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CCS Chemistry 2024年第1期6卷 177-195页

作者： Lang Zhao Shao-Hua Zhuo Tian-Yang Wang Jun-Jun Wu Jing-Yun Su wen-hao li Bo-Dou Zhang Yan-Mei li Key Lab of Bioorganic Phosphorus Chemistry&Chemical Biology Department of ChemistryTsinghua UniversityBeijing 100084 Beijing Institute for Brain Disorders Beijing 100069 Center for Synthetic and Systems Biology Tsinghua UniversityBeijing 100084

Cyclic dinucleotides(CDNs)are natural agonists of the stimulator of interferon genes(STING),which is an attractive immunotherapy target.Currently,CDNs and their derivatives are being investigated clinically.However,the poor bioavailability of exogenous CDNs has limited their application in immunotherapy.Although nanocarriers are widely used for cytosolic delivery of CDNs,their loading capacity is insufficient,and their complicated composition and purification process raises bio-compatibility concerns.Herein,we report a super-simplified CDN self-assembly strategy for carrier-free delivery of CDNs.In the presence of excess K^(+),CDNs form oligomers which further self-assemble with divalent metal ions(such as Mn^(2+))to form nanoparticles(NPs)in aqueous solution.We demonstrate that the self-assembled CDN NPs promote cellular uptake of CDNs and enhance tumor immunogenicity by remodeling the tumor microenvironment,inducing immunogenic tumor cell death and increasing tumorinfiltrating lymphocytes,which is conducive to the generation of tumor neoantigen-specific T-cell responses.We also demonstrate that the use of CDN NPs alone or in combination with immune checkpoint blockades inhibits tumor growth,highlighting the fact that CDN NPs are a potent platform for cancer immunotherapy.

关键词： cyclic dinucleotide STING carrierfree delivery tumor immunogenicity cancer immunotherapy

An analytical model of hot rolling force for a thick plate by combining globally optimal approximation yield criterion and egg-circular velocity field

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Journal of Iron and Steel Research(International) 2024年第3期31卷 647-659页

作者： Shun-hu Zhang Yi Zhang wen-hao Tian Yan li Shagang School of Iron and Steel Soochow UniversitySuzhou 215021JiangsuChina

For the sake of solving the problem that it is difficult to be integrated for the Mises specific plastic power due to its nonlinearity,a new linear criterion,named the globally optimal approximation criterion,is constructed by the polygonal approximation to the Mises circle.The new criterion is proved to be the linear function of the principal stress componentsσ1,σ2 andσ3 and the trajectory of it on theπ-plane is a non-equiangular but equilateral dodecagon intersecting the Mises circle.The theoretical results of the current criterion described by the Lode stress parameters are in excellent accordance with the experimental results.Meanwhile,according to the trend that the metallic flow velocity between rollers aggrandizes gradually from the inlet to the outlet during the hot rolling of a thick plate,a biomimetic velocity field is proposed in which the horizontal velocity component fits the egg-circular curve distribution.The velocity field and its simulated results agree quite well.Subsequently,using the determined linear criterion,energy analysis of the constructed velocity field is utilized to obtain the interior deformation power,while the vector decomposition approach is utilized to obtain the frictional power and shear power.On this basis,the overall power is obtained and the analytical solutions are generated for the rolling torque,rolling force and the coefficient of the stress state under different egg curves by minimizing the neutral angle.Furthermore,the parameter optimization of the characteristic parameterρwhich affects the slope of the egg-circular curve is carried out and the best egg-circular curve which can minimize the energy consumption is determined.The best agreement between the theoretical and observed values of rolling force and rolling torque is under this curve,and the mean relative errors of the rolling torque and rolling force are no more than 2.93%,while the maximum error is no more than 8.35%.

关键词： Yield criterion Plastic deformation Rolling force Velocity field Analytical solution

Current Status and Perspectives of Dual-Atom Catalysts Towards Sustainable Energy Utilization

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Nano-Micro Letters 2024年第7期16卷 402-440页

作者： Yizhe li Yajie li hao Sun liyao Gao Xiangrong Jin Yaping li Zhi LV lijun Xu wen liu Xiaoming Sun State Key Laboratory of Chemical Resource Engineering Beijing Advanced Innovation Center for Soft Matter Science EngineeringCollege of ChemistryBeijing University of Chemical TechnologyBeijing 100029People’s Republic of China Xinjiang Coal Mine Mechanical and Electrical Engineering Technology Research Center Xinjiang Institute of EngineeringUrumqi 830023Xinjiang Uygur Autonomous RegionPeople’s Republic of China

