Repurposing Drugs for Synergistic Combination Therapies to Counteract Monkeypox Virus Tecovirimat Resistance.

The ongoing monkeypox (mpox) disease outbreak has spread to multiple countries in Central Africa and evidence indicates it is driven by a more virulent clade I monkeypox virus (MPXV) strain than the clade II strain associated with the 2022 global mpox outbreak, which led the WHO to declare this mpox outbreak a public health emergency of international concern. The FDA-approved small molecule antiviral tecovirimat (TPOXX) is recommended to treat mpox cases with severe symptoms, but the limited efficacy of TPOXX and the emergence of TPOXX resistant MPXV variants has challenged this medical practice of care and highlighted the urgent need for alternative therapeutic strategies. In this study we have used vaccinia virus (VACV) as a surrogate of MPXV to assess the antiviral efficacy of combination therapy of TPOXX together with mycophenolate mofetil (MMF), an FDA-approved immunosuppressive agent that we have shown to inhibit VACV and MPXV, or the N-myristoyltransferase (NMT) inhibitor IMP-1088.

Perspective on the 65-Year Anniversary of the Discovery of Cytomegalovirus.

This volume presents research and reviews bringing forward new insights into cytomegalovirus (CMV) pathogenesis and biology; CMV is a herpesvirus that has long been recognized as being medically significant [...

Impact of Combined Antiretroviral Treatment (cART) on Latent Cytomegalovirus Infection.

Cytomegalovirus infections and reactivations are more frequent in people living with HIV (PLWH) and have been associated with increased risk of HIV progression and immunosenescence. We explored the impact of combination antiretroviral therapy (cART) on latent CMV infection in 225 young adults parenterally infected with HIV during childhood. Anti-CMV IgG antibodies were present in 93.

Dufulin Impacts Plant Defense Against Tomato Yellow Leaf Curl Virus Infecting Tomato.

(TYLCV) poses a significant threat to tomato production, leading to severe yield losses. The current control strategies primarily rely on the use of pesticides, which are often nonselective and costly. Therefore, there is an urgent need to identify more environmentally friendly alternatives.

eEF-2K Deficiency Boosts the Virus-Specific Effector CD8 T Cell Responses During Viral Infection.

In this study, we revealed a critical role of eukaryotic elongation factor-2 kinase (eEF-2K), a negative regulator of protein synthesis, in regulating T cells during vaccinia virus (VACV) infection. We found that eEF-2K-deficient (eEF-2K⁻/⁻) mice exhibited a significantly higher proportion of VACV-specific effector CD8 T cells without compromising the development of VACV-specific memory CD8 T cells. RNA sequencing demonstrated that eEF-2K⁻/⁻ VACV-specific effector CD8 T cells had enhanced functionality, which improves their capacity to combat viral infection during the effector phase.

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.

Effect of Fusion to the LTB Carrier Protein on Coronavirus Spike Protein Vaccine Candidates Produced in Maize.

Coronaviruses continue to disrupt health and economic productivity worldwide. Porcine epidemic diarrhea virus (PEDV) is a devastating swine disease and SARS-CoV-2 is the latest coronavirus to infect the human population. Both viruses display a similar spike protein on the surface that is a target of vaccine development.

Identifying Allosteric Small-Molecule Binding Sites of Inactive NS2B-NS3 Proteases of Pathogenic .

Dengue, West Nile, Zika, Yellow fever, and Japanese encephalitis viruses persist as significant global health threats. The development of new therapeutic strategies based on inhibiting essential viral enzymes or viral-host protein interactions is problematic due to the fast mutation rate and rapid emergence of drug resistance. This study focuses on the NS2B-NS3 protease as a promising target for antiviral drug development.

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Development of Spray-Dried Micelles, Liposomes, and Solid Lipid Nanoparticles for Enhanced Stability.

Micelles, liposomes, and solid lipid nanoparticles (SLNs) are promising drug delivery vehicles; however, poor aqueous stability requires post-processing drying methods for maintaining long-term stability. The objective of this study was to compare the potential of lipid-based micelles, liposomes, and SLNs for producing stable re-dispersible spray-dried powders with trehalose or a combination of trehalose and L-leucine. This study provides novel insights into the implementation of spray drying as a technique to enhance long-term stability for these lipid-based nanocarriers.

Investigations of Long-Acting Formulations in Children, Adolescents, and Pregnant Women: A Systematic Review.

Long-acting and extended-release drug delivery strategies have greatly improved treatment for a variety of medical conditions. Special populations, specifically infants, children, young people, and pregnant and postpartum women, could greatly benefit from access to these strategies but are often excluded from clinical trials. We conducted a systematic review of all clinical studies involving the use of a long-acting intramuscular injection or implant in infants, children, young people, and pregnant and postpartum people.

Single Exposure to Low-Intensity Focused Ultrasound Causes Biphasic Opening of the Blood-Brain Barrier Through Secondary Mechanisms.

The blood-brain barrier (BBB) is selectively permeable, but it also poses significant challenges for treating CNS diseases. Low-intensity focused ultrasound (LiFUS), paired with microbubbles is a promising, non-invasive technique for transiently opening the BBB, allowing enhanced drug delivery to the central nervous system (CNS). However, the downstream physiological effects following BBB opening, particularly secondary responses, are not well understood.

Preparation of pH-Responsive Tanshinone IIA-Loaded Calcium Alginate Nanoparticles and Their Anticancer Mechanisms.

Tanshinone IIA (Tan IIA) is a lipophilic active constituent derived from the rhizomes and roots of (Danshen), a common Chinese medicinal herb. However, clinical applications of Tan IIA are limited due to its poor solubility in water. : To overcome this limitation, we developed a calcium alginate hydrogel (CA) as a hydrophilic carrier for Tan IIA, which significantly improved its solubility.

