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Optimal transcorneal electrical stimulation parameters for preserving photoreceptors in a mouse model of retinitis pigmentosa

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Neural Regeneration Research 2024年第11期19卷 2543-2552页

作者： Sam Enayati Karen Chang Anton Lennikov Menglu Yang Cherin Lee Ajay Ashok Farris Elzaridi Christina Yen Kasim Gunes Jia Xie Kin-Sang Cho Tor Paaske Utheim Dong Feng Chen Schepens Eye Research Institute of Massachusetts Eye and Ear Department of OphthalmologyHarvard Medical SchoolBostonMAUSA Institute of clinical medicine Faculty of MedicineUniversity of OsloOsloNorway Department of medical biochemistry Oslo University HospitalUniversity of OsloOsloNorway Department of Ophthalmology Drammen HospitalVestre Viken Hospital TrustDrammenNorway Department of Histology and Embryology School of MedicineMarmara UniversityIstanbulTurkiye

Retinitis pigmentosa is a hereditary retinal disease that affects rod and cone photoreceptors,leading to progressive photoreceptor *** research supports the beneficial effect of electrical stimulation on photoreceptor *** study aims to identify the most effective electrical stimulation parameters and functional advantages of transcorneal electrical stimulation(tcES)in mice affected by inherited retinal ***,the study seeked to analyze the electric field that reaches the retina in both eyes in mice and post-mortem *** this study,we recorded waveforms and voltages directed to the retina during transcorneal electrical stimulation in C57BL/6J mice using an intraocular needle probe with rectangular,sine,and ramp *** investigate the functional effects of electrical stimulation on photoreceptors,we used human retinal explant cultures and rhodopsin knockout(Rho^(-/-))mice,demonstrating progressive photoreceptor degeneration with *** retinal explants isolated from the donors’eyes were then subjected to electrical stimulation and cultured for 48 hours to simulate the neurodegenerative environment in *** density was evaluated by rhodopsin *** vivo Rho^(-/-)mice were subjected to two 5-day series of daily transcorneal electrical stimulation using rectangular and ramp *** function and visual perception of mice were evaluated by electroretinography and optomotor response(OMR),*** was used to assess the morphological and biochemical changes of the photoreceptor and bipolar cells in mouse *** recordings indicated effective delivery of rectangular,sine,and ramp waveforms to the retina by transcorneal electrical stimulation,of which the ramp waveform required the lowest *** of the total conductive resistance of the post-mortem human compared to the mouse eyes indicated higher cornea-to-retina resistance in human *** tem

关键词： bipolar cells electrical stimulation neuroprotection photoreceptor degeneration retina retinal explants retinitis pigmentosa transcorneal electrical stimulation waveform

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Development and maintenance of the ligular region of maize leaves

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Molecular Plant 2024年第8期17卷 1175-1177页

作者： Josh Strable Alejandro Aragon-Raygoza Department of Molecular and Structural biochemistry North Carolina State UniversityRaleighNCUSA

Roughly 1.2 billion tons of grain produced from maize(Zea mays)hybrids were harvested worldwide in 2022 on more than 200 million hectares(Food and Agricultural Organization statistics).Hybrid maize adapted to increased planting density,largely attributed to the upright angle of leaf blades,is a key factor for driving high grain yields over the last 50 years(Duvick et al.,2004).Leaf angle(LA)is a major breeding target for crop productivity due to its effects on canopy architecture,which impacts the amount of light intercepted by the leaf blade(Cao et al.,2022).

