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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

Genetic interactions between polycystin-1 and Wwtr1 in osteoblasts define a novel mechanosensing mechanism regulating bone formation in mice

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Bone Research 2023年第4期11卷 772-783页

作者： Zhousheng Xiao Li Cao micholas d.an smith Hanxuan Li Wei Li Jeremy C.smith Leigh darryl Quarles department of Medicine University of Tennessee Health Science CenterMemphisTN 38163USA UT/ORNL Center for Molecular Biophysics Oak Ridge National LaboratoryOak RidgeTN 37830USA department of Biochemistry and Cellular and Molecular Biology The University of Tennessee-KnoxvilleKnoxvilleTN 37996-1939USA department of Pharmaceutical Sciences University of Tennessee Health Science CenterMemphisTN 38163USA

Molecular mechanisms transducing physical forces in the bone microenvironment to regulate bone mass are poorly ***,we used mouse genetics,mechanical loading,and pharmacological approaches to test the possibility that polycystin-1 and Wwtr1 have interdependent mechanosensing functions in *** created.and compared the skeletal phenotypes of control Pkd1^(flox/)+;Wwtr1^(flox/)+,Pkd1^(Oc-cKO),Wwtr1^(Oc-cKO),and Pkd1/Wwtr1^(Oc-cKO)mice to investigate genetic *** with an interaction between polycystins and Wwtr1 in bone in vivo,Pkd1/Wwtr1^(Oc-cKO)mice exhibited greater reductions of BMd.and periosteal MAR than either Wwtr1Oc-cKOor Pkd1^(Oc-cKO)***-CT 3d image analysis indicated that the reduction in bone mass was due to greater loss in both trabecular bone volume and cortical bone thickness in Pkd1/Wwtr1Oc-cKO mice compared to either Pkd1Oc-cKOor Wwtr1^(Oc-cKO)***1/Wwtr1^(Oc-cKO)mice also displayed additive reductions in mechanosensing and osteogenic gene expression profiles in bone compared to Pkd1Oc-cKOor Wwtr1^(Oc-cKO)***,we found that Pkd1/Wwtr1^(Oc-cKO)mice exhibited impaired responses to tibia mechanical loading in vivo and attenuation of loadinduced mechanosensing gene expression compared to control ***,control mice treated with a small molecule mechanomimetic,MS2 that activates the polycystin complex resulted in marked increases in femoral BMd.and periosteal MAR compared to vehicle *** contrast,Pkd1/Wwtr1^(Oc-cKO)mice were resistant to the anabolic effects of *** findings suggest that PC1 and Wwtr1 form an anabolic mechanotransduction signaling complex that mediates mechanical loading responses and serves as a potential novel therapeutic target for treating osteoporosis.

关键词： mec impaired additive

Chondroitinase ABC combined with Schwann cell transplantation enhances restoration of neural connection and functional recovery following acute and chronic spinal cord injury

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Neural Regeneration Research 2025年第5期20卷 1467-1482页

作者： Wenrui Qu Xiangbing Wu Wei Wu Ying Wang Yan Sun Lingxiao deng Melissa Walker Chen Chen Heqiao dai Qi Han Ying ding Yongzhi Xia George smith Rui Li Nai-Kui Liu Xiao-Ming Xu Spinal Cord.and Brain Injury Research Group Stark Neurosciences Research InstituteDepartment of Neurological SurgeryIndiana University School of MedicineIndianapolisINUSA department of Hand Surgery the Second Hospital of Jilin UniversityChangchunJilin ProvinceChina Shriners Hospitals Pediatric Research Center Temple University School of MedicinePhiladelphiaPAUSA department of Anatomy&Cell Biology Indiana University School of MedicineIndianapolisINUSA

Schwann cell transplantation is considered one of the most promising cell-based therapy to repair injured spinal cord due to its unique growth-promoting and myelin-forming properties.A the Food.and drug Administration-approved Phase I clinical trial has been conducted to evaluate the safety of transplanted human autologous Schwann cells to treat patients with spinal cord injury.A major challenge for Schwann cell transplantation is that grafted Schwann cells are confined within the lesion cavity,and they do not migrate into the host environment due to the inhibitory barrier formed by injury-induced glial scar,thus limiting axonal reentry into the host spinal *** we introduce a combinatorial strategy by suppressing the inhibitory extracellular environment with injection of lentivirus-mediated transfection of chondroitinase ABC gene at the rostral and caudal borders of the lesion site and simultaneously leveraging the repair capacity of transplanted Schwann cells in adult rats following a mid-thoracic contusive spinal cord *** report that when the glial scar was degraded by chondroitinase ABC at the rostral and caudal lesion borders,Schwann cells migrated for considerable distances in both rostral and caudal *** Schwann cell migration led to enhanced axonal regrowth,including the serotonergic and dopaminergic axons originating from supraspinal regions,and promoted recovery of locomotor and urinary bladder ***,the Schwann cell survival and axonal regrowth persisted up to 6 months after the injury,even when treatment was delayed for 3 months to mimic chronic spinal cord *** findings collectively show promising evidence for a combinatorial strategy with chondroitinase ABC and Schwann cells in promoting remodeling and recovery of function following spinal cord injury.

