Identification and characterisation of two functional antibiotic MATE efflux pumps in the archaeon Halorubrum amylolyticum.

Multidrug efflux pumps have been found to play a crucial role in drug resistance in bacteria and eukaryotes. In this study, we investigated the presence of functional multidrug and toxic compound extrusion (MATE) efflux pumps, inferred from whole genome sequencing, in the halophilic archaeon Halorubrum amylolyticum CSM52 using Hoechst 33342 dye accumulation and antimicrobial sensitivity tests in the presence and absence of efflux pump inhibitors (EPIs). The whole genome sequence of H.

Genetic mutations in Cryptococcus neoformans pyrimidine salvage pathway enzymes contribute to reduced susceptibility against 5-fluorocytosine.

Cryptococcal meningitis is a high-mortality infection. Adding 5-fluorocytosine (5-FC) to its treatment improves outcomes, but resistance to 5-FC presents a significant challenge. We conducted whole-genome sequencing on seven C.

First-line cadonilimab plus chemotherapy in HER2-negative advanced gastric or gastroesophageal junction adenocarcinoma: a randomized, double-blind, phase 3 trial.

Programmed cell death protein-1 (PD-1) inhibitors plus chemotherapy have been the standard of care in the first-line treatment of advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma; however, the survival benefits are modest in patients with low programmed death ligand 1 (PD-L1) expression. Here we investigated the efficacy and safety of cadonilimab (PD-1/cytotoxic T lymphocyte antigen-4 (CTLA-4) bispecific antibody) plus chemotherapy as first-line treatment in G/GEJ adenocarcinoma. The prespecified interim analysis is reported here.

Fine-tuning d-p hybridization in Ni-B cocatalyst for enhanced photocatalytic H production.

The H-evolution kinetics play a pivotal role in governing the photocatalytic hydrogen-evolution process. However, achieving precise regulation of the H-adsorption and H-desorption equilibrium (H/H) still remains a great challenge. Herein, we propose a fine-tuning d-p hybridization strategy to precisely optimize the H/H kinetics in a Ni-B modified CdS photocatalyst (Ni-B/CdS).

Triple-negative breast cancer modifies the systemic immune landscape and alters neutrophil functionality.

Cancer disrupts intratumoral innate-adaptive immune crosstalk, but how the systemic immune landscape evolves during breast cancer progression remains unclear. We profiled circulating immune cells in stage I-III and stage IV triple-negative breast cancer (TNBC) patients and healthy donors (HDs). Metastatic TNBC (mTNBC) patients had reduced T cells, dendritic cells, and differentiated B cells compared to non-metastatic TNBC patients and HDs, partly linked to prior chemotherapy.

Protective effect of low-dose lactulose in dextran sulfate sodium induced ulcerative colitis model of rats.

Although low-dose lactulose has shown a good theoretical foundation for the treatment of ulcerative colitis (UC) in previous studies, the exact effects and mechanism remain unclear. The rats were randomly distributed into 5 groups, i.e.

Mechanism of engineered macrophage membrane bionic gene-carrying nanospheres for targeted drug delivery to promote wound repair in deep second-degree burns.

Hepatocyte growth factor (HGF) is a substance that stimulates the proliferation of hepatocytes which promote healing. We developed a macrophage membrane-encapsulated nanosphere drug delivery system containing HGF for the study of burn wound healing. Twenty-seven Sprague-Dawley rats were randomly divided into three groups: a saline control (NS) group, an engineered macrophage membrane-encapsulated nanospheres (ETMM@NPS) group, and an engineered macrophage membrane-encapsulated nanospheres treatment with HGF-loaded gene (HGF@ETMM@NPS) group.

Intrinsic p53 activation restricts gammaherpesvirus driven germinal center B cell expansion during latency establishment.

Gammaherpesviruses are DNA tumor viruses that establish lifelong latent infections in lymphocytes. For viruses such as Epstein-Barr virus and murine gammaherpesvirus 68, this is accomplished through a viral gene-expression program that promotes cellular proliferation and differentiation, especially of germinal center B cells. Intrinsic host mechanisms that control virus-driven cellular expansion are incompletely defined.

Mgl2 cDC2s coordinate fungal allergic airway type 2, but not type 17, inflammation in mice.

