Cytoplasmic mRNA decay controlling inflammatory gene expression is determined by pre-mRNA fate decision.

The fidelity of immune responses depends on timely controlled and selective mRNA degradation that is largely driven by RNA-binding proteins (RBPs). It remains unclear whether stochastic or directed processes govern the selection of an individual mRNA molecule for degradation. Using human and mouse cells, we show that tristetraprolin (TTP, also known as ZFP36), an essential anti-inflammatory RBP, destabilizes target mRNAs via a hierarchical molecular assembly.

Spatially restricted and ontogenically distinct hepatic macrophages are required for tissue repair.

Our understanding of the functional heterogeneity of resident versus recruited macrophages in the diseased liver is limited. A population of recruited lipid-associated macrophages (LAMs) has been reported to populate the diseased liver alongside resident Kupffer cells (KCs). However, the precise roles of these distinct macrophage subsets remain elusive.

Structures and mRNP remodeling mechanism of the TREX-2 complex.

mRNAs are packaged with proteins into messenger ribonucleoprotein complexes (mRNPs) in the nucleus. mRNP assembly and export are of fundamental importance for all eukaryotic gene expression. Before export to the cytoplasm, mRNPs undergo dynamic remodeling governed by the DEAD-box helicase DDX39B (yeast Sub2).

Long-lived cytokinetic bridges coordinate sister-cell elimination in mouse embryos.

Apoptosis is a key feature of preimplantation development, but whether it occurs in a cell-autonomous or coordinated manner was unknown. Here, we report that plasma membrane abscission, the final step of cell division, is profoundly delayed in early mouse embryos such that a cytokinetic bridge is maintained for the vast majority of the following interphase. Early embryos thus consist of many pairs of sister cells connected by stable cytokinetic bridges that allow them to share diffusible molecules.

A forward genetic screen identifies potassium channel essentiality in SHH medulloblastoma maintenance.

Distinguishing tumor maintenance genes from initiation, progression, and passenger genes is critical for developing effective therapies. We employed a functional genomic approach using the Lazy Piggy transposon to identify tumor maintenance genes in vivo and applied this to sonic hedgehog (SHH) medulloblastoma (MB). Combining Lazy Piggy screening in mice and transcriptomic profiling of human MB, we identified the voltage-gated potassium channel KCNB2 as a candidate maintenance driver.

Ligand interaction landscape of transcription factors and essential enzymes in E. coli.

Knowledge of protein-metabolite interactions can enhance mechanistic understanding and chemical probing of biochemical processes, but the discovery of endogenous ligands remains challenging. Here, we combined rapid affinity purification with precision mass spectrometry and high-resolution molecular docking to precisely map the physical associations of 296 chemically diverse small-molecule metabolite ligands with 69 distinct essential enzymes and 45 transcription factors in the gram-negative bacterium Escherichia coli. We then conducted systematic metabolic pathway integration, pan-microbial evolutionary projections, and independent in-depth biophysical characterization experiments to define the functional significance of ligand interfaces.

Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traits.

Background: Aging increases disease susceptibility and reduces vaccine responsiveness, highlighting the need to better understand the aging immune system and its clinical associations. Studying the human immune system, however, remains challenging due to its complexity and significant inter-individual variability.

Methods: We conducted an immune profiling study of 550 elderly participants (≥60 years) and 100 young controls (20-40 years) from the RESIST Senior Individuals (SI) cohort.

Clinical studies of blood-borne Extracellular vesicles in psychiatry: A systematic review.

Biomarkers for the diagnosis and clinical management of psychiatric disorders are currently lacking. Extracellular vesicles (EVs), lipid membrane-encapsulated vesicles released by cells, hold promise as a source of biomarkers due to their ability to carry molecules that reflect the status of their donor cells and their ubiquitous presence in biofluids. This review examines the literature on EVs in biofluids from psychiatric disorder patients, and discuss how the published studies contribute to our understanding of the pathophysiology of these conditions and to the discovery of potential biomarkers.

Characterization of a cell-adapted completely attenuated genotype GIIa porcine epidemic diarrhea virus strain.