关键词： axonal regrowth bladder function chondroitinase ABC functional recovery glial scar lentivirus migration Schwann cell spinal cord injury transplantation

Challenges in Understanding Genome-Wide dNA Methylation

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Journal of Computer Science & Technology 2010年第1期25卷 26-34页

作者：张伟奇 Andrew d. smith Cold Spring Harbor Laboratory Cold Spring Harbor Bioinformatics division TNLIST and MOE Key Lab of Bioinformatics Tsinghua University department of Biological Sciences University of Southern California

dNA methylation is a chemical modification of the bases in genomes. This modification, most frequently found at CpG dinucleotides in eukaryotes, has been identified as having multiple critical functions in broad.and diverse species of animals and plants, while mysteriously appears to be lacking from several other well-studied species. dNA methylation has well known and important roles in genome stability and defense, its pattern change highly correlates with gene regulation. Much evidence has linked abnormal dNA methylation to human diseases. Most prominently, aberrant dNA methylation is a common feature of cancer genomes. Elucidating the precise functions of dNA methylation therefore has great biomedical significance. Here we provide an update on large-scale experimental technologies for detecting dNA methylation on a genomic scale. We also discuss new prospect and challenges that computational biologist will face when analyzing dNA methylation data.

关键词： dNA methylation epigenome computational epigenomics

Annual-perennial plant relationships and species selection for desert restoration

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Journal of Arid Land 2013年第3期5卷 298-309页

作者： Scott R ABELLA Stanley d smith department of Environmental and Occupational Health University of Nevada Las VegasLas VegasNevada 89154-3064USA School of Life Sciences University of Nevada Las VegasLas VegasNevada 89154-4004USA

Exotic plant invasion is a growing concern in the conservation and management of indigenous arid land ecosystems. By creating areas of ameliorated microclimates and fertile soil below their canopies, perennial plants might influence exotic annual plant invasions. We conducted a quantitative literature review of studies that compared exotic annual plant abundance among native perennial plant species and interspace （open areas） microsites in North America＇s Mojave desert, where exotic plant invasion has corresponded with increasing extent of wildfire and broad-scale ecosystem transformation. Ten studies compared exotic annual plant abundance between inter- spaces and below a total of 36 native perennial species. These studies revealed that：（1） With few exceptions, most native perennial species supported a greater abundance of exotic annuals than interspaces, indicating overall facilitation of exotic species by native perennials. （2） Exotic species abundance varied by orders of magnitude among native perennial species, with some perennial species harboring amounts of exotics similar to interspaces. （3） distributions of dominant exotic species varied, where Bromus rubens displayed a greater affinity for below-perennial microsites than did Schismus spp. and Erodium cicutarium that often were most abundant in interspaces. Results suggest that the degree of facilitation of exotic plants warrants consideration when selecting native perennial species for revegetation and restoration projects.

关键词： Bromus rubens exotic fertile island invasive nurse plant positive plant interaction Schismus

History and evaluation of national-scale geochemical data sets for the United States

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Geoscience Frontiers 2013年第2期4卷 167-183页

作者： david B.smith Steven M.smith John d.Horton U.S.Geological Survey.denver Federal Center MS 973.DenverCO 80225USA

Six national-scale,or near national-scale,geochemical data sets for soils or stream sediments exist for the United *** earliest of these,here termed the ＇Shacklette＇ data set,was generated by a U.S. Geological Survey（USGS） project conducted from 1961 to *** project used soil collected from a depth of about 20 cm as the sampling medium at 1323 sites throughout the conterminous *** National Uranium Resource Evaluation Hydrogeochemical and Stream Sediment Reconnaissance（NUREHSSR） Program of the *** of Energy was conducted from 1975 to 1984 and collected either stream sediments,lake sediments,or soils at more than 378,000 sites in both the conterminous *** *** sampled area represented about 65%of the *** Natural Resources Conservation Service（NRCS）,from 1978 to 1982,collected samples from multiple soil horizons at sites within the major crop-growing regions of the conterminous *** data set contains analyses of more than 3000 *** National Geochemical Survey,a USGS project conducted from 1997 to 2009,used a subset of the NURE-HSSR archival samples as its starting point and then collected primarily stream sediments, with occasional soils,in the parts of the *** covered by the NURE-HSSR *** data set contains chemical analyses for more than 70,000 *** USGS,in collaboration with the Mexican Geological Survey and the Geological Survey of Canada,initiated soil sampling for the North American Soil Geochemical Landscapes Project in *** of three horizons or depths at more than 4800 sites in the *** completed in 2010,and chemical analyses are currently *** NRCS initiated a project in the 1990s to analyze the various soil horizons from selected pedons throughout the *** data set currently contains data from more than 1400 *** paper（1） discusses each data set in terms of its purpose,sample collection protocols,and.analytical methods;and（2） evaluates each data set in terms

