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High-throughput screening of novel TFEB agonists in protecting against acetaminopheninduced liver injury in mice

Acta Pharmaceutica Sinica B 2024年第1期14卷 190-206页

作者： Xiaojuan Chao Mengwei Niu Shaogui Wang Xiaowen Ma Xiao Yang Hua Sun Xujia Hu Hua Wang Li Zhang Ruili Huang Menghang Xia Andrea Ballabio Hartmut Jaeschke Hong-Min Ni Wen-Xing Ding department of Pharmacology Toxicology and TherapeuticsUniversity of Kansas Medical CenterKansas CityKS 66160USA NMPA Key Laboratory for Research and Evaluation of Drug Metabolism&Guangdong Provincial Key Laboratory of New Drug Screening School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China department of Oncology the First Affiliated Hospital of Anhui Medical UniversityAnhui Medical UniversityHefei 230032China National Center for Advancing Translational Sciences National Institutes of HealthBethesdaMD 20892USA Telethon Institute of genetics and Medicine TIGEMPozzuoliNaples 80131Italy Medical genetics Department of Translational MedicineFederico II UniversityNaples 80131Italy department of Molecular and Human genetics Baylor College of MedicineHoustonTX 77030USA department of Internal Medicine Division of GastroenterologyHepatology&MotilityUniversity of Kansas Medical CenterKansas CityKS 66160USA

Macroautophagy(referred to as autophagy hereafter)is a major intracellular lysosomal degradation pathway that is responsible for the degradation of misfolded/damaged proteins and *** studies showed that autophagy protects against acetaminophen(APAP)-induced injury(AILI)via selective removal of damaged mitochondria and APAP protein *** lysosome is a critical organelle sitting at the end stage of autophagy for autophagic degradation via fusion with *** the present study,we showed that transcription factor EB(TFEB),a master transcription factor for lysosomal biogenesis,was impaired by APAP resulting in decreased lysosomal biogenesis in mouse *** loss-of and gain-of function of hepatic TFEB exacerbated or protected against AILI,***,overexpression of TFEB increased clearance of APAP protein adducts and mitochondria biogenesis as well as SQSTM1/p62-dependent non-canonical nuclear factor erythroid 2-related factor 2(NRF2)activation to protect against *** also performed an unbiased cell-based imaging high-throughput chemical screening on TFEB and identified a group of TFEB *** these agonists,salinomycin,an anticoccidial and antibacterial agent,activated TFEB and protected against AILI in *** conclusion,genetic and pharmacological activating TFEB may be a promising approach for protecting against AILI.

关键词： Autophagy DILI Drug screening Hepatotoxicity Lysosome Mitochondria Mitophagy NRF2

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Highly Aligned Ternary Nanofiber Matrices Loaded with MXene Expedite Regeneration of Volumetric Muscle Loss

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Nano-Micro Letters 2024年第4期16卷 269-292页

作者： Moon Sung Kang Yeuni Yu Rowoon Park Hye Jin Heo Seok Hyun Lee Suck Won Hong Yun Hak Kim Dong‑Wook Han department of Cogno‑Mechatronics Engineering College of Nanoscience and NanotechnologyPusan National UniversityBusan 46241Republic of Korea Medical Research Institute School of MedicinePusan National UniversityYangsan 50612Republic of Korea department of Anatomy School of MedicinePusan National UniversityYangsan 50612Republic of Korea Engineering Research Center for Color‑Modulated Extra‑Sensory Perception Technology Pusan National UniversityBusan 46241Republic of Korea department of Biomedical Informatics School of MedicinePusan National UniversityYangsan 50612Republic of Korea Periodontal Disease Signaling Network Research Center and Dental and Life Science Institute School of DentistryPusan National UniversityYangsan 50612Republic of Korea BIO‑IT Fusion Technology Research Institute Pusan National UniversityBusan 46241Republic of Korea present address:Osstem Implant Inc. Seoul 07789Republic of Korea

