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Modulation of the Nogo signaling pathway to overcome amyloid-β-mediated neurite inhibition in human pluripotent stem cell-derived neurites

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Neural Regeneration Research 2025年第9期20卷 2645-2654页

作者： Kirsty Goncalves Stefan Przyborski department of biosciences Durham UniversityDurhamUK Reprocell Europe Ltd. GlasgowUK

Neuronal cell death and the loss of connectivity are two of the primary pathological mechanisms underlying Alzheimer's *** accumulation of amyloid-βpeptides,a key hallmark of Alzheimer's disease,is believed to induce neuritic abnormalities,including reduced growth,extension,and abnormal growth cone morphology,all of which contribute to decreased ***,the precise cellular and molecular mechanisms governing this response remain *** this study,we used an innovative approach to demonstrate the effect of amyloid-βon neurite dynamics in both two-dimensional and three-dimensional cultu re systems,in order to provide more physiologically relevant culture *** utilized various methodologies,including the addition of exogenous amyloid-βpeptides to the culture medium,growth substrate coating,and the utilization of human-induced pluripotent stem cell technology,to investigate the effect of endogenous amyloid-βsecretion on neurite outgrowth,thus paving the way for potential future applications in personalized ***,we also explore the involvement of the Nogo signaling cascade in amyloid-β-induced neurite *** demonstrate that inhibition of downstream ROCK and RhoA components of the Nogo signaling pathway,achieved through modulation with Y-27632(a ROCK inhibitor)and Ibuprofen(a Rho A inhibitor),respectively,can restore and even enhance neuronal connectivity in the presence of amyloid-β.In summary,this study not only presents a novel culture approach that offers insights into the biological process of neurite growth and inhibition,but also proposes a specific mechanism for reduced neural connectivity in the presence of amyloid-βpeptides,along with potential intervention points to restore neurite ***,we aim to establish a culture system that has the potential to serve as an assay for measuring preclinical,predictive outcomes of drugs and their ability to promote neurite outgrowth,both generally and in a patie

关键词： Alzheimer's disease induced pluripotent stem cell neurite outgrowth neuron Nogo Rho A ROCK stem cell three-dimensional culture

Dieback of spruce plantations:Deadwood stands and management heterogeneity enhance beetle diversity and habitat connectivity

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Forest Ecosystems 2025年第1期12卷 121-135页

作者： Eva Plath Kim Ehringhausen Laura Griebel Leon Martiny Michel Schmitz Katharina Schreek Christoph Thiem Klaus Fischer Institute of integrated Natural Sciences Department BiologyUniversity of KoblenzD-56070KoblenzGermany

Forest ecosystems are important for biodiversity conservation and human societies,but are under pressure due to climate change and human *** applies to natural forests as well as tree *** latter are globally widespread and therefore gaining increasing importance for biodiversity ***,even after dieback due to increasing disturbance frequencies,such plantations are primarily managed for economic returns,leading to growing conflicts among *** particular,the impact of forest management on biodiversity is being *** study investigates the effects of five management approaches in a landscape severely affected by spruce(Picea abies L.)dieback on beetle diversity,conservation,and community *** considered direct effects of management and indirect effects of environmental parameters separately in ground-dwelling and flight-active *** diversity was strongly affected by forest management,with nonintervention deadwood stands being most beneficial for *** addition,we show indirect effects of environmental *** general,parameters related to salvage logging(*** canopies,tree stumps)influenced beetle diversity and conservation negatively,while positive effects were found for soil nutrient availability and plant species *** composition differed strongly among management categories and indicated a lack of landscape connectivity for open habitat species,as we found only low proportions of such species even on salvage-logged *** propose a mixture of management approaches after bark beetle outbreaks,including a substantial proportion of non-intervention deadwood stands,to increase landscape heterogeneity and *** may increase overall biodiversity while addressing the concerns of both forestry and species conservation.

