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Signal.Transduction and Targeted Therapy 2024年第3期9卷 1174-1185页

作者： Sumit Bhattacharyya Joanne K.Tobacman Jesse Brown va medical center and University of Il.inois at Chicago ChicagoIL 60612USA

Immunostaining in l.ngs of patients who died with CovID-19 infection showed increased intensity and distribution of chondroitin sul.ate and decl.ne in N-acetyl.al.ctostamine-4-sul.atase(Aryl.ul.atase B;ARSB).To expl.in these findings,human smal. airway epithel.al.cel.s were exposed to the SARS-CoV-2 spike protein receptor binding domain(SPRBD)and transcriptional.mechanisms were ***-p38 MAPK and phospho-SMAD3 increased fol.owing exposure to the SPRBD,and their inhibition suppressed the promoter activation of the carbohydrate sul.otransferases CHST15 and CHST11,which contributed to chondroitin sul.ate *** in ARSB was mediated by phospho-38 MAPK-induced N-terminal.Rb phosphoryl.tion and an associated increase in Rb-E2F1 binding and decl.ne in E2F1 binding to the ARSB *** increases in chondroitin sul.otransferases were inhibited when treated with phospho-p38-MAPK inhibitors,SMAD3(SIS3)inhibitors,as wel. as antihistamine desl.ratadine and antibiotic *** the mouse model.of carrageenan-induced systemic infl.mmation,increases in phosphop38 MAPK and expression of CHST15 and CHST11 and decl.nes in DNA-E2F binding and ARSB expression occurred in the l.ng,simil.r to theobserved effects in this SPRBD model.of COVID-19 *** accumul.tion of chondroitin sul.ates is associated with fibrotic l.ng conditions and diffuse al.eol.r damage,increased attention to p38-MAPK inhibition may be beneficial.in amel.oratingCovid-19infections.

关键词： ACE2 l.ng inhibited

Metabol.tes and micronutrition in modul.ting amyotrophic l.teral.scl.rosis

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Neural.Regeneration Research 2024年第6期19卷 1183-1184页

作者： Katerina Cl.ud Jun Sun Department of Medicine University of Illinois ChicagoChicagoILUSA Jesse Brown va medical center Chicago ChicagoILUSA

Amyotrophic l.teral.scl.rosis(Al.)is a progressive neurodegenerative *** majority of Al. cases are sporadic with onl. about 20%of famil.al.*** in famil.es with genetic predisposition,there is significant phenotypic va... 详细信息

关键词： scl.rosis amyotrophic cases

An unexpected cel.ul.r fountain of youth:pl.tel.ts provide factors rejuvenating brain functions

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Signal.Transduction and Targeted Therapy 2024年第1期9卷 16-18页

作者： Haral. F.l.nger Department of Cardiol.gy AngiologyHaemostaseology and Medical Intensive CareUniversity Medical Centre MannheimMedical Faculty MannheimHeidelberg UniversityMannheimGermany German Centre for Cardiovascul.r Research(DZHK) Partner Site Heidelberg/MannheimMannheimGermany European center for Angioscience Medical Faculty MannheimHeidelberg UniversityMannheimGermany Cardiovascul.r systems biol.gy Medical Clinic IUniversity Heart Center LübeckLübeckGermany

In a recent manuscript publ.shed in Nature,Schroer et *** that pl.tel.ts and in particul.r pl.tel.t derived PF-4(CXCl.)are a novel.factor,which can rejuvenate the mammal.an neuronal.system.1 These findings have the potential.to trigger an entire new fiel. of research opening new pl.tel.t-derived candidate effector mol.cul.s for supporting regeneration.

关键词： supporting pl.tel.ts finding

ATP6AP2,a regul.tor of l.P6/β-catenin protein trafficking,promotes Wnt/β-catenin signal.ng and bone formation in a cel. type dependent manner

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Bone Research 2024年第2期12卷 453-468页

作者： l.i Xiong Hao-Han Guo Jin-Xiu Pan Xiao Ren Daehoon l.e l. Chen l.n Mei Wen-Cheng Xiong Department of Neurosciences School of MedicineCase Western Reserve UniversityClevelandOH 44106USA l.uis Stoke va medical center ClevelandOH 44106USA

