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SARS-CoV-2 spike protein binds to bacterial lipopolysaccharide and boosts proinflammatory activity

journal of Molecular Cell Biology 2020年第12期12卷 916-932页

作者： Ganna Petruk Manoj Puthia jitka Petrlova Firdaus Samsudin Ann-Charlotte Stromdahl Samuel Cerps Lena Uller Sven Kjellstrom peter j.bond Artur Schmidtchen Division of Dermatology and Venereology Department of Clinical SciencesLund UniversitySE-22184 LundSweden Bioinformatics Institute(BI) Agency for ScienceTechnology and Research(A*STAR)Singapore 138671Singapore Unit of Respiratory Immunopharmacology Department of Experimental MedicineLund UniversitySE-22184 LundSweden Division of Mass Spectrometry Department of Clinical SciencesLund UniversitySE-22184 LundSweden Department of Biological Sciences National University of SingaporeSingapore 117543Singapore Copenhagen Wound Healing Center Bispebjerg HospitalDepartment of Biomedical SciencesUniversity of CopenhagenDK 2400 CopenhagenDenmark Dermatology Skane University HospitalSE-22185 LundSweden

There is a link between high lipopolysaccharide(LPS)levels in the blood and the metabolic syndrome,and metabolic syndrome predisposes patients to severe ***,we define an interaction between SARS-CoV-2 spike(S)protein and LPS,leading to aggravated inflammation in vitro and in *** gel electrophoresis demonstrated that SARS-CoV-2 S protein binds to *** thermophoresis yielded a of〜47 nM for the *** modeling and all-atom molecular dynamics simulations further substantiated the experimental results,identifying a main LPS-binding site in SARS-CoV-2 S protein.S protein,when combined with low levels of LPS,boosted nuclear factor-kappa B(NF-k B)activation in monocytic THP-1 cells and cytokine responses in human blood and peripheral blood mononuclear cells,*** in vitro inflammatory response was further validated by employing NF-kB reporter mice and in vivo *** light scattering,transmission electron microscopy,and LPS-FITC analyses demonstrated that S protein modulated the aggregation state of LPS,providing a molecular explanation for the observed boosting *** together,our results provide an interesting molecular link between excessive inflammation during infection with SARS-CoV-2 and comorbidities involving increased levels of bacterial endotoxins.

关键词： COVID-19 SARS-CoV-2 spike protein lipopolysaccharide inflammation aggregation metabolic syndrome

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SARS-CoV-2 spike protein as a bacterial lipopolysaccharide delivery system in an overzealous inflammatory cascade

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journal of Molecular Cell Biology 2022年第9期14卷 26-39页

作者： Firdaus Samsudin Palur Raghuvamsi Ganna Petruk Manoj Puthia jitka Petrlova Paul MacAry Ganesh S.Anand peter j.bond Artur Schmidtchen Bioinformatics Institute(BIl) Agency for ScienceTechnology and Research(A*STAR)Singapore 138671Singapore Department of Biological Sciences National University of SingaporeSingapore 117543Singapore Division of Dermatology and Venereology Department of Clinical SciencesLund UniversitySE-22184 LundSweden Life Sciences Institute Centre for Life SciencesNational University of SingaporeSingapore 117546Singapore Department of Chemistry The Pennsylvania State UniversityPA 16801USA Copenhagen Wound Healing Center Bispebjerg HospitalDepartment of Biomedical SciencesUniversity of CopenhagenDK-2400 CopenhagenDenmark

Accumulating evidence indicates a potential role for bacterial lipopolysaccharide(LPs)in the overactivation of the immune response during SARS-CoV-2 *** is recognized by Toll-like receptor 4,mediating proinflammatory *** previously reported that LPS directly interacts with SARS-CoV-2 spike(S)protein and enhances proinflammatory *** native gel electrophoresis and hydrogen-deuterium exchange mass spectrometry,we showed that LPS binds to multiple hydrophobic pockets spanning both the S1 and S2 subunits of the S *** simulations validated by a microscale thermophoresis binding assay revealed that LPS binds to the S2 pocket with a lower affinity compared to S1,suggesting a role as an intermediate in LPS ***,nuclear factor-kappa B(NF-kB)activation in monocytic THP-1 cells is strongly boosted by *** NF-kB reporter mice followed by bioimaging,a boosting effect was observed for both S1 and S2,with the former potentially facilitated by *** Omicron S variant binds to LPS,but with reduced affinity and LPS boosting in vitro and in *** together,the data provide a molecular mechanism by which S protein augments LPS-mediated hyperinflammation.

关键词： COVID-19 SARS-CoV-2 spike protein lipopolysaccharide TLR4 hyperinflammation

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Stable diffusion gradients in microfluidic conduits bounded by fluid walls

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Microsystems & Nanoengineering 2024年第3期10卷 357-367页

作者： Federico Nebuloni Cyril Deroy peter R.Cook Edmond j.Walsh Department of Engineering Science Osney Thermo-Fluids InstituteUniversity of OxfordOxford OX20ESUK Sir William Dunn School of Pathology University of OxfordOxford OX13REUK

Assays mimicking in vitro the concentration gradients triggering biological responses like those involved in fighting infections and blood clotting are essential for biomedical *** assays prove especially attractive as they allow precise control of gradient shape allied to a reduction in *** microfluidic devices are fabricated using solid plastics that prevent direct access to responding ***-walled microfluidics allows the manufacture of circuits on standard Petri dishes in seconds,coupled to simple operating methods;cell-culture medium sitting in a standard dish is confined to circuits by fluid walls made of an immiscible *** develop and experimentally validate an analytical model of diffusion between two or more aqueous streams flowing at different rates into a fluid-walled conduit with the cross-section of a circular *** solid walls,fluid walls morph during flows as pressures fall,with wall shape changing down the *** model is validated experimentally for Fourier numbers<0.1 using fluorescein diffusing between laminar *** enables a priori prediction of concentration gradients throughout a conduit,so allowing rapid circuit design as well as providing bioscientists with an accurate way of predicting local concentrations of bioactive molecules around responsive and nonresponsive cells.

关键词： walls diffusion attractive

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The Global Energy and Water Exchanges(GEWEX)Project in Central Asia:The Case for a Regional Hydroclimate Project

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Advances in Atmospheric Sciences 2024年第5期41卷 777-783页

作者： Michael BRODY Maksim KULIKOV Sagynbek ORUNBAEV peter j.VAN OEVELEN International Agricultural University Tashkent 111200Uzbekistan George Mason University FairfaxVirginia 22030USA University of Central Asia Bishkek 720001Kyrgyz Republic American University of Central Asia Bishkek 720060Kyrgyz Republic International GEWEX project George Mason UniversityFairfaxVirginia 22030USA

Central Asia consists of the former Soviet Republics,Kazakhstan,Kyrgyz Republic,Tajikistan,Turkmenistan,and *** region’s climate is continental,mostly semi-arid to *** is a significant part of the region’s *** its nature of intensive water use,agriculture is extremely vulnerable to climate *** growth and irrigation development have significantly increased the demand for water in the *** climate change issues include melting glaciers and a shrinking snowpack,which are the foundation of the region’s water resources,and a changing precipitation *** glaciers are located in Kyrgyzstan and Tajikistan,leading to transboundary water resource *** already has extremely high *** indicate that Central Asia has been warming and precipitation might be *** warming is expected to increase,but its spatial and temporal distribution depends upon specific global *** of future precipitation show significant uncertainties in type,amount,and *** Hydroclimate Projects(RHPs)are an approach to studying these *** steps to develop an RHP began in 2021 with a widely distributed online survey about these climate *** was followed up with an online workshop and then,in 2023,an in-person workshop,held in Tashkent,*** for the Global Energy and Water Exchanges(GEWEX)project for the region include both observations and modeling,as well as development of better and additional precipitation observations,all of which are topics for the next workshop.A well-designed RHP should lead to reductions in critical climate uncertainties in policy-relevant timeframes that can influence decisions on necessary investments in climate adaptation.

关键词： GEWEX Central Asia climate change agriculture

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Enhancing prognostic accuracy in predicting rectal neuroendocrine neoplasms

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World journal of Gastroenterology 2024年第37期30卷 4087-4089页

作者： Renin peter AA Raj Abdulqadir j Nashwan Department of Medicine Aston Medical SchoolBirmingham B47ETUnited Kingdom Department of Nursing&Midwifery Research Hamad Medical CorporationDoha 3050Qatar

The recently published retrospective study introduces the GATIS score,a new predictive model for rectal neuroendocrine *** analyzing data from a large Chinese multicenter cohort,the study shows that the GATIS score,incor-porating tumor grade,T stage,tumor size,age,and prognostic nutritional index,demonstrates superior predictive power for overall survival and progression-free survival compared to traditional World Health Organization grade and tumor,nodes and metastases staging *** editorial aims to discuss the impor-tance of the GATIS score,its potential impact on clinical practice,and the strengths and limitations of the ***,it explores the significance,methodology,and clinical implications of these findings.

