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CXCR5^(+)PD-1^(++)CD4^(+)T cells colonize infant intestines early in life and promote B cell maturation

Cellular & Molecular Immunology 2023年第2期20卷 201-213页

作者： Ana Jordan-Paiz Glòria Martrus Fenja L.Steinert Max Kaufmann Adrian F.Sagebiel Renée R.C.E.Schreurs Anne Rechtien Martin E.Baumdick Johannes M.Jung Kimberly J.Möller Lucy Wegner Cordula Grüttner Laura Richert Roland Thünauer jennifer schroeder-schwarz Johannes Bvan Goudoever Teunis B.H.Geijtenbeek Marcus Altfeld Steven T.Pals Daniel Perez Paul L.Klarenbeek Christian Tomuschat Guido Sauter Ingo Königs Udo Schumacher Manuel A.Friese Nathaniel Melling Konrad Reinshagen Madeleine J.Bunders Department of Virus Immunology Leibniz Institute of VirologyHamburg20251Germany University Medical Center Hamburg-Eppendorf Hamburg20246Germany Institute of Neuroimmunology and Multiple Sclerosis Center for Molecular Neurobiology HamburgUniversity Medical Center Hamburg-EppendorfHamburg20251Germany Department of General Visceral and Thoracic SurgeryUniversity Medical Center Hamburg-EppendorfHamburg20246Germany Department of Experimental Immunology Amsterdam Infection&Immunity InstituteAmsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Pediatrics Emma Children’s HospitalAmsterdam University Medical CenterUniversity of Amsterdam and Vrije Universiteit AmsterdamAmsterdam1105 AZThe Netherlands I.Department of Medicine University Medical Center Hamburg-EppendorfHamburg20246Germany Partner Site Hamburg-Lübeck-Borstel-Riems German Center for Infection Research(DZIF)Hamburg20246Germany University of Bordeaux Institut National de la Santéet de la Recherche MédicaleBordeaux Population Health Research Center UMR1219 and INRIA SISTM TeamBordeaux33000France Institute of Anatomy and Experimental Morphology University Medical Center Hamburg-EppendorfHamburg20246Germany Department of Pathology Amsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Rheumatology and Clinical Immunology and Department of Experimental Immunology Amsterdam Infection&Immunity InstituteAmsterdam University Medical CenterUniversity of AmsterdamAmsterdam1007 MBThe Netherlands Amsterdam Rheumatology&Immunology Center Amsterdam University Medical CenterUniversity of AmsterdamAmsterdam1105 AZThe Netherlands Department of Pediatric Surgery University Medical Center Hamburg-EppendorfHamburg20246Germany Institute of Pathology University Medical Center Hamburg-EppendorfHamburg20246Germany Department of Pediatric Surgery Altona Children’s HospitalHamburg22763Germany III.Department of Medicine University M

Gastrointestinal infections are a major cause for serious clinical complications in *** induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++CD4+T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++CD4+T cells in human *** CXCR5+PD-1++CD4+T cells were absent in fetal intestines,CXCR5+PD-1++CD4+T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to *** findings were supported by scRNAseq analyses,showing increased frequencies of CD4+T cells with a TFH gene signature in infant intestines compared to ***-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B *** together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.

关键词： TFH cells B cells Antibodies Intestine Pediatrics

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Neuroprotection by resveratrol-glucuronide and quercetin-glucuronide via binding to polyphenol-and glycosaminoglycan-binding sites in the laminin receptor

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Neural Regeneration Research 2025年第3期20卷 819-820页

作者： Rayudu Gopalakrishna jennifer Aguilar Emily Lee William J.Mack Department of Integrative Anatomical Sciences Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA Department of Neurological Surgery Keck School of MedicineUniversity of Southern CaliforniaLos AngelesCAUSA

The dietary polyphenolic compounds resveratrol and quercetin prevent neurodegenerative diseases in experimental models;however, they reach the brain only in nanomolar concentrations in the glucuronidated and sulfated ... 详细信息

关键词： resveratrol molar dated

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A functional tacrolimus-releasing nerve wrap for enhancing nerve regeneration following surgical nerve repair

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Neural Regeneration Research 2025年第1期20卷 291-304页

