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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

Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

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Neural Regeneration Research 2025年第2期20卷 354-365页

作者： Li Xu Huiming Xu Changyong tang department of Neurology The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong ProvinceChina

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor *** date,no effective treatment exists as the exact causative mechanism remains ***,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic *** most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets *** experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum *** this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model *** addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

关键词： aquaporin-4 experimental model neuromyelitis optica spectrum disorder pathogenesis

Soluble epoxide hydrolase:a next-generation drug target for Alzheimer's disease and related dementias

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Neural Regeneration Research 2025年第9期20卷 2585-2586页

作者： Andrew Gregory Chengyun tang Fan Fan department of Physiology Medical College of GeorgiaAugusta UniversityAugustaGAUSA

Alzheimer's disease(Ad)and Alzheimer's diseaserelated dementias(AdRd)represent a significant public health challenge,with projections indicating a substantial increase in affected individuals due to the aging global *** the World Health Organization,Ad/AdRd has affected more than 55 million individuals worldwide,with an additional 10 million cases diagnosed each year.

关键词： Alzheimer population drug

Polyethylene glycol fusion repair of severed sciatic nerves accelerates recovery of nociceptive sensory perceptions in male and female rats of different strains

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Neural Regeneration Research 2025年第9期20卷 2667-2681页

作者： Liwen Zhou Karthik Venkudusamy Emily A.Hibbard Yessenia Montoya Alexa Olivarez Cathy Z.Yang Adelaide Leung Varun Gokhale Guhan Periyasamy Zeal Pathak dale R.Sengelaub George d.Bittner department of Neuroscience University of TexasAustinTXUSA Program in Neuroscience Indiana UniversityBloomingtonINUSA department of Molecular Biosciences University of TexasAustinTXUSA

Successful polyethylene glycol fusion(PEG-fusion)of severed axons following peripheral nerve injuries for PEG-fused axons has been reported to:(1)rapidly restore electrophysiological continuity;(2)prevent distal Wallerian degeneration and maintain their myelin sheaths;(3)promote primarily motor,voluntary behavioral recoveries as assessed by the Sciatic Functional Index;and,(4)rapidly produce correct and incorrect connections in many possible combinations that produce rapid and extensive recovery of functional peripheral nervous system/central nervous system connections and reflex(e.g.,toe twitch)or voluntary *** preceding companion paper describes sensory terminal field reo rganization following PEG-fusion repair of sciatic nerve transections or ablations;howeve r,sensory behavioral recovery has not been explicitly explored following PEG-fusion *** the current study,we confirmed the success of PEG-fusion surgeries according to criteria(1-3)above and more extensively investigated whether PEG-fusion enhanced mechanical nociceptive recovery following sciatic transection in male and female outbred Sprague-dawley and inbred Lewis *** nociceptive responses were assessed by measuring withdrawal thresholds using von Frey filaments on the dorsal and midplantar regions of the *** von Frey filament tests were a more reliable method than plantar von Frey filament tests to assess mechanical nociceptive sensitivity following sciatic nerve *** withdrawal thresholds of the sciatic-mediated lateral dorsal region differed significantly across strain but not *** thresholds did not change significantly from baseline in chronic Unoperated and Sham-operated *** sciatic transection,all rats exhibited severe hyposensitivity to stimuli at the lateral dorsal region of the hindpaw ipsilateral to the ***,PEG-fused rats exhibited significantly earlier return to baseline withdrawal thresholds than Negative

关键词： autophagia axotomy collateral sprouting neuropathic pain peripheral nerve repair polyethylene glycol fusion(PEG-fusion) saphenous nerve sensory neurons sex and strain Wallerian degeneration

Impact of ocean data assimilation on the seasonal forecast of the 2014/15 marine heatwave in the Northeast Pacific Ocean

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Atmospheric and Oceanic Science Letters 2025年第1期18卷 24-31页

作者： Tiantian tang Jiaying He Huihang Sun Jingjia Luo Institute for Climate and Application Research(ICAR)/Key Laboratory of Meteorological disaster Nanjing University of Information Science and TechnologyNanjingChina

