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Treatment with a JAK1/2 inhibitor ameliorates murine autoimmune cholangitis induced by IFN overexpression

Cellular & molecular Immunology 2022年第10期19卷 1130-1140页

作者： Tihong Shao Patrick S.C.Leung Weici Zhang Koichi Tsuneyama william m.ridgway Howard A.Young Zongwen Shuai Aftab A.Ansari m.Eric Gershwi Department of Rheumatology and Immunology The First Affiliated Hospital of Anhui Medical UniversityHefeiChina Division of Rheumatology Allergyand Clinical ImmunologySchool of MedicineUniversity of CaliforniaDavisCAUSA Department of Pathology and Laboratory medicine Institute of Biomedical SciencesTokushima University Graduate SchoolTokushimaJapan Center for Cancer Research National Cancer Institute-FrederickFrederickMDUSA

The interferon(IFN)signaling pathways are major immunological checkpoints with clinical significance in the pathogenesis of *** have generated a unique murine model named ARE-Del,with chronic overexpression of IFNγ,by altering IFNγ***,these mice develop an immunologic and clinical profile similar to patients with primary biliary cholangitis,including high titers of autoantibodies and portal *** hypothesized that the downregulation of IFN signaling pathways with a JAK1/2 inhibitor would inhibit the development and progression of *** study this hypothesis,ARE-Del^(+/−)mice were treated with the JAK1/2 inhibitor ruxolitinib and serially *** inhibition resulted in a significant reduction in portal inflammation and bile duct damage,associated with a significant reduction in splenic and hepatic CD4^(+)T cells and CD8^(+)T ***,ruxolitinib inhibited the secretion of the proinflammatory cytokines IFNγand TNF from splenic CD4^(+)T ***,ruxolitinib treatment also decreased the frequencies of germinal center B(GC B)cells and T follicular helper(Tfh)cells and led to lower serological AmA *** note,liver and peritoneal macrophages were sharply decreased and polarized from m1 to m2 with a higher level of IRF4 expression after ruxolitinib ***,ruxolitinib inhibited the secretion of IL-6,TNF and mCP1 and the expression of STAT1 but promoted the expression of STAT6 in macrophages in vitro,indicating that m1 macrophage polarization to m2 occurred through activation of the STAT6-IRF4 *** data highlight the significance,both immunologically and clinically,of the JAK/STAT signaling pathway in autoimmune cholangitis.

关键词： Primary biliary cholangitis Autoimmunity Interferons Janus Kinase Inhibitors Ruxolitinib

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Liver-resident NK cells suppress autoimmune cholangitis and limit the proliferation of CD4^(+) T cells

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Cellular & molecular Immunology 2020年第2期17卷 178-189页

作者： Zhi-Bin Zhao Fang-Ting Lu Hong-Di ma Yin-Hu Wang Wei Yang Jie Long Qi miao Weici Zhang Zhigang Tian william m.ridgway Jie Cao m.Eric Gershwin Zhe-Xiong Lian Department of General Surgery Guangzhou Digestive Disease CenterGuangzhou First People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhouGuangdong 510180China Chronic Disease Laboratory Institutes for Life Sciences and School of MedicineSouth China University of TechnologyGuangzhou 510006China Institute of Immunology and School of Life Sciences University of Science and Technology of ChinaHefeiAnhui 230027China Center for Reproductive medicine Anhui Provincial Hospital Affiliated to Anhui Medical UniversityHefeiAnhuiChina Department of Gastroenterology and Hepatology Renji HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Division of Rheumatology Allergy and Clinical ImmunologyUniversity of California at Davis School of MedicineDavisCAUSA Division of Immunology Allergy and RheumatologyUniversity of CincinnatiCincinnatiOH 45267USA

Liver-resident NK cells are distinct from conventional NK cells and play an important role in the maintenance of liver *** liver-resident NK cells participate in autoimmune cholangitis remains ***,we extensively investigated the impact of NK cells in the pathogenesis of autoimmune cholangitis utilizing the well-established dnTGFβRII cholangitis model,NK cell-deficient(Nfil3−/−)mice,adoptive transfer and in vivo antibody-mediated NK cell *** data demonstrated that disease progression was associated with a significantly reduced frequency of hepatic NK *** of NK cells resulted in exacerbated autoimmune cholangitis in dnTGFβRII *** further confirmed that the DX5−CD11c^(hi) liver-resident NK cell subset colocalized with CD4^(+) T cells and inhibited CD4^(+) T cell *** expression microarray analysis demonstrated that liver-resident NK cells had a distinct gene expression pattern consisting of the increased expression of genes involved in negative regulatory functions in the context of the inflammatory microenvironment.

