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A DL-4- and tNFα-based culture system to generate high numbers of nonmodified or genetically modified immunotherapeutic human t-lymphoid progenitors

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Cellular & Molecular Immunology 2021年第7期18卷 1662-1676页

作者： Ranjita Devi Moirangthem Kuiying Ma Sabrina Lizot Anne Cordesse juliette Olivré Corinne de Chappedelaine Akshay joshi Agata Cieslak john tchen Nicolas Cagnard Vahid Asnafi Antonio Rausell Laura Simons julien Zuber tom taghon frank j.t.staal Françoise Pflumio Emmanuelle Six Marina Cavazzana Chantal Lagresle-Peyrou tayebeh Soheili Isabelle André Universitéde Paris Imagine InstituteLaboratory of Human LymphohematopoiesisINSERM UMR 1163ParisFrance Laboratory of Onco-Hematology AP-HPHôpital Necker-Enfants Malades.ParisFrance Universitéde Paris Institut Necker-Enfants Malades(INEM)INSERM UMR 1151ParisFrance Plateforme Bio-informatique UniversitéParis DescartesStructure Fédérative de Recherche NeckerINSERM US24/CNRS UMS 3633ParisFrance Universitéde Paris Imagine InstituteLaboratory of Clinical BioinformaticsINSERM UMR 1163ParisFrance Department of Biotherapy Clinical Investigation Center AP-HPHôpital Necker-Enfants MaladesParisFrance Department of Adult Kidney transplantation AP-HPHôpital NeckerParisFrance Cancer Research Institute Ghent(CRIG) GhentBelgium Department of Diagnostic Sciences Faculty of Medicine and Health SciencesGhent UniversityGhentBelgium Department of Immunohematology&Blood transfusion Leiden University Medical CenterLeidenthe Netherlands team Niche and Cancer in Hematopoiesis Universitéde Paris and UniversitéParis-SaclayINSERMiRCM/IBFJ CEAUMR StabilitéGénétique Cellules Souches et RadiationsFontenay-aux-RosesFrance

Several obstacles to the production,expansion and genetic modification of immunotherapeutic t cells in vitro have restricted the widespread use of t-cell *** the context of HSCt,delayed naïve t-cell recovery contributes to poor outcomes.A novel approach to overcome the major limitations of both t-cell immunotherapy and HSCt would be to transplant human t-lymphoid progenitors(HtLPs),allowing reconstitution of a fully functional naïve t-cell pool in the patient ***,it is challenging to produce HtLPs in the high numbers required to meet clinical ***,we found that adding tumor necrosis factor alpha(tNFα)to a DL-4-based culture system led to the generation of a large number of nonmodified or genetically modified HtLPs possessing highly efficient in vitro and in vivo t-cell potential from either CB HSPCs or mPB HSPCs through accelerated t-cell differentiation and enhanced HtLP cell cycling and *** study provides a clinically suitable cell culture platform to generate high numbers of clinically potent nonmodified or genetically modified HtLPs for accelerating immune recovery after HSCt and for t-cell-based immunotherapy(including CAR t-cell therapy).

关键词： Human t-lymphoid progenitor tumor necrosis factor alpha Delta-like ligand 4 Hematopoietic stem and progenitor cells Mobilized peripheral blood

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Nano-chromium picolinate and heat stress enhance insulin sensitivity in cross-bred sheep

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Animal Nutrition 2023年第2期13卷 173-184页

作者： Alex t.Hung Brian j.Leury Matthew A.Sabin Fahri Fahri Kristy DiGiacomo tu-Fa Lien frank R.Dunshea Faculty of Veterinary and Agricultural Sciences The University of MelbourneParkvilleVIC 3010Australia Murdoch Children's Research Institute The University of MelbourneParkvilleVIC 3010Australia Department of Animal Science National Chiayi UniversityChiayiChina Faculty of Biological Sciences The University of LeedsLeeds LS29JTUnited Kingdom

this study evaluated the effects of heat stress(HS)and dietary nano chromium picolinate(nCrPic)on metabolic responses of sheep to an intravenous glucose tolerance test(IVGtt),an intravenous insulin tolerance test(Itt)and an intramuscular adrenocorticotropin hormone(ACtH)challenge in ***-six sheep housed in metabolic cages were randomly allocated within 3 dietary groups(0,400 and 800 mg/kg supplemental nCrPic)to either thermoneutral(22℃)or cyclic HS(22 to 40℃)conditions for 3 *** plasma glucose tended to be increased during HS(P=0.052)and decreased by dietary nCrPic(P=0.013)while plasma non-esterified fatty acid concentrations were decreased(P=0.010)by ***-etary nCrPic reduced the plasma glucose area under the curve(P=0.012)while there were no significant effects of HS on plasma glucose area under the curve in response to the *** plasma insulin response over the first 60 min after the IVGtt was decreased by HS(P=0.013)and dietary nCrPic(P=0.022)with the effects being *** response to the Itt plasma glucose reached a nadir sooner(P=0.005)in sheep exposed to HS,although there was no effect on the depth of the *** nCrPic decreased(P=0.007)the plasma glucose nadir after *** the duration of the Itt plasma insulin concentrations were lower in sheep exposed to HS(P=0.013)whereas there was no significant effect of supplemental *** was no effect of either HS or nCrPic on cortisol response to *** nCrPic supple-mentation decreased(P=0.013)mitogen-activated protein kinase-8(jNK)and increased(P=0.050)carnitine palmitoyltransferase 1B(CPt1B)mRNA expression in skeletal *** of this experiment demonstrated that animals under HS and supplemented with nCrPic had greater insulin sensitivity.

关键词： Chromium picolinate Sheep Heat stress Insulin sensitivity

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Exome sequencing identifies a likely causative variant in 53%of families with ciliopathy-related features on renal ultrasound after excluding NPHP1 deletions

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Genes & Diseases 2024年第5期11卷 40-43页

作者： Konstantin Deutsch Verena Klambt thomas M.Kitzler tilman jobst-Schwan Ronen Schneider Florian Buerger Steve Seltzsam Sherif El Desoky jameela A.Kari Farkhanda Hafeez Maria Szczepanska Loai A.Eid Hazem S.Awad Muna Al-Saffar Neveen A.Soliman Velibor tasic Camille Nicolas-frank Kirollos Yousef Luca M.Schierbaum Sophia Schneider Abdul Halawi Izzeldin Elmubarak Katharina Lemberg Shirlee Shril Shrikant M.Mane Nancy Rodig Friedhelm Hildebrandt Division of Nephrology Department of PediatricsBoston Children’s HospitalHarvard Medical SchoolBostonMA 02215USA Department of Pediatric Gastroenterology Nephrology and Metabolic DiseasesCharite Universitatsmedizin BerlinBerlin 13353Germany Berlin Institute of Health at Charitee Universitatsmedizin Berlin BIH Biomedical Innovation AcademyBIH Charite Clinician Scientist ProgramBerlin 10178Germany Department of Nephrology and Hypertension FriedrichAlexander-Universitat Erlangen-NurnbergErlangen 91054Germany Department of Pediatrics Faculty of Medicine King Abdulaziz UniversityPediatric Nephrology Center of ExcellenceKing Abdulaziz University HospitalJeddah 21589Saudi Arabia Department of Pediatric Nephrology The Children’s Hospital and Institute of Child HealthLahore 54000Pakistan Department of Pediatrics Faculty of Medical Sciences in ZabrzeMedical University of Silesia in KatowiceKatowice 40-752Poland Dubai Hospital and Al-jalila Children’s Specialty Hospital Kidney Center of ExcellenceDubai 4545United Arab Emirates Department of Genetics and Genomics UAE UniversityAbu Dhabi 15551United Arab Emirates Department of Pediatrics Division of Genetics and GenomicsBoston Children’s HospitalHarvard Medical SchoolBostonMA 02215USA Department of Pediatrics Center of Pediatric Nephrology and TransplantationKasr Al Ainy School of MedicineCairo UniversityCairo 11562Egypt Egypt Center for Research and Regenerative Medicine(ECRRM) Cairo 11511Egypt Medical Faculty Skopje University Children’s HospitalSkopje 1000North Macedonia Department of Genetics Yale University School of MedicineNew HavenCT 06520USA

Nephronophthisis-related ciliopathies(NPHP-RC)represent one of the most common causes of chronic kidney disease in the first three decades of life and are characterized by a broad genetic and clinical heterogeneity.1 to date,more than 90 genes have been identified that cause autosomalrecessive NPHP-RC if mutated,accounting for up to 60%of cases.1 Among these,homozygous deletions of NPHP1 are the most common *** genes localize to primary cilia,basal bodies,or the centrosome and lead to a primary ciliary disruption if mutated,thereby causing a broad phenotypical spectrum.1 Patients that suffer from NPHP-RC can either have an isolated renal phenotype,such as polyuria,polydipsia,decreased urinary concentration ability,and secondary enuresis due to loss of tubular function,or present with extrarenal symptoms including retinal degeneration,cerebellar vermis hypoplasia,or hepatic *** are often diagnosed in early adolescence,reaching end-stage renal disease before 25 years of age,but early onset and rapidly progressive forms of NPHP-RC also exist.1 Renal ultrasound indicates kidneys of normal or reduced renal length with increased echogenicity and corticomedullary cysts.

