December 2024 · 6 Articles · Pages 401–481
December 2024
Open Access6 Articles · Pages 401–481
Chimeric antigen receptor T-cell (CAR-T) therapy has achieved remarkable success against hematologic malignancies, yet its application to solid tumors remains challenging. This review examines the key barriers to CAR-T efficacy in solid tumor microenvironments, including antigen heterogeneity, immunosuppressive signaling, and T-cell exhaustion. We survey emerging strategies such as armored CARs, tandem targeting constructs, and combinatorial approaches with immune checkpoint inhibitors that show promise in preclinical and early clinical trials.
Ferroptosis is a form of regulated cell death driven by lipid peroxidation, yet the full repertoire of its regulatory genes remains incomplete. We performed genome-wide CRISPRi screens in three cancer cell lines to systematically identify genes whose knockdown sensitizes or confers resistance to ferroptosis induction. Our screens reveal 23 novel regulators, including several endoplasmic reticulum-resident proteins that modulate phospholipid remodeling and iron homeostasis.
The African wild dog (Lycaon pictus) is among the most endangered carnivores on the continent, with fewer than 7,000 individuals remaining in fragmented populations. We generated whole-genome sequence data from 48 individuals across six geographically isolated populations and assessed genetic diversity, population structure, and signatures of inbreeding depression. Our results reveal critically low effective population sizes in three populations and identify genomic regions under purifying selection that may harbor deleterious variants, informing translocation and genetic rescue strategies.
The molecular circadian clock orchestrates daily rhythms in hepatic lipid metabolism, and its disruption is associated with metabolic syndrome. Using liver-specific Bmal1 knockout mice subjected to time-restricted feeding paradigms, we demonstrate that circadian misalignment exacerbates hepatic steatosis through dysregulation of de novo lipogenesis and fatty acid oxidation pathways. Time-restricted feeding partially rescues these metabolic defects, suggesting circadian-aligned dietary interventions as a therapeutic approach.
We report the development of two novel fluorescent probes that enable real-time visualization of autophagosome formation and autophagic flux in living cells. These pH-sensitive probes exhibit high photostability and minimal cytotoxicity, and their ratiometric fluorescence shift allows quantitative measurement of lysosomal acidification during autophagy. We validate their utility in nutrient-starved HeLa cells and primary murine neurons.
We present the first evidence of an integrated viral genome functioning as a mutualistic endosymbiont in a deep-sea isopod crustacean collected from the Mariana Trench. Metagenomic assembly and fluorescence in situ hybridization confirm stable vertical transmission of the viral element, which encodes metabolic genes involved in sulfur oxidation. This finding expands our understanding of the diversity and functional roles of viral symbioses in deep-sea ecosystems.