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Polyethylene glycol fusion repair of severed rat sciatic nerves reestablishes axonal continuity and reorganizes sensory terminal fields in the spinal cord

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Neural Regeneration Research 2025年第7期20卷 2095-2107页

作者： Emily A.Hibbard Liwen Zhou Cathy Z.Yang Karthik Venkudusamy Yessenia Montoya Alexa Olivarez George d.Bittner dale R.Sengelaub Program in Neuroscience Indiana UniversityBloomingtonINUSA department of Neuroscience University of Texas at AustinAustinTXUSA

Peripheral nerve injuries result in the rapid degeneration of distal nerve segments and immediate loss of motor and sensory functions;behavioral recovery is typically *** used a plasmalemmal fusogen,polyethylene glycol(PEG),to immediately fuse closely apposed open ends of severed proximal and distal axons in rat sciatic *** have previously reported that sciatic nerve axons repaired by PEG-fusion do not undergo Wallerian degeneration,and PEG-fused animals exhibit rapid(within 2–6 weeks)and extensive locomotor ***,our previous report showed that PEG-fusion of severed sciatic motor axons was non-specific,i.e.,spinal motoneurons in PEG-fused animals were found to project to appropriate as well as inappropriate target *** this study,we examined the consequences of PEG-fusion for sensory axons of the sciatic *** adult male and female rats(Sprague–dawley)received either a unilateral single cut or ablation injury to the sciatic nerve and subsequent repair with or without(Negative Control)the application of *** action potentials recorded immediately after PEG-fusion repair confirmed conduction across the injury *** success of PEG-fusion was confirmed through Sciatic Functional Index testing with PEG-fused animals showing improvement in locomotor function beginning at 35 days *** 2–42 days postoperatively,we anterogradely labeled sensory afferents from the dorsal aspect of the hindpaw following bilateral intradermal injection of wheat germ agglutinin conjugated horseradish ***-fusion repair reestablished axonal *** to unoperated animals,labeled sensory afferents ipsilateral to the injury in PEG-fused animals were found in the appropriate area of the dorsal horn,as well as inappropriate mediolateral and rostrocaudal ***,despite having intact peripheral nerves,similar reorganizations of labeled sensory afferents were also observed contralateral to the injury and repa

关键词： axotomy dorsal horn peripheral nerve injury plasticity polyethylene glycol(PEG) sciatic nerve sensory terminals wheat germ agglutinin horseradish peroxidase

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Pd-1^(+)and TIM-3^(+)T cells widely express commonγ-chain cytokine receptors in multiple myeloma patients,and IL-2,IL-7,IL-15 stimulation up-regulates Pd-1 and TIM-3 on T cells

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Oncology Research 2024年第10期32卷 1575-1587页

作者： EGOR V.BATOROV ALISA d.INESHINA TATIANA A.ARISTOVA VERA V.dENISOVA SVETLANA A.SIZIKOVA dARIA S.BATOROVA GALINA Y.USHAKOVA EKATERINA Y.SHEVELA ELENA R.CHERNYKH Laboratory of Cellular Immunotherapy Research Institute of Fundamental and Clinical ImmunologyNovosibirsk630099Russia V.Zelman Institute of Medicine and Psychology Novosibirsk National Research State UniversityNovosibirsk630090Russia department of Hematology and Bone Marrow Transplantation Research Institute of Fundamental and Clinical ImmunologyNovosibirsk630099Russia

