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Neural Regeneration Research 2024年第11期19卷 2339-2340页

作者： Valerie M.K.Verge Nataliya Tokarska Justin M.Naniong Department of Anatomy Physiology and PharmacologyUniversity of SaskatchewanSaskatoonSKCanada Cameco MS Neuroscience Research center University of SaskatchewanSaskatoonSKCanada

Multiple sclerosis(MS)is a debilitating inflammatory disease of the central nervous system characterized by immune-mediated segmental demyelination and variable degrees of axonal and neuronal degeneration that contribute to *** efficient and effective repair programs following demyelination is a major goal and challenge in *** MS therapies focus largely on modulating the immune aspects of the disease contributing to *** this alleviates some symptoms and mitigates damage,it does not tackle the fundamental challenge of effective remyelination,which few MS patients experience,especially in the progressive phase of the disease.

关键词： sclerosis degeneration damage

Interfacial Electronic Modulation of Dual-Monodispersed Pt–Ni_(3)S_(2) as Efficacious Bi-Functional Electrocatalysts for Concurrent H_(2) Evolution and Methanol Selective Oxidation

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Nano-Micro Letters 2024年第4期16卷 415-431页

作者： Qianqian Zhao Bin Zhao Xin Long Renfei Feng Mohsen Shakouri Alisa Paterson Qunfeng Xiao Yu Zhang Xian‑Zhu Fu Jing‑Li Luo Shenzhen Key Laboratory of Energy Electrocatalytic Materials Shenzhen Key Laboratory of Polymer Science and TechnologyGuangdong Research Center for Interfacial Engineering of Functional MaterialsCollege of Materials Science and EngineeringShenzhen UniversityShenzhen 518060People’s Republic of China Canadian Light Source Inc. SaskatoonSK S7N 0X4Canada Instrumental Analysis center of Shenzhen University(Lihu Campus) Shenzhen UniversityShenzhen 518055People’s Republic of China

Constructing the efficacious and applicable bifunctional electrocatalysts and establishing out the mechanisms of organic electro-oxidation by replacing anodic oxygen evolution reaction(OER) are critical to the development of electrochemicallydriven technologies for efficient hydrogen production and avoid CO_(2) emission. Herein, the hetero-nanocrystals between monodispersed Pt(~ 2 nm) and Ni_(3)S_(2)(~ 9.6 nm) are constructed as active electrocatalysts through interfacial electronic modulation, which exhibit superior bi-functional activities for methanol selective oxidation and H_(2) generation. The experimental and theoretical studies reveal that the asymmetrical charge distribution at Pt–Ni_(3)S_(2) could be modulated by the electronic interaction at the interface of dual-monodispersed heterojunctions, which thus promote the adsorption/desorption of the chemical intermediates at the interface. As a result, the selective conversion from CH_(3)OH to formate is accomplished at very low potentials(1.45 V) to attain 100 m A cm^(-2) with high electronic utilization rate(~ 98%) and without CO_(2) emission. Meanwhile, the Pt–Ni_(3)S_(2) can simultaneously exhibit a broad potential window with outstanding stability and large current densities for hydrogen evolution reaction(HER) at the cathode. Further, the excellent bi-functional performance is also indicated in the coupled methanol oxidation reaction(MOR)//HER reactor by only requiring a cell voltage of 1.60 V to achieve a current density of 50 m A cm^(-2) with good reusability.

关键词： Dual-monodispersed heterostructure Electronic interactive modulation Reaction mechanism Methanol oxidation reaction Hydrogen generation

Increased glacier melt enhances future extreme floods in the southern Tibetan Plateau

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Advances in Climate Change Research 2024年第3期15卷 431-441页

作者： He SUN Tan-Dong YAO Feng-Ge SU Tinghai Ou Zhihua HE Guoqiang TANG Deliang CHEN State Key Laboratory of Tibetan Plateau Earth System Environment and Resources(TPESER)Institute of Tibetan Plateau ResearchChinese Academy of SciencesBeijing 100101China Regional Climate Group Department of Earth SciencesUniversity of GothenburgGothenburg 40530Sweden Centre for Hydrology University of SaskatchewanSaskatoon S7N 1K2Canada Climate and Global Dynamics National Center for Atmospheric ResearchBoulder CO 80307USA

