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Modeling tuberous sclerosis complex with human induced pluripotent stem cells

World Journal of Pediatrics 2024年第3期20卷 208-218页

作者： Weibo Niu Benjamin Siciliano Zhexing Wen Department of Psychiatry and Behavioral sciences Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA 30322USA The graduate Program in Molecular and Systems Pharmacology Laney Graduate SchoolEmory UniversityAtlanta.GA 30322.USA Department of Cell Biology Emory University School of MedicineWhitehead Research Building 447615 Michael StreetAtlantaGA30322USA Department of Neurology Emory University School of MedicineWhitehead Research Building 447.615 Michael StreetAtlantaGA 30322USA

Background Tuberous sclerosis complex(TSC)is an autosomal dominant genetic disorder with a birth incidence of I:6000 in the United States that is characterized by the growth of non-cancerous tumors in multiple organ systems including the brain,kidneys,lungs,and skin.Importantly,TSCis also associated with signicant neurological manifestations including epilepsy TSC-associated neuropsychiatric disorders,intellectual disabilities,and autism spectrum disorder.Mutations in the TSCI or TSC2 genes are well-established causes of TSC,which lead to TSC1/TSC2 deficiency in organs and hyper-activation of the mammalian target of rapamycin signaling pathway.Animal models have been widely used to study the effect of TSCl/2 genes on the development and function of the brain.Despite considerable progress in understanding the molecular mechanisms underlying TSC in animal models,a human-specific model is urgently needed to investigate the effects of TSCl/2 mutations that are unique to human neurodevelopment.Data sources Literature reviews and research articles were published in PubMed-indexed journals.Results Human-induced pluripotent stem cells(iPSCs),which capture risk alleles that are identical to their donors and have the capacity to differentiate into virtually any cell type in the human body,pave the way for the empirical study of previously inaccessible biological systems such as the developing human brain.Conclusions In this review,we present an overview of the recent progress in modeling TSC with human iPSC models,the existing limitations,and potential directions for future research.

关键词： Induced pluripotent stem cells Three-dimensional cultures Tuberous sclerosis complex Two-dimensional cultures

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Biogenic volatile organic compounds dominated the near-surface ozone generation in Sichuan Basin,China,during fall and wintertime

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Journal of Environmental sciences 2024年第7期141卷 215-224页

作者： Dasheng Huang Qing Li Yan Han Shi-Yong Xia Jiawei Zhou Hanxiong Che Keding Lu Fumo Yang Xin Long Yang Chen Research Center for Atmospheric Environment Chongqing Institute of Green and Intelligent TechnologyChinese Academy of SciencesChongqing 400714China Chongqing Institute of Green and Intelligent Technology Chinese Academy of SciencesChongqing 400714China College of Resources and Environment Chongqing SchoolUniversity of the Chinese Academy of Sciences(UCAS Chongqing)Chongqing 400714China College of Environmental and Chemical Engineering Chongqing Three Gorges UniversityChongqing 404199China Key Laboratory for Urban Habitat Environmental Science and Technology School of Environment and EnergyPeking University Shenzhen Graduate SchoolLishui RoadNanshan DistrictShenzhen 518055China SKL-ESPC and BIC-ESAT College of Environmental Sciences and EngineeringPeking UniversityBeijing 100871China College of Architecture&Environment Sichuan UniversityChengdu 610065China