关键词： degeneration urinary likely

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HIV protease:late action to prevent immune detection

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Signal transduction and targeted therapy 2021年第5期6卷 1408-1409页

作者： Konstantin M.j.Sparrer frank Kirchhoff Institute of Molecular Virology Ulm University Medical CenterUlmGermany

A recent study published in Science by Wang and colleagues shows that premature activation of the HIV-1 protease leads to caspase activation and recruitment domain 8(CARD8)inflammasome-mediated pyroptosis of infected macrophages and CD4+t cells(Fig.1).these findings might help to improve approaches aiming to eliminate the latent viral reservoirs upon HIV-1 *** invading viral pathogens trigger the innate immune system and are usually rapidly controlled and eventually *** sense viral intruders via so-called pattern recognition receptors(PRRs)capable of detecting pathogen-associated molecular patterns(PAMPs)allowing discrimination between self and *** many cases,these patterns are viral nucleic acids that show pathogen-specific structures or emerge at the wrong localization in the ***,activation of PRRs by their respective ligands leads to the induction of various anti-viral signaling cascades,among them the inflammasome.

关键词： eventually action eliminate

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Acute right insular ischaemic lesions and poststroke left ventricular dysfunction

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Stroke & Vascular Neurology 2023年第4期8卷 301-306页

作者： Klemens Winder Carolina Villegas Millar Gabriela Siedler Michael Knott Arnd Dörfler Anna Engel Stephan Achenbach Max j Hilz Bernd Kallmünzer Stefan Schwab frank Seifert Kilian Fröhlich Neurology University Hospital ErlangenFriedrich-Alexander-Universität(FAU)Erlangen-NürnbergErlangenGermany Neurology University Hospital and University of ZürichZürichSwitzerland Neuroradiology University Hospital ErlangenFriedrich-Alexander Universität(FAU)Erlangen-NürnbergErlangenGermany Cardiology University Hospital ErlangenFriedrich-Alexander-Universität(FAU)Erlangen-NürnbergErlangenGermany

Introduction Myocardial injury related to acute ischaemic stroke is common even without primary cardiac *** intended to determine associations between values of left ventricular ejection fraction(LVEF)and ischaemic stroke lesion *** Of a local database,patients with acute first-ever ischaemic stroke confirmed by brain imaging but without pre-existing heart disease were *** cardiac morphology and LVEF were obtained from transthoracic or transesophageal echocardiography,and impaired LVEF was categorised as mild(35%-50%),moderate(34%-25%)and severe(tient age,stroke severity,ischaemic lesion volume,prevalence of troponin I increase(>0.1 ng/mL),atrial fibrillation and cardiac wall motion abnormalities were assessed and compared between patients with and without impaired LVEF after stroke(significance:ptivariate voxelwise lesion analysis correlated LVEF after stroke with sites of ischaemic *** Of 1209 patients who had a stroke,231(mean age 66.3±14.0 years)met the inclusion criteria;40 patients(17.3%)had an impaired LVEF after *** with impaired LVEF had higher infarct volumes(53.8 mL vs 30.0 mL,p=0.042),a higher prevalence of troponin increase(17.5%vs 4.2%,p=0.006),cardiac wall motion abnormalities(42.5%vs 5.2%,ptrial fibrillation(60.0%vs 26.2%,pthan patients with LVEF of>50%.the multivariate voxelwise lesion analysis yielded associations between decreased LVEF and damaged voxels in the insula,amygdala and operculum of the right *** Our imaging analysis unveils a prominent role of the right hemispheric central autonomic network,especially of the insular cortex,in the brain-heart *** results support preliminary evidence that acute ischaemic stroke in distinct brain regions of the central autonomic network may directly impair cardiac function and thus further supports the concept of a distinct stroke-heart syndrome.