Background:Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma(MM)***,previous studies showed the possibility of Pd-1 and TIM-3 expression on T cells upon stimulation with commonγ-chain family cytokines in vitro and during homeostatic *** aim of the present work was to study the impact of homeostatic proliferation on the expansion of certain T cell subsets upregulating Pd-1 and TIM-3 checkpoint ***:The expression of Cd25,Cd122,Cd127 commonγ-chain cytokine receptors,phosphorylated signal transducer and activator of transcription-5(pSTAT5)and eomesodermin(EOMES)was comparatively assessed with flow cytometry in Pd-1-and TIM-3-negative and positive T cells before the conditioning and during the first post-transplant month in peripheral blood samples of MM ***:Substantial proportions of Pd-1-and TIM-3-positive T lymphocytes expressed commonγ-chain cytokine receptors and *** of cytokine receptor expressing cells were significantly higher within TIM-3+T cells compared to Pd-1+TIM-3−*** proportions of both Pd-1-/TIM-3-negative and positive Cd8+T cells express EOMES,while only moderate frequencies of Cd4+Pd-1+/TIM-3+T cells up-regulate this transcription ***,the surface presence of Cd25 and intranuclear expression of EOMES in Cd4+T cells were mutually exclusive regardless of Pd-1 and TIM-3 *** stimulation with commonγ-chain cytokines up-regulates Pd-1 and TIM-3 during the proliferation of initially Pd-1/TIM-3-negative T cells but fails to expand initially Pd-1+and TIM-3+T cell subsets in ***:Both Pd-1 and TIM-3 expressing T cells appear to be able to respond to homeostatic cytokine *** in commonγ-chain cytokine receptor expression between Pd-1+and TIM-3+T cells may reflect functional dissimilarity of these cell *** blockade appears to alleviate lymphopenia-induced prolif

关键词： Autologous hematopoietic stem cell transplantation(AHSCT) Cd25 Cd122 Eomesodermin(EOMES) Homeostatic proliferation

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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

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Honey vesicle-like nanoparticles protect aged liver from non-alcoholic steatohepatitis

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3661-3679页

作者： Baolong Liu Phuong Linh Nguyen Han Yu Xingzhi Li Huiren Wang Tram Gia Bao Nguyen Prakash Kumar Sahoo Meghna Sur Jay Reddy Sarah Sillman Stephen d.Kachman Bara Altartouri Guoqing Lu Sathish Kumar Natarajan Mahesh Pattabiraman Jiujiu Yu department of Nutrition and Health Sciences University of Nebraska-LincolnLincolnNE 68583USA Shaanxi Key Laboratory of Molecular Biology for Agriculture College of Animal Science and TechnologyNorthwest A&F UniversityYangling 712100China department of Nutrition Case Western Reserve UniversityClevelandOH 44106USA School of Veterinary Medicine and Biomedical Sciences University of Nebraska-LincolnLincolnNE 68583USA department of Statistics University of Nebraska-LincolnLincolnNE 68583USA Center for Biotechnology University of Nebraska-LincolnLincolnNE 68588USA department of Biology University of Nebraska OmahaOmahaNE 68182USA department of Chemistry University of Nebraska-KearneyKearneyNE 68849USA

Non-alcoholic steatohepatitis(NASH),an advanced form of non-alcoholic fatty liver disease(NAFLd),has emerged as the leading cause of liver failure and related ***,no medication is specifically approved to treat NAFLd or *** we report that oral administration of honey vesiclelike nanoparticles(H-VLNs)to naturally aged mice protects the liver from NASH development.H-VLNs are dominantly taken up by Kupffer cells in the liver and suppress hepatic chronic inflammation and further development of fibrosis and nodule formation in aged *** their reported antiinflammasome function,H-VLNs are found to inhibit the transcriptional activities of C-JUN and nuclear factor-kappa B(NF-κB).MicroRNAs miR5119 and miR5108 and phenolic compound luteolin in H-VLNs are identified in suppressing both the C-JUN and NF-kB ***,oral intake of H-VLNs represents a promising new user-friendly modality to prevent the development of NASH.

