HBV Precore G1896A Mutation Promotes Malignancy of Hepatocellular Carcinoma by Activating Endoplasmic Reticulum Stress to Enhance Aerobic Glycolysis.

Hepatitis B virus (HBV) precore G1896A mutation is closely associated with poor prognosis of liver disease. We previously revealed that the G1896A mutation could enhance HBV replication and promote hepatocellular carcinoma (HCC) cell growth both in vitro and in vivo. However, the in-depth mechanisms by which this mutation promotes the malignancy of HCC still need to be explored.

ChREBP-Mediated Choline Deprivation and Chemokine Secretion Shape Tumor-Associated Macrophages to Promote Immune Evasion.

Tumor metabolic reprogramming has been recognized as a critical determinant in tumor development and cancer immunotherapy response. Aberrant choline metabolism is emerging as a defining hallmark of cancer. Here, we found that carbohydrate responsive element binding protein (ChREBP)-mediated choline deprivation induced tumor-associated macrophage (TAM) reprogramming and maintained an immunosuppressive tumor microenvironment (TME).

Genome-Wide Simplification of the AcMNPV Genome Using Synthetic Biology.

Large-scale genome simplification represents a fundamental goal in synthetic biology. Baculoviruses, with their biphasic life cycle and inherent genomic plasticity, have emerged as ideal models for synthetic genome engineering. Although modified baculovirus genomes are widely used as expression vectors for robust recombinant protein production, many genomic regions are dispensable for in vitro budded virus (BV) production.

Ubiquitously expressed transcript isoform 2 (UXT-V2) restricts HSV-2 replication by targeting glycoprotein B for degradation through ubiquitin-proteasome pathway.

Herpes simplex virus 2 (HSV-2) is a major pathogen causing neonatal herpes and increasing the risk of human immunodeficiency virus 1 (HIV-1) infection. However, the mechanisms underlying host restriction of HSV-2 infection are still not fully understood. The ubiquitously expressed transcript isoform 2 (UXT-V2), an α-type prefoldin protein, functions as a versatile transcription factor associated with numerous human tumors, but its role in viral infection remains unclear.

Salvianolic acid A from Salvia miltiorrhiza identified as a cap-dependent endonuclease inhibitor for pathogenic arenaviruses.

Negative-stranded segmented RNA viruses (NSVs) employ a cap-snatching mechanism for transcription, which makes cap-dependent endonuclease (CEN) an attractive target for drug development. Pathogenic arenaviruses pose a serious threat to humans, yet no approved treatments exist, underscoring the importance of discovering novel compounds targeting arenaviral CENs. Therefore, this study aimed to identify novel CEN inhibitors for arenaviruses and investigate their antiviral mechanisms.

An alphavirus vaccine development utilizing RNA replication-defective strategy.

Alphaviruses are arthropod-borne viruses that cause widespread disease. However, many pathogenic alphaviruses are classified as risk group 3 human pathogens, which hampers the development of vaccines and therapeutic agents targeting alphavirus infections. In this study, we developed a RNA replication-defective Venezuelan equine encephalitis virus that has a complete nsP4 gene deletion (VEEV-△nsP4).

Combined use of vitamin C and antifolates induces cuproptosis-like bacterial death.

Combined use of antimicrobial agents is a key strategy to combat antimicrobial resistance. After several decades of approval, clinical application of the classical combination co-trimoxazole has gradually become limited, mainly due to the prevalence of resistance. Vitamin C is a natural antimicrobial and redox agent.

Mechanistic insights into Nipah virus 5' UTR functionality reveal an antiviral target.

The highly pathogenic Nipah virus (NiV), a World Health Organization priority pathogen with pandemic potential, remains a critical public health threat due to its capacity to cause fatal encephalitis and respiratory disease. Despite its 1998 emergence, no approved therapeutics exist against NiV infection, underscoring the urgent need to identify genomic regulatory elements as antiviral targets. Our study focuses on the extended 5' UTRs characteristic of NiV transcripts, a distinctive genomic feature whose functional significance remained enigmatic.