关键词： Ips typographus Post-disturbance management Coleoptera Natural disturbances Biodiversity loss Beetle assemblages Nature conservation Forest dieback

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

Dieback of spruce plantations: Deadwood stands and management heterogeneity enhance beetle diversity and habitat connectivity

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Forest Ecosystems 2025年第01期 121-135页

Forest ecosystems are important for biodiversity conservation and human societies, but are under pressure due to climate change and human interventions. This applies to natural forests as well as tree plantations. The latter are globally widespread and therefore gaining increasing importance for biodiversity conservation. However, even after dieback due to increasing disturbance frequencies, such plantations are primarily managed for economic returns, leading to growing conflicts among stakeholders. In particular, the impact of forest management on biodiversity is being discussed. This study investigates the effects of five management approaches in a landscape severely affected by spruce(Picea abies L.) dieback on beetle diversity, conservation, and community *** considered direct effects of management and indirect effects of environmental parameters separately in ground-dwelling and flight-active beetles. Beetle diversity was strongly affected by forest management, with nonintervention deadwood stands being most beneficial for beetles. In addition, we show indirect effects of environmental factors. In general, parameters related to salvage logging(e.g. open canopies, tree stumps) influenced beetle diversity and conservation negatively, while positive effects were found for soil nutrient availability and plant species richness. Community composition differed strongly among management categories and indicated a lack of landscape connectivity for open habitat species, as we found only low proportions of such species even on salvage-logged sites. We propose a mixture of management approaches after bark beetle outbreaks, including a substantial proportion of non-intervention deadwood stands, to increase landscape heterogeneity and connectivity. This may increase overall biodiversity while addressing the concerns of both forestry and species conservation.

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Polyethylene glycol has immunoprotective effects on sciatic allografts, but behavioral recovery and graft tolerance require neurorrhaphy and axonal fusion

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Neural Regeneration Research 2025年第4期20卷 1192-1206页

作者： Tyler A.Smith Liwen Zhou Cameron L.Ghergherehchi Michelle Mikesh Cathy Z.Yang Haley O.Tucker JuliAnne Allgood Jared S.Bushman George D.Bittner department of Molecular biosciences University of Texas at AustinAustinTXUSA department of Neuroscience University of Texas at AustinAustinTXUSA Division of Pharmaceutical Sciences University of WyomingLaramieWYUSA

Behavioral recovery using(viable)peripheral nerve allografts to repair ablation-type(segmental-loss)peripheral nerve injuries is delayed or poor due to slow and inaccurate axonal ***,such peripheral nerve allografts undergo immunological rejection by the host immune *** contrast,peripheral nerve injuries repaired by polyethylene glycol fusion of peripheral nerve allografts exhibit excellent behavioral recovery within weeks,reduced immune responses,and many axons do not undergo Wallerian *** relative contribution of neurorrhaphy and polyethylene glycol-fusion of axons versus the effects of polyethylene glycol per se was unknown prior to this *** hypothesized that polyethylene glycol might have some immune-protective effects,but polyethylene glycol-fusion was necessary to prevent Wallerian degeneration and functional/behavioral *** examined how polyethylene glycol solutions per se affect functional and behavioral recovery and peripheral nerve allograft morphological and immunological responses in the absence of polyethylene glycol-induced axonal ***-type sciatic nerve injuries in outbred Sprague–Dawley rats were repaired according to a modified protocol using the same solutions as polyethylene glycol-fused peripheral nerve allografts,but peripheral nerve allografts were loose-sutured(loose-sutured polyethylene glycol)with an intentional gap of 1–2 mm to prevent fusion by polyethylene glycol of peripheral nerve allograft axons with host *** to negative control peripheral nerve allografts not treated by polyethylene glycol and in contrast to polyethylene glycol-fused peripheral nerve allografts,animals with loose-sutured polyethylene glycol peripheral nerve allografts exhibited Wallerian degeneration for all axons and myelin degeneration by 7 days postoperatively and did not recover sciatic-mediated behavioral functions by 42 days *** morphological signs of rejection,such as col

关键词： allograft rejection axotomy macrophage myelin nerve repair polyethylene glycol(PEG) sciatic nerve T cell transplantation Wallerian degeneration

Emodin promotes the recovery of rheumatoid arthritis by regulating the crosstalk between macrophage subsets and synovial fibroblast subsets

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Animal Models and Experimental Medicine 2025年第1期8卷 44-56页

作者： Lianying Cheng Xiaofeng Rong department of integrated Traditional Chinese and Western Medicine The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

Background : To study the relationships among emodin, synovial fibroblasts (FLSs), and macrophages (STMs) to provide guidance for the use of emodin in rheumatoid arthritis (RA) treatment. Methods : RA clinical samples from patients with different pathological processes were collected, and the correlations between the subsets of FLSs and STMs and pathological processes were analyzed via flow cytometry. In vitro experimental methods such as enzyme linked immunosorbent assay (ELISA), Western blotting, Transwell assays, CCK- 8 assays and cell coculture were used to assess cell proliferation, migration and secretion of inflammatory factors. A collagen- induced arthritis mouse model was constructed to investigate the therapeutic potential of emodin in RA by flow cytometry, micro- CT and staining. Results : Unique subsets of FLSs and STMs, namely, FAPα ^(+)THY1 − FLSs, FAPα ^(+)THY1 ^(+)FLSs, and MerTK ^(pos) TREM2 ^(high) STMs, were identified in synovial tissues from RA patients. The number of MerTK ^(pos) TREM2 ^(high) STMs was negatively correlated with the degree of damage in RA, while the number of FAPα ^(+)THY1 − FLSs was positively correlated with damage. On the one hand, emodin promoted the aggregation of MerTKposTREM2high STMs. Moreover, MerTK pos TREM2 high STM- mediated secretion of exosomes was promoted, which can inhibit the secretion of pro- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs and promote the secretion of anti- inflammatory factors by FAPα ^(+)THY1 ^(+)FLSs, thereby inhibiting FAPα ^(+)THY1 − FLS proliferation and migration, improving the local immune microenvironment, and inhibiting RA damage. Conclusion : Emodin was shown to regulate the aggregation of STM subsets and exosome secretion, affecting the secretion, proliferation and migration of inflammatory factors in FLS subsets, and ultimately achieving good therapeutic efficacy in RA patients, suggesting that it has important clinical value.

关键词： emodin fibroblast synoviocytes macrophages rheumatoid arthritis

Huanglian-Renshen-Decoction Maintains Isletβ-Cell Identity in T2DM Mice through Regulating GLP-1 and GLP-1R in Both Islet and Intestine

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Chinese Journal of Integrative Medicine 2025年第1期31卷 39-48页

作者： WU Wen-bin GAO Fan TANG Yue-heng WANG Hong-zhan DONG Hui LU Fu-er YUAN Fen Institution of integrated Traditional Chinese and Western Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China department of integrated Traditional Chinese and Western Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan430030China

Objective: To elucidate the effect of Huanglian-Renshen-Decoction(HRD) on ameliorating type 2 diabetes mellitus by maintaining islet β-cell identity through regulating paracrine and endocrine glucagon-like peptide-1(GLP-1)/GLP-1 receptor(GLP-1R) in both islet and intestine. Methods: The db/db mice were divided into the model(distilled water), low-dose HRD(LHRD, 3 g/kg), high-dose HRD(HHRD, 6 g/kg), and liraglutide(400 μg/kg) groups using a random number table, 8 mice in each group. The db/m mice were used as the control group(n=8, distilled water). The entire treatment of mice lasted for 6 weeks. Blood insulin, glucose, and GLP-1levels were quantified using enzyme-linked immunosorbent assay kits. The proliferation and apoptosis factors of islet cells were determined by immunohistochemistry(IHC) and immunofluorescence(IF) staining. Then,GLP-1, GLP-1R, prohormone convertase 1/3(PC1/3), PC2, v-maf musculoaponeurotic fibrosarcoma oncogene homologue A(MafA), and pancreatic and duodenal homeobox 1(PDX1) were detected by Western blot, IHC,IF, and real-time quantitative polymerase chain reaction, respectively. Results: HRD reduced the weight and blood glucose of the db/db mice, and improved insulin sensitivity at the same time(P<0.05 or P<0.01). HRD also promoted mice to secrete more insulin and less glucagon(P<0.05 or P<0.01). Moreover, it also increased the number of islet β cell and decreased islet α cell mass(P<0.01). After HRD treatment, the levels of GLP-1,GLP-1R, PC1/3, PC2, MafA, and PDX1 in the pancreas and intestine significantly increased(P<0.05 or P<0.01).Conclusion: HRD can maintain the normal function and identity of islet β cell, and the underlying mechanism is related to promoting the paracrine and endocrine activation of GLP-1 in pancreas and intestine.