关键词： Honey Extracellular vesicles Exosomes Nanoparticles microRNAs Aging Inflammation Non-alcoholic steatohepatitis

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Mechanisms of pulmonary endothelial barrier dysfunction in acute lung injury and acute respiratory distress syndrome

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Chinese Medical Journal Pulmonary and Critical Care Medicine 2024年第2期2卷 80-87页

作者： Yunchao Su Rudolf Lucas david J.R.Fulton Alexander d.Verin department of Pharmacology&Toxicology Medical College of GeorgiaAugusta UniversityAugustaGA 30912USA division of Pulmonary and Critical Care Medicine Department of MedicineMedical College of GeorgiaAugusta UniversityAugustaGA 30912USA Vascular Biology Center Medical College of GeorgiaAugusta UniversityAugustaGA 30912USA Research Service Charlie Norwood Veterans Affairs Medical CenterAugustaGA 30912USA

Endothelial cells(ECs)form a semi-permeable barrier between the interior space of blood vessels and the un-derlying *** endothelial barrier integrity is maintained through coordinated cellular processes involving receptors,signaling molecules,junctional complexes,and protein-regulated cytoskeletal *** acute lung injury(ALI)or its more severe form acute respiratory distress syndrome(ARdS),the loss of endothelial barrier integrity secondary to endothelial dysfunction caused by severe pulmonary inflamma-tion and/or infection leads to pulmonary edema and ***-inflammatory agonists such as histamine,thrombin,bradykinin,interleukin 1𝛽,tumor necrosis factor𝛼,vascular endothelial growth factor,angiopoietin-2,and platelet-activating factor,as well as bacterial toxins and reactive oxygen species,cause dynamic changes in cytoskeletal structure,adherens junction disorganization,and detachment of vascular endothelial cadherin(VE-cadherin)from the actin cytoskeleton,leading to an increase in endothelial *** interactions with leukocytes,platelets,and coagulation enhance the inflammatory ***,inflammatory infil-tration and the associated generation of pro-inflammatory cytokines during infection cause EC death,resulting in further compromise of the structural integrity of lung endothelial *** the use of potent antibiotics and aggressive intensive care support,the mortality of ALI is still high,because the mechanisms of pulmonary EC barrier disruption are not fully *** this review,we summarized recent advances in the studies of endothelial cytoskeletal reorganization,inter-endothelial junctions,endothelial inflammation,EC death,and endothelial repair in ALI and ARdS,intending to shed some light on the potential diagnostic and therapeutic targets in the clinical management of the disease.

关键词： Lung Endothelium Pulmonary edema Acute lung injury Acute respiratory distress syndrome

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Polymer Fiber Rigid Network with High Glass Transition Temperature Reinforces Stability of Organic Photovoltaics

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Nano-Micro Letters 2024年第11期16卷 56-69页

作者： Qiao Zhou Cenqi Yan Hongxiang Li Zhendong Zhu Yujie Gao Jie Xiong Hua Tang Can Zhu Hailin Yu Sandra P.Gonzalez Lopez Jiayu Wang Meng Qin Jianshu Li Longbo Luo Xiangyang Liu Jiaqiang Qin Shirong Lu Lei Meng Frédéric Laquai Yongfang Li Pei Cheng College of Polymer Science and Engineering State Key Laboratory of Polymer Materials EngineeringSichuan UniversityChengdu 610065People’s Republic of China KAUST Solar Center Physical Science and Engineering DivisionKing Abdullah University of Science and Technology(KAUST)ThuwalKingdom of Saudi Arabia Beijing National Laboratory for Molecular Sciences CAS Key Laboratory of Organic SolidsInstitute of ChemistryChinese Academy of SciencesBeijing 100190People’s Republic of China department of Material Science and Technology Taizhou UniversityTaizhou 318000People’s Republic of China

Organic photovoltaics(OPVs)need to overcome limitations such as insufficient thermal stability to be *** reported approaches to improve stability either rely on the development of new materials or on tailoring the donor/acceptor morphology,however,exhibiting limited ***,it is timely to develop an easy method to enhance thermal stability without having to develop new donor/acceptor materials or donor–acceptor compatibilizers,or by introducing another third ***,a unique approach is presented,based on constructing a polymer fiber rigid network with a high glass transition temperature(T_(g))to impede the movement of acceptor and donor molecules,to immobilize the active layer morphology,and thereby to improve thermal stability.A high-T_(g) one-dimensional aramid nanofiber(ANF)is utilized for network *** OPVs with ANF network yield superior thermal stability compared to the ANF-free *** ANF network-incorporated active layer demonstrates significantly more stable morphology than the ANF-free counterpart,thereby leaving fundamental processes such as charge separation,transport,and collection,determining the device efficiency,largely *** strategy is also successfully applied to other photovoltaic *** strategy of incorporating a polymer fiber rigid network with high T_(g) offers a distinct perspective addressing the challenge of thermal instability with simplicity and universality.

