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Trials of testosterone replacement reporting cardiovascular adverse events

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Asian Journal of Andrology 2018年第2期20卷 131-137页

作者： Thiago Gagliano-Juca Shehzad Basaria research program in Men's Health: aging and metabolism Brigham and Women's Hospital Harvard Medical School Boston MA 02115 USA

The numbers of testosterone prescriptions written have increased several-fold worldwide, but the incidence of pathological hypogonadism due to hypothalamic, pituitary, and testicular disease has remained unchanged. Most of these prescriptions are being dispensed to middle-aged and older men who have experienced age-related decline in serum testosterone levels; a subset of the population in which benefits of testosterone replacement is at best, modest. Recently, some randomized controlled trials have reported increased cardiovascular events in men （mainly older men and those with prevalent cardiovascular disease） with testosterone use, and a few recent meta-analyses have confirmed these findings, in this review, we discuss trials of testosterone therapy that have reported higher cardiovascular events, relevant trials that have not reported increased cardiovascular events and large trials that have focused on cardiovascular risk （mainly atherosclerosis progression） as their main outcome. We also review findings from meta-analyses that have evaluated cardiovascular events in various testosterone trials. Finally, we discuss some potential mechanisms by which testosterone use might result in an increased cardiovascular risk. As none of the trials conducted to date were adequately powered to evaluate cardiovascular events, no firm conclusions can be drawn regarding the cardiovascular safety of testosterone therapy at this time. In the interim, we hope that this review will help practitioners make informed decisions regarding the care of their patients.

关键词： atherosclerosis cardiovascular frailty testosterone thromboembolism

Sequence-activated chemiluminescence probes: programmable illumination for high-contrast in vivo sensing and imaging

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Science China Chemistry 2025年第01期 26-34页

作者： Yutao Zhang Juan Li Wei-Hong Zhu Zhiqian Guo Shanghai Key Laboratory of Functional Materials Chemistry Joint International Research Laboratory of Precision Chemistry and Molecular Engineering Institute of Fine Chemicals School of Chemistry and Molecular Engineering East China University of Science and Technology State Key Laboratory of Bioreactor Engineering Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell MetabolismEast China University of Science & Technology

Sequence-activated chemiluminescence(CL) technique offers a unique approach to detecting specific biomolecules or cellular events with high sensitivity and spatial resolution. The fundamental principle behind sequence-activated CL probes involves tailoring highly-controllable CL signals in response to specific sequences or events of interest, thus enabling high-contrast signals under complex physiological conditions. This sequential activation could be triggered by enzymes, reactive oxygen species(ROS), biothiols or changes in the microenvironment. These unique sequence-activated CL probes bestow several advantages, including minimal background, deep-tissue penetration, and the ability of non-invasive or minimally invasive detection. The sequence-activated CL techniques represent a significant advancement in molecular imaging and diagnostics. In this mini-review, we focus on the latest developments in sequential CL probes, addressing the technical challenges and discussing the future trajectory by harnessing CL signaling and molecular recognition.

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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

Induced pluripotent stem cell-related approaches to generate dopaminergic neurons for Parkinson's disease

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Neural Regeneration research 2025年第11期20卷 3193-3206页

作者： Ling-Xiao Yi Hui Ren Woon Genevieve Saw Li Zeng Eng King Tan Zhi Dong Zhou National Neuroscience Institute Singapore Nanyang Technology University Singapore Department of Neurology Singapore General HospitalSingapore Signature research program in Neuroscience and Behavioral Disorders Duke-NUS Medical SchoolSingapore

