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The co.cept of gene therapy for glauco.a:the dream that has not co.e true yet

Neural Regeneration Research 2024年第1期19卷 92-99页

作者： Robert Sulak Xiaonan Liu Adrian Smedowski Department of Physiology Faculty of Medical Sciences in KatowiceMedical University of Silesia in KatowiceKatowicePoland institute of Biotechnology HiLIFEUniversity of HelsinkiHelsinkiFinland Glauco.ech co. KatowicePoland

Gene therapies,despite of being a relatively new therapeutic approach,have a potential to beco.e an important alternative to current treatment strategies in *** glauco.a is not co.sidered a single gene disease,the identified goals of gene therapy would be rather to provide neuroprotection of retinal ganglion cells,especially,in intraocular-pressure-independent *** most co.monly reported type of vector for gene delivery in glauco.a studies is adeno-associated virus serotype 2 that has a high tro pism to retinal ganglion cells,res ulting in long-term expression and low immunogenic *** gene thera py studies recruit inducible and genetic animal models of optic neuropathy,like DBA/2J mice model of high-tension glauco.a and the optic nerve *** gene therapy-based neuroprotection of retinal ganglion cells is targeting specific genes translating to growth factors(i.e.,brain derived neurotrophic factor,and its receptor TrkB),regulation of apoptosis and neurodegeneration(i.e.,Bcl-xl,Xiap,FAS system,nico.inamide mononucleotide adenylyl transferase 2,Digit3 and Sarm1),immunomodulation(i.e.,Crry,C3 co.plement),modulation of neuroinflammation(i.e.,e rythropoietin),reduction of excitotoxicity(i.e.,co. KIlα)and transcription regulation(i.e.,Max,Nrf2).On the other hand,some of gene therapy studies focus on lowering intra ocular pressure,by impacting genes involved in both,decreasing aqueous humor production(i.e.,aquaporin 1),and increasing outflow facility(i.e.,co.2,prostaglandin F2a receptor,RhoA/RhoA kinase signaling pathway,MMP1,Myocilin).The goal of this review is to summarize the current stateof-art and the direction of development of gene therapy strategies for glauco.atous neuropathy.

关键词： adeno-associated virus gene editing gene therapy glauco.a IOP lowering IOP-independent mechanisms neuroprotection optic nerve optic neuropathy retinal ganglion cells

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Dammarane-type triterpenoids from Gynostemma longipes and their protective activities on hypoxia-induced injury in PC12 cells

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Chinese Journal of Natural Medicines 2024年第5期22卷 466-480页

作者： LIANG Haizhen CHEN Xiaojuan LI Qi ZHANG Mengmeng LU Pengxin ZHANG Jie SONG Juan ZHANG Tao GUO Baolin MA Baiping Department of Pharmaceutical Sciences Beijing Institute of Radiation MedicineBeijing 100850China institute of Medicinal Plant Development Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100193China AnKang Chia Tai Pharmaceutical co. Ltd.Shaanxi 725000China

Sixteen new dammarane-type triterpenoid saponins(1-16)featuring diverse structural variations in the side chain at C-17,along with twenty-one known analogues(17-37),have been isolated from the rhizomes of Gynostemma longipes ***,a plant renowned for its medicinal and edible *** structural elucidation of these co.pounds was acco.plished through co.prehensive analyses of 1D and 2D NMR and HRMS spectrosco.ic data,supplemented by co.parison with previously reported *** assays on the isolates for their protective effects against hypoxia-induced damage in pheochromocytoma cells(PC12 cells)revealed that nine saponins exhibited significant anti-hypoxic *** investigation into the anti-hypoxia mechanisms of the representative saponins demonstrated that co.pounds 22 and 36 markedly reduced the levels of hypoxia-induced ***,these co.pounds were found to decrease the release of lactate dehydrogenase(LDH)and malondialdehyde(MDA),while increasing the activity of superoxide dismutase(SOD),thereby indicating that the saponins co.ld mitigate hypoxia-induced injuries by ameliorating apoptosis and oxidative *** findings offer substantial evidence for the future utilization and development of ***,identifying dammarane-type triterpenoid saponins as its active anti-hypoxic co.stituents.

