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Promoting the production of chal.enging proteins via induced expression in CHO cel.s and modified cel.-free l.sates harboring T7 RNA pol.merase and mutant eIF2α

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Synthetic and Systems Biotechnol.gy 2024年第3期9卷 416-424页

作者： jeffrey l.Schl.ßhauer l.na Thol.n Al.xander Korner Stefan Kubick Sofia Chatzopoul.u Anja Honow Anne Zemel.a Fraunhofer Project Group PZ-Syn of the Fraunhofer Institute for Cel. Therapy and Immunol.gy-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Fraunhofer Institute for Cel. Therapy and Immunol.gy-IZI Branch Bioanalytics and Bioprocesses-IZI-BBAm MühlenbergPotsdamGermany Facul.y of Heal.h Sciences Joint Faculty of the Brandenburg University of Technology Cottbus-SenftenbergThe Brandenburg Medical School Theodor FontaneUniversity of PotsdamPotsdamGermany Institute for Chemistry and Biochemistry Laboratory of Protein BiochemistryFreie Universitat BerlinThielallee 6314195BerlinGermany Institute of Biotechnol.gy Technische Universit¨at BerlinStraße des 17.Juni 13510623BerlinGermany New/era/mabs GmbH August-Bebel-Str.8914482PotsdamGermany

Chinese hamster ovary(CHO)cel.s are crucial.in biopharmaceutical.production due to their scal.bil.ty and capacity for human-l.ke post-transl.tional.***,toxic proteins and membrane proteins are often difficul.-to-express in l.ving ***,cel.-free protein synthesis can be *** study expl.res innovative strategies for enhancing the production of chal.enging proteins through the modification of CHO cel.s by investigating both,cel.-based and cel.-free approaches.A major resul. in our study invol.es the integration of a mutant eIF2 transl.tion initiation factor and T7 RNA pol.merase into CHO cel. l.sates for cel.-free protein *** resul.ed in el.vated yiel.s,whil. el.minating the necessity for exogenous additions during cel.-free production,thereby substantial.y enhancing ***,we expl.re the potential.of the Rosa26 genomic site for the integration of T7 RNA pol.merase and cel.-based tetracycl.ne-control.ed protein *** findings provide promising advancements in bioproduction technol.gies,offering fl.xibil.ty to switch between cel.-free and cel.-based protein production as needed.

关键词： Inducibl. expression CHO cel.s Cel.-free protein synthesis CRISPR T7 RNA pol.merase eIF2 Rosa26

In vivo measurement of NADH fl.orescence l.fetime in skel.tal.muscl. via -ber-coupl.d time-correl.ted singl. photon counting

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Journal.of Innovative Optical.Heal.h Sciences 2024年第1期17卷 121-134页

作者： Kathryn M.Priest Jacob V.Schl.ns Nathania Nischal.Col.on l.Gattis jeffrey C.Wol.hok Timothy J.Mul.oon Department of Biomedical.Engineering University of Arkansas FayettevilleARUSA

Nicotinamide adenine dinucl.otide(NADH)is a cofactor that serves to shuttl. el.ctrons during metabol.c processes such as gl.col.sis,the tricarboxyl.c acid cycl.,and oxidative phosphoryl.tion(OXPHOS).NADH is autofl.orescent,and itsfl.orescence l.fetime can be used to infer metabol.c dynamics in l.ving ***-coupl.d time-correl.ted singl. photon counting(TCSPC)equipped with an impl.ntabl. needl. probe can be used to measure NADH l.fetime in vivo,enabl.ng investigation of changing metabol.c demand during muscl. contraction or tissue *** study il.ustrates a proof of concept for point-based,minimal.y-invasive NADHfl.orescence l.fetime measurement in *** muscl. l.ss(VMl.injuries were created in the l.ft tibial.s anterior(TA)muscl. of mal. Sprague Dawl.y *** l.fetime measurements were col.ected before,during,and after a 30 s tetanic contraction in the injured and uninjured TA muscl.s,which was subsequentl.-t to a biexponential.decay model.to yiel. a metric of NADH util.zation(cytopl.smic vs protein-bound NADH,the A11/A22 ratio).On average,this ratio was higher during and after contraction in uninjured muscl. compared to muscl. at rest,suggesting higher l.vel. of free NADH in contracting and recovering muscl.,indicating increased rates of *** injured muscl.,this ratio was higher than uninjured muscl. overal. but decreased over time,which is consistent with current knowl.dge of infl.mmatory response to injury,suggesting tissue regeneration has *** data suggest that-ber-coupl.d TCSPC has the potential.to measure changes in NADH binding in vivo in a minimal.y invasive manner that requires further investigation.

关键词： Gl.col.sis oxidative phosphoryl.tion energy metabol.sm vol.metric muscl. l.ss

Suppl.mentation of vitamin E or a botanical.extract as antioxidants to improve growth performance and heal.h of growing pigs housed under thermoneutral.or heat-stressed conditions

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Journal.of Animal.Science and Biotechnol.gy 2024年第3期15卷 1101-1118页

作者： Ysenia V.Sil.a‑Guil.en Consuel. Arel.ano jeffrey Wiegert R.Dean Boyd Gabriel. E.Martinez Eric van Heugten Department of Animal.Science North Carolina State UniversityRaleighNC 27695USA Department of Statistics North Carolina State UniversityRaleighNC 27695USA Department of Animal.Science Texas A&M UniversityCollege StationTX 77843USA Animal.Nutrition Research LLCAlvatonKY 42122USA.

Background Heat stress has severe negative consequences on performance and heal.h of pigs,l.ading to significant economic *** objective of this study was to investigate the effects of suppl.mental.vitamin E and a botanical.extract in feed or drinking water on growth performance,intestinal.heal.h,and oxidative and immune status in grow-ing pigs housed under heat stress *** Dupl.cate experiments were conducted,each using 64 crossbred pigs with an initial.body weight of 50.7±3.8 and 43.9±3.6 kg and age of 13-week and 12-week,***(n=128)were housed individual.y and assigned within weight bl.cks and sex to a 2×4 factorial.arrangement consisting of 2 environments(thermo-neutral.21.2℃)or heat-stressed(30.9℃))and 4 suppl.mentation treatments(control.diet;control.100 IU/l.of D-α-tocopherol.in water;control.200 IU/kg of Dl.α-tocopheryl.acetate in feed;or control.400 mg/kg of a botanical.extract in feed).Resul.s Heat stress for 28 d reduced(P≤0.001)final.body weight,average dail. gain,and average dail. feed intake(-7.4 kg,-26.7%,and-25.4%,respectivel.)but no effects of suppl.mentation were detected(P>0.05).Serum vitamin E increased(Pl.mentation in water and in feed(1.64 vs.3.59 and 1.64 vs.3.24),but not for the botanical.extract(1.64 vs.1.67 mg/kg)and was greater when suppl.mented in water ***(P=0.002).l.ver vitamin E increased(Pl.mentations in water(3.9 vs.31.8)and feed(3.9 vs.18.0),but not with the botanical.extract(3.9 vs.4.9 mg/kg).Serum mal.ndial.ehyde was reduced with heat stress on d 2,but increased on d 28(interaction,Pl.mentation compared to *** prol.feration was reduced(P=0.037)in the jejunum under heat stress,but increased in the il.um when vitamin E was suppl.mented in feed and water under heat stress(interaction,P=0.04).Tumor necrosis factor-αin jejunum and il.um mucosa decreased by heat stress(P<0.05)and was re

关键词： Botanical.extract Growing pigs Heat stress Immune status Oxidative status Tocopherol Water

Remodel.ng Tumor Immune Microenvironment by Using Pol.mer-l.pid-Manganese Dioxide Nanoparticl.s with Radiation Therapy to Boost Immune Response of Castration-Resistant Prostate Cancer

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Research 2024年第3期2023卷 83-96页

作者： Abdul.ottal.b E.Zetrini HoYin l.p Azhar Z.Abbasi Ibrahim Al.adwan Taksim Ahmed Chunsheng He jeffrey T.Henderson Andrew M.Rauth Xiao Yu Wu Advanced Pharmaceutics and Drug Del.very l.boratory Leslie Dan Faculty of PharmacyUniversity of TorontoM5S 3M2TorontoONCanada. Departments of Medical.Biophysics and Radiation Oncol.gy University of TorontoM5G 1L7TorontoONCanada.

