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Optimized RNA interference therapeutics combined with interleukin-2 mRNA for treating hepatitis B virus infection

Signal Transduction and Targeted Therapy 2024年第7期9卷 3063-3076页

作者： Wenjing Zai Min Yang Kuan Jiang Juan Guan Huijing Wang Kongying Hu Chao Huang Jieliang Chen Wei Fu Changyou Zhan Zhenghong Yuan Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) Research Unit of Cure of Chronic Hepatitis B Virus Infection(CAMS)Shanghai Frontiers Science Center of Pathogenic Microbes and InfectionSchool of Basic Medical SciencesShanghai Medical CollegeFudan UniversityShanghaiP.R.China Department of Pharmacology School of Basic Medical SciencesFudan UniversityShanghaiP.R.China shanghai Engineering Research Center for Synthetic Immunology Fudan UniversityShanghaiP.R.China Eye Institute and Department of Ophthamology Eye and ENT HospitalFudan UniversityShanghaiP.R.China Pharmacy Department of Huashan Hospital Fudan UniversityShanghaiP.R.China Institute of Pediatric Translational Medicine Shanghai Institute for Pediatric Congenital Heart DiseaseShanghai Children’s Medical CenterSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina shanghai Institute of Infectious Disease and Biosecurity ShanghaiP.R.China

This study aimed to develop a pan-genotypic and multifunctional small interfering RNA(siRNA)against hepatitis B virus(HBV)with an efficient delivery system for treating chronic hepatitis B(CHB),and explore combined RNA interference(RNAi)and immune modulatory modalities for better viral *** synthetic siRNAs targeting consensus motifs distributed across the whole HBV genome were designed and *** lipid nanoparticle(LNP)formulation was optimized by adopting HO-PEG_(2000)-DMG lipid and modifying the molar ratio of traditional polyethylene glycol(PEG)lipid in LNP *** efficacy and safety of this formulation in delivering siHBV(tLNP/siHBV)along with the mouse IL-2(mIL-2)mRNA(tLNP/siHBVIL2)were evaluated in the rAAVHBV1.3 mouse model.A siRNA combination(terms“siHBV”)with a genotypic coverage of 98.55%was selected,chemically modified,and encapsulated within an optimized LNP(tLNP)of high efficacy and security to fabricate a therapeutic formulation for *** results revealed that tLNP/siHBV significantly reduced the expression of viral antigens and DNA(up to 3log_(10)reduction;vs PBS)in dose-and time-dependent manners at single-dose or multi-dose frequencies,with satisfactory safety *** studies showed that tLNP/siHBVIL2 enables additive antigenic and immune control of the virus,via introducing potent HBsAg clearance through RNAi and triggering strong HBV-specific CD4^(+)and CD8^(+)T cell responses by expressed mIL-2 *** adopting tLNP as nucleic acid nanocarriers,the co-delivery of siHBV and mIL-2 mRNA enables synergistic antigenic and immune control of HBV,thus offering a promising translational therapeutic strategy for treating CHB.

关键词： formulation enable offering

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Decoupled deep hough voting for point cloud registration

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Frontiers of Computer Science 2024年第2期18卷 147-155页

作者： Mingzhi YUAN Kexue FU Zhihao LI Manning WANG Digital Medical Research Center School of Basic Medical SciencesFudan UniversityShanghai 200032China shanghai Key Laboratory of Medical Image Computing and Computer Assisted Intervention Shanghai 200032China

Estimating rigid transformation using noisy correspondences is critical to feature-based point cloud ***,a series of studies have attempted to combine traditional robust model fitting with deep *** them,DHVR proposed a hough voting-based method,achieving new state-of-the-art ***,we find voting on rotation and translation simultaneously hinders achieving better ***,we proposed a new hough voting-based method,which decouples rotation and translation ***,we first utilize hough voting and a neural network to estimate *** based on good initialization on rotation,we can easily obtain accurate rigid *** experiments on 3DMatch and 3DLoMatch datasets show that our method achieves comparable performances over the state-of-the-art *** further demonstrate the generalization of our method by experimenting on KITTI dataset.