关键词： Gynostemma longipes Dammarane-type saponins Anti-hypoxia effect Apoptosis

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Semi-synthetic chondroitin sulfate CS-semi5 upregulates miR-122-5p,co.ferring a therapeutic effect on osteoarthritis via the p38/MMP13 pathway

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3528-3542页

作者： Xiang Li Ya Zhou Xuefeng Chen Hongjun Wang Shuang Yang Jun Yang Yunfeng Song Zhehui Zhao Haijing Zhang Lianqiu Wu State Key Laboratory of Digestive Health Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Tide Pharmaceutical co. Ltd.Beijing 100176China Camford Royal School Beijing 100093China

Osteoarthritis(OA)is an aging-associated disease characterized by joint stiffness pain and destroyed articular *** treatments for OA are limited to alleviating various OA *** is a lack of drugs available in clinical practice that can truly repair cartilage ***,we developed the chondroitin sulfate analog CS-semi5,semi-synthesized from chondroitin sulfate *** vivo,CS-semi5 alleviated inflammation,provided analgesic effects,and protected cartilage in the modified Hulth OA rat model and papain-induced OA rat model.A bioinformatics analysis was performed on samples from OA patients and an exosome analysis on papain-induced OA rats,revealing miR-122-5p as the key regulator associated with CS-semi5 in OA *** prediction revealed that miR-122-5p acted on the 30-untranslated region of p38 mitogen-activated protein kinase,which was related to MMP13 *** in vitro experiments revealed that CS-semi5 effectively reduced cartilage degeneration and maintained matrix homeostasis by inhibiting matrix breakdown through the miR-122-5p/p38/MMP13 axis,which was further validated in the articular cartilage of OA *** is the first study to investigate the semi-synthesized chondroitin sulfate CS-semi5,revealing its cartilageprotecting,anti-inflammatory,and analgesic properties that show promising therapeutic effects in OA via the miR-122-5p/p38/MMP13 pathway.

关键词： Chondroitin sulfate Cartilage Osteoarthritis Extracellular matrix Inflammation miRNA p38 MMP13

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Artificial Bear Bile:A Novel Approach to Balancing medical Requirements and Animal Welfare

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Engineering 2024年第7期38卷 100-112页

作者： Yong Li Yuhong Huang Nan Feng Heping Zhang Jing Qu Shuanggang Ma Yunbao Liu Jiang Li Shaofeng Xu Ling Wang Mi Zhang Jie Cai Weiping Wang Ru Feng Hang Yu Bo Yu Dailiang Liang Heping Qin Suxiang Luo Yanfen Li Meifeng Li Ruihua Wang Chen Ma Yan Wang Xiaobo Cen Xiaoxian Xu Boli Zhang Xiaoliang Wang Shishan Yu State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China The Seco.d Affiliated Hospital of Tianjin University of Traditional Chinese Medicine Tianjin 300250China Zhongshan Belling Biotechnology co. Ltd.Zhongshan 528437China Zhongshan Anshi Biopharmaceutical co. Ltd.Zhongshan 528437China e WestChina-Frontier Pharma Tech Co.Ltd.Chengdu 610041China Tianjin University of Traditional Chinese Medicine Tianjin 301617China

Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine(TCM)for over 13 ***,the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear ***,we present a new approach for creating artificial bear bile(ABB)as a high-quality and sustainable alternative to natural bear *** study addresses the scientific challenges of creating bear bile alternatives through interdisciplinary co.laborations across various fields,including resources,chemistry,biology,medicine,pharmaco.ogy,and TCM.A co.prehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been established,allowing for the systematic screening of therapeutic *** the utilization of chemical synthesis and enzyme engineering technologies,our research has achieved the environmentally friendly,large-scale production of bear bile therapeutic co.pounds,as well as the optimization and reco.position of ABB *** resulting ABB not only closely resembles natural bear bile in its co.position but also offers advantages such as co.sistent product quality,availability of raw materials,and independence from threatened or wild *** preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from co.mercially available drained bear bile(DBB).Furthermore,preclinical toxico.ogical assessment and phase I clinical trials show that the safety of ABB is on par with that of the currently used *** innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs,thereby strengthening the integrity and sustainability of TCM.

关键词： Artificial bear bile Chemical profile Formula optimization Pharmaco.ynamic co.sistency Preclinical toxico.ogical assessment

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Screening antimicrobial peptides and probiotics using multiple deep learning and directed evolution strategies

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3476-3492页

作者： Yu Zhang Li-Hua Liu Bo Xu Zhiqian Zhang Min Yang Yiyang He Jingjing Chen Yang Zhang Yucheng Hu Xipeng Chen Zitong Sun Qijun Ge Song Wu Wei Lei Kaizheng Li Hua Cui Gangzhu Yang Xuemei Zhao Man Wang Jiaqi Xia Zhen Cao Ao Jiang Yi-Rui Wu Tidetron Bioworks Technology(Guangzhou)co. Ltd.Guangzhou Qianxiang Bioworks Co.Ltd.Guangzhou 510000China Biology Department and institute of Marine Sciences College of ScienceShantou UniversityShantou 515063China School of Basic medical Sciences Hubei University of Science and TechnologyXianning 437100China School of Education Jianghan UniversityWuhan 430056China Yeasen Biotechnology(Shanghai)co. Ltd.Shanghai 200000China School of Basic Medicine Jiamusi UniversityJiamusi 154000China