Current therapeutic approaches for volumetric muscle loss(VML)face challenges due to limited graft availability and insufficient *** overcome these limitations,tissue-engineered scaffolds have emerged as a promising *** this study,we developed aligned ternary nanofibrous matrices comprised of poly(lactide-co-ε-caprolactone)integrated with collagen and Ti_(3)C_(2)T_(x)MXene nanoparticles(NPs)(PCM matrices),and explored their myogenic potential for skeletal muscle tissue *** PCM matrices demonstrated favorable physicochemical properties,including structural uniformity,alignment,microporosity,and *** vitro assays revealed that the PCM matrices promoted cellular behaviors and myogenic differentiation of C2C12 ***,in vivo experiments demonstrated enhanced muscle remodeling and recovery in mice treated with PCM matrices following VML *** insights from next-generation sequencing revealed that MXene NPs facilitated protein and ion availability within PCM matrices,leading to elevated intracellular Ca^(2+)levels in myoblasts through the activation of inducible nitric oxide synthase(i NOS)and serum/glucocorticoid regulated kinase 1(SGK1),ultimately promoting myogenic differentiation via the m TOR-AKT ***,upregulated i NOS and increased NO–contributed to myoblast proliferation and fiber fusion,thereby facilitating overall myoblast *** findings underscore the potential of MXene NPs loaded within highly aligned matrices as therapeutic agents to promote skeletal muscle tissue recovery.

关键词： Ti_(3)C_(2)T_(x)MXene nanoparticle Ternary nanofibrous matrices Myogenesis Regeneration of volumetric muscle loss Next generation sequencing

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The next decade of SET:from an oncoprotein to beyond

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Journal of Molecular Cell Biology 2024年第1期16卷 1-14页

作者： Han Yao Meng Zhang Donglai Wang State Key Laboratory of Common Mechanism Research for Major Diseases&department of Medical genetics Institute of Basic Medical Sciences&School of Basic MedicineChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100005China

This year marks the fourth decade of research into the protein SET,which was discovered in *** was initially identified as an oncoprotein but later shown to be a multifaceted protein involved in regulating numerous biological processes under both physiological and pathophysiological *** dysfunction is closely associated with diseases,such as cancer and Alzheimer's *** the increasing understanding of how SET works and how it is regulated in cells,targeting aberrant SET has emerged as a potential strategy for disease *** this review,we present a comprehensive overview of the advancements in SET studies,encompassing its biological functions,regulatory networks,clinical implications,and pharmacological ***,we provide insights into the future prospects of SET research,with a particular emphasis on its promising potential in the realm of immune modulation.

关键词： SET biological process regulatory mechanism disease therapy

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Gas microchannel plate-pixel detector for X-ray polarimetry

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Nuclear Science and Techniques 2024年第5期35卷 60-73页

作者： Huan-Bo Feng Hong-Bang Liu Dong Wang Zi-Li Li Shu-Lin Liu Qian Liu Hang-Zhou Li Bin-Long Wang Yan-Jun Xie Zong-Wang Fan Hui Wang Ran Chen Di-Fan Yi Rui-Ting Ma Fei Xie Bo Peng Xiang-Ming Sun Jin Li En-Wei Liang present address:Guangxi Key Laboratory for Relativistic Astrophysics School of Physical Science and TechnologyGuangxi UniversityNanning 530004China PLAC Key Laboratory of Quark and Lepton Physics(MOE)Central China Normal UniversityWuhan 430079China School of Science Huzhou UniversityHuzhou 313000China Institute of High Energy Physics Chinese Academy of SciencesBeijing 100049China School of Nuclear Science and Technology University of Chinese Academy of SciencesBeijing 100049China School of Physical Science University of Chinese Academy of SciencesBeijing 100049China The 13th Research Institute of China Electronics Technology Group Corporation Shijiazhuang 050057China

POLAR-2 is a gamma-ray burst(GRB)polarimeter that is designed to study the polarization in GRB radiation emissions,aiming to improve our knowledge of related ***-2 is expected to utilize an on-board polarimeter that is sensitive to soft X-rays(2-10 keV),called low-energy polarization *** have developed a new soft X-ray polari-zation detector prototype based on gas microchannel plates(GMCPs)and pixel chips(Topmetal).The GMCPs have bulk resistance,which prevents charging-up effects and ensures gain stability during *** detector is composed of low outgassing materials and is gas-sealed using a laser welding technique,ensuring long-term stability.A modulation factor of 41.28%±0.64% is obtained for a 4.5 keV polarized X-ray beam.A residual modulation of 1.96%±0.58% at 5.9 keV is observed for the entire sensitive area.