A Series of Novel Alleles of Modulating Heading and Salt Tolerance in Rice.

Rice ( L.) is a staple crop for nearly half of the global population and one of China's most extensively cultivated cereals. Heading date, a critical agronomic trait, determines the regional and seasonal adaptability of rice varieties.

Infection in Lemon Influences Host Preference of the Citrus Whitefly by Affecting the Host Metabolite Composition.

Plant viruses have been known to alter host metabolites that influence the attraction of insect vectors. Our study investigated whether (CYVCV) infection influences vector attractiveness, focusing on the citrus whitefly, (Ashmead). Free choice assays showed that citrus whiteflies exhibited a preference for settling on CYVCV-infected lemon plants versus healthy control plants.

Central Asia Cold Case: Siberian Pine Fingers New Suspects in Growth Decline CA 1700 CE.

Tree-ring width chronologies of Du Tour from near the upper treeline in the Western Sayan, Southern Siberia are found to have an exceptional (below mean-3SD) multi-year drop near 1700 CE, highlighted by the seven narrowest-ring years in a 1524-2022 regional chronology occurring in the short span of one decade. Tree rings are sometimes applied to reconstruct seasonal air temperatures; therefore, it is important to identify other factors that may have contributed to the growth suppression. The spatiotemporal scope of the "nosedive" in tree growth is investigated with a large network of (14 sites) and Ledeb.

Lignin Metabolism Is Crucial in the Plant Responses to (Shen) in L.

(Shen) (Hemiptera: Cicadellidae) is a devastating insect pest species of , significantly affecting the yield and quality of tea. Due to growing concerns over the irrational use of insecticides and associated food safety, it is crucial to better understand the innate resistance mechanism of tea trees to . This study aims to explore the responses of tea trees to different levels of infestation.

Exploring the Potential of Selenium-Containing Amine (Se-AMA) to Enhance Photosynthesis and Leaf Water Content: New Avenues for Carbonic Anhydrase Modulation in .

Global changes and growing demands have led to the development of new molecular approaches to improve crop physiological performances. Carbonic anhydrase (CA) enzymes, ubiquitous across various life kingdoms, stand out for their critical roles in plant photosynthesis and water relations. We hypothesize that the modulators of human CAs could affect plant physiology.

Dual Regulation of Ionic Effect on L. Seed Germination and Leaf Differentiation in Low-Salinity Conditions.

Low-salinity conditions are generally used in land-based cultivation to promote the germination and growth of L. and to improve the restoration effect of seagrass beds. Different salinity conditions lead to morphological and physiological differences.

Brid., a Bryophyta from Northwest Argentina as a Source of Antioxidants and Antimicrobials.

In recent years, numerous studies have emerged on the biological activities of bryophytes and their potential for therapeutic use. However, mosses appear to be a relatively overlooked group. The objective of this study was to conduct a phytochemical analysis of one hydroalcoholic extract of and to evaluate its potential as an antioxidant and antimicrobial agent.

Enhancement of Fertilizer Efficiency Through Chinese Milk Vetch and Rice Straw Incorporation.

The incorporation of rice straw (RS) and Chinese milk vetch (CMV) with reduced chemical fertilizers (CFs) is a viable solution to reduce the dependency on CF. However, limited research has been conducted to investigate the impact of CMV and RS with reduced CF on rice production. A field trial was conducted from 2018 to 2021 with six treatments: CK (no fertilizer), F100 (100% NPK fertilizer (CF)), MSF100 (100% CF+CMV and RS incorporation), MSF80 (80% CF+CMV+RS), MSF60 (60% CF+CMV+RS), and MSF40 (40% CF+CMV+RS).

Advancing the Taxonomy of the Diatom Through an Integrative Study Conducted in the Central and Southeastern Adriatic Sea.

The marine diatom genus comprises cosmopolitan phytoplankton species commonly present in the Adriatic Sea. Species within the genus have been of significant concern because they produce domoic acid (DA), which can cause amnesic shellfish poisoning (ASP). In this study, we identified species along the Central and Southeastern Adriatic Sea, where monthly sampling carried out from February 2022 to February 2024 allowed for comprehensive species documentation.

Effects of Intercropping and Mowing Frequency on Biological Nitrogen Fixation Capacity, Nutritive Value, and Yield in Alfalfa ( L. cv. Vernal).

Intercropping with legume forages is recognized as an effective strategy for enhancing nitrogen levels in agroforestry, while mowing may influence nitrogen fixation capacity and yield. This study investigated the rooting, nitrogen fixation, nutritive value, and yield of alfalfa ( L.) under intercropping and varying mowing frequencies (CK, 2, and 3) from 2021 to 2023, using walnut ( L.

Evolutionary Trajectories of Shoots vs. Roots: Plant Volatile Metabolomes Are Richer but Less Structurally Diverse Belowground in the Tropical Tree Genus .

The breadth and depth of plant leaf metabolomes have been implicated in key interactions with plant enemies aboveground. In particular, divergence in plant species chemical composition-amongst neighbors, relatives, or both-is often suggested as a means of escape from insect herbivore enemies. Plants also experience strong pressure from enemies such as belowground pathogens; however, little work has been carried out to examine the evolutionary trajectories of species' specialized chemistries in both roots and leaves.

Medicinal Plant Use in North Karelia, Finland, in the 2010s.

Finnish North Karelia is a region with a rich cultural history of ethnomedicinal plant use, shaped by centuries of interactions among various ethnic groups. This study identified both similarities and divergences between local Finns, Karelians war refugees, and individuals of mixed origin compared to historical records. Based on 67 semi-structured interviews, we documented the use of 43 medicinal plant taxa from 25 families, of which 31 remain in use.