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Photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes to promote PD-L1 multivalent binding for effective immune checkpoint blockade therapy

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Acta Pharmaceutica Sinica B 2024年第3期14卷 1428-1440页

作者： Youngjoo Lee Sukyung Song Suah Yang Jinseong kim Yujeong Moon Nayeon Shim Hong Yeol Yoon Sehoon kim man Kyu Shim Kwangmeyung kim KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea Medicinal Materials Research Center Biomedical Research DivisionKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea College of Pharmacy Graduate School of Pharmaceutical SciencesEwha Womans UniversitySeoul 03760Republic of Korea Department of Bioengineering Korea UniversitySeoul 02841Republic of Korea

Immune checkpoint blockade(ICB)therapy targeting PD-L1 via monoclonal antibody(m Ab)has shown extensive clinical benefits in the diverse types of advanced ***,most patients are completely refractory to ICB therapy owing to the PD-L1 recycling ***,we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes(immune checkpoint blockade liposomes;ICB-LPs)to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor *** ICB-LPs are prepared by formulation of DC_(8,9)PC with photo-polymerized diacetylenic moiety,1,2-dipalmitoylphosphatidylcholine(DPPC)and anti-PD-L1peptide(D-form NYSKPTDRQYHF)-conjugated DSPE-PEG_(2k)(anti-PD-L1-DSPE-PEG_(2k))in a molar ratio of 45:45:10,followed by cross-linking of liposomal bilayer upon UV *** 10 mol% antiPD-L1-DSPE-PEG_(2k)incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7±1.04 nm,showing a high stability in serum ***,the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane,which are endocytosed with aim to deliver PD-L1 to the lysosomes,wherein the durable PD-L1 degradation is observed for72 h,in contrast to anti PD-L1 m Abs showing the rapid PD-L1 recycling within 9 *** in vitro coculture experiments with CD8^(+)T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 *** ICB-LPs are intravenously injected into colon tumor-bearing mice,they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting,inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 ***,this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward

关键词： Cancer immunotherapy Immune checkpoint blockade PEGylated liposome Crosslinked lipid nanoparticles Anti-PD-L1 peptide Tumor-targeting PD-L1 multivalent binding Lysosomal PD-L1 degradation

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Roots extracts of Adenophora triphylla *** improve obesity in 3T3-L1 adipocytes and high-fat diet-induced obese mice

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Asian Pacific Journal of Tropical Medicine 2015年第11期8卷 879-886页

作者： Dong-Ryung Lee Young-Sil Lee Bong-Keun Choi Hae Jin Lee Sung-Bum Park tack-man kim Han Jin Oh Seung Hwan Yang Joo-Won Suh NutraPham Tech Center for Nutraceutical and Pharmaceutical Materials Myongji University Interdisciplinary Program of Biomodulation Myongji University DONG IL Pharmtec Department of Family Medicine.VIEVIS NAMUH Hospital

Objective:To investigate the anti-obesity activity and the action mechanism of the roots of Adenophora triphylla *** extract(ATE) in high-fat diet(HFD)-induced obese mice and 3T3-LI ***:The roots of Ademption triphylla were extracted with 70%*** demonstrate the compounds,linoleic acid was analyzed by using gas chromatography:and the anti-obesity effects and possible mechanisms of ATE were examined in 3T3-L1 adipocytes and HFD-induced obese ***:Treatment with ATE inhibited the lipid accumulation without cytotoxicity in 3T3-L1 ***,200 and 400 mg/kg ATE treatment significantly decreased the body weight gain,white adipose tissues(WATs) weight and plasma triglyceride level,while 100 and 200 mg/kg ATE treatment increased the plasma high-density lipoprotein cholesterol level in the HFD-induced obese mice,as compared with the HFD *** with 200 and 400 mg/kg ATE also lowered the size of adipocytes in adipose tissue and reduced the lipid accumulation in *** treatment showed significantly lower expression level of adipogenesis-relatcd proteins,such as peroxisome proliferator-activated receptor y,fatty acid binding protein(aP2),fatty acid synthase in 3T3-L1 adipocytes;and furthermore,decreased peroxisome proliferatoractivated receptor γ,aP2,fatty acid synthase,sterol regulatory element binding protein-1c,and lipoprotein lipase mRNA expression levels in WAT of the HFD-induced obese ***:These results suggested that the ATE has an anti-obesity effect,which may be elicited by regulating the expression of adipogenesis and lipogenesis-related genes and proteins in adipocytes and WAT of the HFD-induced obese mice.

