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Functionality of a bicistronic construction containing HEXA and HEXB genes encoding β-hexosaminidase A for cell-mediated therapy of GM2 gangliosidoses

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Neural Regeneration Research 2022年第1期17卷 122-129页

作者： Alisa A.shaimardanova Daria s.Chulpanova Valeriya V.solovyeva Aleksandr M.Aimaletdinov albert A.Rizvanov Institute of Fundamental Medicine and Biology Kazan Federal UniversityKazanRussia

Tay-sachs disease and sandhoff disease are severe hereditary neurodegenerative disorders caused by a deficiency ofβ-hexosaminidase A(HexA)enzyme,which results in the accumulation of GM2 gangliosides in the nervous system *** this work,we analyzed the efficacy and safety of cell-mediated gene therapy for sandhoff disease and sandhoff disease using a bicistronic lentiviral vector encoding cDNA of HexAα-andβ-subunit genes separated by the nucleotide sequence of a P2A peptide(HEXA-HEXB).The functionality of the bicistronic construct containing the HEXA-HEXB genetic cassette was analyzed in a culture of HEK293T cells and human umbilical cord blood mononuclear cells(hUCBMCs).Our results showed that the enzymatic activity of HexA in the conditioned medium harvested from genetically modified HEK293T-HEXA-HEXB and hUCBMCs-HEXA-HEXB was increased by 23 and 8 times,respectively,compared with the conditioned medium of native *** blot analysis showed that hUCBMCs-HEXA-HEXB secreted both completely separated HEXA and HEXB proteins,and an uncleaved protein containing HEXA+HEXB linked by the P2A *** injection of genetically modified hUCBMCs-HEXA-HEXB to laboratory Wistar rats was carried out,and the HexA enzymatic activity in the blood plasma of experimental animals,as well as the number of live cells of immune system organs(spleen,thymus,bone marrow,lymph nodes)were determined.A significant increase in the enzymatic activity of HexA in the blood plasma of laboratory rats on days 6 and 9(by 2.5 and 3 times,respectively)after the administration of hUCBMCsHEXA-HEXB was *** the same time,the number of live cells in the studied organs remained ***,the functionality of the bicistronic genetic construct encoding cDNA of the HEXA and HEXB genes separated by the nucleotide sequence of the P2A peptide was shown in vitro and in *** hypothesize that due to the natural ability of hUCBMCs to overcome biological barriers,such a strategy can rest

关键词： bicistronic vector cell-mediated gene therapy GM2 gangliosidosis P2A peptide sandhoff disease Tay-sachs disease umbilical cord blood mononuclear cells β-hexosaminidase

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sequestration of carbon as carbonate in the critical zone：insights from the Himalayas and Tibetan Plateau

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Acta Geochimica 2017年第3期36卷 389-391页

作者： albert Galy Yibo Yang Xiaomin Fang Centre de Recherches Pétrographiques et Géochimiques (CRPG) UMR7358 CNRS Université de Lorraine 15 rue Notre Dame des Pauvres 54500 Vandoeuvre les Nancy France Key Laboratory of Continental Collision and Plateau Uplift Institute of Tibetan Plateau Research Chinese Academy of Sciences Beijing 100085 China CAs Center for Excellence in Tibetan Plateau Earth sciences Beijing 100085 China

The carbon pool stored in soil carbonate is comparable to the soil organic ***,secondary calcite precipitation in supersaturated catchment could be an important,yet poorly constrained,carbon sink within the modern global carbon *** chemical analysis of some dissolved species transported by rivers,such as elevated sr/Ca and Mg/Ca ratios but also heavy stable Ca isotopic compositions,witness the formation of secondary calcite in rivers draining arid ***,in areas affected by active tectonics and rapid physical erosion,co-variations in the fluvial sr/Ca and Mg/Ca ratios could also be related to incongruent carbonate weathering ***,we present a model to assess the roles played by incongruent carbonate dissolution and secondary calcite precipitation in modern weathering *** tested and applied the model to rivers draining the Himalayan–Tibetan *** results suggest that regional aridity in the drainage basin promotes carbon sequestration as secondary carbonate but that for a given runoff,incongruent dissolution of carbonate possibly related to rapid physical erosion amplifies such *** isotopic compositions(^(13)C/^(12)C and^(18)O/^(16)O)of detrital carbonate transported by the main rivers in south and south-East Tibet imply that around 1%of the suspended material transported by those rivers corresponds to secondary carbonate and can represent between 5%and 15%of the alkalinity *** of these alkalinity transported as particulate material is,nevertheless related to the weathering of carbonate lithologies and is also subjected to dissolution prior its final storage in sedimentary ***,on glacial-interglacial timescale this will amplify the significant role of mountain weathering on climatic variations.

