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Problem identification and revitalization strategies for the recovery and reconstruction of traditional villages in the Ms 6.8 Luding Earthquake

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Journal of Mountain Science 2024年第2期21卷 361-379页

作者： HUANG Chao QIU Jian LIU Chun JIANG Rui ZHAO Chuanrong ZHANG Yi School of Architecture and Research Center of Space Planning and Engineering Design Southwest Jiaotong UniversityChengdu 611756China sichuan provincial Rural Construction and Development Center Chengdu 610041China sichuan institute of Urban and Rural Construction Chengdu 610043China China Association for Promoting Democracy(CAPD)sichuan provincial Committee Chengdu 610016China sichuan provincial Architectural Design and Research institute(SADI) Chengdu 610095China

Post-disaster reconstruction is a topic of global concern,and traditional villages have special heritage attributes and need to face more requirements and obstacles in post-disaster *** paper summarizes four concepts based on the research on post-disaster reconstruction both domestically and internationally,as well as the recovery and reconstruction of cultural *** a field survey of traditional villages in the Ms 6.8 Luding earthquake-stricken area,it is found that there are problems such as insufficient awareness of heritage value,misalignment of scientific reconstruction technology,and insufficient protection of reconstruction elements during the reconstruction *** villages face the risk of declining or even loss of heritage *** order to effectively protect traditional villages and inherit the carrier of regional culture,four targeted reconstruction response strategies are proposed,i.e.,to"establish special planning for traditional village preservation","emphasize recovery of the authenticity of village heritage","ensure elements for village heritage recovery"and"promote the activation and utilization of village heritage",based on the problems discovered during the survey and the four concepts summarized in the research on post-disaster reconstruction of traditional *** research results hope to provide useful reference for ancient cultural areas affected by earthquakes on how to protect cultural heritage during the post-disaster reconstruction process.

关键词： Seismic hazard Decision making Traditional village Cultural heritage protection Post-earthquake recovery and reconstruction Revitalization strategy

Epileptic brain network mechanisms and neuroimaging techniques for the brain network

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Neural Regeneration Research 2024年第12期19卷 2637-2648页

作者： Yi Guo Zhonghua Lin Zhen Fan Xin Tian Department of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina sichuan provincial Center for Mental Health Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Geriatrics Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Department of Neurology Chongqing Key Laboratory of NeurologyThe First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Epilepsy can be defined as a dysfunction of the brain network,and each type of epilepsy involves different brain-network changes that are implicated diffe rently in the control and propagation of interictal or ictal *** more detailed information on brain network alterations can help us to further understand the mechanisms of epilepsy and pave the way for brain network-based precise therapeutic approaches in clinical *** increasing number of advanced neuroimaging techniques and electrophysiological techniques such as diffusion tensor imaging-based fiber tra ctography,diffusion kurtosis imaging-based fiber tractography,fiber ball imagingbased tra ctography,electroencephalography,functional magnetic resonance imaging,magnetoencephalography,positron emission tomography,molecular imaging,and functional ultrasound imaging have been extensively used to delineate epileptic *** this review,we summarize the relevant neuroimaging and neuroelectrophysiological techniques for assessing structural and functional brain networks in patients with epilepsy,and extensively analyze the imaging mechanisms,advantages,limitations,and clinical application ranges of each technique.A greater focus on emerging advanced technologies,new data analysis software,a combination of multiple techniques,and the construction of personalized virtual epilepsy models can provide a theoretical basis to better understand the brain network mechanisms of epilepsy and make surgical decisions.

关键词： electrophysiological techniques epilepsy functional brain network functional magnetic resonance imaging functional near-infrared spectroscopy machine leaning molecular imaging neuroimaging techniques structural brain network virtual epileptic models

The m^(6)A reader YTHDC2 maintains visual function and retinal photoreceptor survival through modulating translation of PPEF2 and PDE6B

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Journal of Genetics and Genomics 2024年第2期51卷 208-221页

作者： Yeming Yang Xiaoyan Jiang Junyao Chen Lu Liu Guo Liu Kuanxiang Sun Wenjing Liu Xianjun Zhu Qiuyue Guan The sichuan provincial Key Laboratory for Human Disease Gene Study Center for Medical GeneticsSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Geriatrics Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences(2019RU026) Sichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduSichuan 610072China Qinghai Key Laboratory of Qinghai Tibet Plateau Biological Resources Chinese Academy of Sciences and Qinghai Provincial Key Laboratory of Tibetan Medicine ResearchNorthwest Institute of Plateau BiologyXiningQinghai 810008China Henan Eye institute Henan Eye HospitalPeople's Hospital of Zhengzhou UniversityHenan Provincial People's HospitalZhengzhouHenan 450003China