关键词： Inverted organic photovoltaics Thermal stability Aramid nanofibers Morphology control Charge carrier dynamics

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Neuroprotective and neuroregenerative potential of pharmacologically-induced hypothermia with d-alanine d-leucine enkephalin in brain injury

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Neural Regeneration Research 2018年第12期13卷 2029-2037页

作者： M.grant Liska Marci G.Crowley Julian P.Tuazon Cesar V.Borlongan Center of Excellence for Aging and Brain Repair University of South Florida College of Medicine

Neurovascular disorders, such as traumatic brain injury and stroke, persist as leading causes of death and disability - thus, the search for novel therapeutic approaches for these disorders continues. Many hurdles have hindered the translation of effective therapies for traumatic brain injury and stroke primarily because of the inherent complexity of neuropathologies and an inability of current treatment approaches to adapt to the unique cell death pathways that accompany the disorder symptoms. Indeed, developing potent treatments for brain injury that incorporate dynamic and multiple disorder-engaging therapeutic targets are likely to produce more effective outcomes than traditional drugs. The therapeutic use of hypothermia presents a promising option which may fit these criteria. While regulated temperature reduction has displayed great promise in preclinical studies of brain injury, clinical trials have been far less consistent and associated with adverse effects, especially when hypothermia is pursued via systemic cooling. Accordingly, devising better methods of inducing hypothermia may facilitate the entry of this treatment modality into the clinic. The use of the delta opioid peptide d-alanine d-leucine enkephalin（dAdLE） to pharmacologically induce temperature reduction may offer a potent alternative, as dAdLE displays both the ability to cause temperature reduction and to confer a broad profile of other neuroprotective and neuroregenerative processes. This review explores the prospect of dAdLE-mediated hypothermia to treat neurovascular brain injuries, emphasizing the translational steps necessary for its clinical translation.

关键词： stroke traumatic brian injury neurodegeneration temperature management regenerative medicine delta opioids metabolic suppression cerebrovascular disease neurovascular disease

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A multi-shot target wheel assembly for high-repetition-rate, laser-driven proton acceleration

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High Power Laser Science and Engineering 2024年第2期 91-98页

作者： J.Pe?as A.Bembibre d.Cortina-Gil L.Martín A.Reija C.Ruiz M.Seimetz A.Alejo J.Benlliure Instituto Galego de Física de Altas Enerxías Universidade de Santiago de Compostela Laboratorio Láser de Aceleración y Aplicaciones RIAIDT Universidade de Santiago de Compostela Instituto Universitario de Física Fundamental y Matemáticas y dpto.de didáctica de la Matemática y de las Ciencias Experimentales Universidad de Salamanca Instituto de Instrumentación para Imagen Molecular (I3M) CSIC-Universitat Politècnica de València

A multi-shot target assembly and automatic alignment procedure for laser–plasma proton acceleration at high repetition rate are introduced. The assembly is based on a multi-target rotating wheel capable of hosting more than 5000 targets,mounted on a 3d motorized stage to allow rapid replenishment and alignment of the target material between laser irradiations. The automatic alignment procedure consists of a detailed mapping of the impact positions at the target surface prior to the irradiation that ensures stable operation of the target, which alongside the purpose-built design of the target wheel, enables operation at rates up to 10 Hz. Stable and continuous laser-driven proton acceleration at 10 Hz is demonstrated, with observed cut-off energy stability about 15%.

