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Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy

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Signal Transduction and Targeted Therapy 2024年第3期9卷 1147-1164页

作者： Yan Guo Pan Xiang Xiaojiao Sun Wei Liu Jiafeng Zhou Bin Yin Lin Hou Boqin Qiang Huiliang Li Pengcheng Shu Xiaozhong Peng Department of Molecular Biology and Biochemistry Institute of Basic Medical SciencesMedical Primate Research CenterNeuroscience CenterChinese Academy of Medical SciencesSchool of Basic Medicine Peking Union Medical CollegeBeijingChina State Key Laboratory of Common Mechanism Research for Major Diseases Beijing 100005China Wolfson Institute for Biomedical Research University College LondonGower StreetLondon WC1E 6BTUK Chinese Institute for Brain Research Beijing 102206China State Key Laboratory of Respiratory Health and Multimorbidity Beijing 100005China Institute of Laboratory Animal Science Chinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100021China

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits,and this process requires the proper recruitment of adaptor molecules to selectively activate downstream pathways.Here,we identified that DOK6,a member of the Dok(downstream of tyrosine kinases)family,is required for the maintenance of peripheral axons,and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice,manifested as impaired sensory,abnormal posture,paw deformities,blocked nerve conduction,and dysmyelination.Furthermore,Dok6 is highly expressed in peripheral neurons but not in Schwann cells,and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding,axon destruction,and hindered retrograde axonal transport.Specifically,DOK6 acts as an adaptor protein for selectivitymediated neurotrophic signal transduction and retrograde transport for TrkC and Ret but not for TrkA and TrkB.DOK6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation,including MAP1B,Tau and Dynein for axonal transport,and specifically activates the downstream ERK1/2 kinase pathway to maintain axonal survival and homeostasis.This finding provides new clues to potential insights into the pathogenesis and treatment of hereditary peripheral neuropathies and other degenerative diseases.

关键词： impaired restrain peripheral

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Contribution of Temperature Increase to restrain the Transmission of COVID-19

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The Innovation 2021年第1期2卷 74-81页

作者： Mengyuan Ren Rongjuan Pei Bahabaike Jiangtulu Junxi Chen Tao Xue Guofeng Shen Xiaoru Yuan Kexin Li Changxin Lan Zhen Chen Xinwen Chen Yun Wang Xiaoqian Jia Zewu Li Audil Rashid Tippawan Prapamontol Xiuge Zhao Zhaomin Dong Yali Zhang Le Zhang Rongwei Ye Zhiwen Li Wuxiang Guan Bin Wang Institute of Reproductive and Child Health Peking University/Key Laboratory of Reproductive HealthNational Health Commission of the People's Republic of ChinaBeijing 100191P.R.China Department of Epidemiology and Biostatistics School of Public HealthPeking UniversityBeijing 100191P.R.China Wuhan Institute of Virology Center for Biosafety Mega-ScienceChinese Academy of SciencesWuhanHubeiChina College of Urban and Environmental Sciences Peking UniversityBeijing 100871P.R.China Key Laboratory of Machine Perception(Ministry of Education) and School of EECSPeking UniversityBeijingChina Institute of Geographic Sciences and Natural Resources Research CASBeijing 100101P.R.China Faculty of Science Botany DepartmentUniversity of GujratHafiz Hayat CampusGujrat-50700Pakistan Research Institute for Health Sciences Chiang Mai UniversityChiang Mai 50200Thailand State Key Laboratory of Environmental Criteria and Risk Assessment Chinese Research Academy of Environmental SciencesBeijing 100012P.R.China Beijing Advanced Innovation Center for Big Data-Based Precision Medicine Beihang UniversityBeijing 100191China

The COVID-19 outbreak has already become a global pandemic and containing this rapid worldwide transmission is of great challenge.The impacts of temperature and humidity on the COVID-19 transmission rate are still under discussion.Here,we elucidated these relationships by utilizing two unique scenarios,repeated measurement and natural experiment,using the COVID-19 cases reported from January 23–February 21,2020,in China.The modeling results revealed that higher temperature was most strongly associated with decreased COVID-19 transmission at a lag time of 8 days.Relative humidity(RH)appeared to have only a slight effect.These findings were verified by assessing SARSCoV-2 infectivity under the relevant conditions of temperature(4C–37C)and RH(>40%).We concluded that temperature increase made an important,but not determined,contribution to restrain the COVID19 outbreak in China.It suggests that the emphasis of other effective controlling polices should be strictly implemented to restrain COVID19 transmission in cold seasons.

关键词： restrain humidity COV

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Fatty is not that bad: feeding short-chain fatty acids to restrain autoimmunity

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Cellular & Molecular Immunology 2017年第11期14卷 878-880页

作者： Arianna Brevi Matteo Bellone Department of Immunology Transplantation and Infectious DiseasesCellular Immunology UnitSan Raffaele Scientific InstituteMilan 20132Italy Univeristà Vita-Salute San Raffaele Milan 20132Italy

Do environmental cues,and commensal bacteria in particular,have an impact on autoimmunity,and can we modulate the production of gut microbial metabolites to re-equilibrate immune responses as well as restrain autoimmune diseases?Mari?o et al.1 elegantly addressed these issues in a very recent Nature Immunology paper.They report that diets designed to release large amounts of the microbial metabolites acetate and butyrate finely tune autoreactive immune responses,which lends weight to the fascinating hypothesis that medicinal foods and metabolites might contribute to treating autoimmune diseases.