关键词： breeding planting maize

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Materials advancements for the safety and patency of implantable cardiovascular devices

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Nano Research 2024年第10期17卷 8977-8989页

作者： Zulmari Silva Pedraza Bo Liu Xudong Wang Department of Materials Science and Engineering University of Wisconsin−MadisonMadisonWisconsin 53706USA departments of Cell and Regenerative Biology University of Wisconsin-MadisonMadisonWisconsin 53705USA

Implantable cardiovascular devices have revolutionized the management of cardiovascular diseases,significantly enhancing patients’quality of *** the increasing demand of cardiac implantable electronic devices,the imperative for novel device development is *** review article first elaborates the mechanisms underlying foreign body response and infection,elucidating the complex interplay between implanted constructs and host *** discussion then focuses on current advancements in materials science and engineering aimed at mitigating these *** innovations,such as drugeluting materials,surface modifications,and biomimetic materials,are explored as strategies to modulate these responses and to prevent fibrotic or thrombotic complications and ***,future directions in materials development for implantable cardiovascular devices are *** addressing safety and patency concerns through innovative material strategies,this article aims to guide the research and development of advanced materials for both current and future cardiovascular implantable devices,ultimately improving patient outcomes and advancing cardiovascular disease treatment.

关键词： biomaterials implantable devices cardiovascular diseases implantable materials

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Nanoparticle targeting cGAS-STING signaling in disease therapy

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Nano Research 2024年第8期17卷 7315-7336页

作者： Lan Zhou Yu Huang Yuzhang Wu Shupei Tang Frontier medical Training Brigade Third Military Medical UniversityHutubi 831200China Department of Gastroenterology Xinqiao HospitalThird Military Medical UniversityChongqing 400037China Institute of Immunology Third Military Medical UniversityChongqing 400038China Shigatse Branch Xinqiao HospitalThird Military Medical UniversityShigatse 857000China

The cyclic guanosine monophosphate-adenosine monophosphate synthase-stimulator of interferon(IFN)genes(cGAS-STING)signaling pathway is crucial for sensing abnormal DNA accumulation in the *** binds to abnormal DNA,cGAS catalyzes the production of second messenger cyclic dinucleotides,followed by the activation of downstream *** activation induces the expression of type I interferon and other inflammatory cytokines,ultimately initiating an immune *** to the involvement of the cGAS-STING pathway in various diseases,including infection,tumor,autoimmune disease and kidney disease,ongoing research is focused on developing drugs and treatment methods to target and regulate this *** the development of nanotechnology,nanomedicines targeting cGAS-STING signaling are of great significance in clinical applications due to their targeted delivery,controlled drug release,improved solubility,multifunctionality,and enhanced *** comprehensive review focuses on the most recent progress of nanoplatforms targeting cGAS-STING in disease therapy,aiming to provide references and guidelines for further design and optimization of nanomedicines.

关键词： nanomedicine cGAS-STING pathway and related disease anti-tumor nanotherapy anti-viral nanotherapy

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Diabetes mellitus in patients with type 1 autoimmune pancreatitis at diagnosis and after corticosteroid therapy

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 393-398页

作者： Mei-Zi Li Tao Guo Yun-Lu Feng Sheng-Yu Zhang Xiao-Yin Bai Xi Wu Kai Xu Ai-Ming Yang Department of Gastroenterology State Key Laboratory of Complex Severe and Rare DiseasesPeking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China Department of Radiology Peking Union Medical College HospitalPeking Union Medical College and Chinese Academy of Medical SciencesBeijing 100730China

