2025
Mapping pesticide-induced metabolic alterations in human gut bacteria
Chen L, Yan H, Di S, Guo C, Zhang H, Zhang S, Gold A, Wang Y, Hu M, Wu D, Johnson C, Wang X, Zhu J. Mapping pesticide-induced metabolic alterations in human gut bacteria. Nature Communications 2025, 16: 4355. PMID: 40348778, PMCID: PMC12065874, DOI: 10.1038/s41467-025-59747-6.Peer-Reviewed Original ResearchConceptsModulating gut microbiota compositionGut bacteria speciesGut microbial speciesHuman gut bacteriaGut microbiota compositionGut bacterial metabolismPesticide exposureHost healthGut bacteriaMicrobiota compositionMicrobial speciesBacterial metabolismBacteria speciesMolecular mechanismsComprehensive atlasLipid metabolismGutIn vivo mouse modelPesticidesHostMetabolismSpeciesInteractive atlasMouse modelMetabolic changesPredicting adenine base editing efficiencies in different cellular contexts by deep learning
Kissling L, Mollaysa A, Janjuha S, Mathis N, Marquart K, Weber Y, Moon W, Lin P, Fan S, Muramatsu H, Vadovics M, Allam A, Pardi N, Tam Y, Krauthammer M, Schwank G. Predicting adenine base editing efficiencies in different cellular contexts by deep learning. Genome Biology 2025, 26: 115. PMID: 40340964, PMCID: PMC12060317, DOI: 10.1186/s13059-025-03586-7.Peer-Reviewed Original ResearchConceptsBase editing efficiencyEditing efficiencyCell linesPathogenic mutationsBase editingPrimary cells in vivoBase editing screensBase editing outcomesCells in vivoHEK293T cellsAdenine base editingIn vivo settingTarget lociT cellsLipid nanoparticlesCellular contextTarget sequenceMRNA deliveryBase pairsOn-target editingBystander effectEditing outcomesBase editorsIn vitro datasetsMurine liverLiver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis
Sakuma I, Gaspar R, Nasiri A, Dufour S, Kahn M, Zheng J, LaMoia T, Guerra M, Taki Y, Kawashima Y, Yimlamai D, Perelis M, Vatner D, Petersen K, Huttasch M, Knebel B, Kahl S, Roden M, Samuel V, Tanaka T, Shulman G. Liver lipid droplet cholesterol content is a key determinant of metabolic dysfunction–associated steatohepatitis. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2502978122. PMID: 40310463, DOI: 10.1073/pnas.2502978122.Peer-Reviewed Original ResearchConceptsCholine-deficient l-amino acid-defined high-fat dietBempedoic acidLiver fibrosisLiver diseaseL-amino acid-defined high-fat dietAdvanced liver diseaseCholesterol contentHSD17B13 variantsHigh-fat dietTotal liver cholesterol contentTreated miceActivate signaling pathwaysVariant rs738409Liver cholesterol contentLiver lipidsFibrotic responsePromote inflammationTherapeutic approachesSteatotic liver diseaseDietary cholesterol supplementationFibrosisHuman liver samplesI148MAntisense oligonucleotidesProgressive formPreclinical Activity of Datopotamab Deruxtecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2, in Uterine Serous Carcinoma.