关键词： Rectal neuroendocrine neoplasm Nomogram Random forest Prognosis Overall survival Progression-free survival

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Adaptation in brain structure and respiratory and olfactory structures across environmental gradients in African and North American muroid rodents

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Integrative Zoology 2024年第1期19卷 165-181页

作者： peter j.TAYLOR Aluwani NENGOVHELA Christiane DENYS Graham R.SCOTT Catherine M.IVY Department of Zoology School of Natural and Mathematical SciencesUniversity of VendaThohoyandouSouth Africa Afromontane Unit Department of Zoology and EntomologyUniversity of the Free StatePhuthaditjhabaSouth Africa Department of Mammalogy National MuseumBloemfonteinSouth Africa Institut de Systématique EvolutionBiodiversité(ISYEB)Muséum National d’Histoire NaturelleCNRSSorbonne UniversitéEPHEUniversitéDes AntillesParisFrance Department of Biology McMaster UniversityHamiltonOntarioCanada Guglielmo and Shoemaker Labs Advanced Facility for Avian ResearchUniversity of Western OntarioLondonOntarioCanada

Morphometric studies of 3D micro CT-scanned images can provide insights into the evolution of the brain and sensory structures but such data are still scarce for the most diverse mammalian order of *** reviewed and new data,we tested for convergence to extreme aridity and high elevation in the sensory and brain morphology of rodents,from morphometric data from micro-CT X-ray scans of 174 crania of 16 species of three distantly re-lated African murid(soft-furred mice,Praomyini,laminate-toothed rats,Otomyini,and gerbils,Gerbillinae)clades and one North American cricetid(deer mice and white-footed mice,Peromyscus)*** studies demon-strated convergent evolution acting on the oval window area of the cochlea(enlarged in extremely arid-adapted species of Otomyini and Gerbillinae)and on endocranial volume(reduced in high elevation taxa of Otomyini and Peromyscus).However,contrary to our predictions,we did notfind evidence of convergence in brain struc-ture to aridity,or in the olfactory/respiratory system(turbinate bones)to high *** structure differed,particularly in the petrosal lobules of the cerebellum and the olfactory bulbs,between Otomyini and Gerbillinae,with extreme arid-adapted species in each clade being highly divergent(not convergent)from other species in the same *** observed greater“packing”of the maxillary turbinate bones,which have important respiratory functions,in Peromyscus mice from high and low elevations compared to the high-elevation African Praomyini,but more complex patterns within Peromyscus,probably related to trade-offs in respiratory physiology and heat exchange in the nasal epithelium associated with high-elevation adaptation.

关键词： 3D morphometrics Africa brain size North America Rodentia sensory evolution

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Full-spectrum Bi@SrTiO_(3) for bi-directional promotion effects on photocatalytic redox reaction:Insight into intermediates and mechanism

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journal of Rare Earths 2024年第5期42卷 917-929,I0004页

作者： Bin Liu Nanhao Zhou jun Liu Xinglei Wang peter K.j.Robertson Xiaoyuan Chen Chao Chen jianmin Luo Chuanyi Wang School of Chemistry and Civil Engineering Shaoguan UniversityShaoguan512005China Chengdu Customs Technology Center Chengdu610041China Key Laboratory of Pollutant Chemistry and Environmental Treatment College of Chemistry and Environmental ScienceYili Normal UniversityYining835000China School of Chemistry and Chemical Engineering Queen's University BelfastStranmillis RoadBelfastBT95AGUnited Kingdom Guangzhou Institute of Industrial Intelligence(GIII) Guangzhou511400China

