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Autolysosomal acidification impairment as a mediator for TNFR1 induced neuronal necroptosis in Alzheimer’s disease

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Neural Regeneration Research 2024年第9期19卷 1869-1870页

作者： Evridiki Asimakidou richard Reynolds Anna m.Barron Chih Hung Lo Department of Clinical Neurosciences University of CambridgeCambridgeUK Department of Brain Sciences Faculty of MedicineImperial College LondonLondonUK Lee Kong Chian School of medicine Nanyang Technological UniversitySingaporeSingapore

Neuronal necroptosis-an emerging form of regulated cell death associated with neuroinflammatory signaling:Alzheimer’s disease(AD)is characterized by the presence of extracellular amyloid-β(Aβ)plaques and intracellular tau neurofibrillary tangles as well as progressive neuronal *** evidence has suggested that prolonged neuroinflammation with increased levels of cytokines,arising from neuronal injury,innate immune responses from glial cells,and peripheral inflammation,leads to neuronal death and AD progression.

关键词： Alzheimer death tau Aβ

Biofabrication of nanocomposite-based scaffolds containing human bone extracellularmatrix for the differentiation of skeletal stem and progenitor cells

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Bio-Design and manufacturing 2024年第2期7卷 121-136页

作者： Yang-Hee Kim Janos m.Kanczler Stuart Lanham Andrew Rawlings marta Roldo Gianluca Tozzi Jonathan I.Dawson Gianluca Cidonio richard O.C.Oreffo Faculty of medicine Bone and Joint Research GroupCentre for Human DevelopmentStem Cells and RegenerationInstitute of Developmental SciencesUniversity of SouthamptonSouthampton SO166YDUK School of Pharmacy and Biomedical Science University of PortsmouthPortsmouth PO12DTUK School of Engineering Faculty of Engineering and ScienceUniversity of GreenwichGreenwich ME44TBUK Center for Life Nano-and Neuro-Science(CLN2S) Italian Institute of Technology00161 RomeItaly

Autograft or metal implants are routinely used in skeletal ***,they fail to provide long-term clinical resolution,necessitating a functional biomimetic tissue engineering *** use of native human bone tissue for synthesizing a biomimeticmaterial inkfor three-dimensional(3D)bioprintingof skeletal tissueis anattractivestrategyfor ***,human bone extracellular matrix(bone-ECm)offers an exciting potential for the development of an appropriate microenvironment for human bone marrow stromal cells(HBmSCs)to proliferate and differentiate along the osteogenic *** this study,we engineered a novel material ink(LAB)by blending human bone-ECm(B)with nanoclay(L,Laponite®)and alginate(A)polymers using extrusion-based *** inclusion of the nanoﬁller and polymeric material increased the rheology,printability,and drug retention properties and,critically,the preservation of HBmSCs viability upon *** composite of human bone-ECm-based 3D constructs containing vascular endothelial growth factor(VEGF)enhanced vascularization after implantation in an ex vivo chick chorioallantoic membrane(CAm)*** inclusion of bone morphogenetic protein-2(BmP-2)with the HBmSCs further enhanced vascularization and mineralization after only seven *** study demonstrates the synergistic combination of nanoclay with biomimetic materials(alginate and bone-ECm)to support the formation of osteogenic tissue both in vitro and ex vivo and offers a promising novel 3D bioprinting approach to personalized skeletal tissue repair.

关键词： Extracellular matrix Nanoclay Bone 3D bioprinting

Dual-Fields Rotational Total Skin Electron Therapy: Investigation and Implementation

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International Journal of medical Physics, Clinical Engineering and Radiation Oncology 2024年第1期13卷 1-15页

作者： m. ming Xu Iris Rusu richard P. Garza Northwestern medicine Cancer Center Warrenville and Geneva Illinois USA Department of Radiation Oncology Loyola University Medical Center Maywood Illinois USA The Austin Center for Radiation Oncology Austin Texas USA

Purpose: To present a protocol of a dual-field rotational (DFR) total skin electron therapy (TSET) and to provide an assessment of clinical implementation, dosimetry properties, and skin dose evaluation. methods and materials: The DFR-TSET combined the Stanford 6-field and mcGill rotational methods. Dual 6 meV electron beams in high dose total skin electron mode were used for DFR-TSET on a commercial linac. Beam profiles and dosimetric properties were measured using solid phantoms. The dose rate at expanded source-to-surface distance (SSD) was a combination of static rate and rotational rate. In vivo dosimetry of patient skin was performed on patients’ skin using film, metal oxide semiconductor field-effect transistors (mOSFET), and optically stimulated luminescent dosimeters (OSLD). Results: Dual field rotational total skin electron therapy exhibited good (≤±10%) uniformity in the beam profiles in the vertical direction at an extended SSD of 332 cm with a gantry angulation of ±20˚ deviated from the horizontal direction. In-vivo measurements confirmed acceptable uniformity of the patients’ total body surfaces and revealed anatomically self-blocked or shielded areas where underdosing occurred. Conclusions: The clinical implementation of DFR-TSET effectively utilizes the special mode on a linac. This technique provides short beam-on times, uniform dose distribution, large treatment field, and reduced dose of x-ray contamination to the patients. In-vivo measurements indicate satisfactory delivery and dose uniformity of the prescribed dose. Electron boost fields are recommended at normal SSDs to address underdosed areas.