关键词： X-ray polarimetry Gas microchannel plate-pixel detector Gamma-ray bursts

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Human biomonitoring of novel brominated flame retardants:A review on invasive and non-invasive biomarkers

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Emerging Contaminants 2024年第3期10卷 374-385页

作者： Oluwatoyin M.Olagoke Temilola O.Oluseyi Kelechi L.Njoku Stuart Harrad Mohamed Abou-Elwafa Abdallah department of Cell Biology and genetics Faculty of ScienceUniversity of LagosAkokaLagos101017Nigeria department of Chemistry Faculty of ScienceUniversity of LagosAkokaLagos101017Nigeria School of Geography Earth and Environmental SciencesUniversity of BirminghamBirminghamB152TTUnited Kingdom

Novel brominated flame retardants(NBFRs)are a group of chemicals applied mainly as alternatives to the phased-out polybrominated diphenyl ethers(PBDEs).However,toxicological studies show that NBFRs may pose health risks similar to *** present study reviews available information on the biomonitoring of NBFRs and their metabolites in humans through invasive and non-invasive biomarkers,as well as the toxicological effects of these chemicals both in vivo and in *** general,higher concentrations of NBFRs were reported in tissues of occupationally exposed adults from NBFR production facilities,e-waste recycling facilities and inhabitants living close to these areas,compared to the general *** is worth noting that NBFR human biomonitoring data are limited to few countries located in North America,Europe and Asia,while data from developing countries are *** from in vivo and in vitro toxicity studies show that several NBFRs can cause adverse health effects through various modes of action,mainly:hormone disruption,genotoxicity,endocrine disruption,and behavioural *** few studies have investigated the biotransformation of NBFRs in humans,evidence suggests that the toxicity of some NBFRs may be augmented through their metabolites,as in the case of 2,3,4,5-tetrabromobenzoic acid(TBBA),which may exhibit higher toxicity than its parent compound 2-ethylhexyl-2,3,4,5-tetrabromobenzoate(EH-TBB).More research is required to assess toxicity thresholds,toxic endpoints,and tolerable intakes for various NBFRs,and their metabolites in *** epidemiological studies are highly recommended to further understand the risk arising from human exposure to different NBFRs,particularly in occupational settings.

关键词： NBFRs Human biomonitoring Human exposure Biomarkers Metabolites

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Cellular and Molecular Requirements for Polar PIN Targeting and Transcytosis in Plants

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Molecular Plant 2008年第6期1卷 1056-1066页

作者： Jurgen Kleine-Vehn tukasz tangowski Justyna Wisniewska Pankaj Dhonukshe Philip B Brewer Jiri Friml department of Plant Systems Biology VIB and Department of Molecular Genetics Ghent University 9052 Gent Belgium Zentrum fur Molekularbiologie der Pflanzen (ZMBP) Universitat Tubingen 72076 Tubingen Germany present address: Institute of General and Molecular Biology Nicolas Copernicus University 87-100 Torun Poland present address: department of Biology Utrecht University 3508 TB Utrecht The Netherlands present address: Centre for Integrative Legume Research University of Queensland Brisbane Australia

The polar, sub-cellular localization of PIN auxin efflux carriers determines the direction of intercellular auxin flow, thus defining the spatial aspect of auxin signalling. Dynamic, transcytosis-like relocalizations of PIN proteins occur in response to external and internal signals, integrating these signals into changes in auxin distribution. Here, we examine the cellular and molecular mechanisms of polar PIN delivery and transcytosis. The mechanisms of the ARF-GEF-dependent polar targeting and transcytosis are well conserved and show little variations among diverse Arabidopsis ecotypes consistent with their fundamental importance in regulating plant development. At the cellular level, we refine previous findings on the role of the actin cytoskeleton in apical and basal PIN targeting, and identify a previously unknown role for microtubules, specifically in basal targeting. PIN protein delivery to different sides of the cell is mediated by ARFdependent trafficking with a previously unknown complex level of distinct ARF-GEF vesicle trafficking regulators. Our data suggest that alternative recruitment of PIN proteins by these distinct pathways can account for cell type- and cargo-specific aspects of polar targeting, as well as for polarity changes in response to different signals. The resulting dynamic PIN positioning to different sides of cells defines a three-dimensional pattern of auxin fluxes within plant tissues.

关键词： cytoskeleton polarity protein targeting.