关键词： Geochemical mapping National-scale geochemical data Geochemical baselines United States

An Approach to Reducing Input Parameter Volume for Fault Classifiers

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International Journal of Automation and computing 2019年第2期16卷 199-212页

作者： Ann smith Fengshou Gu Andrew d.Ball Centre for Efficiency and Performance Engineering University of Huddersfield

As condition monitoring of systems continues to grow in both complexity and application, an overabundance of data is amassed. Computational capabilities are unable to keep abreast of the subsequent processing requirements. Thus, a means of establishing computable prognostic models to accurately reflect process condition, whilst alleviating computational burdens, is essential. This is achievable by restricting the amount of information input that is redundant to modelling algorithms. In this paper, a variable clustering approach is investigated to reorganise the harmonics of common diagnostic features in rotating machinery into a smaller number of heterogeneous groups that reflect conditions of the machine with minimal information redundancy. Na?ve Bayes classifiers established using a reduced number of highly sensitive input parameters realised superior classification powers over higher dimensional classifiers,demonstrating the effectiveness of the proposed approach. Furthermore, generic parameter capabilities were evidenced through confirmatory factor analysis. Parameters with superior deterministic power were identified alongside complimentary, uncorrelated, ***, variables with little explanatory capacity could be eliminated.and lead to further variable reductions. Their information sustainability is also evaluated with Na?ve Bayes classifiers, showing that successive classification rates are sufficiently high when the first few harmonics are used. Further gains were illustrated on compression of chosen envelope harmonic features. A Na?ve Bayes classification model incorporating just two compressed input variables realised.an 83.3% success rate, both an increase in classification rate and.an immense improvement volume-wise on the former ten parameter model.

关键词： Fault diagnosis classification variable clustering data compression big data

Co-deposition of Co-Ni alloys and their microstructure analysis by PoSAP

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Chinese Science Bulletin 1997年第23期42卷 2013-2014页

作者： R.A.d.Mackenzie G.d.W.smith department of Materials University of Oxford Parks Road Oxford OX1 3PH UKDepartment of Materials University of Oxford Parks Road Oxford OX1 3PH UK

PULSEd-co-electrodeposition （PCd） is a new and promising technique for producing alloymaterials of nanometer grain size. In this letter, Co-Ni alloys were produced by PCd, and theeffect of CO+2 ion concentration in the depositing baths on the Co content and the microstruc-ture in the corresponding deposit was studied by the position sensitive atom probe （PoSAP）,TEM and X-ray diffraction. The Co-Ni phase diagram shows that, at room temperature,there are two phases in Co-Ni alloys, one is εCo with hcp lattice, the other is αCo of fcc lat-tice. A Co-Ni alloy with a Ni content below 27% consists of single εCo, beyond 36% consistsof single αCo, in between consists of εCo + αCo. The examination results of TEM, SEM andX-ray diffraction indicated that the Co-Ni deposits with average grain size of 70 nm and thick-

关键词： Co-deposition of Co-Ni alloys and their microstructure analysis by PoSAP Ni

Utility of arthroscopic guided synovial biopsy in understanding synovial tissue pathology in health and disease states

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World Journal of Orthopedics 2014年第5期5卷 566-573页

作者： Mihir d Wechalekar Malcolm d smith Rheumatology Research Unit Repatriation General Hospital Daw Park SA 5041 Australia

The synovium is the soft tissue lining diarthrodial joints, tendon sheaths and bursae and is composed of intimal and subintimal layers. The intimal layer is composed of type A cells(macrophages) and type B cells(fibroblasts); in health, the subintima has few inflammatory cells. The synovium performs several homeostatic functions and is the primary target in several inflammatory arthritides. Inflammatory states are characterised by thickening of the synovial lining, macrophage recruitment and fibroblast proliferation, and.an influx of inflammatory cells including lymphocytes, monocytes and plasma cells. Of the various methods employed to perform synovial biopsies arthroscopic techniques are considered the "gold standard", and have an established safety record. Synovial biopsy has been of critical importance in understanding disease pathogenesis and has provided insight into mechanisms of action of targeted therapies by way of direct evidence about eventsin the synovial tissue in various arthritides. It has been very useful as a research tool for proof of concept studies to assess efficacy and mechanisms of new therapies, provide tissue for in vitro studies, proteomics and microarrays and allow evaluation for biomarkers that may help predict response to therapy and identify new targets for drug development. It also has diagnostic value in the evaluation of neoplastic or granulomatous disease or infection when synovial fluid.analysis is noncontributory.

关键词： Synovium Synovial biopsy Arthroscopy Inflammatory arthritis Synovial pathology