关键词： point cloud registration robust model fitting deep learning hough voting

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The in-depth transmission and reception process of the factors influencing review helpfulness from the signaling timeline perspective

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中国科学技术大学学报 2024年

作者： Mohan Wang Fei Wan Jiaying Zhang Songyun Xia Key Laboratory of Brain–Machine Intelligence for Information Behavior (Ministry of Education and shanghai) School of Business and Management Shanghai International Studies University Mckelvey School of Engineering Washington University in St.Louis

Many existing studies have considered the factors influencing review helpfulness, mainly focusing on reviewer impact, review informativeness, and managerial response, based on signaling theory. However, previous studies have simply regarded these factors as independent signals, thus ignoring their in-depth transmission and reception *** conclusions about the impact of reviewers on review helpfulness are also inconsistent due to the inaccurate measurement of variables. To fill the above gaps, we followed the signaling timeline theoretical framework used in signaling theory and employed a bootstrapping analysis to examine how reviewer impact, review informativeness, and hotel managerial responses interact to influence review helpfulness. In this study, we used a unique dataset that included official labels from one leading online travel agency. The results show that reviewer impact may affect review helpfulness sequentially through review informativeness and hotel managerial response. Furthermore, by using official labels, both reviewer expertise and reviewer experience significantly affect review helpfulness. Finally, we discuss the theoretical and practical implications of these findings.

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Dissociation cross sections ofψ(3770),ψ(4040),ψ(4160),andψ(4415)mesons with nucleons

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Communications in Theoretical Physics 2024年第4期76卷 93-112页

作者： Ruo-Qing Ding Xiao-Ming Xu H J Weber Department of Physics Shanghai UniversityBaoshanShanghai 200444China Department of Physics University of VirginiaCharlottesvilleVA 22904United States of America

We study the dissociation of ψ(3770), ψ(4040), ψ(4160), and ψ(4415) mesons in collision with nucleons, which takes place in high-energy proton-nucleus collisions. The quark interchange between a nucleon and a ■ meson leads to the dissociation of the ■ meson. We consider the reactions:■, and■, where R stands for ψ(3770), ψ(4040), ψ(4160), or ψ(4415). A reaction of a neutron and a ■ meson corresponds to a reaction of a proton and the ■ meson by replacing the up quark with the down quark and vice versa. Transition-amplitude formulas are derived from the S-matrix *** cross sections are calculated with the transition amplitudes for scattering in the prior form and in the post form. The cross sections relate to nodes in the radial wave functions of ψ(3770), ψ(4040), ψ(4160), and ψ(4415) mesons.

关键词： inelastic nucleon-charmonium scattering quark interchange relativistic constituent quark potential model

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Eugenol targeting CrtM inhibits the biosynthesis of staphyloxanthin in Staphylococcus aureus

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Food Science and Human Wellness 2024年第3期13卷 1368-1377页

作者： Jiang Chang Bo Chen Zeqian Du Bowen Zhao Jiahui Li Ziyi Li Kannappan Arunachalam Ting Shi Dongqing Wei Chunlei Shi MOST-USDA Joint Research Center for Food Safety School of Agriculture and BiologyState Key Laboratory of Microbial MetabolismShanghai Jiao Tong UniversityShanghai 200240China School of Life Sciences and Biotechnology Shanghai Jiao Tong UniversityShanghai 200240China

Staphylococcus aureus is a serious foodborne pathogen threatening food safety and public *** the emergence of methicillin-resistant Staphylococcus aureus(MRSA)increased the difficulty of *** *** is a crucial virulence factor of *** staphyloxanthin production could help the host immune system counteract the invading *** *** this study,we first screened for staphyloxanthin inhibitors using a virtual screening *** outcome of the virtual screening method resulted in the identification of eugenol(300μg/mL),which significantly inhibits the staphyloxanthin production in *** ATCC 29213,*** Newman,MRSA ATCC 43300 and MRSA ATCC BAA1717by 84.2%,63.5%,68.1%,and 79.5%,*** outcome of the growth curve assay,field-emission scanning electron,and confocal laser scanning microscopy analyses confirmed that eugenol at the test concentration did not affect the morphology and growth of ***,the survival rate of *** ATCC 29213 and MRSA ATCC 43300 under H_(2)O_(2) pressure decreased to 51.9%and 45.5%in the presence of eugenol,*** quantitative RT-PCR and molecular simulation studies revealed that eugenol targets staphyloxanthin biosynthesis by downregulating the transcription of the crtM gene and inhibiting the activity of the CrtM *** together,we first determined that eugenol was a prominent compound for staphyloxanthin inhibitor to combat *** especially MRSA infections.

