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

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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Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report

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Neural Regeneration Research 2025年第4期20卷 1207-1216页

作者： Pascal j.Goldschmidt-clermont Aisha Khan George jimsheleishvili Patricia Graham Adriana Brooks Risset Silvera Alexander j.P.Goldschmidt Damien D.Pearse w.Dalton Dietrich Allan D.Levi james D.Guest Miller School of Medicine University of MiamiMiamiFLUSA Stem cell Institute Miller School of MedicineUniversity of MiamiMiamiFLUSA The Miami Project to cure Paralysis Miller School of MedicineUniversity of MiamiMiamiFLUSA Alzady International LLc MiamiFLUSA Neurological Surgery Miller School of MedicineUniversity of MiamiMiamiFLUSA

Schwann cells are essential for the maintenance and function of motor neurons,axonal networks,and the neuromuscular *** amyotrophic lateral sclerosis,where motor neuron function is progressively lost,Schwann cell function may also be ***,important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been *** case report describes the treatment of a patient with advanced amyotrophic lateral sclerosis using serial intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles,marking,to our knowledge,the first instance of such *** 81-year-old male patient presented with a 1.5-year history of rapidly progressive amyotrophic lateral *** initial diagnosis,the patient underwent a combination of generic riluzole,sodium phenylbutyrate for the treatment of amyotrophic lateral sclerosis,and *** patient volunteered to participate in an FDA-approved single-patient expanded access treatment and received weekly intravenous infusions of allogeneic Schwann cell-derived exosomal vesicles to potentially restore impaired Schwann cell and motor neuron *** confirmed that cultured Schwann cells obtained from the amyotrophic lateral sclerosis patient via sural nerve biopsy appeared impaired(senescent)and that exposure of the patient’s Schwann cells to allogeneic Schwann cell-derived exosomal vesicles,cultured expanded from a cadaver donor improved their growth capacity in *** a period of observation lasting 10 weeks,during which amyotrophic lateral sclerosis Functional Rating Scale-Revised and pulmonary function were regularly monitored,the patient received weekly consecutive infusions of 1.54×1012(×2),and then consecutive infusions of 7.5×1012(×6)allogeneic Schwann cell-derived exosomal vesicles diluted in 40 mL of Dulbecco’s phosphate-buffered *** of the infusions were associated with adverse events such as infusion reactions(allergic or otherwise)or

关键词： allogeneic amyotrophic lateral sclerosis exosomes infusion neuromuscular junction Schwann cell

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Physical scientists research biomedicine: a call for caution

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chinese journal of cancer Research 2015年第1期27卷 94-95页

作者： Yì-Xiáng j.wáng Department of Imaging and Interventional Radiology Faculty of Medicine The Chinese University of Hong Kong Prince of Wales Hospital

It is noticeable that nowadays there are more and more scientists with physical science or engineering background working on or started to work on biomedical projects, but rarely vice versa. This reflects the multi-discipline nature of some projects, however, also at least partially can be explained that biomedical research is seen as trendy, fundable, and likely to get more citations and with results more publishable in high impact journals （1,2）. It is also apparent with some publications and lectures that not all these physical scientists/engineers are well-prepared to work on projects which do not align with their own expertise. Some studies are against very basic principles of pharmacology or biology, while others try to solve medical problems which do not exist clinically. I reviewed a number of submissions including a few from prestigious American universities to Nature journals which made no sense with the study design. Much of manpower and financial resource are being wasteful spent. There are also examples of clinical trials which were ill-planned right from the start and in the end only causing much inconvenience to patients to say at the least. In addition, ample examples exist where experienced physical scientists worked with inexperienced medical scientists and resulted in avoidable failures.

关键词： a call for caution very Physical scientists research biomedicine

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control of settlement and volume loss induced by tunneling under recently reclaimed land

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Underground Space 2019年第4期4卷 289-301页

作者： A.K.L.Kwong c.c.w.ng A.Schwob AEcOM Hong KongChina Dragages-Bouygues joint Venture Hong KongChina

The proposed Tuen Mun-chek Lap Kok Link(TM-cLKL)project comprises a 9-km-long dual two-lane carriageway between Tuen Mun and North Lantau,Hong *** of the two tunnels at the Northern Landfall Fall was carried out by two TBMs:the northbound is referred to as ML03 and has an excavated diameter of 17.63 m,and the southbound is referred to as ML02 and has an excavated diameter of 14.00 *** use of TBMs minimized the amount of dredging and removal of soft marine deposits,resulting in less impact to the environment within and near the work site of the *** treatment in the form of deep vibro-compaction was carried out at the sand fill and band drains installed in the marine deposit.A surcharge was also added above the final formation level to limit the residual settlement and differential settlement of the reclaimed land to less than 500 mm and 1 in 300,respectively,for a design life of 50 *** element analyses were performed to predict the settlement trough under different confinement pressures along the tunnel *** monitoring of the ground movement was carried out during the driving of the two TBMs to ensure that the design confinement pressure of the slurry would not cause excessive settlement,heave,or blow out at the shallow tunnel sections or different facilities along the tunnel *** monitoring data was then used to back-calculate the percentage of volume loss,which is a key index describing the behavior of the ground during *** monitoring data showed that the measured settlement and back-calculated volume loss were much lower than the predicted values.

