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M1-polarized macrophage-derived cellular nanovesicle-coated lipid nanoparticles for enhanced cancer treatment through hybridization of gene therapy and cancer immunotherapy

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Acta Pharmaceutica Sinica B 2024年第7期14卷 3169-3183页

作者： Ha Eun Shin Jun-Hyeok Han Seungyong Shin Ga-Hyun Bae Boram Son Tae-Hyung kim hee Ho Park Chun Gwon Park Wooram Park Department of Integrative Biotechnology Sungkyunkwan University(SKKU)SuwonGyeonggi 16419Republic of Korea Deparment of Inteligent Precision Healthcare Convergence SKKUSuwonGyeonggi 16419Republic of Korea Department of MetaBioHealth SKKU Institute for ConvergenceSKKUSuwonGyeonggi 16419Republic of Korea Department of Bioengineering Hanyang UniversitySeoul 04763Republic of Korea Department of Integrative Engineering Chung-Ang UniversitySeoul 06974Republic of Korea Department of Biomedical Engineering SKKUSuwonGyeonggi 16419Republic of Korea Korea Institute of Science and Technology(KIST) Seoul 02792Republic of Korea

Optimum genetic delivery for modulating target genes to diseased tissue is a major obstacle for profitable gene *** nanoparticles(LNPs),considered a prospective vehicle for nucleic acid delivery,have demonstrated efficacy in human use during the COVID-19 *** study introduces a novel biomaterial-based platform,M1-polarized macrophage-derived cellular nanovesicle-coated LNPs(M1-C-LNPs),specifically engineered for a combined gene-immunotherapy approach against solid *** dual-function system of M1-C-LNPs encapsulates Bcl2-targeting siRNA within LNPs and immune-modulating cytokines within M1 macrophage-derived cellular nanovesicles(M1-NVs),effectively facilitating apoptosis in cancer cells without impacting T and NK cells,which activate the intratumoral immune response to promote granule-mediating killing for solid tumor *** retention within tumor was observed upon intratumoral administration of M1-C-LNPs,owing to the presence of adhesion molecules on M1-NVs,thereby contributing to superior tumor growth *** findings represent a promising strategy for the development of targeted and effective nanoparticle-based cancer genetic-immunotherapy,with significant implications for advancing biomaterial use in cancer therapeutics.

关键词： Genetic-immunotherapy M1 macrophage-derived cellular nanovesicles Lipid nanoparticles(LNPs) Gene therapy siRNA Cancer immunotherapy Solid tumor Tumor microenvironment(TME)

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Anomaly Detection Using Data Rate of Change on Medical Data

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Computers, Materials & Continua 2024年第9期80卷 3903-3916页

作者： Kwang-cheol Rim Young-Min Yoon Sung-Uk kim Jeong-In kim AI Convergence Research Institute Chosun UniversityGwangju61452Republic of Korea Interdisciplinary Program of Architectural Studies Chonnam UniversityGwangju61186Republic of Korea AINTCHAIN SOFT Co. Ltd.Mokpo-si58750Republic of Korea BK21 Human Resources Development Project Group Chosun UniversityGwangju61452Republic of Korea

The identification and mitigation of anomaly data,characterized by deviations from normal patterns or singularities,stand as critical endeavors in modern technological landscapes,spanning domains such as Non-Fungible Tokens(NFTs),cyber-security,and the burgeoning *** paper presents a novel proposal aimed at refining anomaly detection methodologies,with a particular focus on continuous data *** essence of the proposed approach lies in analyzing the rate of change within such data streams,leveraging this dynamic aspect to discern anomalies with heightened precision and *** empirical evaluation,our method demonstrates a marked improvement over existing techniques,showcasing more nuanced and sophisticated result ***,we envision a trajectory of continuous research and development,wherein iterative refinement and supplementation will tailor our approach to various anomaly detection scenarios,ensuring adaptability and robustness in real-world applications.

关键词： Anomaly data anomaly detection medical anomaly data cyber security rate of change

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Non-surgical treatment of diabetic foot ulcers on the dorsum of the foot with polydeoxyribonucleotide injection:Two case reports

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World Journal of Clinical Cases 2024年第20期12卷 4446-4451页

作者： Yooseok Ha Jeong-hee kim Jiyoung kim Hyeokjae Kwon Department of Plastic and Reconstructive Surgery Chungnam National University HospitalDaejeon 35015South Korea College of Nursing Woosuk UniversityWanju-gun 55338South Korea

BACKGROUND Diabetic foot ulcers are caused by a variety of factors,including peripheral neuropathy,peripheral arterial disease,impaired wound healing mechanisms,and repetitive *** with diabetic foot ulcer on the dorsum of the foot are often treated ***,the right non-surgical therapy must be chosen if surgical choices are contraindicated or if the patient prefers conservative treatment over *** SUMMARY The purpose of this case report is to highlight the efficacy of polydeoxyribonucleotide(PDRN)injection as a non-surgical treatment option for diabetic foot ulcers on the dorsum of the foot,particularly in patients who choose against surgical *** case report presents two cases of diabetic foot ulcers located on the dorsum of the foot that were successfully treated with PDRN injection as a non-surgical *** If the patient declines surgery for diabetic ulcers with Wagner grade II or below,PDRN injection can be effective if necrotic tissue is removed and the wound bed kept clean.

关键词： Diabetic foot Wound healing Regenerative medicine Polydeoxyribonucleotides Case report

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Oral transforming growth factor-beta receptor 1 inhibitor vactosertib promotes osteosarcoma regression by targeting tumor proliferation and enhancing anti-tumor immunity

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Cancer Communications 2024年第8期44卷 884-888页

作者： Sung hee Choi Jay Thomas Myers Suzanne Louise Tomchuck Melissa Bonner Saada Eid Daniel Tyler Kingsley Kristen Ashley Van Heyst Seong-Jin kim Byung-Gyu kim Alex Yee-Chen Huang Department of Pediatrics CaseWestern Reserve University School of MedicineClevelandOhioUSA Case Comprehensive Cancer Center CaseWestern Reserve University School of MedicineClevelandOhioUSA Department of Pathology CaseWestern Reserve University School of MedicineClevelandOhioUSA MedPacto Inc. SeoulRepublic of Korea Center for Pediatric Immunotherapy Angie Fowler AYA Cancer InstituteUH Rainbow Babies and Children’s HospitalClevelandOhioUSA

Osteosarcoma is an aggressive malignant bone sarcoma common among children,adolescents,and young *** 20%of patients present with pulmonary metastasis,and an additional 40%develop pulmonary osteosarcoma *** survival ou... 详细信息

关键词： osteosarcoma immunity patients

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The processed C-terminus of AvrRps4 effector suppresses plant immunity via targeting multiple WRKYs

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Journal of Integrative Plant Biology 2024年第8期66卷 1769-1787页

作者： Quang-Minh Nguyen Arya Bagus Boedi Iswanto Hobin Kang Jiyun Moon Kieu Anh Thi Phan Geon Hui Son Mi Chung Suh Eui-Hwan Chung Walter Gassmann Sang hee kim Division of Applied Life Science(BK21 Four Program) Plant Molecular Biology and Biotechnology Research CenterGyeongsang National UniversityJinju 52828Korea Department of Life Science Sogang UniversitySeoul 04107Korea Department of Plant Biotechnology Korea UniversitySeoul 02841Korea Division of Plant Science and Technology Christopher S.Bond Life Sciences Center and Interdisciplinary Plant GroupUniversity of MissouriColumbiaMissouri 65211USA Division of Life Science and Research Institute of Molecular Alchemy Gyeongsang National UniversityJinju 52828Korea

Pathogens generate and secrete effector proteins to the host plant cells during pathogenesis to promote virulence and *** the plant carries resistance(R)proteins that recognize pathogen effectors,effector-triggered immunity(ETI)is activated,resulting in a robust immune response and hypersensitive response(HR).The bipartite effector AvrRps4 from Pseudomonas syringae *** has been well studied in terms of avirulence *** planta,AvrRps4 is processed into two *** Cterminal fragment of AvrRps4(AvrRps4^(C))induces HR in turnip and is recognized by the paired resistance proteins AtRRS1/AtRPS4 in ***,we show that AvrRps4^(C)targets a group of Arabidopsis WRKY,including WRKY46,WRKY53,WRKY54,and WRKY70,to induce its virulence ***,AvrRps4^(C)suppresses the general binding and transcriptional activities of immune-positive regulator WRKY54 and WRKY54-mediated ***4^(C)interferes with WRKY54's binding activity to target gene SARD1 in vitro,suggesting WRKY54 is sequestered from the SARD1 promoter by AvrRps4^(C).Through the interaction of Avr Rps4^(C)with four WRKYs,AvrRps4 enhances the formation of homo-/heterotypic complexes of four WRKYs and sequesters them in the cytoplasm,thus inhibiting their function in plant ***,our results provide a detailed virulence mechanism of AvrRps4 through its C-terminus.

关键词： AvrRps4 bacterial effector effector-triggered immunity immune response suppression transcription factor WRKY

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High Na-ion conductivity andmechanical integrity of anion-exchanged polymeric hydrogel electrolytes for flexible sodium ion hybrid energy storage

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SusMat 2024年第1期4卷 140-153页

作者： JungWoo Hong Harpalsinh H.Rana Jeong hee Park Jun Su kim Sang Joon Lee Gun Jang Tae Hoon Kang Kang Ho Shin Sang Ha Baek Wooseok Yang Kwang Ho kim Ju-Hyuk Lee Ho Seok Park School of Chemical Engineering Sungkyunkwan UniversitySuwonRepublic of Korea Clean Energy Research Center Korea Institute of Science and Technology(KIST)SeoulRepublic of Korea KIST-SKKU Carbon-Neutral Research Center Sungkyunkwan University(SKKU)SuwonRepublic of Korea SKKU Institute of Energy Science and Technology(SIEST) Sungkyunkwan UniversitySuwonRepublic of Korea COSMOS LAB/92 Jomaru-ro 385beon-gilBucheon-siRepublic of Korea SKKU Advanced Institute of Nano Technology(SAINT) Sungkyunkwan UniversitySuwonRepublic of Korea Department of Health Sciences and Technology Samsung Advanced Institute for Health Sciences and Technology(SAIHST)Sungkyunkwan UniversitySuwonRepublic of Korea

The polymeric gel electrolytes are attractive owing to their higher ionic conductivities than those of dry polymer electrolytes and lowered water activity for enlarged potential ***,the ionic conductivity and mechanical strength of the Na-ion conducting polymeric gel electrolytes are limited by below 20 mS cm−1 and 2.2 ***,we demonstrate Na-ion conducting and flexible polymeric hydrogel electrolytes of the chemically coupled poly(diallyldimethylammonium chloride)-dextrin-N,N′-methylene-bisacrylamide film immersed in NaClO_(4) solution(ex-DDA-Dex+NaClO_(4))for flexible sodium-ion hybrid capacitors(f-NIHC).In particular,the anion exchange reaction and synergistic interaction of ex-DDA-Dex with the optimum ClO_(4)−enable to greatly improve the ionic conductivity up to 27.63 mS cm−1 at 25◦C and electrochemical stability window up to 2.6 V,whereas the double networking structure leads to achieve both the mechanical strength(7.48 MPa)and softness of hydrogel ***,the f-NIHCs with the ex-DDA-Dex+NaClO_(4) achieved high specific and high-rate capacities of 192.04 F g^(−1)at 500 mA g^(−1)and 116.06 F g^(−1)at 10000 mA g^(−1),respectively,delivering a large energy density of 120.03Wh kg^(−1)at 906Wkg^(−1)and long cyclability of 70%over 500 cycles as well as demonstrating functional operation under mechanical stresses.

关键词： anion exchange chemistry flexible energy storage hybrid energy storage hydrogel electrolytes renewable electrolytes sodium storage

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Glucose-mediated mitochondrial reprogramming by cholesterol export at TM4SF5-enriched mitochondria-lysosome contact sites

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Cancer Communications 2024年第1期44卷 47-75页

作者： Ji Eon kim So-Young Park Chulhwan Kwak Yoonji Lee Dae-Geun Song Jae Woo Jung Haesong Lee Eun-Ae Shin Yangie Pinanga Kyung-hee Pyo Eun Hae Lee Wonsik kim Soyeon kim Chang-Duck Jun Jeanho Yun Sun Choi Hyun-Woo Rhee Kwang-Hyeon Liu Jung Weon Lee Department of Pharmacy College of PharmacySeoul National UniversitySeoulRepublic of Korea Research Institute of Pharmaceutical Sciences College of PharmacySeoul National UniversitySeoulRepublic of Korea BK21 FOUR Community-Based Intelligent Novel Drug Discovery Education Unit College of Pharmacy and Research Institute of Pharmaceutical SciencesKyungpook National UniversityDaeguRepublic of Korea Department of Chemistry Seoul National UniversitySeoulRepublic of Korea College of Pharmacy Chung-Ang UniversitySeoulRepublic of Korea Natural Product Informatics Research Center Korea Institute of Science and Technology(KIST)Gangneung-siGangwon-doRepublic of Korea School of Life Sciences Gwangju Institute of Science and Technology(GIST)GwangjuRepublic of Korea Department of Biochemistry College of MedicineDong-A UniversityBusanRepublic of Korea Global AI Drug Discovery Center College of Pharmacy and Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoulRepublic of Korea Interdisciplinary Program in Genetic Engineering Seoul National UniversitySeoulRepublic of Korea

