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Extracellular Disintegration of Viral Proteins as an Innovative Strategy for Developing Broad-Spectrum Antivirals Against Coronavirus

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CCS Chemistry 2024年第2期6卷 487-496页

作者： Ke Sun Zhe Ding Xiaoying jia Haonan Cheng Yingwen Li Yan Wu Zhuoyu Li Xiaohua Huang Fangxu Pu Entao Li Guiyou Wang Wei Wang Yun Ding gary Wong Sandra Chiu jiaming Lan Aiguo Hu Shanghai Key Laboratory of Advanced Polymeric Materials School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237 CAS Key Laboratory of Molecular Virology&Immunology Chinese Academy of SciencesShanghai 200031 University of the Chinese Academy of Sciences Beijing 100049 State Key Laboratory of Virology Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071 Division of Life Sciences and Medicine University of Science and Technology of ChinaHefeiAnhui 230027 Department of Clinical Laboratory The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001

The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has claimedmillions of lives and caused innumerable economic losses ***,state-of-the-art treatments still lag behind the continual emergence of new *** to resolving this issue is developing antivirals to deactivate coronaviruses regardless of their structural ***,we report an innovative antiviral strategy involving extracellular disintegration of viral proteins with hyperanion-grafted enediyne(EDY)*** core EDY generates reactive radical species and causes significant damage to the spike protein of coronavirus,while the hyperanion groups ensure negligible cytotoxicity of the *** EDYs exhibit antiviral activity down to nanomolar concentrations,and the selectivity index of up to 20,000 against four kinds of human coronavirus,including the SARS-CoV-2 Omicron variant,suggesting the high potential of this new strategy in combating the COVID-19 pandemic and a future“disease X.”

关键词： enediyne broad spectrum antiviral protein disintegration coronavirus polyanions

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Endogenous testosterone and mortality risk

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Asian journal of Andrology 2018年第2期20卷 115-119页

作者： Emily j Meye gary Wittert Endocrine Diabetes and Metabolic Unit Royal Adelaide Hospital Port Road SA 5000 Australia Discipline of Medicine University of Adelaide Adelaide SA 5000 Australia Discipline of Medicine and Freemasons Foundation Centre for Men's Health University of Adelaide SA 5000 Australia

In men, obesity and metabolic complications are associated with lower serum testosterone （T） and dihydrotestosterone （DHT） and an increased risk of, and mortality from, multiple chronic diseases in addition to cardiovascular disease （CVD）. The causal interrelationships between these factors remain a matter of debate. In men with untreated congenital and lifelong forms of hypogonadotropic hypogonadism, there appears to be no increased risk. Men with Klinefelter＇s syndrome have an increased risk of various types of cancers, as well as CVD, which persist despite T therapy. In the absence of pathology of the hypothalamic-pituitary- gonadal axis, the effect of modest reductions in serum T in aging men is unclear. The prevalence of low serum T concentrations is high in men with cancer, renal disease, and respiratory disease and is likely to be an indicator of severity of systemic disease, not hypogonadism. Some population-based studies have found low serum T to be associated with a higher risk of deaths attributed to cancer, renal disease, and respiratory disease, while others have not. Although a meta-analysis of longitudinal studies has shown an association between low serum T and all-cause mortality, marked heterogeneity between studies limited a firm conclusion. Therefore, while a decrease in T particularly occurring later in life may be associated with an increase in all-cause and specific types of mortality in men, the differential effects, if any, of T and other sex steroids as compared to health and lifestyle factors are unknown at the current time.

关键词： hypogonadism mortality testosterone

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Analysis of Longitudinal Profiles along the Eastern Margin of the Qinghai-Tibetan Plateau

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journal of Mountain Science 2013年第4期10卷 643-657页

作者： Simon j. Aiken gary j. Brierley School of Environment the University of AucklandAuckland 1010 New Zealand

Resulting from the collision of the Eurasian and Indian plates, the Qinghai-Tibetan Plateau is commonly known as the ＇roof of the world＇. Collectively the Yarlung Tsangpo, Nu, Laneang, Yangtze, Yalong, and Yellow River basins drain the eastern margin of the plateau. In this paper, we utilize Shuttle Radar Topography Mission elevation data to examine morphometric and relief attributes of these basins to reveal insights rates of incision. A robust into tectonic activity and technique using Maflab is proposed to alleviate errors associated with SRTM data in the derivation of river longitudinal profiles. Convex longitudinal profiles are interpreted to be a product of uplift rates that exceed rates of channel incision along the entire margin of the Qinghai- Tibetan Plateau. Highest relief towards the south reflects extensive fluvial incision. High relief is also prominent along major active faults. Erosion patterns are related to distance from knickpoints. Highest rates of erosion and incision are evident towards the south, with decreasing values towards the north, suggesting a link between tectonic activity and erosion.