The exploration of sustainable energy utilization requires the imple-mentation of advanced electrochemical devices for efficient energy conversion and storage,which are enabled by the usage of cost-effective,high-performance electro-catalysts.Currently,heterogeneous atomically dispersed catalysts are considered as potential candidates for a wide range of applications.Compared to conventional cata-lysts,atomically dispersed metal atoms in carbon-based catalysts have more unsatu-rated coordination sites,quantum size effect,and strong metal-support interactions,resulting in exceptional catalytic activity.Of these,dual-atomic catalysts(DACs)have attracted extensive attention due to the additional synergistic effect between two adja-cent metal atoms.DACs have the advantages of full active site exposure,high selectiv-ity,theoretical 100%atom utilization,and the ability to break the scaling relationship of adsorption free energy on active sites.In this review,we summarize recent research advancement of DACs,which includes(1)the comprehensive understanding of the synergy between atomic pairs;(2)the synthesis of DACs;(3)characterization meth-ods,especially aberration-corrected scanning transmission electron microscopy and synchrotron spectroscopy;and(4)electrochemical energy-related applications.The last part focuses on great potential for the electrochemical catalysis of energy-related small molecules,such as oxygen reduction reaction,CO_(2) reduction reaction,hydrogen evolution reaction,and N_(2) reduction reaction.The future research challenges and opportunities are also raised in prospective section.

关键词： Dual-atom catalysts Synergetic effect Electrocatalysis Oxygen reduction reaction CO_(2)reduction reaction Hydrogen evolution reaction N2 reduction reaction

A new integrated model of deformation resistance and its application in prediction of rolling force of a thick plate

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Journal of Iron and Steel Research(International) 2024年第4期31卷 882-893页

作者： Shun-hu Zhang Yan li li-zhi Che wen-hao Tian Shagang School of Iron and Steel Soochow UniversitySuzhou 215021JiangsuChina

The prediction accuracy of existing models of the rolling force of a thick plate is always very low.To address this problem,a high-precision genetic algorithm-backpropagation network(GA-BP)model of deformation resistance was built,and its integration with the traditional fitted model was further established.Then,a novel rolling force model was obtained by embedding the integration model of deformation resistance in the original model of rolling force.According to this research idea,the industrial data are normalized at first.On this basis,the interactions among the process parameters were disclosed through the variance analysis,and then described by various virtual factors.These factors are set as part of input parameters.Then,the optimal structure of the GA-BP model of deformation resistance was determined and an integration model of deformation resistance was built.Finally,a novel rolling force model is obtained by substituting the traditional fitted deformation resistance into the Sims model with the integration model of the deformation resistance.The results proves that the introduction of virtual factors can increase the hit rate of±5%from 75.8%to 78%and can reduce the root mean square error from 4.72%to 4.48%.Besides,it is found that the mean relative error of the traditional fitted deformation resistance is 0.142,while that of the modified deformation resistance is only 0.03.In addition,the mean relative error in the original rolling force model is 0.145,while that of the present model is only 0.03.

关键词： Integration model-Deformation resistance Variance analysis Virtual factor Genetic algorithm-backpropagation network model

Long noncoding RNAs HAND2-AS1 ultrasound microbubbles suppress hepatocellular carcinoma progression by regulating the miR-873-5p/tissue inhibitor of matrix metalloproteinase-2 axis

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1547-1563页

作者： Qiang Zou hao-wen Wang Xi-liang Di Yuan li Hui Gao Department of Interventional Therapy Tianjin Medical University Cancer Institute and HospitalTianjin 300060China National Clinical Research Center for Cancer Key Laboratory of Cancer Prevention and TherapyTianjin’s Clinical Research Center for CancerTianjin 300060China College of Animal Science and Technology Northeast Agricultural UniversityHarbin 150030Heilongjiang ProvinceChina Department of Hematology and Oncology Linyi People’s HospitalLinyi 251500Shandong ProvinceChina Department of Comprehensive Oncology Baotou Cancer HospitalBaotou 014030Inner Mongolia Autonomous RegionChina

