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Casein kinase-2 inhibition promotes retinal ganglion cell survival after acute intraocular pressure elevation

Neural Regeneration Research 2024年第5期19卷 1112-1118页

作者： Meng Wang Shi-Qi Yao Yao Huang Jia-Jian Liang Yanxuan Xu Shaowan Chen Yuhang Wang Tsz kin Ng Wai Kit Chu Qi Cui Ling-Ping Cen Joint Shantou International Eye Center of Shantou University and The Chinese University of Hong Kong ShantouGuangdong ProvinceChina Shantou University Medical College ShantouGuangdong ProvinceChina beijing Tongren Eye Center Beijing Tongren HospitalCapital Medical UniversityBeijingChina Department of Ophthalmology and Visual Sciences The Chinese University of Hong KongHong Kong Special Administrative RegionChina

Intraocular pressure elevation can induce retinal ganglion cell death and is a clinically reversible risk factor for glaucoma,the leading cause of irreversible *** previously demonstrated that casein kinase-2 inhibition can promote retinal ganglion cell survival and axonal regeneration in rats after optic nerve *** investigate the underlying mechanism,in the current study we increased the intraocular pressure of adult rats to 75 mmHg for 2 hours and then administered a casein kinase-2 inhibitor(4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole)by intravitreal *** found that intravitreal injection of 4,5,6,7-tetrabromo-2-azabenzimidazole or 2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole promoted retinal ganglion cell survival and reduced the number of infiltrating *** analysis showed that the mitogen activated protein kinase signaling pathway was involved in the response to intraocular pressure elevation but was not modulated by the casein kinase-2 ***,casein kinase-2 inhibition downregulated the expression of genes(Cck,Htrsa,Nef1,Htrlb,Prph,Chat,Slc18a3,Slc5a7,Scn1b,Crybb2,Tsga10ip,and Vstm21)involved in intraocular pressure *** data indicate that inhibition of casein kinase-2 can enhance retinal ganglion cell survival in rats after acute intraocular pressure elevation via macrophage inactivation.

关键词： casein kinase-2 glaucoma intraocular pressure elevation macrophages retinal ganglion cells

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Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

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Neural Regeneration Research 2024年第2期19卷 409-415页

作者： Hongmei Duan Shulun Li Peng Hao Fei Hao Wen Zhao Yudan Gao Hui Qiao Yiming Gu Yang Lv Xinjie bao kin Chiu Kwok-Fai So Zhaoyang Yang Xiaoguang Li Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina beijing Key Laboratory for biomaterials and Neural Regeneration School of Engineering MedicineBeihang UniversityBeijingChina Department of Epidemiology and Statistics School of Public Health and ManagementNingxia Medical UniversityYinchuanNingxia Hui Autonomous RegionChina Department of Physical Education Capital University of Economics and BusinessmBeijingChina Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Psychology State Key Lab of Brain and Cognitive SciencesThe University of Hong KongHong Kong Special Administration RegionChina Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State Key Laboratory of brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina Center for brain Science and brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain ***,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still *** this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in *** gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional *** study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

关键词： adult endogenous neurogenesis angiogenesis basic fibroblast growth factor-chitosan gel chitosan functional recovery ischemic stroke neural stem cell newborn neuron

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ALS-linked C9orf72 dipeptide repeats inhibit starvation-induced autophagy through modulating bCL2–bECN1 interaction

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Acta Pharmaceutica Sinica b 2024年第5期14卷 2026-2038页

作者： Shiqiang Xu Qilian Ma Junwen Shen Ningning Li Shan Sun Nana Wang Yang Chen Chunsheng Dong kin Yip Tam Jochen H.M.Prehn Hongfeng Wang Zheng Ying Jiangsu Key Laboratory of Neuropsychiatric Diseases and College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China MOE Key Laboratory of Geriatric Diseases and Immunology College of Pharmaceutical SciencesSuzhou Medical College of Soochow UniversitySuzhou 215123China Jiangsu Province Engineering Research Center of Precision Diagnostics and Therapeutics Development Soochow UniversitySuzhou 215123China Dept.of Physiology&Medical Physics and FUTURE-NEURO Research Centre Royal College of Surgeons in IrelandDublin D02 YN77Ireland Faculty of Health Sciences University of MacaoTaipaMacao 999078China Insititutes of biology and Medical Science Soochow UniversitySuzhou 215123China