作者： Simeon C.Daeschler Katelyn J.W.So Konstantin Feinberg Marina Manoraj Jenny Cheung jennifer Zhang Kaveh Mirmoeini JPaul Santerre Tessa Gordon Gregory HBorschel SickKids Research Institute Neuroscience and Mental Health ProgramTorontoONCanada Institute of Biomaterials and Biomedical Engineering University of TorontoTorontoONCanada Indiana University School of Medicine IndianapolisINUSA Division of Plastic and Reconstructive Surgery the Hospital for Sick ChildrenTorontoONCanada Translational Biology and Engineering Program Ted Rogers Centre for Heart ResearchInstitute of Biomedical EngineeringFaculty of DentistryUniversity of TorontoTorontoONCanada

Axonal regeneration following surgical nerve repair is slow and often incomplete,resulting in poor functional recovery which sometimes contributes to lifelong ***,there are no FDA-approved therapies available to promote nerve *** accelerates axonal regeneration,but systemic side effects presently outweigh its potential benefits for peripheral nerve *** authors describe herein a biodegradable polyurethane-based drug delivery system for the sustained local release of tacrolimus at the nerve repair site,with suitable properties for scalable production and clinical application,aiming to promote nerve regeneration and functional recovery with minimal systemic drug *** is encapsulated into co-axially electrospun polycarbonate-urethane nanofibers to generate an implantable nerve wrap that releases therapeutic doses of bioactive tacrolimus over 31 *** and drug loading are adjustable for applications in small and large caliber nerves,and the wrap degrades within 120 days into biocompatible *** released from the nerve wrap promotes axon elongation in vitro and accelerates nerve regeneration and functional recovery in preclinical nerve repair models while off-target systemic drug exposure is reduced by 80%compared with systemic *** its surgical suitability and preclinical efficacy and safety,this system may provide a readily translatable approach to support axonal regeneration and recovery in patients undergoing nerve surgery.

关键词： biodegradable local drug delivery nerve injury nerve regeneration nerve wrap tacrolimus

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Inflammasome links traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1644-1664页

作者： Gabriela Seplovich Yazan Bouchi Juan Pablo de Rivero Vaccari jennifer C.Munoz Pareja Andrew Reisner Laura Blackwell Yehia Mechref Kevin K.Wang J.Adrian Tyndall Binu Tharakan Firas Kobeissy Department of Surgery Morehouse School of MedicineAtlantaGAUSA Department of Neurobiology Center for NeurotraumaMultiomics&Biomarkers(CNMB)Neuroscience InstituteMorehouse School of MedicineAtlantaGAUSA Department of Neurological Surgery and the Miami Project to Cure Paralysis University of Miami Miller School of MedicineMiamiFLUSA Division of Pediatric Critical Care Department of PediatricsUniversity of Miami Miller School of MedicineMiamiFLUSA Department of Pediatrics Emory UniversityAtlantaGAUSA Department of Neurosurgery Children’s Healthcare of AtlantaAtlantaGAUSA Department of Chemistry and Biochemistry Texas Tech UniversityLubbockTXUSA Morehouse School of Medicine AtlantaGAUSA

Traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease are three distinct neurological disorders that share common pathophysiological mechanisms involving neuroinflammation. One sequela of neuroinflammation includes the pathologic hyperphosphorylation of tau protein, an endogenous microtubule-associated protein that protects the integrity of neuronal cytoskeletons. Tau hyperphosphorylation results in protein misfolding and subsequent accumulation of tau tangles forming neurotoxic aggregates. These misfolded proteins are characteristic of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease and can lead to downstream neuroinflammatory processes, including assembly and activation of the inflammasome complex. Inflammasomes refer to a family of multimeric protein units that, upon activation, release a cascade of signaling molecules resulting in caspase-induced cell death and inflammation mediated by the release of interleukin-1β cytokine. One specific inflammasome, the NOD-like receptor protein 3, has been proposed to be a key regulator of tau phosphorylation where it has been shown that prolonged NOD-like receptor protein 3 activation acts as a causal factor in pathological tau accumulation and spreading. This review begins by describing the epidemiology and pathophysiology of traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease. Next, we highlight neuroinflammation as an overriding theme and discuss the role of the NOD-like receptor protein 3 inflammasome in the formation of tau deposits and how such tauopathic entities spread throughout the brain. We then propose a novel framework linking traumatic brain injury, chronic traumatic encephalopathy, and Alzheimer's disease as inflammasomedependent pathologies that exist along a temporal continuum. Finally, we discuss potential therapeutic targets that may intercept this pathway and ultimately minimize long-term neurological decline.

关键词： Alzheimer's disease caspase-1 chronic traumatic encephalopathy inflammasomes neurodegeneration neuroinflammation NLRP1 NLRP3 pyroptosis tauopathy traumatic brain injury

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The sexually dimorphic expression of glutamate transporters and their implication in pain after spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3317-3329页

作者： jennifer M.Colón-Mercado Aranza I.Torrado-Tapias Iris K.Salgado Jose M.Santiago Samuel E.Ocasio Rivera Dina P.Bracho-Rincon Luis H.Pagan Rivera Jorge D.Miranda Department of Physiology University of Puerto RicoMedical Sciences CampusSan JuanPRUSA National Institutes of Health National Human Genome Research InstituteBethesdaMDUSA Universidad Central del Caribe School of MedicineBayamónPRUSA University of Puerto Rico Carolina CampusCarolinaPRUSA Institute of Neurobiology San JuanPRUSA

In addition to the loss of motor function,~60% of patients develop pain after spinal cord *** cellular-molecular mechanisms are not well understood,but the data suggests that plasticity within the rostral,epicenter,and caudal penumbra of the injury site initiates a cellularmolecular interplay that acts as a rewiring mechanism leading to central neuropathic *** can lead to the formation of new connections triggering abnormal sensory *** excitatory glutamate transporters are responsible for the reuptake of extracellular glutamate which makes them a critical target to prevent neuronal hyperexcitability and *** previous studies showed a sexually dimorphic therapeutic window for spinal cord injury after treatment with the selective estrogen receptor modulator *** this study,we investigated the anti-allodynic effects of tamoxifen in male and female rats with spinal cord *** hypothesized that tamoxifen exerts anti-allodynic effects by increasing the expression of glutamate transporters,leading to reduced hyperexcitability of the secondary neuron or by decreasing aberrant *** and female rats received a moderate contusion to the thoracic spinal cord followed by subcutaneous slow-release treatment of tamoxifen or matrix pellets as a control(placebo).We used von Frey monofilaments and the“up-down method”to evaluate mechanical *** treatment decreased allodynia only in female rats with spinal cord injury revealing a sexdependent *** expression profile of glutamatergic transporters(excitatory amino acid transporter 1/glutamate aspartate transporter and excitatory amino acid transporter 2/glutamate transporter-1)revealed a sexual dimorphism in the rostral,epicenter,and caudal areas of the spinal cord with a pattern of expression primarily on *** rodents showed a significantly higher level of excitatory amino acid transporter-1 expression while male rodents showed increased

关键词： allodynia central neuropathic pain EAAT-1/GLAST EAAT-2/GLT-1 glutamate transporters selective estrogen receptor modulator sexual dimorphism spinal cord injury trauma

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Emergent reintubation following elective cervical surgery:A case series

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World Journal of Orthopedics 2017年第6期8卷 465-470页

作者： Joshua schroeder Stephan N Salzmann Alexander P Hughes James D Beckman jennifer Shue Federico P Girardi Spine Service Hospital for Special Surgery

AIM To review cases of emergent reintubation after cervical *** Patients who were emergently intubated in the postoperative period following cervical surgery were identified. The patients' prospectively documented demographic parameters, medical history and clinical symptoms were ascertained. Pre-operative radiographs were examined for the extent of their pathology. The details of the operative procedure were *** Eight hundred and eighty patients received anterioror combined anterior-posterior cervical surgery from 2008-2013. Nine patients(1.02%) required emergent reintubation. The interval between extubation to reintubation was 6.2 h [1-12]. Patients were kept intubated after reintubation for 2.3 d [2-3]. Seven patients displayed moderate postoperative edema. One patient was diagnosed with a compressive hematoma whichwas subsequently evacuated in the OR. Another patient was diagnosed with a pulmonary effusion and treated with diuretics. One patient received a late debridement for an infected hematoma. Six patients reported residual symptoms and three patients made a complete recovery. CONCLUSION Respiratory compromise is a rare but potentially life threatening complication following cervical surgery. Patients at increased risk should be monitored closely for extended periods of time post-operatively. If the airway is restored adequately in a timely manner through emergent re-intubation, the outcome of the patients is generally favorable.

