Short-term effect of coil handle orientations on fMRI-guided rTMS on insomnia: A case report.

Introduction: The coil handle orientation plays a pivotal role in the therapeutic efficacy of repetitive transcranial magnetic stimulation (rTMS). However, there is currently no consensus on the optimal individualized coil handle orientation, especially for non-motor areas. Case presentation: The present case reported a short-term effect of functional connectivity (FC)-guided rTMS with coil handle posterior-anterior 45° (PA45°) and posterior-anterior 135° (PA135°) on a patient with insomnia. Notably, in this case, the PA45° orientation was nearly perpendicular to the adjacent sulcus, while the PA135° orientation was almost parallel to it. Local brain activity and functional connectivity were assessed using resting-state functional magnetic resonance imaging (RS-fMRI). Additionally, motor evoked potentials (MEPs) were captured both pre and post-rTMS sessions. Findings: The coil handle orientation PA45° outperformed the PA135° in both RS-fMRI and MEP outcomes. Moreover, a 9-day rTMS treatment led to discernible improvements in symptoms of depression and anxiety, complemented by a modest enhancement in sleep quality.

SIRT6 is an epigenetic repressor of thoracic aortic aneurysms via inhibiting inflammation and senescence.

Thoracic aortic aneurysms (TAAs) develop asymptomatically and are characterized by dilatation of the aorta. This is considered a life-threating vascular disease due to the risk of aortic rupture and without effective treatments. The current understanding of the pathogenesis of TAA is still limited, especially for sporadic TAAs without known genetic mutation. Sirtuin 6 (SIRT6) expression was significantly decreased in the tunica media of sporadic human TAA tissues. Genetic knockout of Sirt6 in mouse vascular smooth muscle cells accelerated TAA formation and rupture, reduced survival, and increased vascular inflammation and senescence after angiotensin II infusion. Transcriptome analysis identified interleukin (IL)-1ß as a pivotal target of SIRT6, and increased IL-1ß levels correlated with vascular inflammation and senescence in human and mouse TAA samples. Chromatin immunoprecipitation revealed that SIRT6 bound to the Il1b promoter to repress expression partly by reducing the H3K9 and H3K56 acetylation. Genetic knockout of Il1b or pharmacological inhibition of IL-1ß signaling with the receptor antagonist anakinra rescued Sirt6 deficiency mediated aggravation of vascular inflammation, senescence, TAA formation and survival in mice. The findings reveal that SIRT6 protects against TAA by epigenetically inhibiting vascular inflammation and senescence, providing insight into potential epigenetic strategies for TAA treatment.

Comprehensive assessment of cellular senescence in the tumor microenvironment.

Cellular senescence (CS), a state of permanent growth arrest, is intertwined with tumorigenesis. Due to the absence of specific markers, characterizing senescence levels and senescence-related phenotypes across cancer types remain unexplored. Here, we defined computational metrics of senescence levels as CS scores to delineate CS landscape across 33 cancer types and 29 normal tissues and explored CS-associated phenotypes by integrating multiplatform data from ~20 000 patients and ~212 000 single-cell profiles. CS scores showed cancer type-specific associations with genomic and immune characteristics and significantly predicted immunotherapy responses and patient prognosis in multiple cancers. Single-cell CS quantification revealed intra-tumor heterogeneity and activated immune microenvironment in senescent prostate cancer. Using machine learning algorithms, we identified three CS genes as potential prognostic predictors in prostate cancer and verified them by immunohistochemical assays in 72 patients. Our study provides a comprehensive framework for evaluating senescence levels and clinical relevance, gaining insights into CS roles in cancer- and senescence-related biomarker discovery.