Sherlock et al. examine an IRES RNA that initiates translation of a small downstream coding region within a viral genome. The structure, function, and mechanism of this IRES are interrogated experimentally. Differential translation efficiencies between two IRESs within one viral genome exemplify RNA-structure-based tuning of gene expression.
This RedJournal article presents a first step towards continuous dosimetry in targeted radiopharmaceutical therapy by developing a sparse sensor system to reconstruct continuous time-activity curves in preclinical 177Lu-based therapies, demonstrating high accuracy with short scan times.
177Lu-based radiopharmaceutical therapy (RPT) has shown increasing promise in the treatment of neuroendocrine and metastatic prostate cancer. Delivering optimal radiation dose to tumors while minimizing dose to organs-at-risk (OAR) remains an unmet need due to significant patient-to-patient heterogeneity in treatment response, necessitating multiple snapshots of the in vivo activity distribution. Towards this goal, here we present a high temporal-resolution activity reconstruction method demonstrated on preclinical prostate cancer models.
Editor’s Note: Associate Editor Pablo Penaloza-MacMaster provides context for Long et al. on targeting the host factor HGS-viral membrane protein interaction: https://doi.org/10.1172/JCI200225
While current antivirals primarily target viral proteins, host-directed strategies remain underexplored. Here, we performed a genome-wide CRISPR inhibition (CRISPRi) screening to identify the host protein, hepatocyte growth factor-regulated tyrosine kinase substrate (HGS), facilitating the pan-coronavirus infection both in vitro and in vivo. Mechanistically, HGS interacts with the viral membrane (M) protein, facilitating its trafficking to the ER-Golgi intermediate compartment for virion assembly. Conversely, HGS deficiency caused M retention in the ER, blocking assembly. Leveraging this interaction, we designed M-derived peptides and screened over 5,000 FDA-approved or commonly used drugs, identifying riboflavin tetrabutyrate (RTB).
Researchers at Washington University in St. Louis have developed a novel cell therapy for Alzheimer’s disease using genetically modified astrocytes — the brain’s most abundant cells. By equipping these cells with a chimeric antigen receptor (CAR), scientists enabled them to specifically target and clear beta-amyloid plaques, the toxic protein deposits that accumulate in brain tissue and drive neurodegeneration. In mouse trials, a single injection prevented plaque formation in young healthy rodents and reduced existing plaque levels by half in older mice. While the approach is still being refined to minimize side effects and must be evaluated for human safety, it holds promise both as a preventive measure and as a treatment at various stages of Alzheimer’s. The same technology may eventually be adapted for cancer therapy by reprogramming the cells to target tumor markers.
Alzheimer’s disease (AD) is the leading cause of dementia and is characterized by progressive amyloid accumulation followed by tau-mediated neurodegeneration. Despite advances in anti-amyloid immunotherapies, important limitations remain, highlighting the need for new therapeutic strategies. Here, we introduce anti-amyloid chimeric antigen receptors expressed in astrocytes (CAR-A) and validate their function in vitro. We show that two CAR-A designs reduce amyloid and associated pathology after plaque formation and prevent early plaque deposition in vivo. Single-nucleus RNA sequencing shows that CAR-A treatment induces a distinct glial response to amyloid pathology involving coordinated activity of astrocytes and microglia. Each construct additionally elicits distinctive, receptor-specific effects in astrocytes or microglia.
As metals fuse and sparks fly, one researcher’s work takes the form of DNA, a bacteriophage, a nucleosome, and more.
Complementary and alternative medicine use among US children rose from 4.6% in 2007 to 17.7% in 2022, especially yoga and meditation, with the biggest increases in younger age groups.
This cross-sectional study estimates the prevalence of complementary and alternative medicine use among US youths aged 4 to 17 years in 2007, 2012, and 2022 overall and by sociodemographic factors.
Psilocybin—the psychoactive compound in “magic mushrooms”—is gaining scientific attention for its potential in treating neuropsychiatric conditions including depression, anxiety, substance use disorders and certain neurodegenerative diseases. However, its hallucinogenic effects may limit broader therapeutic applications. Researchers publishing in the Journal of Medicinal Chemistry synthesized modified versions of psilocin, the active form of psilocybin, that retained its activity while producing fewer hallucinogenic-like effects than pharmaceutical-grade psilocybin in a preliminary study in mice.
“Our findings are consistent with a growing scientific perspective suggesting that psychedelic effects and serotonergic activity may be dissociated,” says Andrea Mattarei, a corresponding author of the study. “This opens the possibility of designing new therapeutics that retain beneficial biological activity while reducing hallucinogenic responses, potentially enabling safer and more practical treatment strategies.”
Mood disorders and some neurodegenerative diseases, such as Alzheimer’s disease, involve imbalances of the neurotransmitter molecule serotonin, which helps regulate mood and other brain functions. For decades, scientists have been investigating the therapeutic use of psychedelics such as psilocybin on serotonin-signaling pathways. However, the hallucinations that can accompany these drugs may make people wary of taking them, even if there is a medical benefit.
Despite overall improvements, women with STEMI in China still face longer pre-hospital delays than men, especially in rural areas. The gap is driven mostly by delayed EMS calls. Cardiology.
HealthEquity STEMI
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Chronic rhinosinusitis may be linked to an increased risk for cancer, according to a study of patients in Asia.
The study found that chronic rhinosinusitis was linked to an 18% increased risk for cancer in Korean patients and a 63% increased risk for cancer in patients from Japan. The results provide the first large-scale evidence for an association between chronic rhinosinusitis and the risk for cancer, suggesting a possible role for cancer surveillance in patients with the inflammatory condition, researchers said.
Results from Asia suggest chronic rhinosinusitis is associated with an increased risk for cancer, but whether these results apply to the US population remains uncertain.