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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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Multi-omics integration reveals potential stage-specific druggable targets in T-cell acute lymphoblastic leukemia

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Genes & Diseases 2024年第5期11卷 374-389页

作者： Zijun Yan jie Xia Ziyang Cao Hongyang Zhang Jinxia Wang Tienan feng Yi Shu Lin Zou Clinical Research Unit Shanghai Children’s HospitalSchool of MedicineShanghai Jiao Tong UniversityShanghai 200062China Institute of Pediatric Infection Immunityand Critical Care MedicineShanghai Jiao Tong University School of MedicineShanghai 200062China Center for Clinical Molecular Laboratory Medicine of Children’s Hospital of Chongqing Medical University Chongqing 400014China Clinical Research Institute Shanghai Jiao Tong University School of MedicineShanghai 200025China Bioinformatics and BioMedical Bigdata Mining Laboratory School of Big HealthGuizhou Medical UniversityGuiyangGuizhou 554300China

T-cell acute lymphoblastic leukemia(T-ALL),a heterogeneous hematological malignancy,is caused by the developmental arrest of normal T-cell *** development of targeted therapeutic regimens is impeded by poor knowledge of the stage-specific aberrances in this *** this study,we performed multi-omics integration analysis,which included mRNA expression,chromatin accessibility,and gene-dependency database analyses,to identify potential stage-specific druggable targets and repositioned drugs for this *** multi-omics integration helped identify 29 potential pathological genes for *** genes exhibited tissue-specific expression profiles and were enriched in the cell cycle,hematopoietic stem cell differentiation,and the AMPK signaling *** these,four known druggable targets(CDK6,TUBA1A,TUBB,and TYMS)showed dysregulated and stage-specific expression in malignant T cells and may serve as stage-specific targets in *** TUBA1A expression level was higher in the early T cell precursor(ETP)-ALL cells,while TUBB and TYMS were mainly highly expressed in malignant T cells arrested at the CD4 and CD8 double-positive or single-positive ***6 exhibited a U-shaped expression pattern in malignant T cells along the naıve to maturation ***,mebendazole and gemcitabine,which target TUBA1A and TYMS,respectively,exerted stage-specific inhibitory effects on T-ALL cell lines,indicating their potential stage-specific antileukemic role in ***,our findings might aid in identifying potential stage-specific druggable targets and are promising for achieving more precise therapeutic strategies for T-ALL.

关键词： Multi-omics Stage-specific druggable targets Targeted therapeutic strategies T-cell acute lymphoblastic leukemia Drug repositioning

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Stable sodium metal anode enabled by interfacial room-temperature liquid metal engineering for high-performance sodium–sulfur batteries with carbonate-based electrolyte

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Interdisciplinary Materials 2024年第3期3卷 425-436页

作者： Kangdong Tian Chuanliang Wei Zhengran Wang Yuan Li Baojuan Xi Shenglin xiong Jinkui feng Key Laboratory for Liquid-Solid Structural Evolution&Processing of Materials(Ministry of Education) School of Materials Science and EngineeringShandong UniversityJinanChina School of Chemistry and Chemical Engineering Shandong UniversityJinanChina

Sodium(Na)metal is a competitive anode for next-generation energy storage applications in view of its low cost and high-energy ***,the uncontrolled side reactions,unstable solid electrolyte interphase(SEI)and dendrite growth at the electrode/electrolyte interfaces impede the practical application of Na metal as ***,a heterogeneous Na-based alloys interfacial protective layer is constructed in situ on the surface of Na foil by self-diffusion of liquid metal at room temperature,named“HAIP Na.”The interfacial Na-based alloys layer with good electrolyte wettability and strong sodiophilicity,and assisted in the construction of NaF-rich *** means of direct visualization and theoretical simulation,we verify that the interfacial Na-based alloys layer enabling uniform Na^(+)flux deposition and suppressing the dendrite *** a result,in the carbonate-based electrolyte,the HAIP Na||HAIP Na symmetric cells exhibit a remarkably enhanced cycling life for more than 650 h with a capacity of 1mAh cm^(−2)at a current density of 1mAcm^(−2).When the HAIP Na anode is paired with sulfurized polyacrylonitrile(SPAN)cathode,the SPAN||HAIP Na full cells demonstrate excellent rate performance and cycling stability.

关键词： interfacial Na-based alloy layer liquid metal Na dendrite Na metal anode Na–S battery

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Peritoneal fluid indocyanine green test for diagnosis of gut leakage in anastomotic leakage rats and colorectal surgery patients

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World Journal of Gastrointestinal Surgery 2024年第6期16卷 1825-1834页

作者： Yu Huang Tian-Yang Li jie-feng Weng Hui Liu Yu-jie Xu Shuai Zhang Wei-Li Gu Department of Surgery Guangzhou First People's HospitalGuangzhou 510180Guangdong ProvinceChina

BACKGROUND Application of indocyanine green(ICG)fluorescence has led to new developments in gastrointestinal ***,little is known about the use of ICG for the diagnosis of postoperative gut leakage(GL).In addition,there is a lack of rapid and intuitive methods to definitively diagnose postoperative *** To investigate the effect of ICG in the diagnosis of anastomotic leakage in a surgical rat GL model and evaluate its diagnostic value in colorectal surgery *** Sixteen rats were divided into two groups:GL group(n=8)and sham group(n=8).Approximately 0.5 mL of ICG(2.5 mg/mL)was intravenously injected *** peritoneal fluid was collected for the fluorescence test at 24 and 48 *** patients with rectal cancer who had undergone laparoscopic rectal cancer resection plus enterostomies were injected with 10 mL of ICG(2.5 mg/mL)on postoperative day *** ostomy fluids were collected 24 h after ICG injection to identify the possibility of the ICG excreting from the peripheral veins to the enterostomy *** who had undergone colectomy or rectal cancer resection were enrolled in the diagnostic *** peritoneal fluids from drainage were collected 24 h after ICG *** ICG fluorescence test was conducted using OptoMedic endoscopy along with a near-infrared fluorescent imaging *** The peritoneal fluids from the GL group showed ICG-dependent green fluorescence in contrast to the sham *** samples of ostomy fluids showed green fluorescence,indicating the possibility of ICG excreting from the peripheral veins to the enterostomy stoma in *** peritoneal fluid ICG test exhibited a sensitivity of 100%and a specificity of 83.3%for the diagnosis of *** positive predictive value was 71.4%,while the negative predictive value was 100%.The likelihood ratios were 6.0 for a positive test result and 0 for a negative *** The postoperative ICG test in a drainage tube is a valuable and simple t

关键词： Gut leakage Indocyanine green Anastomotic leakage model Diagnostic test Diagnostic technique

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Improving treatment plan and mental health in children with abdominal infection for broad-spectrum bacterial infections

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World Journal of Psychiatry 2024年第9期14卷 1319-1325页

作者： Gui-Bo Wang Xue-feng Zhang Bing Liang jie Lei Jun Xue Department of Pediatric Surgery the First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina Department of General Surgery the First Affiliated Hospital of Hebei North UniversityZhangjiakou 075000Hebei ProvinceChina

BACKGROUND Pediatric abdominal infection is a common but serious disease that requires timely and effective *** surgical treatment,accurate diagnosis and rational application of antibiotics are the keys to improving treatment *** To investigate the effect of broad-spectrum bacterial detection on postoperative antibiotic *** A total of 100 children with abdominal infection who received surgical treatment in our hospital from September 2020 to July 2021 were *** observation group collected blood samples upon admission and sent them for broad-spectrum bacterial infection nucleic acid testing,and collected pus or exudate during the operation for bacterial culture and drug sensitivity testing;the control group only sent bacterial culture and drug sensitivity testing during the *** White blood cell count,C-reactive protein,procalcitonin,3 days after surgery,showed better postoperative index than the control group(P<0.05).The hospital stay in the observation group was significantly shorter than that in the control *** hospitalization cost in the observation group was significantly lower than that in the control group,and the difference between the two groups was statistically significant(P<0.05).CONCLUSION Early detection of broad-spectrum bacterial infection nucleic acids in pediatric abdominal infections can help identify pathogens sooner and guide the appropriate use of antibiotics,improving treatment outcomes and reducing medical costs to some extent.

关键词： Pediatric abdominal infection Nucleic acid detection of broad-spectrum bacterial infection Bacterial culture Drug sensitivity testing Treatment effect Cost Mental health

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A hydrogen-bonded organic framework containing fluorescent carbazole and responsive pyridyl units for sensing organic acids

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Chinese Chemical Letters 2024年第9期35卷 458-463页

作者： Liangji Chen Zhen Yuan Fudong feng Xin Zhou Zhile xiong Wuji Wei Hao Zhang Banglin Chen Shengchang Xiang Zhangjing Zhang Fujian Key Laboratory of Polymer Materials College of Chemistry and Materials ScienceFujian Normal UniversityFuzhou 350007China

Hydrogen-bonded organic frameworks(HOFs)are a promising candidate for optical sensing,but the lack of effective design strategies poses significant challenges to the construction of HOFs for organic acid *** this work,the first HOF for organic acid sensing is reported by constructing a multiplepyridine carbazole-based dense HOF,namely HOF-FJU-206,from a tripyridine-carbazole molecular 3,6-bis(pyridin-4-yl)-9-(4-(pyridin-4-yl)phenyl)-9H-carbazole(CPPY)with carbazole center for luminescence,pyridyl sites for its responsive of hydrogen proton,and narrow channels in the dense framework for the diffusion of hydrogen ***-FJU-206 exhibits differential responsively fluorescence sensing and recovery properties to formic,acetic,and propionic acids with different molecular sizes and p Kavalue(acid dissociation constant).The dissociation degree of various acids can be determined by analyzing the slope of changes in both peak wavelength and intensity of in-situ fluorescence,which easily enables the dual-corrective recognition of different *** varying degree of protonation at pyridine sites is proved to be the reason for differential sensing of various acids,as demonstrated by1H NMR spectra,X-ray photoelectron spectroscopy(XPS)characterization,and modeling studies.

关键词： Hydrogen-bonded organic framework Organic acid sensing Acids recognition Carbazole luminescence Pyridine protonation

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Exploring cerebral structural and functional abnormalities in a mouse model of post-traumatic headache induced by mild traumatic brain injury

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Zoological Research 2024年第3期45卷 648-662页

作者： Dan Yang Bin-Bin Nie Jin-Gang He Zong-Qiang Lv feng-feng Mo Si-Yi Ouyang jie Wang Ju-Xiang Chen Tao Tao Department of Anesthesiology Central People’s Hospital of ZhanjiangZhanjiangGuangdong 524045China Key Laboratory of Nuclear Radiation and Nuclear Energy Technology Institute of High Energy PhysicsChinese Academy of SciencesBeijing 100049China Key Laboratory of Magnetic Resonance in Biological Systems State Key Laboratory of Magnetic Resonance and Atomic and Molecular PhysicsNational Center for Magnetic Resonance in WuhanWuhan Institute of Physics and MathematicsInnovation Academy for Precision Measurement Science and TechnologyChinese Academy of Sciences-Wuhan National Laboratory for OptoelectronicsWuhanHubei 430071China Department of Neurosurgery Changhai HospitalNaval Medical UniversityShanghai 200082China Department of Nutrition and Food Hygiene Faculty of Naval MedicineNaval Medical UniversityShanghai 200433China Department of Anesthesiology Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China Institute of Neuroscience and Brain Diseases/Xiangyang Central Hospital Affiliated Hospital of Hubei University of Arts and ScienceXiangyangHubei 441021China Songjiang Hospital and Songjiang Research Institute Shanghai Jiao Tong University School of MedicineShanghai 201600China Department of Anesthesiology Zhujiang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

Mild traumatic brain injury(mTBI)-induced post-traumatic headache(PTH)is a pressing public health concern and leading cause of disability *** PTH is often accompanied by neurological disorders,the exact underlying mechanism remains largely *** potential biomarkers may prompt the diagnosis and development of effective treatments for mTBI-induced *** this study,a mouse model of mTBI-induced PTH was established to investigate its effects on cerebral structure and function during short-term *** indicated that mice with mTBI-induced PTH exhibited balance deficits during the early post-injury *** kinetics revealed that variations in neurotransmitters were most prominent in the cerebellum,temporal lobe/cortex,and hippocampal regions during the early stages of ***,variations in brain functional activities and connectivity were further detected in the early stage of PTH,particularly in the cerebellum and temporal cortex,suggesting that these regions play central roles in the mechanism underlying ***,our results suggested that GABA and glutamate may serve as potential diagnostic or prognostic biomarkers for *** studies should explore the specific neural circuits involved in the regulation of PTH by the cerebellum and temporal cortex,with these two regions potentially utilized as targets for non-invasive stimulation in future clinical treatment.

关键词： Post-traumatic headache(PTH) Mild traumatic brain injury(mTBI) Metabolic kinetics fMRI Cerebellum

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Introduction of rare-earth element Sc in alloy design to modify wear features of dual-phase high-entropy alloy

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Rare Metals 2024年第2期43卷 817-828页

作者： Hao Ren Rui-Run Chen Xue-feng Gao Tong Liu Gang Qin Yu-Lung Chiu Shi-Ping Wu Jing-jie Guo Guo National Key Laboratory for Precision Hot Processing of Metals School of Materials Science and EngineeringHarbin Institute of TechnologyHarbin150001China School of Metallurgy and Materials University of BirminghamBirminghamB152TTUK

Tailoring the alloy composition,which induces the hard secondary phase to increase hardness and strength to improve the wear features,is a feasible approach for developing wear-resistant metal ***,a group of(AlCoCrFeNi)_(100–x)Sc_(x)(x=0–2.0,at%)high-entropy alloys(HEAs)are designed and the phase compositions and wear behaviors are ***-doped HEA series contain the primary body-centered cubic(BCC)and eutectic phases,in which the eutectic phase is composed of the alternately grown BCC and Laves *** addition promotes the diffusion of Ni atoms from BCC phase to form the Sc-rich Laves phase at the grain *** hardness increases due to solid solution strengthening and second phase *** the second phase strengthening plays a more significant role relative to solid solution *** phase and the oxides caused by wear heating prevent the direct contact between friction pair and HEAs,thus inducing a decreased wear rate from 6.82×10^(−5) to 3.47×10^(−5)m^(3)·N^(−1)·m^(−1).Moreover,the wear mechanism changes from adhesive wear,abrasive wear and oxidative wear to abrasive wear and oxidative wear.