关键词： Total Skin Electron Therapy Stanford 6 Field mcGill Rotation Therapy In-Vivo Dosimetry

COVID-19 vaccination produces exercise-responsive SARS-CoV-2 specific T-cells regardless of infection history

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Journal of Sport and Health Science 2024年第1期13卷 99-107页

作者： Kyle A.Smith Tiffany m.Zúñiga Forrest L.Baker Helena Batatinha Charles R.Pedlar Shane C.Burgess michael P.Gustafson Emmanuel Katsanis richard J.Simpson School of Nutritional Sciences and Wellness The University of ArizonaTucsonAZ 85721USA Department of Pediatrics The University of ArizonaTucsonAZ 85724USA Faculty of Sport Allied Health and Performance ScienceSt.Mary's UniversityTwickenham TW14SXUK Institute of Sport Exercise and Health University College LondonLondon WC1E 7HUUK Department of Animal and Comparative Biomedical Sciences The University of ArizonaTucsonAZ 85721USA The University of Arizona Cancer Center The University of ArizonaTucsonAZ 85719USA Laboratory medicine and Pathology Mayo Clinic ArizonaPhoenixAZ 85054USA Department of Immunobiology The University of ArizonaTucsonAZ 85724USA Department of medicine The University of ArizonaTucsonAZ 85724USA Department of Pathology The University of ArizonaTucsonAZ 85724USA

Background:The mobilization and redistribution of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)specific T-cells and neutralizing antibodies(nAbs)during exercise is purported to increase immune surveillance and protect against severe coronavirus disease 2019(COVID-19).We sought to determine if COVID-19 vaccination would elicit exercise-responsive SARS-CoV-2 T-cells and transiently alter nAb ***:Eighteen healthy participants completed a 20-min bout of graded cycling exercise before and/or after receiving a COVID-19 *** major leukocyte subtypes were enumerated before,during,and after exercise by flow cytometry,and immune responses to SARS-CoV-2 were determined using whole blood peptide stimulation assays,T-cell receptor(TCR)-βsequencing,and SARS-CoV-2 nAb ***:COVID-19 vaccination had no effect on the mobilization or egress of major leukocyte subsets in response to intensity-controlled graded ***,non-infected participants had a significantly reduced mobilization of CD4+and CD8+naive T-cells,as well as CD4+central memory T-cells,after vaccination(synthetic immunity group);this was not seen after vaccination in those with prior SARS-CoV-2 infection(hybrid immunity group).Acute exercise after vaccination robustly mobilized SARS-CoV-2 specific T-cells to blood in an intensity-dependent *** groups mobilized T-cells that reacted to spike protein;however,only the hybrid immunity group mobilized T-cells that reacted to membrane and nucleocapsid *** increased significantly during exercise only in the hybrid immunity ***:These data indicate that acute exercise mobilizes SARS-CoV-2 specific T-cells that recognize spike protein and increases the redistribution of nAbs in individuals with hybrid immunity.

关键词： Anti-viral COVID-19 Exercise immunology SARS-CoV-2 T-Cells Vaccine

Beyond cotton and polyester: An evaluation of emerging feedstocks and conversion methods for the future of fashion industry

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Journal of Bioresources and Bioproducts 2024年第2期9卷 130-159页

作者： Ryen m.Frazier Keren A.Vivas Ivana Azuaje Ramon Vera Alonzo Pifano Naycari Forfora Hasan Jameel Ericka Ford Joel J.Pawlak richard Venditti Ronalds Gonzalez Department of Forest Biomaterials North Carolina State UniversityRaleighNC 27695USA Department of Textile Engineering Chemistry and ScienceThe Nonwovens InstituteNorth Carolina State UniversityRaleighNC 27695USA

