Protein & Cell

Ergothioneine, Ovothiol and Selenoneine are sulfur/selenium-containing histidine-derived natural products widely distributed across different organisms. They exhibit significant antioxidant properties, making them as potential lead compounds for promoting health. Increasing evidence suggests that Ergothioneine is positively correlated with healthy ageing and longevity. The mechanisms underlying Ergothioneine regulation of the ageing process at cellular and molecular level are beginning to be understood. In this review, we provide an in-depth and extensive coverage of the anti-ageing studies on Ergothioneine and discuss its possible intracellular targeting pathways...

Polyploid cells, which contain more than one set of chromosome pairs, are very common in nature. Polyploidy can provide cells with several potential benefits over their diploid counterparts, including an increase in cell size, contributing to organ growth and tissue homeostasis, and improving cellular robustness via increased tolerance to genomic stress and apoptotic signals. Here, we focus on why polyploidy in the cell occurs and which stress responses and molecular signals trigger cells to become polyploid...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Ubiquitination/ubiquitylation, one of the most fundamental post-translational modifications (PTMs), regulates almost every critical cellular process in eukaryotes. Emerging evidence has shown that essential components of numerous biological processes undergo ubiquitination in mammalian cells upon exposure to diverse stresses, from exogenous factors to cellular reactions, causing a dazzling variety of functional consequences. Various forms of ubiquitin signals generated by ubiquitylation events in specific milieus, known as ubiquitin codes, constitute an intrinsic part of myriad cellular stress responses...

The exposure to either medical sources or accidental radiation can cause varying degrees of radiation injury (RI). RI is a common disease involving multiple human body parts and•organs, yet effective treatments are currently limited. Accumulating evidence suggests gut microbiota are closely associated with the development and prevention of various RI. This article summarizes ten common types of RI and their possible mechanisms. It also highlights the changes and potential microbiota-based treatments for RI, including probiotics, metabolites, and microbiota transplantation...

Continual evolution of the SARS-CoV-2 virus has allowed for its gradual evasion of neutralizing antibodies (nAbs) produced in response to natural infection or vaccination. The rapid nature of these changes has incited a need for the development of superior broad nAbs and/or the rational design of an antibody cocktail that can protect against the mutated virus strain. Here, we report two ACE2 competing nAbs-8H12 and 3E2-with synergistic neutralization but evaded by some Omicron subvariants. Cryo-EM reveals the two nAbs synergistic neutralizing virus through a rigorous pairing permitted by rearrangement of the 472-489 loop in the RBD to avoid steric clashing...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Aging increases the risk of liver diseases and systemic susceptibility to aging-related diseases. However, cell-type-specific changes and the underlying mechanism of liver aging in higher vertebrates remain incompletely characterized. Here, we constructed the first single-nucleus transcriptomic landscape of primate liver aging, in which we resolved cell-type-specific gene expression fluctuation in hepatocytes across three liver zonations and detected aberrant cell-cell interactions between hepatocytes and niche cells...

No abstract text is available yet for this article.

No abstract text is available yet for this article.

Colorectal cancer (CRC) is a highly heterogeneous cancer and exploring novel therapeutic options is a pressing issue that needs to be addressed. Here, we established human CRC tumor-derived organoids that well represent both morphological and molecular heterogeneities of original tumors. To efficiently identify repurposed drugs for CRC, we developed a robust organoid-based drug screening system. By combining the repurposed drug library and computation-based drug prediction, 335 drugs were tested and 34 drugs with anti-CRC effects were identified...

The discovery of G-protein coupled receptor (GPCR) accessory proteins has fundamentally redefined the pharmacological concept of GPCR signaling, demonstrating a more complex molecular basis for receptor specificity on the plasma membrane and impressionable downstream intracellular cascades. GPCR accessory proteins not only contribute to the proper folding and trafficking of receptors, but also exhibit selectable receptor preferences. The melanocortin receptor accessory proteins (MRAP1 and MRAP2) as well as receptor activity-modifying proteins (RAMPs) are two well-known single transmembrane partners for the regulation of the melanocortin receptors (MC1R-MC5R) and the glucagon receptor (GCGR), respectively...

The seat of human intelligence is the human cerebral cortex, which is responsible for our exceptional cognitive abilities. Identifying principles that lead to the development of the large-sized human cerebral cortex will shed light on what makes the human brain and species so special. The remarkable increase in the number of human cortical pyramidal neurons and the size of the human cerebral cortex is mainly because human cortical radial glial cells, primary neural stem cells in the cortex, generate cortical pyramidal neurons for more than 130 days, whereas the same process takes only about 7 days in mice...

No abstract text is available yet for this article.

Here, we report a previously unrecognized syndromic neurodevelopmental disorder associated with bi-allelic loss-of-function variants in the RBM42 gene. The patient is a two-year-old female with severe central nervous system abnormalities, hypotonia, hearing loss, congenital heart defects, and dysmorphic facial features. Familial whole-exome sequencing reveals that the patient has two compound heterozygous variants, c.304C>T (p.R102*) and c.1312G>A (p.A438T), in the RBM42 gene which encodes an integral component of splicing complex in the RNA-binding motif protein family...

Molecular knowledge of human gastric corpus epithelium remains incomplete. Here, by integrated analyses using single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, and single-cell assay for transposase accessible chromatin sequencing (scATAC-seq) techniques, we uncovered the spatially resolved expression landscape and gene-regulatory network of human gastric corpus epithelium. Specifically, we identified a stem/progenitor cell population in the isthmus of human gastric corpus, where EGF and WNT signaling pathways were activated...

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells...