Synthesis and antifungal activity of arecoline derivatives containing amino acid fragments.

A series of new arecoline derivatives containing amino acid fragments were synthesized, and their fungicidal activities were investigated. All synthesized compounds were characterized by H NMR, CNMR, and HRMS. Preliminary bioactivity assays demonstrated that Compounds 3k, 3n, 3p, 3q, 3r, and 3s exhibited significant antifungal activity against Botryosphaeria cactivora, Botryosphaeria dothidea, and Fusarium pseudograminearum at a concentration of 100 μg/mL.

Silencing superoxide dismutases (SOD1&SOD2) potentiates ROS-induced apoptosis in chordoma cells.

Background: Chordoma, characterized as a slow growing yet locally invasive and destructive bone tumor mainly emerging in the sacrum and clivus, presents a unique challenge due to its rarity, hampering the development of effective treatment strategies. Comprehensive understanding of tumor biology is crucial to suggest novel treatment modalities. Reactive oxygen species (ROS), a family of chemically reactive and unstable oxygen derivatives, are controlled by an intracellular antioxidant system to maintain homeostasis.

Polychlorinated biphenyls induced toxicities upon cell lines and stem cells: a review.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants emitted during e-waste activities. Upon release into the environment, PCBs can pose harmful effects to the humans and environment. The present review focused on the effects of PCBs on cell proliferation, apoptosis, functional and developmental toxicity and potential possible molecular mechanisms upon cells and stem cells.

Identification of Cell Fate Determining Transcription Factors for Generating Brain Endothelial Cells.

Reliable models of the blood-brain barrier (BBB), wherein brain microvascular endothelial cells (BMECs) play a key role in maintenance of barrier function, are essential tools for developing therapeutics and disease modeling. Recent studies explored generating BMEC-like cells from human pluripotent stem cells (hPSCs) by mimicking brain-microenvironment signals or genetic reprogramming. However, due to the lack of comprehensive transcriptional studies, the exact cellular identity of most of these cells remains poorly defined.

Sestrin2 ameliorates age-related spontaneous benign prostatic hyperplasia via activation of AMPK/mTOR dependent autophagy.

Benign prostatic hyperplasia (BPH), characterized as a chronic disease with unregulated enlargement of prostatic gland, is commonly observed in elderly men leading to lower urinary tract dysfunction. Sestrin2 plays a role in the maintenance of cellular homeostasis and protects organisms from various stimuli. The exact role of Sestrin2 in the etiology of BPH, a common age-related disease, remains unknown.

Marine natural products as a source of novel anticancer drugs: an updated review (2019-2023).

Marine natural products have long been recognized as a vast and diverse source of bioactive compounds with potential therapeutic applications, particularly in oncology. This review provides an updated overview of the significant advances made in the discovery and development of marine-derived anticancer drugs between 2019 and 2023. With a focus on recent research findings, the review explores the rich biodiversity of marine organisms, including sponges, corals, algae, and microorganisms, which have yielded numerous compounds exhibiting promising anticancer properties.

The diversity of natural killer cell functional and phenotypic states in cancer.

The role of natural killer (NK) cells as immune effectors is well established, as is their utility as immunotherapeutic agents against various cancers. However, NK cells' anti-cancer roles are suppressed in cancer patients by various immunomodulatory mechanisms which alter these cells' identity, function, and potential for immunosurveillance. This manifests in abnormal NK cell responses accompanied by changes in phenotypic or genotypic identity, giving rise to specific NK cell subsets that are either hypofunctional or, more broadly, defective in their responses.

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.

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.

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.

The Effector Protease FgTPP1 Suppresses Immune Responses and Facilitates Fusarium Head Blight Disease.

Most plant pathogens secrete effector proteins to circumvent host immune responses, thereby promoting pathogen virulence. One such pathogen is the fungus , which causes Fusarium Head Blight (FHB) disease on wheat and barley. Transcriptomic analyses revealed that expresses many candidate effector proteins during early phases of the infection process, some of which are annotated as proteases.

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.

Novel mutations found in genes involved in global developmental delay and intellectual disability by whole-exome sequencing, homology modeling, and systems biology.

Background: Genes associated with global developmental delay (GDD) and intellectual disability (ID) are increasingly being identified through next-generation sequencing (NGS) technologies. This study aimed to identify novel mutations in GDD/ID phenotypes through whole-exome sequencing (WES) and additional analyses.

Material And Methods: WES was performed on 27 subjects, among whom 18 were screened for potential novel mutations.

Revealing the role of natural killer cells in ankylosing spondylitis: identifying diagnostic biomarkers and therapeutic targets.

Background: Ankylosing spondylitis (AS) is a chronic autoimmune disease that primarily affects the axial joints. Immune cells play a key role in the pathogenesis of AS. This study integrated bioinformatics methods with experimental validation to explore the role of natural killer (NK) cells in AS.

Resolving spatiotemporal dynamics in bacterial multicellular populations: approaches and challenges.

SUMMARYThe development of multicellularity represents a key evolutionary transition that is crucial for the emergence of complex life forms. Although multicellularity has traditionally been studied in eukaryotes, it originates in prokaryotes. Coordinated aggregation of individual cells within the confines of a colony results in emerging, higher-level functions that benefit the population as a whole.

The stress-protectant molecule trehalose mediates fluconazole tolerance in .

The incidence of non- infections has witnessed a substantial rise in recent decades. ), an opportunistic human fungal pathogen, is accountable for both superficial mucosal and life-threatening bloodstream infections, particularly in immunocompromised individuals. Distinguished by its remarkable resilience to environmental stressors, exhibits intrinsic tolerance to azoles and a high propensity to swiftly develop azole resistance during treatment.

Genomic analyses reveal high diversity and rapid evolution of within a neonatal intensive care unit in Delhi, India.

causes life-threatening infections in immunocompromised hosts, including hospitalized neonates. This pathogen is intrinsically resistant to fluconazole, while uncommon strains resistant to multiple antifungal drugs, including voriconazole, amphotericin B, and echinocandins, have also been reported from healthcare environments. Thus, understanding how spread, persist, and adapt to healthcare settings could help us develop better infection management strategies.

Dynamics and regulatory roles of RNA mA methylation in unbalanced genomes.

-methyladenosine (mA) in eukaryotic RNA is an epigenetic modification that is critical for RNA metabolism, gene expression regulation, and the development of organisms. Aberrant expression of mA components appears in a variety of human diseases. RNA mA modification in has proven to be involved in sex determination regulated by and may affect X chromosome expression through the MSL complex.

Automated cell annotation in multi-cell images using an improved CRF_ID algorithm.

Cell identification is an important yet difficult process in data analysis of biological images. Previously, we developed an automated cell identification method called CRF_ID and demonstrated its high performance in whole-brain images (Chaudhary et al., 2021).

Venoms and Extracellular Vesicles: A New Frontier in Venom Biology.

Extracellular vesicles (EVs) are nanoparticle-sized vesicles secreted by nearly all cell types under normal physiological conditions. In toxicological research, EVs have emerged as a crucial link between public health and multi-omics approaches, offering insights into cellular responses to disease-causing injury agents such as environmental and biological toxins, contaminants, and drugs. Notably, EVs present a unique opportunity to deepen our understanding of the pathophysiology of envenomation by natural toxins.

Single Dose of Attenuated Vaccinia Viruses Expressing H5 Hemagglutinin Affords Rapid and Long-Term Protection Against Lethal Infection with Highly Pathogenic Avian Influenza A H5N1 Virus in Mice and Monkeys.

Background/objectives: In preparation for a potential pandemic caused by the H5N1 highly pathogenic avian influenza (HPAI) virus, pre-pandemic vaccines against several viral clades have been developed and stocked worldwide. Although these vaccines are well tolerated, their immunogenicity and cross-reactivity with viruses of different clades can be improved.

Methods: To address this aspect, we generated recombinant influenza vaccines against H5-subtype viruses using two different strains of highly attenuated vaccinia virus (VACV) vectors.

Jet Injection of Naked mRNA Encoding the RBD of the SARS-CoV-2 Spike Protein Induces a High Level of a Specific Immune Response in Mice.

Although mRNA vaccines encapsulated in lipid nanoparticles (LNPs) have demonstrated a safety profile with minimal serious adverse events in clinical trials, there is opportunity to further reduce mRNA reactogenicity. The development of naked mRNA vaccines could improve vaccine tolerability. Naked nucleic acid delivery using the jet injection method may be a solution.

Genetically Engineered Bacterial Ghosts as Vaccine Candidates Against Infection.

Bacterial ghosts (BGs), non-living empty envelopes of bacteria, are produced either through genetic engineering or chemical treatment of bacteria, retaining the shape of their parent cells. BGs are considered vaccine candidates, promising delivery systems, and vaccine adjuvants. The practical use of BGs in vaccine development for humans is limited because of concerns about the preservation of viable bacteria in BGs.

Transcriptional Systems Vaccinology Approaches for Vaccine Adjuvant Profiling.

Adjuvants are a diverse group of substances that can be added to vaccines to enhance antigen-specific immune responses and improve vaccine efficacy. The first adjuvants, discovered almost a century ago, were soluble crystals of aluminium salts. Over the following decades, oil emulsions, vesicles, oligodeoxynucleotides, viral capsids, and other complex organic structures have been shown to have adjuvant potential.

Antigen Delivery Platforms for Next-Generation Coronavirus Vaccines.

The COVID-19 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), is in its sixth year and is being maintained by the inability of current spike-alone-based COVID-19 vaccines to prevent transmission leading to the continuous emergence of variants and sub-variants of concern (VOCs). This underscores the critical need for next-generation broad-spectrum pan-Coronavirus vaccines (pan-CoV vaccine) to break this cycle and end the pandemic. The development of a pan-CoV vaccine offering protection against a wide array of VOCs requires two key elements: (1) identifying protective antigens that are highly conserved between passed, current, and future VOCs; and (2) developing a safe and efficient antigen delivery system for induction of broad-based and long-lasting B- and T-cell immunity.