关键词： Liver-resident NK Cholangitis CD4^(+)T cell Suppression

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Sb^(3+)and Sm^(3+)co-doped lead-free Cs_(2)NaInCl_(6)double perovskite nanocrystals for single-component cold white emitter

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Journal of Rare Earths 2024年第9期42卷 1646-1651,I0001页

作者： Biao Zhou Xiangtong Zhang Ranran Hu Ruixue Hou william W.Yu Key Laboratory for Special Functional materials of ministry of Education National&Local Joint Engineering Research Centre for High-Efficiency Display and Lighting TechnologySchool of Materials and EngineeringCollaborative Innovation Centre of Nano Functional Materials and ApplicationsHenan UniversityKaifeng475000China School of Chemistry and Chemical Engineering Shandong UniversityJinan250100China

metal halide perovskites exhibit promising prospect in light-emitting diodes,solar cells,photodetectors and ***,the workhorse of metal halide perovskites relies on toxicity lead element,which severely damages human body and *** lead-free perovskites,Cs_(2)NaInCl_(6)double perovskite is one of the most promising candidates because of its great stability and easy synthesis,but suffers inadequate optical ***,we doped Sb^(3+)and Sm^(3+)into Cs_(2)NaInCl_(6)nanocrystals by a hot injection ***_(2)NaInCl_(6):Sb^(3+)exhibits blue emission at 447 ***_(2)NaInCl_(6):Sm^(3+),Sb^(3+)nanocrystals simultaneously generate the blue emission of Sb^(3+)and the multiple emissions of Sm^(3+)at 565,602,650 and 710 *** the increase of Sm^(3+)feed ratio,the emission color of Cs_(2)NaInCl_(6):Sm^(3+),Sb^(3+)gradually moves to cold white region at(0.27,0.28)in CIE chromaticity diagram and correlated color temperature of 11840 *** work shows the potential application of Cs_(2)NaInCl_(6):Sm^(3+),Sb^(3+)nanocrystals as a single-component cold white emitter.

关键词： Lead-free Double perovskites Single component White emitter Doping Rare earths

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Detection of onset of agglomeration in a bubbling fluidized bed biomass combustor using reactive Eulerian computational fluid dynamics

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Particuology 2024年第7期90卷 504-515页

作者： Abdullah Tasleem Atta Ullah Fei Li Qun Yi william Nimmo Syed Sheraz Daood Department of Chemical Engineering Pakistan Institute of Engineering and Applied Sciences(PIEAS)Lehtrar RoadP.O.Nilore45650IslamabadPakistan Institute of Process Engineering Chinese Academy of SciencesBeijing100190China School of Chemical Engineering and Pharmacy Wuhan Institute of TechnologyWuhan430205China Energy Engineering Group Energy 2050Department of Mechanical EngineeringUniversity of SheffieldSheffieldS37RDUnited Kingdom Institute of Energy and Environmental Engineering Faculty of ElectricalEnergy&Environmental EngineeringUniversity of the PunjabQuaid-e-Azam CampusLahorePakistan Energy Engineering Research and Development Centre Faculty of ElectricalEnergy&Environmental EngineeringUniversity of the PunjabQuaid-e-Azam CampusLahorePakistan

The choice of a type of combustion technology to be used for heat or power generation depends on economic,technical,operational and fuel availability *** benefits associated with the evolving market driven by the fluidised bed combustion(FBC)technology cannot be overlooked especially when gauged at 65 GWth of worldwide installed capacity alongside added benefits of handling fuel variation,low pollutant emissions and high combustion *** or biomass waste will continue to have a vital role to play in the future FBC technology-based power *** often contains high levels of inorganic species that can form sticky agglomerates posing a significant risk to boiler operation resulting in unscheduled *** added complexity of the behaviour of the fuel and bed material mix highlights the requirement for simulation models to identify agglomeration to help improve the overall performance and reliability of FBC *** resolve this problem,this research devised a simulation strategy for the detection of agglomeration using the Eulerian–Eulerian *** developed modelling strategy is validated with the experimental data available in literature for two-dimensional simplified geometry of a pilot-scale fluidised bed *** model results were found promising and robust to predict bed defluidisation times and other parameters consistent with the experimental data.

