Core Viewpoint - The study identifies mitochondrial dysfunction as a potential mechanism for autism-related social deficits through the elevation of H₂S levels and subsequent sulfhydration of synaptic proteins [3][6]. Group 1: Research Findings - Mitochondrial dysfunction leads to increased H₂S levels, which mediates the sulfhydration of the synaptic protein mGluR5, potentially contributing to social deficits associated with autism [3][6]. - The research focused on the anterior cingulate cortex (ACC) and found that overexpression of cystathionine β-synthase (CBS) in wild-type mice impaired synaptic transmission and social function, while its knockdown effectively restored these functions in two autism mouse models [4][6]. - Significant changes in the sulfhydration of synaptic proteins were observed in Shank3b−/− ACC, confirming excessive sulfhydration of mGluR5 in both autism mouse models [4][6]. Group 2: Implications and Mechanisms - The study suggests that excessive H₂S and the sulfhydration of synaptic proteins may be underlying mechanisms for social function impairments in autism [6][7]. - Reducing the intake of sulfur-containing amino acids improved social dysfunction in Shank3b−/− and Fmr1−/y mice, as well as synaptic defects in corresponding human neurons [4][7].

Core Viewpoint - CAR-T cell therapy is one of the most promising cancer treatment methods, but its efficacy is significantly limited by aging-related factors, particularly the decline in nicotinamide adenine dinucleotide (NAD) levels, which drives CAR-T cell failure [2][8]. Group 1: Research Findings - A study published by researchers from the University of Lausanne and Geneva University Hospitals indicates that restoring NAD levels can enhance the therapeutic effects of aging CAR-T cells, providing a promising approach to improve CAR-T therapy [2][8]. - The study demonstrates that aging is a limiting factor for effective CAR-T cell responses, with evidence showing that CAR-T cells derived from aged female mice exhibit mitochondrial dysfunction due to NAD depletion, leading to poor stem-like characteristics and impaired anti-tumor function [7][8]. - Human data analysis further supports that both age and NAD metabolism influence the response to CAR-T cell therapy, highlighting the potential of targeting NAD pathways to restore mitochondrial health and function in CAR-T cells from older patients [7][8]. Group 2: Importance of NAD in T Cell Function - NAD metabolism plays a critical regulatory role in T cell fate and function, with alterations in NAD homeostasis linked to impaired T cell responses [5][6]. - Aging is a primary risk factor associated with cancer, with approximately 75% of cancer patients eligible for immunotherapy being over 65 years old, indicating the need for strategies that address age-related declines in treatment efficacy [5][6]. - The maintenance of stem cell-like T cell populations is crucial for the success of CAR-T cell therapy, and recent studies suggest that enhancing mitochondrial metabolism through metabolic interventions can improve CAR-T cell efficacy [4][8].