The progressive loss of dopaminergic neurons in affected patient brains is one of the pathological features of Parkinson's disease,the second most common human neurodegenerative *** the detailed pathogenesis accounting for dopaminergic neuron degeneration in Parkinson's disease is still unclear,the advancement of stem cell approaches has shown promise for Parkinson's disease research and *** induced pluripotent stem cells have been commonly used to generate dopaminergic neurons,which has provided valuable insights to improve our understanding of Parkinson's disease pathogenesis and contributed to anti-Parkinson's disease *** current review discusses the practical approaches and potential applications of induced pluripotent stem cell techniques for generating and differentiating dopaminergic neurons from induced pluripotent stem *** benefits of induced pluripotent stem cell-based research are *** dopaminergic neuron differentiation protocols from induced pluripotent stem cells are *** emerging three-dimension-based brain organoid models compared with conventional two-dimensional cell culture are ***,limitations,challenges,and future directions of induced pluripotent stem cell–based approaches are analyzed and proposed,which will be significant to the future application of induced pluripotent stem cell-related techniques for Parkinson's disease.

关键词： dopaminergic neurons induced pluripotent stem cells Parkinson's disease stem cell approaches

Leveraging ROTI map derived from Indonesian GNSS receiver network for advancing study of Equatorial Plasma Bubble in Southeast/East Asia

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Earth and Planetary Physics 2025年第1期9卷 101-116页

作者： Prayitno Abadi Ihsan N.Muafiry Teguh N.Pratama Angga Y.Putra Suraina Gatot H.Pramono Sidik T.Wibowo Febrylian F.Chabibi Umar A.Ahmad Wildan P.Tresna Asnawi research Center for Climate and Atmosphere Indonesian National Research and Innovation Agency(BRIN)BandungIndonesia School of Electrical Engineering Telkom UniversityBandungIndonesia Directorate of Laboratory Management Facilities and Science and Technology Park Indonesian National Research and Innovation Agency(BRIN)PontianakIndonesia Geophysics Laboratory Master Program in PhysicsUniversitas Gadjah Mada(UGM)YogyakartaIndonesia research Center for Space Indonesian National Research and Innovation Agency(BRIN)BandungIndonesia Indonesian Geospatial Information Agency(BIG) JakartaIndonesia research Center for Photonics Indonesian National Research and Innovation Agency(BRIN)Tangerang SelatanIndonesia Department of Earth and Planetary Sciences Hokkaido UniversitySapporoJapan

This paper highlights the crucial role of Indonesia’s GNSS receiver network in advancing Equatorial Plasma Bubble(EPB)studies in Southeast and East Asia,as ionospheric irregularities within EPB can disrupt GNSS signals and degrade positioning *** by the Indonesian Geospatial Information Agency(BIG),the Indonesia Continuously Operating Reference Station(Ina-CORS)network comprises over 300 GNSS receivers spanning equatorial to southern low-latitude ***-CORS is uniquely situated to monitor EPB generation,zonal drift,and dissipation across Southeast *** provide a practical tool for EPB research,by sharing two-dimensional rate of Total Electron Content(TEC)change index(ROTI)derived from this *** generate ROTI maps with a 10-minute resolution,and samples from May 2024 are publicly available for further scientific *** preliminary findings from the ROTI maps of Ina-CORS are ***,the Ina-CORS ROTI maps reveal that the irregularities within a broader EPB structure persist longer,increasing the potential for these irregularities to migrate farther ***,we demonstrate that combined ROTI maps from Ina-CORS and GNSS receivers in East Asia and Australia can be used to monitor the development of ionospheric irregularities in Southeast and East *** have demonstrated the combined ROTI maps to capture the development of ionospheric irregularities in the Southeast/East Asian sector during the G5 Geomagnetic Storm on May 11,*** observed simultaneous ionospheric irregularities in Japan and Australia,respectively propagating northwestward and southwestward,before midnight,whereas Southeast Asia’s equatorial and low-latitude regions exhibited irregularities *** sharing ROTI maps from Indonesia and integrating them with regional GNSS networks,researchers can conduct comprehensive EPB studies,enhancing the understanding of EPB behavior across Southeast and East Asia and contributing significantly to ionosphe

关键词： Equatorial Plasma Bubble(EPB) GNSS receivers’network Indonesia Continuously Operating Reference Station(Ina-CORS) ionospheric map Rate of TEC change index(ROTI)map