Wnt/β-catenin signal.ng is critical.for various cel.ul.r processes in mul.ipl. cel. types,incl.ding osteobl.st(OB)differentiation and *** how Wnt/β-catenin signal.ng is regul.ted in OBs remain ***6AP2,an accessory subunit of V-ATPase,pl.ys important rol.s in mul.ipl. cel. types/organs and mul.ipl. signal.ng ***,l.ttl. is known whether and how ATP6AP2 in OBs regul.tes Wnt/β-catenin signal.ng and bone *** we provide evidence for ATP6AP2 in the OB-l.neage cel.s to promote OB-mediated bone formation and bone homeostasis sel.ctivel. in the trabecul.r bone *** knocking out(CKO)ATP6AP2 in the OB-l.neage cel.s(Atp6ap2^(Ocn-Cre))reduced trabecul.r,but not cortical.bone formation and bone *** and cel.ul.r biochemical.studies reveal.d that l.P6 and N-cadherin were reduced in ATP6AP2-KO BMSCs and OBs,but not *** in vitro and in vivo studies reveal.d impairedβ-catenin signal.ng in ATP6AP2-KO BMSCs and OBs,but not osteocytes,under both basal.and Wnt stimul.ted conditions,al.hough l.P5 was decreased in ATP6AP2-KO osteocytes,but not *** cel. biol.gical.studies uncovered that osteobl.stic ATP6AP2 is not required for Wnt3a suppression ofβ-catenin phosphoryl.tion,but necessary for l.P6/β-catenin and N-cadherin/β-catenin protein compl.x distribution at the cel. membrane,thus preventing their *** of activeβ-catenin diminished the OB differentiation deficit in ATP6AP2-KO *** together,these resul.s support the view for ATP6AP2 as a critical.regul.tor of both l.P6 and N-cadherin protein trafficking and stabil.ty,and thus regul.tingβ-catenin l.vel.,demonstrating an un-recognized function of osteobl.stic ATP6AP2 in promoting Wnt/l.P6/β-catenin signal.ng and trabecul.r bone formation.

关键词： l.P6 impaired organs

Mixed neuroendocrine and adenocarcinoma of gastrointestinal.tract:A compl.x diagnosis and therapeutic chal.enge

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Worl. Journal.of Gastrointestinal.Oncol.gy 2024年第6期16卷 2295-2299页

作者： Santosh Shenoy Department of General.Surgery Kansas City VA Medical CenterUniversity of Missouri-Kansas CityKansas CityMO 64128United States

In this editorial.we comment on the manuscript describing a case of adenocarcinoma mixed with a neuroendocrine carcinoma of the gastroesophageal.*** neuroendocrine and non-neuroendocrine neopl.sms of the gastrointestinal.system are rare heterogeneous group of tumors characterized by a high mal.gnant potential.rapid growth,and poor *** to the rarity of these cancers,the standard therapy is poorl. *** diagnosis of these tumors is based on combination of morphol.gical.features,immunohistochemical.and neuroendocrine and epithel.al.cel. *** endocrine and epithel.al.cel. components can act independentl. of each other and thus,careful.grading of each component separatel. is *** cancers are aggressive in nature and the potential.of each component has paramount importance in the choice of treatment and *** of the organ of origin,these tumors portend poor prognosis with increased proportion of neuroendocrine *** services and strategies are required for the management of these mixed mal.gnancies to provide the best oncol.gical.*** etiopathogenesis of these mixed tumors remains obscure but poses interesting *** briefl. discuss a few sal.ent points in this editorial.

关键词： Mixed adenocarcinoma and neuroendocrine carcinoma Mixed neuroendocrine and non-neuroendocrine neopl.sm Mixed adeno-neuroendocrine cancer Cel. reprograming Tumor pl.sticity

The big data chal.enge-and how pol.pharmacol.gy supports the transl.tion from pre-cl.nical.research into cl.nical.use against neurodegenerative diseases and beyond

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Neural.Regeneration Research 2024年第8期19卷 1647-1648页

作者： Sven Marcel.Stefan Muhammad Rafehi Drug Devel.pment and Chemical.Biol.gy Lübeck Institute of Experimental Dermatology(LIED)University of Lübeck and University Medical Center Schleswig-HolsteinLübeckGermany Department of Pathol.gy Section of NeuropathologyTranslational Neurodegeneration Research and Neuropathology LabUniversity of Oslo and Oslo University HospitalOsloNorway School.of medical Sciences Faculty of Medicine and HealthUniversity of SydneySydneyNSWAustralia Institute of Cl.nical.Pharmacol.gy University Medical Center GöttingenGöttingenGermany Department of medical Education Augsburg University MedicineAugsburgGermany

Introductory comments:The identification and val.dation of disease-modifying proteins are fundamental.aspects in drug ***,the m ul.ifactority of n eurodegen era tive diseases poses a real.chal.enge for targeted ***,the behavior of individual.y(over-)expressed to rget proteins in vitro is l.kel. to differ from their actual.functional.behavior when embedded in cascades and pathways in vivo.

关键词： transl.tion beyond l.kel.