关键词： Roots of Adenophora triphylla var. japonica extrac

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Double-chambered left ventricle with a thrombus in an asymptomatic patient:A case report

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World Journal of Clinical Cases 2024年第2期12卷 460-465页

作者： Narae kim In-Ho Yang Hui-Jeong Hwang Il-Suk Sohn Department of Medicine Kyung Hee UniversitySeoul 02447South Korea Department of Cardiology Kyung Hee University Hospital at GangdongSeoul 05278South Korea

BACKGROUND Double-chambered left ventricle(DCLV)is an extremely rare congenital disease in which the left ventricle(LV)is divided by abnormal muscle *** to its rarity,there is a lack of data on the disease,including its diagnosis,treatment,and ***,we report a case in which DCLV was diagnosed and followed *** SUMMARY A 45-year-old man presented to our hospital due to abnormal findings on an electrocardiogram recorded during a health *** had no specific cardiac symptoms,comorbidities or relevant past medical *** revealed that the LV was divided into two by muscle *** were no findings of ischemia on coronary angiography and coronary computed tomography angiography performed to exclude differential *** comprehensive analysis of the images,DCLV was *** it seemed to be asymptomatic DCLV,we decided the patient was to be observed without administering any ***,follow-up echocardiography revealed a thrombus in the accessory chamber(AC).Anticoagulant medication was initiated,the thrombus resolved,and the patient is currently undergoing follow-up without any specific *** Asymptomatic,uncomplicated DCLV was diagnosed through multimodal imaging;however,a thrombus in the AC occurred during the *** findings highlight that multimodal imaging is essential in diagnosing DCLV,and that anticoagulation is important in its management.

关键词： Double-chambered left ventricle Congenital heart disease Left ventricular aneurysm Echocardiography Coronary computed tomography angiography Contrast echocardiography Case report

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Endoscopic ultrasound-guided tissue sampling induced pancreatic duct leak resolved by the placement of a pancreatic stent:A case report

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World Journal of Clinical Cases 2024年第9期12卷 1677-1684页

作者： Ki-Hyun kim Chang Hwan Park Eunae Cho Yohan Lee Department of Internal Medicine Chonnam National University HospitalGwangju 61469South Korea Department of Gastroenterology Chonnam National University HospitalGwangju 61469South Korea

BACKGROUND Pancreatic ductal leaks complicated by endoscopic ultrasonography-guided tissue sampling(EUS-TS)can manifest as acute *** SUMMARY A 63-year-old man presented with persistent abdominal pain and weight ***:Laboratory findings revealed elevated carbohydrate antigen 19-9(5920 U/mL)and carcinoembryonic antigen(23.7 ng/mL)*** resonance imaging of the pancreas revealed an approximately 3 cm ill-defined space-occupying lesion in the inferior aspect of the head,with severe encasement of the superior mesenteric *** ductal adenocarcinoma was confirmed after pathological examination of specimens obtained by EUS-TS using the fanning *** and outcomes:The following day,the patient experienced severe abdominal pain with high amylase(265 U/L)and lipase(1173 U/L)*** tomography of the abdomen revealed edematous wall thickening of the second portion of the duodenum with adjacent fluid collections and a suspicious leak from either the distal common bile duct or the main pancreatic duct in the *** retrograde cholangiopancreatography revealed dye leakage in the head of the main pancreatic ***,a 5F 7 cm linear plastic stent was deployed into the pancreatic duct to divert the pancreatic *** patient’s abdominal pain improved immediately after pancreatic stent insertion,and amylase and lipase levels normalized within a *** chemotherapy was then *** Using the fanning method in EUS-TS can inadvertently cause damage to the pancreatic duct and may lead to clinically significant *** a pancreatic stent may immediately resolve acute pancreatitis and shorten the waiting time for curative *** using the fanning method during EUSTS,ductal structures should be excluded to prevent pancreatic ductal leakage.

关键词： Endoscopic ultrasound-guided tissue sampling Pancreatitis Pancreatic duct leak Pancreatic stent Case report

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Primary Ewing sarcoma of the kidney mimicking cystic papillary renal cell carcinoma in an older patient:A case repor

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World Journal of Clinical Cases 2024年第15期12卷 2606-2613页

作者： Suhong kim Jongsoo Park Young Hwii Ko Hee Jung Kwon Department of Radiology Yeungnam UniversityDaegu 42415South Korea Department of Urology Yeungnam UniversityDaegu 42415South Korea Department of Pathology Yeungnam UniversityDaegu 42415South Korea