Inherited retinal dystrophies (IRDs) are major causes of visual impairment and irreversible blindness worldwide, while the precise molecular and genetic mechanisms are still elusive. N6-methyladenosine (m^(6)A) modification is the most prevalent internal modification in eukaryotic mRNA. YTH domain containing 2 (YTHDC2), an m^(6)A reader protein, has recently been identified as a key player in germline development and human cancer. However, its contribution to retinal function remains unknown. Here, we explore the role of YTHDC2 in the visual function of retinal rod photoreceptors by generating rod-specific Ythdc2 knockout mice. Results show that Ythdc2 deficiency in rods causes diminished scotopic ERG responses and progressive retinal degeneration. Multi-omics analysis further identifies Ppef2 and Pde6b as the potential targets of YTHDC2 in the retina. Specifically, via its YTH domain, YTHDC2 recognizes and binds m^(6)A-modified Ppef2 mRNA at the coding sequence and Pde6b mRNA at the 5′-UTR, resulting in enhanced translation efficiency without affecting mRNA levels. Compromised translation efficiency of Ppef2 and Pde6b after YTHDC2 depletion ultimately leads to decreased protein levels in the retina, impaired retinal function, and progressive rod death. Collectively, our finding highlights the importance of YTHDC2 in visual function and photoreceptor survival, which provides an unreported elucidation of IRD pathogenesis via epitranscriptomics.

关键词： Epitranscriptomics N^(6)-methyladenosine(m^(6)A) Inherited retinal dystrophies YTHDC2 Retina function Photoreceptor degeneration

Mild synthesis of ultra-bright carbon dots with solvatochromism for rapid lipid droplet monitoring in varied physiological processes

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Regenerative Biomaterials 2024年第3期3卷 30-42页

作者： Borui Su Dong Gao Nini Xin Kai Wu Mei Yang Shichao Jiang Yusheng Zhang Jie Ding Chengheng Wu Jing Sun Dan Wei Hongsong Fan Zhenzhen Guo National Engineering Research Center for Biomaterials College of Biomedical EngineeringSichuan UniversityChengduSichuan 610064China institute of Regulatory Science for Medical Devices Sichuan UniversityChengduSichuan 610064China Department of Gastroenterology Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610o72China

Lipid droplets(LDs)participating in various cellular activities and are increasingly being *** imaging provides powerful tool for dynamic tracking of LDs,however,most current LDs probes remain inconsistent performance such as low Photoluminescence Quantum Yield(PLQY),poor photostability and tedious washing ***,a novel yellow-emissive carbon dot(OT-cD)has been synthesized conveniently with high PLQY up to 90%.Besides,OT-CD exhibits remarkable amphiphilicity and solvatochromic property with lipid-water partition coefficient higher than 2,which is much higher than most LDs *** characters enable OT-CD high brightness,stable and wash-free LDs probing,and feasible for in vivo ***,detailed observation of LDs morphological and polarity variation dynamically in different cellular states were recorded,including ferroptosis and other diseases ***,fast whole imaging of zebrafish and identifed LD enrichment in injured liver indicate its further feasibility for in vivo *** contrast to the reported studies to date,this approach provides a versatile conventional synthesis system for high-performance LDs targeting probes,combing the advantages of easy and high-yield production,as well as robust brightness and stability for long-term imaging,facilitating investigations into organelle interactions and LD-associated diseases.

关键词： lipid droplet probe carbon dots fluorescence imaging wash-free dynamic monitoring

The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

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Neural Regeneration Research 2024年第2期19卷 282-288页

作者： Zhuoyang Yu Yan Teng Jing Yang Lu Yang institute of Neurology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina Laboratory of Aging Research School of MedicineUniversity of Electronic Science and Technology of ChinaChengduSichuan ProvinceChina

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in *** are widely distributed in a range of body fluids,including urine,blood,milk,and *** exert biological function by transporting factors between different cells and by regulating biological pathways in recipient *** an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous *** neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal *** the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate *** increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the *** recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease ***,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative *** emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in *** addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

关键词： adult neurogenesis Alzheimer’s disease amyotrophic lateral sclerosis exosome Huntington’s disease neurodegenerative disease neurogenic niches Parkinson’s disease

The endoplasmic reticulum membrane protein complex subunit Emc6 is essential for rhodopsin localization and photoreceptor cell survival

