Neferine inhibits Zika virus replication by targeting viral protease.

Background: Zika virus (ZIKV) belonging to the Flaviviridae family causes critical neurological abnormalities, including congenital microcephaly and Guillain-Barré syndrome. Despite being a major public health concern, effective therapeutic interventions against ZIKV remain unavailable. NS2B-NS3 (ZIKVpro), the viral serine protease critical for polyprotein processing as well as viral replication, is a potential target for developing antiviral agents PURPOSE: This study aims to develop ZIKV inhibitors targeting the ZIKVpro from natural products.

SLFN11 Restricts LINE-1 Mobility.

Long interspersed element-1 (LINE-1) is the only active autonomous transposon comprising about 17% of human genomes. LINE-1 transposition can cause the mutation and rearrangement of the host's genomic DNA. The host has, therefore, developed multiple mechanisms to restrict LINE-1 mobility.

Chimeric hemagglutinin and M2 mRNA vaccine for broad influenza subtype protection.

Since multiple and unpredicted influenza viruses cause seasonal epidemics and even high-risk pandemics, developing a universal influenza vaccine is essential to provide broad protection against various influenza subtypes. Combined with the mRNA lipid nanoparticle-encapsulated (mRNA-LNP) vaccine platform and chimeric immunogen strategy, we developed a novel cocktail mRNA vaccine encoding chimeric HAs (cH5/1-BV, cH7/3) and intact M2 (termed Fluaxe), which confers broad protection against major circulating IAVs and IBVs, as well as highly pathogenic avian influenza. Two-dose intramuscular immunization of Fluaxe in mice elicited cross-reactive neutralizing antibodies, T cell responses, and long-lived immunity, resulting in robust protection against multiple lethal influenza virus infections and severe acute lung injuries.

Maximal inhibitory effect of MOV10 on LINE-1 retrotransposition requires both the MOV10/LINE-1 association and granule formation.

LINE-1 is the only active autonomous mobile element in the human, and its mobilization is tightly restricted by the host to maintain genetic stability. We recently reported that human MOV10 recruits DCP2 to decap LINE-1 RNA by liquid-liquid phase separation (LLPS), resulting in the inhibition of LINE-1 retrotransposition, while the detailed mechanism still awaits further exploration. In this report, we found that the extended motif II (563-675aa) and the C-terminal domain (907-1003aa) of MOV10 cooperated to achieve maximal inhibition on LINE-1 retrotransposition.

Microbial-algal symbiotic system drives reconstruction of nitrogen, phosphorus, and methane cycles for purification of pollutants in aquaculture water.

Intensive aquaculture's excessive nitrogen, phosphorus, and methane emissions caused environmental degradation. This study explored how algae-bacteria symbiotic systems (ABSS) enhanced water purification by regulating element cycles. We established a Chlorella pyrenoidosa-Bacillus subtilis symbiotic system.

Study on the Toxicological Impacts of Intraperitoneal Microcystin-LR Injection on GIFT Tilapia () Through Multi-Omics Analysis.

This study employed multi-omics analysis to systematically evaluate the toxic effects of intraperitoneal injection of MC-LR on GIFT tilapia. The results showed that 96 h post injection, serum levels of aspartate GOT, GPT, LYZ, T-AOC, and SOD significantly decreased ( < 0.05).

Protection efficacy of mRNA-based SARS-CoV-2 variant vaccine in non-human primates.

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model.

Thonningianin A disrupts pA104R-DNA binding and inhibits African swine fever virus replication.

African swine fever is a highly lethal disease caused by the African swine fever virus (ASFV), posing a significant threat to the global pig industry, wherease no approved treatments are currently available. The ASFV DNA-binding protein, pA104R, plays a critical role in viral genome packaging and replication, making it a key target for drug discovery. Through structure-based virtual screening, we identified a polyphenolic compound, thonningianin A, which disrupts the pA104R-DNA binding and significantly inhibits ASFV replication.

Discovery and optimization of phenazopyridine hydrochloride as novel SARS-CoV-2 RdRp inhibitors.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is the pathogen of coronavirus disease (COVID-19) causing a pandemic with growing global transmission. The viral RNA-dependent RNA polymerase (RdRp) is conserved especially for variants of concern (VOCs), making it as an effective antivirals target. Due to the proofreading activity of coronavirus nsp14/nsp10, limited the efficacy of nucleoside analogs in vivo.

Polystyrene nanoplastics amplify the toxic effects of PFOA on the Chinese mitten crab (Eriocheir sinensis).

Nanoplastics (NPs), the final form of degraded microplastics in the environment, can adsorb PFOA (an emerging organic pollutant in recent years) in several ways. Current research on these has focused on bony fishes and mollusks, however, the combined toxicity of PFOA and NPs remains unknown in Eriocheir sinensis. Therefore, the effects of single or combined exposure to PFOA and NPs were investigated.

Probiotics Enhance Growth Performance and Nutritional Value by Regulating Glucolipid Metabolism via the Gut-Liver Axis.

Large-scale intensive feeding triggered reduced growth performance and nutritional value. Exogenous probiotics can promote the growth performance and nutritional value of fish through improving the intestinal microbiota. However, detailed research on the correlation between the intestinal microbiota, growth performance, and nutritional value remains to be elucidated.

Novel virulence determinants in VP1 regulate the assembly of enterovirus-A71.

Unlabelled: Enterovirus-A71 (EV-A71) is the second most common causative agent after coxsackievirus A16 of hand, foot, and mouth disease. The capsids of EV-A71 consist of 60 copies of each of the four viral structural proteins (VP1-VP4). VP1 is highly exposed and surface accessible, playing a central role in virus particle assembly, attachment, and entry.