As the global population grows,the demand for textiles is increasing ***,this puts immense pressure on manufacturers to produce more *** synthetic fibers can be pro-duced cheaply,they have a negative impact on the *** the other hand,fibers from wool,sisal,fique,wood pulp(viscose),and man-made cellulose fibers(mmCFs)from cotton can-not alone meet the growing fiber demand without major stresses on land,water,and existing markets using these *** a greater emphasis on transparency and circular economy practices,there is a need to consider natural non-wood alternative sources for mmCFs to supple-ment other fiber ***,introducing new feedstocks with different compositions may require different biomass conversion ***,based on existing work,this review ad-dresses the technical feasibility of various alternative feedstocks for conversion to textile-grade ***,alternative feedstocks are introduced,and then conventional(dissolving pulp)and emerging(fibrillated cellulose and recycled material)conversion technologies are evaluated to help select the most suitable and promising processes for these emerging alternative sources of *** is important to note that for alternative feedstocks to be adopted on a meaningful scale,high biomass availability and proximity of conversion facilities are critical *** North America,soybean,wheat,rice,sorghum,and sugarcane residues are widely available and most suitable for conventional conversion through various dissolving pulp production methods(pre-hydrolysis kraft,acid sulfite,soda,SO2-ethanol-water,and potassium hydroxide)or by emerging cellulose fibrillation *** dissolving pulp conversion is well-established,fibrillated cel-lulose methods could be beneficial from cost,efficiency,and environmental ***,the authors strongly encourage more work in this growing research ***,conducting thorough cost and sustainability assessment

关键词： Non-wood Residue Regenerated cellulose Dissolving pulp man-made cellulose fiber Apparel textile

CD8+T cell metabolic flexibility elicited by CD28-ARS2 axisdriven alternative splicing of PKm supports antitumor immunity

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Cellular & molecular Immunology 2024年第3期21卷 260-274页

作者： G.Aaron Holling Colin A.Chavel Anand P.Sharda mackenzie m.Lieberman Caitlin m.James Shivana m.Lightman Jason H.Tong Guanxi Qiao Tiffany R.Emmons Thejaswini Giridharan Shengqi Hou Andrew m.Intlekofer richard m.Higashi Teresa W.m.Fan Andrew N.Lane Kevin H.Eng Brahm H.Segal Elizabeth A.Repasky Kelvin P.Lee Scott H.Olejniczak Department of Immunology Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Department of medicine Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Human Oncology and Pathogenesis Program Memorial Sloan Kettering Cancer CenterNew YorkNY 10065USA Center for Environmental Systems Biochemistry Department of Toxicology and Cancer Biology and Markey Cancer CenterLexingtonKY 40536USA Department of Cancer Genetics and Genomics Roswell Park Comprehensive Cancer CenterBuffaloNY 14263USA Present address:University of Colorado Boulder BoulderCO 80309USA Present address:Dana Farber Cancer Institute BostonMA 02215USA Present address:massachusetts Institute of Technology BostonMA 02139USA Present address:melvin and Bren Simon Comprehensive Cancer Center Indiana University School of MedicineIndianapolisIN 46202USA

metabolic flexibility has emerged as a critical determinant of CD8+T-cell antitumor activity,yet the mechanisms driving the metabolic flexibility of T cells have not been *** this study,we investigated the influence of the nuclear cap-binding complex(CBC)adaptor protein ARS2 on mature T *** doing so,we discovered a novel signaling axis that endows activated CD8+T cells with flexibility of glucose ***2 upregulation driven by CD28 signaling reinforced splicing factor recruitment to pre-mRNAs and affected approximately one-third of T-cell activation-induced alternative splicing *** these effects,the CD28-ARS2 axis suppressed the expression of the m1 isoform of pyruvate kinase in favor of PKm2,a key determinant of CD8+T-cell glucose utilization,interferon gamma production,and antitumor effector ***,PKm alternative splicing occurred independently of CD28-driven PI3K pathway activation,revealing a novel means by which costimulation reprograms glucose metabolism in CD8+T cells.

关键词： Immunometabolism mRNA splicing CD8 T cells ARS2 PKm2

Are there sex-based disparities in cataract surgery?

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International Journal of Ophthalmology(English edition) 2024年第1期17卷 137-143页

作者： matthew D.Geiger Anne m.Lynch Alan G.Palestine Nathan C.Grove Karen L.Christopher richard S.Davidson michael J.Taravella Naresh mandava Jennifer L.Patnaik Department of Ophthalmology University of Colorado School of MedicineAuroraCO 80045USA

