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Suppression of monosodium urate crystal-induced inflammation by inhibiting TGF-β-activated kinase 1-dependent signaling:role of the ubiquitin proteasome system

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Cellular & Molecular Immunology 2021年第1期18卷 162-170页

作者： anil k.singh Mahamudul Haque kayla O'Sullivan Mukesh Chourasia Madhu M.Ouseph Salahuddin Ahmed Department of Pharmaceutical Sciences Washington State University College of PharmacySpokaneWAUSA Center for Computational Biology and Bioinformatics Amity Institute of BiotechnologyAmity UniversityNoidaUttar PradeshIndia Department of Pathology Stanford University School of MedicineStanfordCAUSA Division of Rheumatology University of Washington School of MedicineSeattleWAUSA

Monosodium urate(MSU)crystals activate inflammatory pathways that overlap with interleukin-1β(IL-1β)***,the post-translational mechanisms involved and the role of signaling proteins in this activation are *** the present study,we investigated the intracellular signaling mechanisms involved in MSU-induced activation of THP-1 macrophages and human nondiseased synovial fibroblasts(NLSFs)and the in vivo efficacy of an inhibitor of tumor grovArth factor-β(TGF-β)-activated kinase 1(TAk1),5Z-7-oxozeaenoI,in MSU-induced paw inflammation in C57BL76 ***-1 macrophage activation with MSU crystals(25-200 ng/ml)resulted in the rapid and sustained phosphorylation of interleukin-1 receptor-activated kinase 1(IRAk1 Thr^(209))and TAk1(Thr^(184/187))and their association with the E3 ubiquitin ligase *** the cellular level,MSU inhibited the deubiquitinases A20 and UCHL2 and increased 20s proteasomal activity,leading to a global decrease in k^(63)-linked ubiquitination and increase in k^(48)-linked ubiquitination in THP-1 *** MSU did not stimulate cytokine produaion in NLSFs,it significantly amplified IL-1β-induced IL-6,IL-8,and ENA-78/CXCL5 *** studies and MD simulations followed by TAk1 in vitro kinase assays revealed that uric acid molecules are capable of arresting TAk1 in an active-state conformation,resulting in sustained TAk1 kinase ***,MSU-induced proinflammatory cytokine production was completely inhibited by 5Z-7-oxozeaenol but not IRAk1/4 or TRAF6 *** of 5Z-7-oxozeaenol(5 or 15 mg/kg;orally)significantly inhibited MSU-induced paw inflammation in C57BL/6 *** study identifies a novel post-translational mechanism of TAk1 activation by MSU and suggests the therapeutic potential of TAk1 in regulating MSU-induced Inflammation.

关键词： Monosodium urate crystals Gout TAk1 Ubiquitination 5Z-7-oxozeaenol

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Extracellular sulfatase-2 is overexpressed in rheumatoid arthritis and mediates the TNF-α-induced inflammatory activation of synovial fibroblasts

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Cellular & Molecular Immunology 2022年第10期19卷 1185-1195页

作者： Ruby J.Siegel anil k.singh Paul M.Panipinto Farheen S.Shaikh Judy Vinh Sang U.Han H.Mark kenney Edward M.Schwarz Cynthia S.Crowson Sadik A.khuder Basil S.khuder David A.Fox Salahuddin Ahmed Department of Pharmaceutical Sciences Washington State University College of Pharmacy and Pharmaceutical SciencesSpokaneWAUSA Department of Pathology and Laboratory Medicine University of Rochester Medical CenterRochesterNYUSA Center for Musculoskeletal Research University of Rochester Medical CenterRochesterNYUSA Department of Quantitative Health Sciences and Division of Rheumatology Mayo ClinicRochesterMNUSA Department of Medicine and Public Health University of ToledoToledoOHUSA Department of Pathology and Laboratory Medicine Phoenix Children’s HospitalPhoenixAZUSA Department of Medicine Division of Rheumatology and Clinical Autoimmunity Center of ExcellenceUniversity of Michigan Medical SystemAnn ArborMIUSA Division of Rheumatology University of Washington School of MedicineSeattleWAUSA

