Drosophila modeling to identify causative genes and reveal the underlying molecular mechanisms for primary ovarian insufficiency.

Primary ovarian insufficiency (POI) is a disease defined as a reduction in ovarian function under the age of 40 and represents the main cause of female infertility. In recent years, many genetic mutations associated with POI have been identified using high-throughput sequencing technology. However, one big challenge today is to determine the disease-causing gene associations through functional assessment.

Spinal cord cross sign: a potential marker for hereditary spastic paraplegia type 5.

Purpose: Spastic paraplegia type 5 (SPG5) is a rare neurodegenerative disease diagnosed primarily through genetic testing.We identified a specific spinal cord sign on conventional MR imaging to help narrow the scope of genetic screening.

Methods: In 25 patients with SPG5 and 21 healthy controls (HCs), the spinal cord cross sign was evaluated on T2*-weighted imaging.

Enhancing Photodynamic Therapy Efficacy via Photo-Triggered Calcium Overload and Oxygen Delivery in Tumor Hypoxia Management.

: Photodynamic therapy (PDT) has emerged as a promising treatment for cancer, primarily due to its ability to generate reactive oxygen species (ROS) that directly induce tumor cell death. However, the hypoxic microenvironment commonly found within tumors poses a significant challenge by inhibiting ROS production. This study aims to investigate the effect of improving tumor hypoxia on enhancing PDT.

Follow-Up Analysis Enhances Understanding of Molecular Residual Disease in Localized Non-Small Cell Lung Cancer.

Purpose: The prognostic value of molecular residual disease (MRD) in non-small cell lung cancer (NSCLC) is well-established, with treatment-guiding results anticipated. Here, we present updated analyses from our previous published cohort study of 261 NSCLC patients undergoing complete resection.

Experimental Design: 261 patients with stage I-III lung cancer who underwent radical surgery were enrolled.

RNase T2 deficiency promotes TLR13-dependent replenishment of tissue-protective Kupffer cells.

Lysosomal stress due to the accumulation of nucleic acids (NAs) activates endosomal TLRs in macrophages. Here, we show that lysosomal RNA stress, caused by the lack of RNase T2, induces macrophage accumulation in multiple organs such as the spleen and liver through TLR13 activation by microbiota-derived ribosomal RNAs. TLR13 triggered emergency myelopoiesis, increasing the number of myeloid progenitors in the bone marrow and spleen.

Single-cell transcriptomics predict novel potential regulators of acute epithelial restitution in the ischemia-injured intestine.

Intestinal ischemic injury damages the epithelial barrier predisposes patients to life-threatening sepsis unless that barrier is rapidly restored. There is an age-dependency of intestinal recovery in that neonates are the most susceptible to succumb to disease of the intestinal barrier versus older patients. We have developed a pig model that demonstrates age-dependent failure of intestinal barrier restitution in neonatal pigs which can be rescued by the direct application of juvenile pig mucosal tissue, but the mechanisms of rescue remain undefined.

Optimized genetic tools for neuroanatomical and functional mapping of the Aedes aegypti olfactory system.

The mosquito Aedes aegypti is an emerging model insect for invertebrate neurobiology. We detail the application of a dual transgenesis marker system that reports the nature of transgene integration with circular donor template for CRISPR-Cas9-mediated homology-directed repair at target mosquito chemoreceptor genes. Employing this approach, we demonstrate the establishment of cell-type-specific T2A-QF2 driver lines for the A.

Di-Genic Inheritance in Genodermatoses: Insights from Two Consanguineous Cases in a Reference Lebanese Center within the Middle East and North Africa (MENA) Region.

Introduction: Genodermatoses refer to a group of heterogenous rare genetic diseases with cutaneous expression. Several genodermatoses present with multisystem involvement that can range from mild to life-threatening conditions leading to increased morbidity and mortality.

Objective: Given the paucity in the literature in the field of genodermatoses, especially in the Middle East and North Africa (MENA) region, and building upon the first established genodermatoses database based in Lebanon, this study aimed to decipher the genetic basis of two different types of skin-inherited diseases (androgenic alopecia and vitiligo).