A remarkable marine heatwave,known as the“Blob”,occurred in the Northeast Pacific Ocean from late 2013 to early 2016,which displayed strong warm anomalies extending from the surface to a depth of 300 *** study employed two assimilation schemes based on the global Climate Forecast System of Nanjing University of Information Science(NUIST-CFS 1.0)to investigate the impact of ocean data assimilation on the seasonal prediction of this extreme marine *** sea surface temperature(SST)nudging scheme assimilates SST only,while the deterministic ensemble Kalman filter(EnKF)scheme assimilates observations from the surface to the deep *** latter notably improves the forecasting skill for subsurface temperature anomalies,especially at the depth of 100-300 m(the lower layer),outperforming the SST nudging *** excels in predicting both horizontal and vertical heat transport in the lower layer,contributing to improved forecasts of the lower-layer warming during the *** improvements stem from the assimilation of subsurface observational data,which are important in predicting the upper-ocean *** results suggest that assimilating ocean data with the EnKF scheme significantly enhances the accuracy in predicting subsurface temperature anomalies during the Blob and offers better understanding of its underlying mechanisms.

关键词： Seasonal forecast Ocean data assimilation Marine heatwave Subsurface temperature

Potential role of tanycyte-derived neurogenesis in Alzheimer's disease

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Neural Regeneration Research 2025年第6期20卷 1599-1612页

作者： Guibo Qi Han tang Jianian Hu Siying Kang Song Qin department of Anatomy Histologyand EmbryologySchool of Basic Medical SciencesFudan UniversityShanghaiChina State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science Fudan UniversityShanghaiChina

Tanycytes, specialized ependymal cells located in the hypothalamus, play a crucial role in the generation of new neurons that contribute to the neural circuits responsible for regulating the systemic energy balance. The precise coordination of the gene networks controlling neurogenesis in naive and mature tanycytes is essential for maintaining homeostasis in adulthood. However, our understanding of the molecular mechanisms and signaling pathways that govern the proliferation and differentiation of tanycytes into neurons remains limited. This article aims to review the recent advancements in research into the mechanisms and functions of tanycyte-derived neurogenesis. Studies employing lineage-tracing techniques have revealed that the neurogenesis specifically originating from tanycytes in the hypothalamus has a compensatory role in neuronal loss and helps maintain energy homeostasis during metabolic diseases. Intriguingly,metabolic disorders are considered early biomarkers of Alzheimer's disease. Furthermore,the neurogenic potential of tanycytes and the state of newborn neurons derived from tanycytes heavily depend on the maintenance of mild microenvironments, which may be disrupted in Alzheimer's disease due to the impaired blood–brain barrier ***, the specific alterations and regulatory mechanisms governing tanycyte-derived neurogenesis in Alzheimer's disease remain unclear. Accumulating evidence suggests that tanycyte-derived neurogenesis might be impaired in Alzheimer's disease, exacerbating neurodegeneration. Confirming this hypothesis, however, poses a challenge because of the lack of long-term tracing and nucleus-specific analyses of newborn neurons in the hypothalamus of patients with Alzheimer's disease. Further research into the molecular mechanisms underlying tanycyte-derived neurogenesis holds promise for identifying small molecules capable of restoring tanycyte proliferation in neurodegenerative diseases. This line of investigation could pro

关键词： Alzheimer's disease blood–brain barrier ependymoglial cells hypothalamus metabolic diseases neural stem cells neurogenesis neuroinflammatory diseases neurons tanycyte

Wafer‑Scale Vertical 1d GaN Nanorods/2d MoS_(2)/PEdOT:PSS for Piezophototronic Effect‑Enhanced Self‑Powered Flexible Photodetectors

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Nano-Micro Letters 2025年第3期17卷 102-116页

作者： Xin tang Hongsheng Jiang Zhengliang Lin Xuan Wang Wenliang Wang Guoqiang Li State Key Laboratory of Luminescent Materials and devices South China University of TechnologyGuangzhou 510640People’s Republic of China department of Electronic Materials School of Materials Science and EngineeringSouth China University of TechnologyGuangzhou 510640People’s Republic of China

van der Waals(vdW)heterostructures constructed by lowdimensional(0d,1d,and 2d)materials are emerging as one of the most appealing systems in next-generation flexible ***,hand-stacked vdW-type photodetectors are not compatible with large-areaarray fabrication and show unimpressive performance in self-powered ***,vertical 1d GaN nanorods arrays(NRAs)/2d MoS_(2)/PEdOT:PSS in wafer scale have been proposed for self-powered flexible photodetectors arrays *** as-integrated device without external bias under weak UV illumination exhibits a competitive responsivity of 1.47 A W^(−1)and a high detectivity of 1.2×10^(11)Jones,as well as a fast response speed of 54/71μs,thanks to the strong light absorption of GaN NRAs and the efficient photogenerated carrier separation in type-II ***,the strain-tunable photodetection performances of device have been ***,the device at−0.78%strain and zero bias reveals a significantly enhanced photoresponse with a responsivity of 2.47 A W^(−1),a detectivity of 2.6×10^(11)Jones,and response times of 40/45μs,which are superior to the state-of-the-art self-powered flexible *** work presents a valuable avenue to prepare tunable vdWs heterostructures for self-powered flexible photodetection,which performs well in flexible sensors.