Extracellular sulfatase-2(Sulf-2)influences receptor-ligand binding and subsequent signaling by chemokines and growth factors,yet Sulf-2 remains unexplored in inflammatory cytokine signaling in the context of rheumatoid arthritis(RA).In the present study,we characterized Sulf-2 expression in RA and investigated its potential role in TNF-α-induced synovial inflammation using primary human RA synovial fibroblasts(RASFs).Sulf-2 expression was significantly higher in serum and synovial tissues from patients with RA and in synovium and serum from hTNFtg *** sequencing analysis of TNF-α-stimulated RASFs showed that Sulf-2 siRNA modulated~2500 genes compared to scrambled *** Pathway Analysis of RNA sequencing data identified Sulf-2 as a primary target in fibroblasts and macrophages in *** blot,ELISA,and qRT‒PCR analyses confirmed that Sulf-2 knockdown reduced the TNF-α-induced expression of ICAM1,VCAM1,CAD11,PDPN,CCL5,CX3CL1,CXCL10,and *** studies identified the protein kinase C-delta(PkCδ)and c-Jun N-terminal kinase(JNk)pathways as key in the TNF-α-mediated induction of proteins related to cellular adhesion and *** of Sulf-2 abrogated TNF-α-induced RASF ***-2 knockdown with siRNA and inhibition by OkN-007 suppressed the TNF-α-induced phosphorylation of PkCδand JNk,thereby suppressing the nuclear translocation and DNA binding activity of the transcription factors AP-1 and NF-κBp65 in human ***,Sulf-2 expression positively correlated with the expression of TNF receptor 1,and coimmunoprecipitation assays demonstrated the binding of these two proteins,suggesting they exhibit crosstalk in TNF-α*** study identified a novel role of Sulf-2 in TNF-αsignaling and the activation of RA synoviocytes,providing the rationale for evaluating the therapeutic targeting of Sulf-2 in preclinical models of RA.

关键词： Sulfatase-2 TNF-α Rheumatoid arthritis Synovial fibroblasts Signal transduction

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Prevalence of transfusion transmissible infections among various donor groups:A comparative analysis

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World Journal of Virology 2025年第1期14卷 108-117页

作者： Sanjay k Thakur anil k Sinha Santosh k Sharma Aarzoo Jahan Dinesh k Negi Ruchika Gupta Sompal singh Regional Blood Transfusion Centre Hindu Rao Hospital and NDMC Medical CollegeNorth Delhi 110007DelhiIndia Department of Zoology Veer Kunwar Singh UniversityAra 802301BiharIndia Regional Blood Transfusion Centre and Pathology Hindu Rao Hospital and NDMC Medical CollegeNorth Delhi 110007DelhiIndia Department of Cytopathology ICMR-National Institute of Cancer Prevention and ResearchNoida 201301Uttar PradeshIndia

BACkGROUND Transfusion transmissible infections(TTIs)are illnesses spread through contaminated blood or blood *** India,screening for TTIs such as hepatitis B virus(HBV),hepatitis C virus(HCV),human immunodeficiency virus(HIV)-I/II,malaria,and syphilis is mandatory before blood ***,HCV,HBV,and HIV are the leading viruses causing mortality,affecting millions of people globally,including those with co-infections of HIV/HCV and HIV/*** highlight the impact of TTIs on life expectancy and health risks,such as liver cirrhosis,cancer,and other diseases in individuals with chronic ***,millions of blood donations take place annually,emphasizing the importance of maintaining blood *** To study the prevalence of TTIs,viz.,HBV,HCV,HIV I/II,syphilis,and malaria parasite(MP),among different blood donor *** The study assessed the prevalence of TTIs among different blood donor groups in Delhi,*** included total donors,in-house donors,total camp donors,institutional camp donors,and community camp *** for HIV,HBV,and HCV were done using enzyme-linked immunosorbent assay,while syphilis was tested with rapid plasma reagins and MP rapid card *** prevalence of HBV,HCV,HIV,and syphilis,expressed as *** in infection rates between the groups were analyzed usingχ²tests and P-values(less than 0.05).RESULTS The study evaluated TTIs among 42158 blood donors in *** overall cumulative frequency of TTIs in total blood donors was 2.071%,and the frequencies of HBV,HCV,HIV-I/II,venereal disease research laboratory,and MP were 1.048%,0.425%,0.221%,0.377%,and 0.0024%,***-house donors,representing 37656 donors,had the highest transfusion transmissible infection(TTI)prevalence at 2.167%.Among total camp donors(4502 donors),TTIs were identified in 1.266%of donors,while community camp donors(2439 donors)exhibited a prevalence of 1.558%.Institutional camp donors(2063 donors)had the l

关键词： Blood donors Transfusion transmissible infections Hepatitis B virus Human immunodeficiency virus Hepatitis C virus Malaria parasite Syphilis

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pyGWBSE:a high throughput workflow package for GW-BSE calculations

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npj Computational Materials 2023年第1期9卷 2127-2136页

作者： Tathagata Biswas Arunima k.singh Department of Physics Arizona State UniversityTempe 85287 AZUSA