BACKGROUND Increasing data indicated that long noncoding RNAs(lncRNAs)were directly or indirectly involved in the occurrence and development of tumors,including hepatocellular carcinoma(HCC).Recent studies had found that the expression of lncRNA HAND2-AS1 was downregulated in HCC tissues,but its role in HCC progression is unclear.Ultrasound targeted microbubble destruction mediated gene transfection is a new method to overexpress genes.AIM To study the role of ultrasound microbubbles(UTMBs)mediated HAND2-AS1 in the progression of HCC,in order to provide a new reference for the treatment of HCC.METHODS In vitro,we transfected HAND2-AS1 siRNA into HepG2 cells by UTMBs,and detected cell proliferation,apoptosis,invasion and epithelial-mesenchymal transition(EMT)by cell counting kit-8 assay,flow cytometry,Transwell invasion assay and Western blotting,respectively.In addition,we transfected miR-837-5p mimic into UTMBs treated cells and observed the changes of cell behavior.Next,the UTMBs treated HepG2 cells were transfected together with miR-837-5p mimic and tissue inhibitor of matrix metalloproteinase-2(TIMP2)overexpression vector,and we detected cell proliferation,apoptosis,invasion and EMT.In vivo,we established a mouse model of subcutaneous transplantation of HepG2 cells and observed the effect of HAND2-AS1 silencing on tumor formation ability.RESULTS We found that UTMBs carrying HAND2-AS1 restricted cell proliferation,invasion,and EMT,encouraged apoptosis,and HAND2-AS1 silencing eliminated the effect of UTMBs.Additionally,miR-873-5p targets the gene HAND2-AS1,which also targets the 3’UTR of TIMP2.And miR-873-5p mimic counteracted the impact of HAND2-AS1.Further,miR-873-5p mimic solely or in combination with pcDNA-TIMP2 had been transformed into HepG2 cells exposed to UTMBs.We discovered that TIMP2 reversed the effect of miR-873-5p mimic caused by the blocked signalling cascade for matrix metalloproteinase(MMP)2/MMP9.In vivo results showed that HAND2-AS1 silencing significantly inhibited tumor formation in mice.CON

关键词： Hepatocellular carcinoma Ultrasound microbubbles Long noncoding RNA HAND2-AS1 miR-873-5p Tissue inhibitor of matrix metalloproteinase-2

Ketogenic diet therapy in children with epilepsy caused by SLC2A1 mutations:a single-center single-arm retrospective study

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World Journal of Pediatrics 2024年第5期20卷 517-524页

作者： Ying-Yan Wang Yun-Qing Zhou li-Juan Luo Cui-Jin Wang Nan Shen hao li Ji-wen Wang Department of Neurology Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Department of Infectious Diseases Shanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina Clinical Research Ward Clinical Research CenterShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina

Background This retrospective study assessed the efficacy and safety of ketogenic diet therapies in children with epilepsy caused by SLC2A1 genetic mutations and glucose transporter type 1 deficiency syndrome.Methods Pediatric patients with epilepsy symptoms admitted to our medical center between January 2017 and October 2021 were included if they presented with an SLC2A1 genetic mutation on whole-exome sequencing.We analyzed the patients’convulsions and treatment with antiepileptic drugs.The patients were followed up at different time periods after ketogenic diet therapies.Results Six patients with SLC2A1 mutations were included in this study.The patients had seizures of different types and frequencies,and they took antiepileptic drugs to relieve their symptoms.They were then treated with a ketogenic diet for at least four months.We analyzed epilepsy control rates at 1,2,3,6,and 12 months after ketogenic diet treatment.All patients were seizure-free within a month of receiving the diet therapy.All patients were followed up for six months,three were followed up for 12 months after the treatment,and there was no recurrence of epilepsy during this period.After antiepileptic drug withdrawal,none of the patients experienced seizure relapse when receiving ketogenic diet treatment alone.No severe adverse events occurred during the therapy.Conclusions Ketogenic diet therapy is very effective and safe for the treatment of epilepsy caused by SLC2A1 mutations.Therefore,patients with glucose transporter type 1 deficiency syndrome caused by SLC2A1 mutations should begin ketogenic diet treatment as soon as possible.

关键词： Epilepsy Glucose transporter type 1 Ketogenic diet SLC2A1

P-and SV-wave dispersion and attenuation in saturated microcracked porous rock with aligned penny-shaped fractures

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Petroleum Science 2024年第1期21卷 143-161页

作者： Sheng-Qing li wen-hao Wang Yuan-Da Su Jun-Xin Guo Xiao-Ming Tang School of Geosciences China University of Petroleum(East China)Qingdao 266580ShandongChina Laoshan National Laboratory Qingdao 266071ShangdongChina Guangdong Provincial Key Laboratory of Geophysical High-resolution Imaging Technology Southern University of Science and TechnologyShenzhen 518055GuangdongChina Department of Earth and Space Sciences Southern University of Science and TechnologyShenzhen 518055GuangdongChina