Mountainous areas are of special hydrological concern because topography and atmospheric conditions can result in large and sudden floods,posing serious risks to water-related safety in neighbouring *** Yarlung Zangbo(YZ)River basin is the largest river basin on the Tibetan Plateau(TP),but how floods will discharge in this basin and how the role of glacier melt in floods will change throughout the 21st-century under shared socioeconomic pathways scenarios(SSP2-4.5 and SSP5-8.5)remain ***,we comprehensively address this scientific question based on a well-validated large-scale glacier-hydrology *** results indicate that extreme floods was projected to increase in the YZ basin,and was mainly reflected in increased duration(4–10 d per decade)and intensity(153–985 m^(3)s^(−1)per decade).Glacier runoff was projected to increase(2–30 mm per decade)throughout the 21st-century,but there was also a noticeable decrease or deceleration in glacier runoff growth in the late first half of the century under the SSP2-4.5,and in the latter half of the century under the *** melt was projected to enhance the duration(12%–23%)and intensity(15%–21%)of extreme floods under both SSPs,which would aggravate the impact of future floods on the socioeconomics of the YZ *** effect was gradually overwhelmed by precipitation-induced floods from glacier areas to YZ *** study takes the YZ basin as a projection framework example to help enrich the understanding of future flood hazards in basins affected by rainfall-or meltwater across the TP,and to help policy-makers and water managers develop future plans.

关键词： floods glacier Tibetan

The global,prevalence,and risk factors of postoperative fever after percutaneous nephrolithotomy:A systematic review and meta-analysis

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Asian Journal of Urology 2024年第2期11卷 253-260页

作者： Reza Falahatkar Siavash Falahatkar Mohammad Amin Khajavi Gaskarei Masoomeh Afzalipoor Ali Mojtahedi Neda Aligolighasemabadi Ahmad Deilami Samaneh Mirzaei Dahka Mohammad-Hossein Keivanlou Alireza Jafari Urology Research center Guilan University of Medical SciencesGuilanRashtIran Department of Surgery University of SaskatchewanSaskatoonCanada Microbiology Department School of MedicineGuilan University of Medical SciencesRashtIran Department of Internal Medicine School of MedicineGuilan University of Medical SiencesRashtIran School of Nursing and Midwifery Guilan University of Medical SciencesGuilanRashtIran

Objective:This study aimed to explore the global,prevalence,and risk factors of fever after percutaneous nephrolithotomy(PCNL)by conducting a systematic review and ***:The high-sensitivity searching was conducted without time limitation until December 30,2020 in Web of Sciences,Scopus,and PubMed based on inclusion and exclusion ***:The prevalence rates of fever and sepsis among patient undergoing PCNL were estimated 9.5%(95%confidence interval[CI]:9.3%-9.7%),and 4.5%(95%CI:4.2%-4.8%),*** tube was used in 9.96%(95%CI:9.94%-9.97%)of *** mean preoperative white blood cells of patients were 6.401×109/L;18.3%and 4.55%of patients were considered as the positive urinary culture and pyuria,*** 20.4%of patients suffered from residual *** odds ratios(ORs)of fever in patients who suffering from diabetes mellitus,hydronephrosis,staghorn stones,and blood transfusion were 4.62(95%CI:2.95-7.26),1.04(95%CI:0.81-1.34),2.57(95%CI:0.93-7.11),and 2.65(95%CI:1.62-4.35),*** who underwent PCNL in prone position were more likely to develop fever(OR:1.23;95%CI:0.75-2.00)than patients in supine ***:The current study showed that patients who suffer from diabetes mellitus,hydronephrosis,staghorn stones,nephrostomy tube or double-J stent,blood transfusion,and also patients who underwent PCNL in prone position surgery are more likely to develop a postoperative fever after PCNL.

