A hidden “jack-in-the-box” mechanism inside T cells may hold the key to unlocking more powerful cancer immunotherapies.
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Reactivation of mammalian regeneration by turning on an evolutionarily disabled genetic switch
Mammals display prominent diversity in the ability to regenerate damaged ear pinna, but the genetic changes underlying the failure of regeneration remain elusive. We performed comparative single-cell and spatial transcriptomic analyses of rabbits and mice recovering from pinna damage. Insufficient retinoic acid (RA) production, caused by the deficiency of rate-limiting enzyme Aldh1a2 and boosted RA degradation, was responsible for the failure of mouse pinna regeneration. Switching on Aldh1a2 or RA supplementation reactivated regeneration. Evolutionary inactivation of multiple Aldh1a2-linked regulatory elements accounted for the deficient Aldh1a2 expression upon injury in mice and rats. Furthermore, the activation of Aldh1a2 by a single rabbit enhancer was sufficient to improve ear pinna regeneration in transgenic mice.
Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics
Ma, X., Huang, T., Chen, X. et al. Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics. Sig Transduct Target Ther 10, 63 (2025). https://doi.org/10.1038/s41392-024-02104-8
Brain implant helps man with paralysis regain movement
A brain implant used for the first time is helping a patient with paralysis regain use of his limbs. The use of artificial intelligence is helping in the process, also making it possible for the man to feel objects again. NBC News’ Sam Brock reports.
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Diaphragmatic EMG Findings in a Patient With Radiation-Induced Myopathy of the Hemidiaphragm
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Elevated mtDNA copy number in older adults is linked to methylation of mitochondrial and nuclear regulatory regions
Growing evidence shows that epigenetic modification and mitochondrial dysfunction are hallmarks of aging and are associated with the development of a wide range of age-related diseases. Mitochondrial biogenesis, which is marked by mitochondrial DNA copy number (mtDNAcn), is one of the major regulations of mitochondrial function by a set of transacting elements, including mitochondrial DNA polymerase gamma (POLG), working on the mtDNA control region. In this study, we investigated the mtDNAcn and the methylation status at both mtDNA control and POLGA promoter regions in human blood cells from individuals with a wide range of ages. A total of 119 blood samples were collected, including 24 umbilical cord blood samples from newborns and 95 peripheral blood samples from individuals aged 18 to 96 years.
Allosteric binding site for anthraquinones at the human P2X4 receptor
Sarcomas comprise a heterogeneous group of malignant neoplasms that include genomically simple and genomically complex subtypes. This consensus provides guidelines for efficient, rational use of next-generation sequencing in their clinical management.
This consensus review establishes guidelines for the rational and efficient use of next-generation sequencing−based technology in the clinical management of sarcoma.
Altered regional brain activity underlying the higher postoperative analgesic requirements in abstinent smokers: A prospective cohort study
New in JNeurosci from Wei, Tao, Bi et al: Smokers who have quit their nicotine use have altered brain activity linked to heightened pain sensitivity and a need for more postoperative pain relief.
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Perioperative abstinent smokers experience heightened pain sensitivity and increased postoperative analgesic requirements, likely due to nicotine withdrawal-induced hyperalgesia. However, the underlying neural mechanisms in humans remain unclear. To address this issue, this study enrolled 60 male patients (30 abstinent smokers and 30 nonsmokers) undergoing partial hepatectomy, collecting clinical data, smoking history, pain-related measures, and resting-state functional magnetic resonance imaging (rs-fMRI). Compared to nonsmokers, abstinent smokers showed lower pain threshold and higher postoperative analgesic requirements. Neuroimaging revealed altered brain function in abstinent smokers, including reduced fractional amplitude of low-frequency fluctuations (fALFF, 0.01 – 0.1 Hz) in the ventromedial prefrontal cortex (vmPFC), increased regional homogeneity (ReHo) in the left middle occipital gyrus, and decreased functional connectivity (FC) between the vmPFC to both the bilateral middle temporal gyrus and precuneus. Preoperative pain threshold was positively correlated with abstinence duration and specific regional brain activities and connectivity. Further, the observed association between abstinent time and pain threshold was mediated by the calcarine and posterior cingulate cortex activity. The dysfunction in vmPFC and left anterior cingulate cortex was totally mediated by the association between withdrawal symptoms and postoperative analgesic requirements. These findings suggest that nicotine withdrawal might alter brain functional activity and contribute to hyperalgesia for the abstinent smokers. This study provided novel insights into the supraspinal neurobiological mechanisms underlying nicotine withdrawal-induced hyperalgesia and potential therapeutic targets for postoperative pain in abstinent smokers.
Significance statement Abstinent smokers experienced heightened pain and require more analgesics after surgery, yet the underlying neural mechanisms remain poorly understood. This prospective cohort study identified altered regional brain activity associated with reduced pain thresholds and increased postoperative analgesic requirements in abstinent smokers. We found specific brain regions that were functionally altered and correlated with pain-related outcomes, which mediated the relationship between abstinence and pain-related behaviors. These findings provided novel insights into the supraspinal mechanisms of nicotine withdrawal-induced hyperalgesia and point to potential therapeutic targets for improving postoperative pain management in abstinent smokers.