We develop an open-source python workflow package,pyGWBSE to perform automated first-principles calculations within the GW-BSE(Bethe-Salpeter)***-BSE is a many body perturbation theory based approach to explore the quasiparticle(QP)and excitonic properties of *** approximation accurately predicts bandgaps of materials by overcoming the bandgap underestimation issue of the more widely used density functional theory(DFT).BSE formalism produces absorption spectra directly comparable with experimental *** package achieves complete automation of the entire multi-step GW-BSE computation,including the convergence tests of several parameters that are crucial for the accuracy of these *** is integrated with Wannier90,to generate QP bandstructures,interpolated using the maximally-localized wannier *** also enables the automated creation of databases of metadata and data,including QP and excitonic properties,which can be extremely useful for future material discovery studies in the field of ultra-wide bandgap semiconductors,electronics,photovoltaics,and photocatalysis.

关键词： automated python enable

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Chemical hardness-driven interpretable machine learning approach for rapid search of photocatalysts

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npj Computational Materials 2021年第1期7卷 1850-1862页

作者： Ritesh kumar Abhishek k.singh Materials Research Centre Indian Institute of ScienceBangaloreKarnataka 560012India

Strategies combining high-throughput(HT)and machine learning(ML)to accelerate the discovery of promising new materials have garnered immense attention in recent *** knowledge of new guiding principles is usually scarce in such studies,essentially due to the‘black-box’nature of the ML ***,we devised an intuitive method of interpreting such opaque ML models through SHapley Additive exPlanations(SHAP)values and coupling them with the HT approach for finding efficient 2D watersplitting *** developed a new database of 30992D materials consisting of metals connected to six ligands in an octahedral geometry,termed as 2DO(octahedral 2D materials)*** ML models were constructed using a combination of composition and chemical hardness-based features to gain insights into the thermodynamic and overall *** importantly,it distinguished the target properties of the isocompositional 2DO materials differing in bond connectivities by combining the advantages of both elemental and structural *** interpretable ML regression,classification,and data analysis lead to a new hypothesis that the highly stable 2DO materials follow the HSAB *** most stable 2DO materials were further screened based on suitable band gaps within the visible region and band alignments with respect to standard redox potentials using the GW method,resulting in 21 potential ***,HfSe_(2)and ZrSe_(2)were found to have high solar-tohydrogen efficiencies reaching their theoretical *** proposed methodology will enable materials scientists and engineers to formulate predictive models,which will be accurate,physically interpretable,transferable,and computationally tractable.

关键词： intuitive formulate visible

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Diagenesis,facies and palaeocurrent analysis of Upper Rewa Sandstone around Sagar,Central India

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Journal of Palaeogeography 2023年第4期12卷 546-563页

作者： Gaurav k.singh Ashish k.Rai Arvind k.singh Department of Applied Geology Dr.Harisingh Gour VishwavidyalayaSagar 470003Madhya PradeshIndia Geological Survey of India ShillongIndia

The stratigraphic surface represented by a major contact between the Archean Bundelkhand Granite and the extensive Proterozoic Vindhyan sediments is a regional basement cover *** crystalline—sedimentary interface reflects an intense weathering of continental crust during marine *** time-transgressive sand deposition events ***,Rewa and Bhander are mainly witnessed during the entire Vindhyan ***,the Upper Rewa Sandstone comprises one of these events in the Vindhyan *** progress has been made in interpreting these sandstones as a function of entirely marine process to a combination of tidal—fluvio—eolian *** the results have so far been attained on the basis of sedimentary facies,provenance,palaeocurrent analysis,and some of petrography.A distinct differentiation between marine and fluvial components of the Upper Rewa Sandstone still remains ***,we use diagenesis as a parameter for the first time along with facies and palaeocurrent analysis to acquire a clear comprehension of marine-and fluvial-dominated *** present study spans 27 square kilometer area covering 15 stratigraphic sections with a collection of 571directional data from the facies specific sedimentary structures,and 28 samples obtained for the thin section *** lower unit of the Upper Rewa Sandstone shows facies association typical of tidal environment,along with polymodal *** rocks are well sorted and dominantly lithified by authigenic *** development of a complex of syntaxial,passive pore fills,and grain replacive cements reflect normally pressured nature of the lower unit *** upper unit of the Upper Rewa Sandstone however,reveals a facies pattern resembling fluvial processes and unimodal palaeocurrent *** exhibit poor sorting,siliceous,and ferruginous matrix,and development of intense ***,pressure solution is a dominant mode of l

关键词： Palaeocurrent Diagenesis Facies Upper Rewa Sandstone Vindhyan Basin

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Excitonic effects in absorption spectra of carbon dioxide reduction photocatalysts