关键词： Percutaneous nephrolithotomy Fever Hydronephrosis Diabetes Meta-analysis

Distinct roles but cooperative effect of TLR3/9 agonists and PD-1 blockade in converting the immunotolerant microenvironment of irreversible electroporation-ablated tumors

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Cellular & Molecular Immunology 2021年第12期18卷 2632-2647页

作者： Fatma Babikr Jiangbo Wan Aizhang Xu Zhaojia Wu Shahid Ahmed Andrew Freywald Rajni Chibbar Yue Wu Michael Moser Gary Groot Wenjun Zhang Bing Zhang Jim Xiang saskatoon cancer center Saskatchewan Cancer AgencySaskatoonSKCanada Department of Oncology University of SaskatchewanSaskatoonSKCanada Department of Hematology Xinhua HospitalAffiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Pathology University of SaskatchewanSaskatoonSKCanada Department of Surgery University of SaskatchewanSaskatoonSKCanada Department of Bioengineering University of SaskatchewanSaskatoonSKCanada Biomedical Science and Technology Research center Shanghai UniversityShanghaiChina

Irreversible electroporation(IRE)is a new cancer ablation technology,but methods to improve IRE-induced therapeutic immunity are only beginning to be *** developed a mouse model bearing large primary(300 mm^(3))and medium distant(100 mm^(3))EG7 lymphomas engineered to express ovalbumin(OVA)as a nominal tumor *** established experimental protocols including IRE alone and IRE combined with Toll-like receptor(TLR)3/9 agonists(poly I:C/CpG)(IRE+pIC/CpG),PD-1 blockade(IRE+PD-1 blockade),or both(IRE+Combo)to investigate therapeutic effects on primary and distant EG7 tumors and conversion-promoting effects on the immunotolerant tumor microenvironment(TME).We demonstrated that IRE alone simulated very weak OVA-specific CD8^(+)T cell responses and did not inhibit primary tumor ***+pIC/CpG synergistically stimulated more efficient OVA-specific CD8^(+)T cell responses and primary tumor growth inhibition than IRE+PD-1 ***+pIC/CpG played a major role in the modulation of immune cell profiles but a minor role in the downregulation of PD-L1 expression in the TME and vice versa for IRE+PD-1 ***+Combo cooperatively induced potent OVA-specific CD8^(+)T cell immunity and rescued exhausted intratumoral CD8^(+)T cells,leading to eradication of not only primary tumors but also untreated concomitant distant tumors and lung ***+Combo efficiently modulated immune cell profiles,as evidenced by reductions in immunotolerant type-2(M2)macrophages,myeloid-derived suppressor-cells,plasmacytoid dendritic cells,and regulatory T cells and by increases in immunogenic M1 macrophages,CD169^(+)macrophages,type-1 conventional dendritic cells,and CD8^(+)T cells,leading to conversion of immunotolerance in not only primary TMEs but also untreated distant ***+Combo also showed effective therapeutic effects in two breast cancer ***,our results suggest that IRE+Combo is a promising strategy to improve IRE ablation therapy in cancer.

关键词： IRE ablation TLR3/9-agonists PD-1-blockade CD8+T-cell response antitumor immunity

Transgenic 4-1BBL-engineered vaccine stimulates potent Gag-specific therapeutic and long-term immunity via increased priming of CD44＋CD62Lhigh IL-7R＋ CTLs with up- and downregulation of anti- and pro-apoptosis genes

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Cellular & Molecular Immunology 2015年第4期12卷 456-465页

作者： Rong Wang Andrew Freywald Yue Chen Jianqing Xu Xin Tan Jim Xiang cancer Research Unit Saskatchewan Cancer Agency Saskatoon Saskatchewan Canada Department of Oncology University of Saskatchewan Saskatoon Saskatchewan Canada Department of Pathology University of Saskatchewan Saskatoon Saskatchewan Canada Department of Epidemiology and Community Health University of Ottawa Canada Shanghai Public Health Clinical center Fudan University Shanghai China School of Life Science Beijing Institute of Technology Beijing China

