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Combination of epidural electrical stimulation with ex vivo triple gene therapy for spinal cord injury:a proof of principle study

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Neural Regeneration Research 2021年第3期16卷 550-560页

作者： Filip Olegovich Fadeev Farid Vagizovich Bashirov Vahe Arshaluysovich markosyan Andrey Alexandrovich Izmailov Tatyana Vyacheslavovna Povysheva mikhail Evgenyevich Sokolov maxim Sergeevich Kuznetsov Anton Alexandrovich Eremeev Ilnur Ildusovich Salafutdinov Albert Anatolyevich Rizvanov Hyun Joon Lee Rustem Robertovich Islamov Department of medical Biology and Genetics Kazan State Medical UniversityKazanRussia Federal University KazanRussia Department of Neurology University of Mississippi Medical CenterJacksonMSUSA Research Service G.V.(Sonny)Montgomery VA Medical CenterJacksonMSUSA

Despite emerging contemporary biotechnological methods such as gene-and stem cell-based therapy,there are no clinically established therapeutic strategies for neural regeneration after spinal cord *** previous studies have demonstrated that transplantation of genetically engineered human umbilical cord blood mononuclear cells producing three recombinant therapeutic molecules,including vascular endothelial growth factor(VEGF),glial cell-line derived neurotrophic factor(GDNF),and neural cell adhesion molecule(NCAm)can improve morpho-functional recovery of injured spinal cord in rats and *** investigate the efficacy of human umbilical cord blood mononuclear cells-mediated triple-gene therapy combined with epidural electrical stimulation in the treatment of spinal cord injury,in this study,rats with moderate spinal cord contusion injury were intrathecally infused with human umbilical cord blood mononuclear cells expressing recombinant genes VEGF165,GDNF,NCAm1 at 4 hours after spinal cord *** days after injury,epidural stimulations were given simultaneously above the lesion site at C5(to stimulate the cervical network related to forelimb functions)and below the lesion site at L2(to activate the central pattern generators)every other day for 4 *** subjected to the combined treatment showed a limited functional improvement of the knee joint,high preservation of muscle fiber area in tibialis anterior muscle and increased H/m ratio in gastrocnemius muscle 30 days after spinal cord ***,beneficial cellular outcomes such as reduced apoptosis and increased sparing of the gray and white matters,and enhanced expression of heat shock and synaptic proteins were found in rats with spinal cord injury subjected to the combined epidural electrical stimulation with gene *** study presents the first proof of principle study of combination of the multisite epidural electrical stimulation with ex vivo triple gene therapy(VEGF,GDNF and NCAm

关键词： adenoviral vector epidural electrical stimulation gene therapy glial cell-line derived neurotrophic factor human umbilical cord blood mononuclear cell neural cell adhesion molecule spinal cord injury vascular endothelial growth factor

Human allograft rejection in humanized mice： a historica perspective

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Cellular & molecular Immunology 2012年第3期9卷 225-231页

作者： michael A Brehm Leonard D Shultz Program in molecular medicine University of Massachusetts Medical School Worcester MA USA The jackson Laboratory Bar Harbor M_E usA

Basic research in transplantation immunology has relied primarily on rodent models. Experimentation with rodents has laid the foundation for our basic understanding of the biological events that precipitate rejection of non-self or allogeneic tissue transplants and supported the development of novel strategies to specifically suppress allogeneic immune responses, However, translation of these studies to the clinic has met with limited success, emphasizing the need for new models that focus on human immune responses to allogeneic tissues. Humanized mouse models are an exciting alternative that permits investigation of the rejection of human tissues mediated by human immune cells without putting patients at risk. However, the use of humanized mice is complicated by a diversity of protocols and approaches, including the large number of immunodeficient mouse strains available, the choice of tissue to transplant and the specific human immune cell populations that can be engrafted. Here, we present a historical perspective on the study of allograft rejection in humanized mice and discuss the use of these novel model systems in transplant biology.