关键词： TBM excavation Settlement trough Volume loss Ground treatment confinement pressure

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Status and prospects for symmetric organic redox flow batteries

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journal of Energy chemistry 2025年第1期100卷 125-143页

作者： Md Al Raihan c.Adam Dyker Department of chemistry University of New Brunswick

As environmental concerns from fossil fuel consumption intensify, large-scale energy storage becomes imperative for the integration of renewable sources like wind, hydro, and solar with the electrical *** flow batteries, particularly those employing organic molecules, are positioned as a key technology for this purpose. This review explores the growing field of symmetric organic redox flow batteries(ORFBs) within this context. Unlike traditional asymmetric designs based on unique active materials for each electrode, symmetric ORFBs involve a single bipolar species for both electrodes. This review highlights the benefits of a symmetric design, and categorizes five distinct classes of organic bipolar molecules used in both aqueous and non-aqueous solvents. By providing a comprehensive overview of their cell cycling and performance characteristics, the strengths and weaknesses of the diverse categories of bipolar molecules are highlighted for both solvent systems, as are opportunities for future development. This should guide new research directions and advance the development of practical symmetric ORFBs.

关键词： Redox flow battery Symmetric battery Organic battery Aqueous electrolyte Non-aqueous electrolyte

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On pancreatic cancer screening by magnetic resonance imaging with the recent evidence by Del chiaro and colleagues

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chinese journal of cancer Research 2015年第4期27卷 417-422页

作者： Yì-Xiáng j.wáng jing-Shan Gong Romaric Loffroy Department of Imaging and Interventional Radiology Faculty of Medicine The Chinese University of Hong Kong Prince of Wales Hospital Department of Radiology Shenzhen People’s Hospital Second clinical Medicine college of jinan University Department of Vascular Oncologic and Interventional Radiology Le2i UMR CNRS 6306 University of Dijon School of Medicine Bocage Teaching Hospital

Pancreatic cancer is a lethal disease because incidence and mortality rates are nearly *** 5-year survival rate in western countries is 4%,the lowest among all types of cancer（1）.In china,pancreatic cancer is the sixth leading cause of death from malignant disease,with an overall cumulative 5-year survival rate of 1%to 3%（2,3）.

关键词： screening mortality intraductal cumulative lethal identical mucinous incidence familial pancreas

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Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： christopher j.O’connell Matthew j.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA james L.winkle college of Pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

Traumatic brain injury(TBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(capizzi et al.,2020).TBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(capizzi et al.,2020).

关键词： sustained orange dynamic

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Estimation of j—R curves for Small-Sized cOEc Specimens and Its Application considering crack-Tip cons tr aints

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Acta Mechanica Solida Sinica 2019年第3期32卷 261-276页

作者： G.w.He c.Bao L.X.cai Y.j.wu Applied Mechanics and Structure Safety Key Laboratory of Sichuan Province School of Mechanics and Engineering Southwest Jiaotong University Chengdu 610031 China

The normalization method has been employed to estimate the j-resistance (j—R) curves for c-shaped outside edge-notched compression (cOEc) specimens of SA-508 steel. The cOEc specimens present the lowest j—R curves in comparison with other three types of specimens. Based on the j—Q—M met hod, the constraint parame ter Q determined at the mid-plane in the through-thickness direction of the specimen is used to approximately quantify the threedimensional crack-tip constraint for cOEc specimens. combining with the previous experiments on j—R curves, the constraint-coirected j—R curves for SA-508 steel specimens are given, which may be used to predict the fracture toughness of actual cracked components in structural integrity assessment.

关键词： Ductile fracture toughness cOEc specimen Dimensionless load separation principle Normalization method crack-tip constraint j-Q-M method

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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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Mechanical and hydraulic properties of carbonate rock:The critical role of porosity

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journal of Rock Mechanics and Geotechnical Engineering 2023年第4期15卷 814-825页

作者： Kam ng j.carlos Santamarina Department of civil and Architectural Engineering and construction Management University of WyomingLaramieWY82071USA Physical Science and Engineering Division King Abdullah University of Science and TechnologyThuwal23955-6900Saudi Arabia

carbonate rocks are extensively used in civil infrastructure and play a critical role in geoenergy geoengineering,either as hydrocarbon reservoirs or potential repositories for cO_(2)geological *** genesis and diagenetic overprint determine the properties of carbonate *** study combines recent data gathered from Madison Limestone and an extensive dataset compiled from published sources to analyze the hydraulic and mechanical properties of limestone carbonate *** models and data analyses recognize the inherently granular genesis of carbonate rocks and explain the strong dependency of physical properties on *** asymptotically-correct power model in terms of(1-Ф/Ф*)a is a good approximation to global trends of unconfined stiffness E and unconfined compressive strength UcS,cohesive intercept in Mohr-coulomb failure envelopes,and the brittle-toductile transition *** power model is the analytical solution for the mechanical properties of percolating granular *** adopted a limiting granular porosityФ*=0.5 for all models,which was consistent with the loosest packing of monosize *** fitted power model has exponent(α=2)in agreement with percolation theory and highlights the sensitivity of mechanical properties to *** and models confirm a porosity-independent ratio between unconfined stiffness and strength,and the ratio follows a log-normal distribution with mean(E/UcS)≈*** high angle of internal shear strength measured for carbonate rocks reflects delayed contact failure with increased confinement,and it is not sensitive to *** spans more than six orders of *** size controls pore size and determines the reference permeability k^(*)at the limiting porosityФ*=*** a given grain size from fine to coarse-grained dominant carbonates,permeability is very sensitive to changes in porosity,suggesting preferential changes in the internal pore network during compaction.

关键词： Rock porosity carbonate permeability Rock unconfined stiffness Unconfined compressive strength(UcS)

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