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Multifaceted role of mTOR (mammalian target of rapamycin) signaling pathway in human health and disease

Signal Transduction and Targeted Therapy 2023年第11期8卷 5159-5183页

作者： Vivek Panwar Aishwarya Singh Manini bhatt Rajiv K.Tonk Shavkatjon Azizov Agha Saquib Raza Shinjinee Sengupta deepak Kumar Manoj Garg Department of Pharmaceutical Chemistry School of Pharmaceutical SciencesShoolini UniversitySolanHimachal Pradesh173229India Amity Institute of Molecular Medicine and Stem Cell Research(AIMMSCR) Amity University Uttar PradeshSector-125NoidaUttar Pradesh201313India Department of Biomedical Engineering Indian Institute of TechnologyRoparPunjab140001India Department of Pharmaceutical Chemistry School of Pharmaceutical SciencesDelhi Pharmaceutical Sciences and Research University(DPSRU)New Delhi110017India laboratory of Biological Active Macromolecular Systems Institute of Bioorganic ChemistryAcademy of Sciences UzbekistanTashkent100125Uzbekistan Faculty of life Sciences Pharmaceutical Technical University100084TashkentUzbekistan Rajive Gandhi Super Speciality Hospital TahirpurNew Delhi110093India

The mammalian target of rapamycin(mTOR)is a protein kinase that controls cellular metabolism,catabolism,immune responses,autophagy,survival,proliferation,and migration,to maintain cellular *** mTOR signaling cascade consists of two distinct multi-subunit complexes named mTOR complex 1/2(mTORC1/2).mTOR catalyzes the phosphorylation of several critical proteins like AKT,protein kinase C,insulin growth factor receptor(IGF-1R),4E binding protein 1(4E-BP1),ribosomal protein S6 kinase(S6K),transcription factor EB(TFEB),sterol-responsive element-binding proteins(SREBPs),lipin-1,and Unc-51-like autophagy-activating *** signaling plays a central role in regulating translation,lipid synthesis,nucleotide synthesis,biogenesis of lysosomes,nutrient sensing,and growth factor *** emerging pieces of evidence have revealed that the constitutive activation of the mTOR pathway due to mutations/amplification/deletion in either mTOR and its complexes(mTORC1 and mTORC2)or upstream targets is responsible for aging,neurological diseases,and human ***,we provide the detailed structure of mTOR,its complexes,and the comprehensive role of upstream regulators,as well as downstream effectors of mTOR signaling cascades in the metabolism,biogenesis of biomolecules,immune responses,and ***,we summarize the potential of long noncoding RNAs(lncRNAs)as an important modulator of mTOR ***,we have highlighted the potential of mTOR signaling in aging,neurological disorders,human cancers,cancer stem cells,and drug ***,we discuss the developments for the therapeutic targeting of mTOR signaling with improved anticancer efficacy for the benefit of cancer patients in clinics.

关键词： metabolism homeostasis mTOR

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成人缺血性卒中早期处理指南

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国际脑血管病杂志 2007年第6期15卷 401-450页

作者： Harold P. Adams Gregory del Zoppo Mark J. Alberts deepak l. bhatt lawrence Brass Anthony Furlan Robert l. Grubb Randall T. Higashida Edward C. Jauch Chelsea Kidwell Patrick D. lyden lewis B. Morgenstern Adnan I. Qureshi Robert H. Rosenwasser Phillip A. Scott Eelco F.M. Wijdicks 李焰生（译）熊昕丽（译）林岩（译）沈沸（译）俞羚（译）邹静（译）张静芳（译）孙亚蒙（译）周洁茹（译）蒋仙国（译）陈莺（译）不详上海交通大学医学院附属仁济医院神经内科 200127

本指南旨在对成年急性缺血性卒中患者评价和治疗各要素的现有证据做一回顾。目标读者是那些为发病后48h内的卒中患者提供治疗的内科医生和其他急诊医疗保健人员。另外，也包括向医疗保健政策制定者提供的信息。方法：专家小组成员由美... 详细信息