The complex air pollution driven by both Ozone(O_(3))and fine particulate matter(PM2.5)sig nificantly influences the air quality in the Sichuan Basin(SCB).Understanding the O_(3)for mation during autumn and winter is necessary to understand the atmospheric oxidative capacity.Therefore,continuous in-site field observations were carried out during the late summer,early autumn and winter of 2020 in a rural area of Chongqing.The total volatile organic compounds(VOCs)concentration reported by a Proton-Transfer-Reaction Time-of Flight Mass Spectrometry(PTR-ToF-MS)were 13.66±9.75 ppb,5.50±2.64 ppb,and 9.41±5.11 ppb in late summer,early autumn and winter,respectively.The anthropogenic VOCs(AVOCs)and biogenic VOCs(BVOCs)were 8.48±7.92 ppb and 5.18±2.99 ppb in late sum mer,3.31±1.89 ppb and 2.19±0.93 ppb in autumn,and 6.22±3.99 ppb and 3.20±1.27ppb in winter.A zero-dimensional atmospheric box model was employed to investigate the sensitivity of O_(3)-precursors by relative incremental reactivity(RIR).The RIR values of AV OCs,BVOCs,carbon monoxide(CO),and nitrogen oxides(NOx)were 0.31,0.71,0.09,and-0.36 for late summer,0.24,0.59,0.22,and-0.38 for early autumn,and 0.30,0.64,0.33 and-0.70 for winter,and the results showed that the O_(3)formation of sampling area was in the VOC-limited region,and O_(3)was most sensitive to BVOCs(with highest RIR values,>0.6)This study can be helpful in understanding O_(3)formation and interpreting the secondary formation of aerosols in the winter.

关键词： VOCs PTR-MS Model Ozone

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Double DQN Method For Botnet Traffic Detection System

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Computers, Materials & Continua 2024年第4期79卷 509-530页

作者： Yutao Hu Yuntao Zhao Yongxin Feng Xiangyu Ma school of Information Science and Engineering Shenyang Ligong UniversityShenyang110159China graduate school Shenyang Ligong UniversityShenyang110159China

In the face of the increasingly severe Botnet problem on the Internet,how to effectively detect Botnet traffic in realtime has become a critical problem.Although the existing deepQnetwork(DQN)algorithminDeep reinforcement learning can solve the problem of real-time updating,its prediction results are always higher than the actual results.In Botnet traffic detection,although it performs well in the training set,the accuracy rate of predicting traffic is as high as%;however,in the test set,its accuracy has declined,and it is impossible to adjust its prediction strategy on time based on new data samples.However,in the new dataset,its accuracy has declined significantly.Therefore,this paper proposes a Botnet traffic detection system based on double-layer DQN(DDQN).Two Q-values are designed to adjust the model in policy and action,respectively,to achieve real-time model updates and improve the universality and robustness of the model under different data sets.Experiments show that compared with the DQN model,when using DDQN,the Q-value is not too high,and the detectionmodel has improved the accuracy and precision of Botnet traffic.Moreover,when using Botnet data sets other than the test set,the accuracy and precision of theDDQNmodel are still higher than DQN.

关键词： DQN DDQN deep reinforcement learning botnet detection feature classification

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Diabetes is affecting everyone everywhere

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World Journal of Diabetes 2024年第2期15卷 305-307页

作者： Parul Chawla Gupta Mona Duggal Arvind Kumar Morya Department of Ophthalmology Post Graduate Institute of Medical Education&ResearchChandigarh 160012PunjabIndia school of Public Health Post Graduate Institute of Medical Education and ResearchChandigarh 160002PunjabIndia Department of Ophthalmology All India Institute of Medical SciencesHyderabad 508126TelanganaIndia

The article titled“Accessibility and Utilization of Healthcare Services Among Diabetic Patients:Is Diabetes a Poor Man’s Ailment?”gave insights into a pandemic systemic disease known as diabetes mellitus.This modern-era pandemic affects everyone,regardless of their financial background.As a result,diabetes is not a systemic disease which just involves people of low socioeconomic status.

关键词： Diabetes Incidence and prevalence Diabetes mellitus

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Development of a cell-permeable adenine-derived probe for capture of nucleotide-binding proteins in living cells

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Chinese Chemical Letters 2024年第3期35卷 243-246页

作者： Lihong Liu Rui Chen Gang Xue Chenzhou Hao Weizhi Weng Zhengying Pan State Key Laboratory of Chemical Oncogenomics School of Chemical Biology and BiotechnologyPeking University Shenzhen Graduate SchoolShenzhen 518055China

Adenine is an essential building block of genetic material and a range of coenzymes.Chemical probes containing an adenine moiety have been used in kinase profiling studies in cell lysates.Here we report that adenine-derived small-molecule probes with an activated ester reactive group can covalently modify a conserved lysine residue of protein kinases and capture a number of nucleotide-binding proteins within living cells.