Interferon-stimulated gene screening identifies CCND3 as a host restriction factor against emerging high-pathogenic bandaviruses.

Severe fever with thrombocytopenia syndrome virus (SFTSV) is a representative high-pathogenic bandavirus (Bandavirus genus, Phenuiviridae family). Inducible expression of interferon-stimulated genes (ISGs) is the foundation of host antiviral defense; however, their roles in bandavirus infection remain elusive. Here, we identify over 200 ISGs potentially inhibiting or promoting bandaviral replication.

Recombinant live attenuated measles virus-based vaccines inducing comprehensive protection against Ebola and Marburg viruses.

Filoviruses, including Ebola and Marburg viruses, present significant global health challenges due to their high mortality rates. Despite the availability of several Ebola virus vaccines, none provide cross-protection against multiple filovirus species. In this study, we developed recombinant live attenuated measles virus-based vaccine candidates designed to express Ebola or Marburg virus glycoproteins and generate virus-like particles for pan-filovirus immunization.

Emergence of IIc Subtype and Assemblage E in AIDS Patients in Central China: Evidence for Neglected Transmission Dynamics.

Zoonotic opportunistic enteric protozoa represent a significant global health threat to immunocompromised populations, especially individuals with human immunodeficiency virus (HIV). Despite China's severe HIV burden, molecular epidemiological data on enteric protozoa remain limited in this population. In this study, we investigated the occurrence and molecular characteristics of species, , and among 150 AIDS patients with severe immunodeficiency in Wuhan city, Hubei Province, China.

A Randomized, Open-Label, Single-Dose, Parallel-Group Bioequivalence Study of Ferric Carboxymaltose Injection Under Fasting Conditions in Chinese Adult Subjects With Iron Deficiency Anemia.

The objectives of this study were to compare the pharmacokinetics and safety profiles of the test (T) preparation (Ferric carboxymaltose injection, BrightGene Bio-Medical Technology Co. Ltd.) and reference (R) preparation (Ferinject, Vifor France) after intravenous injection in Chinese adult subjects with iron deficiency anemia (IDA) under fasting conditions.

Soluble MFGE8 mediates cell entry of Crimean-Congo hemorrhagic fever virus.

Unlabelled: Crimean Congo hemorrhagic fever virus (CCHFV) causes fatal tick-borne disease in humans and is a priority pathogen of the World Health Organization. No licensed vaccines or specific antiviral drugs are available. To understand the cell entry of CCHFV and identify potential antiviral targets to combat the disease, here, we perform the CRISPR knockout screen in wild-type cells, followed by a complementary CRISPR activation screen in cells deficient in common attachment factors (heparan sulfate, AXL, TIM-1).

Metagenomic evidence of viral secretion from tick salivary glands to saliva: implications for potential horizontal transmission.

Ticks transmit diverse viral pathogens to hosts during blood-feeding via saliva secretion. This study characterized viral compositions in salivary glands and saliva from adults of four tick species (Ixodes persulcatus, Rhipicephalus microplus, Haemaphysalis longicornis, and Haemaphysalis concinna) collected in China. Meta-transcriptomic analysis revealed distinct viromes across species, with Flaviviridae dominant in R.

The mRNA vaccine encoding Gc protein confers complete protection against severe fever with thrombocytopaenia syndrome virus.

Severe fever with thrombocytopaenia syndrome virus (SFTSV), an emerging tick-borne pathogen, causes haemorrhagic fever in infected patients and is associated with a high mortality rate in humans. The imperative need for vaccines against this lethal virus is underscored by a lack of effective preventive measures. The results of this study yield notable advancements: the successful development of an SFTSV mRNA vaccine encoding the glycoprotein C (Gc) gene, achieving N-linked glycosylation in the expressed protein.

