zDHHC8 suppresses infection-induced necroptosis in monocyte/macrophages through palmitoylation of necrosome components in large yellow croaker (Larimichthys crocea).

Palmitoylation, a reversible post-translational modification, regulates a wide range of cellular processes by modulating protein localization, stability, and interactions. The zinc finger Asp-His-His-Cys (zDHHC) family of palmitoyltransferases is central to this process, yet their functions in immune cell death of lower vertebrates, remain poorly understood. Here, we investigate the role of zDHHC8 in modulating immune responses and necroptosis during infection in large yellow croaker (LczDHHC8).

A fish-specific antimicrobial peptide Piscidin2 inactivates MSRV and confers protection in largemouth bass.

Antimicrobial peptides (AMPs) represent an evolutionarily conserved component of innate immunity with broad-spectrum antimicrobial and antiviral activities. However, the antiviral potential of fish-specific piscidins against emerging aquatic viruses largely remains to be explored. In this study, we evaluated the antiviral properties of three piscidins (designated here as Piscidin1, Piscidin2 and Piscidin3) identified from largemouth bass () against rhabdovirus (MSRV), a major pathogen causing high mortality in farmed largemouth bass.

Clinical, radiological, pathological and prognostic features of general paresis: a cohort study.

General paresis is a rare type of syphilis characterized by progressive cognitive impairment and psychiatric syndromes. It is often misdiagnosed because of its rarity and similarity to other diseases. We aimed to investigate the clinical, radiological, pathological and prognostic features of general paresis comprehensively and to compare it with other dementias.

Exome sequencing identifies protein-coding variants associated with loneliness and social isolation.

Background: Loneliness and social isolation are serious yet underappreciated public health problems, with their genetic underpinnings remaining largely unknown. We aimed to explore the role of protein-coding variants in the manifestation of loneliness and social isolation.

Methods: We conducted the first exome-wide association analysis on loneliness and social isolation, utilizing 336,115 participants of white-British ancestry for loneliness and 346,115 for social isolation.

Palmitoylation-mediated NLRP3 inflammasome activation in teleosts highlights evolutionary divergence in immune regulation.

NLRP3 inflammasome activation is pivotal for cytokine secretion and pyroptosis in response to diverse stimuli, playing a crucial role in innate immunity. While extensively studied in mammals, the regulatory mechanisms governing NLRP3 activation in non-mammalian vertebrates remain largely unexplored. Teleosts, as basal vertebrates, represent an ideal model for exploring the evolutionary trajectory of inflammasome regulation.

Molecular cloning and functional characterization of Caspase-8 in goldfish (Carassius auratus L.).

Apoptosis, a form of programmed cell death, is essential for maintaining homeostasis within the internal environment. Caspase-8, an initiator caspase, plays a pivotal role in activating the caspase cascade during the apoptotic process. This study cloned and expressed Caspase-8 from goldfish, aimed to investigate the role of Caspase-8 in the immune response of fish to bacterial infections, specifically those caused by Aeromonas hydrophila.

Consecutive palmitoylation and phosphorylation orchestrates NLRP3 membrane trafficking and inflammasome activation.

NLRP3 inflammasome activation, essential for cytokine secretion and pyroptosis in response to diverse stimuli, is closely associated with various diseases. Upon stimulation, NLRP3 undergoes subcellular membrane trafficking and conformational rearrangements, preparing itself for inflammasome assembly at the microtubule-organizing center (MTOC). Here, we elucidate an orchestrated mechanism underlying these ordered processes using human and murine cells.

The anti-inflammatory role of zDHHC23 through the promotion of macrophage M2 polarization and macrophage necroptosis in large yellow croaker ().

Zinc finger Asp-His-His-Cys motif-containing (zDHHC) proteins, known for their palmitoyltransferase (PAT) activity, play crucial roles in diverse cellular processes, including immune regulation. However, their non-palmitoyltransferase immunomodulatory functions and involvement in teleost immune responses remain underexplored. In this study, we systematically characterized the zDHHC family in the large yellow croaker (), identifying 22 members.

Genetic associations of protein-coding variants in venous thromboembolism.

Previous genetic studies of venous thromboembolism (VTE) have been largely limited to common variants, leaving the genetic determinants relatively incomplete. We performed an exome-wide association study of VTE among 14,723 cases and 334,315 controls. Fourteen known and four novel genes (SRSF6, PHPT1, CGN, and MAP3K2) were identified through protein-coding variants, with broad replication in the FinnGen cohort.

Exome sequencing identifies genes associated with sleep-related traits.

Sleep is vital for human health and has a moderate heritability. Previous genome-wide association studies have limitations in capturing the role of rare genetic variants in sleep-related traits. Here we conducted a large-scale exome-wide association study of eight sleep-related traits (sleep duration, insomnia symptoms, chronotype, daytime sleepiness, daytime napping, ease of getting up in the morning, snoring and sleep apnoea) among 450,000 participants from UK Biobank.