P-and SV-wave dispersion and attenuation have been extensively investigated in saturated poroelastic media with aligned fractures.However,there are few existing models that incorporate the multiple wave attenuation mechanisms from the microscopic scale to the macroscopic scale.Hence,in this work,we developed a unified model to incorporate the wave attenuation mechanisms at different scales,which includes the microscopic squirt flow between the microcracks and pores,the mesoscopic wave-induced fluid flow between fractures and background(FB-WIFF),and the macroscopic Biot's global flow and elastic scattering(ES)from the fractures.Using Tang's modified Biot's theory and the mixed-boundary conditions,we derived the exact frequency-dependent solutions of the scattering problem for a single penny-shaped fracture with oblique incident P-and SV-waves.We then developed theoretical models for a set of aligned fractures and randomly oriented fractures using the Foldy approximation.The results indicated that microcrack squirt flow considerably influences the dispersion and attenuation of P-and SV-wave velocities.The coupling effects of microcrack squirt flow with the FB-WIFF and ES of fractures cause much higher velocity dispersion and attenuation for P waves than for SV waves.Randomly oriented fractures substantially reduce the attenuation caused by the FB-WIFF and ES,particularly for the ES attenuation of SV waves.Through a comparison with existing models in the limiting cases and previous experimental measurements,we validated our model.

关键词： Aligned fractures P-and SV-wave Dispersion and attenuation Microcracked porous background FB-WIFF Elastic scattering Squirt flow

Isotopic insights on quantitative assessments of interaction of eco-hydrological processes in multi-scale karst watersheds

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International Soil and Water Conservation Research 2024年第1期12卷 156-170页

作者： Zhuo hao Yang Gao Qingwen Zhang wen wen Agricultural Clean Watershed Research Group Institute of Environment and Sustainable Development in AgricultureCAASBeijing100081China Key Laboratory of Ecosystem Network Observation and Modeling Institute of Geographic Sciences and Natural Resources ResearchCASBeijing100101China School of Humanities and Social Sciences Beijing Institute of TechnologyBeijing100081China

The dynamics of hydrological processes and the storage mechanisms of karst water resources are the most important issues in karst hydrology.The impact of environmental changes on water quantity,and the evaluation and quantification of eco-hydrological processes remain poorly addressed.In this study,high-frequency continuous monitoring in multi-scale karst watersheds in Southwest China combined the approaches of water isotopes and the hybrid single-particle lagrangian integrated trajectory(HYSPliT)model to identify the recharge mechanisms between atmospheric vapor,rainfall,surface water,and groundwater,and to reveal the interaction of eco-hydrological processes.The dominant moisture sources in Puding(PD)County were the Indian Ocean(43-69%)and local moisture(24-33%).Theδ^(18)O and deuterium excess(d-excess)values showed a positive correlation indicating that secondary or sub-cloud evaporation was prominent in the wet seasons.Karst water line-conditioned excess(lc-excess)indicated that karst water interacted with recent precipitation,groundwater,and evaporation across seasons.Owing to its specific hydrogeological structure,surface water and rainwater have a higher contribution rate to groundwater replenishment.The Chenqi stream replenished the Houzhai River mainly in the form of groundwater,with percentages ranging from 38.1 to 93.5%in the wet season,and 47.8-80.1%in the dry season.In the Houzhai outlet,surface water and groundwater interconverted frequently with a percentage of 45.6-49.1%.We believe this is the first systematic study to quantify the supply relationship between water vapor transport,rainfall,surface water and groundwater in the Chinese karst zone,making a significant move forward in the field of karst hydrological processes and improving the efficiency of water resource evaluation and management.

关键词： Stable isotope Moisture sources Water cycle Karst watersheds

Activation of endogenous neurogenesis and angiogenesis by basic fibroblast growth factor-chitosan gel in an adult rat model of ischemic stroke

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Neural Regeneration Research 2024年第2期19卷 409-415页

作者： Hongmei Duan Shulun li Peng hao Fei hao wen Zhao Yudan Gao Hui Qiao Yiming Gu Yang Lv Xinjie Bao Kin Chiu Kwok-Fai So Zhaoyang Yang Xiaoguang li Department of Neurobiology School of Basic Medical SciencesCapital Medical UniversityBeijingChina Beijing Key Laboratory for Biomaterials and Neural Regeneration School of Engineering MedicineBeihang UniversityBeijingChina Department of Epidemiology and Statistics School of Public Health and ManagementNingxia Medical UniversityYinchuanNingxia Hui Autonomous RegionChina Department of Physical Education Capital University of Economics and BusinessmBeijingChina Department of Neurosurgery Peking Union Medical College HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijingChina Department of Psychology State Key Lab of Brain and Cognitive SciencesThe University of Hong KongHong Kong Special Administration RegionChina Guangdong-Hongkong-Macao Institute of CNS Regeneration Ministry of Education CNS Regeneration Collaborative Joint LaboratoryJinan UniversityGuangzhouGuangdong ProvinceChina Bioland Laboratory(Guangzhou Regenerative Medicine and Health Guangdong Laboratory) GuangzhouGuangdong ProvinceChina Department of Ophthalmology and State Key Laboratory of Brain and Cognitive Sciences The University of Hong KongHong Kong Special Administration RegionChina Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhouGuangdong ProvinceChina Co-innovation Center of Neuroregeneration Nantong UniversityNantongJiangsu ProvinceChina Department of Biomedical Engineering School of Biological Science and Medical EngineeringBeihang UniversityBeijingChina

Attempts have been made to use cell transplantation and biomaterials to promote cell proliferation,differentiation,migration,and survival,as well as angiogenesis,in the context of brain injury.However,whether bioactive materials can repair the damage caused by ischemic stroke by activating endogenous neurogenesis and angiogenesis is still unknown.In this study,we applied chitosan gel loaded with basic fibroblast growth factor to the stroke cavity 7 days after ischemic stroke in rats.The gel slowly released basic fibroblast growth factor,which improved the local microenvironment,activated endogenous neural stem/progenitor cells,and recruited these cells to migrate toward the penumbra and stroke cavity and subsequently differentiate into neurons,while enhancing angiogenesis in the penumbra and stroke cavity and ultimately leading to partial functional recovery.This study revealed the mechanism by which bioactive materials repair ischemic strokes,thus providing a new strategy for the clinical application of bioactive materials in the treatment of ischemic stroke.

关键词： adult endogenous neurogenesis angiogenesis basic fibroblast growth factor-chitosan gel chitosan functional recovery ischemic stroke neural stem cell newborn neuron

Tumor-derived exosomes induce initial activation by exosomal CD19 antigen but impair the function of CD19-specific CAR T-cells via TGF-βsignaling

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Frontiers of Medicine 2024年第1期18卷 128-146页

作者： Yuanyuan hao Panpan Chen Shanshan Guo Mengyuan li Xueli Jin Minghuan Zhang wenhai Deng Ping li wen Lei Aibin liang wenbin Qian Department of Hematology The Second Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou310009China Department of Hematology Henan Provincial People’s HospitalZhengzhou University People’s HospitalZhengzhou450003China Key Laboratory of Laboratory Medicine Ministry of EducationSchool of Laboratory Medicine and Life SciencesWenzhou Medical UniversityWenzhou325000China Department of Hematology Tongji Hospital of Tongji UniversityShanghai200065China

Tumor-derived exosomes (TEXs) enriched in immune suppressive molecules predominantly drive T-cell dysfunction and impair antitumor immunity. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment for refractory and relapsed hematological malignancies, but whether lymphoma TEXs have the same impact on CAR T-cell remains unclear. Here, we demonstrated that B-cell lymphoma-derived exosomes induce the initial activation of CD19-CAR T-cells upon stimulation with exosomal CD19. However, lymphoma TEXs might subsequently induce CAR T-cell apoptosis and impair the tumor cytotoxicity of the cells because of the upregulated expression of the inhibitory receptors PD-1, TIM3, and LAG3 upon prolonged exposure. Similar results were observed in the CAR T-cells exposed to plasma exosomes from patients with lymphoma. More importantly, single-cell RNA sequencing revealed that CAR T-cells typically showed differentiated phenotypes and regulatory T-cell (Treg) phenotype conversion. By blocking transforming growth factor β (TGF-β)-Smad3 signaling with TGF-β inhibitor LY2109761, the negative effects of TEXs on Treg conversion, terminal differentiation, and immune checkpoint expression were rescued. Collectively, although TEXs lead to the initial activation of CAR T-cells, the effect of TEXs suppressed CAR T-cells, which can be rescued by LY2109761. A treatment regimen combining CAR T-cell therapy and TGF-β inhibitors might be a novel therapeutic strategy for refractory and relapsed B-cell lymphoma.

关键词： tumor-derived exosome chimeric antigen receptor T-cell lymphoma TGF-β