BACKGROUND Ewing’s sarcoma(ES)is a neuroectodermal tumor that typically occurs in the bones and soft tissues of children and young *** renal ES is rare;only a few cases and a small case series have been documented,and only four cases involved primary renal ES in older people(>65 years old).CASE SUMMARY Herein,we describe the radiological and pathological features of primary renal ES in an older person.A 76-year-old man complained of poor oral intake and was found to have a large cystic renal mass with indistinct margins on computed ***-guided biopsy revealed that the tumor contained small round blue *** patient underwent a right radical *** tumor cells showed diffuse membranous CD99,and nuclear friend leukemia integration 1 transcription factor and NK2 Homeobox *** in situ hybridization revealed EWSR1 ***,18F-fluorodeoxyglucose positron emission tomography revealed no evidence of *** patient was diagnosed with primary renal *** months following the surgery,local recurrence and distant metastasis were *** renal ES is rare and often lethal in older *** specific imaging findings are unknown,and treatment protocols have not been *** This case report describes the radiological and pathological features of primary renal ES in an older person.

关键词： Ewing sarcoma Elder Renal Kidney Neuroectodermal Case report

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Prothrombin kringle-2, a mediator of microglial activation: new insight in Alzheimer’s disease pathogenesis

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Neural Regeneration Research 2022年第12期17卷 2675-2676页

作者： Jae man Lee Sang Ryong kim Department of Biochemistry and Cell Biology Cell and Matrix Research InstituteSchool of MedicineKyungpook National UniversityDaeguKorea Brain Science and Engineering Institute Kyungpook National UniversityDaeguKorea School of Life Sciences BK21 FOUR KNU Creative BioResearch GroupInstitute of Life Science and BiotechnologyKyungpook National UniversityDaeguKorea

Microglial activation in Alzheimer’s disease(AD):In 1907,*** Alzheimer,a Bavarian-born German psychiatrist and neuropathologist,published an article describing the clinical and neuropathological features of an unclassified psychiatric *** disorder was later named AD and is currently the most common brain disorder(Takata et al.,2021).AD involves the accumulation of amyloid-β(Aβ)and hyperphosphorylated tau proteins in the brain,which are associated with senile plaques and neurofibrillary tangles,respectively(Vergara et al.,2019;Takata et al.,2021).AD is characterized by cognitive impairment and memory loss with hippocampal neurodegeneration(kim et al.,2021).

关键词： Alzheimer Aβ tau

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Cathepsin B-responsive prodrugs for cancer-targeted therapy:Recent advances and progress for clinical translation

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Nano Research 2022年第8期15卷 7247-7266页

作者： Seong Ik Jeon Suah Yang man Kyu Shim Kwangmeyung kim Biomedical Research Institute Korea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea KU-KIST Graduate School of Converging Science and Technology Korea UniversitySeoul 02841Republic of Korea

The cathepsin B-responsive prodrugs are promising strategies to reduce the serious adverse effects of anticancer drugs by improving the cancer selectivity that can be specifically activated by overexpressed cathepsin B in targeted cancer ***,clinical translation of such therapeutic approaches has been restricted by low antitumor efficacy that is mainly attributable to undesirable pharmacokinetic profiles and inefficient tumor-targeting of cathepsin B-responsive prodrugs,due to their small-molecule *** recent decades,many researchers have widely investigated the drug delivery system(DDS)to improve the in vivo pharmacokinetic profiles and tumor-targeting efficiency of cathepsin B-responsive prodrugs via the application of polymers,dendrimers,antibodies,lipids,and inorganic nanoparticles as drug *** addition,the potential therapeutic efficacy of DDS for cathepsin B-responsive prodrugs is demonstrated in multiple studies and combinatorial treatment with typical therapeutic modalities can effectively overcome the challenges of tumor heterogeneity and multidrug *** this review,recent advances and progress of new DDS for cathepsin B-responsive prodrugs are outlined,and their clinical trials are ***,potential challenges and the outlooks for clinical translation of cathepsin B-responsive prodrugs are highlighted.

关键词： cathepsin B prodrug chemotherapy drug delivery system targeted cancer therapy

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Graphene Bridge Heterostructure Devices for Negative Differential Transconductance Circuit Applications

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Nano-Micro Letters 2023年第2期15卷 161-171页