Background:Transmembrane 4 L six family member 5(TM4SF5)translocates subcellularly and functions metabolically,although it is unclear how intracellu-lar TM4SF5 translocation is linked to metabolic *** is thus of interests to understand how the traffic dynamics of TM4SF5 to subcellular endosomal membranes are correlated to regulatory roles of ***:Here,we explored the metabolic significance of TM4SF5 localization at mitochondria-lysosome contact sites(MLCSs),using in vitro cells and in vivo animal systems,via approaches by immunofluorescence,proximity labelling based proteomics analysis,organelle reconstitution ***:Upon extracellular glucose repletion following depletion,TM4SF5 became enriched at MLCSs via an interaction between mitochondrial FK506-binding protein 8(FKBP8)and lysosomal *** labeling showed molecular clustering of phospho-dynamic-related protein I(DRP1)and certain mitophagy receptors at TM4SF5-enriched MLCSs,leading to mitochondrial fis-sion and ***4SF5 bound NPC intracellular cholesterol transporter 1(NPC1)and free cholesterol,and mediated export of lysosomal cholesterol to mitochondria,leading to impaired oxidative phosphorylation but intact tri-carboxylic acid(TCA)cycle andβ-*** mouse models,hepatocyte Tm4sf5 promoted mitophagy and cholesterol transport to mitochondria,both with positive relations to liver ***:Our findings suggested that TM4SF5-enriched MLCSs regu-late glucose catabolism by facilitating cholesterol export for mitochondrial reprogramming,presumably while hepatocellular carcinogenesis,recapitulating aspects for hepatocellular carcinoma metabolism with mitochondrial repro-gramming to support biomolecule synthesis in addition to glycolytic energetics.

关键词： cholesterol fluorescent imaging glucose catabolism hepatocellular carcinogenesis mem-brane contact sites mitochondria function mitophagy oxidative phosphorylation protein-protein interaction tetraspanin

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Strengthening mechanisms analysis and tailoring of bimodal grain structures for enhanced strength in CoCrFeMnNi high-entropy alloys

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Rare Metals 2024年第8期43卷 3893-3903页

作者： Jaesoung Lee Seulgi kim Taehyun Kwon Young II kim Suyeon kim Sung Ho Song Bin Lee Dongju Lee Department of Urban Energyand Environmental EngineeringChungbuk National UniversityCheongju 28644Republic of Korea Division of Advanced Materials Engineering Kongju National UniversityChungnam 330-717Republic of Korea Department of Advanced Materials Engineering for Information and Electronics Integrated-Education Institute for Frontier Science and Technology(BK21 Four)Kyung Hee UniversityYongin17104Republic of Korea

The CoCrFeMnNi high-entropy alloys(HEAs)with a(face-centered cubic) FCC structure has garnered considerable attention for its exceptional ductility and strain hardening ***,its yield strength is insufficient for structural *** this study,strengthening mechanisms in these HEAs were investigated to gain insight into the mechanical properties according to alloy powder ***,we present a novel approach to achieve both high strength and high ductility through the creation of a bimodal structure consisting of both coarse and fine grains via gas atomization and spark plasma sintering processes.A bimodally structured HEA prepared with a mass ratio of 2:8 between coarse particles(75-106 μm) and fine particles(≤25 μm)yielded optimal results,with a strength of 491.95 MPa and elongation of 19.64%.This strength value represents an~41% increase compared with the sample that displayed a fine single microstructure(347.08 MPa for yield strength).The strength enhancement was attributed to the prevention of plastic deformation initiation from the fine particles during *** innovative approach to the creation of HEAs with bimodal structures shows promise for various applications,such as structural components that require a combination of high strength and high ductility.