关键词： Adenine-derived probe Cell-permeable Lysine residue Protein kinases Nucleotide-binding proteins

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Xuebijing improves intestinal microcirculation dysfunction in septic rats by regulating the VEGF-A/PI3K/Akt signaling pathway

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World Journal of Emergency Medicine 2024年第3期15卷 206-213页

作者： A-ling Tang Yan Li Li-chao Sun Xiao-yu Liu Nan Gao Sheng-tao Yan Guo-qiang Zhang Department of Emergency China-Japan Friendship HospitalBeijing 100029China graduate school Beijing University of Chinese MedicineBeijing 100105China

BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

关键词： Sepsis Xuebijing Vascular endothelial growth factor A Microcirculation Rat Phosphoinositide 3-kinase Protein kinase B

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Multiple-dimensioned defect engineering for graphite felt electrode of vanadium redox flow battery

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Carbon Energy 2024年第2期6卷 143-153页

作者： Yingqiao Jiang Yinhui Wang Gang Cheng Yuehua Li Lei Dai Jing Zhu Wei Meng Jingyu Xi Ling Wang Zhangxing He school of Chemical Engineering North China University of Science and TechnologyTangshanChina Tsinghua Shenzhen International graduate school Institute of Materials ResearchTsinghua UniversityShenzhenChina

The scarcity of wettability,insufficient active sites,and low surface area of graphite felt(GF)have long been suppressing the performance of vanadium redox flow batteries(VRFBs).Herein,an ultra-homogeneous multipledimensioned defect,including nano-scale etching and atomic-scale N,O codoping,was used to modify GF by the molten salt system.NH_(4)Cl and KClO_(3) were added simultaneously to the system to obtain porous N/O co-doped electrode(GF/ON),where KClO_(3) was used to ultra-homogeneously etch,and O-functionalize electrode,and NH4Cl was used as N dopant,respectively.GF/ON presents better electrochemical catalysis for VO_(2)+/VO_(2)+ and V3+/V2+ reactions than only O-functionalized electrodes(GF/O)and GF.The enhanced electrochemical properties are attributed to an increase in active sites,surface area,and wettability,as well as the synergistic effect of N and O,which is also supported by the density functional theory calculations.Further,the cell using GF/ON shows higher discharge capacity,energy efficiency,and stability for cycling performance than the pristine cell at 140 mA cm^(−2) for 200 cycles.Moreover,the energy efficiency of the modified cell is increased by 9.7% from 55.2% for the pristine cell at 260 mA cm^(−2).Such an ultra-homogeneous etching with N and O co-doping through“boiling”molten salt medium provides an effective and practical application potential way to prepare superior electrodes for VRFB.

关键词： graphite felt molten salt N O co-doping ultra-homogeneous etching vanadium redox flow battery

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Therapeutic potential of stem cells in subarachnoid hemorrhage

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Neural Regeneration Research 2025年第4期20卷 936-945页

作者： Hideki Kanamaru Hidenori Suzuki Department of Neurosurgery Mie University Graduate School of MedicineTsuJapan

Aneurysm rupture can result in subarachnoid hemorrhage,a condition with potentially severe consequences,such as disability and death.In the acute stage,early brain injury manifests as intracranial pressure elevation,global cerebral ischemia,acute hydrocephalus,and direct blood–brain contact due to aneurysm rupture.This may subsequently cause delayed cerebral infarction,often with cerebral vasospasm,significantly affecting patient outcomes.Chronic complications such as brain volume loss and chronic hydrocephalus can further impact outcomes.Investigating the mechanisms of subarachnoid hemorrhage-induced brain injury is paramount for identifying effective treatments.Stem cell therapy,with its multipotent differentiation capacity and anti-inflammatory effects,has emerged as a promising approach for treating previously deemed incurable conditions.This review focuses on the potential application of stem cells in subarachnoid hemorrhage pathology and explores their role in neurogenesis and as a therapeutic intervention in preclinical and clinical subarachnoid hemorrhage studies.