Interferon-induced MXB protein restricts vimentin-dependent viral infection.

Type I interferon (IFN) inhibits a wide spectrum of viruses through stimulating the expression of antiviral proteins. As an IFN-induced protein, myxovirus resistance B (MXB) protein was reported to inhibit multiple highly pathogenic human viruses. It remains to be determined whether MXB employs a common mechanism to restrict different viruses.

Integrative analysis of metagenome and metabolome provides new insights into intestinal health protection in Coilia nasus larvae via probiotic intervention.

With the development of large-scale intensive feeding, growth performance and animal welfare have attracted more and more attention. Exogenous probiotics can promote the growth performance of fish through improving intestinal microbiota; however, it remains unclear whether intestinal microbiota influence physiological biomarkers. Therefore, we performed metagenomic and metabolomic analysis to investigate the effects of a 90-day Lactiplantibacillus plantarum supplementation to a basal diet (1.

CX-6258 hydrochloride hydrate: A potential non-nucleoside inhibitor targeting the RNA-dependent RNA polymerase of norovirus.

Human norovirus (HuNoV), a primary cause of non-bacterial gastroenteritis, currently lacks approved treatment. RdRp is vital for virus replication, making it an attractive target for therapeutic intervention. By application of structure-based virtual screening procedure, we present CX-6258 hydrochloride hydrate as a potent RdRp non-nucleoside inhibitor, effectively inhibiting HuNoV RdRp activity with an IC of 3.

The novel small molecule E0924G dually regulates bone formation and bone resorption through activating the PPARδ signaling pathway to prevent bone loss in ovariectomized rats and senile mice.

Osteoporosis is particularly prevalent among postmenopausal women and the elderly. In the present study, we investigated the effect of the novel small molecule E0924G (N-(4-methoxy-pyridine-2-yl)-5-methylfuran-2-formamide) on osteoporosis. E0924G significantly increased the protein expression levels of osteoprotegerin (OPG) and runt-related transcription factor 2 (RUNX2), and thus significantly promoted osteogenesis in MC3T3-E1 cells.

Metagenomic Insight into the Effect of Probiotics on Nitrogen Cycle in the Aquaculture Pond Water.

Recently, probiotics have been widely applied for the in situ remediation of aquatic water. Numerous studies have proved that probiotics can regulate water quality by improving the microbial community. Nitrogen cycling, induced by microorganisms, is a crucial process for maintaining the balance of the aquatic ecosystem.

Prometryn exposure disrupts the intestinal health of Eriocheir sinensis: Physiological responses and underlying mechanism.

Most toxicity studies of prometryn in non-target aquatic animals have focused on hepatotoxicity, cardiotoxicity, embryonic developmental and growth toxicity, while studies on the molecular mechanisms of intestinal toxicity of prometryn are still unknown. In the current study, the intestinal tissues of the Chinese mitten crab (Eriocheir sinensis) were used to uncover the underlying molecular mechanisms of stress by 96-h acute in vivo exposure to prometryn. The results showed that prometryn activated the Nrf2-Keap1 pathway and up-regulated the expression of downstream antioxidant genes.

Genome wide analysis revealed conserved domains involved in the effector discrimination of bacterial type VI secretion system.

Type VI secretion systems (T6SSs) deliver effectors into target cells. Besides structural and effector proteins, many other proteins, such as adaptors, co-effectors and accessory proteins, are involved in this process. MIX domains can assist in the delivery of T6SS effectors when encoded as a stand-alone gene or fused at the N-terminal of the effector.

Involvement of reactive oxygen species (ROS) in the hepatopancreatic cytotoxicity, oxidative stress, and apoptosis induced by microcystin-LR in Eriocheir sinensis.

There is limited knowledge about the toxicity of Microcystin-LR (MC-LR) in crustaceans, despite its high toxicity to aquatic organisms. This research aimed to explore the effects of MC-LR on cytotoxicity, oxidative stress, and apoptosis in the hepatopancreas of Eriocheir sinensis, as well as elucidate the involvement of reactive oxygen species (ROS) and potential mechanisms of toxicity. In vivo and in vitro exposures of crabs to MC-LR and N-acetylcysteine (NAC) were performed, followed by assessments of cell morphology, viability, tissue pathology, biochemical indicators, gene expression, and hepatopancreatic transcriptome.

A cell-based assay to discover inhibitors of Zika virus RNA-dependent RNA polymerase.

Zika virus (ZIKV) belongs to Flaviviridae, the Flavivirus genus. Its infection causes congenital brain abnormalities and Guillain-Barré syndrome. However, there are no effective vaccines, no FDA-approved drugs to manage ZIKV infection.

Schlafen-5 inhibits LINE-1 retrotransposition.

Long interspersed element 1 (LINE-1) is the only currently known active autonomous transposon in humans, and its retrotransposition may cause deleterious effects on the structure and function of host cell genomes and result in sporadic genetic diseases. Host cells therefore developed defense strategies to restrict LINE-1 mobilization. In this study, we demonstrated that IFN-inducible Schlafen5 (SLFN5) inhibits LINE-1 retrotransposition.

Effects of Prometryn Exposure on Hepatopancreas Oxidative Stress and Intestinal Flora in (Crustacea: Decapoda).

There is growing evidence that long-term exposure to prometryn (a widely used herbicide) can induce toxicity in bony fish and shrimp. Our previous study demonstrated its 96 h acute toxicity on the crab . However, studies on whether longer exposure to prometryn with a lower dose induces toxicity in are scarce.