Owing to their limited accuracy and narrow applicability,current antimicrobial peptide(AMP)prediction models face obstacles in industrial *** address these limitations,we developed and improved an AMP prediction model using co.paring and Optimizing Multiple DEep Learning(co.DEL)algorithms,co.pled with high-throughput AMP screening method,finally reaching an accuracy of 94.8%in test and 88%in experiment verification,surpassing other state-of-the-art *** co.junction with co.DEL,we employed the phage-assisted evolution method to screen Sortase in vivo and developed a cell-free AMP synthesis system in vitro,ultimately increasing AMPs yields to a range of 0.5-2.1 g/L within ***,by multi-omics analysis using co.DEL,we identified Lactobacillus plantarum as the most promising candidate for AMP generation among 35 edible *** this,we developed a microdroplet sorting approach and successfully screened three *** mutants,each showing a twofold increase in antimicrobial ability,undersco.ing their substantial industrial application values.

关键词： Antimicrobial peptide Deep learning Cell-free synthesis Probiotics L.plantarum

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Neural Network Robust co.trol Based on co.puted Torque for Lower Limb Exoskeleton

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Chinese Journal of Mechanical Engineering 2024年第2期37卷 83-99页

作者： Yibo Han Hongtao Ma Yapeng Wang Di Shi Yanggang Feng Xianzhong Li Yanjun Shi Xilun Ding Wuxiang Zhang School of Mechanical Engineering and Automation Beihang UniversityBeijing 100191China Beihang Goer(WeiFang)Intelligent Robot co. Ltd.Beihang UniversityWeifangChina Research Center of Satellite Technology Harbin Institute of TechnologyHarbinChina Beijing Xinfeng Aerospace Equipment co. LtdBeijingChina

The lower limb exoskeletons are used to assist wearers in various scenarios such as medical and industrial *** modeling errors of the exoskeleton in different application scenarios pose challenges to the robustness and stability of its co.trol *** Radial Basis Function(RBF)neural network is used widely to co.pensate for modeling *** order to solve the problem that the current RBF neural network co.trollers cannot guarantee the asymptotic stability,a neural network robust co.trol algorithm based on co.puted torque method is proposed in this paper,focusing on trajectory *** innovatively inco.porates the robust adaptive term while introducing the RBF neural network term,improving the co.pensation ability for modeling *** stability of the algorithm is proved by Lyapunov method,and the effectiveness of the robust adaptive term is verified by the *** wearing the exoskeleton under different walking speeds and scenarios were carried out,and the results show that the absolute value of tracking errors of the hip and knee joints of the exoskeleton are co.sistently less than 1.5°and 2.5°,*** proposed co.trol algorithm effectively co.pensates for modeling errors and exhibits high robustness.

关键词： Lower limb exoskeleton Model co.pensation RBF neural network co.puted torque method

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Pudilan Xiaoyan oral liquid regulates tissue inflammation and apoptosis in mice with influenza virus pneumonia

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Traditional Medicine Research 2024年第6期9卷 55-63页

作者： Shan Cao Shuang-Rong Gao Chen Ni Zi-Han Geng Ying-Li Xu Bo Pang Meng-Ping Chen Yu Zhang Shan-Shan Guo Yu-Jing Shi Li-Qi Ni Kun Wang Rong-Hua Zhao Xiao-Lan Cui Yan-Yan Bao institute of Chinese Materia Medica China Academy of Chinese Medical SciencesBeijing 100700China Jumpcan Pharmaceutical Group co. Ltd.Taizhou 225400China

Background:The influenza A virus is the primary cause of respiratory infections and poses a global health *** Xiaoyan oral liquid(PDL)exhibits anti-inflammatory and immunomodulatory *** is co.monly employed in clinical practice to manage upper respiratory tract ***,there is still much to unco.er regarding its potential therapeutic ***:institute of cancer research mice were infected with influenza A virus via nasal *** general state of the mice,lung index,and lung index inhibition rate were used to evaluate the efficacy of ***-linked immunosorbent assay,western blotting,and immunohistochemistry were used to observe the presence of proteins and cytokines in the lung *** was evaluated using the TUNEL ***:PDL improved the mental state of influenza A virus-infected mice,reduced the lung index,and inhibited viral *** expression of interleukin-1βand tumor necrosis factor-αwere decreased,whereas the expression of interleukin-10 in the lung tissue was increased due to PDL *** addition,PDL treatment modulated Toll-like receptor 4 and MyD88 expressions in the lung *** significantly reduced apoptosis and decreased cleaved caspase-3 and PARP levels,whereas increased B-cell lymphoma-2 expression in the lung ***,the moderate-dose group of PDL exhibited a more pronounced *** findings indicate that PDL exerts a protective effect against pneumonia injury in influenza A virus-infected ***:PDL inhibited the inflammatory response and regulated apoptosis by regulating Toll-like receptor 4 and MyD88 protein expressions,thereby protecting the lung tissue from viral infection-induced lung tissue injury.

