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Unraveling the potential of acute intermittent hypoxia as a strategy for inducing robust repair in multiple sclerosis

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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

Synthesis of boron nitride nanorod and its performance as a metalfree catalyst for oxidative desulfurization of diesel fuel

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Chinese Journal of Chemical Engineering 2024年第4期68卷 120-132页

作者： Tanaz Ghanadi Gholamreza Moradi Alimorad Rashidi Catalyst research center Faculty of Chemical and Petroleum EngineeringRazi UniversityKermanshahIran Nanotechnology research center Research Institute of Petroleum Industry(RIPI)TehranIran

In order to reduce the sulfur compounds in diesel fuel,boron nitride(BN)has been used as a novel metal-free catalyst in the present *** nanocatalyst was synthesized via template-free approach followed by heating treatment at 900℃ in nitrogen atmosphere that the characteristics of the sample were identified by the X-ray diffraction,Fourier-transform infrared spectroscopy,Raman spectroscopy,field emission scanning electron microscopy,transmission electron microscopy,atomic force microscopy,and N2 adsorption-desorption *** results of structural and morphological analysis represented that BN has been successfully *** efficacy of the main operating parameters on the process was studied by using response surface methodology based on the Box-Behnken design *** prepared catalyst showed high efficiency in oxidative desulfurization of diesel fuel with initial sulfur content of 8040 mg·kg^(-1)*** statistical analysis,a significant quadratic model was obtained to predict the sulfur removal as a function of efficient *** maximum efficiency of 72.4%was achieved under optimized conditions at oxidant/sulfur molar ratio of 10.2,temperature of 71℃,reaction time of 113 min,and catalyst dosage of 0.36 ***,the reusability of the BN was studied,and the result showed little reduction in activity of the catalyst after 10 times ***,a plausible mechanism was proposed for oxidation of sulfur compounds on the surface of the *** present study shows that BN materials can be selected as promising metal-free catalysts for desulfurization process.

关键词： Desulfurization Boron nitride(BN)nanostructure Experimental design BoxeBehnken

Comparative analysis between single-train passing and double-train intersection in a tunnel

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Journal of Zhejiang University-Science A(Applied Physics & Engineering) 2024年第5期25卷 429-442页

作者： Jianming DU Qian FANG Xuan ZHANG Hualao WANG Bridge and Tunnel research center Research Institute of Highway Ministry of TransportBeijing 100088China Tunnel and Underground Engineering research center of Ministry of Education Beijing Jiaotong UniversityBeijing 00044China

Aerodynamic pressure significantly impacts the scientific evaluation of tunnel service *** aerodynamic pressure of two trains running in a double-track tunnel is considerably more complicated than that of a single *** used the numerical method to investigate the difference in aerodynamic pressure between a single train and two trains running in a double-track ***,the numerical method was verified by comparing the results of numerical simulation and on-site ***,the characteristics of aerodynamic pressure were ***,the influence of various train-tunnel factors on the characteristics of aerodynamic pressure was *** results show that the aerodynamic pressure variation can be divided into stage I:irregular pressure fluctuations before the train tail leaves the tunnel exit,and stage II:periodic pressure declines after the train tail leaves the tunnel *** addition,the aerodynamic pressure simultaneously jumps positively or drops negatively for a single train or two trains running in double-track tunnel *** pressure amplitude in the two-train case is higher than that for a single *** maximum positive peak pressure difference(P_(STP))and maximum negative peak pressure difference(P_(STN))increase as train speed rises to the power from 2.256 to 2.930 in stage *** P_(STP) and P_(STN) first increase and then decrease with the increase of tunnel length in stage *** P_(STP) and P_(STN) increase as the blockage ratio rises to the power from 2.032 to 2.798 in stages I and II.