Greenman M, Demirkiran C, Bellone S, Hartwich T, McNamara B, Ettorre V, Santin N, Sethi N, Yang-Hartwich Y, Papatla K, Ratner E, Santin A. Preclinical Activity of Datopotamab Deruxtecan, an Antibody-Drug Conjugate Targeting Trophoblast Cell-Surface Antigen 2, in Uterine Serous Carcinoma. Cancer Research Communications 2025, 5: 774-782. PMID: 40299780, PMCID: PMC12062949, DOI: 10.1158/2767-9764.crc-25-0057.Peer-Reviewed Original ResearchConceptsTrophoblast cell surface antigen 2Uterine serous carcinomaAntibody-dependent cell-mediated cytotoxicityAntibody-drug conjugatesCell-mediated cytotoxicitySerous carcinomaPreclinical activityCell linesTargets trophoblast cell-surface antigen-2Presence of peripheral blood lymphocytesTreatment of uterine serous carcinomaInduce antibody-dependent cell-mediated cytotoxicityPrimary USC cell linesRecurrent uterine serous carcinomaUSC xenograftsUterine serous carcinoma cell linesAntigen 2In vivoPrimary tumor cell linesTROP2 overexpressionBiomarker-targeted therapiesControl ADCChromium release assayHigher recurrence rateTumor growth suppressionNatural killer cells’ functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes
Rodriguez-Sevilla J, Ganan-Gomez I, Kumar B, Thongon N, Ma F, Chien K, Kim Y, Yang H, Loghavi S, Tan R, Adema V, Li Z, Tanaka T, Uryu H, Kanagal-Shamanna R, Al-Atrash G, Bejar R, Banerjee P, Lynn Cha S, Montalban-Bravo G, Dougherty M, Fernandez Laurita M, Wheeler N, Jia B, Papapetrou E, Izzo F, Dueñas D, McAllen S, Gu Y, Todisco G, Ficara F, Della Porta M, Jain A, Takahashi K, Clise-Dwyer K, Halene S, Bertilaccio M, Garcia-Manero G, Daher M, Colla S. Natural killer cells’ functional impairment drives the immune escape of pre-malignant clones in early-stage myelodysplastic syndromes. Nature Communications 2025, 16: 3450. PMID: 40216768, DOI: 10.1038/s41467-025-58662-0.Peer-Reviewed Original ResearchConceptsHematopoietic stem cellsMyelodysplastic syndromeImmune escapeMyelodysplastic syndrome hematopoietic stem cellsNatural killer (NK) cellsAberrant hematopoietic stem cellsEarly-stage myelodysplastic syndromeDevelopment of myelodysplastic syndromeStage of myelodysplastic syndromeAdoptive cell therapyFunctional in vitro studiesNatural killer cellsTime of diagnosisPreclinical in vivo studiesPre-malignant clonesDisease-related comorbiditiesPre-malignant stageSlow down disease progressionRegenerate hematopoiesisClonal cytopeniaNK cellsImmune surveillanceKiller cellsHealthy donorsPharmacological therapyTiming Matters: Lessons From Perinatal Neurogenesis in the Olfactory Bulb
Liberia T, Han K, Spence N, Meller S, Martin‐Lopez E, Greer C. Timing Matters: Lessons From Perinatal Neurogenesis in the Olfactory Bulb. The Journal Of Comparative Neurology 2025, 533: e70045. PMID: 40128105, DOI: 10.1002/cne.70045.Peer-Reviewed Original ResearchConceptsOlfactory bulbGranule cellsTiming of neurogenesisProjection neuronsCoding of odor informationSynaptic circuitsInhibitory granule cellsDendrites of projection neuronsLocal synaptic circuitsMitral cellsOdor processingSynaptic integrationPlexiform layerOdor informationAnatomical configurationLaminar distributionEmbryogenesis to adulthoodNeurogenesisSecondary dendritesMaturation patternGlomeruliNeuronsDevelopmental continuumCellsBulbNotch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice
Gaspar R, Macêdo A, Nakandakari S, Muñoz V, Abud G, Vieira R, de Sousa Neto I, Pavan I, da Silva L, Simabuco F, da Silva A, Salgado W, Marchini J, Nonino C, Cintra D, Ropelle E, Pajvani U, de Freitas E, Pauli J. Notch1 Signalling Is Downregulated by Aerobic Exercise, Leading to Improvement of Hepatic Metabolism in Obese Mice. Liver International 2025, 45: e70068. PMID: 40078075, DOI: 10.1111/liv.70068.Peer-Reviewed Original ResearchConceptsNotch1 signalingAerobic exerciseRegulation of hepatic glucoseObese miceImpact of aerobic exerciseEffects of Notch1 signalingAerobic exercise trainingMTORC1 pathway activationNotch1 pathwayObese individualsTissue of obese miceCross-sectional studyNotch1 mRNA levelsMitochondrial respirationExercise trainingLivers of obese individualsTreadmill runningGluconeogenic enzymesHepG2 cell lineLipid accumulationTraining groupHepatic glucoseHepatic metabolismNotch1 proteinPathway activationMAP Kinase Phosphatase-5 Deficiency Improves Endurance Exercise Capacity
Perales J, Lawan A, Bajpeyi S, Han S, Bennett A, Min K. MAP Kinase Phosphatase-5 Deficiency Improves Endurance Exercise Capacity. Cells 2025, 14: 410. PMID: 40136658, PMCID: PMC11941502, DOI: 10.3390/cells14060410.Peer-Reviewed Original ResearchConceptsResponse to aerobic exerciseEndurance exercise capacityAerobic exerciseExercise capacityProgressive exercise stress testExercise training programEnhance endurance performanceCardiac adaptationPhysiological cardiac adaptationExercise stress testExercise habituationEndurance performanceRunning distanceCardiovascular healthTreadmill exerciseTraining programExerciseImproving cardiovascular functionSedentary miceTreadmillCardiac muscleEnduranceMitogen-activated protein kinaseMuscleStress testDepletion of Fkbp5 Protects Against the Rapid Decline in Ovarian Reserve Induced by Prenatal Stress in Female Offspring of Wild-Type Mice
Moore M, Cetinkaya-Un B, Sarkar P, Kayisli U, Semerci-Gunay N, Teng M, Lockwood C, Guzeloglu-Kayisli O. Depletion of Fkbp5 Protects Against the Rapid Decline in Ovarian Reserve Induced by Prenatal Stress in Female Offspring of Wild-Type Mice. International Journal Of Molecular Sciences 2025, 26: 2471. PMID: 40141115, PMCID: PMC11942629, DOI: 10.3390/ijms26062471.Peer-Reviewed Original ResearchConceptsOvarian reservePrenatal stressFKBP51 levelsPostnatal ovarian functionReduced ovarian reserveOvarian steroid synthesisWild-type miceMaternal restraint stressPrenatal stress groupPrenatally stressed offspringExpression of FKBP51Inhibit glucocorticoidProgesterone receptorTertiary folliclesEmbryonic day 8Granulosa cellsOvarian functionRestraint stressSteroidogenic enzymesMiddle-aged groupOvarian expressionFollicle atresiaPrenatal stress effectsDay 8Steroid synthesisSubcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease
Cai Y, Kanyo J, Wilson R, Bathla S, Cardozo P, Tong L, Qin S, Fuentes L, Pinheiro-de-Sousa I, Huynh T, Sun L, Mansuri M, Tian Z, Gan H, Braker A, Trinh H, Huttner A, Lam T, Petsalaki E, Brennand K, Nairn A, Grutzendler J. Subcellular proteomics and iPSC modeling uncover reversible mechanisms of axonal pathology in Alzheimer’s disease. Nature Aging 2025, 5: 504-527. PMID: 40065072, PMCID: PMC11922768, DOI: 10.1038/s43587-025-00823-3.Peer-Reviewed Original ResearchConceptsAlzheimer's diseaseProximity labeling approachIPSC-derived neuronsSubcellular proteomicsCytoskeleton dynamicsPhosphorylated mTOR levelsDystrophic neuritesLipid transportBiological processesProtein turnoverAD modelHuman induced pluripotent stem cellsAmyloid depositsIPSC modelsProteomicsInduced pluripotent stem cellsPluripotent stem cellsMTOR inhibitionTherapeutic targetAxonal pathologyLabeling approachMTOR levelsMouse brainSpheroid formationAlzheimerMulticilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions
Mao S, Song R, Jin S, Pang S, Jovanovic A, Zimmerman A, Li P, Wu X, Wendland M, Lin K, Chen W, Choksi S, Chen G, Holtzman M, Reiter J, Wan Y, Xuan Z, Xiang Y, Xu C, Upadhyayula S, Hess H, He L. Multicilia dynamically transduce Sonic Hedgehog signaling to regulate choroid plexus functions. Cell Reports 2025, 44: 115383. PMID: 40057957, DOI: 10.1016/j.celrep.2025.115383.Peer-Reviewed Original ResearchConceptsCSF productionChoroid plexusCerebrospinal fluidSonic hedgehog signalingWater channel AQP1Increased CSF productionHedgehog signalingChoroid plexus functionMotile ciliaMulticiliaSensory ciliaShh signalingNeonatal hydrocephalusSonic hedgehogCiliary lengthRegulate CSF productionSignal intensityCiliary ultrastructureChoroidEpithelial monolayersAQP1Developmental dynamicsCiliaATP1A2PlexusAn atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis
El Bounkari O, Zan C, Yang B, Ebert S, Wagner J, Bugar E, Kramer N, Bourilhon P, Kontos C, Zarwel M, Sinitski D, Milic J, Jansen Y, Kempf W, Sachs N, Maegdefessel L, Ji H, Gokce O, Riols F, Haid M, Gerra S, Hoffmann A, Brandhofer M, Avdic M, Bucala R, Megens R, Willemsen N, Messerer D, Schulz C, Bartelt A, Harm T, Rath D, Döring Y, Gawaz M, Weber C, Kapurniotu A, Bernhagen J. An atypical atherogenic chemokine that promotes advanced atherosclerosis and hepatic lipogenesis. Nature Communications 2025, 16: 2297. PMID: 40055309, DOI: 10.1038/s41467-025-57540-z.Peer-Reviewed Original ResearchConceptsApoE-/- miceHyperlipidemic apoE-/- miceCoronary artery diseaseDecreased plasma lipid levelsPlasma lipid levelsHepatic lipid accumulationAtherogenic chemokinesFoam-cell formationFLIM-FRET microscopyArtery diseasePlasma concentrationsVascular inflammationInflammatory conditionsMetabolic dysfunctionAtherosclerotic patientsLipid accumulationAdvanced atherosclerosisMyocardial infarctionLipid levelsSuppressed hepatic lipid accumulationAdvanced atherogenesisCarotid plaquesDisease severityIschemic strokeChemokinesp53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells
Miller K, Li B, Pierce-Hoffman H, Patel S, Lei X, Rajesh A, Teneche M, Havas A, Gandhi A, Macip C, Lyu J, Victorelli S, Woo S, Lagnado A, LaPorta M, Liu T, Dasgupta N, Li S, Davis A, Korotkov A, Hultenius E, Gao Z, Altman Y, Porritt R, Garcia G, Mogler C, Seluanov A, Gorbunova V, Kaech S, Tian X, Dou Z, Chen C, Passos J, Adams P. p53 enhances DNA repair and suppresses cytoplasmic chromatin fragments and inflammation in senescent cells. Nature Communications 2025, 16: 2229. PMID: 40044657, PMCID: PMC11882782, DOI: 10.1038/s41467-025-57229-3.Peer-Reviewed Original ResearchConceptsCytoplasmic chromatin fragmentsDNA repairGenome integrityChromatin fragmentsNuclear DNA damage signalsGenomic instabilitySenescent cellsActivation of p53Controlling DNA repairATM-dependent mannerDNA damage signalingSignatures of agingAge-associated accumulationActivate p53P53 activationHallmarks of agingDamage signalingAge-associated diseasesSignaling circuitsP53Molecular circuitsEnhanced DNA repairGenomePharmacological inhibitionAge-associated inflammationSex differences in the microglial response to stress and chronic alcohol exposure in mice