关键词： Longitudinal profile Erosion Relief Tectonics Qinghai-Tibetan Plateau

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Recovery rates of persistent post-COVID-19 olfactory dysfunction using psychophysical assessment:A longitudinal cohort study

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World journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 79-87页

作者： jeremy P.Tervo Patricia T.jacobson Brandon j.Vilarello Tiana M.Saak Francesco F.Caruana Liam W.Gallagher joseph B.gary David A.Gudis Paule V.joseph D.P.Devanand Terry E.Goldberg jonathan B.Overdevest Columbia University Vagelos College of Physicians and Surgeons New YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery New York-Presbyterian/Columbia University Irving Medical CenterNew YorkNew YorkUSA Department of Otolaryngology-Head and Neck Surgery University of PittsburghPittsburghPennsylvaniaUSA Department of Otolaryngology-Head and Neck Surgery University of MinnesotaMinneapolisMinnesotaUSA National Institute of Alcohol Abuse and Alcoholism Section of Sensory Science and Metabolism&National Institute of Nursing ResearchBethesdaMarylandUSA New York-Presbyterian/Columbia University Irving Medical Center New YorkNew YorkUSA

Objectives:Persistent olfactory dysfunction(OD)following loss of smell associated with SARS-CoV-2 infection is a major feature of long *** on the prevalence of persistent OD predominantly rely on self-reported olfactory *** studies have tracked longitudinal rates of recovery using psychophysical assessment among patients presenting for evaluation of persistent OD beyond a window of acute *** anchored in standardized testing methods are needed to counsel patients who fail to acutely regain their sense of *** study aims to quantify the degree of persistent OD in post-COVID-19 patients who experience subjective and psychophysical ***:We grouped participants presenting for OD evaluation into cohorts based on both subjective and psychophysical olfactory status at a baseline assessment and assessed their olfactory abilities with a visual analogue scale and the Sniffin'Sticks extended test at baseline and 1-year time *** had confirmed a history of COVID-19 by lab evaluation or clinical diagnosis if lab evaluation was not ***:Baseline olfactory evaluation was completed by 122 participants,53 of whom completed the 1-year follow-up *** participants presenting with perceived OD,74.5%had confirmed psychophysical OD at baseline,with 55.1%at 1-year *** had reliable trends in self-rated versus psychophysically tested olfactory function at both time *** total threshold,discrimination,and identification(TDI)score improved by+3.25 points in the cohort with psychophysical OD(p=0.0005),with this improvement largely attributable to an increase in median threshold scores(+2.75 points;p=0.0004).Conclusions:OD persists in a significant number of patients who fail to acutely recovery their sense of smell after COVID-19,with many demonstrating lingering deficits at *** in threshold,but not discrimination or identification,most significantly mediate improvement

关键词： long COVID olfaction post-COVID condition smell dysfunction

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Nitric oxide: promoter or suppressor of programmed cell death?

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Protein & Cell 2010年第2期1卷 133-142页

作者： Yiqin Wang Chen Chen gary j.Loake Chengcai Chu National Key Laboratory of Plant Genomics and National Centre for Plant Gene Research Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijing 100101China Beijing Forestry University Beijing 100083China Institute of Molecular Plant Sciences School of Biological SciencesUniversity of EdinburghKing’s BuildingsEdinburgh EH93JRUnited Kingdom

Nitric oxide(NO)is a short-lived gaseous free radical that predominantly functions as a messenger and effector *** affects a variety of physiological processes,including programmed cell death(PCD)through cyclic guanosine monophosphate(cGMP)-dependent and-independent *** this field,dominant discoveries are the diverse apoptosis networks in mammalian cells,which involve signals primarily via death receptors(extrinsic pathway)or the mitochondria(intrinsic pathway)that recruit caspases as effector *** plants,PCD shares some similarities with animal cells,but NO is involved in PCD induction via interacting with pathways of *** has both promoting and suppressing effects on cell death,depending on a variety of factors,such as cell type,cellular redox status,and the flux and dose of local *** this article,we focus on how NO regulates the apoptotic signal cascade through protein S-nitrosylation and review the recent progress on mechanisms of PCD in both mammalian and plant cells.

关键词： nitric oxide S-nitrosylation programmed cell death

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Intrinsically photosensitive retinal ganglion cells

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Science China(Life Sciences) 2010年第1期53卷 58-67页

作者： gary E.PICKARD Patricia j.SOLLARS School of Veterinary Medicine and Biomedical Sciences University of Nebraska

A new mammalian photoreceptor was recently discovered to reside in the ganglion cell layer of the inner *** intrinsically photosensitive retinal ganglion cells(ipRGCs) express a photopigment,melanopsin,that confers upon them the ability to respond to light in the absence of all rod and cone photoreceptor *** relatively few in number,ipRGCs extend their dendrites across large expanses of the retina making them ideally suited to function as irradiance detectors to assess changes in ambient light *** in ipRGCs appears to be mediated by transient receptor potential channels more closely resembling the phototransduction cascade of invertebrate rather than vertebrate *** convey irradiance information centrally via the optic nerve to influence several *** are the primary retinal input to the hypothalamic suprachiasmatic nucleus(SCN),a circadian oscillator and biological clock,and this input entrains the SCN to the day/night *** contribute irradiance signals that regulate pupil size and they also provide signals that interface with the autonomic nervous system to regulate rhythmic gene activity in major organs of the *** also provide excitatory drive to dopaminergic amacrine cells in the retina,providing a novel basis for the restructuring of retinal circuits by *** we review the ground-breaking discoveries,current progress and directions for future investigation.

关键词： melanopsin circadian rhythms suprachiasmatic nucleus retina pupillary light reflex

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Using NMR-detected hydrogen-deuterium exchange to quantify protein stability in cosolutes,under crowded conditions in vitro and in cells

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Magnetic Resonance Letters 2023年第4期3卷 319-326页

作者： I-Te Chu gary j.Pielak Department of Chemistry University of North Carolina at Chapel Hill(UNC-CH)Chapel HillNC27599-3290United States Department of Biochemistry and Biophysics UNC-CHChapel HillNC27599-3290United States Lineberger Cancer Center UNC-CHChapel HillNC27599-3290United States Integrative Program for Biological and Genome Sciences UNC-CHChapel HillNC27599-7100United States

We review the use of nuclear magnetic resonance(NMR)spectroscopy to assess the exchange of amide protons for deuterons(HDX)in efforts to understand how high concentration of cosolutes,especially macromolecules,affect the equilibrium thermodynamics of protein *** NMR is the only method that can routinely provide such data at the level of individual amino *** begin by discussing the properties of the protein systems required to yield equilibrium thermodynamic data and then review publications using osmolytes,sugars,denaturants,synthetic polymers,proteins,cytoplasm and in cells.

关键词： Amide proton exchange Cosolutes Equilibrium thermodynamics Macromolecular Crowding Osmolytes Protein stability

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Preliminary Insights into the Habitat Preferences of the Centralian Bandy Bandy (Vermicella vermiformis)(Squamata: Elapidae) in Central Australia

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Asian Herpetological Research 2014年第1期5卷 49-53页

作者： Peter j.MCDONALD gary W.LUCK Flora and Fauna Division Department of Land Resource Management Northern Territory Government School of Environmental Sciences Charles Sturt University Institude for Land Water and Society Charles Sturt University

Bandy Bandy’s（Vermicella spp.）are a striking,black-and-white ringed genus of small elapid snakes endemic to *** taxa are burrowers and little is known of their biology and *** investigated the habitat preferences of the only arid-dwelling species,the centralian bandy bandy（Vermicella vermiformis）,in the MacDonnell Ranges west of Alice Springs in the Northern *** systematic road-cruising,we encountered *** over a 12 months period between 2009 and *** used logistic regression to model the occurrence of the species against a range of different habitat variables collected at multiple *** the small sample size,*** exhibited a clear preference for acacia shrubland habitats,with acacia variables present in all AICc ranked models in the 95%confidence *** factors driving this association,together with the preference for habitat not burnt in the most recent wildfires,may be related to the abundance of their only known prey,blind snakes（Ramphotyphlops spp.）.

关键词： Snake Arid Acacia Fire Ramphotyphlops

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H_2O_2-induced Leaf Cell Death and the Crosstalk of Reactive Nitric/Oxygen Species

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journal of Integrative Plant Biology 2013年第3期55卷 202-208页

作者： Yiqin Wang Aihong Lin gary j. Loake Chengcai Chu State Key Laboratory of Plant Genomics and National Center for Plant Gene Research (Beijing) Institute of Genetics and Developmental Biologythe Chinese Academy of Sciences National Agricultural Technology Park Institute of Molecular Plant Sciences School of Biological SciencesUniversity of Edinburgh

In plants, the chloroplast is the main reactive oxygen species （ROS） producing site under high light stress. Catalase （CAT）, which decomposes hydrogen peroxide （H2O2）, is one of the controlling enzymes that maintains leaf redox homeostasis. The catalase mutants with reduced leaf catalase activity from different plant species exhibit an H2O2-induced leaf cell death phenotype. This phenotype was differently affected by light intensity or photoperiod, which may be caused by plant species, leaf redox status or growth conditions. In the rice CAT mutant nitric oxide excess 1 （noe1）, higher H2O2 levels induced the generation of nitric oxide （NO） and higher S-nitrosothiol （SNO） levels, suggesting that NO acts as an important endogenous mediator in H2O2-induced leaf cell death. As a free radical, NO could also react with other intracellular and extracellular targets and form a series of related molecules, collectively called reactive nitrogen species （RNS）. Recent studies have revealed that both RNS and ROS are important partners in plant leaf cell death. Here, we summarize the recent progress on H2O2-induced leaf cell death and the crosstalk of RNS and ROS signals in the plant hypersensitive response （HR）, leaf senescence, and other forms of leaf cell death triggered by diverse environmental conditions.

关键词： H2O2 induced leaf cell death hypersensitive response leaf senescence nitric oxide reactive nitrogen species reactive oxygenspecies.

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Systems Analysis and Design; gary B. Shelly, Thomas j. Cashman, Harry j. Rosenblatt 4th ed.

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2001年

作者： gary B. Shelly Thomas j. Cashman Harry j. Rosenblatt

Includes index.

ISBN: (纸本)0789559579

Includes index.

关键词： System design.

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