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T3D Therapeutics alleges that contract researchers delivered “medically impossible” results on its candidate drug

Bones from a Moroccan quarry belonged to a hominin that lived when the human lineage was splitting

Parkinson's disease (PD) is a progressive neurodegenerative disease that casts a significant shadow over global health and the identification of therapeutic targets for PD will empower more effective clinical treatment. The gene encoding the deubiquitinating enzyme USP25 has been identified as a susceptible locus for PD, but the role of USP25 in PD remains unknown. In this study, we found that USP25 exacerbated dopaminergic neuronal loss and motor deficits in murine models of PD by sabotaging...

The CD4^(+) cytotoxic T lymphocytes (CD4-CTLs) with cytotoxic potential are reported to be the components of protective immune response in many diseases. However, the lack of understanding about their lineage, molecular character, and cytolytic potential in comparison to CD8^(+)(CD8)-CTLs has restricted their utility. Thus, here, by parallelly analyzing the human peripheral CD4-CTLs and CD8-CTLs, we demonstrate that they are indistinguishable for the cytotoxic program. Furthermore, using an...

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Lifelong oligodendrogenesis and myelination is critical for healthy brain aging. Using cumulative labelling with thymidine analogue, 5-ethynyl-2'-deoxyuridine (EdU) for 6-weeks commencing at 2-, 12- and 18-months of age in C57BL/6 mice, we found that oligodendrocyte progenitor cell (OPC) proliferation and oligodendroglial densities are relatively stable in the adult mouse optic nerve, corpus callosum and somatosensory cortex. We also found that more proliferative adult OPCs differentiate into...

Paroxetine, a widely prescribed selective serotonin reuptake inhibitor (SSRI), is known for its metabolic side effects, yet its long-term physiological impacts remain incompletely understood. This study investigated the effects of paroxetine on lifespan, feeding behavior, and fat accumulation in Caenorhabditis elegans across different developmental stages and dietary conditions. We found that low-dose paroxetine extended lifespan when exposure began early, while high doses consistently reduced...

Previous studies had confirmed an association between Body Roundness Index (BRI) and stroke, but it remains unclear whether this association holds across different countries and populations. This study aimed to investigate the association between BRI and stroke across different national cohorts. Data were obtained from the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 and the English Longitudinal Study of Aging (ELSA) from 2012 to 2013, and multifactorial logistic...

Ischemia-reperfusion injury (IRI) represents a major challenge in liver transplantation, driving acute dysfunction and contributing to long-term allograft rejection. This process triggers a robust inflammatory response, leading to hepatocyte damage, senescence, and impaired liver regeneration. While the underlying mechanisms remain incompletely understood, increasing evidence highlights macrophage-derived signaling as a pivotal driver of hepatocyte fate during IRI. Here, we identify iRhom2 as a...

The North Atlantic Meridional Overturning Circulation (AMOC) ventilates a large part of the world ocean via the formation of mode waters and North Atlantic Deep Water. The extent to which human activities have impacted this ventilation system remains unclear. To assess the temporal variations of ocean ventilation in the North Atlantic, we calculated the "age" of seawater, that is, the duration since its last contact with the ocean surface, from both observed and simulated chlorofluorocarbon-12...

Changes in cell state are often accompanied by altered metabolic demands, and homeostasis depends on cells adapting to their changing needs. One major cell state change is senescence, which is associated with dramatic changes in cell metabolism, including increases in lipid metabolism, but how cells accommodate such alterations is poorly understood. Here we show that the transcription factor p53 increases recycling of the lipid headgroups required to meet the increased demand for membrane...

Expansions and contractions of tandem DNA repeats generate genetic variation in human populations and in human tissues. Some expanded repeats cause inherited disorders and some are also somatically unstable^(1,2). Here we analysed DNA sequencing data from over 900,000 participants in the UK Biobank and the All of Us Research Program using computational approaches to recognize, measure and learn from DNA-repeat instability. Repeats at different loci exhibited widely variable tissue-specific...

Decreased cross-presentation by antigen-presenting cells induces the scarcity of tumour-reactive T cells within the tumour bed, rendering in situ T cell rejuvenation through immunogenicity reprogramming highly desirable yet challenging^(1-3). Here we developed an intratumoural vaccination chimera (iVAC) to reprogram tumour cells into an antigen-presenting state (APC-like tumour cells) with restored anti-tumour immunity. The iVAC chimeras consist of a covalently engineered PD-L1 degrader...

Systemic inflammation following ischemic stroke is driven by a complex interplay among pro-inflammatory cytokines, immune cell activation, and neurovascular dysfunction. Both aging and obesity significantly amplify this inflammatory response, exacerbating stroke severity and impeding recovery. Aging induces a chronic low-grade inflammatory state-referred to as inflammaging-that heightens vulnerability to stroke-induced brain injury. Similarly, obesity promotes a persistent pro-inflammatory...

CONCLUSION: The findings demonstrate a significant association between physical frailty and cognitive impairment among older adults in Bangladesh, emphasizing the role of social determinants in shaping these outcomes. The results highlight the need for targeted interventions and policy strategies addressing these determinants to promote healthy aging and mitigate cognitive decline in this population.

Locomotion in animals depends on muscle activity, controlled by the central nervous system. The neuromuscular junctions (NMJs) are specialized synapses pivotal in neural control of muscle function. Declining muscle function is a characteristic of aging (sarcopenia), and gradual loss of NMJ function could contribute to sarcopenia. The NMJs are cellular ensembles comprising presynaptic axon terminals, postsynaptic muscle cell, and the perisynaptic glial cells, and a coordination between these...

Aging is a dysbiotic and pro-inflammatory process that increases susceptibility to multiple chronic comorbidities. Centenarians and supercentenarians offer a unique biological model for elucidating the molecular determinants of healthy aging and exceptional longevity, as they display distinctive epigenetic signatures and a gut microbiome configuration that diverges from both younger and typically aging individuals, although substantial interindividual variability exists. The gut microbiota...

Understanding the direct connections between metabolism and chromatin dynamics may uncover potential mechanisms involved in the aging process of renal physiology. Despite known differences in incidence and aging renal disease, how biological aging intersects with renal metabolism and epigenetics in a sex-specific context remains poorly understood. Here, we determined the effect of age on renal metabolic pathways and metabolite cofactors of epigenetic modifiers in a sex-specific manner. We...