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npj Computational Materials 2021年第1期7卷 1752-1761页

作者： Tathagata Biswas Arunima k.singh Department of Physics Arizona State UniversityTempeAZ 85287USA

The formation and disassociation of excitons play a crucial role in any photovoltaic or photocatalytic ***,excitonic effects are seldom considered in materials discovery studies due to the monumental computational cost associated with the examination of these ***,we study the excitonic properties of nearly 50 photocatalysts using state-of-the-art Bethe–Salpeter ***~50 materials were recently recognized as promising photocatalysts for CO_(2) reduction through a data-driven screening of 68,860 ***,we propose three screening criteria based on the optical properties of these materials,taking excitonic effects into account,to further down select six ***,we study the correlation between the exciton binding energies obtained from the Bethe–Salpeter formalism and those obtained from the computationally much lessexpensive Wannier–Mott model for these chemically diverse~50 *** work presents a paradigm towards the inclusion of excitonic effects in future materials discovery for solar-energy harvesting applications.

关键词： materials properties dioxide

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Inflammation and retinal degenerative diseases

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Neural Regeneration Research 2023年第3期18卷 513-518页

作者： Geetika kaur Nikhlesh k.singh Integrative Biosciences Center Wayne State UniversityDetroitMIUSA Department of Ophthalmology Visual and Anatomical SciencesWayne State University School of MedicineDetroitMIUSA

Vision is an ability that depends on the precise structure and functioning of the *** kind of stress or injury can disrupt the retinal architecture and leads to vision impairment,vision loss,and *** system and immune response function maintain homeostasis in the *** genetic,metabolic,and environmental factors may alter retinal homeostasis,and these events may initiate various inflammatory *** prolonged inflammatory state may contribute to the initiation and development of retinal disorders such as glaucoma,age-related macular degeneration,diabetic retinopathy,and retinitis pigmentosa,which pose a threat to *** the current review,we attempted to provide sufficient evidence on the role of inflammation in these retinal ***,this review paves the way to focus on therapeutic targets of the disease,which are found to be promising.

关键词： age-related macular degeneration diabetic retinopathy glaucoma retina retinal degeneration retinitis pigmentosa

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RBFOX2: a key factor in suppressing PDAC metastasis through regulation of alternative splicing events

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Signal Transduction and Targeted Therapy 2023年第10期8卷 4431-4432页

作者： Laura Urbach Shiv k.singh Department of Gastroenterology Gastrointestinal Oncology and EndocrinologyUniversity Medical Center GottingenGottingenGermany Clinical Research Unit 5002 KFO5002University Medical Center GöttingenGottingenGermany

A new study published in Nature by Jbara et *** identified the splicing factor“RBFOX2,”which halts metastatic spread of pancreatic ductal adenocarcinoma(PDAC)through regulating alternative splicing events.1 The results of the study provide new insights into the molecular mechanisms underlying the start of metastatic spread of PDAC *** study also indicates that pathways involved in splicing modulation could be targeted for potential therapeutic interventions in an advanced-stage PDAC.

关键词： metastasis al. metastatic

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kinetic Energy Recovery from the Chimney Flue Gases Using Ducted Turbine System

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Chinese Journal of Mechanical Engineering 2017年第2期30卷 472-482页

作者： Harjeet S.Mann Pradeep k.singh Department of Mechanical Engineering Sant LongowalInstitute of Engineering and TechnologyLongowalPunjab 148106India

An innovative idea of extracting kinetic energy from man-made wind resources using ducted turbine system for on-site power generation is introduced in this paper. A horizontal axis ducted turbine is attached to the top of the chimney to harness the kinetic energy of flue gases for producing electricity. The turbine system is positioned beyond the chimney outlet, to avoid any negative impact on the chimney performance. The convergentdivergent duct causes increase in the flue gas velocity and hence enhances the performance of the turbine. It also acts as a safety cover to the energy recovery system. The results from the CFD based simulation analysis indicate that sig- nificant power 34 kW can be harnessed from the chimney exhaust. The effect of airfoils NACA4412 and NACA4416 and the diffuser angle on the power extraction by the energy recovery system using a 6-bladed ducted turbine has been studied with the CFD simulation. It is observed that the average flue gas velocity in the duct section at the throat is approximately twice that of the inlet velocity, whereas maximum velocity achieved is 2.6 times the inlet velocity. The simulated results show that about power may be extracted from the chimney flue gases of 660 MW power plant. The system can be retrofitted to existing chimneys of thermal power plants, refineries and other industries.

关键词： Chimney flue gases Energy recovery system ·kinetic energy Ducted turbine CFD

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