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ROS-responsive nanoparticles targeting inflamed colon for synergistic therapy of inflammatory bowel disease via barrier repair and anti-inflammation

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Nano Research 2024年第6期17卷 5409-5423页

作者： ding Wang Qi Jiang Ruoyu Shen Lijun Peng Wentao zhou Tingting Meng Fuqiang Hu Jianwei Wang Hong Yuan College of Pharmaceutical Science Zhejiang UniversityHangzhou 310058China Jinhua Institute of Zhejiang University Jinhua 321299China The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310009China

The destruction of the intestinal barrier is likely to cause an increase in intestinal permeability and cause pathological *** studies have demonstrated that intestinal barrier function plays an important role in the occurrence and development of inflammatory bowel disease(IBD).Oral administration is the most common route for intestinal *** this study,a synergistic strategy is proposed for IBD management through active barrier repair combined with anti-inflammatory treatment,which can interrupt the pathological process of IBD,resulting in the significantly improved efficacy of existing *** on the specific pH values and high reactive oxygen species(ROS)levels in inflammatory sites of IBD,an orally administrated ROS-responsive drug delivery system targeting inflamed colon has been designed,and confirmed in vitro and in *** anti-inflammatory drug dexamethasone acetate(Dex)and the barrier function regulator LY294002 are delivered by the synthesized nanocarrier to treat IBD synergistically by inhibiting inflammation and actively repairing the intestinal barrier through tight junctions(TJs).The accumulation of nanocarriers in the inflamed colon and synergistic efficacy has been validated in mice with *** brief,a drug delivery system and a therapeutic strategy for IBD are successfully developed.

关键词： nanotechnology reactive oxygen species(ROS)-responsive targeted delivery inflammatory bowel disease(IBD) intestinal barrier combination treatment

Natural evidence of coronaviral 2′-O-methyltransferase activity affecting viral pathogenesis via improved substrate RNA binding

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2819-2834页

作者： Jikai Deng Shimin yang Yingjian Li Xue Tan Jiejie Liu Yanying Yu Qiang ding Chengpeng Fan Hongyun Wang Xianyin Chen Qianyun Liu Xiao Guo Feiyu Gong Li zhou Yu Chen State Key Laboratory of Virology RNA InstituteCollege of Life Sciences and Frontier Science Center for Immunology and MetabolismWuhan UniversityWuhanChina School of Medicine Tsinghua UniversityBeijingChina School of Basic Medical Sciences Wuhan UniversityWuhanChina Animal Bio-Safety Level Ⅲ Laboratory/Institute for Vaccine Research Wuhan University School of MedicineWuhanChina

Previous studies through targeted mutagenesis of K-D-K-E motif have demonstrated that 2′-O-MTase activity is essential for efficient viral replication and immune ***,the K-D-K-E catalytic motif of 2′-O-MTase is highly conserved across numerous viruses,including flaviviruses,vaccinia viruses,coronaviruses,and extends even to ***,we observed a stronger 2′-O-MTase activity in SARS-CoV-2 compared to SARS-CoV,despite the presence of a consistently active catalytic *** further identified critical residues(Leu-36,Asn-138 and Ile-153)which served as determinants of discrepancy in 2′-O-MTase activity between SARS-CoV-2 and *** residues significantly enhanced the RNA binding affinity of 2′-O-MTase and boosted its versatility toward RNA *** interest,a triple substitution(Leu^(36)→Ile^(36),Asn^(138)→His^(138),Ile^(153)→Leu^(153),from SARS-CoV-2 to SARS-CoV)within nsp16 resulted in a proportional reduction in viral 2′-O-methylation and impaired viral ***,it led to a significant upregulation of type I interferon(IFN-I)and proinflammatory cytokines both in vitro and vivo,relying on the cooperative sensing of melanoma differentiation-associated protein 5(MDA5)and laboratory of genetics and physiology 2(LGP2).In conclusion,our findings demonstrated that alterations in residues other than K-D-K-E of 2′-O-MTase may affect viral replication and subsequently influence *** changes in nsp16 residues is crucial as it may aid in identifying and assessing future alteration in viral pathogenicity resulting from natural mutations occurring in nsp16.