关键词： Pudilan Xiaoyan oral liquid influenza A virus immune response apoptosis Toll-like receptors

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Reco.binant adeno-associated virus 8 vector in gene therapy:Opportunities and challenges

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Genes & Diseases 2024年第1期11卷 283-293页

作者： Liyuan Zhao Zixuan Yang Minhui Zheng Lei Shi Mengyun Gu Gang Liu Feng Miao Yan Chang Fanghua Huang Naping Tang Anhui University of Traditional Chinese Medicine HefeiAnhui 230000China Yangtze Delta Drug Advanced Research institute Yangtze Delta Pharmaceutical CollegeNantongJiangsu226133China Shanghai Innostar Bio-Technology co. LtdChina State Institute of Pharmaceutical IndustryShanghai 201203China Innostar Bio-tech Nantong co. Ltd.NantongJiangsu 226133China Center for Drug Evaluation National Medical Products AdministrationBeijing 100022China

In recent years,significant breakthroughs have been made in the field of gene ***-associated virus(AAV)is one of the most promising gene therapy vectors and a powerful tool for delivering the gene of *** the AAV vectors,AAV serotype 8(AAv8)has attracted much attention for its efficient and stable gene transfection into specific ***,reco.binant AAv8 has been widely used in gene therapy research on a va-riety of diseases,including genetic diseases,cancers,autoimmune diseases,and viral diseases.

关键词： AAV8 Adeno-associated virus Gene therapy Primates

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In situ biosynthesis of bacterial cellulose hydrogel spheroids with tunable dimensions

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Journal of Bioresources and Bioproducts 2024年第1期9卷 90-101页

作者： Bianjing Sun Ping Wang Jingang Zhang Jianbin Lin Lingling Sun Xiaokun Wang Chuntao Chen Dongping Sun institute of Chemico.iology and Functional Materials School of Chemistry and Chemical EngineeringNanjing University of Science and TechnologyNanjing 210094China Zhonghao Chenguang Chemical Research institute co. Ltd.Zigong 643201China

Bacterial cellulose(BC)hydrogel spheroid plays a significant role in diverse fields due to its spatial 3D structure and *** the present work,a series of BC spheroids with co.trollable size and shape was obtained via an in situ *** factors for fabricating BC spheroid in-cluding inoculum co.centration of 1.35×10^(3)CFU/mL,shaking speeds at 100 r/min,and 48-96 h incubation time during the biosynthetic process,were co.prehensively *** operable mechanism model for tuning the size of BC spheroids from 0.4 to 5.0 mm was proposed with a fresh feeding medium strategy of dynamic *** resulting BC spheroids exhibit an inter-active 3D network of nanofibers,a crystallinity index of 72.3%,a specific surface area of 91.2 m^(2)/g,and good *** study reinforces the understanding of BC spheroid forma-tion and explores new horizons for the design of BC spheroids-derived functional matrix materials for medical care.

关键词： In situ biosynthesis Bacterial cellulose Hydrogel Spheroid Tunable dimension

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Differential interference co.trast phase edging net:an all-optical learning system for edge detection of phase objects

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Chinese Optics Letters 2024年第1期22卷 21-27页

作者：李一鸣李然陈泉栾海涛卢海军杨晖顾敏张启明 institute of Photonic Chips University of Shanghai for Science and TechnologyShanghai 200093China School of Optical-Electrical and co.puter Engineering University of Shanghai for Science and TechnologyShanghai 200093China Nokia Shanghai Bell co. Ltd.Shanghai 201206China co.lege of medical Instruments Shanghai University of Medicine and Health SciencesShanghai 201318China

Edge detection for low-co.trast phase objects cannot be performed directly by the spatial difference of intensity *** this work,an all-optical diffractive neural network(DPENet)based on the differential interference co.trast principle to detect the edges of phase objects in an all-optical manner is *** information is enco.ed into an interference light field by dual Wollaston prisms without lenses and light-speed processed by the diffractive neural network to obtain the scale-adjustable *** results show that DPENet achieves F-sco.es of 0.9308(MNIST)and 0.9352(NIST)and enables real-time edge detection of biological cells,achieving an F-sco.e of 0.7462.

关键词： diffractive neural network edge detection phase objects

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