Correlation network analysis shows divergent effects of a long-term,high-fat diet and exercise on early stage osteoarthritis phenotypes in mice

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Journal of Sport and Health Science 2020年第2期9卷 119-131页

作者： Timothy M.Griffin Albert Batushansky Joanna Hudson Erika Barboza Prado Lopes aging and metabolism research program Oklahoma Medical Research Foundation(OMRF)Oklahoma CityOK 73104USA Reynolds Oklahoma Center on aging and Departments of Biochemistry and Molecular Biology Physiologyand Geriatric MedicineUniversity of Oklahoma Health Sciences CenterOklahoma CityOK 73104USA

Background:Obesity increases knee osteoarthritis(OA) risk through metabolic,inflammatory,and biomechanical factors,but how these systemic and local mediators interact to drive OA pathology is not well *** tested the effect of voluntary running exercise after chronic diet-induced obesity on knee OA-related cartilage and bone pathology in *** then used a correlation-based network analysis to identify systemic and local factors associated with early-stage knee OA phenotypes among the different diet and exercise ***:Male C57 BL/6 J mice were fed a defined control(10% kcal fat) or high fat(HF)(60% kcal fat) diet from 6 to 37 weeks of *** 25 weeks,one-half of the mice from each diet group were housed in cages with running wheels for the remainder of the ***,micro computed tomography,and magnetic resonance imaging were used to evaluate changes in joint tissue structure and OA *** local variables were then compared to systemic metabolic(body mass,body fat,and glucose tolerance),inflammatory(serum adipokines and inflammatory mediators),and functional(mechanical tactile sensitivity and grip strength) outcomes using a correlation-based network *** and exercise effects were evaluated by two-way analysis of ***:An HF diet increased the infrapatellar fat pad size and posterior joint osteophytes,and wheel running primarily altered the subchondral cortical and trabecular *** HF diet nor exercise altered average knee cartilage OA scores compared to control ***,the coefficient of variation was≥25% for many outcomes,and some mice in both diet groups developed moderate OA(>33% maximum score).This supported using correlation-based network analyses to identify systemic and local factors associated with early-stage knee OA *** wheel-running cohorts,an HF diet reduced the network size compared to the control diet group despite similar running distances,suggesting that diet-induced obesi

关键词： Inflammation Knee Mouse Obesity Wheel running

Endogenous Glucocorticoids and Bone

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Bone research 2013年第2期1卷 107-119页

作者： Hong Zhou Mark S. Cooper Markus J. Seibel Bone research program ANZAC Research Institute Concord Clinical School The University of Sydney Department of Endocrinology & metabolism Concord Hospital

While the adverse effects of glucocorticoids on bone are well described, positive effects of glucocorticoids on the differentiation of osteoblasts are also observed. These paradoxical effects of glucocorticoids are dose dependent. At both physiologicaland supraphysiological levels of glucocorticoids, osteoblasts and osteocytes are the major glucocorticoid target cells. However, the response of the osteoblasts to each of these is quite distinct. At physiology levels, glucocorticoids direct mesenchymal progenitor cells to differentiate towards osteoblasts and thus increase bone formation in a positive way. In contrast with ageing, the excess production of glucocorticoids, at both systemic and intracellular levels, appear to impact on osteoblast and osteocytes in a negative way in a similar fashion to that seen with therapeutic glucocorticoids. This review will focus on therole of glucocorticoids in normal bone physiology, with particular emphasis on the mechanism by which endogenous glucocorticoids impact on bone and its constituent cells.

关键词： glucocorticoids mechanisms of action bone osteoblasts skeletal development Wnt signaling

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

Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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Neural Regeneration research 2025年第2期20卷 343-353页

作者： Ana Milena Silva Olaya Fernanda Martins Almeida Ana Maria Blanco Martinez Suelen Adriani Marques PhD program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate program in Pathological Anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy