Evolution of H7N9 highly pathogenic avian influenza virus in the context of vaccination.

Human infections with the H7N9 influenza virus have been eliminated in China through vaccination of poultry; however, the H7N9 virus has not yet been eradicated from poultry. Carefully analysis of H7N9 viruses in poultry that have sub-optimal immunity may provide a unique opportunity to witness the evolution of highly pathogenic avian influenza virus in the context of vaccination. Between January 2020 and June 2023, we isolated 16 H7N9 viruses from samples we collected during surveillance and samples that were sent to us for disease diagnosis.

Characterization of galactosyltransferase and sialyltransferase genes mediating the elongation of the extracellular O-GlcNAc glycans.

O-GlcNAc is a unique post-translational modification found in cytoplasmic, nuclear, and mitochondrial proteins. In a limited number of extracellular proteins, O-GlcNAc modifications occur through the action of EOGT, which specifically modifies subsets of epidermal growth factor-like (EGF) domain-containing proteins such as Notch receptors. The abnormalities due to EOGT mutations in mice and humans and the increased EOGT expression in several cancers signify the importance of EOGT pathophysiology and extracellular O-GlcNAc.

Engineering Temperature-Responsive Polymer Nanoparticles that Load and Release Paclitaxel, a Low-Molecular-Weight Anticancer Drug.

Poly(-isopropylacrylamide) (pNIPAm) undergoes a hydrophilicity/hydrophobicity change around its lower critical solution temperature (LCST). Therefore, pNIPAm-based polymer nanoparticles (NPs) shrink above their LCST and swell below their LCST. Although temperature responsiveness is an important characteristic of synthetic polymers in drug and gene delivery, few studies have investigated the temperature-responsive catch and release of low-molecular-weight drugs (LMWDs) as their affinity to the target changes.

Evolution and biological characterization of H5N1 influenza viruses bearing the clade 2.3.2.1 hemagglutinin gene.

H5N1 avian influenza viruses bearing the clade 2.3.2.

Analysis of avian influenza A (H3N8) viruses in poultry and their zoonotic potential, China, September 2021 to May 2022.

BackgroundTwo human cases of avian influenza A (H3N8) virus infection were reported in China in 2022.AimTo characterise H3N8 viruses circulating in China in September 2021-May 2022.MethodsWe sampled poultry and poultry-related environments in 25 Chinese provinces.

Anti-influenza Activity of Povidone-Iodine-Integrated Materials.

Personal protective equipment (PPE), including medical masks, should be worn for preventing the transmission of respiratory pathogens via infective droplets and aerosols. In medical masks, the key layer is the filter layer, and the melt-blown nonwoven fabric (NWF) is the most used fabric. However, the NWF filter layer cannot kill or inactivate the pathogens spread via droplets and aerosols.

Improvement of LXR-mediated lipid metabolism in nephrotic model kidney accompanied by suppression of inflammation and fibrosis.

Kidney disease affects millions of people worldwide. Chronic kidney diseases, such as diabetic nephropathy, are often accompanied by nephrotic syndrome, which causes a large amount of protein and lipid to leak out into the urine. Leaked lipids are well known to accumulate in the proximal tubules as lipid droplets.

Increasing the siRNA knockdown efficiency of lipid nanoparticles by morphological transformation with the use of dihydrosphingomyelin as a helper lipid.

Lipid nanoparticles (LNPs), comprising ionizable lipids, helper lipids, cholesterol, and PEG lipids, can act as delivery carriers for nucleic acids and have achieved clinical success in the delivery of siRNA and mRNA. It has been shown that the morphology of LNPs varies depending on their lipid composition, but the influence of their morphology on nucleic acid efficacy has not been fully elucidated. In this study, we used our previously developed novel lipid, dioleoylglycerophosphate-diethylenediamine conjugate (DOP-DEDA), to create pH-responsive LNPs (DOP-DEDA LNPs).

Treatment of PTEN-Null Breast Cancer by a Synthetic Lethal Approach Involving PARP1 Gene Silencing.

The loss of the phosphatase and tensin homolog (PTEN) deleted from chromosome 10 is frequently observed in a variety of human cancers and appears to be an ideal target in synthetic lethality-based treatment. In this study, the synthetic lethal interaction between PTEN loss and the gene silencing of poly [ADP-ribose] polymerase 1 (PARP1) was examined in human triple-negative breast cancer cells (PTEN-null MDA-MB-468 and PTEN-positive MDA-MB-231 cells). Polycation liposomes previously developed by us were employed to deliver the small interfering ribonucleic acid (siRNA) targeted toward PARP1 (siPARP1) into the cancer cells.

Secretory expression of mammalian NOTCH tandem epidermal growth factor-like repeats based on increased O-glycosylation.

The Notch pathway represents evolutionarily conserved intercellular signaling essential for cell-to-cell communication during development. Dysregulation of Notch signaling has been implicated in various diseases, and its control represents a potential cancer treatment strategy. Notch signaling is initiated by the interaction of NOTCH receptors with their ligands on neighboring cells.

Immune Escape Adaptive Mutations in Hemagglutinin Are Responsible for the Antigenic Drift of Eurasian Avian-Like H1N1 Swine Influenza Viruses.

The continuous antigenic variation of influenza A viruses remains a major hurdle for vaccine selection; however, the molecular determinants and mechanisms of antigenic change remain largely unknown. In this study, two escape mutants were generated by serial passages of the Eurasian avian-like H1N1 swine influenza virus (EA H1N1 SIV) A/swine/Henan/11/2005 (HeN11) in the presence of two neutralizing monoclonal antibodies (mAbs) against the hemagglutinin (HA) protein, which were designated HeN11-2B6-P5 and HeN11-4C7-P8, respectively. The HeN11-2B6-P5 mutant simultaneously harbored the N190D and I230M substitutions in HA, whereas HeN11-4C7-P8 harbored the M269R substitution in HA (H3 numbering).