AIm:To investigate sex-based differences in the occurrence of intra-operative and post-operative complications and associated visual outcomes following cataract ***:This was a retrospective study of patients who had phacoemulsification cataract surgery at the University of Colorado School of *** collected included the patient’s health history,ocular comorbidities,operative and post-operative complications,and the post-operative best corrected visual acuity(BCVA).The data were analyzed using univariate and multivariable logistic regression with generalized estimating equations to account for the correlation of some patients having two eyes included in the ***:A total of 11977 eyes from 7253 patients were included in the *** comorbidities differed by sex,with males having significantly higher percentages of traumatic cataracts(males 0.7%vs females 0.1%),prior ocular surgery(6.7%vs 5.5%),and mature cataracts(2.8%vs 1.9%).Conversely,females had significantly higher rates of pseudoexfoliation(2.0%vs 3.2%).In unadjusted analysis,males had higher rates of posterior capsular rupture(0.8%vs 0.4%)and vitreous loss(1.0%vs 0.6%),but this difference was not significant after adjustment for *** had a significantly increased risk of post-operative retinal detachment,but in multivariable analysis this was no longer *** were significantly less likely to undergo post-operative neodymium-doped yttrium aluminum garnet(Nd:YAG)laser capsulotomy for posterior capsule opacification(OR=0.8,95%CI=0.7-0.9,P=0.0005).The BCVA was slightly worse for males pre-operatively;but post-operatively,both sexes exhibited similar visual acuity of Snellen equivalent 20/***:The study finds that in a cohort of patients presenting for cataract surgery,sex differences exist in pre-operative comorbidities and surgical characteristics that contribute to higher rates of some complications for ***,observed surgical complicatio

关键词： cataract surgery sex-based disparity phacoemulsification outcomes

Effect of drug therapies on self-reported chemosensory outcomes after COVID-19

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World Journal of Otorhinolaryngology-Head and Neck Surgery 2024年第2期10卷 88-96页

作者： marco A.Fornazieri Bruno m.Cunha Samuel P.Nicácio Lucas K.Anzolin JoséL.B.da Silva Aristides Fernandes Neto Deusdedit Brandão Neto richard L.Voegels Fábio D.R.Pinna Department of Surgery Londrina State UniversityLondrinaBrazil Department of medicine Pontifical Catholic University of ParanáLondrinaBrazil Department of Otorhinolaryngology University of São PauloSao PauloBrazil Department of Otorhinolaryngology:Head and Neck Surgery Perelman School of MedicineSmell and Taste CenterUniversity of PennsylvaniaPhiladelphiaPennsylvaniaUSA

Objective:The aim of this study was to assess the relative efficacy of medications used following severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)infection on self-reported alterations in taste and/or smell ***:Seven hundred and fourteen persons with self-reported postcoronavirus disease 2019(post-COVID-19)chemosensory disorders were personally interviewed regarding specific medications they were administered following the acute phase of the *** dependent measure—self-reported total recovery of chemosensory symptoms—was subjected to stepwise logistic *** predictors included demographic and clinical variables,in addition to specific medications used to mitigate disease symptoms(i.e.,systemic corticosteroids,oseltamivir,vitamin C,ibuprofen,hydroxychloroquine,azithromycin,ivermectin,nitazoxanide,anticoagulants,and zinc).Results:The median time between COVID-19 symptom onset and the interviews was 81 days(interquartile range:60-104).Of the 714 subjects,249(34.9%)reported total recovery of their chemosensory function;437(61.2%)had at least one treatment since the beginning of the *** and those with more comorbidities had undergone more *** recovery rates of the treated and nontreated groups did not differ ***,respondents who had used nitazoxanide tended to have a higher rate of self-reported taste or smell *** who took oral zinc were less likely to ***:No medication employed during the first months after SARS-CoV-2 infection had a clear positive effect on returning self-reported smell or taste function to normal,although nitrazoxide trended in a positive *** zinc had a negative effect on the reported recovery of these senses.

关键词： chemosensory disorder coronavirus infections COVID-19 drug therapy SARS-CoV-2 smell loss taste loss

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基于卷积神经网络预测南海海底地形

大地测量与地球动力学 2024年第3期44卷 287-292页

作者：王怀兵万晓云 richard Fiifi Annan 中国地质大学(北京)土地科学技术学院北京市100083

针对南海区域,使用3种重力信号(垂线偏差、重力异常、垂直重力梯度异常)训练卷积神经网络模型,并将预测结果与船测数据和国外模型结果进行对比分析。将3种重力信号分成4组数据:重力异常,重力异常与垂直重力梯度异常,重力异常与垂线偏差... 详细信息

针对南海区域,使用3种重力信号(垂线偏差、重力异常、垂直重力梯度异常)训练卷积神经网络模型,并将预测结果与船测数据和国外模型结果进行对比分析。将3种重力信号分成4组数据:重力异常,重力异常与垂直重力梯度异常,重力异常与垂线偏差,以及重力异常、垂线偏差和垂直重力梯度异常。4种组合方式的反演结果与船测水深之间的标准差分别为104.780 m、102.778 m、93.788 m、88.289 m,表明随着不同类型重力数据的加入,水深预测精度明显提高,并且在深度大于2000 m时,反演结果精度提升效果更为显著。将训练集占总数据集的比例分别设置为80%、70%、60%和50%,反演结果与船测水深之间的标准差分别为88.289 m、91.256 m、92.833 m、96.022 m,表明数据量的增多可以有效提高模型学习结果的精度。

关键词：卷积神经网络重力场信息深度学习海底地形频域法