Acute Cholangitis With Non-O1 and Non-O139 Vibrio cholerae Bacteremia: A Case Report.

We describe a case of acute cholangitis with bacteremia caused by non-O1 and non-O139 (NOVC) in a 76-year-old man following acute gastroenteritis. The strain, isolated from blood cultures, was identified as serogroup O120. It lacked the cholera toxin gene, but it harbored multiple virulence genes, including , , , and .

Effectiveness and Safety of Dupilumab Monotherapy in Japanese Patients With Chronic Rhinosinusitis With Nasal Polyps.

Objectives: The randomized, double-blind, placebo-controlled LIBERTY SINUS-24 and SINUS-52 studies demonstrated that dupilumab is effective for chronic rhinosinusitis with nasal polyps (CRSwNP) when used with an intranasal corticosteroid (INCS); however, INCSs are not approved for CRSwNP in Japan. The current study aimed to investigate the effectiveness and safety of dupilumab monotherapy in Japanese individuals with CRSwNP.

Methods: This phase 4, open-label, single-arm, multicenter study enrolled adult individuals with CRSwNP inadequately controlled with standard care therapies, including systemic corticosteroids and/or surgery.

Disseminated cat-scratch disease during abatacept therapy for rheumatoid arthritis in an older patient: A case report and review of the literature.

Cat-scratch disease (CSD) is a zoonotic infection primarily caused by Bartonella henselae following cat scratches. It typically presents with localized skin symptoms and self-limiting lymphadenopathy; however, in some cases, it can progress to disseminated lesions, leading to severe complications. We report a case of CSD with multiorgan involvement in a 79-year-old woman undergoing abatacept treatment for rheumatoid arthritis.

DBeQ derivative targets vacuolar protein sorting 4 functions in cancer cells and suppresses tumor growth in mice.

Vacuolar protein sorting 4 (VPS4) is an AAA-ATPase that catalyzes the endosomal sorting complex required for transport-III disassembly, mediating various cellular membrane-remodeling processes including endolysosomal membrane repair and autophagosome closure. Humans have 2 VPS4 paralogs, VPS4A and VPS4B, and the loss of either paralog has been identified in a significant proportion of cancers, rendering them dependent on the remaining paralog for survival. In this study, we explored VPS4 inhibition as an anticancer strategy by investigating the mechanisms of VPS4 inhibition-induced cell death and developing small-molecule compounds that target VPS4 functions.

The contribution of metagenomic next-generation sequencing to a diagnosis of gas-producing Fusobacterium-induced septic hip arthritis: A case report.

Pyogenic arthritis with gas gangrene triggered by intra-articular steroid injections can occasionally result in fatal complications. Clostridium perfringens is typically the causative pathogen, with infections caused by Fusobacterium species being relatively rare. Fusobacterium species are known to cause pyogenic infections, but due to their extreme sensitivity to oxygen, they can be difficult to detect with traditional culture methods.

Rapid Biodegradation Assessment of Biomass Plastics Using Closed Recirculating Aquaculture Systems: A Novel Approach for Environmental Sustainability.

The increasing plastic production causes serious problems in the marine environment, and the main source of plastic waste comes from the fishing and aquaculture industries. Although there have been various efforts to develop aquaculture equipment with marine biodegradable plastics, an urgent need is to develop an assay to evaluate their biodegradation in aquaculture environments. This study focused on evaluating the biodegradation of biomass plastic in recirculating aquaculture systems (RAS) that mimic freshwater, brackish water, and saltwater aquacultures.

Physiological insights into ESCRT-mediated phagophore closure: potential cytoprotective roles for ATG8ylated membranes.

The endosomal sorting complex required for transport (ESCRT) machinery is a membrane abscission system that mediates various intracellular membrane remodeling processes, including macroautophagy/autophagy. In our recent study, we established the unique requirement of the ubiquitin E2 variant-like (UEVL) domain of the ESCRT-I subunit VPS37A for phagophore closure, the final step in autophagosome biogenesis, and determined the physiological impact of systemically inhibiting closure by targeting this region in mice. While the mutant mice exhibited phenotypes similar to those reported in mice deficient in generating ATG8 (mammalian Atg8 homologs)-conjugated (ATG8ylated) phagophores, certain phenotypes, such as neonatal lethality and liver injury, were found to be notably milder.

Discovery and characterization of stereodefined PMO-gapmers targeting tau.