Correction: Pre-activation of toll-like receptor 2 enhances CD8+ T-cell responses and accelerates hepatitis B virus clearance in the mouse models.

[This corrects the article DOI: 10.3389/fimmu.2018.

Stepwise degradation of bisphenol A into various monocyclic aromatic hydrocarbons by a P450 enzyme BisdB in Sphingobium yanoikuyae GDP.

Bisphenol A (BPA) is a frequently used endocrine-disrupting chemical widely distributed in the environment, necessitating effective removal strategies. This study aimed to isolate and characterize a highly efficient BPA-degrading bacterial strain, Sphingobium yanoikuyae GDP, and to elucidate the enzymatic degradation pathways of BPA mediated by the P450 enzyme BisdB, including the identification of novel metabolites using C stable isotope-assisted untargeted liquid chromatography-tandem mass spectrometry. In this study, a BPA-degrading microbial community, D45, was isolated from contaminated soil and degraded 400 mg L of BPA within 24 h.

Non-coding RNA mediates the defense-associated reverse transcriptase (DRT) anti-phage oligomerization transition.

Defense-associated reverse transcriptase (DRT) systems are implicated in prokaryotic resistance to viral infections, yet the molecular mechanisms underlying their functionality remain largely unknown. Here, we characterize a two-component DRT9 system, composed of a reverse transcriptase (RT) and a non-coding RNA (ncRNA), which exhibits a protein-primed DNA synthesis activity upon phage infection. We also determine its cryo-electron microscopy (cryo-EM) structures in different functional states.

Potential of antibacterial polysaccharides to serve as a promising alternative to conventional antibiotics: challenges and future prospects.

Antibacterial polysaccharides are emerging as viable substitutes for conventional antibiotics by combining a variety of bactericidal mechanisms with their inherent biocompatibility and biodegradability. This study reviewed findings from articles (approximately 110 manuscripts published between 2013 and 2024), reporting sources, extraction and use of polysaccharides (with antibacterial properties) from nature such as microbiological exopolysaccharides, chitosan and alginate. A lot of natural polysaccharides, like chitosan and alginate, possess the ability to break down bacterial cell walls and biofilms, but they don't harm human cells or even commensal microbiota.

RNAi-based antiviral immunity.

RNA interference (RNAi) is a gene silencing mechanism mediated by small RNAs derived from double-stranded RNA (dsRNA), capable of silencing specific genes. Following viral invasion, the dsRNA produced during viral replication is cleaved by the host cell's Dicer protein, generating virus-derived small interfering RNAs (virus-derived small interference RNAs, vsiRNA). These vsiRNAs then guide the cleavage and degradation of viral RNA the RNAi pathway, exerting an antiviral effect.

An African swine fever virus-specific antibody reactome reveals antigens as potential candidates for vaccine development.

Developing an efficient and safe vaccine for African swine fever (ASF), a devastating disease of pigs, remains a significant challenge mainly due to limited knowledge of the immune correlates of protection. Identifying protective determinants is difficult because ASF virus (ASFV) is a large and complex DNA virus encoding over 160 proteins. Here, we constructed an ASFV proteome microarray containing 160 full-length proteins for profiling ASFV-specific antibodies.

MMP-9 regulates disulphide isomerase activity of TGM2 to enhance fusion glycoprotein-mediated syncytium formation of respiratory syncytial virus.

Respiratory syncytial virus (RSV) exploits host proteases to enhance its replication efficiency; however, the precise mechanisms remain unclear. Through high-throughput screening, we identified four matrix metalloproteinase 9 (MMP-9) inhibitors (including JNJ0966 and doxycycline hyclate) that suppress RSV infection in vitro and in vivo. Mechanistic studies revealed a proteolytic cascade wherein MMP-9 cleaves transglutaminase 2 (TGM2) at the PVP375↓VR site, generating an N-terminal fragment (1-375) that activates its protein disulfide isomerase (PDI) activity.