关键词： High entropy alloy(HEA) Laves phase Hardness Wear mechanism

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Mechanical performance of 22SiMn2TiB steel welded with lowtransformation- temperature filler wire and stainless steel filler wire

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Journal of Iron and Steel Research International 2024年第4期31卷 967-981页

作者： Zi-dong Lin Kai-jie Song Zhen Sun Zi-qian Zhu Xue-feng Zhao Constantinos Goulas Wei Ya Xing-hua Yu School of Materials Science and Engineering Beijing Institute of TechnologyBeijing 100081China Beijing Institute of Technology Chongqing Innovation Center Chongqing 401120China Department of Design Production and Management Faculty of Engineering Technology.University of TwenteEnschede 7500 AETheNetherlands Rotterdam Additive Manufacture Fieldlab(RAMLAB) Rotterdam 3089 JWTheNetherlands

TX-80 low-transformation-temperature(LTT)welding wire was used to replace the traditional ER 307Si welding wire to realize the connection of 22SiMn2TiB armor steel in manual overlay *** previously existing issues,such as welding cracks,large welding deformation,and severe welding residual stress,were solved to ensure good strength and ductility *** particular,with the same welding conditions,TX-80 LTT wire eliminates welding *** reduces the welding deformation no matter the base pretreatment of pre-setting angle or no pre-setting *** comparison,it was found that the microstructure at the TX-80 weld is mainly composed of martensite and a small amount of retained *** contrast,the microstructure of the ER 307Si weld consists of a large amount of austenite and a small amount of skeleton-like *** variation trend of residual stress and microhardness from the weld to the base were investigated and compared with the mechanical properties of base *** TX-80 and the ER 307Si tensile samples elongation is 6.76%and 6.01%,while the ultimate tensile strengths are 877 and 667 MPa,*** average impact toughness at room temperature of the ER 307Si weld is 143.9 J/cm^(2),much higher than that of the TX-80 weld,which is only 36.7 J/cm^(2).The relationship between impact and tensile properties with microstructure species and distribution was *** addition,the fracture surface of the tensile and the impact samples was observed and *** dimples,fewer pores,larger radiation zone,and shear lips of TX-80 samples indicate better tensile ductility and worse impact toughness than those of ER 307Si weld.

关键词： Low-transformation-temperature material 22SiMn2TiB steel Welding deformation Residual stress Martensitic transformation Mechanical property

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A Hf-doped dual-phase high-entropy alloy: phase evolution and wear features

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Rare Metals 2024年第1期43卷 324-333页

作者： Hao Ren Rui-Run Chen Xue-feng Gao Tong Liu Gang Qin Yu-Lung Chiu Shi-Ping Wu Jing-jie Guo National Key Laboratory for Precision Hot Processing of Metals School of Materials Science and EngineeringHarbin Institute of TechnologyHarbin 150001China School of Metallurgy and Materials University of BirminghamEdgbastonBirmingham B152TTUK

Initially defined high entropy alloys(HEAs)usually exhibit a single-phase solid-solution ***,two and/or more types of phases in HE As possibly induce the desired microstructure features,which contribute to improving the wear properties of HE ***,we prepare a series of(AlCoCrFeNi)_(100-x)Hf_(x)(x=0,2,4and 6;at%) HEAs and concern their phase compositions,micro structures and wear *** leads to the formation of(Ni,Co)_(2)Hf-type Laves phase and tailors the microstructure from a body-centered cubic(BCC) singlephase structure to a hypoeutectic *** increased hardness from~HV 512.3 to~HV 734.1 is due to solid-solution strengthening,grain refinement strengthening and precipitated phase *** a few oxides(Al_(2)O_(3)+Cr_(2)O_(3)) caused by the wear heating contribute to an 85.5% decrease in wear rate of the HEA system from6.71×10^(-5) to 0.97×10^(-5) m^(3)·N^(-1)·m^(-1).In addition,Hf addition changes the wear mechanism from abrasive wear,mild oxidative wear and adhesive wear to oxidative wear and adhesive wear.

关键词： High entropy alloy Laves phase Hardness Wear mechanism

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