Microbial biopesticides: A one health perspective on benefits and risks.

Controlling insect pests that destroy crop and spread diseases will become increasingly crucial for addressing the food demands of a growing global population and the expansion of vector-borne diseases. A key challenge is the development of a balanced approach for sustainable food production and disease control in 2050 and beyond. Microbial biopesticides, derived from bacteria, viruses, fungi, protozoa, or nematodes, offer potentially significant benefits for promoting One Health and contributing to several United Nations Sustainable Development Goals (SDGs).

Generation and characterization of OX40-ligand fusion protein that agonizes OX40 on T-Lymphocytes.

OX40, a member of the tumor necrosis factor (TNF) receptor superfamily, is expressed on the surface of activated T cells. Upon interaction with its cognate ligand, OX40L, OX40 transmits costimulatory signals to antigen-primed T cells, promoting their activation, differentiation, and survivalprocesses essential for the establishment of adaptive immunity. Although the OX40-OX40L interaction has been extensively studied in the context of disease treatment, developing a substitute for the naturally expressed membrane-bound OX40L, particularly a multimerized OX40L trimers, that effectively regulates OX40-driven T cell responses remains a significant challenge.

Interferon activation in bone marrow long-lived plasma cells in systemic lupus erythematosus.

While durable antibody responses from long-lived plasma cell (LLPC) populations are important for protection against pathogens, LLPC may be harmful if they produce antibodies against self-proteins or self-nuclear antigens as occurs in autoimmune diseases such as systemic lupus erythematosus (SLE). Thus, the elimination of autoreactive LLPC may improve the treatment of antibody-driven autoimmune diseases. However, LLPC remain a challenging therapeutic target.

Mixed histiocytic sarcoma in a Bernese Mountain Dog.

An 8-y-old, spayed female Bernese Mountain Dog was presented to a referral center for evaluation of right thoracic limb lameness and previously suspected Evans syndrome that had been poorly responsive to immunosuppressive therapy. Based on review of examination findings and laboratory data, Evans syndrome was deemed unlikely and hemophagocytic histiocytic sarcoma (HHS) was strongly suspected. On blood smear evaluation, atypical, histiocytic cells were noted, some of which exhibited siderophagia.

Antiviral effects and mechanism of Qi pi pill against influenza viruses.

Background: Qi pi pill (QPP), which contains Renshen, Baizhu, Fuling, Gancao, Chenpi, Shanyao, Lianzi, Shanzha, Liushenqu, Maiya, and Zexie, was recommended for preventing and treating COVID-19 in Shandong Province (China). However, the mechanism by which QPP treats infectious diseases remains unclear. This study aims to investigate the therapeutic effect of QPP in vitro and on acute influenza infection in mice, exploring its mechanism of action against influenza A virus (IAV).

Tumor-derived extracellular vesicle PD-1 promotes tumor immune evasion via disruption of peripheral T cell homeostasis.

The programmed cell death 1 (PD-1)/PD-1 ligand 1 (PD-L1) axis mediates immune evasion of tumor, and targeting this axis has achieved some clinical benefits. The regulation of PD-1 expression in immune cells has been well studied. However, whether any other potential source of immune cell-expressed PD-1 exists remains unknown.

HIV co-infection is associated with increased HLA-DR expression by Mycobacterium tuberculosis-specific CD4 T cells in people with latent tuberculosis infection.

Infection with HIV is associated with dysregulated CD4 T cell responses to Mycobacterium tuberculosis (Mtb) and increased risk of developing tuberculosis. Mtb-specific CD4 T cells in people with HIV have diminished Th1 cytokine production capacity, thus we utilized a flow cytometry-based assay to measure CD40L expression by Mtb-specific CD4 T cells in a cytokine-independent manner. We evaluated the frequency and phenotype of Mtb-specific CD4 responses in Kenyan adults with latent Mtb infection and found that the majority of Mtb-specific CD4 T cells expressed CD40L in the absence of IFN-γ, regardless of HIV infection status.

Cytosolic DNA composition is determined by genomic instability mechanism and regulates dendritic cell-mediated anti-tumor immunity.