Accumulation of CD38 in Hybrid Epithelial/Mesenchymal Cells Promotes Immune Remodeling and Metastasis in Breast Cancer.

Triple-negative breast cancer (TNBC) is a highly metastatic subtype of breast cancer. The epithelial-to-mesenchymal transition is a nonbinary process in the metastatic cascade that generates tumor cells with both epithelial and mesenchymal traits known as hybrid EM cells. Recent studies have elucidated the enhanced metastatic potential of cancers featuring the hybrid EM phenotype, highlighting the need to uncover molecular drivers and targetable vulnerabilities of the hybrid EM state.

A Regulatory Circuits Analysis Tool, "miRCuit," Helps Reveal Breast Cancer Pathways: Toward Systems Medicine in Oncology.

A systems medicine understanding of the regulatory molecular circuits that underpin breast cancer is essential for early cancer detection and precision/personalized medicine in clinical oncology. Transcription factors (TFs), microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) control gene expression and cell biology, and by extension, serve as pillars of the regulatory circuits that determine human health and disease. We report here the development of a regulatory circuit analysis program, , constructing 10 different types of regulatory elements involving messenger RNA, miRNA, lncRNA, and TFs.

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat Accelerates Wound Healing in a Mouse Hind limb Lymphedema Model.

Drugs regulating hypoxia-inducible factor (HIF)-1α have not been investigated for wound healing in lymphedema. Therefore, we examined the effects of drug modulation of HIF-1α activity for wound healing in our previously developed mouse model of nonirradiated hind limb lymphedema. Mouse hind limb lymphedema models ( = 17) and a sham group ( = 6) were created using 8- to 10-week-old male C57BL/6N mice.

Vesicular mechanisms of drug resistance in apicomplexan parasites.

Vesicular mechanisms of drug resistance are known to exist across prokaryotes and eukaryotes. Vesicles are sacs that form when a lipid bilayer 'bends' to engulf and isolate contents from the cytoplasm or extracellular environment. They have a wide range of functions, including vehicles of communication within and across cells, trafficking of protein intermediates to their rightful organellar destinations, and carriers of substrates destined for autophagy.

Signal peptidase SpsB coordinates staphylococcal cell cycle, surface protein septal trafficking, and LTA synthesis.

Unlabelled: Cell wall-anchored surface proteins of Gram-positive bacteria, harboring a highly conserved YSIRK/G-S signal peptide (SP), are deposited at cell division septum and anchored to septal peptidoglycan. The mechanisms supporting YSIRK protein septal trafficking remain elusive. Previously, we identified that LtaS-mediated lipoteichoic acid (LTA) synthesis restricts septal trafficking of YSIRK+ proteins in .

Acrylamide Induces Antiapoptotic Autophagy and Apoptosis by Activating PERK Pathway in SH-SY5Y Cells.

Acrylamide (ACR) is a commonly used organic compound that exhibits evident neurotoxicity in humans. Our previous studies showed that the mechanisms of ACR-caused neurotoxicity included apoptosis, PERK-mediated endoplasmic reticulum stress, and autophagy, but the relationships among them were still unclear. This paper investigated the relationships among apoptosis, autophagy, and the PERK pathway to demonstrate the mechanism of ACR neurotoxicity further.

Characterisation of Strains and Their Prophages That Carry Horse-Specific Leukocidin Genes .

Leukocidins of (.) are bicomponent toxins that form polymeric pores in host leukocyte membranes, leading to cell death and/or triggering apoptosis. Some of these toxin genes are located on prophages and are associated with specific hosts.

Stem Cell Therapy for Diseases of Livestock Animals: An In-Depth Review.

Stem cells are unique, undifferentiated cells that have the ability to both replicate themselves and develop into specialized cell types. This dual capability makes them valuable in the development of regenerative medicine. Current development in stem cell research has widened their application in cell therapy, drug discovery, reproductive cloning in animals, and cell models for various diseases.