关键词： transplantation immunodeficient mice human

Effect of Wetting-Drying Cycles on Redistribution of Lead in Some Semi-Arid Zone Soils Spiked with a Lead Salt

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Pedosphere 2012年第3期22卷 304-313页

作者： H.KHODAVERDILOO m.RAHmANIAN S.REZAPOUR S.GHORBANI DASHTAKI H.HADI F.X.HAN Department of Soil Science Urmia UniversityUrmia 57135-165 (Iran) Department of Soil Science Shahrekord UniversityShahrekord 88186/34141 (Iran) Department of Agronomy and Plant Breeding Urmia UniversityUrmia 57135-165 (Iran) Department of Chemistry and Biochemistry JacksonState UniversityJacksonMS 39217-0510 (USA)

mobility and bioavailability of lead （Pb） could be affected considerably by soil physicochemical properties; however, less is known about the effect of Pb levels and aging time. This study was conducted to evaluate the effects of Pb levels and wetting-drying （WD） cycles on distribution and bioavailability of Pb in three semi-arid zone soils treated with different levels of Pb（NO3）2. Wetting-drying cycles simulated the actual field irrigation in the semi-arid soils. A soil with a long history of Pb contamination was also taken as a reference soil. The soils were spiked with various levels of Pb and incubated under WD cycles for 160 d. Sequential extractions and batch sorption experiments were performed to assess the fractionation of Pb in the spiked soils. Redistribution index （Uts） and reduced partitioning parameter （IR） were applied to semi-quantify the distribution of Pb in the spiked soils. A small amount of Pb sorbed was desorbed by the soils, indicating a strong and irreversible binding of Pb in the studied soils. Contribution of carbonate-bound （Car） and residual （Res） Pb fl＇actions to the total Pb of the soils was more than 97%. The Car, soluble plus exchangeable （SE）, and organic matter-bound （OmB） fractions of Pb were transferred to the Res fraction under the WD cycles. The IR and Uts values were influenced by Pb loading levels and WD; therefore, the Pb lability and/or redistribution pattern could semi-quantitatively be assessed via these parameters. At the end of the experiment, the Ia and Uts values for the Pb salt-spiked soils did not show the quasi- equilibrium state. The lability of Pb in the soils decreased with increasing incubation time and showed a strong dependence on Pb levels and soil chemical composition. WD cycles significantly affected the overall lability of Pb in soils through influencing the redistribution of Pb among solid-phase components.

关键词： bioavailability heavy metals mobility redistribution index reduced partitioning parameter

Experimental analysis for the dynamic initiation mechanism of debris flows

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Journal of mountain Science 2016年第4期13卷 581-592页

作者： LI Chi ZHU Wen-hui LI Lin LU Xiao-bing YAO De Farshad AmINI College of Civil Engineering Inner Mongolia University of Technology Department of Civil and Environmental Engineering Jackson State University Institute of mechanics Chinese Academy of Science

Debris flow is one of the major secondary mountain hazards following the earthquake. This study explores the dynamic initiation mechanism of debris flows based on the strength reduction of soils through static and dynamic triaxial tests. A series of static and dynamic triaxial tests were conducted on samples in the lab. The samples were prepared according to different grain size distribution, degree of saturation and earthquake magnitudes. The relations of dynamic shear strength, degree of saturation, and number of cycles are summarized through analyzing experimental results. The findings show that the gravelly soil with a wide and continuous gradation has a critical degree of saturation of approximately 87%, above which debris flows will be triggered by rainfall, while the debris flow will be triggered at a critical degree of saturation of about 73% under the effect of rainfall and earthquake(m>6.5). Debris flow initiation is developed in the humidification process, and the earthquake provides energy for triggering debris flows. Debris flows are more likely to be triggered at the relatively low saturation under dynamic loading than under static loading. The resistance of debris flow triggering relies more on internal frication angle than soil cohesion under the effect of rainfall and earthquake. The conclusions provide an experimental analysis method for dynamic initiation mechanism of debris flows.

关键词： mountain hazard Debris flows Initiation mechanism Humidification process Rainfall Earthquake Triaxial test

Delivery of Cas9 Protein into mouse Zygotes through a Series of Electroporation Dramatically Increases the Efficiency of model Creation

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Journal of Genetics and Genomics 2016年第5期43卷 319-327页

作者： Wenbo Wang Peter m.Kutny Shannon L.Byers Charles J.Longstaff michael J.DaCosta Changhong Pang Yingfan Zhang Robert A.Taft Frank W.Buaas Haoyi Wang The jackson Laboratory Bar Harbor ME 04609 USA State Key Laboratory of Stem Cell and Reproductive Biology Institute of Zoology Chinese Academy of Sciences Beijing 100101 China

Previously we established Zygote Electroporation of Nucleases（ZEN） technology as an efficient and high-throughput way to generate genetically modified mouse ***,there were significant variations of the targeting efficiency among different genomic loci using our previously published *** this study,we improved the ZEN technology by delivering Cas9 protein into mouse zygotes through a series of *** this approach,we were able to introduce precise nucleotide substitutions,large segment deletion and short segment insertion into targeted loci with high efficiency.