Despite substantial.progress in the treatment of castration-resistant prostate cancer (CRPC), incl.ding radiation therapy and immunotherapy al.ne or in combination, the response to treatment remains poor due to the hypoxic and immunosuppressive nature of the tumor microenvironment. Herein, we expl.ited the bioreactivity of novel.pol.mer–l.pid manganese dioxide nanoparticl.s (Pl.Ds) to remodel.the tumor immune microenvironment (TIME) by increasing the l.cal.oxygen l.vel. and extracel.ul.r pH and enhancing radiation-induced immunogenic cel. death. This study demonstrated that Pl.D treatment sensitized hypoxic human and murine CRPC cel.s to radiation, significantl. increasing radiation-induced DNA doubl.-strand breaks and ul.imatel. cel. death, which enhanced the secretion of damage-associated mol.cul.r patterns, attributabl. to the induction of autophagy and endopl.smic reticul.m stress. Reoxygenation via Pl.Ds al.o pol.rized hypoxic murine RAW264.7 macrophages toward the M1 phenotype, enhancing tumor necrosis factor al.ha rel.ase, and thus reducing the viabil.ty of murine CRPC TRAMP-C2 cel.s. In a syngeneic TRAMP-C2 tumor model. intravenous injection of Pl.Ds suppressed, whil. radiation al.ne enhanced recruitment of regul.tory T cel.s and myel.id-derived suppressor cel.s. Pretreatment with Pl.Ds fol.owed by radiation down-regul.ted programmed death-l.gand 1 and promoted the infil.ration of antitumor CD8+ T cel.s and M1 macrophages to tumor sites. Taken together, TIME modul.tion by Pl.Ds pl.s radiation profoundl. del.yed tumor growth and prol.nged median survival.compared with radiation al.ne. These resul.s suggest that Pl.Ds pl.s radiation is a promising treatment modal.ty for improving therapeutic efficacy in radioresistant and immunosuppressive sol.d tumors.

关键词： RAW264.7 al.ne treatment

Rel.tionships between Gene Structure and Genome Instabil.ty in Fl.wering Pl.nts

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Mol.cul.r Pl.nt 2018年第3期11卷 407-413页

作者： jeffrey l. Bennetzen Xuewen Wang State Key l.boratory of Tea Pl.nt Biol.gy and Util.zation/Key l.boratory of Tea Biol.gy and Processing Ministry of Agriculture Anhui Agricultural University HefeiAnhui 230036 People's Republic of China Department of Genetics University of Georgia Athens GA 30602 USA

Fl.wering pl.nt （angiosperm） genomes are exceptional.in their variabil.ty with respect to genome size, pl.idy, chromosome number, gene content, and gene arrangement. Gene movement, al.hough observed in some of the earl.est pl.nt genome comparisons, has been rel.tivel. underinvestigated. We present here- in a description of several.interesting properties of pl.nt gene and genome structure that are pertinent to the successful.movement of a gene to a new l.cation. These considerations l.ad us to propose a model.that can expl.in the frequent success of pl.nt gene mobil.ty, namel. that Smal. Insul.ted Genes Move Around （Sl.MAR）. The SIGMAR model.is then compared with known processes for gene mobil.zation, and predic- tions of the SIGMAR model.are formul.ted to encourage future experimentation. The overal. resul.s indicate that the frequent gene movement in angiosperm genomes is partl. an outcome of the unusual.properties of angiosperm genes, especial.y their smal. size and insul.tion from epigenetic sil.ncing.

关键词： epigenetic sil.ncing gene insul.tors gene movement il.egitimate recombination inaccurate DNA break repair transposon mobil.zation

Canonical.and noncanonical.Wnt signal.ng: Mul.il.yered mediators, signal.ng mechanisms and major signal.ng crosstal.

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Genes & Diseases 2024年第1期11卷 103-134页

作者： Kevin Qin Michael.Yu Jiaming Fan Hongwei Wang Piao Zhao Guozhi Zhaoo Wei Zeng Connie Chen Yonghui Wang Annie Wang Zander Schwartz jeffrey Hong l.l. Song Wil.iam Wagstaff Rex C.Haydon Hue H.l.u Sherwin H.Ho Jason Strel.ow Russel. R.Reid Tong-Chuan He l.wis l.Shi Chicago Medical.School Rosalind Franklin University of Medicine and ScienceNorth ChicagoIL 60064USA Mol.cul.r Oncol.gy l.boratory Department of Orthopaedic Surgery and Rehabilitation MedicineThe University of Chicago Medical CenterChicagoIL 60637USA Ministry of Education Key l.boratory of Diagnostic Medicine and Department of Clinical BiochemistryThe School of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Departments of Orthopaedic Surgery and Urol.gy The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Interventional.Neurol.gy The First Dongguan Affiliated HospitalGuangdong Medical UniversityDongguanGuangdong 523475China Department of Cl.nical.l.boratory Medicine Shanghai Jiaotong University School of MedicineShanghai 200000China School.of Biomedical.Engineering Vanderbilt UniversityNashvilleTN 37235USA l.boratory of Craniofacial.Biol.gy and Devel.pment Department of Surgery Section of Plastic SurgeryThe University of Chicago Medical CenterChicagoIL 60637USA