关键词： Fluidized bed combustion Eulerian models Biomass Agglomeration Defluidisation

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Enhancing the clinical relevance of haemorrhage prediction models in trauma

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military medical Research 2024年第3期11卷 467-468页

作者： Sankalp Tandle Jared m.Wohlgemut max E.R.marsden Erhan Pisirir Evangelia Kyrimi Rebecca S.Stoner william marsh Zane B.Perkins Nigel R.m.Tai Centre for Trauma Sciences Blizard InstituteQueen Mary University of LondonLondon E12ATUK The Royal London Hospital Barts Health NHS TrustLondon E11FRUK Academic Department of military Surgery and Trauma Research and Clinical InnovationThe Royal Centre for Defence MedicineBirmingham B152WBUK Department of Electronic Engineering and Computer Science Queen Mary University of LondonLondon E14NSUK

We read with interest the recent systematic reviewaArtificial intelligence and machine learning for hemorrhagic trauma careoby Peng et al.[1],which evaluated literature on machine learning(mL)in the management of trau... 详细信息

关键词： Trauma Injury Blood transfusion massive transfusion Prediction Artificial intelligence machine learning

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The secondary injury cascade after spinal cord injury: an analysis of local cytokine/chemokine regulation

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Neural Regeneration Research 2024年第6期19卷 1308-1317页

作者： Daniel J.Hellenbrand Charles m.Quinn Zachariah J.Piper Ryan T.Elder Raveena R.mishra Taylor L.marti Phoebe m.Omuro Rylie m.Roddick Jae Sung Lee william L.murphy Amgad S.Hanna Department of Neurosurgery University of Wisconsin-Madison School of Medicine and Public Health Department of Biomedical Engineering University of Wisconsin-Madison Department of Orthopedics and Rehabilitation University of Wisconsin-Madison Department of materials Science and Engineering University of Wisconsin-Madison Forward BIO Institute University of Wisconsin-Madison

After spinal cord injury, there is an extensive infiltration of immune cells, which exacerbates the injury and leads to further neural degeneration. Therefore, a major aim of current research involves targeting the immune response as a treatment for spinal cord injury. Although much research has been performed analyzing the complex inflammatory process following spinal cord injury, there remain major discrepancies within previous literature regarding the timeline of local cytokine regulation. The objectives of this study were to establish an overview of the timeline of cytokine regulation for 2 weeks after spinal cord injury, identify sexual dimorphisms in terms of cytokine levels, and determine local cytokines that significantly change based on the severity of spinal cord injury. Rats were inflicted with either a mild contusion, moderate contusion, severe contusion, or complete transection, 7 mm of spinal cord centered on the injury was harvested at varying times post-injury, and tissue homogenates were analyzed with a Cytokine/Chemokine 27-Plex assay. Results demonstrated pro-inflammatory cytokines including tumor necrosis factor α, interleukin-1β, and interleukin-6 were all upregulated after spinal cord injury, but returned to uninjured levels within approximately 24 hours post-injury, while chemokines including monocyte chemoattractant protein-1 remained upregulated for days post-injury. In contrast, several anti-inflammatory cytokines and growth factors including interleukin-10 and vascular endothelial growth factor were downregulated by 7 days post-injury. After spinal cord injury, tissue inhibitor of metalloproteinase-1, which specifically affects astrocytes involved in glial scar development, increased more than all other cytokines tested, reaching 26.9-fold higher than uninjured rats. After a mild injury, 11 cytokines demonstrated sexual dimorphisms; however, after a severe contusion only leptin levels were different between female and male rats. In conclus

关键词： astrocytes chemokines cytokines inflammation macrophages microglia secondary damage spinal cord injury

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Additively manufactured Ti–Ta–Cu alloys for the next-generation load-bearing implants

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International Journal of Extreme manufacturing 2024年第1期6卷 353-374页

作者： Amit Bandyopadhyay Indranath mitra Sushant Ciliveri Jose D Avila william Dernell Stuart B Goodman Susmita Bose W.m.Keck Biomedical materials Research Laboratory School of Mechanical and Materials EngineeringWashington State UniversityPullmanWA 99164United States of America Veterinary Clinical Sciences College of Veterinary MedicineWashington State UniversityPullmanWA 99164United States of America Department of Orthopedic Surgery Stanford University Medical CenterRedwood CityCA 94063United States of America

Bacterial colonization of orthopedic implants is one of the leading causes of failure and clinical complexities for load-bearing metallic implants. Topical or systemic administration of antibiotics may not offer the most efficient defense against colonization, especially in the case of secondary infection, leading to surgical removal of implants and in some cases even limbs. In this study, laser powder bed fusion was implemented to fabricate Ti3Al2V alloy by a 1:1 weight mixture of CpTi and Ti6Al4V powders. Ti-Tantalum(Ta)–Copper(Cu) alloys were further analyzed by the addition of Ta and Cu into the Ti3Al2V custom alloy. The biological,mechanical, and tribo-biocorrosion properties of Ti3Al2V alloy were evaluated. A 10 wt.% Ta(10Ta) and 3 wt.% Cu(3Cu) were added to the Ti3Al2V alloy to enhance biocompatibility and impart inherent bacterial resistance. Additively manufactured implants were investigated for resistance against Pseudomonas aeruginosa and Staphylococcus aureus strains of bacteria for up to 48 h. A 3 wt.% Cu addition to Ti3Al2V displayed improved antibacterial efficacy, i.e.78%–86% with respect to CpTi. mechanical properties for Ti3Al2V–10Ta–3Cu alloy were evaluated, demonstrating excellent fatigue resistance, exceptional shear strength, and improved tribological and tribo-biocorrosion characteristics when compared to Ti6Al4V. In vivo studies using a rat distal femur model revealed improved early-stage osseointegration for alloys with10 wt.% Ta addition compared to CpTi and Ti6Al4V. The 3 wt.% Cu-added compositions displayed biocompatibility and no adverse infammatory response in vivo. Our results establish the Ti3Al2V–10Ta–3Cu alloy’s synergistic effect on improving both in vivo biocompatibility and microbial resistance for the next generation of load-bearing metallic implants.

关键词： Ti6Al4V load-bearing implants additive manufacturing 3D printing antibacterial performance

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Smoking cessation prior to elective total joint arthroplasty results in sustained abstinence postoperatively

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World Journal of Orthopedics 2024年第7期15卷 627-634页

作者： Billy Insup Kim Jeffrey O'Donnell Colleen m Wixted Thorsten markus Seyler william A Jiranek michael Paul Bolognesi Sean Patrick Ryan Department of Orthopedic Surgery Hospital for Special SurgeryNew YorkNY 10021United States Department of Orthopedic Surgery New York UniversityNew YorkNY 10003United States Department of Orthopedic Surgery Duke University HospitalDurhamNC 27560United States

BACKGROUND Tobacco use is a well-documented modifiable risk factor for perioperative *** To determine the tobacco abstinence rates of patients who made cessation efforts prior to a total joint arthroplasty(TJA)*** A retrospective evaluation was performed on 88 self-reported tobacco users who underwent TJA between 2014-2022 and had tobacco cessation dates within 3 mo of *** patients were contacted via phone survey to understand their tobacco use pattern,and patient reported outcomes.A total of 37 TJA patients *** Our cohort was on average 61-years-old,60%(n=22)women,with an average body mass index of 30 kg/m^(2).The average follow-up time was 2.9±1.9 years.A total of 73.0%(n=27)of patients endorsed complete abstinence from tobacco use prior to *** cessation methods were used perioperatively including prescription therapy(13.5%),over the counter nicotine replacement(18.9%),cessation programs(5.4%).At final follow up,43.2%(n=16)of prior tobacco smokers reported complete *** who were able to maintain cessation postoperatively had improved Patient-Reported Outcomes measurement Information System(PROmIS)-10 mental health scores(49 vs 58;P=0.01),and hip dysfunction and osteoarthritis outcome score for joint replacement(***)scores(63 vs 82;P=0.02).No patients in this cohort had a prosthetic joint infection or required revision *** We report a tobacco cessation rate of 43.2%in patients undergoing elective TJA nearly 3 years *** undergoing TJA who were able to remain abstinent had improved PROmIS-10 mental health scores and *** *** perioperative period provides clinicians a unique opportunity to assist active tobacco smokers with cessation efforts and improve postoperative outcomes.