Porcine epidemic diarrhea virus (PEDV) has caused significant harm to the global pig industry since its discovery. In this study, a highly pathogenic strain of GIIa PEDV CH/HBXT/2018, isolated previously, was continuously passaged in Vero cells up to passage (P)240, resulting in a completely attenuated virus. The proliferation characteristics of different passages of the strain in Vero cells, pathogenicity in newborn piglets, and mutations in S gene sequence indicated that as the passage number increased, the replication efficiency of PEDV in Vero cells gradually improved, with a more pronounced cytopathic effect.

Anticancer diiron aminocarbyne complexes with labile N-donor ligands.

The novel diiron amine complexes [FeCp(CO)(NHR')(μ-CO){μ-CN(Me)(Cy)}]CFSO [R' = H, 3; Cy, 4; CHCHNH, 5; CHCHNMe, 6; CHCH(4-CHOMe), 7; CHCH(4-CHOH), 8; Cp = η-CH, Cy = CH = cyclohexyl] were synthesized in 49-92 % yields from [FeCp(CO)(μ-CO){μ-CN(Me)(Cy)}]CFSO, 1a, using a straightforward two-step procedure. They were characterized by IR and multinuclear NMR spectroscopy, and the structure of 7 was confirmed through X-ray diffraction analysis. Complexes 3-8 and the acetonitrile adducts [FeCp(CO)(NCMe)(μ-CO){μ-CN(Me)(R)}]CFSO (R = Cy, 2a; Me, 2b; Xyl = 2,6-CHMe, 2c) were assessed for their water solubility, octanol-water partition coefficient and stability in physiological-like solutions.

Antibacterial activity and multi-target mechanism of harmane against Escherichia coli O157:H7 and its application on ready-to-eat leafy greens.

Escherichia coli O157:H7 has caused many foodborne disease outbreaks and resulted in unimaginable economic losses. With the evolution of food consumption, people prefer natural preservatives. In this study, the natural agent harmane exhibited potential activity against E.

A novel genetically encoded indicator for deciphering cytosolic and mitochondrial nitric oxide in live cells.

Nitric oxide (NO) has been highlighted as a key gaseous signaling molecule in the body, playing a central role in various physiological and pathological processes. However, a comprehensive analysis of NO metabolism dynamics in living cells remains a significant challenge. To address this, we have developed and characterized a novel genetically encoded NO fluorescence sensor, GefiNO, to investigate NO metabolism dynamics in living cells and subcellular organelles.

α-amanitin induces hepatotoxicity via PPAR-γ inhibition and NLRP3 inflammasome activation.

Mushroom poisoning, predominantly caused by α-amanitin, is a critical food safety concern in worldwide, with severe cases leading to hepatotoxicity and fatalities. This study delves into the hepatotoxic effects of α-amanitin, focusing on the NLRP3 inflammasome and PPAR-γ's regulatory role in inflammation. In vitro studies with L-02 cells showed that α-amanitin reduces cell viability and triggers NLRP3 inflammasome activation, increasing NF-κB phosphorylation and pro-inflammatory cytokines IL-18 and IL-1β.

Emerging roles for tubulin PTMs in neuronal function and neurodegenerative disease.

Neurons are equipped with microtubules of different stability with stable and dynamic domains often coexisting on the same microtubule. While dynamic microtubules undergo random transitions between disassembly and assembly, stable ones persist long enough to serve as platforms for tubulin-modifying enzymes (known as writers) that attach molecular components to the α- or β-tubulin subunits. The combination of these posttranslational modifications (PTMs) results in a "tubulin code," dictating the behavior of selected proteins (known as readers), some of which were shown to be crucial for neuronal function.

A new vaccination approach for Salmonellosis employing a multi-epitope vaccine based on live microbial cell factory from Lactococcus lactis.

A major health and financial burden in the chicken sector is salmonella infection. It is difficult to create an oral vaccination that can provide strong intestinal mucosal immunity in birds, particularly cross-protection against several Salmonella serotypes. As a result, the poultry industry needs a powerful oral vaccination platform that uses live bacterial vectors to prevent various Salmonella serotypes.

A single-cell sequencing-based analysis of a 13-year-old with maxillary sinus NUT carcinoma.

NUT carcinoma is a rare and highly aggressive malignancy, predominantly affecting adolescents and young adults. This tumor demonstrates rapid progression, resistance to conventional anti-cancer treatments, and an extremely poor prognosis. Currently, research on NUT carcinoma is limited, and effective treatment options remain scarce.

