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Lymph node-biomimetic scaffold boosts CAR-T therapy against solid tumor

National Science Review 2024年第4期11卷 206-215页

作者： Ziyan Liao jie Jiang Wei Wu Jiaqi shi Yanfang Wang Yuejun Yao Tao Sheng Feng liu Wei liu Peng Zhao Feifei Lv jie Sun Hongjun Li Zhen Gu National Key Laboratory of Advanced Drug Delivery and Release Systems College of Pharmaceutical Sciences Zhejiang University Key Laboratory of Advanced Drug Delivery Systems of Zhejiang Province College of Pharmaceutical SciencesZhejiang University Liangzhu Laboratory Zhejiang University Bone Marrow Transplantation Center of the First Affiliated Hospital and Department of Cell Biology Zhejiang University School of Medicine Department of Medical Oncology The First Affiliated Hospital School of Medicine Zhejiang University Department of Laboratory Medicine The First Affiliated Hospital Zhejiang University School of Medicine Department of Hepatobiliary and Pancreatic Surgery The Second Affiliated HospitalSchool of MedicineZhejiang University Jinhua Institute of Zhejiang University MOE Key Laboratory of Macromolecular Synthesis and Functionalization of Ministry of Education Department of Polymer Science and EngineeringZhejiang University Department of General Surgery Sir Run Run Shaw Hospital School of Medicine Zhejiang University

The limited infiltration and persistence of chimeric antigen receptor(CAR)-T cells is primarily responsible for their treatment deficits in solid tumors. Here, we present a three-dimensional scaffold, inspired by the physiological process of T-cell proliferation in lymph nodes. This scaffold gathers the function of loading,delivery, activation and expansion for CAR-T cells to enhance their therapeutic effects on solid tumors. This porous device is made from poly(lactic-co-glycolic acid) by a microfluidic technique with the modification of T-cell stimulatory signals, including anti-CD3, anti-CD28 antibodies, as well as cytokines. This scaffold fosters a 50-fold CAR-T cell expansion in vitro and a 15-fold cell expansion in vivo. Particularly, it maintains long-lasting expansion of CAR-T cells for up to 30 days in a cervical tumor model and significantly inhibits the tumor growth. This biomimetic delivery strategy provides a versatile platform of cell delivery and activation for CAR-T cells in treating solid tumors.

关键词： drug delivery cell therapy bioinspired biomaterials cancer immunotherapy

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Grain boundary engineering for enhancing intergranular damage resistance of ferritic/martensitic steel P92

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Nuclear Science and Techniques 2024年第5期35卷 186-199页

作者： Lei Peng Shang-Ming Chen Jing-Yi shi Yong-jie Sun Yi-Fei liu Yin-Zhong Shen Hong-Ya He Hui-Juan Wang jie Tian State Key Laboratory of Particle Detection and Electronics University of Science and Technology of ChinaHefei 230026China School of Nuclear Science and Technology University of Science and Technology of ChinaHefei 230027China School of Materials Engineering Shanghai University of Engineering Science333 Long Teng RoadShanghai 201620China Experimental Center of Engineering and Material Science University of Science and Technology of ChinaHefei 230026China

Ferritic/martensitic(F/M)steel is widely used as a structural material in thermal and nuclear power ***,it is susceptible to intergranular damage,which is a critical issue,under service *** this study,to improve the resistance to intergranular damage of F/M steel,a thermomechanical process(TMP)was employed to achieve a grain boundary engineering(GBE)microstructure in F/M steel *** TMP,including cold-rolling thickness reduction of 6%,9%,and 12%,followed by austenitization at 1323 K for 40 min and tempering at 1053 K for 45 min,was applied to the as-received(AR)P92 *** prior austenite grain(PAG)size,prior austenite grain boundary character distribution(GBCD),and connectivity of prior austenite grain boundaries(PAGBs)were *** to the AR specimen,the PAG size did not change *** fraction of coincident site lattice boundaries(CSLBs,3≤Σ≤29)and Σ3^(n) boundaries along PAGBs decreased with increasing reduction ratio because the recrystallization fraction increased with increasing reduction *** PAGB connectivity of the 6%deformed specimen slightly deteriorated compared with that of the AR ***,potentiodynamic polarization studies revealed that the intergranular damage resistance of the studied steel could be improved by increasing the fraction of CSLBs along the PAGBs,indicating that the TMP,which involves low deformation,could enhance the intergranular damage resistance.

关键词： Grain boundary engineering Ferritic/martensitic steel Prior austenite grain boundary character distribution Grain boundary connectivity Intergranular damage resistance

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Prolonged Alzheimer-like Tau Hyperphosphorylation Induced by Simultaneous Inhibition of Phosphoinositol-3 Kinase and Protein Kinase C in N2a cells

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Acta Biochimica et Biophysica Sinica 2005年第5期37卷 349-354页

作者： Guo-Gang XU Yan-Qiu DENG shi-jie liu Hong-Lian LI Jian-Zhi WANG Department of Pothophysiology,Institute of Neuroscience,Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China Department of Pathophysiology Institute of Neuroscience Tongji Medical College Huazhong University of Science and TechnologyWuhan 430030 China

Co-injection of wortmannin（inhibitor of phosphatidylinositol-3 kinase,PI3K）and GF109203X（inhibitor of protein kinase C,PKC）into the rat brain was found to induce spatial memory deficiency andenhance tau hyperphosphorylation in the hippocampus of rat *** establish a cell model with durativeAlzheimer-like tau hyperphosphorylation in this study,we treated N2a neuroblastoma cells with wortmanninand GF109203X separately and simultaneously,and measured the glycogen synthase kinase 3（GSK-3）activity by γ-（32）P-labeling and the level of tau phosphorylation by Western *** was found that theapplication of wortmannin alone only transitorily increased the activity of GSK-3（about 1 h）and the level oftau hyperphosphorylation at Ser396/Ser404 and Ser199/Ser202 sites（no longer than 3 h）;however,a prolongedand intense activation of GSK-3（over 12 h）and enhanced tan hyperphosphorylation（about 24 h）wereobserved when these two selective kinase inhibitors were applied *** conclude that the simultaneousinhibition of PI3K and PKC can induce GSK-3 overactivation,and further strengthen and prolong the Alzheimer-like tau hyperphosphorylation in N2a cells,suggesting the establishment of a cell model with early pathologicalevents of Alzheimer’s disease.

关键词： Alzheimer’s disease(AD) tau glycogen synthase kinase 3(GSK-3) protein kinase C(PKC) phosphatidylinositol-3 kinase(PI3K) N2a cells

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Dielectric polymer grafted electrodes enhanced aqueous supercapacitors

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Nano Research 2024年第3期17卷 1525-1534页

作者： shian Dong Kunming shi jie Chen Yingke Zhu Hongfei Li Weihang Gao Zhenli Xu Qinglei liu Xingyi Huang Shanghai Key Laboratory of Electrical Insulation and Thermal Aging Department of Polymer Science and EngineeringState Key Laboratory of Metal Matrix CompositesShanghai Jiao Tong UniversityShanghai 200240China School of Mathematical Sciences Institute of Natural Sciences and MOE−LSCShanghai Jiao Tong UniversityShanghai 200240China State Key Laboratory of Metal Matrix Composites Shanghai Jiao Tong UniversityShanghai 200240China

Supercapacitors(SCs)have become increasingly important in electrical energy storage and delivery owing to their high power densities and long *** SCs are promising for large-scale engineering applications because of their low cost and ***,the low operating voltage and low energy density of aqueous SCs severely limit their practical *** this study,a nanoscale dielectric layer is grafted onto a graphene electrode to achieve both a high operating voltage and enhanced *** with an SC without dielectric grafting,a dielectric-enhanced SC(DESC)shows a higher capacitance by 2200%.The mechanism of the capacitance enhancement can be attributed to three factors:the dielectric polarization,the ions desolvation by the dielectric,and the enhanced quantum capacitance from charge transfer and ion adsorption in the polymer *** addition,a 2.5 V pouch DESC with a 1 M KCl electrolyte is confirmed to cycle up to 50,000 times with a capacitance retention of 87.5%.The DESC presents the optimal electrochemical properties after it is grafted with a 5 nm dielectric *** study provides new insights into the design of high-voltage and high-energy-density aqueous SCs.

