65)postoperatively.The preoperative scores of the affected children were significantly lower in all scales than age-matched healthy children(P<0.001).All the postoperative scores were significantly higher than the preoperative scores in affected children and their parents(P<0.001).In the physical functioning evaluation,the preoperative score reported by parents of girls was higher than parents of boys(P=0.041),and the postoperative score of girls was higher than that of boys(P=0.036).CONCLUSION:CEL is associated with significantly worse quality of life in preschool children.Surgical intervention can significantly improve the HRQoL in affected children from both personal and family perspective.

关键词： congenital ectopia lentis surgical intervention health-related quality of life preschool children

Factors influencing willingness to participate in ophthalmic clinical trials and strategies for effective recruitment

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 157-163页

作者： Jia-En Liang Meng-Yin Liang En-En Zhang Yu-Ying Peng Ling-Ling Chen Jia-Yu Deng Ting Lin Jun Fu Jia-Ni Zhang Shao-Li Li Fei Li Hui-Ming Xaio Wen-Min Huang Yu-Hong Liu State key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangdong Provincial Clinical Research Center for Ocular DiseasesGuangzhou 510060Guangdong ProvinceChina

AIM:To explore the factors influencing individuals’willingness to participate in ophthalmic clinical trials.METHODS:A questionnaire survey was conducted from January to April 2021 among patients and their family members at Zhongshan Ophthalmic Center,Sun Yat-sen University,in Guangzhou,China.The survey gathered data on respondents’willingness,demographic and socioeconomic profiles,as well as their reasons and concerns regarding engagement in clinical trials.RESULTS:Of the 1078 residents surveyed(mean age 31.2±13.1y;65.8%females)in Guangzhou,749(69.5%)expressed a willingness to participate in future ophthalmic clinical trials.Specific characteristics associated with greater willingness included a younger age,lower annual income,higher education,prior participation experience,previous ophthalmic treatment,and a better understanding of clinical trials.With the exception of age,these characteristics were significantly linked to a higher willingness.The primary barrier to participation,expressed by 64.8%of those willing and 54.4%of those unwilling,was“Uncertain efficacy”.In terms of motivations,the willing group ranked“Better therapeutic benefits”(35.0%),“Professional monitoring”(34.3%),and“Trust in healthcare professionals”(33.1%)as their top three reasons,whereas the unwilling participants indicated“Full comprehension of the protocol”(46.2%)as the key facilitator.CONCLUSION:This study reveals a substantial willingness to participate in ophthalmic clinical trials and demonstrates the predictive role of demographic and socioeconomic factors.Variations in motivators and concerns between willing and unwilling participants highlight the significance of tailored recruitment strategies.Importantly,the need for and trust in healthcare professionals stand out as powerful motivations,underscoring the importance of enhancing physician-patient relationships,adopting patient-centered communication approaches,and addressing individualized needs to improve accrual rates.

关键词： participation willingness recruitment strategy ophthalmic clinical trial

Classification of congenital cataracts based on multidimensional phenotypes and its association with visual outcomes

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International Journal of Ophthalmology(English edition) 2024年第3期17卷 473-479页

作者： Yuan Tan Ying-Shi Zou Ying-Lin Yu Le-Yi Hu Ting Zhang Hui Chen Ling Jin Duo-Ru Lin Yi-Zhi Liu Hao-Tian Lin Zhen-Zhen Liu State key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangdong Provincial Key Laboratory of Ophthalmology and Visual ScienceGuangdong Provincial Clinical Research Center for Ocular DiseasesGuangzhou 510060Guangdong ProvinceChina

●AIM:To establish a classification for congenital cataracts that can facilitate individualized treatment and help identify individuals with a high likelihood of different visual outcomes.●METHODS:Consecutive patients diagnosed with congenital cataracts and undergoing surgery between January 2005 and November 2021 were recruited.Data on visual outcomes and the phenotypic characteristics of ocular biometry and the anterior and posterior segments were extracted from the patients’medical records.A hierarchical cluster analysis was performed.The main outcome measure was the identification of distinct clusters of eyes with congenital cataracts.●RESULTS:A total of 164 children(299 eyes)were divided into two clusters based on their ocular features.Cluster 1(96 eyes)had a shorter axial length(mean±SD,19.44±1.68 mm),a low prevalence of macular abnormalities(1.04%),and no retinal abnormalities or posterior cataracts.Cluster 2(203 eyes)had a greater axial length(mean±SD,20.42±2.10 mm)and a higher prevalence of macular abnormalities(8.37%),retinal abnormalities(98.52%),and posterior cataracts(4.93%).Compared with the eyes in Cluster 2(57.14%),those in Cluster 1(71.88%)had a 2.2 times higher chance of good best-corrected visual acuity[<0.7 logMAR;OR(95%CI),2.20(1.25–3.81);P=0.006].●CONCLUSION:This retrospective study categorizes congenital cataracts into two distinct clusters,each associated with a different likelihood of visual outcomes.This innovative classification may enable the personalization and prioritization of early interventions for patients who may gain the greatest benefit,thereby making strides toward precision medicine in the field of congenital cataracts.

关键词： classification congenital cataract phenotype visual acuity cluster analysis

Targeting tau in Alzheimer's disease:from mechanisms to clinical therapy

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Neural Regeneration Research 2024年第7期19卷 1489-1498页

作者： Jinwang Ye Huali Wan Sihua Chen Gong-Ping Liu Shenzhen key laboratory of Marine Biotechnology and Ecology College of Life Sciences and OceanographyShenzhen UniversityShenzhenGuangdong ProvinceChina Department of laboratory Medicine Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong ProvinceChina Co-innovation Center of Neurodegeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Pathophysiology School of Basic Medicine and the Collaborative Innovation Center for Brain ScienceKey Laboratory of Ministry of Education of China and Hubei Province for Neurological DisordersTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the cells.While there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side effects.Mounting evidence suggests significant involvement of tau protein in Alzheimer’s disease-related neurodegeneration.As an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth.In fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the brain.Various therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s disease.Specifically,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular missorting.This causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive deficits.This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.

关键词： acetylation Alzheimer’s disease cognitive deficits gliosis mitochondria damage neuroinflammation phosphorylation synaptic impairments tau tau immunotherapy

Palladium-Catalyzed anti-Markovnikov Halosulfonamidation of Unactivated Alkene

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Chinese Journal of Chemistry 2024年第5期42卷 464-470页

作者： Bowen Wang Jianxiao Li Wanqing Wu Huanfeng Jiang State key laboratory of Pulp and Paper Engineering Key Laboratory of Functional Molecular Engineering of Guangdong ProvinceSchool of Chemistry and Chemical EngineeringSouth China University of TechnologyGuangzhouGuangdong510641 China

Palladium-catalyzed regioselective amination of unactivated alkene remains a challenge and is of great interest.Herein,a three-component coupling of unactivated alkene,sulfonamide,and N-halo compounds accessing vicinal haloamine has been conceived.This aminohalogenation represents a modular and regioselective strategy.The electrophilic halogenating agent enables regioselective anti-Markovnikov aminopalladation and facilitates subsequent halogenation events.And this protocol is characterized by gram-scale syntheses and late-stage functionalizations.Of note,the recovered byproduct phthalimide allows for reusing by conversion to the starting material.

关键词： Unactivated alkene anti-Markovnikov aminopalladation Vicinal haloamine Palladium catalysis Halosulfonamidation Selectivity N-Halo compounds