The development of full-spectrum photocatalysts active in the near-infrared(NIR)region has gained increasing attention for deleterious pollutant *** integration of plasmonic metals with semico nductors is an effective way to widen the light re sponse range of photocatalysts due to the strong light absorption and fast plasmonic energy transfer of the localized surface plasmon resonance(LSPR).In this work,the full-spectrum responsive Bi@SrTiO_(3) was prepared via facile solvothermal chemical *** optimal Bi@SrTiO_(3) achieves exceptional photocatalytic Cr(VI)reduction efficiency and tetracycline degradation,realizing bi-directional promotion effects on redox *** to density functional theory(DFT)simulations,the extraordinary photocatalytic performance is attributed to the tunable builtin electric field(IEF)of the Ohmic *** favorable adaptability in real water and high stability of BSTO-25 were proved by experime ntal *** the po ssible photocatalytic mechanism was proposed based on theoretical calculation and experimental ***,the non-toxicity of the BSTO-25 was evaluated by *** cultivation,which further proves the feasibility of treating wastewater with *** work provides a new perspective on constructing full-spectrum-driven photocatalysts for applications dealing with environmental remediation.

关键词： Full-spectrum photocatalysts Localized surface plasmon resonance Ohmic contact Cr(Ⅵ)reduction Antibiotic degradation Rare earths

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Effect of age on the standardized ileal amino acid digestibility of soybean meal and canola meal in broilers

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Animal Nutrition 2024年第1期16卷 11-22页

作者： Mukti Barua M.Reza Abdollahi Faegheh Zaefarian Timothy j.Wester Channarayapatna K.Girish peter V.Chrystal Velmurugu Ravindran Monogastric Research Center School of Agriculture and EnvironmentMassey UniversityPalmerston North 4442New Zealand Department of Animal Science and Nutrition Faculty of Veterinary MedicineChattogram Veterinary and Animal Sciences UniversityKhulshiChattogram 4225Bangladesh Nutrition and Care Animal NutritionEvonik(SEA)Pte.Ltd609927 Singapore Complete Feed Solutions Howick 2145AucklandNew Zealand

Standardized ileal digestibility coefficients(SIDC)of nitrogen(N)and amino acids(AA)in two protein sources(soybean meal[SBM]and canola meal[CM])were investigated at six broiler ages(d 7,14,21,28,35,and 42).Two assay diets were formulated to contain either SBM(413 g/kg)or CM(553 g/kg)as the sole dietary AA *** dioxide(5 g/kg)was added as an indigestible marker.A total of 696 male broilers at 1 d old were allotted to 12 replicate cages per age *** assay diet was offered to birds for 4 d prior to the ileal digesta collection on d 7(14 birds/cage),14(12 birds/cage),21(10 birds/cage),28(8 birds/cage),35(8 birds/cage)and 42(6 birds/cage),*** apparent digestibility coefficients were standardized using age-specific basal endogenous AA *** the SBM group,though the SIDC of N tended to be influenced(quadratic;P=0.075)by age,no linear or quadratic response of age effect was observed on the average SIDC of indispensable(IAA)and total AA(TAA).An age effect(quadratic;P<0.05)was observed on the average SIDC of dispensable AA(DAA)in SBM with the highest value recorded at d 7,followed by a decrease from d 14 to 28,which increased beyond d *** SIDC of some individual AA(Arg,Thr,Trp,Cys,Pro)were affected(P<0.05 or P<0.001)in a quadratic manner by *** the CM,the SIDC of N,average SIDC of IAA,DAA and TAA were influenced(quadratic;P<0.05 or P<0.001)by *** SIDC of N and average SIDC of DAA and TAA were higher from d 7 to 14,declined at d 21,and then increased beyond d *** average SIDC of IAA was low between d 7 and 28 and increased *** SIDC of individual AA were affected(linear or quadratic;P<0.05 or P<0.001)by different magnitudes by *** age influence on the SIDC AA was variable,depending on the protein source and *** results demonstrate that age-specific SIDC AA data might need consideration in broiler feed formulations.

关键词： Age Amino acid Broiler Digestibility Protein source

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Identific tion of quantitative trait loci and associated candidate genes for pregnancy success in Angus–Brahman crossbred heifers

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journal of Animal Science and Biotechnology 2024年第1期15卷 162-170页

作者： Quinn A.Hoorn Gabriel A.Zayas Eduardo E.Rodriguez Laura M.jensen Raluca G.Mateescu peter j.Hansen Department of Animal Sciences Donald Henry Barron Reproductive and Perinatal Biology Research Programand the Genetics InstituteUniversity of FloridaGainesvilleFLUSA School of Applied Systems Biology La Trobe UniversityBundooraVIC 3083Australia