Background:A high prevalence of diabetes mellitus(DM)coexisting with autoimmune pancreatitis(AIP)is ***,evidence on the circumstances under which corticosteroid therapy(CST)for AIP improves or worsens DM is *** study aimed to demonstrate and identify predictors of DM control under the influence of ***:Patients diagnosed with type 1 AIP were enrolled from a prospectively maintained cohort and were classified into three groups according to the chronology in which AIP and DM were diagnosed:pre-existing DM(pDM),concurrent DM(cDM),and non-DM(nDM).The responses of DM to CST were assessed when corticosteroid was ceased or tapered to a maintenance dose and classified as‘improvement’and‘non-improvement’(including‘no change’and‘exacerbation’).Results:Among 101 patients with type 1 AIP,52(51.5%)patients were complicated with DM at the time of AIP diagnosis,with 36 patients in the cDM group and 16 patients in the pDM *** incidences of diffuse pancreatic swelling(72.2%)and pancreatic body/tail involvement(91.7%)were significantly higher in the cDM group than in both the pDM and nDM *** the 52 patients with DM,CST was administered in 48 *** logistic analysis identified that elevated serum gamma-glutamyl transferase(GGT)level at AIP diagnosis[odds ratio(OR)=0.032,95%confidence interval(CI):0.003-0.412,P=0.008]and pancreatic atrophy after CST(OR=0.027,95%CI:0.003-0.295,P=0.003)were negatively associated with DM control ***:Patients with diffuse pancreatic swelling and pancreatic body/tail involvement in pancreatitis tended to be complicated with cDM at AIP *** exerted a beneficial effect on the clinical course of DM in nearly half of the AIP patients complicated with DM at diagnosis,particularly in those without elevated serum GGT levels at diagnosis and who did not experience pancreatic atrophy after CST.

关键词： Type 1 autoimmune pancreatitis Diabetes mellitus Corticosteroid therapy Predictive factor Pancreatic atrophy

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FOXO1 reshapes neutrophils to aggravate acute brain damage and promote late depression after traumatic brain injury

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Military medical Research 2024年第4期11卷 521-542页

作者： Mi Zhou Yang-Wu-Yue Liu Yu-Hang He Jing-Yu Zhang Hao Guo Hao Wang Jia-Kui Ren Yi-Xun Su Teng Yang Jia-Bo Li Wen-Hui He Peng-Jiao Ma Man-Tian Mi Shuang-Shuang Dai Department of biochemistry and Molecular Biology School of Basic MedicineArmy Medical UniversityChongqing 400038China Research Center for Nutrition and Food Safety Chongqing Key Laboratory of Nutrition and HealthInstitute of Military Preventive MedicineArmy Medical UniversityChongqing 400038China Department of Neurosurgery Daping HospitalArmy Medical UniversityChongqing 400042China Department of Trauma and Emergency Southwest HospitalArmy Medical UniversityChongqing 400038China Department of Histology and Embryology Chongqing Key Laboratory of NeurobiologyBrain and Intelligence Research Key Suyixun Laboratory of Chongqing Education CommissionArmy Medical UniversityChongqing 400038China Research Center Seventh Affiliated Hospital of Sun Yat-Sen UniversityShenzhen 518107GuangdongChina

Background:Neutrophils are traditionally viewed as first responders but have a short onset of action in response to traumatic brain injury(TBI).However,the heterogeneity,multifunctionality,and time-dependent modulation of brain damage and outcome mediated by neutrophils after TBI remain poorly ***:Using the combined single-cell transcriptomics,metabolomics,and proteomics analysis from TBI patients and the TBI mouse model,we investigate a novel neutrophil phenotype and its associated effects on TBI outcome by neurological deficit scoring and behavioral *** also characterized the underlying mechanisms both invitro and invivo through molecular simulations,signaling detections,gene expression regulation assessments[including dual-luciferase reporter and chromatin immunoprecipitation(ChIP)assays],primary cultures or co-cultures of neutrophils and oligodendrocytes,intracellular iron,and lipid hydroperoxide concentration measurements,as well as forkhead box protein O1(FOXO1)conditional knockout ***:We identified that high expression of the FOXO1 protein was induced in neutrophils after TBI both in TBI patients and the TBI mouse *** of these FOXO1high neutrophils in the brain was detected not only in the acute phase but also in the chronic phase post-TBI,aggravating acute brain inflammatory damage and promoting late TBI-induced *** the acute stage,FOXO1 upregulated cytoplasmic Versican(VCAN)to interact with the apoptosis regulator B-cell lymphoma-2(BCL-2)-associated X protein(BAX),suppressing the mitochondrial translocation of BAX,which mediated the antiapoptotic effect companied with enhancing interleukin-6(IL-6)production of FOXO1high *** the chronic stage,the“FOXO1-transferrin receptor(TFRC)”mechanism contributes to FOXO1high neutrophil ferroptosis,disturbing the iron homeostasis of oligodendrocytes and inducing a reduction in myelin basic protein,which contributes to the progression of late depression afte