关键词： restrain autoimmunity release

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Factors behind not using child restrain(t) among hospital employees and general population：A case control study

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World Journal of Emergency Medicine 2017年第4期8卷 269-275页

作者： Emad Siddiqui Badar Afzal Ghazala Kazi Asher Feroz Rubaba Naeem Tarab Mansoor Ahreen Allana Saif Siddiqui Zain Siddiqui Department of Emergency Medicine Aga Khan University Hospital Karachi Pakistan

BACKGROUND: Motor vehicle crash(MVC) related injury has been identified as a major public health concern. Child restrain(CR) seat belts can minimize the mortality and morbidity from MVC. The use for seat belts is substantially low in developing countries like Pakistan even though its use has been shown to decrease morbidity and mortality by a significant extent.METHODS: This was a case control study with cases from the general population(GP) and controls from the Aga Khan University(AKU) employees in a 3:1 ratio. The study questionnaire was based on parameters like gender, education level, awareness and presence of CR and also assessed the frequency of usage, reasons for not using CR and the source of knowledge regarding CR use.RESULTS: Out of 848 respondents, 212 were from AKU and 636 were from the GP. 96.7% from AKU had at least a bachelor's degree while less than half(42.6%) of those from the GP were graduate or above(Prestraint use(Prestraint seat belts.

关键词： Child restrain Seat belt Injury Pakistan

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Suppression of PFKFB3-driven glycolysis restrains endothelial-to-mesenchymal transition and fibrotic response

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Signal Transduction and Targeted Therapy 2022年第10期7卷 3867-3883页

作者： Hao Zeng Ting Pan Meiling Zhan Renaguli Hailiwu Baolin Liu Hua Yang Ping Li State Key Laboratory of Natural Medicines School of Traditional Chinese PharmacyChina Pharmaceutical UniversityNanjing 210009China

Endothelial-to-mesenchymal transition(EndoMT),the process wherein endothelial cells lose endothelial identity and adopt mesenchymal-like phenotypes,constitutes a critical contributor to cardiac fibrosis.The phenotypic plasticity of endothelial cells can be intricately shaped by alteration of metabolic pathways,but how endothelial cells adjust cellular metabolism to drive EndoMT is incompletely understood.Here,we identified 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3(PFKFB3)as a critical driver of EndoMT via triggering abnormal glycolysis and compromising mitochondrial respiration.Pharmacological suppression of PFKFB3 with salvianolic acid C(SAC),a phenolic compound derived from Salvia miltiorrhiza,attenuates EndoMT and fibrotic response.PFKFB3-haplodeficiency recapitulates the anti-EndoMT effect of SAC while PFKFB3-overexpression augments the magnitude of EndoMT and exacerbates cardiac fibrosis.Mechanistically,PFKFB3-driven glycolysis compromises cytoplasmic nicotinamide adenine dinucleotide phosphate(reduced form,NADPH)production via hijacking glucose flux from pentose phosphate pathway.Efflux of mitochondrial NADPH through isocitrate/α-ketoglutarate shuttle replenishes cytoplasmic NADPH pool but meanwhile impairs mitochondrial respiration by hampering mitochondrial iron-sulfur cluster biosynthesis.SAC disrupts PFKFB3 stability by accelerating its degradation and thus maintains metabolic homeostasis in endothelial cells,underlying its anti-EndoMT effects.These findings for the first time identify the critical role of PFKFB3 in triggering EndoMT by driving abnormal glycolysis in endothelial cells,and also highlight the therapeutic potential for pharmacological intervention of PFKFB3(with SAC or other PFKFB3 inhibitors)to combat EndoMT-associated fibrotic responses via metabolic regulation.

关键词： transition restrain maintain

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Erratum to DYRK1A suppression restrains Mcl-1 expression and sensitizes NSCLC cells to Bcl-2 inhibitors

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Cancer Biology & Medicine 2022年第7期19卷 1109-1110页

作者： Yangling Li Dongmei Zhou Shuang Xu Mingjun Rao Zuoyan Zhang Linwen Wu Chong Zhang Nengming Lin Department of Clinical Pharmacology Hangzhou First People’s HospitalNanjing Medical UniversityHangzhou 310006China Department of Clinical Pharmacology Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang ProvinceHangzhou First People’s HospitalZhejiang University School of MedicineHangzhou 310006China Institute of Pharmacology College of Pharmaceutical SciencesZhejiang Chinese Medical UniversityHangzhou 311402China School of Medicine Zhejiang University City CollegeHangzhou 310015China

In the published paper1,errors appeared in Figure 1D on page 391.In Figure 1D,an incorrect gel image was shown for Bcl-xL in NCI-H1299 cells.Figure 1D has been updated to correct the mistake above.The errors do not af... 详细信息