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Phylogenetic, phylogeographic and divergence time analysis of Anopheles subpictus species complex using ITS2 and COI sequences

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Asian Pacific Journal of Tropical Medicine 2024年第5期17卷 214-225,I0004-I0038页

作者： Lihini Sandaleka Muthukumarana Methsala Madurangi Wedage Samanthika Rathnayake Nissanka Kolitha De Silva department of Zoology Faculty of Applied SciencesUniversity of Sri JayewardenepuraGangodawilaNugegodaSri Lanka genetics and Molecular Biology Unit Faculty of Applied SciencesUniversity of Sri JayewardenepuraGangodawilaNugegodaSri Lanka Sri Lanka Institute of Biotechnology PitipanaHomagamaSri Lanka

Objective:To address the phylogenetic and phylogeographic relationship between different lineages of Anopheles(An.)subpictus species complex in most parts of the Asian continent by maximum utilization of Internal Transcriber Spacer 2(ITS2)and cytochrome C oxidase I(COI)sequences deposited at the ***:Seventy-five ITS2,210 COI and 26 concatenated sequences available in the NCBI database were *** analysis was performed using Bayesian likelihood trees,whereas median-joining haplotype networks and time-scale divergence trees were generated for phylogeographic *** diversity indices and genetic differentiation were also ***:Two genetically divergent molecular forms of *** species complex corresponding to sibling species A and B are *** A evolved around 37-82 million years ago in Sri Lanka,India,and the Netherlands,and species B evolved around 22-79 million years ago in Sri Lanka,India,and ***,Thailand,and Cambodia have two molecular forms:one is phylogenetically similar to species *** forms differ from species A and B and evolved recently in the above mentioned countries,Indonesia and the *** subdivision among Sri Lanka,India,and the Netherlands is almost absent.A substantial genetic differentiation was obtained for some populations due to isolation by large geographical *** diversity indices reveal the presence of a long-established stable mosquito population,at mutation-drift equilibrium,regardless of population ***:*** species complex consists of more than two genetically divergent molecular *** A is highly divergent from the *** Lanka and India contain only species A and B.

关键词： Molecular systematics ITS2 COI DNA sequences Phylogeny Phylogeography

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Exome sequencing identifies a likely causative variant in 53%of families with ciliopathy-related features on renal ultrasound after excluding NPHP1 deletions

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Genes & Diseases 2024年第5期11卷 40-43页

作者： Konstantin Deutsch Verena Klambt Thomas M.Kitzler Tilman Jobst-Schwan Ronen Schneider Florian Buerger Steve Seltzsam Sherif El Desoky Jameela A.Kari Farkhanda Hafeez Maria Szczepanska Loai A.Eid Hazem S.Awad Muna Al-Saffar Neveen A.Soliman Velibor Tasic Camille Nicolas-Frank Kirollos Yousef Luca M.Schierbaum Sophia Schneider Abdul Halawi Izzeldin Elmubarak Katharina Lemberg Shirlee Shril Shrikant M.Mane Nancy Rodig Friedhelm Hildebrandt Division of Nephrology Department of PediatricsBoston Children’s HospitalHarvard Medical SchoolBostonMA 02215USA department of Pediatric Gastroenterology Nephrology and Metabolic DiseasesCharite Universitatsmedizin BerlinBerlin 13353Germany Berlin Institute of Health at Charitee Universitatsmedizin Berlin BIH Biomedical Innovation AcademyBIH Charite Clinician Scientist ProgramBerlin 10178Germany department of Nephrology and Hypertension FriedrichAlexander-Universitat Erlangen-NurnbergErlangen 91054Germany department of Pediatrics Faculty of Medicine King Abdulaziz UniversityPediatric Nephrology Center of ExcellenceKing Abdulaziz University HospitalJeddah 21589Saudi Arabia department of Pediatric Nephrology The Children’s Hospital and Institute of Child HealthLahore 54000Pakistan department of Pediatrics Faculty of Medical Sciences in ZabrzeMedical University of Silesia in KatowiceKatowice 40-752Poland Dubai Hospital and Al-Jalila Children’s Specialty Hospital Kidney Center of ExcellenceDubai 4545United Arab Emirates department of genetics and Genomics UAE UniversityAbu Dhabi 15551United Arab Emirates department of Pediatrics Division of Genetics and GenomicsBoston Children’s HospitalHarvard Medical SchoolBostonMA 02215USA department of Pediatrics Center of Pediatric Nephrology and TransplantationKasr Al Ainy School of MedicineCairo UniversityCairo 11562Egypt Egypt Center for Research and Regenerative Medicine(ECRRM) Cairo 11511Egypt Medical Faculty Skopje University Children’s HospitalSkopje 1000North Macedonia department of genetics Yale University School of MedicineNew HavenCT 06520USA