关键词： Cervical surgery Complication Airway compromise Reintubation Hematoma

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Investigation of Influencing Parameters for Tribological Conditions in Dry Forming Processes

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Acta Metallurgica Sinica(English Letters) 2015年第12期28卷 1435-1441页

作者： jennifer Steiner Marion Merklein Institute of Manufacturing Technology Friedrich-Alexander-Universitat Erlangen-Nürnberg

Environmental awareness and a growing demand for efficient resource utilization encourage the realization of lubricant-free forming processes. A first step in accomplishing dry sheet metal forming is to gain knowledge about the changing tribological conditions and to identify the relevant influencing parameters. The commonly used flat strip drawing test was selected to investigate the tribological conditions in the flange area of deep drawing processes. The influencing factors of contact pressure and varying drawing velocities were analyzed under dry and lubricated conditions. Additionally,the tool and workpiece surfaces were characterized. Besides lubrication, the contact pressure mainly determines the tribological conditions. In lubricated tests higher normal pressure reduces friction, whereas without lubrication higher pressure results in slightly increasing friction. A changing drawing velocity affects the friction when lubricant is applied. In dry experiments, no influence of velocity was found. Results of surface characterization reveal adhesion as main wear mechanism under dry conditions. Based on the investigated influence of the process parameters, an increase in process understanding for dry forming operations is derived.

关键词： Deep drawing Tribology Friction Dry forming

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The Effect of Natural Hazard Damage on Manufacturing Value Added and the Impact of Spatiotemporal Data Variations on the Results

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International Journal of Disaster Risk Science 2022年第5期13卷 691-704页

作者： Douglas Thomas jennifer Helgeson National Institute of Standards and Technology GaithersburgMD 20899USA

This study examined the effect of natural hazards on manufacturing industry value added and the sensitivity of the results from changes to spatiotemporal resolution of the *** measured the negative effects of hazards,rather than the net *** models were developed with varying spatio temporal units for the continental United States:annual/county units;annual/state units;and quarterly/state *** simulations were run using each model to estimate the negative effect of damage from all natural hazards on value added across spatiotemporal ***,an investment analysis was conducted to examine the return from public investments in hazard *** results do not demonstrate that,locally,natural hazards reduce value ***,the evidence suggests that natural hazards in the upstream supply chain have statistically significant impact when modeled at the annual/county scale and at the quarterly/state *** local nor supply chain hazards have a statistically significant effect when modeled at the annual/state scale,suggesting that broader spatiotemporal units may obscure the true downstream effects of natural *** investment analysis,utilizing model results,suggests that an investment of USD 100 billion or less is economical if it results in a reduction in losses of 10% or more.

关键词： Manufacturing Natural hazards Spatiotemporal impacts United States Value added

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Klotho and neurons: mutual crosstalk between autophagy, endoplasmic reticulum, and inflammatory response

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Neural Regeneration Research 2021年第8期16卷 1542-1543页

作者： jennifer Mytych Department of Animal Physiology and Reproduction Institute of Biology and BiotechnologyCollegium Scientarium NaturaliumUniversity of RzeszowWerynia 236-100 KolbuszowaPoland

Klotho is one of a number of well-known longevity-associated *** depletion in aging or disease may promote several neuropathologies associated with the central nervous system,including hypomyelination and phosphorylat... 详细信息

关键词： Klotho inflammation reticulum

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First CRISPR-Based Therapy Poised to Reach Patients

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Engineering 2023年第11期30卷 3-6页

作者： jennifer Welsh Senior Technology Writer

Ten years after the discovery of clustered regularly interspaced short palindromic repeats(CRISPR),the first gene-editing therapy is expected to soon receive US Food and Drug Administration(FDA)approval for commercial... 详细信息

关键词： CRISPR approval editing

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