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Bacterial and cancerous cell membrane fused liposome coordinates with PD-L1 inhibitor for cancer immunotherapy

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Nano research 2024年第9期17卷 8389-8401页

作者： Xianjin Luo Chenglong Li Zhaofei Guo Hairui Wang Penghui He Yuanhao Zhao Yi Lin Chunting He Yingying Hou Yongshun Zhang Guangsheng Du Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Precision Industrial TechnologyWest China School of PharmacySichuan UniversityChengdu 610064China pharmaceutical biotechnology Department of PharmacyLMU MunichButenandt Strasse 5-13Munich 81377Germany Department of Biomedical Engineering College of Future TechnologyPeking UniversityBeijing 100871China

Although tumor cell membranes with broad-spectrum antigens have been explored for cancer vaccines for decades,their relatively poor capacity to stimulate immune responses,especially cellular immune responses,has limited their ***,we presented a novel bacterial and cancerous cell membrane fusogenic liposome for co-delivering cell membrane-derived antigens and ***,a programmed death-ligand 1(PD-L1)inhibitor,JQ-1,was incorporated into the formulation to tackle the up-regulated PD-L1 expression of antigen-presenting cells(APCs)upon vaccination,thereby augmenting its anti-tumor *** fusogenic liposomes demonstrated significantly improved cellular uptake by APCs and effectively suppressed PD-L1 expression in bone marrow-derived dendritic cells(BMDCs)in *** subcutaneous vaccination,the nano-vaccines efficiently drained to the tumor-draining lymph nodes(TDLNs),and significantly inhibited PD-L1 expression of both dendritic cells(DCs)and macrophages within the TDLNs and *** a result,the liposomal vaccine induced robust innate and cellular immune responses and inhibited tumor growth in a colorectal carcinoma-burden mouse *** summary,the fabricated cell membrane-based fusogenic liposomes offer a safe,effective,and easily applicable strategy for tumor immunotherapy and hold potential for personalized cancer immunotherapy.

关键词： fusogenic liposome tumor cell membrane adjuvant programmed death-ligand 1(PD-L1)inhibitor tumor draining lymph nodes

SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics to induce robust virus propagation

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Signal Transduction and Targeted Therapy 2024年第6期9卷 2702-2715页

作者： Hye Jin Shin Wooseong Lee Keun Bon Ku Gun Young Yoon Hyun-Woo Moon Chonsaeng Kim Mi-Hwa Kim Yoon-Sun Yi Sangmi Jun Bum-Tae Kim Jong-Won Oh Aleem Siddiqui Seong-Jun Kim Department of Convergent research of Emerging Virus Infection Korea Research Institute of Chemical TechnologyDaejeon 34114Republic of Korea Gyeongnam Biohealth research Center Gyeongnam Branch InstituteKorea Institute of ToxicologyJinju 52834Republic of Korea Center for research Equipment Korea Basic Science InstituteCheongjuChungcheongbuk-do 28119Republic of Korea Department of biotechnology Yonsei UniversitySeoul 03722Republic of Korea division of Infectious Diseases School of MedicineUniversity of CaliforniaSan DiegoLa JollaCA 92093USA Present address:Department of Microbiology Chungnam National University School of MedicineDaejeon 35015Republic of Korea

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)is a‘highly transmissible respiratory pathogen,leading to severe multiorgan ***,knowledge regarding SARS-CoV-2-induced cellular alterations is *** this study,we report that SARSCoV-2 aberrantly elevates mitochondrial bioenergetics and activates the EGFR-mediated cell survival signal cascade during the early stage of viral ***-CoV-2 causes an increase in mitochondrial transmembrane potential via the SARS-CoV-2 RNAnucleocapsid cluster,thereby abnormally promoting mitochondrial elongation and the OXPHOS process,followed by enhancing ATP ***,SARS-CoV-2 activates the EGFR signal cascade and subsequently induces mitochondrial EGFR trafficking,contributing to abnormal OXPHOS process and viral *** EGFR inhibitors remarkably reduce SARS-CoV-2 propagation,among which vandetanib exhibits the highest antiviral *** of SARS-CoV-2-infected cells with vandetanib decreases SARS-CoV-2-induced EGFR trafficking to the mitochondria and restores SARS-CoV-2-induced aberrant elevation in OXPHOS process and ATP generation,thereby resulting in the reduction of SARS-CoV-2 ***,oral administration of vandetanib to SARS-CoV-2-infected hACE2 transgenic mice reduces SARS-CoV-2 propagation in lung tissue and mitigates SARS-CoV-2-induced lung *** also exhibits potent antiviral activity against various SARS-CoV-2 variants of concern,including alpha,beta,delta and omicron,in in vitro cell culture *** together,our findings provide novel insight into SARS-CoV-2-induced alterations in mitochondrial dynamics and EGFR trafficking during the early stage of viral infection and their roles in robust SARS-CoV-2 propagation,suggesting that EGFR is an attractive host target for combating COVID-19.