Nephronophthisis-related ciliopathies(NPHP-RC)represent one of the most common causes of chronic kidney disease in the first three decades of life and are characterized by a broad genetic and clinical heterogeneity.1 To date,more than 90 genes have been identified that cause autosomalrecessive NPHP-RC if mutated,accounting for up to 60%of cases.1 Among these,homozygous deletions of NPHP1 are the most common *** genes localize to primary cilia,basal bodies,or the centrosome and lead to a primary ciliary disruption if mutated,thereby causing a broad phenotypical spectrum.1 Patients that suffer from NPHP-RC can either have an isolated renal phenotype,such as polyuria,polydipsia,decreased urinary concentration ability,and secondary enuresis due to loss of tubular function,or present with extrarenal symptoms including retinal degeneration,cerebellar vermis hypoplasia,or hepatic *** are often diagnosed in early adolescence,reaching end-stage renal disease before 25 years of age,but early onset and rapidly progressive forms of NPHP-RC also exist.1 Renal ultrasound indicates kidneys of normal or reduced renal length with increased echogenicity and corticomedullary cysts.

关键词： degeneration urinary likely

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OsWRKY62 is a Negative Regulator of Basal and Xa21-Mediated Defense against Xanthomonas orvzae pv. orvzae in Rice

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Molecular Plant 2008年第3期1卷 446-458页

作者： Ying Peng Laura E. Bartley Xuewei Chen Christopher Dardick Mawsheng Chern Randy Ruan Patrick E. Canlas Pamela C. Ronald department of Plant Pathology University of California Davis CA 95616 USA present address: Monsanto Corporation Davis CA 95616 USA present address: USDA-ARS Appalachian Fruit Research Station Kearneysville WV 25430 USA

The rice Xa21 gene, which confers resistance to the bacterial pathogen Xanthomonas oryzae pv. oryzae （Xoo）, encodes a receptor-like kinase, Few components involved in transducing the Xa21-mediated defense response have yet been identified. Here, we report that XA21 binds to a WRKY transcription factor, called OsWRKY62. The OsWRKY62 gene encodes two splice variants （OsWRKY62.1 and OsWRKY62.2）. OsWRKY62.1：smGFP2 and OsWRKY62.2：smGFP2 fusion pro- teins partially localize to the nucleus. Transgenic plants overexpressing OsWRKY62.1 are compromised in basal defense and Xa21-mediated resistance to Xoo. Furthermore, overexpression of OsWRKY62.1 suppresses the activation of defenserelated genes. These results imply that OsWRKY62 functions as a negative regulator of innate immunity in rice, and serves as a critical mediator of both basal and race-specific defense responses.

关键词： rice OsWRKY62 Xa21 defense response.

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A deterministic model for homologous antibody dependant enhancement on influenza infection

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Infectious Disease Modelling 2024年第4期9卷 1265-1275页

作者： Shilian Xu Jiaru Yang department of Environment and genetics School of AgricultureBiomedicine and EnvironmentLa Trobe UniversityBundooraVIC3086Australia department of Mathematical and Physical Sciences La Trobe UniversityBundooraVIC3086Australia department of Biochemistry and Molecular Biology Biomedicine Discovery InstituteMonash UniversityClaytonVIC3800Australia The Institute for Tropical Medicine School of Basic Medical SciencesKunming Medical UniversityKunming650500China

Antibody dependant enhancement refers that viral infectivity was unexpectedly enhanced at low antibody concentration compared to when antibodies were absent,such as Dengue,Zika and influenza *** mathematically describe switch from enhancement to neutralisation with increase of antibody concentration,one hyperbolic tangent variant is used as switching function in existed ***,switching function with hyperbolic tangent contains four parameters,and does not always increase with antibody *** address this problem,we proposed a monotonically increasing Logistical function variant as switching function,which only contains position parameter and magnitude *** influenza viral titre estimated from 21 focus reduction assay(FRA)datasets from neutralisation group(viral titre lower than negative control on all serial dilutions)and 20 FRA dataset from enhancement group(viral titre higher than negative control on high serial dilution),switching function with Logistic function performs better than existed model independent of both groups and exhibited different behaviour/character;specifically,magnitude parameter estimated from enhancement group is lower,but position parameter estimated from enhancement group is higher.A lower magnitude parameter refers that enhancement group more rapidly switches from enhancement to neutralisation with increase of antibody concentration,and a higher position parameter indicates that enhancement group provides a larger antibody concentration interval corresponding to *** estimated neutralisation kinetics with viral replication,we demonstrated that antibody-induced bistable influenza kinetics exist independent of both ***,comparing with neutralisation group,enhancement group provides higher threshold value of antibody concentration corresponding to influenza *** explains the observed phenomenon that antibody dependent enhancement enhances susceptibility,severity,a

关键词： Antibody dependent enhancement Logistical function Switching function Influenza virus

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