Growing evidences indicate that dysfunction of autophagy contributes to the disease pathogenesis of amyotrophic lateral sclerosis(ALS)and frontotemporal dementia(FTD),two neurodegenerative *** GGGGCC·GGCCCC repeat RNA expansion in chromosome 9 open reading frame 72(C9orf72)is the most genetic cause of both ALS and *** to the previous studies,GGGGCC·GGCCCC repeat undergoes the unconventional repeat-associated non-ATG translation,which produces dipeptide repeat(DPR)*** there is a growing understanding that C9orf72 DPRs have a strong ability to harm neurons and induce C9orf72-linked ALS/FTD,whether these DPRs can affect autophagy remains *** the present study,we find that poly-GR and poly-PR,two arginine-containing DPRs which display the most cytotoxic properties according to the previous studies,strongly inhibit starvation-induced ***,our data indicate that arginine-rich DPRs enhance the interaction between bCL2 and bECN1/beclin 1 by inhibiting bCL2 phosphorylation,therefore they can impair autophagic clearance of neurodegenerative disease-associated protein aggregates under starvation condition in ***,our study not only highlights the role of C9orf72 DPR in autophagy dysfunction,but also provides novel insight that pharmacological intervention of autophagy using SW063058,a small molecule compound that can disrupt the interaction between bECN1 and bCL2,may reduce C9orf72 DPR-induced neurotoxicity.

关键词： Amyotrophic lateral sclerosis Frontotemporal dementia C9orf72 Autophagy bCL2 bECN1/beclin 1 Dipeptide repeat Neurodegeneration

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Small-molecule agents for cancer immunotherapy

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Acta Pharmaceutica Sinica b 2024年第3期14卷 905-952页

作者： Fang Wang Kai Fu Yujue Wang Can Pan Xueping Wang Zeyu Liu Chuan Yang Ying Zheng Xiaopeng Li Yu Lu Kenneth kin Wah To Chenglai Xia Jianye Zhang Zhi Shi Zeping Hu Min Huang Liwu Fu State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Esophageal Cancer InstituteGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences Tsinghua-Peking Center for Life SciencesBeijing Frontier Research Center for Biological StructureTsinghua UniversityBeijing 100084China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Department of Cell biology&Institute of biomedicine National Engineering Research Center of Genetic MedicineMOE Key Laboratory of Tumor Molecular BiologyGuangdong Provincial Key Laboratory of Bioengineering MedicineCollege of Life Science and TechnologyJinan UniversityGuangzhou 510632China Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target&Clinical Pharmacology NMPA and State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou 511436China School of Pharmacy The Chinese University of Hong KongHong Kong 999077China Affiliated Foshan Maternity and Child Healthcare Hospital Southern Medical UniversityFoshan 528000China

Cancer immunotherapy,exemplified by the remarkable clinical benefits of the immune checkpoint blockade and chimeric antigen receptor T-cell therapy,is revolutionizing cancer *** induce long-term tumor regression and overall survival benefit in many types of *** the advances in our knowledge about the tumor immune microenvironment,remarkable progress has been made in the development of small-molecule drugs for *** molecules targeting PRR-associated pathways,immune checkpoints,oncogenic signaling,metabolic pathways,cytokine/chemokine signaling,and immune-related kinases have been extensively *** of smallmolecule immunotherapeutic drugs and their combinations with other antitumor modalities are under active clinical investigations to overcome immune tolerance and circumvent immune checkpoint inhibitor ***,we review the latest development of small-molecule agents for cancer immunotherapy by targeting defined pathways and highlighting their progress in recent clinical investigations.

关键词： Cancer immunotherapy Small-molecule agents Immune checkpoints Oncogenic signaling Metabolic pathways Cytokine/chemokine signaling Antitumor immunity Tumor immune microenvironment

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Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease

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Military Medical Research 2024年第2期11卷 206-227页

作者： Guang-Hui Deng Chao-Feng Wu Yun-Jia Li Hao Shi Wei-Chao Zhong Mu-Keng Hong Jun-Jie Li Jia-Min Zhao Chang Liu Meng-Chen Qin Zhi-Yun Zeng Wei-Min Zhang Ken kin Lam Yung Zhi-Ping Lv Lei Gao Department of Gastroenterology Integrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China School of Traditional Chinese Medicine Southern Medical UniversityGuangzhou 510515China Department of Hepatology Cancer CenterIntegrated Hospital of Traditional Chinese MedicineSouthern Medical UniversityGuangzhou 510315China Shenzhen Traditional Chinese Medicine Hospital Shenzhen 518033GuangdongChina Department of biology Hong Kong Baptist UniversityKowloon TongKowloonHong Kong SAR 999077China

background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron *** previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the *** study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in ***:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this ***-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in ***,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload ***,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and *** related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and ***:Significant disorder of lipid and iron metabolism occurred in *** expression of Cav-1 was decreased in NAFLD hepatocytes(Pby iron metabolism ***-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the ***,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in *** correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that reg

关键词： Caveolin-1 Nonalcoholic fatty liver disease Iron metabolism Ferritin Oxidative stress