关键词： Vertical nanorod arrays van der Waals heterostructure Piezophototronic effect Self-powered photodetection Flexible sensors

Cell polarization in ischemic stroke: molecular mechanisms and advances

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Neural Regeneration Research 2025年第3期20卷 632-645页

作者： Yuanwei Li Xiaoxiao Xu Xuan Wu Jiarui Li Shiling Chen danyang Chen Gaigai Li Zhouping tang department of Neurology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei ProvinceChina

Ischemic stroke is a cerebrovascular disease associated with high mortality and disability rates. Since the inflammation and immune response play a central role in driving ischemic damage, it becomes essential to modulate excessive inflammatory reactions to promote cell survival and facilitate tissue repair around the injury site. Various cell types are involved in the inflammatory response, including microglia, astrocytes, and neutrophils, each exhibiting distinct phenotypic profiles upon stimulation. They display either proinflammatory or anti-inflammatory states, a phenomenon known as ‘cell polarization.’ There are two cell polarization therapy strategies. The first involves inducing cells into a neuroprotective phenotype in vitro, then reintroducing them autologously. The second approach utilizes small molecular substances to directly affect cells in vivo. In this review, we elucidate the polarization dynamics of the three reactive cell populations(microglia, astrocytes, and neutrophils) in the context of ischemic stroke, and provide a comprehensive summary of the molecular mechanisms involved in their phenotypic switching. By unraveling the complexity of cell polarization, we hope to offer insights for future research on neuroinflammation and novel therapeutic strategies for ischemic stroke.

关键词： astrocyte polarization immune regulation inflammation ischemic injury microglia polarization neutrophil polarization signaling pathways stroke

Enhanced autophagic clearance of amyloid-βvia histone deacetylase 6-mediated V-ATPase assembly and lysosomal acidification protects against Alzheimer's disease in vitro and in vivo

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Neural Regeneration Research 2025年第9期20卷 2633-2644页

作者： Zhimin Long Chuanhua Ge Yueyang Zhao Yuanjie Liu Qinghua Zeng Qing tang Zhifang dong Guiqiong He Institute of Neuroscience School of Basic Medical SciencesChongqing Medical UniversityChongqingChina department of Anatomy Chongqing Medical UniversityChongqingChina department of Physiology Chongqing Medical UniversityChongqingChina Pediatric Research Institute Children’s Hospital of Chongqing Medical UniversityChongqingChina Ministry of Education Key Laboratory of Child development and disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina National Clinical Research Center for Child Health and disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina Chongqing Key Laboratory of Child Neurodevelopment and Cognitive disorders Children’s Hospital of Chongqing Medical UniversityChongqingChina

Recent studies have suggested that abnormal acidification of lysosomes induces autophagic accumulation of amyloid-βin neurons,which is a key step in senile plaque ***,resto ring normal lysosomal function and rebalancing lysosomal acidification in neurons in the brain may be a new treatment strategy for Alzheimer's *** acetylation/deacetylation plays a central role in lysosomal ***,we show that inhibiting the classic microtubule deacetylase histone deacetylase 6 with an histone deacetylase 6 shRNA or thehistone deacetylase 6 inhibitor valproic acid promoted lysosomal reacidification by modulating V-ATPase assembly in Alzheimer's *** rthermore,we found that treatment with valproic acid markedly enhanced *** clearance of amyloid-βaggregates,and ameliorated cognitive deficits in a mouse model of Alzheimer's *** findings demonstrate a previously unknown neuroprotective mechanism in Alzheimer's disease,in which histone deacetylase 6 inhibition by valproic acid increases V-ATPase assembly and lysosomal acidification.

关键词： Alzheimer's disease amyloid-β APP/PS1 mice autophagy cognitive impairment histone deacetylase 6 lysosomal acidification microtubule acetylation valproic acid V-ATPase