Antisense oligonucleotides (ASOs) are an important class of therapeutics to treat genetic diseases, and expansion of this modality to neurodegenerative disorders has been an active area of research. To realize chronic administration of ASO therapeutics to treat neurodegenerative diseases, new chemical modifications that improve activity and safety profiles are still needed. Furthermore, it is highly desirable to develop a single stereopure ASO with a defined activity and safety profile to avoid any efficacy and safety concerns due to the batch-to-batch variation in the composition of diastereomers.

Blocking autophagosome closure manifests the roles of mammalian Atg8-family proteins in phagophore formation and expansion during nutrient starvation.

Macroautophagy/autophagy, an evolutionarily conserved cellular degradation pathway, involves phagophores that sequester cytoplasmic constituents and mature into autophagosomes for subsequent lysosomal delivery. The gene family, comprising the and subfamilies in mammals, encodes ubiquitin-like proteins that are conjugated to phagophore membranes during autophagosome biogenesis. A central question in the field is how Atg8-family proteins are precisely involved in autophagosome formation, which remains controversial and challenging, at least in part due to the short lifespan of phagophores.

A Japanese Case of COVID-19 Caused by Omicron Strain with Y453F Substitution.

Frequent mutations of SARS-CoV-2 change the strain more transmissible, leading to the pandemic in worldwide. We detected Y453F substitution on Omicron strain, isolated from a Japanese patient in July 2022. While Y453F substitution was identified B1.

ER stress elicits non-canonical CASP8 (caspase 8) activation on autophagosomal membranes to induce apoptosis.

The gene encodes a subunit of the endosomal sorting complex required for transport (ESCRT)-I complex that is frequently lost in a wide variety of human solid cancers. We have previously demonstrated the role of VPS37A in directing the ESCRT membrane scission machinery to seal the phagophore for autophagosome completion. Here, we report that -deficient cells exhibit an accumulation of the apoptotic initiator CASP8 (caspase 8) on the phagophore and are primed to undergo rapid apoptosis through the intracellular death-inducing signaling complex (iDISC)-mediated CASP8 activation upon exposure to endoplasmic reticulum (ER) stress.

High serum IgA levels in patients with IgG4-related disease are associated with mild inflammation, sufficient disease-specific features, and favourable responses to treatments.

Objectives: Although elevated serum immunoglobulin A (IgA) levels are thought to exclude a diagnosis of IgG4-related disease (IgG4-RD), IgG4-RD has been definitively diagnosed in some patients despite elevated serum IgA levels. This study aimed to clarify the prevalence of elevated IgA levels in patients with IgG4-RD and to compare the clinical features of IgG4-RD patients with and without elevated IgA levels.

Methods: The clinical features of 169 IgG4-RD patients were retrospectively compared among those with and without elevated serum IgA levels.

Water-soluble protein from walleye pollock () suppresses lipopolysaccharide-induced inflammation by attenuating TLR4-MyD88 expression in macrophages.

Water-soluble protein (WSP) from fish meat is abundant in the waste effluent generated via the surimi manufacturing process. This study investigated the anti-inflammatory effects and mechanisms of fish WSP using primary macrophages (MΦ) and animal ingestion. MΦ were treated with digested-WSP (d-WSP, 500 µg/mL) with or without lipopolysaccharide (LPS) stimulation.

A Pediatric Case of Septic Pulmonary Embolism Caused by Tsukamurella paurometabola.

We herein report a three-year-old boy with septic pulmonary embolism caused by Tsukamurella paurometabola bacteremia during chemotherapy for rhabdomyosarcoma. During the interval of chemotherapy, the patient was temporarily discharged with a peripherally inserted central venous catheter but was re-admitted to the hospital with a fever on the same day. A blood culture taken at the time of re-admission showed T.

Identification of potent siRNA targeting complement C5 and its robust activity in pre-clinical models of myasthenia gravis and collagen-induced arthritis.

Complement component 5 (C5), an important molecule in the complement cascade, blockade by antibodies shows clinical efficacy in treating complement-mediated disorders. However, insufficient blockading induced by single-nucleotide polymorphisms in the C5 protein or frequent development of "breakthrough" intravascular hemolysis in patients with paroxysmal nocturnal hemoglobinuria treated with eculizumab have been reported. Herein, we developed a lipid nanoparticle (LNP)-formulated siRNA targeting C5 that was efficiently delivered to the liver and silenced C5 expression.