关键词： supercapacitors dielectric polymer high voltage capacitance enhancement

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Ethanol extract of Cyathulae Radix inhibits osteoclast differentiation and bone loss

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Chinese Journal of Natural Medicines 2024年第3期22卷 212-223页

作者： shi Liying REN liuyi LI Jinping liu Xin LU Jingjing JIA Lujuan XIE Baoping TANG Siyuan liu Wei ZHANG jie Department of Pharmachemistry Xiangya School of Pharmaceutical SciencesCentral South UniversityChangsha 410013China Hunan Key laboratory of Diagnostic and Therapeutic Drug Research for Chronic Diseases Central South UniversityChangsha 410013China Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases Ministry of EducationGannan Medical UniversityGanzhou 341000China Xiangya Nursing School Central South UniversityChangsha 410013China The Third Xiangya Hospital Central South UniversityChangsha 410013China

Cyathulae Radix,a traditional Chinese medicine and a common vegetable,boasts a history spanning *** enhances bone density,boosts metabolism,and effectively alleviates osteoporosis-induced *** its historical use,the molecular mechanisms behind Cyathulae Radix’s impact on osteoporosis remain *** this study,we investigated the effects and mechanisms of Cyathulae Radix ethanol extract(CEE)in inhibiting osteoporosis and ***-week-old female mice underwent ovariectomy and were treated with CEE for eight ***-computed tomography(micro-CT)assessed histomorphometric parameters,bone tissue staining observed distal femur histomorphology,and three-point bending tests evaluated tibia mechanical ***-linked immunosorbent assay(ELISA)measured serum estradiol(E2),receptor activator for nuclear factor B ligand(RANKL),and osteoprotegerin(OPG)***-related markers were analyzed via Western blotting(WB)and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,CEE effects on RANKL-induced osteoclast formation and bone resorption were investigated in vitro using tartrate-resistant acid phosphatase(TRAP)staining,qRT-PCR,and WB *** with the ovariectomy(OVX)group,CEE treatment enhanced trabecular bone density,maximal load-bearing capacity,and various histomorphometric *** E2 and OPG levels significantly increased,while Receptor activator of nuclear factor-κB(RANK)decreased in the CEE *** downregulated matrix metallopeptidase 9(MMP-9),Cathepsin K(CTSK),and TRAP gene and protein *** bone marrow macrophages(BMMs),CEE reduced mature osteoclasts,bone resorption pit areas,and MMP-9,CTSK,and TRAP expression during osteoclast *** with DMSO treatment,CEE markedly inhibited RANK,TNF receptor associated factor 6(TRAF6),Proto-oncogene c-Fos(c-Fos),Nuclear factor of activated T-cells cytoplasmic 1(NFATc1)expressions,and Extracellular regula

关键词： Osteoporosis Osteoclast BMMs Cyathulae Radix RANKL ER/RANK/NFATc1 signaling pathway

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A compact bimorph rotary piezoelectric actuator with customized small power supply

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Science China(Technological Sciences) 2024年第4期67卷 1185-1195页

作者： DENG jie liu DaQing WANG WeiYi liu YingXiang School of Mechatronics and Engineering Harbin Institute of TechnologyHarbin 150001China