关键词： CRISPR-Cas9 Electroporation mouse zygote

COVID-19 and hepatorenal syndrome

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World Journal of Gastroenterology 2022年第39期28卷 5666-5678页

作者： henry H L Wu Varinder S Athwal Philip A Kalra Rajkumar Chinnadurai Kolling Institute of medical Research Royal North Shore HospitalSydney 2065New South WalesAustralia Faculty of Biology Medicine&Health(Division of DiabetesMetabolism&Gastroenterology)The University of ManchesterManchester M139PLUnited Kingdom Department of Renal medicine Northern Care Alliance NHS Foundation TrustSalford M68HDUnited Kingdom

Coronavirus disease 2019(COVID-19)is a highly infectious disease which emerged into a global *** it primarily causes respiratory symptoms for affected patients,COVID-19 was shown to have multi-organ *** liver enzymes appear to be commonly observed during the course of COVID-19,and there have been numerous reports of liver injury secondary to COVID-19 *** has been established that patients with pre-existing chronic liver disease(CLD)are more likely to have poorer outcomes following COVID-19 infection compared to those without ***-morbidities such as diabetes,hypertension,obesity,cardiovascular and chronic kidney disease frequently co-exist in individuals living with CLD,and a substantial population may also live with some degree of *** mechanisms of how COVID-19 induces liver injury have been *** syndrome(HRS)is the occurrence of kidney dysfunction in patients with severe CLD/fulminant liver failure in the absence of another identifiable cause,and is usually a marker of severe decompensated liver *** reports of HRS following acute COVID-19 infection have been presented,although the risk factors and pathophysiological mechanisms leading to HRS in COVID-19 infection or following COVID-19 treatment remain largely unestablished due to the relative lack and novelty of published *** discussing the management of HRS in highdependency care and intensive care contexts is only *** this article,we provide an overview on the speculative pathophysiological me-chanisms of COVID-19 induced HRS and propose strategies for clinical diagnosis and management to optimize outcomes in this scenario.

关键词： COVID-19 Hepatorenal syndrome Pathophysiology Clinical assessment management Prognosis

Stratal Slice Recognition of Thin Shallow-Water Delta Sandbodies in the Songliao Basin

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Acta Geologica Sinica(English Edition) 2016年第2期90卷 763-764页

作者： ZHU Xiaomin ZENG Hongliu DONG Yanlei ZHU Shifa China University of Petroleum Beijing 102249 China Bureau of Economic Geology Jackson School of Geosciences The University of Texas at Austin Texas 78712 USA

Objective China＇s petroleum exploration has entered a new stage of finding deeply buried thin sandbodies lbr the abundant oil resources they contain. Here thin sandbodies refer to those less than 10 m in thickness, or even less than 1-2 m. It is difficult to depict thin-layer sandbodies of different genetic types using conventional core, well logging and seismic data due to their limited vertical resolution in petroliferous basins. However, seismic sedimentology provides a new research method especially tbr thin sandbody interpretation, i.e., validating interpreted sedimentary sandbodies from 3D seismic data based on horizontal resolution, stratal slice and seismic geomorphology interpretation. At present, a series of studies on seismic sedimentology in North America marine basins and elsewhere have been completed successfully and are relevant to the exploration and development of oil and gas fields.