Human immunodeficiency virus type-1 （HIV-1）-specific dendritic cell （DC） vaccines have been used in clinical trials. However, they have been found to only induce some degree of immune responses in these studies. We previously demonstrated that the HIV-1 Gag-specific Gag-Texo vaccine stimulated Gag-specific effector CD8＋ cytotoxic T lymphocyte （CTL） responses, leading to completely protective, but very limited, therapeutic immunity. In this study, we constructed a recombinant adenoviral vector, adenovirus （AdV）4-1BBL, which expressed mouse 4-1BB ligand （4-1BBL）, and generated transgenic 4-1BBL-engineered OVA-Texo/4.1BSL and Gag-Texo/4.1BSL vaccines by transfecting ovalbumin （OVA）-Texo and Gag-＇rexo cells with AdV4.1BBL, respectively. We demonstrate that the OVA-specific OVA-Texo/*** vaccine stimulates more efficient OVA-specific CTL responses （3.26%） compared to OVA-Texo-activated responses （1.98%） in wild-type C57BIJ6 mice and the control OVA-TeXO/Nu, vaccine without transgenic 4-1BBL expression, leading to enhanced therapeutic immunity against 6-day established OVA-expressing B16 melanoma BL6-1OovA cells. OVA-Texo/4.1BBL-stimulated CTLs, which have a CD44＋CD62Lhigh IL-7R＋ phenotype, are likely memory CTL precursors, demonstrating prolonged survival and enhanced differentiation into memory CTLs with functional recall responses and long-term immunity against BL6-1OovA melanoma. In addition, we demonstrate that OVA-Texo/4_ZBBL-Stimulated CTLs up- and downregulate the expression of anti-apoptosis （Bcl2110, Naipl, No13, Pak7 and Tnfrsfllb） and pro-apoptosis （Casp12, Trp63 and Trp73） genes, respectively, by RT2 Profiler PCR array analysis. Importantly, the Gag-specific Gag-Texo/4.1BBL vaccine also stimulates more efficient Gag-specific therapeutic and long-term immunity against HLA-A2/Gag-expressing B 16 melanoma BL6-1OGag/A2 cells than the control Gag-TeXO/NuH vaccine in transgenic HLA-A2 mice. Taken together, our novel Gag-Texo/4-ZBBL vaccine, which is capable of st

关键词： 4-1BBL Gag HLA-A2 mice T cell-based vaccine therapeutic immunity

Enriched electrophilic oxygen species facilitate acidic oxygen evolution on Ru-Mo binary oxide catalysts

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Nano Research 2024年第3期17卷 1165-1172页

作者： Yaya Wang Yunzhou Wen Yumeng Cheng Xinhong Chen Mengjiao Zhuansun Tongbao Wang Jun Li Debora Meira Huarui Sun Jun Wei Jia Zhou Yuhang Wang Sisi He Shenzhen Key Laboratory of Flexible Printed Electronics Technology Harbin Institute of Technology(Shenzhen)University TownShenzhen 518055China School of Science Harbin Institute of Technology(Shenzhen)University TownShenzhen 518055China Institute of Functional Nano&Soft Materials(FUNSOM) Jiangsu Key Laboratory of Advanced Negative Carbon TechnologiesSoochow UniversitySuzhou 215123China Frontiers Science center for Transformative Molecules Shanghai Jiao Tong UniversityShanghai 200240China Science Division Canadian Light SourceSaskatoonSKS7N 2V3Canada Photon Science Division Argonne National LaboratoryLemontIL60439USA School of Materials Science and Engineering Harbin Institute of Technology(Shenzhen)University TownShenzhen 518055China

The polymer electrolyte membrane(PEM)electrolyzers are burdened with costly iridium(Ir)-based catalysts and high operation overpotentials for the oxygen evolution reaction(OER).The development of earth-abundant,highly active,and durable electrocatalysts to replace Ir is a critical step in reducing the cost of green hydrogen *** we develop a Ru5Mo4Ox binary oxide catalyst that exhibits high activity and stability in acidic *** electron-withdrawing property of Mo enriches the electrophilic surface oxygen species,which promotes acidic OER to proceed via the adsorbate evolution *** a result,we achieve a 189 mV overpotential at 10 mA·cm^(-2) and a Tafel slope of 48.8 mV·dec^(-1).Our catalyst demonstrates a substantial 18-fold increase in intrinsic activity,as evaluated by turnover frequency,compared to commercially available RuO_(2) and IrO_(2) ***,we report a stable OER operation at 10 mA·cm^(-2) for 100 h with a low degradation rate of 2.05 mV·h^(-1).

关键词： electrocatalysis oxygen evolution reaction(OER) ruthenium(Ru)-based oxide molybdenum electrophilic oxygen

TLR9 agonist enhances radiofrequency ablation-induced CTL responses, leading to the potent inhibition of primary tumor growth and lung metastasis

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Cellular & Molecular Immunology 2019年第10期16卷 820-832页

作者： Aizhang Xu Lifeng Zhang Jingying Yuan Fatma Babikr Andrew Freywald Rajni Chibbar Michael Moser Wenjun Zhang Bing Zhang Zhaoying Fu Jim Xiang cancer Research Saskatchewan Cancer AgencyUniversity of SaskatchewanSaskatoonSKCanada Department of Oncology University of SaskatchewanSaskatoonSKCanada Department of General Surgery The First Affiliated Hospital of Soochow UniversitySuzhouChina Department of Pathology University of SaskatchewanSaskatoonSKCanada Department of Surgery University of SaskatchewanSaskatoonSKCanada Department of Bioengineering University of SaskatchewanSaskatoonSKCanada Biomedical Science and Technology Research center School of Mechatronic Engineering and AutomationShanghai UniversityShanghaiChina Department of Immunology College of MedicineYian-An UniversityYian-AnChina

Radiofrequency ablation(RFA)is the most common approach to thermal ablation for cancer ***,its efficacy is limited by incomplete ablation,and further optimization of RFA is ***,we demonstrate that incubation at 65°C triggers more EG7 tumor cell death by necrosis than treatment at 45°C,and the 65°C-treated cells are more effective at inducing antigen-specific CD8^(+)cytotoxic T lymphocyte(CTL)responses after injection in mice than the 45°C-treated *** cells(DCs)that phagocytose 65°C-treated EG7 cells become mature with upregulated MHCII and CD80 expression and are capable of efficiently inducing effector CTLs in mouse tumor ***(65°C)therapy of EG7 tumors induces large areas of tumor necrosis and stimulates CTL *** leads to complete regression of small(~100 mm^(3))tumors but fails to suppress the growth of larger(~350 mm^(3))*** administration of the Toll-like receptor-9(TLR9)agonist unmethylated cytosine-phosphorothioate-guanine oligonucleotide(CpG)to DCs phagocytosing 65°C-treated EG7 cells enhances the expression of MHCII and CD40 on DCs as well as DC-induced stimulation of CTL ***,the intratumoral administration of CpG following RFA also increases the frequencies of tumor-associated immunogenic CD11b−CD11c^(+)CD103^(+)DC2 and CD11b+F4/80+MHCII+M1 macrophages and increases CD4^(+)and CD8^(+)T-cell tumor infiltration,leading to enhanced CD4^(+)T cell-dependent CTL responses and potent inhibition of primary RFA-treated or distant untreated tumor growth as well as tumor lung metastasis in mice bearing larger ***,our data indicate that CpG administration,which enhances RFA-induced CTL responses and ultimately potentiates the inhibition of primary tumor growth and lung metastasis,is a promising strategy for improving RFA treatment,which may assist in optimizing this important cancer therapy.

关键词： TLR9 agonist RFA CTL response antitumor immunity metastasis

Brief electrical nerve stimulation enhances intrinsic repair capacity of the focally demyelinated central nervous system

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Neural Regeneration Research 2022年第5期17卷 1042-1050页

作者： Lydia Ayanwuyi Nataliya Tokarska Nikki A.McLean Jayne M.Johnston Valerie M.K.Verge Department of Anatomy Physiology and PharmacologyUniversity of SaskatchewanSaskatoonSKCanada Cameco MS Neuroscience Research center University of SaskatchewanSaskatoonSKCanada