关键词： alterations aberrant thereby

Development of vehicle-recognition method on water surfaces using LiDAR data:SPD^(2)(spherically stratified point projection with diameter and distance)

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Defence Technology（防务技术） 2024年第6期36卷 95-104页

作者： Eon-ho Lee Hyeon Jun Jeon Jinwoo Choi Hyun-Taek Choi Sejin Lee The Department of Mechanical Engineering Kongju National University1223-24 Cheonan-daeroCheonan 31080Republic of Korea Ocean System Engineering research division Korea Research Institute of Ships and Ocean Engineering(KRISO)Daejeon 34103Republic of Korea The division of Mechanical&Automotive Engineering Kongju National University1223-24 Cheonan-daeroCheonan 31080Republic of Korea

Swarm robot systems are an important application of autonomous unmanned surface vehicles on water *** monitoring natural environments and conducting security activities within a certain range using a surface vehicle,the swarm robot system is more efficient than the operation of a single object as the former can reduce cost and save *** is necessary to detect adjacent surface obstacles robustly to operate a cluster of unmanned surface *** this purpose,a LiDAR(light detection and ranging)sensor is used as it can simultaneously obtain 3D information for all directions,relatively robustly and accurately,irrespective of the surrounding environmental *** the GPS(global-positioning-system)error range exists,obtaining measurements of the surface-vessel position can still ensure stability during platoon *** this study,a three-layer convolutional neural network is applied to classify types of surface *** aim of this approach is to redefine the sparse 3D point cloud data as 2D image data with a connotative meaning and subsequently utilize this transformed data for object classification ***,we have proposed a descriptor that converts the 3D point cloud data into 2D image *** use this descriptor effectively,it is necessary to perform a clustering operation that separates the point clouds for each *** developed voxel-based clustering for the point cloud ***,using the descriptor,3D point cloud data can be converted into a 2D feature image,and the converted 2D image is provided as an input value to the *** intend to verify the validity of the proposed 3D point cloud feature descriptor by using experimental data in the ***,we explore the feasibility of real-time object classification within this framework.

关键词： Object classification Clustering 3D point cloud data LiDAR(light detection and ranging) Surface vehicle

Two types of coumarins-specific enzymes complete the last missing steps in pyran- and furanocoumarins biosynthesis

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Acta Pharmaceutica Sinica B 2024年第2期14卷 869-880页

作者： Yucheng Zhao Yuedong He Liangliang Han Libo Zhang Yuanzheng Xia Fucheng Yin Xiaobing Wang Deqing Zhao Sheng Xu Fei Qiao Yibei Xiao Lingyi Kong Department of Resources Science of Traditional Chinese Medicines School of Traditional Chinese Pharmacyand State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China College of Bioscience and biotechnology Hunan Agricultural UniversityChangsha 410128China Jiangsu Key Laboratory of Bioactive Natural Product research and State Key Laboratory of Natural Medicines Department of Natural Medicinal ChemistryChina Pharmaceutical UniversityNanjing 210009China Key Laboratory of Crop Gene Resources and Germplasm Enhancement in Southern China Ministry of AgricultureTropical Crops Genetic Resources InstituteChinese Academy of Tropical Agricultural SciencesHaikou 517317China Institute of Botany Jiangsu Province and Chinese Academy of SciencesNanjing 210014China Department of Pharmacology School of Pharmacyand State Key Laboratory of Natural MedicinesChina Pharmaceutical UniversityNanjing 210009China

Pyran-and furanocoumarins are key representatives of tetrahydropyrans and tetrahydrofurans,respectively,exhibiting diverse physiological and medical ***,the biosynthetic mechanisms for their core structures remain poorly *** we combined multiomics analyses of biosynthetic enzymes in Peucedanum praeruptorum and in vitro functional verification and identified two types of key enzymes critical for pyran and furan ring biosynthesis in *** included three distinct *** prenyltransferases(PpPT1e3)responsible for the prenylation of the simple coumarin skeleton 7 into linear or angular precursors,and two novel CYP450 cyclases(PpDC and PpOC)crucial for the cyclization of the linear/angular precursors into either tetrahydropyran or tetrahydrofuran *** analyses of cyclases indicated that acid/base-assisted epoxide ring opening contributed to the enzyme-catalyzed tetrahydropyran and tetrahydrofuran ring *** possible acid/base-assisted catalytic mechanisms of the identified cyclases were theoretically investigated and assessed using site-specific *** identified two possible acidic amino acids Glu303 in PpDC and Asp301 in PpOC as vital in the catalytic *** study provides new enzymatic tools in the epoxide formation/epoxide-opening mediated cascade reaction and exemplifies how plants become chemically diverse in terms of enzyme function and catalytic process.

关键词： Tetrahydropyrans Tetrahydrofurans Baldwin rules Coumarins CYP450cyclase

Decreased eggshell strength caused by impairment of uterine calcium transport coincide with higher bone minerals and quality in aged laying hens

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Journal of Animal Science and biotechnology 2024年第3期15卷 1258-1277页

作者： Yu Fu Jianmin Zhou Martine Schroyen Haijun Zhang Shugeng Wu Guanghai Qi Jing Wang Key Laboratory of Feed biotechnology Ministry of Agriculture and Rural AffairsInstitute of Feed ResearchChinese Academy of Agricultural SciencesBeijing 100081China Precision Livestock and Nutrition Laboratory Gembloux Agro‑Bio TechTERRA Teaching and Research CentreUniversity of LiegeGembloux B‑5030Belgium

Background Deteriorations in eggshell and bone quality are major challenges in aged laying *** study compared the differences of eggshell quality,bone parameters and their correlations as well as uterine physiologi-cal characteristics and the bone remodeling processes of hens laying eggs of different eggshell breaking strength to explore the mechanism of eggshell and bone quality reduction and their interaction.A total of 24074-week-old Hy-line Brown laying hens were selected and allocated to a high(HBS,44.83±1.31 N)or low(LBS,24.43±0.57 N)eggshell breaking strength *** A decreased thickness,weight and weight ratio of eggshells were observed in the LBS,accompanied with ultrastructural deterioration and total Ca *** quality was negatively correlated with eggshell quality,marked with enhanced structures and increased components in the *** the LBS,the mammillary knobs and effective layer grew *** the initiation stage of eggshell calcification,a total of 130 differentially expressed genes(DEGs,122 upregulated and 8 downregulated)were identified in the uterus of hens in the LBS relative to those in the *** DEGs were relevant to apoptosis due to the cellular Ca *** values of p62 protein level,caspase-8 activity,Bax protein expression and lower values of Bcl protein expression and Bcl/Bax ratio were seen in the *** assay and hematoxylin-eosin staining showed a significant increase in TUNEL-positive cells and tissue damages in the uterus of the *** few DEGs were identified at the growth stage,similar uterine tissue damages were also observed in the *** expressions of runt-related transcription factor 2 and osteocal-cin were upregulated in humeri of the *** diameter and more structural damages of endocortical bones and decreased ash were observed in femurs of the *** The lower eggshell breaking strength may be attributed to a declined Ca transport due to uterine tissue damages,which

关键词： Bone parameter Calcium transport Eggshell quality Laying hen Tissue damage

An orchestrated ethylene-gibberellin signaling cascade contributes to mesocotyl elongation and emergence of rice direct seeding

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Journal of Integrative Plant Biology 2024年第7期66卷 1427-1439页

作者： Yusong Lyu Xinli Dong Shipeng Niu Ruijie Cao Gaoneng Shao Zhonghua Sheng Guiai Jiao Lihong Xie Shikai Hu Shaoqing Tang Xiangjin Wei Peisong Hu State Key Laboratory of Rice Biology and Breeding China National Center for Rice ImprovementChina National Rice Research InstituteHangzhou 310006China College of Agriculture and biotechnology Zhejiang UniversityHangzhou 310058China

A mechanized direct seeding of rice with less labor and water usage,has been widely ***,this approach requires varieties that exhibit uniform seedling *** elongation(ME)offers the main drive of fast emergence of rice seedlings from soils;nevertheless,its genetic basis remains ***,we identify a major rice quantitative trait locus Mesocotyl Elongation1(qME1),an allele of the Green Revolution gene Semi-Dwarf1(SD1),encoding GA20-oxidase for gibberellin(GA)***1 expression is strongly induced by soil depth and *** rice grains are direct-seeded in soils,the ethylene core signaling factor OsEIL1 directly promotes ME1 transcription,accelerating bioactive GA *** GAs further degrade the DELLA protein SLENDER RICE 1(SLR1),alleviating its inhibition of rice PHYTOCHROME-INTERACTING FACTOR-LIKE13(OsPIL13)to activate the downstream expansion gene OsEXPA4 and ultimately promote rice seedling ME and *** ancient traits of long mesocotyl and strong emergence ability in wild rice and landrace were gradually lost in company with the Green Revolution dwarf breeding process,and an elite ME1-R allele(D349H)is found in some modern Geng varieties(long mesocotyl lengths)in northern China,which can be used in the direct seeding and dwarf breeding of Geng ***,the ectopic and high expression of ME1 driven by mesocotyl-specific promoters resulted in rice plants that could be direct-seeded without obvious plant architecture or yield ***,we reveal the molecular mechanism of rice ME,and provide useful information for breeding new Green Revolution varieties with long mesocotyl suitable for direct-seeding practice.

关键词： rice(Oryza sativa L.) direct seeding Green Revolu-tion mesocotyl elongation ethylene gibberellin semi-dwarf1(SD1)

Practical Synthesis of Valbenazine via 1,3-Dipolar Cycloaddition

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Chinese Journal of Chemistry 2024年第8期42卷 841-845页

作者： Yalan Peng Zuming Lin Lili Zhu Shiqing Han Sha-Hua Huang Ran Hong College of biotechnology and pharmaceutical Engineering Nanjing Tech UniversityNanjingJiangsu211816 China School of Environmental and Chemical Engineering Shanghai Institute of TechnologyShanghai201418 China State Key Laboratory of Chemical Biology Shanghai Institute of Organic ChemistryChinese Academy of SciencesShanghai200032 China Innovation research Institute of Traditional Chinese Medicine(IRI) Shanghai University of Traditional Chinese Medicine1200 Cailun RoadShanghai201203 China

Comprehensive Summary,Valbenazine(Ingrezza),a potent and highly selective inhibitor of vesicular monoamine transporter type 2(VMAT2)through the active metabolite hydrotetrabenazine(HTBZ),has been approved for the treatment of tardive dyskinesia and,very recently,for chorea,which is associated with Huntington's *** numerous synthetic efforts dedicated to the synthesis of HTBZ,the industrial preparation of valbenazine uses dihydroisoquinoline as a starting material and the chiral resolution of racemic HTBZ derived from ketone ***,we present a practical synthesis of HTBZ and valbenazine featuring a highly stereoselective 1,3-dipolar cycloaddition and enzymatic kinetic *** cascade process includes cycloaddition,N—O bond cleavage,and lactamization,which proved to be operationally *** allure of the enzymatic resolution developed in this work offers a rapid access toward affording tetrahydroisoquinoline(THIQ)-fused piperidine in the production of medically significant compounds,such as yohimbine and reserpine.

关键词： Cycloaddition Chemoenzymatic Kinetic resolution Prodrugs VMAT2 inhibitor

Strategies that regulate LSD1 for novel therapeutics

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1494-1507页

作者： Meng Li Mengge Dai Bing Cheng Shaotong Li Enhui Guo Junwei Fu Ting Ma Bin Yu School of pharmaceutical Sciences&Key Laboratory of Advanced Drug Preparation Technologies Ministry of EducationZhengzhou UniversityZhengzhou 450001China College of Chemistry Zhengzhou UniversityZhengzhou 450001China Tianjian Laboratory of Advanced Biomedical Sciences Institute of Advanced Biomedical SciencesZhengzhou UniversityZhengzhou 450000China Pingyuan Laboratory State Key Laboratory of Antiviral DrugsHenan Normal UniversityXinxiang 453007China State Key Laboratory of pharmaceutical biotechnology Nanjing UniversityNanjing 210023China

Histone methylation plays crucial roles in regulating chromatin structure and gene transcrip-tion in epigenetic ***-specific demethylase 1(LSD1),the first identified histone de-methylase,is universally overexpressed in various ***1 dysregulation is closely associated with cancer,viral infections,and neurodegenerative diseases,etc.,making it a promising therapeutic *** LSD1 inhibitors and two small-molecule degraders(UM171 and BEA-17)have entered the clinical ***1 can remove methyl groups from histone 3 at lysine 4 or lysine 9(H3K4 or H3K9),resulting in either transcription repression or *** the roles of LSD1 in transcrip-tional regulation are well-established,studies have revealed that LSDl can also be dynamically regulated by other *** example,the expression or activity of LSD1 can be regulated by many proteins that form transcriptional corepressor complexes with ***,some post-transcriptional modifica-tions and cellular metabolites can also regulate LSD1 expression or its demethylase ***,in this review,we will systematically summarize how proteins involved in the transcriptional corepressor complex,various post-translational modifications,and metabolites act as regulatory factors for LSD1 ac-tivity.

关键词： LSD1 regulation Transcription repression Transcription activation the Corepressor complex Post-transcriptional modifications Metabolites

Smad8 is involvement in follicular development via the regulation of granulosa cell growth and steroidogenesis in mice

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BIOCELL 2024年第1期48卷 139-147页

作者： DAOLUN YU DEYONG SHE KAI GE LEI YANG RUINA ZHAN SHAN LU YAFEI CAI College of biotechnology and pharmaceutical Engineering West Anhui UniversityLu’an237012China Lu’an Academy of Agricultural Sciences Lu’an237001China College of Life Sciences Anhui Normal UniversityWuhu241000China College of Animal Science and Technology Nanjing Agricultural UniversityNanjing210095China

Background:SMAD family proteins(SMADs)are crucial transcription factors downstream of transforming growth factor beta(TGF-ß)/SMAD signaling pathways that have been reported to play a pivotal role in mammalian ***,the role of SMAD family member 8(SMAD8,also known as SMAD9),a member of the SMAD family,in mammalian reproduction remains ***:We employed RNA interference techniques to knock down Smad8 expression in mouse granulosa cells(GCs)to investigate the effects of Smad8 on GC growth and ***:Our findings revealed a significant decrease in the proliferative capacity and a substantial increase in the apoptosis rate of GCs after transfection with Smad8-siRNA for 48 *** hormone assays demonstrated a significant decrease in estradiol(E2)levels,whereas progesterone(P4)remained *** mechanistic analysis showed that the mRNA expression of proliferating cell nuclear antigen(Pcna),Cyclin D2,cell cycle-dependent kinase 4(Cdk4),B-cell lymphoma-2(Bcl-2),estrogen receptor(Er),luteinizing hormone receptor(Lhr)and cytochrome P450 family 19 subfamily A member 1(Cyp19a1)significantly ***,the mRNA of cysteine aspartate proteinase 3(Caspase 3)significantly increased,wheras Bcl2-associated X(Bax),folliclestimulating hormone receptor(Fshr)and cytochrome P450 family 11 subfamily A member 1(Cyp11a1)remained unchanged compared to the ***:This study indicates that Smad8 knockdown inhibits cell proliferation,promotes apoptosis,reduces Er and Lhr transcription,and decreases E2 production in mouse *** findings suggest that Smad8 may serve as a novel genetic marker for mammalian reproduction.

关键词： Mouse Smad8 RNA interference Granulosa cells Growth and steroidogenesis