Prog Neuropsychopharmacol Biol Psychiatry
March 2025
In recent decades, non-invasive brain stimulation (NIBS) has gained attention as a potential tool for promoting dietary regulation by modulating activity in the dorsolateral prefrontal cortex (dlPFC). However, the findings from individual experimental studies and meta-analyses have been inconsistent. To address this, we conducted a meta-analytic and systematic review of past studies focusing on neuromodulation of the dlPFC.
View Article and Find Full Text PDFStress must not be avoided unilaterally because adaptive mindsets toward stress and stress-induced emotions are associated with better mental health outcomes. However, few studies have explored the reciprocal relationships between adaptive mindsets and mental health. This study assessed the role of trait-level stress-is-enhancing mindsets in the dynamic interplay between emotional growth mindsets and mental health in real-life contexts.
View Article and Find Full Text PDFThe heart employs a specialized ribosome in its muscle cells to translate genetic information into proteins, a fundamental adaptation with an elusive physiological role. Its significance is underscored by the discovery of neonatal patients suffering from often fatal heart failure caused by severe dilated cardiomyopathy when both copies of the gene are mutated. RPL3L is a muscle-specific paralog of the ubiquitous ribosomal protein L3 (RPL3), which makes the closest contact of any protein to the ribosome's RNA-based catalytic center.
View Article and Find Full Text PDFAnxiety symptoms are among the most prevalent mental health disorders in adolescents, highlighting the need for scalable and accessible interventions. As anxiety often co-occurs with perceived stress during adolescence, stress interventions may offer a promising approach to reducing anxiety. Previous stress interventions have largely focused on the view that stress is harmful, aiming to manage and mitigate its negative effects.
View Article and Find Full Text PDFGenome-wide translational profiling has uncovered the synthesis in human cells of thousands of microproteins, a class of proteins traditionally overlooked in functional studies. Although an increasing number of these microproteins have been found to play critical roles in cellular processes, the functional relevance of the majority remains poorly understood. Studying these low-abundance, often unstable proteins is further complicated by the challenge of disentangling their functions from the noncoding roles of the associated DNA, RNA, and the act of translation.
View Article and Find Full Text PDFThe majority of the DNA sequence in our genome is noncoding and not intended for synthesizing proteins. Nonetheless, genome-wide mapping of ribosome footprints has revealed widespread translation in annotated noncoding sequences, including long noncoding RNAs (lncRNAs), untranslated regions (UTRs), and introns of mRNAs. How cells suppress the translation of potentially toxic proteins from various noncoding sequences remains poorly understood.
View Article and Find Full Text PDFThe RNA-targeting CRISPR-Cas13 system has enabled precise engineering of endogenous RNAs, significantly advancing our understanding of RNA regulation and the development of RNA-based diagnostic and therapeutic applications. This review aims to provide a summary of Cas13-based RNA targeting tools and applications, discuss limitations and challenges of existing tools and suggest potential directions for further development of the RNA targeting system.
View Article and Find Full Text PDFBackground: Microglia, the brain's resident immune cells, play vital roles in brain development, and disorders like Alzheimer's disease (AD). Human iPSC-derived microglia (iMG) provide a promising model to study these processes. However, existing iMG generation protocols face challenges, such as prolonged differentiation time, lack of detailed characterization, and limited gene function investigation via CRISPR-Cas9.
View Article and Find Full Text PDFTissue lymphatic vessels network plays critical roles in immune surveillance and tissue homeostasis in response to pathogen invasion, but how lymphatic system is remolded during infection is less understood. Here, we observed that influenza infection induces a significant increase of lymphatic vessel numbers in the lung, accompanied with extensive proliferation of lymphatic endothelial cells (LECs). Single-cell RNA sequencing illustrated the heterogeneity of LECs, identifying a novel PD-L1 subpopulation that is present during viral infection but not at steady state.
View Article and Find Full Text PDFStress increases the likelihood of consuming unhealthy food in some individuals. Previous research has demonstrated that the Regulation of Craving - Training (ROC-T) intervention can reduce unhealthy food intake. However, its effectiveness under stress and the underlying mechanism remained uncertain.
View Article and Find Full Text PDFInnate lymphoid cells (ILCs) can quickly switch from a quiescent state to an active state and rapidly produce effector molecules that provide critical early immune protection. How the post-transcriptional machinery processes different stimuli and initiates robust gene expression in ILCs is poorly understood. Here, we show that deletion of the N-methyladenosine (mA) writer protein METTL3 has little impact on ILC homeostasis or cytokine-induced ILC1 or ILC3 responses but significantly diminishes ILC2 proliferation, migration and effector cytokine production and results in impaired antihelminth immunity.
View Article and Find Full Text PDFTranslation is pervasive outside of canonical coding regions, occurring in long noncoding RNAs, canonical untranslated regions and introns, especially in ageing, neurodegeneration and cancer. Notably, the majority of tumour-specific antigens are results of noncoding translation. Although the resulting polypeptides are often nonfunctional, translation of noncoding regions is nonetheless necessary for the birth of new coding sequences.