Our lab has shown that brief electrical nerve stimulation(ES)has a dramatic impact on remyelination of lysophosphatidyl choline(LPC)-induced focally demyelinated rat peripheral nerves,while also inducing an axon-protective phenotype and shifting macrophages from a predominantly pro-inflammatory toward a pro-repair *** this same potential exists in the central nervous system is not ***,for proof of principle studies,the peripheral nerve demyelination and ES model was adapted to the central nervous system,whereby a unilateral focal LPC-induced demyelination of the dorsal column at the lumbar enlargement where the sciatic nerve afferents enter was created,so that subsequent ipsilateral sciatic nerve ES results in increased neural activity in the demyelinated *** reveal a robust focal demyelination at 7 days post-LPC *** of 1-hour ES at 7 days post-LPC polarizes macrophages/microglia toward a pro-repair phenotype when examined at 14 days post-LPC;results in smaller LPC-associated regions of inflammation compared to non-stimulated controls;results in significantly more cells of the oligodendroglial lineage in the demyelinated region;elevates myelin basic protein levels;and shifts the paranodal protein Caspr along demyelinated axons to a more restricted distribution,consistent with reformation of the paranodes of the nodes of *** also significantly enhanced levels of phosphorylated neurofilaments detected in the zones of demyelination,which has been shown to confer axon *** these findings support that strategies that increase neural activity,such as brief electrical stimulation,can be beneficial for promoting intrinsic repair following focal demyelinating insults in demyelinating diseases such as multiple *** animal procedures performed were approved by the University of Saskatchewan's Animal Research Ethics Board(protocol#20090087;last approval date:November 5,2020).

关键词： axon protection demyelination immune response lysophosphatidyl choline macrophage microglia multiple sclerosis myelin nervous system repair neural activity polarization

FOXO3a as a sensor of unilateral nerve injury in sensory neurons ipsilateral, contralateral and remote to injury

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Neural Regeneration Research 2020年第12期15卷 2353-2361页

作者： Jovan CDHasmatali Jolly De Guzman Jayne MJohnston Hossein Noyan Bernhard HJuurlink Vikram Misra Valerie MKVerge Department of Anatomy Physiologyand PharmacologyUniversity of SaskatchewanSaskatoonSKCanada Cameco MS Neuroscience Research center University of SaskatchewanSaskatoonSKCanada Department of Veterinary Microbiology University of SaskatchewanSaskatoonSKCanada

Emerging evidence supports that the stress response to peripheral nerve injury extends beyond the injured neuron,with alterations in associated transcription factors detected both locally and remote to the ***-induced nuclear translocation of the transcription factor forkhead class box O3a(FOXO3a)was initially linked to activation of apoptotic genes in many neuronal ***,a more complex role of FOXO3a has been suggested in the injury response of sensory neurons,with the injured neuron expressing less *** elucidate this response and test whether non-injured sensory neurons also alter FOXO3a expression,the temporal impact of chronic unilateral L4–6 spinal nerve transection on FOXO3a expression and nuclear localization in adult rat dorsal root ganglion neurons ipsilateral,contralateral or remote to injury relative to na?ve controls was *** na?ve neurons,high cytoplasmic and nuclear levels of FOXO3a colocalized with calcitonin gene related peptide,a marker of the nociceptive *** hour post-injury,an acute increase in nuclear FOXO3a in small size injured neurons occurred followed by a significant decrease after 1,2 and 4 days,with levels increasing toward pre-injury levels by 1 week post-injury.A more robust biphasic response to the injury was observed in uninjured neurons contralateral to and those remote to *** levels of FOXO3a peaked at 1 day,decreased by 4 days,then increased by 1 week post-injury,a response mirrored in C4 dorsal root ganglion neurons remote to *** altered expression contralateral and remote to injury supports that spinal nerve damage has broader systemic impacts,a response we recently reported for another stress transcription factor,Luman/*** early decreased expression and nuclear localization of FOXO3a in the injured neuron implicate these changes in the cell body response to injury that may be ***,the broader systemic changes support the existence of stress/inj

关键词： cell body response contralateral response dorsal root ganglion peripheral nerve injury plasticity sciatic nerve sensory neuron stress systemic transcription factor unilateral peripheral nerve injury