关键词： Traumatic brain injury(TBI) Neutrophil Forkhead box protein O1(FOXO1) Acute stage Chronic stage

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Histone demethylase Kdm5c regulates osteogenesis and bone formation via PI3K/Akt/HIF1α and Wnt/β-catenin signaling pathways

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Genes & Diseases 2024年第1期11卷 64-66页

作者： Ying Li Lingli Ding Yage Zhang Bingyu Zhou Gene Chi Wai Man Min Wang Jinglan Li Yamei Liu Weiping Lin Haibin Wang Sien Lin Liangliang Xu Key Laboratory of Orthopaedics&Traumatology Lingnan Medical Research CenterThe First Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou University of Chinese MedicineGuangzhouGuangdong 510000China Department of Orthopaedics&Traumatology Faculty of MedicineThe Chinese University of Hong KongPrince of Wales HospitalShatinHong Kong SAR 999077China departments of Diagnostics of Traditional Chinese Medicine Guangzhou University of Chinese MedicineGuangzhouGuangdong 510000China Orthopaedic Research Lab Affiliated Hospital of Guangdong Medical UniversityGuangdong Medical UniversityZhanjiangGuangdong 524001China

Fractures have an extraordinarily negative impact on individuals'quality of life and functional *** or disability of fracture is a major health issue with important clinical,social,and economic implications.1 Mesenchymal stem cells(MSCs)play an indispensable role in the initiation of the fracture repair process including the formation of a callus which is replaced by new *** use of MSCs in the treatment of fractures is very attractive as they can reduce the time of healing and occurrence of nonunion.

关键词： PI3K/Akt HIF1α healing

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Disulfiram:A novel repurposed drug for cancer therapy

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Chinese medical Journal 2024年第12期137卷 1389-1398页

作者： Min Zeng Baibei Wu Wenjie Wei Zihan Jiang Peiqiang Li Yuanting Quan Xiaobo Hu Department of biochemistry and Molecular Biology School of Basic MedicineHengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China The Key Laboratory of Ecological Environment and Critical Human Diseases Prevention of Hunan Province Department of Education Hengyang Medical SchoolUniversity of South ChinaHengyangHunan 421001China Institute of biochemistry of Hengyang medical School University of South ChinaHengyangHunan 421001China

Cancer is a major global health *** therapeutic strategies can prolong patients’survival and reduce the costs of *** repurposing,which identifies new therapeutic uses for approved drugs,is a promising approach with the advantages of reducing research costs,shortening development time,and increasing efficiency and ***(DSF),a Food and Drug Administration(FDA)-approved drug used to treat chronic alcoholism,has a great potential as an anticancer drug by targeting diverse human *** studies show the antitumor effects of DSF,particularly the combination of DSF and copper(DSF/Cu),on a wide range of cancers such as glioblastoma(GBM),breast cancer,liver cancer,pancreatic cancer,and *** this review,we summarize the antitumor mechanisms of DSF/Cu,including induction of intracellular reactive oxygen species(ROS)and various cell death signaling pathways,and inhibition of proteasome activity,as well as inhibition of nuclear factor-kappa B(NF-κB)***,we highlight the ability of DSF/Cu to target cancer stem cells(CSCs),which provides a new approach to prevent tumor recurrence and ***,DSF/Cu inhibits several molecular targets associated with drug resistance,and therefore it is becoming a novel option to increase the sensitivity of chemo-resistant and radio-resistant *** of DSF/Cu may shed light on its improved application to clinical tumor treatment.