Inertial piezoelectric actuators are widely applied in precision devices with simple structure and accurate ***,existing inertial piezoelectric actuators still face the challenges of rollback motion and bulky power *** this work,an alternate excitation strategy and a customized small power supply for a bimorph rotary piezoelectric actuator(BRPA)are proposed to solve the *** BRPA prototype is designed with a bipedal symmetrical structure,measuring 35 mm in height and 32 mm in diameter,which has a maximum rotation velocity of 0.247 rad/s and a resolution of 0.66μ*** to the bipedal symmetrical structure,the friction directions between the driving feet and the rotor can be coordinated to suppress the *** rollback ratio is almost zero when the phase difference of the exciting signal is set as 180°.The customized power supply is designed and manufactured,whose size is 58 mm×56 mm×46 *** can output signals for the single step mode and the continuous mode,and they are adopted to excite BRPA to achieve a small stroke with one single step and a large stroke with continuous step,***,an experimental system for optical fiber alignment is developed based on the BRPA and the customized small power supply,the experiment has verified the practicability of this work in the precision fields,especially in the miniaturized precision systems.

关键词： inertial piezoelectric actuator customized small power supply single step mode continuous mode rollback suppression miniaturized precision system

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Mg-doped,carbon-coated,and prelithiated SiO_(x) as anode materials with improved initial Coulombic efficiency for lithium-ion batteries

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Carbon Energy 2024年第3期6卷 204-214页

作者： Bin liu jie liu Cheng Zhong Wenbin Hu Key Laboratory of Advanced Ceramics and Machining Technology(Ministry of Education) School of Materials Science and EngineeringTianjin UniversityTianjinChina Tianjin Key Laboratory of Composite and Functional Materials School of Materials Science and EngineeringTianjin UniversityTianjinChina Joint School of National University of Singapore and Tianjin University TianjinChina International Campus of Tianjin University Binhai New CityFuzhouChina

Silicon suboxide(SiO_(x),x≈1)is promising in serving as an anode material for lithium-ion batteries with high capacity,but it has a low initial Coulombic efficiency(ICE)due to the irreversible formation of lithium silicates during the first *** this work,we modify SiO_(x) by solid-phase Mg doping reaction using low-cost Mg powder as a reducing *** show that Mg reduces SiO_(2) in SiO_(x) to Si and forms MgSiO_(3) or Mg_(2)SiO_(4).The MgSiO_(3) or Mg_(2)SiO_(4) are mainly distributed on the surface of SiO_(x),which suppresses the irreversible lithium-ion loss and enhances the ICE of SiO_(x).However,the formation of MgSiO_(3) or Mg_(2)SiO_(4) also sacrifices the capacity of SiO_(x).Therefore,by controlling the reaction process between Mg and SiO_(x),we can tune the phase composition,proportion,and morphology of the Mg-doped SiO_(x) and manipulate the *** obtain samples with a capacity of 1226 mAh g^(–1) and an ICE of 84.12%,which show significant improvement over carbon-coated SiO_(x) without Mg *** the synergistical modification of both Mg doping and prelithiation,the capacity of SiO_(x) is further increased to 1477 mAh g^(–1) with a minimal compromise in the ICE(83.77%).

关键词： initial Coulombic efficiency lithium-ion batteries magnesium doping prelithiation silicon suboxide

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Rebuilding the theory of isotope fractionation for evaporation of silicate melts under vacuum condition

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Acta Geochimica 2024年第4期43卷 661-676页

作者： jie Wang Yun liu Research Center for Planetary Science College of Earth and Planetary SciencesChengdu University of TechnologyChengdu 610059China State Key Laboratory of Ore Deposit Geochemistry Institute of GeochemistryChinese Academy of SciencesGuiyang 550081China CAS Center for Excellence in Comparative Planetology Hefei 230026China