关键词： Railway tunnel Aerodynamic effect Pressure characteristic Train speed Tunnel length Blockage ratio

The evolution of cancer genomic medicine in Japan and the role of the National Cancer center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical Laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of Molecular pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer center research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

Cognitive impairment in cerebral small vessel disease induced by hypertension

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Neural Regeneration research 2024年第7期19卷 1454-1462页

作者： Weipeng Wei Denglei Ma Lin Li Lan Zhang Department of Pharmacy Xuanwu Hospital of Capital Medical UniversityBeijingChina Beijing Geriatric Medical research center Beijing Engineering Research Center for Nervous System DrugsNational Center for Neurological DisordersNational Clinical Research Center for Geriatric DiseasesBeijingChina

Hypertension is a primary risk factor for the progression of cognitive impairment caused by cerebral small vessel disease,the most common cerebrovascular *** r,the causal relationship between hypertension and cerebral small vessel disease remains *** has substantial negative impacts on brain health and is recognized as a risk factor for cerebrovascular *** hypertension and lifestyle factors are associated with risks for stro ke and dementia,and cerebral small vessel disease can cause dementia and *** is the main driver of cerebral small vessel disease,which changes the structure and function of cerebral vessels via various mechanisms and leads to lacunar infarction,leukoaraiosis,white matter lesions,and intracerebral hemorrhage,ultimately res ulting in cognitive decline and demonstrating that the brain is the to rget organ of *** review updates our understanding of the pathogenesis of hypertensioninduced cerebral small vessel disease and the res ulting changes in brain structure and function and declines in cognitive *** also discuss drugs to treat cerebral small vessel disease and cognitive impairment.

关键词： blood-brain barrier cerebral small vessel disease cognitive impairment dementia endothelial dysfunction enlarged perivascular space hypertension lacunar infarction neuroinflammation treatment white matter high signal intensity

Targeting BCL9/BCL9L enhances antigen presentation by promoting conventional type 1 dendritic cell(cDC1)activation and tumor infiltration

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2804-2818页

作者： Fenglian He Zhongen Wu Chenglong Liu Yuanyuan Zhu Yan Zhou Enming Tian Rina Rosin-Arbesfeld Dehua Yang Ming-Wei Wang Di Zhu Department of pharmacology Minhang Hospitaland Key Laboratory of Smart Drug DeliveryShanghai Engineering Research Center of Immune TherapySchool of PharmacyFudan UniversityShanghai 201203China The National center for Drug Screening and the CAS Key Laboratory of Receptor research Shanghai Institute of Materia MedicaChinese Academy of Sciences(CAS)Shanghai 201203China Department of Microbiology and Immunology Sackler Faculty of MedicineTel Aviv UniversityTel AvivIsrael Department of pharmacology School of Basic Medical SciencesFudan UniversityShanghai 200032China research center for Deepsea Bioresources SanyaChina Department of Chemistry School of ScienceThe University of TokyoTokyoJapan Engineering research center of Tropical Medicine Innovation and Transformation of Ministry of Education School of PharmacyHainan Medical UniversityHaikouChina Shandong Academy of Pharmaceutical Science JinanChina

Conventional type 1 dendritic cells(cDC1)are the essential antigen-presenting DC subset in antitumor *** B-cell lymphoma 9 and B-cell lymphoma 9-like(BCL9/BCL9L)inhibits tumor growth and boosts immune responses against ***,whether oncogenic BCL9/BCL9L impairs antigen presentation in tumors is still not completely ***,we show that targeting BCL9/BCL9L enhanced antigen presentation by stimulating cDC1 activation and infiltration into *** inhibition of BCL9/BCL9L with a novel inhibitor hsBCL9z96 or Bcl9/Bcl9l knockout mice markedly delayed tumor growth and promoted antitumor CD8^(+)T cell ***,targeting BCL9/BCL9L promoted antigen presentation in *** is due to the increase of cDC1 activation and tumor infiltration by the XCL1-XCR1 ***,using single-cell transcriptomics analysis,we found that Bcl9/Bcl9l deficient cDC1 were superior to wild-type(WT)cDC1 at activation and antigen presentation via NF-κB/IRF1 ***,we demonstrate that targeting BCL9/BCL9L plays a crucial role in cDC1-modulated antigen presentation of tumor-derived antigens,as well as CD8^(+)T cell activation and tumor *** BCL9/BCL9L to regulate cDC1 function and directly orchestrate a positive feedback loop necessary for optimal antitumor immunity could serve as a potential strategy to counter immune suppression and enhance cancer immunotherapy.