Melatonin protects aged oocytes from depalmitoylation-mediated quality reduction by promoting PPT1 degradation and antioxidation.

Oocyte aging is closely related to a decline in female fertility, accompanied by increased reactive oxygen species levels and changes in protein posttranslational modifications. However, the role of protein palmitoylation in oocyte aging has not been investigated. In the present study, a new association between redox and palmitoylation in aging oocytes was found.

HemaScope: A Tool for Analyzing Single-cell and Spatial Transcriptomics Data of Hematopoietic Cells.

Single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics (ST) techniques hold great value in evaluating the heterogeneity and spatial characteristics of hematopoietic cells within tissues. These two techniques are highly complementary, with scRNA-seq offering single-cell resolution and ST retaining spatial information. However, there is an urgent demand for well-organized and user-friendly toolkits capable of handling single-cell and spatial information.

Emerging insights into the impact of systemic metabolic changes on tumor-immune interactions.

Tumors are inherently embedded in systemic physiology, which contributes metabolites, signaling molecules, and immune cells to the tumor microenvironment. As a result, any systemic change to host metabolism can impact tumor progression and response to therapy. In this review, we explore how factors that affect metabolic health, such as diet, obesity, and exercise, influence the interplay between cancer and immune cells that reside within tumors.

The Hao-Fountain syndrome protein USP7 regulates neuronal connectivity in the brain via a novel p53-independent ubiquitin signaling pathway.

Mutation or deletion of the deubiquitinase USP7 causes Hao-Fountain syndrome (HAFOUS), which is characterized by speech delay, intellectual disability, and aggressive behavior and highlights important unknown roles of USP7 in the nervous system. Here, we conditionally delete USP7 in glutamatergic neurons in the mouse forebrain, triggering disease-relevant phenotypes, including sensorimotor deficits, impaired cognition, and aggressive behavior. Although USP7 deletion induces p53-dependent neuronal apoptosis, most behavioral abnormalities in USP7 conditional knockout mice persist following p53 loss.

Protocol for identifying Dicer as dsRNA binding and cleaving reagent in response to transfected dsRNA.

Mammalian Dicer has been proved to be functional on double-stranded RNAs (dsRNAs) and involved in antiviral immunity or immune regulation. Here, we present a protocol for identifying Dicer as a dsRNA binding and cleaving factor to transfected dsRNA in cell lines, based on small RNA sequencing (RNA-seq) and dsRNA-immunoprecipitation (dsRNA-IP). We detail both experimental processes and analysis on small RNA-seq data.

Protocol for extraction of gut interstitial fluid in mice with two-front nutrient supply.

The intestine features a two-front nutrient supply environment, comprising an enteral side enriched with microbial and dietary metabolites and a serosal side supplied by systemic nutrients, collectively supporting intestinal and systemic homeostasis, but there is currently no optimal approach for extracting and assessing the local intestinal microenvironment. Here, we present a protocol for constructing a nutrient supply model in mice and extracting gut interstitial fluid (GIF) via centrifugation. This model and the extracted GIF are suitable for downstream analyses.

Pro-cumulin addition in a biphasic in vitro oocyte maturation system modulates human oocyte and cumulus cell transcriptomes.

Biphasic in vitro oocyte maturation (IVM) can be offered as a patient-friendly alternative to conventional ovarian stimulation in in vitro fertilization (IVF) patients predicted to be hyper-responsive to ovarian stimulation. However, cumulative live birth rates after IVM per cycle are lower than after conventional ovarian stimulation for IVF. In different animal species, supplementation of IVM media with oocyte-secreted factors (OSFs) improves oocyte developmental competence through the expression of pro-ovulatory genes in cumulus cells.

Telomerase in cancer- ongoing quest and future discoveries.

Telomerase, constituted by the dynamic duo of telomerase reverse transcriptase (TERT), the catalytic entity, and an integral RNA component (TERC), is predominantly suppressed in differentiated human cells due to postnatal transcriptional repression of the TERT gene. Dysregulation of telomerase significantly contributes to cancer development via telomere-dependent and independent mechanisms. Telomerase activity is often elevated in advanced cancers, with TERT reactivation and upregulation of TERC observed in early tumorigenesis.