关键词： Carbonate Weathering Isotope Tectonic forcing

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Potential applications and implications of large language models in primary care

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Family Medicine and Community Health 2024年第S01期12卷 6-11页

作者： albert Andrew Medical student The University of Auckland School of MedicineAucklandNew Zealand

The recent release of highly advanced generative artificial intelligence(AI)chatbots,including ChatGPT and Bard,which are powered by large language models(LLMs),has attracted growing mainstream interest over its diverse applications in clinical practice,including in health and *** potential applications of LLM-based programmes in the medical field range from assisting medical practitioners in improving their clinical decision-making and streamlining administrative paperwork to empowering patients to take charge of their own ***,despite the broad range of benefits,the use of such AI tools also comes with several limitations and ethical concerns that warrant further consideration,encompassing issues related to privacy,data bias,and the accuracy and reliability of information generated by *** focus of prior research has primarily centred on the broad applications of LLMs in *** the author’s knowledge,this is,the first article that consolidates current and pertinent literature on LLMs to examine its potential in primary *** objectives of this paper are not only to summarise the potential benefits,risks and challenges of using LLMs in primary care,but also to offer insights into considerations that primary care clinicians should take into account when deciding to adopt and integrate such technologies into their clinical practice.

关键词： primarily benefits administrative

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Impaired endothelial progenitor cells mobilization: a novel concept for reduce post-ischemia neovascularization in diabetes

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上海医学 2007年第S1期30卷 59-60页

作者： albert FERRO Department of Clinical Pharmacology Cardiovascular DivisionKing's College LondonLondon UK

Objective The aim of the present study was to explore potential mechanism underlying reduced basal circulating endothelial progenitor cells (EPCs) in diabetes, and to determine how diabetes impairs ischemia-induced mobilization of bone marrow-derived EPCs. Methods Circulating c-Kit+/sca-1+/flk-1+ EPCs and CD31bright/Annexin V+ endothelial microparticles (EMPs) were analyzed by flow cytometry in control and streptozotocin-induced diabetic C57BL/6 mice. Results Compared with nondiabetic controls, diabetic mice had lower level of circulating EPCs, higher level of plasma EMPs, and increased ratio of EMPs to EPCs. Circulating EMPs count and EPCs level were negatively associated with each other. In a hindlimb ischemia model, diabetes suppressed bone marrow-derived EPCs mobilization, accompanied by insufficient upregulaiton of vascular endothelial growth factor (VEGF) and over-activation of matrix metalloproteinases (MMPs) system. As a consequence, diabetic mice showed deficient increase of capillary density and hampered restoration of transcutaneous oxygen pressure (tcpO2) in the ischemic *** These results suggest that lower circulating EPCs level detected in diabetes may be partly attributed to consumptive loss of EPCs due to increased endothelial damage. Impairment in ischemia-induced EPCs mobilization presents a novel mechanism for defective post-ischemia neovascularization in diabetes.

关键词： mobilization progenitor EPCs streptozotocin circulating cytometry restoration underlying suppressed

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First 100 cases of transvesical single-port robotic radical prostatectomy

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Asian Journal of Urology 2023年第4期10卷 416-422页

作者： Roxana Ramos-Carpinteyro Ethan L.Ferguson Jaya s.Chavali albert Geskin Jihad Kaouk Glickman Urological&Kidney Institute Cleveland Clinic FoundationClevelandOHUSA