The emerging roles of lysine-specific demethylase 4A in cancer: Implications in tumorigenesis and therapeutic opportunities.

Lysine-specific demethylase 4 A (KDM4A, also named JMJD2A, KIA0677, or JHDM3A) is a demethylase that can remove methyl groups from histones H3K9me2/3, H3K36me2/3, and H1.4K26me2/me3. Accumulating evidence suggests that KDM4A is not only involved in body homeostasis (such as cell proliferation, migration and differentiation, and tissue development) but also associated with multiple human diseases, especially cancers.

Current understanding of the cGAS-STING signaling pathway: Structure, regulatory mechanisms, and related diseases.

The innate immune system protects the host from external pathogens and internal damage in various ways. The cGAS-STING signaling pathway, comprised of cyclic GMP-AMP synthase (cGAS), stimulator of interferon genes (STING), and downstream signaling adaptors, plays an essential role in protective immune defense against microbial DNA and internal damaged-associated DNA and is responsible for various immune-related diseases. After binding with DNA, cytosolic cGAS undergoes conformational change and DNA-linked liquid-liquid phase separation to produce 2'3'-cGAMP for the activation of endoplasmic reticulum (ER)-localized STING.

Taxifolin Inhibits WSSV Infection and Transmission by Increasing the Innate Immune Response in .

An outbreak of white spot syndrome virus (WSSV) can hit shrimp culture with a devastating blow, and there are no suitable measures to prevent infection with the virus. In this study, the activity of active molecules from Chinese herbs against WSSV was evaluated and screened. Taxifolin had the highest rate (84%) of inhibition of the WSSV infection.

Paramecium bursaria as a Potential Tool for Evaluation of Microplastics Toxicity.

Microplastics (MPs) are normally defined as small plastic wastes with a size of 1 μm to 5 mm in diameter. This tiny plastic debris is abundant in aquatic systems and poses a great threat to aquatic biota. To date, toxicological assessment of MPs is predominantly dependent on metazoan animals, although their applications are sometimes limited due to the high cost, narrow ecological niche, or ethical considerations.

Molecular and functional characterization of a ladderlectin-like molecule from ayu (Plecoglossus altivelis).

Ladderlectin is a member of C-type lectins (CTLs) in teleost fish and involved in innate immune defense. In this study, ayu (Plecoglossus altivelis) ladderlecin-like (PaLL-like) sequence was cloned, which encodes a polypeptide of 172 amino acids that includes a signal peptide and characteristic C-type lectin-like domains (CTLDs). Phylogenetically, PaLL-like was most closely related to its teleost counterpart from shishamo smelt (Spirinchus lanceolatus).

Prior exposure to ciprofloxacin disrupts intestinal homeostasis and predisposes ayu ( ) to subsequent -induced infection.

With the rapid development of intensive farming, the aquaculture industry uses a great many antibiotics for the prevention and treatment of bacterial diseases. Despite their therapeutic functions, the overuse and accumulation of antibiotics also pose a threat to aquaculture organisms. In the present study, ayu ( ) was used as a fish model to study the impacts of ciprofloxacin (CIP) overuse on intestinal homeostasis and immune response during subsequent infection.

Molecular characterization, expression and functional analysis of large yellow croaker (Larimichthys crocea) peroxisome proliferator-activated receptor gamma.

The peroxisome proliferator-activated receptor gamma (PPARγ) are nuclear receptors with distinct roles in energy metabolism and immunity. Although extensively studied in mammals, immunomodulatory roles of this molecule in teleost fish remain to be investigated. In this study, large yellow croaker (Larimichthys crocea) PPARγ (LcPPARγ) sequence was cloned, which encodes a polypeptide of 541 amino acids that include signature domains belonging to the nuclear receptor superfamily.

An Imaging Flow Cytometry Protocol for Studying Immunoregulatory Receptor-Mediated Regulation of Phagocytosis.

Advances in flow cytometry have allowed for innovative functional investigations of innate immune cell responses. Imaging flow cytometers combine the imaging capabilities of microscopy with rapid, high-throughput data acquisition attributes of standard flow cytometers. Here, we describe a detailed method for co-expressing stimulatory and inhibitory immunoregulatory receptor-types in AD293 cells and then measuring receptor cross-talk during the regulation of the phagocytic response.

Potential Applications of Fluorescence-Activated Cell Sorting (FACS) and Droplet-Based Microfluidics in Promoting the Discovery of Specific Antibodies for Characterizations of Fish Immune Cells.

Akin to their mammalian counterparts, teleost fish possess a complex assortment of highly specialized immune cells that are capable of unleashing potent innate immune responses to eradicate or mitigate incoming pathogens, and also differentiate into memory lymphocytes to provide long-term protection. Investigations into specific roles and functions of fish immune cells depend on the precise separation of each cell type. Commonly used techniques, for example, density gradient centrifugation, rely on immune cells to have differing sizes or densities and thus fail to separate between similar cell types (e.