关键词： pathogenesis impaired alterations

Flake channels construction of hydroxyapatite/gelatin cryogel with excellent flame retardant properties for enhancing the capturing of iodine

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Collagen and Leather 2024年第1期5卷 101-112页

作者： Yanxia Wei Bo Wang Liyan Cao Xin Cheng Yuhan Qiao Tao Duan Guiqiang He Pingping ding Yan zhou Jian zhou Engineering Research Center of Biomass Materials School of Life Science and EngineeringMinistry of EducationSouthwest University of Science and Technology The Collelge of Nuclear Technology and Automation Engineering Chengdu University of Technology NHC Key Laboratory of Nuclear Technology Medical Transformation Mianyang Central Hospital

Safe and efficient capturing of volatile radioiodine is of extremely important significance in the treatment of spent ***,the flake channels in gelatin-hydroxyapatite（HAP@Ge） cryogel with excellent flame retardant properties were constructed by immobilizing hydroxyapatite nanorods（HAP） on Gelatin（Ge） cryogel for enhancing the capturing of *** immobilization of HAP nanorods enhanced thermal stability,provided low rates of dynamic heat transfer and dissipation,and remarkably improved the flame retardant and smoke suppression properties of the Ge cryogel,which can effectively prevent the occurrence of safety incidents caused by further thermal degradation or combustion of this *** importantly,it was effective in improving the rapid enrichment of iodine,resulting in a high adsorption *** maximum adsorption capacity of HAP@Ge cryogel for iodine vapor reached2693 mg/g at *** high adsorption capacity for iodine was attributed to the multi-scale porous structure in HAP@Ge cryogel,which offered effective channels for iodine diffusion,whereas the numerous complex and irregular flakes provided sufficient number of active sites for iodine *** adsorption process was chemical in nature and involved the-PO43-,-OH,-C=O,and-NHR groups on HAP@Ge ***,the complex porous structure of HAP@Ge cryogel enhanced the physical capturing of *** advantages,such as low-cost raw material,simple preparation method,good flame retardancy,and excellent capturing performance for iodine indicated that HAP@Ge cryogel is a potential candidate for the removal of radioactive iodine in the exhaust gas stream of post-treatment plants.

关键词： Gelatin Hydroxyapatite nanorod Flake channel Flame retardancy Iodine capture

Deep learning framework for comprehensive molecular and prognostic stratifications of triple-negative breast cancer

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Fundamental Research 2024年第3期4卷 678-689页

作者： Shen Zhao Chao-yang Yan Hong Lv Jing-Cheng yang Chao You Zi-Ang Li ding Ma Yi Xiao Jia Hu Wen-Tao yang Yi-zhou Jiang Jun Xu Zhi-Ming Shao Key Laboratory of Breast Cancer in Shanghai Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghai 200032China Institute for AI in Medicine School of Artificial IntelligenceNanjing University of Information Science and TechnologyNanjing 210044China Department of Pathology Fudan University Shanghai Cancer CenterShanghai 200032China Greater Bay Area Institute of Precision Medicine Guangzhou 511466China Department of Radiology Fudan University Shanghai Cancer CenterShanghai 200032China

Triple-negative breast cancer(TNBC)is the most challenging breast cancer *** stratification and target therapy bring clinical benefit for TNBC patients,but it is difficult to implement comprehensive molecular testing in clinical ***,using our multi-omics TNBC cohort(N=425),a deep learning-based framework was devised and validated for comprehensive predictions of molecular features,subtypes and prognosis from pathological whole slide *** framework first incorporated a neural network to decompose the tissue on WSIs,followed by a second one which was trained based on certain tissue types for predicting different ***-omics molecular features were analyzed including somatic mutations,copy number alterations,germline mutations,biological pathway activities,metabolomics features and immunotherapy *** was shown that the molecular features with therapeutic implications can be predicted including the somatic PIK3CA mutation,germline BRCA2 mutation and PD-L1 protein expression(area under the curve[AUC]:0.78,0.79 and 0.74 respectively).The molecular subtypes of TNBC can be identified(AUC:0.84,0.85,0.93 and 0.73 for the basal-like immune-suppressed,immunomodulatory,luminal androgen receptor,and mesenchymal-like subtypes respectively)and their distinctive morphological patterns were revealed,which provided novel insights into the heterogeneity of TNBC.A neural network integrating image features and clinical covariates stratified patients into groups with different survival outcomes(log-rank P<0.001).Our prediction framework and neural network models were externally validated on the TNBC cases from TCGA(N=143)and appeared robust to the changes in patient *** potential clinical translation,we built a novel online platform,where we modularized and deployed our framework along with the validated *** can realize real-time one-stop prediction for new *** summary,using only pathological WSIs,our proposed framework

关键词： Triple-negative breast cancer Deep learning Digital pathology Patient stratification Online platform

High-performance wood-based thermoelectric sponges for thermal energy harvesting and smart buildings

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Nano Research 2024年第6期17卷 5349-5357页

作者： ding Zhang Qi Li Yanjie Fang Peijia Bai Lili Liu Jiaqi Guo Guangfa Wang Yuetong zhou Rujun Ma School of Materials Science and Engineering National Institute for Advanced MaterialsSmart Sensing Interdisciplinary Science CenterNankai UniversityTianjin 300350China

The development of renewable woods for power generation can help improve the energy efficiency of buildings,and promote the concept design and implementation of“smart buildings”.Here,with specific chemical treatment and hydrothermal synthesis,we demonstrated the practical value of natural wood for thermoelectric power generation in smart *** prepared wood-based thermoelectric sponges show high Seebeck coefficients of 320.5 and 436.6μV/K in the vertical and parallel directions of the longitudinal channel of *** 500 cycles of the compressive strain at 20%,the corresponding Seebeck coefficients increase up to 413.4 and 502.1μV/K,respectively,which is attributed to the improved contact and connection between tellurium thermoelectric *** Seebeck coefficients are much larger than those of most reported inorganic thermoelectric ***,the thermoelectric sponges maintain excellent thermoelectric and mechanical *** further modeled the application value of wood-based thermoelectric sponges in smart buildings for power *** high thermoelectric electricity can be obtained,such as in Beijing with over 1.5 million kWh every year,demonstrating the great potential in thermal energy harvest and energy supply.

关键词： wood thermoelectric effect thermal energy harvesting smart buildings energy supply

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia:a multicenter,randomized,open-label,phase 3 trial

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2669-2678页

作者： Biqi zhou Jia Chen Tianhui Liu Yishan Ye Yanming Zhang Yiyang ding Hong Liu MingQing Zhu Xiao Ma Xiaoli Li Longfei Zhao Zhihong Lin He Huang yang Xu Depei Wu National Clinical Research Center for Hematologic Diseases Jiangsu Institute of HematologyThe First Affiliated Hospital of Soochow UniversitySuzhouChina Institute of Blood and Marrow Transplantation Collaborative Innovation Center of HematologySoochow UniversitySuzhouChina Bone Marrow Transplantation Center The First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiangChina Department of Hematology The Affiliated Huai’an Hospital of Xuzhou Medical University and The Second People’s Hospital of Huai’anHuai’anChina Soochow Hopes Hematology Hospital SuzhouChina Department of Hematology Hygeia Suzhou Yongding HospitalSuzhouChina

Coinfusion of unrelated cord blood(UCB)units in haploidentical hematopoietic cell transplantation(haplo-HCT)(haplo-cord HCT)for hematopoietic malignancies showed promising results in previous reports,but the efficiency of haplo-cord HCT in acute myeloid leukemia(AML)still lacks sufficient *** multicenter,randomized,phase 3 trial(*** NCT03719534)aimed to assess the efficacy and safety of haplo-cord HCT in AML patients.A total of 268 eligible patients aged 18-60 years,diagnosed with measurable residual disease in AML(excluding acute promyelocytic leukemia),with available haploidentical donors and suitable for allotransplantation,were randomly allocated(1:1)to receive haplo-cord HCT(n=134)or haplo-HCT(n=134).The 3-year overall survival(OS)was the primary endpoint in this *** median follow-up was 36.50 months(IQR 24.75-46.50).The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group(80.5%,95%confidence interval[CI]:73.7-87.9 vs.67.8%95%CI 60.0-76.5,p=0.013).Favorable progression-free survival(70.3%,95%CI 62.6-78.8 vs.57.6%,95%CI 49.6-67.0,p=0.012)and cumulative incidence of relapse(12.1%,95%CI 12.0-12.2 vs.30.3%,95%CI 30.1-30.4,p=0.024)were observed in haplo-cord HCT *** 3-4 adverse events(AEs)within two years posttransplantation in the two groups were ***-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery(p=0.026)and increased T-cell reconstitution in the early period ***-cord HCT can improve OS in AML patients without excessive AEs,which may exert additional benefits for recipients of haplo-HCT.

关键词： hematopoietic acute phase

CGG repeat expansion in LOC642361/NUTM2B-AS1 typically presents as oculopharyngodistal myopathy

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Journal of Genetics and Genomics 2024年第2期51卷 184-196页

作者： Yan Shi Chunyan Cao Yiheng Zeng Yuanliang ding Long Chen Fuze Zheng Xuejiao Chen Fanggui zhou Xiefeng yang Jinjing Li Liuqing Xu Guorong Xu Minting Lin Hiroyuki Ishiura Shoji Tsuji Ning Wang Zhiqiang Wang Wan-Jin Chen Kang yang Department of Neurology and Institute of Neurology of First Affiliated Hospital Institute of NeuroscienceFujian Key Laboratory of Molecular NeurologyFujian Medical UniversityFuzhouFujian 350005China Department of Neurology National Regional Medical CenterBinhai Campus of the First Affiliated HospitalFujian Medical UniversityFuzhouFujian 350212China The First Affiliated Hospital College of Clinical Medicine of Henan University of Science and TechnologyLuoyangHenan 471000China Department of Neurology Zhangzhou Municipal Hospital of Fujian Province and Zhangzhou Affiliated Hospital of Fujian Medical UniversityZhangzhouFujian 363000China Department of Neurology Jian'ou Municipal Hospital of Fujian ProvinceJian'ouFujian 353100China Department of Radiology First Affiliated Hospital of Fujian Medical UniversityFuzhouFujian 350005China Department of Neurology Graduate School of MedicineThe University of TokyoTokyo 113-8655Japan Department of Neurology Okayama University Graduate School of MedicineDentistry and Pharmaceutical SciencesOkayama 700-8558Japan Institute of Medical Genomics International University of Health and WelfareChiba 286-0048Japan

CGG repeat expansions in LOC642361/NUTM2B-AS1 have recently been identified as a cause of oculopharyngeal myopathy with ***,since only three patients from a single family were reported,it remains unknown whether their clinicopathological features are typical for CGG repeat expansions in LOC642361/***,using repeat-primed-polymerase chain reaction and long-read sequencing,we identify 12 individuals from 3 unrelated families with CGG repeat expansions in LOC642361/NUTM2B-AS1,typically presenting with oculopharyngodistal *** CGG repeat expansions range from 161 to 669 repeat *** of the patients present with ptosis,restricted eye movements,dysphagia,dysarthria,and diffuse limb muscle *** one patient shows T2-weighted hyperintensity in the cerebellar white matter surrounding the deep cerebellar nuclei on brain magnetic resonance *** biopsies from three patients show a myopathic pattern and rimmed *** of muscle biopsies suggest that CGG repeat expansions in LOC642361/NUTM2B-AS1 may deleteriously affect aggrephagic capacity,suggesting that RNA toxicity and mitochondrial dysfunction may contribute to *** study thus expands the phenotypic spectrum for the CGG repeat expansion of LOC642361/NUTM2B-AS1 and indicates that this genetic variant typically manifests as oculopharyngodistal myopathy with chronic myopathic changes with rimmed vacuoles and filamentous intranuclear inclusions in muscle fibers.