Isotope eff ects are pivotal in understanding silicate melt evaporation and planetary accretion *** on the Hertz-Knudsen equation,the current theory often fails to predict observed isotope fractionations of laboratory experiments due to its oversimplified ***,we point out that the Hertz-Knudsen-equation-based theory is incomplete for silicate melt evaporation cases and can only be used for situations where the vaporized species is identical to the one in the *** propose a new model designed for silicate melt evaporation under *** model considers multiple steps including mass transfer,chemical reaction,and *** derivations reveal a kinetic isotopic fractionation factor(KIFF orα)αour model=[m(^(1)species)/m(^(2)species)]^(0.5),where m(species)is the mass of the reactant of reaction/nucleation-limiting step or species of diffusion-limiting step and superscript 1 and 2 represent light and heavy isotopes,*** model can eff ectively reproduce most reported KIFFs of laboratory experiments for various elements,i.e.,Mg,Si,K,Rb,Fe,Ca,and ***,the KIFF-mixing model referring that an overall rate of evaporation can be determined by two steps jointly can account for the eff ects of low P_(H2)pressure,composition,and *** addition,we find that chemical reactions,diffusion,and nucleation can control the overall rate of evaporation of silicate melts by using the fitting slope in ln(−ln f)versus ln(t).Notably,our model allows for the theoretical calculations of parameters like activation energy(E_(a)),providing a novel approach to studying compositional and environmental eff ects on evaporation processes,and shedding light on the formation and evolution of the proto-solar and Earth-Moon systems.

关键词： Evaporation Kinetic isotopic fractionation Chemical kinetics Hertz-Knudsen equation CAIS

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Melatonin ameliorated okadaic-acid induced Alzheimer-like lesions

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Acta Pharmacologica Sinica 2004年第3期25卷 22-26页

作者： Yi-peng WANG,Xian-tao LI,shi-jie liu,Xin-wen ZHOU,Xiao-chuan WANG,Jian-zhi WANG2 TongjiMedical College,Huazhong University of Science and Technology,Wuhan 430030,China Tongji Medical College Huazhong University of Science and Technology Wuhan 430030

AIM: To explore the protective effects of melatonin (Mel) on the abnormal phosphorylation of neuronal cytoskeletal proteins. METHODS: We generated a neuroblastoma (SH-SY5Y) cell system in which cytoskeletal proteins are abnormally phosphorylated resulting in microtubule disruption due to the marked inhibition of protein phosphatase activities by okadaic acid (OA). RESULTS: OA-induced declines in cell viability and mitochondrial metabolic activity were remarkably prevented by Mel. In addition, the hyperphosphorylation/accumulation of neurofilament- (NF-) H/M subunits and the disruption of microtubules, induced by OA, were significantly inhibited by Mel. CONCLUSION: Our results suggest multiple protective functions of Mel against a series of pathological lesions known to culminate in AD, including abnormal phosphorylation of cytoskeletal proteins, microtubule disassembly and mitochondrion-initiated cell toxicity.

关键词： Alzheimer disease protein phosphatase okadaic acid neurofilament proteins melatonin

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Constructing the Impossible Differential of Type-II GFN with Boolean Function and Its Application to WARP

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Chinese Journal of Electronics 2024年第1期33卷 80-89页

作者： Jiali shi Guoqiang liu Chao LI College of Liberal Arts and Sciences National University of Defense Technology Hunan Engineering Research Center of Commercial Cryptography Theory and Technology Innovation State Key Laboratory of Information Security Institute of Information Engineering

Type-Ⅱ generalized Feist el network(GFN) has attracted a lot of attention for its simplicity and high *** differential attack is one of the powerful cryptanalytic approaches for word-oriented block ciphers such as Feistel-like *** deduce the impossible differential of Type-Ⅱ GFN by analyzing the Boolean function in the middle *** main idea is to investigate the expression with the variable representing the plaintext(ciphertext) difference words for the internal state *** adopting the miss-in-the-middle approach,we can construct the impossible differential of Type-Ⅱ *** an illustration,we apply this approach to WARP,a lightweight 128-bit block cipher with a 128-bit key which was presented by Banik et *** SAC *** structure of WARP is a 32-branch Type-Ⅱ ***,we find two 21-round truncated impossible differentials and implement a 32-round key recovery attack on *** the 32-round key recovery attack on WARP,some observations are used to mount an effective *** the advantage of the early abort technique,the data,time,and memory complexities are 2125.69chosen plaintexts,2126.6832-round encryptions,and 2100-bit,*** the best of our knowledge,this is the best attack on WARP in the single-key scenario.

关键词： Ciphers Boolean functions Parallel processing Complexity theory

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