关键词： Disulfiram Aldehyde dehydrogenase Reactive oxygen species Proteasome activity Cancer stem cells Drug resistance

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Clinical manifestations and spermatogenesis outcomes in Chinese patients with congenital hypogonadotropic hypogonadism caused by inherited or de novo FGFR1 mutations

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Asian Journal of Andrology 2024年第4期26卷 426-432页

作者： Yu-Fan Yang Hai-Lu Ma Xi Wang Min Nie Jiang-Feng Mao Xue-Yan Wu Department of Endocrinology Peking Union Medical College HospitalChinese Academy of Medical SciencesPeking Union Medical CollegeBeijing 100730China.

Fibroblast growth factor receptor 1(FGFR1)mutations are associated with congenital hypogonadotropic hypogonadism(CHH)through inheritance or spontaneous *** detected FGFR1 mutations in a Chinese cohort of 210 CHH patients at Peking Union medical College Hospital(Beijing,China)using next-generation and Sanger *** assessed missense variant pathogenicity using six bioinformatics tools and compared clinical features and treatment outcomes between inherited and de novo mutation *** 19 patients with FGFR1 mutations,three were recurrent,and 16 were novel *** of the novel mutations were likely pathogenic according to the American College of medical Genetics and Genomics(ACMG)guidelines,with the prevalent P366L *** majority of FGFR1 mutations was inherited(57.9%),with frameshift mutations exclusive to the de novo mutation *** inherited mutation group had a lower incidence of cryptorchidism,short stature,and skeletal *** the inherited mutation group,luteinizing hormone(LH)levels were 0.5 IU l−1,follicle-stimulating hormone(FSH)levels were 1.0 IU l−1,and testosterone levels were 1.3 nmol l−*** contrast,the de novo group had LH levels of 0.2 IU l−1,FSH levels of 0.5 IU l−1,and testosterone levels of 0.9 nmol l−1,indicating milder hypothalamus–pituitary–gonadal axis(HPGA)functional deficiency in the inherited *** inherited mutation group showed a tendency toward higher spermatogenesis *** conclusion,this study underscores the predominance of inherited FGFR1 mutations and their association with milder HPGA dysfunction compared to de novo mutations,contributing to our understanding of the genetic and clinical aspects of FGFR1 mutations.

关键词： congenital hypogonadotropic hypogonadism de novo FGFR1 inherited

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Enzymatic self-assembly/disassembly turns “ON”/“OFF” the mimetic hydrolytic activity of histidine nanofibers

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Science China Chemistry 2024年第2期67卷 517-522页

作者： Xianbao Sun Manli Wang Xiaoyang Liu Wenjun Zhan Guangqiong Xu Qiaochu Jiang Hai-Dong Xu Fuqiang Wang Gaolin Liang State Key Laboratory of Digital medical Engineering School of Biological Science and Medical EngineeringSoutheast UniversityNanjing210096China Analysis Center Nanjing Medical UniversityNanjing210029China

Mimetic enzymes are devised as alternates or supplements of natural enzymes in broad fields but regulating their activities in a switchable manner remains ***,we proposed an enzymatic self-assembly/disassembly strategy to address this issue.A peptide molecule Nap FFEYIH(YH) was rationally designed which,after self-assembling into nanofibers,lined up the histidine moieties to form active hydrolysis centers for mimicking hydrolase *** dephosphorylation of Nap FFEYp IH(Yp H) by alkaline phosphatase to yield YH also turned “ON” the hydrolase *** turn,phosphorylation of YH by phosphokinase epidermal growth factor receptor to yield Yp H disassembled the nanofibers and thus turned the activity “OFF”.As such,the “ON”/“OFF” of the mimetic hydrolase activities could be regulated under physiological conditions through ALP/EGFR-mediated self-assembly/disassembly of histidine *** work provides a feasible strategy for the on-demand fabrication of artificial enzymes with controllable and superior activities.

关键词： disassembly hydrolytic activity mimetic enzyme phosphorylation self-assembly

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