关键词： Figure NSCLC restrain

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Reversing epigenetic repression of transposable elements for improving tumor immunogenicity

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Cancer Communications 2022年第3期42卷 266-268页

作者： Xi Wang Qian Zhang Xuetao Cao Institute of Immunology Zhejiang University School of MedicineHangzhouZhejiang 310058P.R.China National Key Laboratory of Medical Immunology Institute of ImmunologyNaval Medical UniversityShanghai 200433P.R.China

In a recent study published in Nature,Zhang et al.[1]revealed a new epigenetic mechanism for restraining tumor intrinsic immunogenicity:Lysine demethylase 5B(KDM5B)recruits SET domain bifurcated histone lysine methyltransferase 1(SETDB1)to repress the transcription of transposable elements(TEs)by H3K9me3 modifica-tion,while TE de-repression by targeting KDM5B conse-quently activated nucleic acid sensing pathways and anti-gen presentation to elicit tumor intrinsic immunity which enhanced host anti-tumor immune response.

关键词： elements restrain tumor

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Vibration Control of an Experimental Flexible Manipulator Against Input Saturation

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IEEE/CAA Journal of Automatica Sinica 2023年第5期10卷 1340-1342页

作者： Zhijia Zhao Sentao Cai Ge Ma F.Richard Yu the School of Mechanical and Electrical Engineering Guangzhou UniversityGuangzhou 510006 the Guangdong Laboratory of Artificial Intelligence and Digital Economy(SZ) Shenzhen 518060China the Guangdong Laboratory of Artificial Intelligence and Digital Economy(SZ) College of Computer Science&Software EngineeringShenzhen UniversityShenzhen 518060China

Dear Editor, This letter considers the control problem of an experimental flexible manipulator in position tracking, vibration suppression, and saturation compensation. Based on the backstepping technology and a Nussbaum function, we develop an anti-windup control to restrain the manipulator’s vibration, realize the desire trajectory tracking, and eliminate the saturation.

关键词： restrain eliminate Vibration

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The Low-Frequency Oscillation restrain Method Research of Converter-Fed Multi-Phase Induction Motor Propulsion system

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Engineering（科研） 2015年第5期7卷 272-284页

作者： Haiyan Zeng Mingzhong Qiao Peng Zhu College of Electric Engineering Naval University of Engineering Wuhan China

The inverter-fed induction motor drive system may become unstable at low frequencies and light load, and phase current and speed of the induction motor may oscillate periodically, which will threaten safety and reliability of the system. This paper chooses nine-phase induction motor simulated propulsion system as the research object, small disturbance model of three-phase induction motor is built, and average equivalent model of the converter is built by introducing switch function. On the basis above, small disturbance mathematic model of the whole system is obtained. As for the limitation of parameters adjustment method of restrain low-frequency oscillation, the restrain method combining current close-loop with dead-time compensation is put forward. Finally, the proposed restrain method is verified respectively on the built simulation and experimental analogue platform. And the simulation and experimental results indicate that the proposed method can not only satisfy the requirement of low-frequency oscillation restraining, but also be expanded widely, and the stability of the system can get improved greatly.

关键词： Induction Motor Propulsion System Low Frequency Oscillation Small Disturbance Model restrain Method

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Understanding a Single-Li-Ion COF Conductor for Being Dendrite Free in a Li-Organic Battery

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Research 2023年第1期2022卷 209-218页

作者： Yongjiang Sun Genfu Zhao Yao Fu Yongxin Yang Conghui Zhang Qi An Hong Guo School of Materials and Energy Yunnan UniversityNo.2Green Lake North RoadKunming 650091China

In addition to improving ion conductivity and the transference number,single-Li-ion conductors(SLCs)also enable the elimination of interfacial side reactions and concentration difference polarization.Therefore,the SLCs can achieve high performance in solid-state batteries with Li metal as anode and organic molecule as cathode.Covalent organic frameworks(COFs)are leading candidates for constructing SLCs because of the excellent 1D channels and accurate chemical-modification skeleton.Herein,various contents of lithium-sulfonated covalently anchored COFs(denoted as LiO,S-COF1 and LiO,S-COF2)are controllably synthesized as SLCs.Due to the directional ion channels,high Li contents,and single-ion frameworks,LiO,SCOF2 shows exceptional Li-ion conductivity of 5.47×10^(-5)S.cm^(-1),high transference number of 0.93,and low activation energy of 0.15eV at room temperature.Such preeminent Li-ion-transported properties of LiO_(3)S-F2 permit stable Li+plating/stripping in a symmetric lithium metal battery,effectively impeding the Li dendrite growth in a liquid cell.Moreover,the designed quasi-solid-state cell(organic anthraquinone(AQ)as cathode,Li metal as anode,and LiO_(3)S-COF2 as electrolyte)shows high-capacity retention and rate behavior.Consequently,LiO_(3)S-COF2 implies a potential value restraining the dissolution of small organic molecules and Li dendrite growth.

关键词： lithium Battery restrain

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