关键词： Staphylococcus aureus Staphyloxanthin Eugenol Virtual screening 4 4’-Diapophytoene synthase(CrtM)

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FERONIA-mediated TIR1/AFB2 oxidation stimulates auxin signaling in Arabidopsis

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Molecular Plant 2024年第5期17卷 772-787页

作者： Baiyan Lu Shengnan Wang Hanqian Feng Jing Wang Kaixing Zhang Yilin Li Ping Wu Minmin Zhang Yanshu Xia Chao Peng Chao Li School of Life Sciences East China Normal UniversityShanghai 200241China National Facilty for Protein Science shanghai Zhangjang LabShanghai Advanced Research InstituteChinese Academy of SciencesShanghai 201210China

The phytohormone auxin plays a pivotal role in governing plant growth and *** the TRANSPORT INHIBITOR RESPONSE1/AUXIN SIGNALING F-BOX(TIR1/AFB)receptors function in both the nucleus and cytoplasm,the mechanism governing the distribution of TIR1/AFBs between these cellular compartments remains *** this study,we demonstrate that auxin-mediated oxidation of TIR1/AFB2 is essential for their targeting to the *** showed that small active molecules,reactive oxygen species(ROS)and nitric oxide(NO),are indispensable for the nucleo-cytoplasmic distribution of TIR1/AFB2 in trichoblasts and root *** studies revealed that this process is regulated by the FERONIA receptor kinase–NADPH oxidase signaling ***,ROS and NO initiate oxidative modifications in TIR1C140/516 and AFB2C135/511,facilitating their subsequent nuclear *** oxidized forms of TIR1C140/516 and AFB2C135/511 play a crucial role in enhancing the function of TIR1 and AFB2 in transcriptional auxin ***,our study reveals a novel mechanism by which auxin stimulates the transport of TIR1/AFB2 from the cytoplasm to the nucleus,orchestrated by the FERONIA–ROS signaling pathway.

关键词： FERONIA TIR1/AFBs oxidative modification nucleo-cytoplasmic distribution root hair development

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Harnessing innate immune pathways for therapeutic advancement in cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1506-1564页

作者： Ankang Hu Li Sun Hao Lin Yuheng Liao Hui Yang Ying Mao Department of Neurosurgery Huashan HospitalFudan UniversityShanghaiP.R.China Institute for Translational Brain Research Shanghai Medical CollegeFudan University ShanghaiPR.China National Center for Neurological Disorders Huashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration Shanghai Clinical Medical Center of NeurosurgeryNeurosurgical Institute of Fudan UniversityHuashan HospitalShanghai Medical CollegeFudan UniversityShanghaiP.R.China State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science and MOE Frontiers Center for Brain Science Institutes of Brain ScienceShanghai Medical CollegeFudan UniversityShanghaiP.R.China shanghai Key Laboratory of Medical Epigenetics International Co-laboratory of Medical Epigenetics and Metabolism(Ministry of Science and Technology)and Key Laboratory of Metabolism and Molecular Medicine(Ministry of Education)and Molecular and Cell Biology LabInstitutes of Biomedical SciencesShanghai Medical College of Fudan UniversityShanghaiP.R.China

The innate immune pathway is receiving increasing attention in cancer *** pathway is ubiquitous across various cell types,not only in innate immune cells but also in adaptive immune cells,tumor cells,and stromal *** targeting the innate immune pathway have shown profound changes in the tumor microenvironment(TME)and improved tumor prognosis in preclinical ***,to date,the clinical success of drugs targeting the innate immune pathway remains ***,recent studies have shown that activation of the innate immune pathway can paradoxically promote tumor *** uncertainty surrounding the therapeutic effectiveness of targeted drugs for the innate immune pathway is a critical issue that needs immediate *** this review,we observe that the role of the innate immune pathway demonstrates heterogeneity,linked to the tumor development stage,pathway status,and specific cell *** propose that within the TME,the innate immune pathway exhibits multidimensional *** diversity is fundamentally rooted in cellular heterogeneity and is manifested as a variety of signaling *** pro-tumor effect of innate immune pathway activation essentially reflects the suppression of classical pathways and the activation of potential pro-tumor alternative *** our understanding of the tumor's innate immune pathway network and employing appropriate targeting strategies can enhance our ability to harness the anti-tumor potential of the innate immune pathway and ultimately bridge the gap from preclinical to clinicalapplication.

关键词： drugs therapeutic innate

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Broadening environmental research in the era of accurate protein structure determination and predictions

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Frontiers of Environmental Science & Engineering 2024年第7期18卷 169-178页

作者： Mingda Zhou Tong Wang Ke Xu Han Wang Zibin Li Wei-xian Zhang Yayi Wang State Key Laboratory of Pollution Control and Resources Reuse Shanghai Institute of Pollution Control and Ecological SecurityCollege of Environmental Science and EngineeringTongji UniversityShanghai 200092China Translational Research Institute of Brain and Brain-Like Intelligence Shanghai Fourth People's HospitalSchool of MedicineTongji UniversityShanghai 200434China

The deep-learning protein structure prediction method AlphaFold2 has garnered enormous attention beyond the realm of structural biology,for its groundbreaking contribution to solving the"protein foiding problem"In this perspective,we explore the connection between protein structure studies and environmental research,delving into the potential for addressing specific environmental *** are promising for environmental applications because of the functional diversity endowed by their structural ***,structural studies on proteins with environmental significance remain ***,we present the opportunity to study proteins by advancing experimental determination and deep-learning prediction ***,the latest progress in environmental research via cryogenic electron microscopy is *** allows us to determine the structure of protein complexes in their native state within cells at molecular resolution,revealing environmentally-associated structural *** the remarkable advancements in computational power and experimental resolution,the study of protein structure and dynamics has reached unprecedented depth and *** advancements will undoubtedly accelerate the establishment of comprehensive environmental protein structural and functional *** opportunities for protein engineering exist to enable innovative solutions for environmental applications,such as the degradation of persistent contaminants,and the recovery of valuable metals as well as rare earth elements.

关键词： Environmental proteins Protein structure Cryogenic electron microscopy Protein structure prediction Protein engineering Artificial Intelligence

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Advances in the study of mitophagy in osteoarthritis

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Journal of Zhejiang university-Science B(Biomedicine & Biotechnology) 2024年第3期25卷 197-211页

作者： Hong CAO Xuchang ZHOU Bowen XU Han HU Jianming GUO Miao WANG Nan LI Jun ZOU Department of Sport Rehabilitation Shanghai University of SportShanghai 200438China National Key Laboratory of Immunity and Inflammation Naval Medical UniversityShanghai 200433China School of Sport Medicine and Rehabilitation Beijing Sport UniversityBeijing 100084China

Osteoarthritis(OA),characterized by cartilage degeneration,synovial inflammation,and subchondral bone remodeling,is among the most common musculoskeletal disorders globally in people over 60 years of *** initiation and progression of OA involves the abnormal metabolism of chondrocytes as an important pathogenic *** degeneration features mitochondrial dysfunction as one of the important causative factors of abnormal chondrocyte ***,maintaining mitochondrial homeostasis is an important strategy to mitigate *** is a vital process for autophagosomes to target,engulf,and remove damaged and dysfunctional mitochondria,thereby maintaining mitochondrial *** studies have revealed a strong association between mitophagy and OA,suggesting that the regulation of mitophagy may be a novel therapeutic direction for *** reviewing the literature on mitophagy and OA published in recent years,this paper elaborates the potential mechanism of mitophagy regulating OA,thus providing a theoretical basis for studies related to mitophagy to develop new treatment options for OA.

关键词： Mitophagy Osteoarthritis Chondrocyte Mitochondria Apoptosis

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SPNS1 ablation drives skeletal muscle atrophy by disrupting mitophagy,mitochondrial function,and apoptosis in mice

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Genes & Diseases 2024年第5期11卷 25-28页

作者： Xianzhong Zhang Fengmin Zhang Haofan Wu Zhen Yu Chengle Zhuang Department of Gastrointestinal Surgery Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghai200092China Colorectal Cancer Center Shanghai Tenth People's HospitalSchool of MedicineTongji UniversityShanghai 200072China

Sarcopenia is characterized by a dramatic decline in muscle mass and function during aging,which of ten leads to reduced mobility,diminished quality of life,and shortened *** recent advances in sarcopenia,the mechanisms that mediate skeletal muscle dysfunction remain unclear.1 Lysosomal plays a vital role in digesting and recycling macromolecules,and several studies have shown that lysosomal acidification and autophagy decrease with age,which may impair the clearance of damaged mitochondria.

关键词： skeletal function spite

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