关键词： type 2 diabetes mellitus Huanglian-Renshen-Decoction isletβcell glucagon-like peptide-1 glucagon-like peptide-1 receptor Chinese medicine

Integration of wearable electronics and heart rate variability for human physical and mental well-being assessment

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Journal of Semiconductors 2025年第1期46卷 58-76页

作者： Feifei Yin Jian Chen Haiying Xue Kai Kang Can Lu Xinyi Chen Yang Li East China Institute of Photo-Elextro ICs Suzhou 215163China Bengbu Representative department Bengbu 233000China School of integrated Circuits Shandong UniversityJinan 250101China

Heart rate variability(HRV)that can reflect the dynamic balance between the sympathetic nervous and parasympathetic nervous of human autonomic nervous system(ANS)has attracted considerable ***,traditional electrocardiogram(ECG)devices for HRV analysis are bulky,and hard wires are needed to attach measuring electrodes to the chest,resulting in the poor wearable experience during the long-term *** with that,wearable electronics enabling continuously cardiac signals monitoring and HRV assessment provide a desirable and promising approach for helping subjects determine sleeping issues,cardiovascular diseases,or other threats to physical and mental *** now,significant progress and advances have been achieved in wearable electronics for HRV monitoring and applications for predicting human physical and mental *** this review,the latest progress in the integration of wearable electronics and HRV analysis as well as practical applications in assessment of human physical and mental health are *** commonly used methods and physiological signals for HRV analysis are briefly ***,we highlighted the research on wearable electronics concerning HRV assessment and diverse applications such as stress estimation,drowsiness detection,***,the current limitations of the integrated wearable HRV system are concluded,and possible solutions in such a research direction are outlined.

关键词： wearable electronics HRV analysis physical and mental well-being machine learning stress detection

Efficacy and Safety of Zihua Wenfei Zhisou Granule in Treatment of Postinfectious Cough: A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase Ⅱ Clinical Trial

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Chinese Journal of Integrative Medicine 2025年第1期31卷 3-10页

作者： LI Ting LIU Xue-mei YANG Mei WU Yan-qing LIU Wei MAO Bing JIANG Hong-li Division of Pulmonary Medicine Department of Internal MedicineInstitute of Integrated Traditional Chinese and Western MedicineWest China HospitalSichuan UniversityChengdu610041China department of Pulmonary Diseases State Key Laboratory of Biotherapy of ChinaWest China HospitalSichuan UniversityChengdu610041China

Objective: To evaluate the efficacy and safety of Chinese medicine(CM) Zihua Wenfei Zhisou Granule(ZWZG) in postinfectious cough(PIC) patients with CM syndrome of wind-cold invading Fei(Lung,WCIF). Methods: This is a multicenter, randomized, double-blind, parallel-group, placebo-controlled phase Ⅱclinical trial. PIC patients with WCIF syndrome were recruited from the Respiratory departments in 6 hospitals across China between March 2019 and December 2020. Eligible patients were randomly assigned to group A(ZWZG-matched placebo 15 g), group B(active ZWZG 15 g), and group C(active ZWZG 10 g plus ZWZGmatched placebo 5 g) in a 1:1:1 ratio. All medications were taken orally 3 times daily for 14 consecutive days. The primary outcomes were cough relief rate and cough disappearance rate. The secondary outcomes included time to cough relief, time to cough disappearance, and changes in cough symptom score(CSS), cough Visual Analog Scale(VAS) value, Cough-Specific Quality of Life Questionnaire(CQLQ) score, and CM syndrome score from baseline(day 0) to post-treatment(day 14). Adverse events(AEs) in each group were recorded. Results: A total of 198 patients were included in the full analysis set(FAS) and safety analysis set(SS), while 183 were enrolled in the per-protocol analysis set(PPS). In the FAS population, the cough relief rate was 47.76%, 90.77% and 84.85%in groups A, B, and C, respectively;while the cough disappearance rate was 31.34%, 72.31% and 68.18%,respectively. The cough relief rates and cough disappearance rates in groups B and C were significantly higher than group A(P<0.0001). Both the median time to cough relief and cough disappearance in groups B and C were shorter than group A(P<0.0001). Compared with group A, groups B and C showed significantly greater improvements from baseline to post-treatment in CSS during daytime and nighttime as well as VAS(P<0.05).There were no significant differences in changes from baseline to post-treatment in CQLQ and CM syndrome

关键词： postinfectious cough Zihua Wenfei Zhisou Granule randomized controlled trial Chinese medicine