关键词： immunity Targeting markedly

Design of Resilient Sensor Networks Balancing Resilience and Efficiency

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International Journal of Disaster Risk Science 2024年第1期15卷 107-115页

作者： Sergey N.Vecherin Kiril D.Ratmanski Luke Hogewood Igor Linkov Cold Regions research and Engineering Laboratory Engineering Research and Development CenterHanoverNH 03755USA Environmental Laboratory Engineering Research and Development CenterVicksburgMS 39180USA

In recent years,the notion of resilience has been developed and applied in many technical areas,becoming exceptionally pertinent to disaster risk *** a disaster situation,accurate sensing information is the key to efficient recovery *** general,resilience aims to minimize the impact of disruptions to systems through the fast recovery of critical functionality,but resilient design may require redundancy and could increase *** this article,we describe a method based on binary linear programming for sensor network design balancing efficiency with *** application of the developed framework is demonstrated for the case of interior building surveillance utilizing infrared sensors in both twoand three-dimensional *** method provides optimal sensor placement,taking into account critical functionality and a desired level of resilience and considering sensor type and *** problem formulation,resilience requirements,and application of the optimization algorithm are described in *** of sensor locations with and without resilience requirements shows that resilient configuration requires redundancy in number of sensors and their intelligent *** tasks are successfully solved by the described method,which can be applied to strengthen the resilience of sensor networks by *** proposed methodology is suitable for large-scale optimization problems with many sensors and extensive coverage areas.

关键词： Binary linear programming Optimal sensor placement Redundant networks Resilience and efciency Resilient sensor networks

SIRT2 as a potential new therapeutic target for Alzheimer's disease

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Neural Regeneration research 2024年第1期19卷 124-131页

作者： Noemi Sola-Sevilla Elena Puerta Department of pharmacology and Toxicology Faculty of PharmacyUniversity of NavarraNavarra Institute for Health Research(IdiSNA)PamplonaSpain

Alzheimer's disease is the most common cause of dementia globally with an increasing incidence over the years,bringing a heavy burden to individuals and society due to the lack of an effective *** this context,sirtuin 2,the sirtuin with the highest expression in the brain,has emerged as a potential therapeutic target for neurodegenerative *** review summarizes and discusses the complex roles of sirtuin 2 in different molecular mechanisms involved in Alzheimer's disease such as amyloid and tau pathology,microtubule stability,neuroinflammation,myelin formation,autophagy,and oxidative *** role of sirtuin 2 in all these processes highlights its potential implication in the etiology and development of Alzheimer's ***,its presence in different cell types and its enormous variety of substrates leads to apparently contra dictory conclusions when it comes to understanding its specific *** studies in sirtuin 2 research with selective sirtuin2 modulators targeting specific sirtuin 2 substrates are necessary to clarify its specific functions under different conditions and to validate it as a novel pharmacological *** will contribute to the development of new treatment strategies,not only for Alzheimer's disease but also for other neurodegenerative diseases.

关键词： Alzheimer's disease amyloid autophagy memory neurodegenerative diseases neuroinflammation sirtuin 2 tau

Movement Trend Alterations in the Periaqueductal Gray(PAG)-Employed Ratbot Navigation Are Correlated with Stimulation Parameters

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Journal of Bionic Engineering 2024年第2期21卷 866-876页

作者： Sina Khajei Abed Khorasani Mohammad Reza Afarinesh Vahid Sheibani Neuroscience research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran Cognitive Neuroscience research center Institute of NeuropharmacologyKerman University of Medical SciencesKerman***Iran

In previous studies,Periaqueductal Gray(PAG)stimulation was used to stop ratbots from *** to the homology between the PAG and the intercollicular nucleus,which has been used for forward movement in birds,we investigated the possibility of PAG application to induce forward locomotion for the first *** a corridor maze,the traveled distances via PAG electrical stimulation were examined in nine Wistar male rats during three sessions.A custom-designed stimulator was developed to apply the *** results showed reductions in responses to stimulation over ***,the traveled distances had negative slopes during the consecutive trials(in 8 out of the 9 rats),and the slope mean was significantly different from *** was a strong correlation between the stimulation parameters(electric Charge per Phase(CPP)and the Number of Pulses(NP))and the observed *** negative Movement Slopes(MS)were highly correlated with the CPP and the NP,as the Pearson's linear correlation coefficients were−0.87 and−0.79,*** MS-CPP coefficients of determination(R-squared)were also between 0.76 and *** addition,the MS-NP coefficients of determination were between 0.63 and ***,it is concluded that the electrical stimulation parameters influence the behavioral outcomes ***,the PAG area may be considered a suitable candidate for forward locomotion control in the future if the area is harnessed effectively to prevent undesirable chaotic behaviors.

关键词： Periaqueductal Gray(PAG) Navigation Ratbot Animal-robot Forward locomotion Movement slope