关键词： impaired ischaemic ventricular

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Dietary nano chromium picolinate can ameliorate some of the impacts of heat stress in cross-bred sheep

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Animal Nutrition 2021年第1期7卷 198-205页

作者： Alex t.Hung Brian j.Leury Matthew A.Sabin Fahri Fahri Kristy DiGiacomo tu-Fa Lien frank R.Dunshea Faculty of Veterinary and Agricultural Sciences The University of MelbourneParkvilleVIC3010Australia Murdoch Children's Research Institute The University of MelbourneParkvilleVIC3010Australia Department of Animal Science National Chiayi UniversityChina Faculty of Biological Sciences The University of LeedsLeeds LS29JTUnited Kingdom

two studies were conducted to evaluate the effect of nano chromium picolinate(nCrPic)during heat stress(HS)in *** the initial study,36 Merino×Poll cross-bred sheep were individually penned and allocated to 3 dietary treatments(0,400 and 800μg/kg nCrPic)for 8 *** composition was determined at the beginning and end of the experiment using dual energy X-ray *** sheep remained in their dietary groups but were then placed in metabolic cages and randomly allocated within the dietary group to differing ambient temperature regimes,i.e.,thermo-neutral(tN)(n=18)and HS(n=18),for 3 *** nCrPic had no effect on growth performance and body composition during the initial study conducted under tN *** stress decreased average daily feed intake(ADFI)(P=0.002)whereas sheep under HS had reduced average daily gain(ADG)and indeed lost weight(Ptary nCrPic increased both ADFI(P=0.041)and ADG(P=0.049)under both tH and HS conditions such that the performance of sheep receiving supplemental nCrPic and exposed to HS was similar to that of control sheep maintained under tN *** stress increased rectal temperature(Ption rate(Pticularly during the hottest parts of the day as indicated by interactions(Ptween time of day and thermal *** temperature was lower in sheep fed nCrPic(P=0.050),particularly under peak HS conditions during the afternoon as indicated by the interactions between dietary nCrPic and time of day(Ptary nCrPic,thermal treat-ment and time of day(P=0.010).Similarly,respiration rate was lower in sheep fed nCrPic under peak HS conditions during the afternoon as indicated by the interactions between dietary nCrPic and thermal treatment(Ptary nCrPic and time of day(P=0.030).In conclusion,dietary nCrPic can partially ameliorate the negative effects of HS as indicated by the maintenance of ADFI and decreased physiological responses,such as elevatio

关键词： Chromium picolinate Sheep Heat stress Nanotechnology Physiology

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Gold-catalysed synthesis of phosphonatesubstituted oxetan-3-ones–an easy access to highly strained HWE reagents

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Organic Chemistry Frontiers 2022年第1期9卷 117-122页

作者： Shaista tahir jonas F.Wunsch Matthias Rudolph frank Rominger A.Stephen K.Hashmi Organisch-Chemisches Institut Heidelberg UniversityIm Neuenheimer Feld 27069120 HeidelbergGermany Chemistry Department Faculty of ScienceKing Abdulaziz University21589 JeddahSaudi Arabia

A convenient approach for the attainment of strained phosphonate-substituted oxetan-3-ones,starting from easy to synthesise alkynyl phosphonates,is *** the aid of a pyridine-N-oxide,in a goldcatalysed step anα-oxo carbene species is generated as a key *** formal OH-insertion,synthetically useful HWE reagents can be *** synthetic utility of the obtained building blocks could be demonstrated,which yielded the 2-alkenyl oxetan-3-one scaffold in high yields after the HWE reaction.

关键词： reaction substituted synthesis

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the jesuits II: Cultures, Sciences, and the Arts, 1540–1773

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2006年

作者： john W. O'Malley Gauvin Alexander Bailey Steven j. Harris t. frank Kennedy (eds.)

ISBN: (纸本)0802038611

Recent years have seen scholars in a wide range of disciplines re-evaluate the history of the Society of jesus. In 1997, a group of scholars convened a major international conference to discuss the world of the jesuits between 1540 and 1773 (the year of its suppression by papal edict). this meeting led to the creation of the first volume in this series, the jesuits, which examined the worldwide jesuit undertaking in such fields as music, art, architecture, devotional writing, mathematics, physics, astronomy, natural history, public performance, and education, with special attention to the jesuits''interaction with non-European *** second volume, following a second conference in 2002, continues in a similar path as its predecessor, complementing the regional coverage with contributions on the Flemish and Iberian provinces, on the missions in japan, and in post-Suppression Russia and the United States. the performing arts, like theatre and music, are broadly treated, and, in addition to continued attention to painting and architecture, the volume contains essays on a range of objets d''art, including statuary, reliquaries, and alter pieces - as well as on gardens, mechanical clocks, and related automata. Other themes include finances, natural theology, censorship within the jesuit order, and the Society''s relationship to *** most important, the volume gives particular attention to the eighteenth century, the''age of disasters''for the jesuits - the negative papal ruling on Chinese Rites, the destruction the of Paraguay Reductions, and the suppressions of the order that began in Portugal and that culminated in the general Suppression of 1773. With contributions from distinguished scholars from a dozen different countries, the jesuits, II continues in the illustrious tradition of its predecessor to make an important contribution to religious memory.