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A multi-shot target wheel assembly for high-repetition-rate, laser-driven proton acceleration

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High Power Laser Science and Engineering 2024年第2期12卷 87-94页

作者： J.Penas A.Bembibre d.Cortina-Gil L.Martin A.Reija C.Ruiz M.Seimetz A.Alejo J.Benlliure Instituto Galego de Fisica de Altas Enerxias Universidade de Santiago de CompostelaSantiago de CompostelaSpain Laboratorio Laser de Aceleracion y Aplicaciones RIAIDTUniversidade de Santiago de CompostelaSantiago de CompostelaSpain Instituto Universitario de Física Fundamental y Matematicas y dpto.de didactica de la Matematica y de las Ciencias Experimentales Universidad de SalamancaSalamancaSpain Instituto de Instrumentación para Imagen Molecular(I3M) CSIC-Universitat Politecnica de ValenciaValenciaSpain

A multi-shot target assembly and automatic alignment procedure for laser–plasma proton acceleration at high repetition rate are *** assembly is based on a multi-target rotating wheel capable of hosting more than 5000 targets,mounted on a 3d motorized stage to allow rapid replenishment and alignment of the target material between laser *** automatic alignment procedure consists of a detailed mapping of the impact positions at the target surface prior to the irradiation that ensures stable operation of the target,which alongside the purpose-built design of the target wheel,enables operation at rates up to 10 *** and continuous laser-driven proton acceleration at 10 Hz is demonstrated,with observed cut-off energy stability about 15%.

关键词： high repetition rate laser-plasma acceleration multi-shot operation proton source target assembly

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Integrated Single-cell Multiomic Analysis of HIV Latency Reversal Reveals Novel Regulators of Viral Reactivation

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Genomics, Proteomics & Bioinformatics 2024年第1期22卷 67-88页

作者： Manickam Ashokkumar Wenwen Mei Jackson J.Peterson Yuriko Harigaya david M.Murdoch david M.Margolis Caleb Kornfein Alex Oesterling Zhicheng Guo Cynthia d.Rudin Yuchao Jiang Edward P.Browne department of Medicine University of North Carolina at Chapel HillChapel HillNC 27599USA HIV Cure Center University of North Carolina at Chapel HillChapel HillNC 27599USA department of Biostatistics University of North Carolina at Chapel HillChapel HillNC 27599USA department of Microbiology and Immunology University of North Carolina at Chapel HillChapel HillNC 27599USA department of Genetics University of North Carolina at Chapel HillChapel HillNC 27599USA department of Medicine Duke UniversityDurhamNC 27708USA department of Computer Science Duke UniversityDurhamNC 27708USA department of Statistics Texas A&M UniversityCollege StationTX 77843USA department of Biology Texas A&M UniversityCollege StationTX 77843USA department of Biomedical Engineering Texas A&M UniversityCollege StationTX 77843USA

despite the success of antiretroviral therapy,human immunodeficiency virus(HIV)cannot be cured because of a reservoir of latently infected cells that evades *** understand the mechanisms of HIV latency,we employed an integrated single-cell RNA sequencing(scRNA-seq)and single-cell assay for transposase-accessible chromatin with sequencing(scATAC-seq)approach to simultaneously profile the transcriptomic and epigenomic characteristics of~125,000 latently infected primary Cd4^(+)T cells after reactivation using three different latency reversing *** expressed genes and differentially accessible motifs were used to examine transcriptional pathways and transcription factor(TF)activities across the cell *** identified cellular transcripts and TFs whose expression/activity was correlated with viral reactivation and demonstrated that a machine learning model trained on these data was 75%-79%accurate at predicting viral ***,we validated the role of two candidate HIV-regulating factors,FOXP1 and GATA3,in viral *** data demonstrate the power of integrated multimodal single-cell analysis to uncover novel relationships between host cell factors and HIV latency.

关键词： HIV latency reversal Primary Cd4þT cell Single-cell multiomics HIV-regulating factor Machine learning

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