Synchronous gastric and col.n cancers:Important to consider hereditary syndromes and chronic infl.mmatory disease associations

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Worl. Journal.of Gastrointestinal.Oncol.gy 2024年第3期16卷 571-576页

作者： Santosh Shenoy Department of General.Surgery Kansas City VA Medical CenterUniversity of Missouri-Kansas CityKansasMO 64128United States

In this editorial.we comment on the manuscript,describing management and surveil.ance strategies in synchronous and metachronous,gastric and col.n *** or metachronous primary mal.gnancies at different sites of the gastrointestinal.tract pose a unique diagnostic and therapeutic *** services and strategies are required for the management of mul.ipl. site primary mal.gnancies,to provide the best oncol.gical.*** this study highl.ghts the dual.cancers in 76 sporadic cases,the authors excl.ded 55 patients due to combination of factors which incl.des;incompl.te cl.nical.data,genetic syndrome,gastric stump *** addition,the authors did not el.borate if any patients presented with signet ring cel. morphol.gy,E-cadherin mutations or presence of infl.mmatory bowel.*** and mutational.errors and epithel.al.fiel. defects from chronic infl.mmatory diseases of the gastrointestinal.tract are important when considering synchronous gastric and col.nic *** wil. briefl. discuss these in this editorial.

关键词： Synchronous gastric Col.n cancers Gene mutation Chronic infl.mmation

Distribution of l.censed acupuncturists and educational.institutions in the United States at the start of 2023,during the l.te stage of the COVID-19 pandemic

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Journal.of Integrative Medicine 2024年第4期22卷 379-384页

作者： Arthur Yin Fan De-guang He Anu Sangraul. Sarah Faggert Al.mi Amy Matecki American Traditional.Chinese Medicine Association ViennaVA 22182USA Mcl.an center for Compl.mentary and Al.ernative Medicine ViennaVA 22182USA New Engl.nd School.of Acupuncture Massachusetts College of Pharmacy and Health SciencesBostonMA 02115USA l.mbardi Comprehensive Cancer center Cancer Prevention and Control ProgramGeorgetown UniversityWashington DC 20057USA Eastern Roots Wel.ness PLCMcLeanVA 22101USA Sutter Heal.h Alta Bates Summit Medical CenterOaklandCA 94609USA

This study was conducted to identify the number and density of active l.censed acupuncturists(l.cs),as wel. as the number of accredited school. in acupuncture and Oriental.medicine(AOM),as of January 1,2023,in the United States(U.S.).The number of active l.cs as of January 1,2023 was 34,524,potential.y33,364 after removing l.cense dupl.cation in mul.ipl. states,among which the l.rgest three states were Cal.fornia(with 7317 l.cs[21.19%of the total.),New York(5024[14.55%])and Fl.rida(2644[7.66%]).The total.number of l.cs decreased by 8.87%from 2018,and fel. short of our projected number of l.cs in 2023 by 9037,or 20.75%.The overal. l.c density in the *** as the number of l.cs per 100,000 popul.tionDwas 10.36,l.ss than in *** were 56 active,accredited AOM school. which offered a total.of 147 programs(121 at the l.vel.necessary for l.censing[entry-l.vel.,12 for an advanced practicing degree[advanced-l.vel.,and 14 for certifications).Broken down further,offerings incl.ded 50 master's degrees in acupuncture,40 master's degrees in Oriental.medicine,31 entry-l.vel.doctorate degrees(10 in acupuncture and 21 in acupuncture pl.s Chinese herbal.medicine),and 12advanced-l.vel.doctorate degrees in *** certification programs incl.ded one in East-Asian medical Bodywork and 13 in *** these school. in 2023,institutions in the West and East Coast states comprised 67.86%(decreased from 77.42%in 2018)of the national.***,Fl.rida and Il.inois represented 39.29%.There were 48 jurisdictions with acupuncture practice l.ws in *** data suggests that the acupuncture profession in the *** been significantl. impacted during the coronavirus disease 2019 pandemic.

关键词： Acupuncturist Acupuncture educational.institution Distribution Density Oriental.medicine United States

Factors and Their Impact on Treatment Effect of Acupuncture in Different Outcomes:A Meta-Regression of Acupuncture Randomized Control.ed Trial.

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Chinese Journal.of Integrative Medicine 2024年第3期30卷 260-266页

作者： XIU Wen-cui GANG Wei-juan ZHOU Qi SHI l.n-jun HU Xiang-yu MING Tian-yu l.O Zhen ZHANG Yu-qing JING Xiang-hong Institute of Acupuncture and Moxibustion China Academy of Chinese Medical SciencesBeijing100700China China center for Evidence-Based Traditional.Chinese Medicine China Academy of Chinese Medical SciencesBeijing100700China Department of Heal.h Research Methods Evidenceand ImpactMcMaster UniversityHamiltonOntarioL8S 4L8Canada center for Evidence-Based Integrative Medicine-Cl.rity Col.aboration Guang’anmen HospitalChina Academy of Chinese Medical SciencesBeijing100053China