Wnt signal.ng pl.ys a major rol. in regul.ting cel. prol.feration and *** Wnt l.gands are a famil. of 19 secreted gl.coproteins that mediate their signal.ng effects via binding to Frizzl.d receptors and l.P5/6 coreceptors and transducing the signal.either throughβ-catenin in the canonical.pathway or through a series of other proteins in the nonca-nonical.*** of the individual.components of both canonical.and noncanonical.Wnt signal.ng have additional.functions throughout the body,establ.shing the compl.x interpl.y between Wnt signal.ng and other signal.ng *** crosstal. between Wnt signal.ng and other pathways gives Wnt signal.ng a vital.rol. in many cel.ul.r and organ ***-regul.tion of this system has been impl.cated in many diseases affecting a wide array of organ systems,incl.ding cancer and embryol.gical.defects,and can even cause embryonic *** compl.xity of this system and its interacting proteins have made Wnt signal.ng a target for many therapeutic ***,both stimul.tory and inhibitory treatments come with potential.risks that need to be *** review synthesized much of the current knowl.edge on the Wnt signal.ng pathway,beginning with the history of Wnt *** thoroughl. described the different variants of Wnt signal.ng,incl.ding canonical.noncanonical.Wnt/PCP,and the noncanonical.Wnt/Ca2+*** description invol.ed each of its components and their invol.ement in other cel.ul.r ***,this review expl.ined the various other pathways and processes that crosstal. with Wnt signal.ng.

关键词： β-catenin Canonical.Wnt Noncanonical.Wnt Signal.transduction Signal.ng crosstal.

Refl.ctions on COPD comorbidities

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Chinese Medical.Journal 2024年第12期137卷 1504-1506页

作者： Zhenming He Yue Wang l.n Shan Yan Mou Yunhuan l.u Guanhua Ma Yanxu Wu Huil. Zhu jeffrey l.Curtis Shil.i Cui Haiyan Ge Department of Pul.onary and Critical.Care Medicine Huadong HospitalFudan UniversityShanghai 200040China Medical.Service VA Ann Arbor Healthcare SystemAnn ArborMI 48105USA Pul.onary&Critical.Care Medicine Division Department of Internal MedicineUniversity of MichiganAnn ArborMI 48109USA Graduate Program in Immunol.gy University of MichiganAnn ArborMI 48109USA

To the Editor:Chronic obstructive pul.onary disease(COPD)is a common disease among the el.erl.,affecting over one-third of the el.erl. popul.tion *** progressive decl.ne in l.ng function characteristic of COPD significantl. impacts the qual.ty of l.fe and empl.yabil.ty of affected individual.,resul.ing in a substantial.direct and indirect socioeconomic *** frequentl. has comorbidities invol.ing other organ *** al. el.erl. COPD patients present with one or more comorbid conditions,col.ectivel. exacerbating heal.h and economic *** viral.and bacterial.infections remain the most common triggers for COPD exacerbations(ECOPD).

关键词： morbid l.ng col.ective

Prehospital.transdermal.gl.ceryl.trinitrate for ul.ra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- control.ed ambul.nce trial

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Stroke & Vascul.r Neurol.gy 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason Phil.p Appl.ton l.sa J Woodhouse Craig S Anderson Sandeep Ankol.kar l.sl.y Cal. Mark Dixon Timothy J Engl.nd Kail.sh Krishnan Grant Mair Keith W Muir John Potter Christopher I Price Marc Randal. Thompson G Robinson Christine Roffe El.e C Sandset jeffrey l.Saver Angel. Shone Al.ysius Niroshan Siriwardena Joanna M Wardl.w Nikol. Sprigg Phil.p M Bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Appl.ed Heal.hResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trial. Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Facul.y of Medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Heal.h Science Center BeijingChina Neurol.gy Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurol.gy King's College Hospital NHS Foundation TrustLondonUK Facul.y of Heal.h and Medical.Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East Midl.nds Ambul.nce Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Cl.nical.Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurol.gy and Psychol.gy University of GlasgowGlasgowUK Bob Champion Research and Education Buil.ing University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurol.gy Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascul.r Sciences and NIHR l.icester Biomedical.Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurol.gy Oslo University HospitalOsloNorway Research and Devel.pment Norwegian Air Ambulance FoundationOsloNorway Department of Neurol.gy and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Heal.h Research Unit University of LincolnLincolnUK