本指南旨在对成年急性缺血性卒中患者评价和治疗各要素的现有证据做一回顾。目标读者是那些为发病后48h内的卒中患者提供治疗的内科医生和其他急诊医疗保健人员。另外，也包括向医疗保健政策制定者提供的信息。方法：专家小组成员由美国心脏协会（AHA）卒中委员会科学声明监督委员会任命，他们代表了来自不同领域的专家。专家小组以2003年后发表的报道为重点，对相关文献进行回顾，采用AHA卒中委员会的证据水平分级标准对证据进行分级并做出推荐。本声明经专家小组认可后，再由AHA科学顾问和协调委员会进行同行评议和正式批准。本指南打算在3年内做全面更新。结果：对急性缺血性卒中患者的处理仍然是多方面的，包括尚未在临床试验中进行过验证的一些医疗诊治方面。本声明包括从急诊医疗服务人员开始接触患者到入院初期处理的推荐意见。静脉重组组织型纤溶酶原激活剂仍然是已得到证实的最有效的卒中急诊治疗干预方法。包括动脉应用溶栓药和机械介入在内的一些方法显示出希望。因为许多推荐是在有限的证据基础上做出的，因此需要对急性缺血性卒中的治疗进行更多的研究。

关键词： AHA科学声明急诊医疗服务卒中急性脑梗死组织型纤溶酶原激活剂

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Neutronic analysis of Indian helium-cooled solid breeder tritium breeding module for testing in ITER

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Plasma Science and Technology 2022年第6期24卷 189-195页

作者： H l SWAMI deepak SHARMA C DANANI P CHAUDHARI R SRINIVASAN Rajesh KUMAR Institute for Plasma Research Gandhinagar 382428India Homi Bhabha National Institute AnushaktinagarMumbai 400094India

India has proposed the helium-cooled solid breeder blanket concept as a tritium breeding module to be tested in *** module has lithium titanate for tritium breeding and beryllium for neutron *** also enhances tritium breeding.A design for the module is prepared for detailed *** analysis is performed to assess the tritium breeding rate,neutron distribution,and heat distribution in the *** tritium production distribution in submodules is evaluated to support the tritium transport *** tritium breeding density in the radial direction of the module is also assessed for further optimization of the *** heat deposition profile of the entire module is generated to support the heat removal circuit *** estimated neutron spectrum in the radial direction also provides a more in-depth picture of the nuclear interactions inside the material *** total tritium produced in the HCSB module is around 13.87 mg per full day of operation of ITER,considering the 400 s ON time and 1400 s dwell *** estimated nuclear heat load on the entire module is around 474 kW,which will be removed by the high-pressure helium cooling *** heat deposition in the test blanket model(TBM)is huge(around 9 GJ)for an entire day of operation of ITER,which demonstrates the scale of power that can be produced through a fusion reactor *** per the Brayton cycle,it is equivalent to 3.6 GJ of electrical *** terms of power production,this would be around 1655 MWh *** evaluation is carried out using the MCNP5 Monte Carlo radiation transport code and FEDNl 2.1 nuclear cross section *** HCSB TBM neutronic performance demonstrates the tritium production capability and high heat deposition.

关键词： HCSB TBM tritium nuclear heat ITER

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Immunotherapy for recurrent hepatocellular carcinoma

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World Journal of Gastroenterology 2023年第15期29卷 2261-2271页

作者： Ahan bhatt Jennifer Wu Division of Hematology and Oncology Perlmutter Cancer Center of NYU Langone HealthNYU School of MedicineNew YorkNY 10016United States

Hepatocellular carcinoma(HCC)is presented frequently in late stages that are not amenable for curative *** for patients who can undergo resection for curative treatment of HCC,up to 50%*** patients who were not exposed to systemic therapy prior to recurrence,recurrence frequently cannot be subjected to curative therapy or local *** patients have several options of immunotherapy(IO).This includes programmed cell death protein 1(PD-1)and cytotoxic T-lymphocyte associated protein 4 treatment,combination of PD-1 and vascular endothelial growth factor inhibitor or single agent PD-1 therapy when all other options are deemed *** are also investigational therapies in this area that explore either PD-1 and tyrosine kinase inhibitors or a novel agent in addition to PD-1 with vascular endothelial growth factor *** minireview explored IO options for patients with recurrent HCC who were not exposed to systemic therapy at the initial *** also discussed potential IO options for patients with recurrent HCC who were exposed to first-line therapy with curative intent at diagnosis.

关键词： liver neoplasms Immune checkpoint blockade Combination drug therapy PD-1-PD-l1 blockade CTlA-4 inhibitor

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Extracellular matrix and biomimetic engineering microenvironment for neuronal differentiation

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Neural Regeneration Research 2020年第4期15卷 573-585页

作者： deepak Jain Sabrina Mattiassi Eyleen l.Goh Evelyn K.F.Yim Department of Chemical Engineering University of WaterlooWaterlooOntarioCanada Neuroscience Academic Clinical Programme Duke-NUS Medical SchoolSingapore

Extracellular matrix(ECM)influences cell differentiation through its structural and biochemical *** nervous system,neuronal behavior is influenced by these ECMs structures which are present in a meshwork,fibrous,or tubular forms encompassing specific molecular *** addition to contact guidance,ECM composition and structures also exert its effect on neuronal *** short report reviewed the native ECM structure and composition in central nervous system and peripheral nervous system,and their impact on neural regeneration and neuronal *** topographies,stem cells have been differentiated to ***,focussing on engineered biomimicking topographies,we highlighted the role of anisotropic topographies in stem cell differentiation to neurons and its recent temporal application for efficient neuronal differentiation.

关键词： biomimetic platforms biophysical cues contact guidance extracellular matrix neuronal development neural regeneration neural stem cell niche neuronal differentiation neuronal maturation stem cell topography

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Optimization of Threshold Ranges for Rapid Flood Inundation Mapping by Evaluating Backscatter Profiles of High Incidence Angle SAR Images

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International Journal of Disaster Risk Science 2012年第2期3卷 113-122页

作者： Panchagnula Manjusree l.Prasanna Kumar Chandra Mohan bhatt Goru Srinivasa Rao Veerubhotla Bhanumurthy Disaster Management Support Group Remote Sensing Applications AreaNational Remote Sensing CentreIndian Space Research Organization(ISRO)BalanagarHyderabad 500625India

Rapid satellite-based flood inundation mapping and delivery of flood inundation maps during a flood event can provide crucial information for planners and decision makers to prioritize relief and rescue operations. The present study is undertaken to optimize the threshold ranges for the classification of flood water in Synthetic Aperture Radar(SAR) images(of 20° to 49° incidence angles) for quick flood inundation mapping and response during flood disasters. This is done through assessing the signature of flood water in Horizontal transmit and Horizontal received(HH), Horizontal transmit and Vertical received(HV), Vertical transmit and Horizontal received(VH), and Vertical transmit and Vertical received(VV) polarization radar data. The mean backscattering signature profiles of various water bodies were analyzed to discriminate flood water from other water bodies. The study shows that there is better demarcation of land-water surface in HH polarization. VV polarization has the potential to identify partially submerged features, which can be useful in flood damage assessments. The backscatter of flood water in HV and VH is the same and both HV and VH polarizations are adequate for the mapping of flood water. At near range to far range,-8 to-12 d B,-15 to-24 d B, and-6 to-15 d B can be used as optimum ranges for the classification of flood water in HH, HV, and VV polarizations. These optimum threshold ranges can be applied to the automation of flood mapping using SAR images in near-real time, where much time was often spent on finding the thresholds in order to produce flood inundation maps in a short time from the onset of flood disasters and deliver such maps to the concerned agencies.

关键词： flood polarization signature

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Gindarudine,a novel morphine alkaloid from Stephania glabra

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Chinese Chemical letters 2009年第7期20卷 823-826页

作者： deepak Kumar Semwal Usha Rawat Department ofChemistry H.N.B.Garhwal University SrinagarUttarakhand 246174 India

A novel morphine alkaloid, named gindarudine 1 has been isolated from ethanol extract of Stephania glabra tubers, together with four known alkaloids, palmatine, dehydrocorydalmine, stepharanine, and 8-（4＇-methoxybenzyl）-xylopinine. Compound 1 was elucidated as 3,6-O,N-detrimethyl-10-hydroxy-l-methoxy-thebaine by means of spectroscopic data including 2D NMR studies. C 2009 deepak Kumar Semwal. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

关键词： Stephania glabra Menispermaceae Gindaru Gindarudine

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Delivery strategies for CRISPR/Cas genome editing tool for retinal dystrophies:challenges and opportunities

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Asian Journal of Pharmaceutical Sciences 2022年第2期17卷 153-176页

作者： Aayushi lohia deepak Kumar Sahel Mohd Salman Vivek Singh Indumathi Mariappan Anupama Mittal deepak Chitkara Department of Pharmacy Birla Institute of Technology and SciencePilani(BITS-Pilani)Vidya Vihar CampusPilani 333031India Prof.Brien Holden Eye Research Center Champalimaud Translational Centre for Eye ResearchL.V.Prasad Eye InstituteKallam Anji Reddy CampusHyderabad 500034India

CRISPR/Cas,an adaptive immune system in bacteria,has been adopted as an efficient and precise tool for site-specific gene editing with potential therapeutic *** has been explored for a variety of applications,including gene modulation,epigenome editing,diagnosis,mRNA editing,*** has found applications in retinal dystrophic conditions including progressive cone and cone-rod dystrophies,congenital stationary night blindness,X-linked juvenile retinoschisis,retinitis pigmentosa,age-related macular degeneration,leber’s congenital amaurosis,*** of the therapies for retinal dystrophic conditions work by regressing symptoms instead of reversing the ***/Cas9 through indel could impart beneficial effects in the reversal of gene mutations in dystrophic *** research has also consolidated on the approaches of using CRISPR systems for retinal dystrophies but their delivery to the posterior part of the eye is a major concern due to high molecular weight,negative charge,and in vivo stability of CRISPR ***,non-viral vectors have gained interest due to their potential in tissue-specific nucleic acid(miRNA/siRNA/CRISPR)*** review highlights the opportunities of retinal dystrophies management using CRISPR/Cas nanomedicine.

关键词： CRISPR/Cas9 Gene editing Retinal dystrophies Non-viral nanocarriers

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long-term open circuit microbial electrosynthesis system promotes methanogenesis

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Journal of Energy Chemistry 2020年第2期29卷 3-6页

作者： Raúl Mateos Adrián Escapa María Isabel San-Martín Heleen De Wever Ana Sotres deepak Pant Chemical and Environmental Bioprocess Engineering Group Natural Resources Institute(IRENA)University of LeonLeon 24071Spain Department of Electrical Engineering and Automatic Systems Universidad de LeonLeon 24071Spain Reparation and Conversion Technology Flemish Institute for Technological Research(VITO)Mol 2400Belgium

Microbial electrosynthesis(MES) can potentially provide a mean for storing renewable energy surpluses as chemical energy. However, the fluctuating nature of these energy sources may represent a threat to MES, as the microbial communities that develop on the biocathode rely on the continuous existence of a polarized electrode. This work assesses how MES performance, product generation and microbial community evolution are affected by a long-period(6 weeks) power off(open circuit). Acetogenic and H2-producing bacteria activity recovered after reconnection. However, few days later syntrophic acetate oxidation bacteria and H2-consuming methanogens became dominant, producing CH4 as the main product, via electromethanogenesis and the syntrophic interaction between eubacterial and archaeal communities which consume both the acetic acid and the hydrogen present in the cathode environment. Thus,the system proved to be resilient to a long-term power interruption in terms of electroactivity. At the same time, these results demonstrated that the system could be extensively affected in both end product generation and microbial communities.

关键词： Biocathode Electromethanogenesis Microbial electrosynthesis Microbial community dynamics Methanogens Acetogens

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Variation in Heat-shock Proteins and Photosynthetic Thermotolerance among Natural Populations of Chenopodium album *** Contrasting Thermal Environments:Implications for Plant Responses to Global Warming

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Journal of Integrative Plant Biology 2008年第11期50卷 1440-1451页

作者： deepak Barua Scott A.Heckathorn James S.Coleman Department of Biology Syracuse University Department of Organismic and Evolutionary Biology Harvard University Department of Environmental Sciences University of Toledo

Production of heat-shock proteins （Hsps） is a key adaptation to acute heat stress and will be important in determining plant responses to climate change. Further, intraspecifc variation in Hsps, which will influence species-level response to global warming, has rarely been examined in naturally occurring plants. To understand intraspecific variation in plant Hsps and its relevance to global warming, we examined Hsp content and thermotolerance in five naturally occurring populations of Chenopodium album l. from contrasting thermal environments grown at low and high temperatures. As expected, Hsp accumulation varied between populations, but this was related more to habitat variability than to mean temperature. Unexpectedly, Hsp accumulation decreased with increasing variability of habitat temperatures. Hsp accumulation also decreased with increased experimental growth temperatures. Physiological thermotolerance was partitioned into basal and induced components. As with Hsps, induced thermotolerance decreased with increasing temperature variability. Thus, populations native to the more stressful habitats, or grown at higher temperatures, had lower Hsp levels and induced thermotolerance, suggesting a greater reliance on basal mechanisms for thermotolerance. These results suggest that future global climate change will differentially impact ecotypes within species, possibly by selecting for increased basal versus inducible thermotolerance.

关键词： acclimation photosynthesis stress proteins temperature.

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