作者： Minjong Lee Tae Wook kim Chang Yong Park kimoon Lee Takashi Taniguchi Kenji Watanabe Min‑gu kim Do Kyung Hwang Young tack Lee Department of Electrical and Computer Engineering Inha UniversityIncheon 22212Republic of Korea Department of Materials Science and Engineering The University of Texas at DallasRichardsonTX 75080USA Center for Opto‑Electronic Materials and Devices Post‑Silicon Semiconductor InstituteKorea Institute of Science and Technology(KIST)Seoul 02792Republic of Korea Department of Physics Kunsan National UniversityGunsan 54150Republic of Korea Advanced Materials Laboratory National Institute for Materials ScienceTsukuba 305‑0044Japan Department of Information and Communication Engineering Inha UniversityIncheon 22212Republic of Korea Division of Nanoscience and Technology KIST SchoolUniversity of Science and Technology(UST)Seoul 02792Republic of Korea Department of Electronic Engineering Inha UniversityIncheon 22212Republic of Korea

Two-dimensional van der Waals(2D vdW)material-based heterostructure devices have been widely studied for high-end electronic applications owing to their heterojunction *** this study,we demonstrate graphene(Gr)-bridge heterostructure devices consisting of laterally series-connected ambipolar semiconductor/Gr-bridge/n-type molybdenum disulfide as a channel material for field-effect transistors(FET).Unlike conventional FET operation,our Gr-bridge devices exhibit nonclassical transfer characteristics(humped transfer curve),thus possessing a negative differential *** phenomena are interpreted as the operating behavior in two series-connected FETs,and they result from the gate-tunable contact capacity of the Gr-bridge ***-value logic inverters and frequency tripler circuits are successfully demonstrated using ambipolar semiconductors with narrow-and wide-bandgap materials as more advanced circuit applications based on non-classical transfer ***,we believe that our innovative and straightforward device structure engineering will be a promising technique for future multi-functional circuit applications of 2D nanoelectronics.

关键词： Graphene bridge Heterostructure device Non-classical transfer characteristics Multi-value logic inverter Frequency tripler

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Vomiting-induced pharyngeal perforation during bowel preparation for colonoscopy:A case report

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World Journal of Clinical Cases 2024年第18期12卷 3615-3621页

作者： Geonhee kim Won Hyuk Lee Seokin Kang Jung Rock Moon Yoon Suk Lee Jun Hyuk Son Nam-Hoon kim Jong Wook kim Department of Internal Medicine Ilsan Paik HospitalInje University College of MedicineGoyang 10380South Korea

BACKGROUND Effective bowel cleansing is essential for a successful ***,such as polyethylene glycol,are commonly used for bowel *** is a frequent complication during bowel preparation,and forceful vomiting can potentially lead to esophageal perforation,as reported in several previous ***,pharyngeal perforation during bowel preparation has not been previously ***,we present a case of pharyngeal perforation induced by forceful vomiting during bowel *** SUMMARY A 38-year-old man with a history of hypertension,dyslipidemia,diabetes mellitus,and end-stage renal disease on hemodialysis was admitted for evaluation of recurrent abdominal *** patient complained of sudden pain in the neck,throat,and anterior chest following forceful vomiting during bowel *** examination revealed crepitus under the skin of the neck and anterior chest on palpation,and upper gastrointestinal endoscopy revealed pharyngeal *** perforation site was located above the upper esophageal sphincter,which distinguished it from Boerhaave’s *** medical management was chosen after consultation with a thoracic surgeon and an otolaryngologist,considering the patient's mild symptoms,stable vital signs,and the small size of the lesion;the perforation resolved without endoscopic or surgical *** patient was discharged from hospital two weeks after the *** Despite its rarity,pharyngeal perforation should be considered a potential complication of bowel preparation for colonoscopy.

关键词： Colonoscopy Pharynx Polyethylene glycols Spontaneous perforation Case report

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Effect of transcranial direct current stimulation on supernumerary phantom limb pain in spinal cord injured patient:A case report

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World Journal of Clinical Cases 2024年第17期12卷 3177-3182页

作者： Hyo-Sik Park Jae-Hyung kim Department of Interventional Physiatry Eulji University Medical CenterSeo-GuDaejeonSouth Korea

BACKGROUND Supernumerary phantom limb(SPL)sensation is the experience of additional limbs,either single or a pair of *** to traumatic spinal cord injuries,we report effect of transcranial direct current stimulation(tDCS)on SPL pain in a patient with cervical cord *** SUMMARY The subject was a 57-year-old man who was diagnosed with complete spinal cord injury(C6/C5,motor level;C5/C5,sensory level;AIS-A)approximately three months *** a period of 2 wk,we administered anodal tDCS over the motor cortex for 15 minutes at an intensity of 1.5 *** that treatment,the patient experienced a decrease of SPL pain intensity and frequency,which lasted for 1 week after the end of *** Targeting the motor cortex through neuromodulation appears to be a promising option for the management of SPL pain.

关键词： Supernumerary phantom limb pain Spinal cord injury transcranial Direct Current Stimulation Neuromodulation Case report

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