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Genes & Diseases 2024年第2期11卷 1035-1049页

作者： Kuanxiang Sun Lu Liu Xiaoyan Jiang Heting Wang Lin Wang Yeming Yang Wenjing Liu Lin Zhang Xiaohui Zhao Xianjun Zhu Health Management Center Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Key Laboratory of Tibetan Medicine Research Chinese Academy of Sciences and Qinghai Provincial Key Laboratory of Tibetan Medicine ResearchNorthwest Institute of Plateau BiologyXiningQinghai 810008China The sichuan provincial Key Laboratory for Human Disease Gene Study and Department of Laboratory Medicine Center for Medical GeneticsSichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences (2019RU026) Sichuan Academy of Medical Sciences and Sichuan Provincial People's HospitalChengduSichuan 610072China Department of Ophthalmology The First People's Hospital of ShangqiuShangqiuHenan 476000China

The endoplasmic reticulum(ER)membrane protein complex(EMC)is responsible for monitoring the biogenesis and synthetic quality of membrane proteins with tail-anchored or multiple transmembrane *** EMC subunit EMC6 is one of the core members of EMC and forms an enclosed hydrophilic vestibule in cooperation with *** studies demonstrating that deletion of EMC3 led to rhodopsin mislocalization in rod photoreceptors of mice,the precise mechanism leading to the failure of rhodopsin trafficking remains ***,we generated the first rod photoreceptor-specific knockout of Emc6(RKO)and cone photoreceptor-specific knockout of Emc6(CKO)mouse *** of Emc6 in rod photoreceptors led to progressive shortening of outer segments(OS),impaired visual function,mislocalization and reduced expression of rhodopsin,and increased gliosis in rod *** addition,CKO mice displayed the progressive death of cone photoreceptors and abnormal localization of cone opsin ***,proteomics analysis of the RKO mouse retina illustrated that several cilium-related proteins,particularly anoctamin-2(ANO2)and transmembrane protein 67(TMEM67),were significantly down-regulated prior to OS *** rod photoreceptor cilia and mislocalized membrane disc proteins were evident in RKO *** data revealed that in addition to monitoring the synthesis of rhodopsin-dominated membrane disc proteins,EMC6 also impacted rod photoreceptors'ciliogenesis by regulating the synthesis of membrane proteins associated with cilia,contributing to the mislocalization of membrane disc proteins.

关键词： ANO2 Cilium EMC6 ER membrane protein complex Mislocalization Photoreceptor degeneration TMEM67

Extensive prediction of drug response in mutation-subtype-specific LUAD with machine learning approach

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Oncology Research 2024年第2期32卷 409-419页

作者： KEGANG JIA YAWEI WANG QI CAO YOUYU WANG Department of Thoracic Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduChina School of Medicine University of Electronic Science and Technology of ChinaChengduChina Department of Assisted Reproductive Medicine Sichuan Provincial Academy of Medical Sciences&Sichuan Provincial People’s HospitalChengduChina

Lung cancer is the most prevalent cancer diagnosis and the leading cause of cancer death *** failure in lung cancer(LUAD)is heavily influenced by drug *** challenge stems from the diverse cell populations within the tumor,each having unique genetic,epigenetic,and phenotypic *** variations lead to varied therapeutic responses,thereby contributing to tumor relapse and disease ***:The Genomics of Drug Sensitivity in Cancer(GDSC)database was used in this investigation to obtain the mRNA expression dataset,genomic mutation profile,and drug sensitivity information of *** Learning(ML)methods,including Random Forest(RF),Artificial Neurol Network(ANN),and Support Vector Machine(SVM),were used to predict the response status of each compound based on the mRNA and mutation characteristics determined using statistical *** most suitable method for each drug was proposed by comparing the prediction accuracy of different ML methods,and the selected mRNA and mutation characteristics were identified as molecular features for the drug-responsive cancer ***,the prognostic influence of molecular features on the mutational subtype of LUAD in publicly available ***:Our analyses yielded 1,564 gene features and 45 mutational features for 46 *** the ML approach to predict the drug response for each medication revealed an upstanding performance for SVM in predicting Afuresertib drug response(area under the curve[AUC]0.875)using CIT,GAS2L3,STAG3L3,ATP2B4-mut,and IL15RA-mut as molecular ***,the ANN algorithm using 9 mRNA characteristics demonstrated the highest prediction performance(AUC 0.780)in Gefitinib with ***:This work extensively investigated the mRNA and mutation signatures associated with drug response in LUAD using a machine-learning approach and proposed a priority algorithm to predict drug response for different drugs.