Background In beef cattle, more than 50% of the energy input to produce a unit of beef is consumed by the female that produced the calf. Development of genomic tools to identify females with high genetic merit for reproductive function could increase the profitability and sustainability of beef *** Genome-wide association studies(GWAS) were performed using a single-step genomic best linear unbiased prediction approach on pregnancy outcome traits from a population of Angus–Brahman crossbred heifers. Furthermore, a validation GWAS was performed using data from another farm. Heifers were genotyped with the Bovine GGP F250 array that contains 221,077 SNPs. In the discovery population, heifers were bred in winter breeding seasons involving a single round of timed artificial insemination(AI) followed by natural mating for 3 months. Two phenotypes were analyzed: pregnancy outcome to first-service AI(PAI;n = 1,481) and pregnancy status at the end of the breeding season(PEBS;n = 1,725). The heritability was estimated as 0.149 and 0.122 for PAI and PEBS, respectively. In the PAI model, one quantitative trait locus(QTL), located between 52.3 and 52.5 Mb on BTA7, explained about 3% of the genetic variation, in a region containing a cluster of γ-protocadherin genes and SLC25A2. Other QTLs explaining between 0.5% and 1% of the genetic variation were found on BTA12 and 25. In the PEBS model, a large QTL on BTA7 was synonymous with the QTL for PAI, with minor QTLs located on BTA5, 9, 10, 11, 19, and 20. The validation population for pregnancy status at the end of the breeding season were Angus–Brahman crossbred heifers bred by natural mating. In concordance with the discovery population, the large QTL on BTA7 and QTLs on BTA10 and 12 were *** In summary, QTLs and candidate SNPs identified were associated with pregnancy outcomes in beef heifers, including a large QTL associated with a group of protocadherin genes. Confirmation of these associations

关键词： Beef cattle Fertility GWAS QTL

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Pre-Cryogenian integrative stratigraphy,biotas,and paleogeographical evolution of the Qinghai-Tibetan Plateau and its surrounding areas

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Science China Earth Sciences 2024年第4期67卷 899-918页

作者： Peiyuan HU Qingguo ZHAI Guochun ZHAO peter A.CAWOOD Yue TANG Yiming LIU Institute of Geology Chinese Academy of Geological SciencesBeijing 100037China Department of Earth Sciences University of Hong KongPokfulam RoadHong Kong 999077China State Key Laboratory of Continental Dynamics Department of GeologyNorthwest UniversityXi’an 710069China School of Earth Atmosphere&EnvironmentMonash UniversityMelbourneVIC 3800Australia

The composition and geological evolution of pre-Cryogenian material in the Tibetan Plateau and its surrounding areas have played an important role in studying the formation and evolution of early supercontinents on *** paper systematically summarizes the characteristics of pre-Cryogenian sedimentation,paleontology,magmatism,and metamorphism in the Tibetan Plateau and its surrounding *** on existing data,the records of pre-Cryogenian sedimentation and paleontology are mainly concentrated in the Meso-Neoproterozoic,with relatively few records from the Paleoproterozoic or *** oldest geological record is the Hadean detrital zircons in the metamorphosed sedimentary rocks of the Himalaya and Qamdo areas(ca.4.0 Ga).The Tibetan Plateau and surrounding areas preserve records related to the formation and evolution of the Kenor supercraton,and the Columbia,Rodinia,and Gondwana ***-Cryogenian basements can be divided into three types:Tarim-,Yangtze-,and *** Tarim-type basement has a paleogeographic affinity with the northern margins of the Australian and Indian continents and lacks detrital zircon age peaks and magmatic-metamorphic records related to the Rodinia assembly(ca.1.3-0.9 Ga).The Yangtze-type basement records volcanic activity related to global cooling in the latest pre-Cryogenian period and contains Meso-Neoproterozoic stromatolite and micropaleoflora fossils,as well as magmaticmetamorphic records related to Rodinia assembly(ca.1.1-1.0 Ga).The Lhasa-type basement is characterized by Neoproterozoic rift-related sediment records(ca.900 Ma)and high-pressure metamorphic events(ca.650 Ma),with a prominent peak of detrital zircon ages of ca.1.2-1.1 *** is likely to have a paleogeographic affinity with the African continent.

关键词： Tibetan Plateau Pre-Cryogenian Sedimentation Fossils Paleogeographic evolution

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