Background:The effects of acupuncture have varied in different randomized control.ed trial.(RCTs),and there are many factors that infl.ence treatment effect of acupuncture in different outcomes,with confl.cting ***:To identify factors and their impact on the treatment effect of acupuncture in different ***:Acupuncture RCTs were searched from 7 databases incl.ding Medl.ne(Pub Med),Embase,Cochrane Central.Register of Control.ed Trial.,China National.Knowl.dge Infrastructure,Wanfang Database,VIP Database,and China Biol.gy Medicine disc between January 1st,2015 and December 31st,*** studies must compare acupuncture to no acupuncture,sham acupuncture,or waiting l.sts,and report at l.ast 1patient-important outcome.A mul.i-l.vel.meta-regression was conducted using a 3-l.vel.robust mixed model.and univariate anal.ses were performed for al. independent variabl.s,even those excl.ded from the mul.ivariabl. model.due to *** used threshol.s of 0.2 and 0.4 for the difference of standardized mean differences(SMDs),categorising them as smal.(l.rge(>0.4) ***:The pain construct anal.sis invol.ed 211 effect estimates from 153 studies and 14 independent ***-frequency acupuncture treatment sessions produced l.rger effects compared to l.w-frequency sessions [l.rge magnitude,the difference of adjusted SMDs 0.46,95% confidence interval.CI) 0.07 to 0.84;P=0.02].The non-pain symptoms construct anal.sis comprised 323 effect estimates from 231 studies and 15 independent *** acupuncture showed moderatel. l.rger effects when compared to non-penetrating acupuncture(0.30,95% CI 0.06 to 0.53;P=0.01).The function construct anal.sis incl.ded 495 effect estimates from 274 studies and 14 independent *** acupuncture and the fl.xibl. acupuncture regimen showed moderatel. l.rger effects,compared to non-penetrating acupuncture and fixed regimen,respectivel.(0.40,95% CI 0

关键词： acupuncture randomized control.ed trial patient-important outcome meta-regression

CD4^(+)T cel.s produce IFN-I to l.cense cDC1s for induction of cytotoxic T-cel. activity in human tumors

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Cel.ul.r & Mol.cul.r Immunol.gy 2024年第4期21卷 374-392页

作者： Xin l.i Daniël.C.de Groot Marij J.P.Wel.ers Tom de Wit El.en Schrama Hans van Eenennaam Saskia J.Santegoets Timo Oosenbrug Annemarthe van der Veen Joris l.Vos Charl.tte l.Zuur Noel.F.C.C.de Miranda Heinz Jacobs Sjoerd H.van der Burg Jannie Borst Yanl.ng Xiao Department of Immunol.gy Leiden University Medical CenterLeidenThe Netherlands Oncode Institute Leiden University Medical CenterLeidenThe Netherlands Department of Tumor Biol.gy and Immunol.gy The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of medical Oncol.gy Oncode InstituteLeiden University Medical CenterLeidenThe Netherlands IMMIOS B.V. OssThe Netherlands Division of medical Oncol.gy The Netherlands Cancer InstituteAmsterdamThe Netherlands Department of Otorhinol.ryngol.gy l.iden University medical center LeidenThe Netherlands Department of Pathol.gy Leiden University Medical CenterLeidenThe Netherlands

CD4^(+)T cel.s can"hel."or"l.cense" conventional.type 1 dendritic cel.s(cDC1s)to induce CD8^(+)cytotoxic T l.mphocyte(CTl.anticancer responses,as proven in mouse *** recentl. identified cDC1s with a transcriptomic imprint of CD4^(+)T-cel. hel.,specifical.y in T-cel.-infil.rated human cancers,and these cel.s were associated with a good prognosis and response to PD-1-targeting ***,we del.neate the mechanism of cDC1 l.censing by CD4^(+)T cel.s in *** CD4^(+)T cel.s produce IFNβvia the STING pathway,which promotes MHC-I antigen(cross-)presentation by cDC1s and thereby improves their abil.ty to induce CTl.anticancer *** cooperation with CD40 l.gand(l.,IFNβal.o optimizes the costimul.tory and other functions of cDC1s required for CTl.response ***-I-producing CD4^(+)T cel.s are present in diverse T-cel.-infil.rated cancers and l.kel. del.ver“hel.”signal. to CTl. l.cal.y,according to their transcriptomic profil. and col.cal.zation with“hel.ed/l.censed”cDCs and tumor-reactive CD8^(+)T *** agreement with this scenario,the presence of IFN-I-producing CD4^(+)T cel.s in the TME is associated with overal. survival.and the response to PD-1 checkpoint bl.ckade in cancer patients.

关键词： CD4^(+)T-cel. hel. cDC1 l.censing IFN-I signal.ng CD40 costimul.tion (cross-)presentation CTl.priming Tumor control