关键词： Lung adenocarcinoma Drug resistance Machine learning Molecular features Personalized treatment

Transcriptomic analysis identifies the neuropeptide cortistatin (CORT) as an inhibitor of temozolomide (TMZ) resistance by suppressing the NF-kB-MGMT signaling axis in human glioma

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Genes & Diseases 2024年第3期11卷 385-399页

作者： Zongze He Bo Peng Qi Wang Jie Tian Ping Liu Jie Feng Yiwei Liao Longyi Chen Ping Jia Jian Tang Department of Neurosurgery Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Rehabilitation Medicine Sichuan Provincial People's HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China Department of Neurosurgery Xiangya HospitalCentral South UniversityChangshaHunan 410008China

Glioma is a common tumor originating in the brain that has a high mortality ***(TMZ)is the first-line treatment for high-grade ***,a large pro-portion of gliomas are resistant to TMZ,posing a great challenge to their *** the study,the specific functions and mechanism(s)by which cortistatin(CORT)regulates TMZ resis-tance and glioma progression were *** decreased expression of CoRT was detected in glioma tissues,and highly expressed CORT was associated with a better survival rate in pa-tients with *** overexpression notably decreased the capacity of glioma cells to pro-liferate and migrate in vitro and to form tumors in *** overexpression also markedly suppressed the viability and enhanced the apoptosis of TMZ-resistant U251 cells by regulating MGMT,p21,and Puma ***,CORT overexpression reduced the resistance of gliomas to TMZ in *** expression Was negatively correlated with MGMT expression in both glioma tissues and cells,and it was found that CORT inhibited NF-kB pathway activation in glioma cells,thereby inhibiting MGMT *** conclusion,CORT regulates glioma cell growth,migration,apoptosis,and TMZ resistance by weakening the activity of NF-kB/p65 and thereby regulating MGMT *** CORT/NF-kB/MGMT axis might be regarded as a molecular mechanism contributing to the resistance of glioma to *** data also suggest that CORT regulates the viability and metastatic potential of glioma cells,independent of its effects on TMZ resistance,providing evidence of novel therapeutic targets for glioma that should be evaluated infurther studies.

关键词： Cortistatin Glioma MGMT NF-kB pathway Temozolomide

Identification of LRRC46 as a novel candidate gene for high myopia

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Science China(Life Sciences) 2024年第9期67卷 1941-1956页

作者： Lingxi Jiang Chao Dai Yao Wei Bo Zhao Qi Li Zhengzheng Wu Liang Zou Zimeng Ye Zhenglin Yang Lulin Huang Yi Shi sichuan provincial Key Laboratory for Human Disease Gene Study and the Center for Medical Genetics Department of Laboratory MedicineSichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Department of Ophthalmology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610072China Research Unit for Blindness Prevention of Chinese Academy of Medical Sciences(2019RU026) Sichuan Academy of Medical Sciences&Sichuan Provincial People’s HospitalChengdu 610072China School of Food and Bioengineering Chengdu UniversityChengdu 610106China School of Medicine University of SydneySydney 2050Australia Jinfeng Laboratory Chongging 400000China

High myopia(HM)is the primary cause of blindness,with the microstructural organization and composition of collagenous fibers in the cornea and sclera playing a crucial role in the biomechanical behavior of these *** a previously reported myopic linkage region,MYP5(17q21-22),a potential candidate gene,LRRC46(c.C235T,p.Q79X),was identified in a large Han Chinese ***46 is expressed in various eye tissues in humans and mice,including the retina,cornea,and *** subsequent cell experiments,the mutation(c.C235T)decreased the expression of LRRC46 protein in human corneal epithelial cells(HCE-T).Further investigation revealed that Lrrc46^(-/-)mice(KO)exhibited a classical myopia *** thickness of the cornea and sclera in KO mice became thinner and more pronounced with age,the activity of limbal stem cells decreased,and microstructural changes were observed in the fibroblasts of the sclera and *** performed RNA-seq on scleral and corneal tissues of KO and normal control wild-type(WT)mice,which indicated a significant downregulation of the collagen synthesis-related pathway(extracellular matrix,ECM)in KO *** in vitro studies further indicated that LRRC46,a member of the important LRR protein family,primarily affected the formation of *** study suggested that LRRC46 is a novel candidate gene for HM,influencing collagen protein VⅢ(Col8a1)formation in the eye and gradually altering the biomechanical structure of the cornea and sclera,thereby promoting the occurrence and development of HM.

关键词： high myopia LRRC46 biomechanics collagen protein VⅢ