Objective:To describe the surgical technique and report the early outcomes of the transvesical(TV)approach to single-port(sP)robot-assisted radical ***:All procedures were performed at a single center by one *** identified the first 100 consecutive patients with clinically localized prostate cancer that underwent sP TV robot-assisted radical prostatectomy using the da Vinci sP robotic surgical *** were collected prospectively and analyzed with descriptive *** primary outcomes assessed were postoperative urinary continence,rate of biochemical recurrence,and sexual ***:All procedures were performed without extra ports or *** median age was 62.1 years and 49.0%of the patients had abdominal surgery *** preoperative median prostate-specific antigen value and prostate volume were 5.0 ng/mL and 33.0 mL,*** were no intraoperative *** median operative time and estimated blood loss were 212.5 min and 100.0 mL,respectively.A total of 92.0%of patients were discharged within 24.0 h,with an overall median length of stay of 5.6 *** 4.0%of patients required opioid prescriptions at *** median Foley catheter duration was 3 *** margins were present in 15.0%of *** follow-up was 10.4 *** rate was immediate after Foley removal in 49.0%of cases,65.0%at 2 weeks,77.4%at 6 weeks,94.1%at 6 months,and 98.9%at 1 *** case of biochemical recurrence(1.0%)was noted 3 months after ***:The sP TV approach for radical prostatectomy cases is a safe and feasible technique for patients with clinically localized prostate *** technique offers advantages of short hospital stay,minimal narcotic use postoperatively,and promising early return of urinary continence,without compromising oncologic outcomes.

关键词： Prostate cancer Radical prostatectomy Robotic-assisted surgery single-port Minimally-invasive surgery

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脉络膜黑素瘤蛋白表达错配修复的改变和微卫星不稳性

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美国医学会眼科杂志（中文版） 2006年第4期18卷 253-253页

作者： Mahmoud R. Hussein, MscPath Anna K Haemel Daniel M. albert Gary s.Wood 刘亮（译）

目的：通过蛋白质微卫星不稳性（MsI）和错配修复（MMR）的改变证明脉络膜黑素瘤基因组的不稳定性，评估这些变化对肿瘤的临床病理特征有无关联。

关键词：错配修复不稳性微卫星黑素瘤脉络膜蛋白表达临床病理特征不稳定性

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stress corrosion cracking behaviour of gas tungsten arc welded super austenitic stainless steel joints

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Defence Technology（防务技术） 2015年第3期11卷 282-291页

作者： M.VINOTH KUMAR V.BALAsUBRAMANIAN s.RAJAKUMAR sHAJU K.albert Department of Manufacturing Engineering Annamalai University Center for Materials Joining and Research (CEMAJOR) Department of Manufacturing Engineering Materials Technology Division Indira Gandhi Centre for Atomic Research (IGCAR)

super 304 H austenitic stainless steel with 3% of copper posses excellent creep strength and corrosion resistance, which is mainly used in heat exchanger tubing of the boiler. Heat exchangers are used in nuclear power plants and marine vehicles which are intended to operate in chloride rich offshore environment. Chloride stress corrosion cracking is the most likely life limiting failure with austenitic stainless steel tubing. Welding may worsen the stress corrosion cracking susceptibility of the material. stress corrosion cracking susceptibility of super 304 H parent metal and gas tungsten arc(GTA) welded joints were studied by constant load tests in 45% boiling Mg Cl2 solution. stress corrosion cracking resistance of super 304 H stainless steel was deteriorated by GTA welding due to the formation of susceptible microstructure in the HAZ of the weld joint and the residual stresses. The mechanism of cracking was found to be anodic path cracking, with transgranular nature of crack propagation. Linear relationships were derived to predict the time to failure by extrapolating the rate of steady state elongation.

关键词：奥氏体不锈钢管应力腐蚀裂纹钨极氩弧焊开裂行为钢接头开裂敏感性焊接接头应力腐蚀开裂

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Extracellular vesicles in the diagnosis and treatment of central nervous system diseases

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Neural Regeneration Research 2020年第4期15卷 586-596页

作者： Alisa A.shaimardanova Valeriya V.solovyeva Daria s.Chulpanova Victoria James Kristina V.Kitaeva albert A.Rizvanov Institute of Fundamental Medicine and Biology Kazan Federal UniversityKazanRussia shemyakin-Ovchinnikov Institute of Bioorganic Chemistry The Russian Academy of SciencesMoscowRussia school of Veterinary Medicine and science University of NottinghamSutton Bonington CampusLeicestershireUK