Patients with colorectal cancers (CRCs) that have microsatellite instability (MSI) (MSI CRCs) face a better prognosis than those with the more common chromosomal instability (CIN) subtype (CIN CRCs) due to improved T cell-mediated anti-tumor immune responses. Previous investigations identified the cytosolic DNA (cyDNA) sensor STING as necessary for chemokine-mediated T cell recruitment in MSI CRCs. Here, we find that cyDNA from MSI CRC cells is inherently more capable of inducing STING activation and improves cytotoxic T cell activation by dendritic cells (DCs).

Evaluating convalescent plasma therapy in severe COVID-19: a retrospective cohort study.

Introduction: Convalescent plasma (CP) therapy is a form of passive immunization which has been used as a treatment for coronavirus disease 2019 (COVID-19). This study aims to evaluate the efficacy and safety of CP therapy in patients with severe COVID-19.

Methodology: In this retrospective cohort study, 50 patients with severe COVID-19 treated with CP at Shahid Beheshti Hospital, Kashan, in 2019 were evaluated.

The first reported case of candidemia caused by the novel Candida tropicalis diploid sequence type 1515.

Introduction: Since the dawn of the new millennium, Candida species have been increasingly implicated as a cause of both healthcare-associated as well as opportunistic yeast infections, due to the widespread use of indwelling medical devices, total parenteral nutrition, systemic corticosteroids, cytotoxic chemotherapy, and broad-spectrum antibiotics. Candida tropicalis is a pathogenic Candida species associated with considerable morbidity, mortality, and drug resistance issues on a global scale.

Methodology: We report a case of a 43-year-old man who was admitted to our hospital for further management of severe coronavirus disease 2019 (COVID-19) pneumonia.

The genus Nocardia as a source of new antimicrobials.

The genus Nocardia comprises over 130 species of soil-dwelling actinomycetes, many of which are opportunistic pathogens. Beyond their pathogenicity, Nocardia exhibits significant biosynthetic potential, producing an array of diverse antimicrobial secondary metabolites. This review highlights notable examples of these compounds and explores modern approaches to unlocking their untapped biosynthetic potential.

Randomized controlled trial on the efficacy of forest walking compared to urban walking in enhancing mucosal immunity.

Scientific research on forest therapy's preventive medical and mental health effects has advanced, but the need for clear evidence for practical applications remains. We conducted an unblinded randomized controlled trial involving healthy men aged 40-70 to compare the physiological and psychological effects of forest and urban walking. Eighty-four participants were randomly assigned to either the forest or urban group, with 78 completing 90-min walks and analysis.

Divergent transcriptional states and kinetics of circulating tumor-infiltrating lymphocyte repertoires with highly homologous T-cell receptor sequences in a patient during immunotherapy.

Evidence has shown that T-cell receptors (TCRs) that recognize the same epitopes may not be the exact TCR clonotypes but have slightly different TCR sequences. However, the changes in the genomic and transcriptomic signatures of these highly homologous T cells during immunotherapy remain unknown. Here, we examined the evolutionary features in circulating TCR clonotypes observed in tumors (tumor-infiltrating lymphocyte (TIL)-TCRs) by combining single-cell RNA/TCR sequencing of longitudinal blood samples and TCR sequencing of tumor tissue from a patient treated with anti-cytotoxic T-lymphocyte-associated protein 4/programmed cell death protein-1 therapy.

Crossing the blood-brain barrier: emerging therapeutic strategies for neurological disease.

The blood-brain barrier is a physiological barrier that can prevent both small and complex drugs from reaching the brain to exert a pharmacological effect. For treatment of neurological diseases, drug concentrations at the target site are a fundamental parameter for therapeutic effect; thus, the blood-brain barrier is a major obstacle to overcome. Novel strategies have been developed to circumvent the blood-brain barrier, including CSF delivery, intracranial delivery, ultrasound-based methods, membrane transporters, receptor-mediated transcytosis, and nanotherapeutics.

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.

Pericytes mediate neuroinflammation via Fli-1 in endotoxemia and sepsis in mice.

Background: Sepsis-associated encephalopathy (SAE) often results from neuroinflammation. Recent studies have shown that brain platelet-derived growth factor receptor β (PDGFRβ) cells, including pericytes, may act as early sensors of infection by secreting monocyte chemoattractant protein-1 (MCP-1), which transmits inflammatory signals to the central nervous system. The erythroblast transformation-specific (ETS) transcription factor Friend leukemia virus integration 1 (Fli-1) plays a critical role in inflammation by regulating the expression of key cytokines, including MCP-1.