Co-occurrence of relapsing polychondritis and autoimmune thyroid diseases.

Background: Relapsing polychondritis (RP) is a rare inflammatory disease characterized by recurrent inflammation and destruction of cartilaginous tissues. RP has characteristics of autoimmune disease and some reports have noted co-occurrence with autoimmune thyroid disease (AITD), consisting of Graves' disease (GD) and Hashimoto thyroiditis (HT). However, there have been no detailed studies on the co-occurrence of RP and AITD.

Easy preparation of a liposome-mediated protein delivery system by freeze-thawing a liposome-protein complex.

Homeostasis can be achieved by adding a protein supplement; however, an appropriate vector is required to deliver the protein into the cell because of the low stability of proteins in the blood and low cell membrane permeability. Here we report an easy one-step method of encapsulating proteins into liposomes for delivery. We used negatively charged superoxide dismutase (SOD) and a polycation liposome as protein and liposome models, respectively.

Novel H5N6 reassortants bearing the clade 2.3.4.4b HA gene of H5N8 virus have been detected in poultry and caused multiple human infections in China.

The globally circulating H5N8 avian influenza viruses bearing the clade 2.3.4.

Other Types of Glycosylation.

O-Linked glycosylation such as O-fucose, O-glucose, and O-N-acetylglucosamine are considered to be unusual. As suggested by the high levels of evolutional conservation, these O-glycans are fundamentally important for life. In the last two decades, our understanding of the importance of these glycans has greatly advanced.

Influence of Purification Process on the Function of Synthetic Polymer Nanoparticles.

Multifunctional synthetic polymers can bind to target molecules and are therefore widely investigated in diagnostics, drug delivery carriers, and separation carriers. Because these polymers are synthesized from nonbiological components, purification processes (e.g.

siRNA Vehicles for High Endosomal Escapability.

Small interfering RNA (siRNA) is a novel therapeutic modality for the treatment of intractable diseases; however, the development of a useful siRNA delivery vector is imperative for clinical use. Since siRNA works in the cytoplasm, the ability of the carrier to escape destruction in the endosomes is a highly required characteristic for the induction of a high knockdown effect. Here, we describe the step-by-step procedure for the evaluation of high endosomal escapability.

Enhancement of target toxin neutralization effect in vivo by PEGylation of multifunctionalized lipid nanoparticles.

Protein-protein (e.g., antibody-antigen) interactions comprise multiple weak interactions.

Release rate is a key variable affecting the therapeutic effectiveness of liposomal fasudil for the treatment of cerebral ischemia/reperfusion injury.

Liposomal fasudil as a treatment for cerebral ischemia/reperfusion (I/R) injury has been demonstrated to be effective in animal models due to the high accumulation of liposomes in damaged brain tissue. However, it is still unclear what effect drug release rate has on the treatment of I/R injury, where pathology progresses dramatically in a short time. In the present study, we assessed four formulations of liposomal fasudil.

Suppression of Cerebral Ischemia/Reperfusion Injury by Efficient Release of Encapsulated Ifenprodil From Liposomes Under Weakly Acidic pH Conditions.

Although N-methyl-d-aspartate receptor antagonists are hopeful therapeutic agents against cerebral ischemia/reperfusion (I/R) injury, effective approaches are needed to allow such agents to pass through the blood-brain barrier, thus increasing bioavailability of the antagonists to realize secure treatment. We previously demonstrated the usefulness of liposomal delivery of neuroprotectants via spaces between the disrupted blood-brain barrier induced after cerebral I/R. In the present study, a liposomal formulation of an N-methyl-d-aspartate receptor antagonist, ifenprodil, was newly designed; and the potential of liposomal ifenprodil was evaluated in transient middle cerebral artery occlusion rats.

Key determinants of siRNA delivery mediated by unique pH-responsive lipid-based liposomes.

Lipid-based nanoparticles, a potential nonviral vector due to their good biocompatibility and biodegradability, have been extensively developed for the delivery of small interfering RNA (siRNA). We designed a unique pH-responsive lipid derivative, a dioleylphosphate-diethylenetriamine conjugate (DOP-DETA). DOP-DETA consists of a pH-responsive triamine and unsaturated fatty acids that accelerate membrane fusion.

Design of a Novel PEGylated Liposomal Vector for Systemic Delivery of siRNA to Solid Tumors.

A small interfering RNA (siRNA) delivery system using dioleylphosphate-diethylenetriamine conjugate (DOP-DETA)-based liposomes (DL) was assessed for systemic delivery of siRNA to tumors. DL carrying siRNA capable of inducing efficient gene silencing with low doses of siRNA were modified with polyethylene glycol (PEG-DL/siRNA) for systemic injection of siRNA. The biodistribution of DL and siRNA in the PEG-DL/siRNA was studied by using radiolabeled DL and fluorescence-labeled siRNA, respectively.

Anticancer Efficacy of the Combination of Berberine and PEGylated Liposomal Doxorubicin in Meth A Sarcoma-Bearing Mice.

Berberine, the main isoquinoline alkaloid obtained from traditional plants, e.g., Berberis, Coptis, Coscinium spps.

Enhanced Efficacy of Doxorubicin by microRNA-499-Mediated Improvement of Tumor Blood Flow.

Genetic therapy using microRNA-499 (miR-499) was combined with chemotherapy for the advanced treatment of cancer. Our previous study showed that miR-499 suppressed tumor growth through the inhibition of vascular endothelial growth factor (VEGF) production and subsequent angiogenesis. In the present study, we focused on blood flow in tumors treated with miR499, since some angiogenic vessels are known to lack blood flow.