关键词： Oculopharyngeal myopathy with leukoencephalopathy Oculopharyngodistal myopathy CGG repeat expansion Rimmed vacuoles

Highly stretchable double-network gel electrolytes integrated with textile electrodes for wearable thermo-electrochemical cells

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SusMat 2024年第4期4卷 77-89页

作者： Yuetong zhou ding Zhang Shuai Zhang Yuqing Liu Rujun Ma Gordon Wallace Jun Chen School of Materials Science and Engineering National Institute for Advanced MaterialsNankai UniversityTianjinChina Intelligent Polymer Research Institute ARC Centre of Excellence for Electromaterials ScienceAustralian Institute for Innovative MaterialsUniversity of WollongongNorth WollongongNew South WalesAustralia State Key Laboratory of Electronic Thin Film and Integrated Devices University of Electronic Science and Technology of ChinaChengduChina

Thermo-electrochemical cells(TECs)provide a new potential for self-powered devices by converting heat energy into ***,challenges still remain in the fabrication of flexible and tough gel electrolytes and their compat-ibility with redox actives;otherwise,contact problems exist between electrolytes and electrodes during stretching or ***,a novel robust and neutral hydrogel with outstanding stretchability was developed via double-network of crosslinked carboxymethyl chitosan and polyacrylamide,which accommodated both n-type(Fe^(2+)/Fe^(3+))and p-type([Fe(CN)_(6)]^(3-)/[Fe(CN)_(6)]^(4-))redox couples and maintained stretchability(>300%)and recoverability(95%compression).Moreover,poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate)textile elec-trodes with porous structure are integrated into gel electrolytes that avoid contact issues and effectively boost the P_(max) of n-and p-type thermocell by 76%and 26%,*** optimized thermocell exhibits a quick current density response and is continually fully operational under deformations,which satisfies the working conditions of wearable *** thermocells(four pairs)are effectively connected in alternating single n-and p-type cells in series and out-putted nearly 74.3 mV atΔT=10℃.The wearable device is manufactured into a soft-pack thermocells to successfully harvest human body heat and illuminate an LED,demonstrating the potential of the actual application of the thermocell devices.

关键词： human body heat porous textile electrodes stretchable double-network hydrogel electrolytes thermo-electrochemical cells wearable devices

Effects of sevoflurane on left ventricular function by speckletracking echocardiography in coronary bypass patients: A randomized trial

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The Journal of Biomedical Research 2024年第1期38卷 76-86页

作者： Chanjuan Gong Xiaokai zhou Yin Fang Yanjuan Zhang Linjia Zhu Zhengnian ding Department of Anesthesiology and Perioperative Medicine the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China Department of Cardiology the First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu 210029China.

The present study aimed to dynamically observe the segmental and global myocardial movements of the left ventricle during coronary artery bypass grafting by transesophageal speckle-tracking echocardiography,and to assess the effect of sevoflurane on cardiac ***-four patients scheduled for the off-pump coronary artery bypass grafting were randomly divided into a sevoflurane-based anesthesia(AS)group and a propofolbased total intravenous anesthesia(AA)*** AS group demonstrated a higher absolute value of left ventricular global longitudinal strain than that of the AA group at both T1(after harvesting all grafts and before coronary anastomosis)and T_(2)(30 min after completing all coronary anastomoses)(Pding artery graft was superior,and the postoperative concentration of troponin T decreased rapidly in the AS group,compared with the AA group(Pdings need to be replicated in larger studies.

关键词： coronary artery bypass grafting speckle-tracking echocardiography sevoflurane transesophageal echocardiography