关键词： High-entropy alloys CrCoFeMoNi Bimodal Gas atomization Mechanical properties

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Inhibiting scar formation via wearable multilayer stacked electret patch:Self-creation of persistent and customizable DC electric field for fibrogenic activity restriction

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InfoMat 2024年第3期6卷 66-80页

作者： Sung-Won kim Sumin Cho Donghan Lee Jiyu Hyun Sunmin Jang Inwoo Seo Hyun Su Park hee Jae Hwang Hyung-Seop Han Dae Hyeok Yang Heung Jae Chun Suk Ho Bhang Dongwhi Choi School of Chemical Engineering Sungkyunkwan UniversitySuwonRepublic of Korea Department of Mechanical Engineering(Integrated Engineering Program) Kyung Hee UniversityYonginGyeonggiRepublic of Korea Biomaterials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)SeoulRepublic of Korea Department of Medical Life Sciences College of MedicineInstitute of Cell and Tissue EngineeringThe Catholic University of KoreaSeoulRepublic of Korea

Electrical stimulation has recently received attention as noninvasive treatment in skin wound healing with its outstanding biological property for clinical set***,the complexity of equipment for applying appropriate electrical stimulation remains an ongoing ***,we proposed a strategy for skin scar inhibition by providing electrical stimulation via a multilayer stacked electret(MS-electret),which can generate direct current(DC)electric field(EF)without any power supply *** addition,the MS-electret can easily control the intensity of EFs by simply stacking electret layers and maintain stable EF with the surface potential of 3400 V over 5 days owing to the injected charges on the electret *** confirmed inhibition of type 1 collagen andα-SMA expression of human dermal fibroblasts(hDFs)by 90%and 44%in vitro,indicating that the transition of hDFs to myofibroblasts was restricted by applying stable electrical *** further revealed a 20%significant decrease in the ratio of myofibroblasts caused by the MS-electret in *** findings present that the MS-electret is an outstanding candidate for effective skin scar inhibition with a battery-free,physiological electrical microenvironment,and noninvasive treatment that allows it to prevent external infection.

关键词： DC electric field dermal fibroblasts electret scar formation restriction self-creation of electrical stimulation

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Galectin 3-binding protein(LGALS3BP)depletion attenuates hepatic fibrosis by reducing transforming growth factor-β1(TGF-β1)availability and inhibits hepatocarcinogenesis

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Cancer Communications 2024年第10期44卷 1106-1129页

作者： Dae-Hwan kim Minjeong Sung Myong-Suk Park Eun-Gene Sun Sumin Yoon Kyung Hyun Yoo Kamalakannan Radhakrishnan Sung Yun Jung Woo-Kyun Bae Sang-hee Cho Ik-Joo Chung Department of Internal Medicine Division of Hematology and OncologyChonnam National University Medical SchoolHwasunSouth Korea Department of Internal Medicine Division of Hematology and OncologyChonnam National University Hwasun HospitalHwasunSouth Korea Combinatorial Tumor Immunotherapy MRC Center Chonnam National University Medical SchoolHwasunSouth Korea National Immunotherapy Innovation Center HwasunSouth Korea BioMedical Sciences Graduate Program Chonnam National UniversityHwasunSouth Korea Department of Biological Science SookmyungWomen’s UniversitySeoulSouth Korea Clinical Vaccine R&D Center Chonnam National UniversityHwasunSouth Korea Department of Biochemistry and Molecular Pharmacology Baylor College of MedicineHoustonTexasUSA

Background:Increased Galectin 3-binding protein(LGALS3BP)serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma(HCC).Considering the crucial role of transforming growth factor-β1(TGF-β1)in the emergence of these diseases,the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling ***:The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis(MASH)and *** omics techniques,such as RNA-sequencing,transposaseaccessible chromatin-sequencing assay,and liquid chromatography-tandem mass spectrometry proteomics,were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 *** effects of altered TGF-β1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout ***:In patients with MASH and HCC,the levels of LGALS3BP and TGFB1 exhibited positive *** of LGALS3BP by the inflammatory cytokine interferonαin HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of *** fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice,with increased TGFB1 ***3BP directly bound to and assembled integrinαV,an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin *** released TGF-β1 activated JunB transcription factor,which in turn promoted the TGF-β1 positive feedback ***3BP deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced ***,LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β***:LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway,making it a promising therapeutic target in TGF-β1-related diseases.

关键词： F-actin FAK hepatic carcinogenesis IntegrinαV Interferonα JunB LGALS3BP metabolic dysfuntion-associated steatohepatitis tensile force TGF-β1

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