关键词： delayed cerebral ischemia early brain injury matricellular protein neurogenesis stem cell therapy subarachnoid hemorrhage

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Engineering high-performance dielectric chiral shells with enhanced chiral fields for sensitive chiral biosensor

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Rare Metals 2024年第3期43卷 1197-1206页

作者： Yi-Fan Wang Shan-Shan Huang Zhen-Dong Dai Shi-Lin Xian Xuan-Nan Wu Fu-Hua Gao Yi-Dong Hou College of Physics Sichuan UniversityChengdu610065China graduate school of Sichuan University Sichuan UniversityChengdu610065China

Chiral metamaterials have been a topic of significant research interest in recent years due to their potential for various applications in nanophotonic devices and chiral biosensors.However,the intrinsic Ohmic loss in surface plasmonic resonance has limited their practical use,resulting in large light dissipation and weak chiroptical resonance.Here,we report on the development of high-performance dielectric chiral shells(DCS)through a two-step Si deposition process on a self-assembled microsphere monolayer.The form DCS sample completely oyercomes the cancelation effect originated from the disorder property of the micro-sphere monolayer in macroscale,and at a wavelength of approximately 710 nm,the measured optimal chiral signal(g-factor)and transmittance can reach up to 0.7 and 0.3,respectively.The strong chiroptical effect comes from the asymmetric circular displacement currents(i.e.,magnetic modes)enabled by the specific shell geometry.The chiral shell geometry,electromagnetic properties,sensor sensitivity of chiral molecules and figure of merit are systematically investigated.The DCSs demonstrate highly sensitive detection of chiral biomolecules owing to their easily accessible geometry and enhanced uniform chiral field.

关键词： Dielectric chiral shells(DCS) Si deposition Magnetic resonance Highly sensitive sensor Chiral field

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Observation of Giant Topological Hall Effect in Room-Temperature Ferromagnet Cr_(0.82)Te

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Chinese Physics Letters 2024年第6期41卷 128-140页

作者：苗伟婷甄伟立陆振王恒宁王杰牛群田明亮 Anhui Key Laboratory of Low-energy Quantum Materials and Devices High Magnetic Field LaboratoryHFIPSChinese Academy of SciencesHefei 230031China Science Island Branch Graduate School of University of Science and Technology of ChinaHefei 230026China school of Physics and Optoelectronic Engineering Anhui UniversityHefei 230601China

Novel magnetic materials with non-trivial magnetic structures have led to exotic magnetic transport properties and significantly promoted the development of spintronics in recent years.Among them is the Crx Tey family,the magnetism of which can persist above room temperature,thus providing an ideal system for potential spintronic applications.Here we report the synthesis of a new compound,Cr_(0.82)Te,which demonstrates a record-high topological Hall effect at room temperature in this family.Cr_(0.82)Te displays soft ferromagnetism below the Curie temperature of 340 K.The magnetic measurement shows an obvious magneto-crystalline anisotropy with the easy axis located in the ab plane.The anomalous Hall effect can be well explained by a dominating skew scattering mechanism.Intriguing,after removing the normal Hall effect and anomalous Hall effect,a topological Hall effect can be observed up to 300 K and reaches up to 1.14μΩ·cm at 10 K,which is superior to most topological magnetic structural materials.This giant topological Hall effect possibly originates from the noncoplanar spin configuration during the spin flop process.Our work extends a new Cr_(x)Te_(y) system with topological non-trivial magnetic structure and broad prospects for spintronics applications in the future.

关键词： mechanism process topological

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