关键词： Stratal Slice Recognition of Thin Shallow-Water Delta Sandbodies in the Songliao Basin

Extragenital chlamydia infection among active-duty women in the United States Navy

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military medical Research 2019年第3期6卷 208-215页

作者： Robert Deiss morgan Byrne Sara mEchols Stephanie mCammarata Lynda Potswald Eduardo Gomez Jennifer ACurry Eric Garges Grace macalino Brian KAgan mary FBavaro Infectious Disease Clinical Research Program Department ofPreventive Medicine and BiostatisticsUniformed Services Universityof the Health Sciences11300Rockville PikeRockvilleMD20850USA The henry m.jackson foundation for the Advancement of militarymedicine Inc6720A Rockledge DriveBethesdaMD20817USA Division of Infectious Diseases Naval Medical Center San Diego34800Bob Wilson DriveSte201San DiegoCA92134USA 32nd StreetBranch medical Clinic Naval Medical Center San Diego2450CravenStSan DiegoCA92104USA Division of Tropical medical Health Department of Preventive Medicine and BiostatisticsUniformedServices University of the Health Sciences4301Jones Bridge RoadBethesdaMD20814-4799USA marimac Insight LLCSimpsonvilleMDUSA.

Background: Pharyngeal and anorectal reservoirs of gonorrhea(GC) and chlamydia(CT) are increasingly recognized among heterosexual women. While a number of studies performed at sexually transmitted disease(STD) clinics have found a high prevalence of extragenital GC/CT infection, such screening is typically not offered during routine primary care visits for women. We sought to define the prevalence of and factors associated with extragenital GC/CT among women in the U.S. ***: We recruited servicewomen stationed in San Diego, California, between the ages of 18 and 25 who presented for an annual physical exam between January and September, 2017. Nucleic acid amplification testing was performed on swabs collected at endocervical, oropharyngeal and anorectal sites to assess the presence of GC/CT. An anonymous behavioral questionnaire was also administered to characterize sexual risk. Descriptive statistics were used to compare women with and without a prior history of any sexually transmitted infection(STI)(self-report) along with a current GC/CT diagnosis. This study was approved by the Institutional Review Board of the Uniformed Services University of Health ***: Of the 75 patients who were approached, 60 subjects were enrolled in the study, including white 20(33.3%), black/African American 18(31.0%), Hispanic/Latina 13(21.7%) and Asian/Pacific Islander 9(15.5%) women. Among all the women, six(10.0%) were diagnosed with CT infection, all via endocervical exam. Of these, five(8.3%) had concurrent anorectal infection, including two cases(3.3%) accompanied by pharyngeal infection. Of the subjects, 15(25.0%) reported anal intercourse in their most recent sexual encounter, most of which was condomless(13/15, 86.7%). A high number of women who reported sex with a casual male partner(19/45, 42.2%) reported rarely or never using condoms;last, 41.7% consuming at least 3 drinks on a typical drinking day, and one-third of the reported drinking more than once

关键词： Chlamydia military Risk behavior Sexually transmitted infection

Radial tidal current field in a semi-enclosed rectangular basin: formation and evolution

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Chinese Journal of Oceanology and Limnology 2015年第4期33卷 1085-1099页

作者：钱学生陈永平张长宽潘毅 DAS Himangshu State Key Laboratory of Hydrology-Water Resources and Hydraulic Engineering Hohai University College of Harbor Coastal and Offshore Engineering Hohai University Department of Civil and Environmental Engineering Jackson State University

The radial tidal current field accounts for the formation of the radial sand ridges in the South Yellow Sea. Understanding the formation and evolution of this radial tidal current field is vital to assessing the morphodynamic features in the area. A semi-enclosed rectangular basin with and without a coastal barrier was schematized from the topography of the Bohai Sea and Yellow Sea. The 2D tidal current field in this basin was simulated using the DELFT3D-FLOW model. The concept of tidal wave refraction, which highlights the effect of the sloped or stepped submarine topography on the propagation of the tidal waves, was introduced to explain the formation of the radial tidal current field. Under the effect of tidal wave refraction, co-phase lines of the counterclockwise rotating tidal wave and incident tidal wave are transformed into clockwise and counterclockwise deflections, respectively, leading to the convergence and divergence of the flow field. Regardless of whether a coastal barrier exists or not, the outer radial tidal current field might emerge over certain topography. The responses of the radial tidal current field in this basin to the environmental variations such as coastline changes and bottom erosions were discussed. Results show that local protrusion near the focal point of the radial tidal current field will have limited effects on the location of the tidal system. However, a remarkable shift of the amphidromic point toward the entrance and central axis of this basin and a movement of the focal point of the radial tidal current field toward the entrance could be caused by the significant seaward coastline advance and submarine slope erosion.

关键词： semi-enclosed rectangular basin coastal barrier m2 tide amphidromic point radial tidal current field