View Article and Find Full Text PDFCRISPR/Cas13 systems are increasingly used for programmable targeting of RNAs. While Cas13 nucleases are capable of degrading both target RNAs and bystander RNAs in vitro and in bacteria, initial studies fail to detect collateral degradation of non-target RNAs in eukaryotic cells. Here we show that RfxCas13d, also known as CasRx, a widely used Cas13 system, can cause collateral transcriptome destruction when targeting abundant reporter RNA and endogenous RNAs, resulting in proliferation defect in target cells.
View Article and Find Full Text PDFObjective: To analysis the relevant infections and risk factors of patients undergoing hemodialysis semi-permanent catheter (tunneled cuffed) placement during for maintenance hemodialysis.
Methods: A total of 158 patients with chronic renal failure (CRF) End stage renal failure (ESRF) treated in our hospital from September 2018 to September 2021 were retrospectively analyzed. All the patients underwent semi-permanent catheter placement during maintenance hemodialysis.
The Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST), also known as the Guoshoujing Telescope, is a major national scientific facility for astronomical research located in Xinglong, China. Beginning with a pilot survey in 2011, LAMOST has been surveying the night sky for more than 10 years. The LAMOST survey covers various objects in the Universe, from normal stars to peculiar ones, from the Milky Way to other galaxies, and from stellar black holes and their companions to quasars that ignite ancient galaxies.
View Article and Find Full Text PDFCRISPR-Cas endonucleases directed against foreign nucleic acids mediate prokaryotic adaptive immunity and have been tailored for broad genetic engineering applications. Type VI-D CRISPR systems contain the smallest known family of single effector Cas enzymes, and their signature Cas13d ribonuclease employs guide RNAs to cleave matching target RNAs. To understand the molecular basis for Cas13d function and explain its compact molecular architecture, we resolved cryoelectron microscopy structures of Cas13d-guide RNA binary complex and Cas13d-guide-target RNA ternary complex to 3.
View Article and Find Full Text PDFAnaplastic thyroid cancer (ATC) represents the most aggressive subtype of thyroid cancer and has a poor prognosis. In addition to surgery, chemotherapy is an important treatment for ATC; however, the therapeutic effects of current chemotherapies for ATC are not particularly promising. There is a high proportion of side population (SP) cells in ATC, which may be a reason for its drug resistance.
View Article and Find Full Text PDFTherapeutic genome editing with Staphylococcus aureus Cas9 (SaCas9) requires a rigorous understanding of its potential off-target activity in the human genome. Here we report a high-throughput screening approach to measure SaCas9 genome editing variation in human cells across a large repertoire of 88,692 single guide RNAs (sgRNAs) paired with matched or mismatched target sites in a synthetic cassette. We incorporate randomized barcodes that enable whitelisting of correctly synthesized molecules for further downstream analysis, in order to circumvent the limitation of oligonucleotide synthesis errors.
View Article and Find Full Text PDFFragile X syndrome (FXS), the most common genetic form of intellectual disability in males, is caused by silencing of the FMR1 gene associated with hypermethylation of the CGG expansion mutation in the 5' UTR of FMR1 in FXS patients. Here, we applied recently developed DNA methylation editing tools to reverse this hypermethylation event. Targeted demethylation of the CGG expansion by dCas9-Tet1/single guide RNA (sgRNA) switched the heterochromatin status of the upstream FMR1 promoter to an active chromatin state, restoring a persistent expression of FMR1 in FXS iPSCs.
View Article and Find Full Text PDFRegulation of RNA polymerase II (Pol II) elongation is a critical step in gene regulation. Here, we report that U1 snRNP recognition and transcription pausing at stable nucleosomes are linked through premature polyadenylation signal (PAS) termination. By generating RNA exosome conditional deletion mouse embryonic stem cells, we identified a large class of polyadenylated short transcripts in the sense direction destabilized by the RNA exosome.
View Article and Find Full Text PDFThe physiological relevance of structures within mammalian mRNAs has been elusive, as these mRNAs are less folded in cells than in vitro and have predicted secondary structures no more stable than those of random sequences. Here, we investigate the possibility that mRNA structures facilitate the 3'-end processing of thousands of human mRNAs by juxtaposing poly(A) signals (PASs) and cleavage sites that are otherwise too far apart. We find that RNA structures are predicted to be more prevalent within these extended 3'-end regions than within PAS-upstream regions and indeed are substantially more folded within cells, as determined by intracellular probing.
View Article and Find Full Text PDFNucleic Acids Res
July 2017
Motifs of only 1-4 letters can play important roles when present at key locations within macromolecules. Because existing motif-discovery tools typically miss these position-specific short motifs, we developed kpLogo, a probability-based logo tool for integrated detection and visualization of position-specific ultra-short motifs from a set of aligned sequences. kpLogo also overcomes the limitations of conventional motif-visualization tools in handling positional interdependencies and utilizing ranked or weighted sequences increasingly available from high-throughput assays.
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