Soares A, Garcia-Rivas V, Fai C, Thomas M, Zheng X, Picciotto M, Mineur Y. Sex differences in the microglial response to stress and chronic alcohol exposure in mice. Biology Of Sex Differences 2025, 16: 19. PMID: 40038827, PMCID: PMC11881309, DOI: 10.1186/s13293-025-00701-y.Peer-Reviewed Original ResearchConceptsResponse to stressSex differencesAlcohol exposureStress-induced alcohol drinkingHeightened reactivity to stressInescapable footshock stressDevelopment of AUDReactivity to stressChronic alcohol exposureProminent sex differencesIncreased alcohol intakeCharacterize sex differencesFemale C57BL/6J miceDark paradigmComorbid moodFootshock stressStress disorderLimbic circuitsNeurobiological processesModify drinkingNeuroimmune signalingAdministered alcoholFemale rodentsMicroglial densityAlcohol drinkingHypercholesterolemia-induced LXR signaling in smooth muscle cells contributes to vascular lesion remodeling and visceral function
Zhang H, de Urturi D, Fernández-Tussy P, Huang Y, Jovin D, Zhang X, Huang S, Lek M, da Silva Catarino J, Sternak M, Citrin K, Swirski F, Gustafsson J, Greif D, Esplugues E, Biwer L, Suárez Y, Fernández-Hernando C. Hypercholesterolemia-induced LXR signaling in smooth muscle cells contributes to vascular lesion remodeling and visceral function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2417512122. PMID: 40035761, PMCID: PMC11912459, DOI: 10.1073/pnas.2417512122.Peer-Reviewed Original ResearchConceptsVascular smooth muscle cellsSmooth muscle cellsLiver X receptorLesion remodelingMuscle cellsVascular functionArterial media layerContribution of lipid metabolismPhenotypic switchingRegulate vascular toneMonocyte-derived macrophagesLipid metabolismPhenotypic switching of vascular smooth muscle cellsSwitching of vascular smooth muscle cellsNecrotic core areaRegulate vascular functionFoam cell populationVisceral myopathyBladder remodelingAortic atheromaFibrous cap thicknessRemodeling in vivoLipid malabsorptionVascular toneAbundant cell typeRecessive genetic contribution to congenital heart disease in 5,424 probands
Dong W, Jin S, Sierant M, Lu Z, Li B, Lu Q, Morton S, Zhang J, López-Giráldez F, Nelson-Williams C, Knight J, Zhao H, Cao J, Mane S, Gruber P, Lek M, Goldmuntz E, Deanfield J, Giardini A, Mital S, Russell M, Gaynor J, Cnota J, Wagner M, Srivastava D, Bernstein D, Porter G, Newburger J, Roberts A, Yandell M, Yost H, Tristani-Firouzi M, Kim R, Seidman J, Chung W, Gelb B, Seidman C, Lifton R, Brueckner M. Recessive genetic contribution to congenital heart disease in 5,424 probands. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2419992122. PMID: 40030011, PMCID: PMC11912448, DOI: 10.1073/pnas.2419992122.Peer-Reviewed Original ResearchConceptsRecessive genotypeCHD probandsCongenital heart diseaseAssociated with laterality defectsGene-based analysisAnalyzed whole-exome sequencingLeft-sided congenital heart diseaseWhole-exome sequencingCongenital heart disease phenotypeAshkenazi Jewish probandsOffspring of consanguineous unionsSingle-cell transcriptomicsCHD geneExome sequencingMouse notochordSecreted proteinsConsanguineous familyFounder variantGenesSignificant enrichmentLaterality phenotypesHeart diseaseProbandsAbnormal contractile functionConsanguineous unionsInhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases
Johnson E, Nowar R, Viola K, Huang W, Zhou S, Bicca M, Zhu W, Kranz D, Klein W, Silverman R. Inhibition of amyloid beta oligomer accumulation by NU-9: A unifying mechanism for the treatment of neurodegenerative diseases. Proceedings Of The National Academy Of Sciences Of The United States Of America 2025, 122: e2402117122. PMID: 40030015, PMCID: PMC11912461, DOI: 10.1073/pnas.2402117122.Peer-Reviewed Original ResearchConceptsProtein aggregationNeurodegenerative diseasesMechanisms of protein aggregationAmyloid-beta oligomersAlzheimer's disease neurodegenerationEndolysosomal traffickingBeta oligomersOligomer accumulationTreatment of neurodegenerative diseasesTDP-43Disease neurodegenerationPeptide aggregationLysosome-dependentCathepsin LProteinHippocampal neuronsPathological accumulationQuantitative assayTraffickingCellular mechanismsCathepsin BBlock neurodegenerationImmunofluorescence imagingPathogenic mechanismsNeurodegenerationBorrelia burgdorferi serine protease HtrA is a pleiotropic regulator of stress response, motility, flagellar hemostasis, and infectivity
Zhang K, Sze C, Zhao H, Liu J, Li C. Borrelia burgdorferi serine protease HtrA is a pleiotropic regulator of stress response, motility, flagellar hemostasis, and infectivity. Communications Biology 2025, 8: 341. PMID: 40025221, PMCID: PMC11873206, DOI: 10.1038/s42003-025-07781-x.Peer-Reviewed Original ResearchConceptsBacterial stress responseStress responseRegulators of bacterial stress responseExpression of htrAFamily of serine proteasesSerine protease HtrACryo-electron tomography analysisRegulation of stress responsesLoss-of-function studiesMurine model of Lyme diseaseChemotaxis proteinsHtrA mutantVirulence determinantsDeletion mutantsFollow-up mechanistic studiesProtease HtrAPleiotropic regulatorProtease AEndogenous promoterHtrAPleiotropic rolesSerine proteasesDeletionBacterial locomotionMutantsComposition and function of AChR chimeric autoantibody receptor T cells for antigen-specific B cell depletion in myasthenia gravis
Oh S, Khani-Habibabadi F, O'Connor K, Payne A. Composition and function of AChR chimeric autoantibody receptor T cells for antigen-specific B cell depletion in myasthenia gravis. Science Advances 2025, 11: eadt0795. PMID: 40020066, PMCID: PMC11870065, DOI: 10.1126/sciadv.adt0795.Peer-Reviewed Original ResearchConceptsChimeric autoantibody receptorsMyasthenia gravisAnti-AChRChimeric autoantibody receptor T cellsSurface expressionSustained surface expressionTarget cell eliminationB-cell depletionT cell cytotoxicityB-cell outgrowthSevere muscle weaknessMouse xenograft modelSuppress immune functionCellular immunotherapyAChR-MGMg therapyT cellsB cellsXenograft modelMuscle weaknessImmune functionNeuromuscular transmissionCell eliminationCD28GravisNorovirus co-opts NINJ1 for selective protein secretion
Song J, Zhang L, Moon S, Fang A, Wang G, Gheshm N, Loeb S, Cao P, Wallace J, Alfajaro M, Strine M, Beatty W, Jamieson A, Orchard R, Robinson B, Nice T, Wilen C, Orvedahl A, Reese T, Lee S. Norovirus co-opts NINJ1 for selective protein secretion. Science Advances 2025, 11: eadu7985. PMID: 40020060, PMCID: PMC11870086, DOI: 10.1126/sciadv.adu7985.Peer-Reviewed Original ResearchConceptsPlasma membrane ruptureDamage-associated molecular patternsNS1 secretionNinjurin-1Programmed cell deathAmino acid residuesViral replication sitesViral protein NS1CRISPR screensIntracellular viral proteinsMutagenesis studiesMembrane ruptureProtein NS1Unconventional pathwayCaspase-3Protein secretionViral proteinsReplication sitesCell deathMolecular patternsGenetic ablationNS1Pharmaceutical inhibitionDAMP releaseProtein
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