Targeting EBV Episome for Anti-Cancer Therapy: Emerging Strategies and Challenges.

As a ubiquitous human pathogen, the Epstein-Barr virus (EBV) has established lifelong persistent infection in about 95% of the adult population. The EBV infection is associated with approximately 200,000 human cancer cases and 140,000 deaths per year. The presence of EBV in tumor cells provides a unique advantage in targeting the viral genome (also known as episome), to develop anti-cancer therapeutics.

Role of the Psi Packaging Signal and Dimerization Initiation Sequence in the Organization of Rous Sarcoma Virus Gag-gRNA Co-Condensates.

Retroviral genome selection and virion assembly remain promising targets for novel therapeutic intervention. Recent studies have demonstrated that the Gag proteins of Rous sarcoma virus (RSV) and human immunodeficiency virus type-1 (HIV-1) undergo nuclear trafficking, colocalize with nascent genomic viral RNA (gRNA) at transcription sites, may interact with host transcription factors, and display biophysical properties characteristic of biomolecular condensates. In the present work, we utilized a controlled in vitro condensate assay and advanced imaging approaches to investigate the effects of interactions between RSV Gag condensates and viral and nonviral RNAs on condensate abundance and organization.

A Comprehensive Review of the Development and Therapeutic Use of Antivirals in Flavivirus Infection.

Flaviviruses are a diverse group of viruses primarily transmitted through hematophagous insects like mosquitoes and ticks. Significant expansion in the geographic range, prevalence, and vectors of flavivirus over the last 50 years has led to a dramatic increase in infections that can manifest as hemorrhagic fever or encephalitis, leading to prolonged morbidity and mortality. Millions of infections every year pose a serious threat to worldwide public health, encouraging scientists to develop a better understanding of the pathophysiology and immune evasion mechanisms of these viruses for vaccine development and antiviral therapy.

Effect of Hepatitis E Virus on the Male Reproductive System: A Review of Current Evidence.

Hepatitis E Virus (HEV) is a globally widespread pathogen that causes acute hepatitis infection. Beyond hepatic pathogenesis, HEV has been proven to cause several extrahepatic manifestations, such as neurological, renal, and hematological manifestations. It was also associated with mortality in pregnant females.

Unveiling the Molecular Architecture of HBV Spherical Subviral Particles: Structure, Symmetry, and Lipid Dynamics.

Since the discovery of the Australia antigen, now known as the hepatitis B surface antigen (HBsAg), significant research has been conducted to elucidate its physical, chemical, structural, and functional properties. Subviral particles (SVPs) containing HBsAg are highly immunogenic, non-infectious entities that have not only revolutionized vaccine development but also provided critical insights into HBV immune evasion and viral assembly. Recent advances in cryo-electron microscopy (cryo-EM) have uncovered the heterogeneity and dynamic nature of spherical HBV SVPs, emphasizing the essential role of lipid-protein interactions in maintaining particle stability.

HDAC1 and HDAC2 Are Involved in Influenza A Virus-Induced Nuclear Translocation of Ectopically Expressed STAT3-GFP.

Influenza A virus (IAV) remains a pandemic threat. Particularly, the evolution and increased interspecies and intercontinental transmission of avian IAV H5N1 subtype highlight the importance of continuously studying the IAV and identifying the determinants of its pathogenesis. Host innate antiviral response is the first line of defense against IAV infection, and the transcription factor, the signal transducer and activator of transcription 3 (STAT3), has emerged as a critical component of this response.

Atlas of Interactions Between Decoration Proteins and Major Capsid Proteins of Coliphage N4.

Coliphage N4 is a representative species of the family of bacteriophages. Originally structurally studied in 2008, the capsid structure was solved to 14 Å to reveal an interesting arrangement of Ig-like decoration proteins across the surface of the capsid. Herein, we present a high-resolution N4 structure, reporting a 2.

Employing the Oncolytic Vesicular Stomatitis Virus in Cancer Virotherapy: Resistance and Clinical Considerations.

Vesicular Stomatitis Virus (VSV) has emerged as a promising candidate for various clinical applications, including vaccine development, virus pseudotyping, and gene delivery. Its broad host range, ease of propagation, and lack of pre-existing immunity in humans make it ideal for therapeutic use. VSV's potential as an oncolytic virus has garnered attention; however, resistance to VSV-mediated oncolysis has been observed in some cell lines and tumor types, limiting its effectiveness.