Extracellular vesicles,including exosomes and microvesicles,play a fundamental role in the activity of the nervous system,participating in signal transmission between neurons and providing the interaction of central nervous system with all body *** many neurodegenerative diseases,neurons pack toxic substances into vesicles and release them into the extracellular space,which leads to the spread of misfolded neurotoxic *** contents of neuron-derived extracellular vesicles may indicate pathological changes in the central nervous system,and the analysis of extracellular vesicle molecular content contributes to the development of non-invasive methods for the diagnosis of many central nervous system *** vesicles of neuronal origin can be isolated from various biological fluids due to their ability to cross the blood-brain ***,the diagnostic potential of almost all toxic proteins involved in nervous system disease pathogenesis,specificallyα-synuclein,tau protein,superoxide dismutase 1,FUs,leucine-rich repeat kinase 2,as well as some synaptic proteins,has been well *** attention is paid to extracellular RNAs mostly associated with extracellular vesicles,which are important in the onset and development of many neurodegenerative *** on parental cell type,extracellular vesicles may have different therapeutic properties,including neuroprotective,regenerative,and *** to nano size,biosafety,ability to cross the blood-brain barrier,possibility of targeted delivery and the lack of an immune response,extracellular vesicles are a promising vehicle for the delivery of therapeutic substances for the treatment of neurodegenerative diseases and drug delivery to the *** review describes modern approaches of diagnosis and treatment of central nervous system diseases using extracellular vesicles.

关键词： biomarkers cell-mediated therapy central nervous system diseases diagnosis exosomes extracellular RNAs extracellular vesicles microRNAs microvesicles neurodegenerative diseases

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spike in phytoplankton biomass in Greenland sea during 2009 and the correlations among chlorophyll-a,aerosol optical depth and ice cover

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Chinese Journal of Oceanology and Limnology 2014年第2期32卷 241-254页

作者：瞿波 albert J. GABRIC 路海浪林道荣 school of science Nantong University school of Environment Griffith University

The distributions and correlations of chlorophyll-a(Chl-a),aerosol optical depth(AOD)and ice cover in the southeast Arctic Ocean-Greenland sea(10°W–10°E,70°–80°N)between 2003 and 2009 were studied using satellite data and statistical *** analysis showed correlations between Chl-a and AOD,Chl-a and ice cover,and AOD and ice cover with different time *** time lag of Chl-a and AOD indicated their long-term equilibrium *** in AOD and Chl-a and generally occurred in May and July,*** the time lag,the correlation between Chl-a and AOD in the study region was as high as *** peak gap between Chl-a and AOD shifted for about 6 weeks during 2003–*** the summer and autumn of 2009,Chl-a and AOD levels were much higher than during the other years,especially in the northern band of the study region(75°–80°N).The driving forces for this localized increase in phytoplankton biomass could be mainly attributed to the very high rate of ice melting in spring and early summer and the high wind speed in autumn,together with the increased deposition of aerosol throughout the *** unusually high AOD in the spring of 2003 was mainly due to a massive fi re in Russia,which occurred in the fi rst half of the *** the 7 years of the study,the sea surface temperature generally *** may have been due to the release of dimethylsulfi de into the air,excreted in large amounts from abundant phytoplankton biomass,and its subsequent reaction,form large amounts of aerosol,and resulting in regional cooling.

关键词： phytoplankton biomass aerosol optical depth (AOD) ice cover wind speed Arctic Ocean

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A histone tale that enCOMPAsses pausing:new insights into the functional repertoire of H3K4me3

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signal Transduction and Targeted Therapy 2023年第8期8卷 3555-3557页

作者： Thomas K.albert Kornelius Kerl Department of Pediatric Hematology and Oncology University Children’s Hospital MuensterMuensterGermany

A recently published study in Nature provides compelling evidence for the involvement of the histone H3K4me3 modification in regulating RNA polymerase II(Pol II)pause-release and elongation.1 The expansion of the functional repertoire of this active chromatin mark and the elucidation of the molecular mechanisms behind it represents a major advance for the field,not least because the epigenetic factors involved are linked to a wide range of human *** term epigenetics derives from the Greek prefix“epi”and describes an inheritable regulatory state that manifests itself beyond the mere genetic information encoded in the DNA.

关键词： involvement functional insight

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