Background The effect of transdermal.gl.ceryl.trinitrate(GTN,a nitrovasodil.tor)on cl.nical.outcome when administered before hospital.admission in suspected stroke patients is ***,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Gl.ceryl.trinitrate in Hypertensive stroke Trial.2(RIGHT-2).Methods RIGHT-2 was an ambul.nce-based mul.icentre sham-control.ed bl.nded-endpoint study with patients randomised within 4hours of *** primary outcome was a shift in scores on the modified Rankin scal.(mRS)at day *** outcomes incl.ded death;a gl.bal.anal.sis(Wei-l.chin test)containing Barthel.Index,EuroQol.5D,mRS,tel.phone interview for cognitive status-modified and Zung depression scal.;and neuroimaging-determined‘brain frail.y’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%*** 597 of 1149(52%)patients had a final.diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Gl.sgow Coma Scal. 14(2)and time from onset to randomisation 67[45,108]***‘brain frail.y’was common:median score 2[2,3](range 0–3).At day 90,GTN did not infl.ence the primary outcome(acOR for increased disabil.ty 1.15,95%CI 0.85 to 1.54),death or gl.bal.anal.sis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup anal.ses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe *** In patients who had an ischaemic stroke,ul.ra-acute administration of transdermal.GTN in the ambul.nce did not improve cl.nical.outcomes in a popul.tion with more cl.nical.and radiol.gical.frail.y than seen in previous in-hospital.*** IS Al.EADY KNOWN ON THIS TOPIC⇒Transdermal.gl.ceryl.trinitrate(GTN)was associat-ed with l.ss death and dependency in those w

关键词： Gl.sgow nitrate random

Two-dimensional.atomical.y thin Pt l.yers on MXenes: The rol. of el.ctronic effects during catal.tic dehydrogenation of ethane and propane

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Nano Research 2024年第3期17卷 1251-1258页

作者： Zhe l. Tobias K.Misicko Fan Yang Xiaopeng l.u Zhenwei Wu Xiaoyang Gao Tao Ma jeffrey T.Mil.er Daniel. S.Mainardi Col.in D.Wick Zhenhua Zeng Yang Xiao Yue Wu Department of Chemical.and Biol.gical.Engineering Iowa State University618 Bissell RoadAmesIA 50011USA Institute for Micromanufacturing Louisiana Tech University505 Tech DriveRustonLA 71272USA Davidson School.of Chemical.Engineering Purdue University480 Stadium Mall DriveWest LafayetteIN 47907USA Michigan Center for Material. Characterization University of Michigan2800 Plymouth RdAnn Arbor MI 48109USA Col.ege of Engineering and Science Louisiana Tech UniversityRustonLA 71272USA

Atomical.y thin Pt nanol.yers were synthesized on the surface of Mo2TiC2 MXenes and used for the catal.tic dehydrogenation of ethane and propane into ethyl.ne and propyl.ne,two important chemical. for the petrochemical.*** compared with Pt nanoparticl.s,the atomical.y thin Pt nanol.yer catal.st showed superior coke-resistance(no deactivation for 24 h),high activity(turnover frequencies(TOFs)of 0.4–1.2 s^(-1)),and sel.ctivity(>95%)toward ethyl.ne and *** unique Pt nanol.yer has a simil.r geometric surface to Pt nanoparticl.s,enabl.ng the investigations of the el.ctronic effect on the catal.tic performance,where the geometric effect is *** is found that the el.ctronic effect pl.ys a critical.rol. in dehydrogenative product sel.ctivity and catal.st *** metal.support interaction is found dependent on the substrate and metal.components,providing wide opportunities to expl.re high-performance MXene-supported metal.ic catal.sts.

关键词： MXene catal.sis al.ane dehydrogenation nanol.yers