关键词： jesuits

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Lantana camara——an Ecological Bioindicator Plant for Decontamination of Pb-Impaired Soil Under Organic Waste-Supplemented Scenarios

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Pedosphere 2019年第2期29卷 248-258页

作者： frank Ogenna ALARIBE Pariatamby AGAMUtHU Institute of Biological Sciences University of Malaya

Heavy metal extraction and processing from ores releases elements into the environment. Soil, being an "unfortunate" sink, has its bionomics impaired and affected by metal pollution. Metals sneak into the food chain and pose risk to humans and other edaphicdependent organisms. For decontamination, the use of an ecosystem-friendly approach involving plants is known as *** this study, different lead(Pb) concentrations(80, 40, 20, and 10 mg kg^(-1)) were used to contaminate a well-characterized soil,(un)supplemented with organic waste empty fruit bunch(EFB) or spent mushroom compost(SMC), with non-edible plant—Lantana camara. Lead removal by L. camara ranged from 45.51% to 88.03% for supplemented soil, and from 23.7% to 57.8% for unsupplemented soil(P the EFB-supplemented and L. camara-remediated soil showed the highest counts of heavy metal-resistant bacteria(HMRB)(79.67 × 10~6–56.0 × 10~6 colony forming units(CFU) g^(-1) soil), followed by SMC-supplemented and L. camara-remediated soil(63.33 × 10~6–39.0 × 10~6 CFU g^(-1) soil). Aerial metal uptake ranged from 32.08 ± 0.8 to 5.03 ± 0.08 mg kg^(-1) dry weight, and the bioaccumulation factor ranged from 0.401 to 0.643(P t_(1/2)) of Pb were 7.24–2.26 d in supplemented soil,18.39–11.83 d in unsupplemented soil, and 123.75–38.72 d in the soil without plants and organic waste. Freundlich isotherms showed that the intensity of metal absorption(n) ranged from 2.44 to 2.51 for supplemented soil, with regression coefficients of determination(R^2) between 0.901 2 and 0.984 0. the computed free-energy change(?G) for Pb absorption ranged from -5.01 to 0.49 kj mol^(-1) K^(-1) for EFB-supplemented soil and -3.93 to 0.49 k j mol^(-1) K^(-1) for SMC-supplemented soil.

关键词： bioaccumulation factor empty fruit bunch first-order kinetics heavy metal metal pollution phytoremediation spent mushroom compost

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Management of Urological Emergencies at the Nianankoro Fomba Hospital in Segou: A Case Report of 72 Patients

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Open journal of Urology 2022年第5期12卷 242-247页

作者： Sory I. Kone Mohamed traore Ibrahim Yattara tièmoko traore Karifala Haidara frank M. Omam Mamadou t. Coulibaly Honoré j. G. Berthe Mamadou L. Diakite Urology Department Nianankoro Fomba Hospital Ségou Mali Liberal Bamako Mali Department of Urology CHU Gabriel TOURE Bamako Mali Department of Urology CHU du point G Bamako Mali

PURPOSE: Our aim was to present the diagnostic and therapeutic aspects of urological emergencies in a regional hospital. MAtERIAL AND MEtHODS: We conducted a prospective study over a period of 6 months (April 2021 to September 2021) collecting all the emergencies received by the on-call urology team at the Nianankoro Fomba Hospital in Segou. this team was led by a DES in urology under the supervision of a urological surgeon. We were interested in age, sex of patients, diagnosis, number of patients hospitalised and type of surgery performed in emergency. RESULtS: We registered 72 patients. the mean age of our patients was 58.8 years with extremes of 6 and 90 years. Acute bladder retention was represented in 61% and total haematuria in 24%. Renal colic was reported in 8%. Acute prostatitis was reported in 4% of cases, and acute pyelonephritis in 1%. Urogenital trauma accounted for 6%. CONCLUSION: Although underestimated, in our context, the management of urological emergencies remains a regular activity of the urology department in view of the number of patients managed. Bladder drainage remains the most frequent procedure.

关键词： Urological Emergency Nianankoro Fomba Hospital Diagnosis treatment

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