关键词： Smoking cessation Total joint arthroplasty Outcomes Tobacco use Postoperative abstinence

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Effect of stress-dependent microannulus aperture on well leakage

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Journal of Rock mechanics and Geotechnical Engineering 2024年第6期16卷 1967-1976页

作者： meng meng Luke P.Frash J.william Carey mohamed mehana Wenfeng Li Bailian Chen Earth and Environmental Sciences Los Alamos National LaboratoryLos AlamosNMUSA

Debonding at the cement-casing interface is recognized as a principal failure mechanism leading to CO_(2) leakage in *** detachment gives rise to a microannulus,which notably possesses greater permeability than undamaged cement,undermining its sealing ***,the permeability of the microannulus is regarded as a uniform value throughout the ***,fundamentally,a microannulus is one type of fracture,and its gap or aperture size is affected by the effective *** this work,we developed a unique experimental *** equipment facilitates the curing of cement inside a steel casing,the formation of a microannulus between the casing and the cement,and the investigation of the fluid flow dynamics along the microannulus under laboratory-replicated in situ *** microannulus was formed by injecting fluid from one end of the setup,and receiving similar amount of fluid on the other end signified the development of the leakage ***,strain gauges affixed to the casing’s external surface yielded key information on the microannulus’s opening and *** observed a noticeable decline in microannulus hydraulic aperture(or permeability)in relation to effective stress and an exponential equation fits their *** findings also indicate a distinct behavior when comparing liquid CO_(2) with ***,it is easier for liquid CO_(2) to create the ***,the hydraulic aperture range for this microannulus(0.7-6 mm)is considerably smaller than that created by water flow(2-17 mm).Finally,we integrated the stressdependent microannulus aperture size into the combined analysis of well mechanical integrity and well *** outcomes consistently demonstrated that when factoring in the stress-dependent aperture sizes,the leakage rates are 3e5 times compared to a fixed aperture *** traditional assumption of a constant aperture significantly underestimates fluid leakage risks.

关键词： microannulus Leakage assessment Aperture size Triaxial experiment Carbon sequestration

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molecular Docking Studies on Streptomycin Antileishmanial Activity

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Open Journal of Physical Chemistry 2024年第2期14卷 36-48页

作者： Todd A. Young matthew George Jr. Ayele Gugssa william m. Southerland Yayin Fang Clarence m. Lee Department of Biology Howard University Washington DC United States Department of Biochemistry and molecular Biology Howard University Washington DC United States

Resistance to pentavalent antimonial drugs and the lack of vaccines make it urgent to find novel therapeutic options to treat Leishmaniasis, a tropical disease caused by the Leishmania protozoan parasite. The study reported here is to investigate if Streptomycin, an aminoglycoside, and Amphotericin B, the second-line treatment drug, exhibit antileishmanial activity through a similar mechanism. By using mOE (molecular Operating Environment), we performed molecular docking studies on these drugs binding to a range of targets including ribosome targets in Leishmania and H. sapiens. Our study shows that the two drugs do not bind to the same pockets in Leishmania targets but to the same pockets in the human ribosome, with some differences in interactions. moreover, our 2D maps indicated that Amphotericin B binds to the A-site in the human cytoplasmic ribosome, whereas streptomycin does not.

关键词： Leishmaniasis Streptomycin Amphotericin B molecular Docking Aminoglycosides Antileishmanial

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