An Improved Method for Extracting Rat Cerebrospinal Fluid with Repeatable Large-Scale Collection.

The aim of this study was to explore an improved method for extracting rat cerebrospinal fluid (CSF), observing the impact on animal health under conditions of large-scale CSF collection and evaluating the feasibility of repeated collections. A total of 20 rats were anesthetized and fixed in a stereotactic frame. A 26G scalp needle, combined with a 1 mL syringe, was used to puncture the atlanto-occipital membrane and collect approximately 170 μL of CSF.

The Long-Term Immunity of a Microneedle Array Patch of a SARS-CoV-2 S1 Protein Subunit Vaccine Irradiated by Gamma Rays in Mice.

Background/objectives: COVID-19 vaccines effectively prevent severe disease, but unequal distribution, especially in low- and middle-income countries, has led to vaccine-resistant strains. This highlights the urgent need for alternative vaccine platforms that are safe, thermostable, and easy to distribute. This study evaluates the immunogenicity, stability, and scalability of a dissolved microneedle array patch (MAP) delivering the rS1RS09 subunit vaccine, comprising the SARS-CoV-2 S1 monomer and RS09, a TLR-4 agonist peptide.

Persistence of the Immune Response to an Intramuscular Bivalent (GI.1/GII.4) Norovirus Vaccine in Adults.

Background: Major global economic and health burdens due to norovirus gastroenteritis could be addressed by an effective vaccine.

Methods: In this study, 428 adult recipients of various compositions of the norovirus vaccine candidate, HIL-214, were followed for 5 years, to assess immune responses to its virus-like particle antigens, GI.1 and GII.

Enhanced Immunogenicity of Foot-and-Mouth Disease Virus-like Particles Using a Water-in-Oil-in-Water Adjuvant.

Background: Foot-and-mouth disease (FMD) causes significant economic losses, prompting vaccination as a primary control strategy. Virus-like particles (VLPs) have emerged as promising candidates for FMD vaccines but require adjuvants to enhance their immunogenicity. In this study, we evaluated the immunogenicity of a VLP-based vaccine with a water-in-oil-in-water (W/O/W) emulsion adjuvant, named WT.

Cell Wall Protein 2 as a Vaccine Candidate Protects Mice Against Infection.

Background/objectives: is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high recurrence rates. Vaccination presents a promising strategy for preventing both CDI and its recurrence.

Antibody-Based Antigen Delivery to Dendritic Cells as a Vaccination Strategy Against Ebola Virus Disease.

Dendritic cells connect innate and adaptive immune responses. This is a particularly important immune checkpoint in the case of emerging infections against which most of the population does not have preexisting antibody immunity. In this study, we sought to test whether antibody-based delivery of Ebola virus (EBOV) antigens to dendritic cells could be used as a vaccination strategy against Ebola virus disease.

Deep-Sea-Derived Isobisvertinol Targets TLR4 to Exhibit Neuroprotective Activity via Anti-Inflammatory and Ferroptosis-Inhibitory Effects.

Neuroinflammation and neuronal cell death are leading causes of death in the elderly and underlie various neurodegenerative diseases. These diseases involve complex pathophysiological mechanisms, including inflammatory responses, oxidative stress, and ferroptosis. Compounds derived from deep-sea fungi exhibit low toxicity and potent neuroprotective effects, offering a promising source for drug development.

Dual Mechanisms of Action: Anti-Candida and Anti-Inflammatory Potential of Fermentation Broth in Treating Vulvovaginal Candidiasis.

Vulvovaginal candidiasis (VVC), a condition predominantly caused by , affects millions of women worldwide, prompting the need for alternative treatments due to the side effects and increasing resistance associated with conventional imidazole antifungals. This study investigated VAGINNE, a novel fermentation broth derived from species, as a potential VVC treatment. Using a BALB/c mouse model of infection, we evaluated VAGINNE's effects on vaginal microbiome composition, inflammatory markers, and tissue integrity.