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Magnetic field regression using artificial neural networks for cold atom experiments

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Chinese Physics b 2024年第2期33卷 46-51页

作者：陈子霆黃建陶 bojeong Seo 黄明琛 Mithilesh K.Parit 何逸飞甄浩廷 Jensen Li Gyu-boong Jo Department of Physics The Hong Kong University of Science and TechnologyKowloon 999077China

Accurately measuring magnetic fields is essential for magnetic-field sensitive experiments in areas like atomic,molecular,and optical physics,condensed matter experiments,and other ***,since many experiments are often conducted in an isolated environment that is inaccessible to experimentalists,it can be challenging to accurately determine the magnetic field at the target ***,we propose an efficient method for detecting magnetic fields with the assistance of an artificial neural network(NN).Instead of measuring the magnetic field directly at the desired location,we detect fields at several surrounding positions,and a trained NN can accurately predict the magnetic field at the target *** training,we achieve a below 0.3%relative prediction error of magnetic field magnitude at the center of the vacuum chamber,and successfully apply this method to our erbium quantum gas apparatus for accurate calibration of magnetic field and long-term monitoring of environmental stray magnetic *** demonstrated approach significantly simplifies the process of determining magnetic fields in isolated environments and can be applied to various research fields across a wide range of magnetic field magnitudes.

关键词： ultracold gases trapped gases measurement methods and instrumentation

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An integrative analysis of miRNA and mRNA expression in the brains of Alzheimer's disease transgenic mice after real-world PM_(2.5)exposure

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Journal of Environmental Sciences 2022年第12期34卷 25-40页

作者： Pengfei Fu Yufei Zhao Chuan Dong Zongwei Cai Ruijin Li Ken kin Lam Yung Department of biology Hong Kong Baptist UniversityHong Kong SARChina Golden Meditech Center for NeuroRegeneration Sciences Hong Kong Baptist UniversityHong Kong SARChina Institute of Environmental Science Shanxi UniversityTaiyuan 237016China State Key Laboratory of Environmental and biological Analysis Hong Kong Baptist UniversityHong Kong SARChina

Fine particulate matter(PM_(2.5))is associated with increased risks of Alzheimer's disease(AD),yet the toxicological mechanisms of PM_(2.5)promoting AD remain *** this study,wildtype and APP/PS1 transgenic mice(AD mice)were exposed to either filtered air(FA)or PM_(2.5)for eight weeks with a real-world exposure system in Taiyuan,China(mean PM_(2.5)concentration in the cage was 61μg/m~3).We found that PM_(2.5)exposure could remarkably aggravate AD mice's ethological and brain ultrastructural damage,along with the elevation of the pro-inflammatory cytokines(IL-6 and TNF-α),Aβ-42 and ACh E levels and the decline of Ch AT levels in the *** on high-throughput sequencing results,some differentially expressed(DE)m RNAs and DE mi RNAs in the brains of AD mice after PM_(2.5)exposure were *** RT-q PCR,seven DE mi RNAs(mmu-mi R-193b-5p,122b-5p,466h-3p,10b-5p,1895,384–5p,and 6412)and six genes(Pcdhgb8,Unc13b,Robo3,Prph,Pter,and Tbata)were evidenced the and *** mi RNA-target gene pairs(mi R-125b-Pcdhgb8 pair and mi R-466h-3p-IL-17Rα/TGF-βR2/Aβ-42/ACh E pairs)were demonstrated that they were more related to PM_(2.5)-induced brain *** of Gene Ontology(GO)pathways and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways predicted that synaptic and postsynaptic regulation,axon guidance,Wnt,MAPK,and m TOR pathways might be the possible regulatory mechanisms associated with pathological *** revealed that PM_(2.5)-elevated pro-inflammatory cytokine levels and PM_(2.5)-altered neurotransmitter levels in AD mice could be the important causes of brain damage and proposed the promising mi RNA and m RNA biomarkers and potential mi RNA-m RNA interaction networks of PM_(2.5)-promoted AD.

关键词： Fine particulate matter mRNAs miRNAs brain Alzheimer’s disease APP/PS1 transgenic mice

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Small Molecule Organic Nanostructures—Fabrication and Properties

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Journal of Materials Science & Technology 2008年第4期24卷 563-568页

作者： A.b.Djurii A.M.C.Ng Kai-Yin CHEUNG Man-kin FUNG Wai-kin CHAN Department of Physics University of Hong KongPokfulam RoadHong KongHong Kong SARChina Department of Chemistry University of Hong KongPokfulam RoadHong KongHong Kong SARChina

Organic materials are of great interest for the development of low cost electronic and optoelectronic devices. Although majority of research on organic materials is concerned with synthesis of novel compounds and organic thin films, organic nanostructures are attracting increasing interest in recent years. We briefly review different growth methods of organic nanostructures, which can be roughly divided into vapor deposition methods and self-assembly techniques in solution. Then we highlight some interesting properties of organic nanostructures, as well as possible applications, includinf field emission, electronic and optoelectronic devices.

关键词： Organic nanostructures Self-assembly Vapor deposition

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Exploring light-cone distribution amplitudes from quantum computing

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Science China(Physics,Mechanics & Astronomy) 2023年第8期66卷 57-65页

作者： Tianyin Li Xingyu Guo Wai kin Lai Xiaohui Liu Enke Wang Hongxi Xing Dan-bo Zhang Shi-Liang Zhu Guangdong Provincial Key Laboratory of Nuclear Science Institute of Quantum MatterSouth China Normal UniversityGuangzhou 510006China Guangdong-Hong Kong Joint Laboratory of Quantum Matter Southern Nuclear Science Computing Center South China Normal University.Guangzhou 510006China Department of Physics and Astronomy University of CaliforniaLos Angeles 90095USA Center of Advanced Quantum Studies Department of PhysicsBeijing Normal UniversityBejing 100875China Center for High Energy Physics Peking UniversityBeijing 100871China Guangdong-Hong Kong Joint Laboratory of Quantum Matter Frontier Research Institute for PhysicsSouth China Normal UniversityGuangzhou 510006China Guangdong Provincial Key Laboratory of Quantum Engineering and Quantum Materials School of Physics and Telecommunication EngineeringSouth China Normal UniversityGuangzhou 510006China

Light-cone distribution amplitudes(LCDAs)are essential nonperturbative quantities for theoretical predictions of exclusive highenergy processes in quantum chromodynamics(QCD).We demonstrate the prospect of calculating LCDAs on a quantum computer by applying a recently proposed quantum algorithm,with staggered fermions,to the simulation of the LCDA in the(1+1)-dimensional Nambu-Jona-Lasinio(NJL)model on classical *** agreement between the result from the classical simulation of the quantum algorithm and that from exact diagonalization justifies the proposed quantum *** find that the resulting LCDA in the NJL model exhibits features shared with the LCDAs obtained from the QCD.

关键词： light-cone distribution amplitude quantum algorithm NJL model

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Clinical results of radical prostatectomy for patients with prostate cancer in Macao

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Chinese Medical Journal 2008年第4期121卷 295-298页

作者： Ho Son-fat Lao Hio-fai Li kin Tse Men-kin Department of Urology Centro Hospitalar Conde de Sáo Januário Macao Special Administrative Region China

background Incidence of prostate cancer has been increasing in recent decades. In the year 2005, prostate cancer became the second most common cancer in males in Macao. The purpose of this report was to review and summarize the clinical features and prognosis of the 54 patients undergoing radical prostatectomy in Macao Special Administrative Region （SAR）, China.Methods From November 2000 to November 2006, retropubic radical prostatectomy were performed in 54 cases for the treatment of prostate cancer. The mean age of patients was 69.8 years （range from 54 to 79）. The preoperative prostate specific antigen （PSA） level, postoperative pathologic stage and Gleason＇s score, operation duration, intraoperative bleeding and intraoperative and postoperative complications were reported. The follow-up duration was 3 months to 6.25 years with a mean of 2.1 years. Postoperative parameters including PSA alteration, biochemical recurrence, local recurrence, distant metastasis and mortality were observed.Results Most of the patients in our study were diagnosed as localized prostate cancer. The patients＇ preoperative serum PSA was 0-4.0 ng/ml （16.7%）, 4.0-10.0 ng/ml （51.8%）, 10.1-20.0 ng/ml （24.1%） and above 20.0 ng/ml （7.4%）. The TNM stage T1a ＋ T1b comprised 7.6% of patients, stage T2a ＋ T2b comprised 20.3%, stage T2c 38.9%, stage T3a 20.3% and over T3a only 12.9%. There were 9.5% cases with Gleason scores of 2-4, 41.5% with scores of 5-6, 30.2% with scores of 7 and 18.8% with scores of 8-10. The average operative duration was 216 minutes and the average intraoperative bleeding was 760 ml. Intraoperative complications included one massive hemorrhage （1.9%）, one rectal injury （1.9%） and one obturator nerve injury （1.9%）. Early postoperative complications consisted of urinary incontinence （14 cases, 25.9%）, bladder neck stricture （5 cases, 9.3%）, acute urinary retention （4 cases, 7.4%）, pelvic effusion （2 cases, 3.8%）, lymphocele （1 case, 1.9%） and vesicorectal fistula （only 1 c

关键词： prostate cancer prostate specific antigen radical prostatectomy

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