Fungal spores are abundant in the environment and a major cause of asthma. Originally characterised as a type 2 inflammatory disease, allergic airway inflammation that underpins asthma can also involve type 17 inflammation, which can exacerbate disease causing failure of treatments tailored to inhibit type 2 factors. However, the mechanisms that determine the host response to fungi, which can trigger both type 2 and type 17 inflammation in allergic airway disease, remain unclear.

How to combine multiple tools for the genetic diagnosis work-up of pediatric B-cell acute lymphoblastic leukemia.

This study investigated the importance of comprehensive genetic diagnosis in pediatric B-cell acute lymphoblastic leukemia (B-ALL). We analyzed 175 B-ALL employing karyotyping, FISH, MLPA, targeted next-generation sequencing (t-NGS), and Optical Genome Mapping (OGM). This approach achieved an 83% classification rate, identifying 17 distinct genetic subtypes.

Multidisciplinary treatment is necessary in glioblastoma with extracerebral metastases.

Purpose: While glioblastoma is the most common malignant brain tumor in adults, extracerebral manifestations are very rare in this highly aggressive disease with poor prognosis.

Methods: We conducted a systematic literature review in the PubMed database and complemented the data by inclusion of a case treated in our clinic. In this context, we report on a 60-year-old woman with a right frontal glioblastoma, IDH wildtype, MGMT methylated.

Policy options for sustainable access to off-patent antibiotics in Europe.

Securing sustainable access to existing antibiotics optimises agent choice for individual treatments and is crucial to curb antibiotic resistance. Access to antibiotics is often restricted in many countries, due to general market unavailability or episodic shortages. This article outlines key policy options to maintain availability of existing antibiotics and enhance antibiotic supply chain resilience focusing on the perspectives of European Union (EU) and European Economic Area (EEA) institutions and member states.

The Future of Microbiome Therapeutics.

The human microbiome exerts profound influence over various biological processes within the body. Unlike many host determinants, it represents a readily accessible target for manipulation to promote health benefits. However, existing commercial microbiome-directed products often exhibit low efficacy.

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Tissue-resident memory CD8 T cell diversity is spatiotemporally imprinted.

Tissue-resident memory CD8 T (T) cells provide protection from infection at barrier sites. In the small intestine, T cells are found in at least two distinct subpopulations: one with higher expression of effector molecules and another with greater memory potential. However, the origins of this diversity remain unknown.

The maternal X chromosome affects cognition and brain ageing in female mice.

Female mammalian cells have two X chromosomes, one of maternal origin and one of paternal origin. During development, one X chromosome randomly becomes inactivated. This renders either the maternal X (X) chromosome or the paternal X (X) chromosome inactive, causing X mosaicism that varies between female individuals, with some showing considerable or complete skew of the X chromosome that remains active.

Multiscale footprints reveal the organization of cis-regulatory elements.

Cis-regulatory elements (CREs) control gene expression and are dynamic in their structure and function, reflecting changes in the composition of diverse effector proteins over time. However, methods for measuring the organization of effector proteins at CREs across the genome are limited, hampering efforts to connect CRE structure to their function in cell fate and disease. Here we developed PRINT, a computational method that identifies footprints of DNA-protein interactions from bulk and single-cell chromatin accessibility data across multiple scales of protein size.

Classification of Molecular Subtypes of Breast Cancer Using Radiomic Features of Preoperative Ultrasound Images.

Radiomics has been used as a non-invasive medical image analysis technique for diagnosis and prognosis prediction of breast cancer. This study intended to use radiomics based on preoperative Doppler ultrasound images to classify four molecular subtypes of breast cancer. A total of 565 female breast cancer patients diagnosed by postoperative pathology in a hospital between 2014 and 2022 were included in this study.

Long-Term Safety of Ixekizumab Treatment in Patients with Psoriasis, Psoriatic Arthritis, or Axial Spondyloarthritis: a Post Hoc Analysis of Cerebro-Cardiovascular Events.

Introduction: Psoriasis (PsO), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) may confer an increased risk for cardiovascular (CV) disease, including major adverse cerebro-cardiovascular events (MACE), deep vein thrombosis (DVT), and pulmonary embolism (PE). Patients with these conditions are often exposed for extended time periods to biologics, such as ixekizumab (IXE). Therefore, understanding the risk of CV events, especially MACE, in patients with PsO, PsA, and axSpA exposed to IXE is important.

Authentic Versus Simulated Patient Videos: Effect on Mental Status Examination-An Educational Randomized Controlled Trial.

Objective: This study evaluated the impact of adding authentic patient video training to a base e-module featuring simulated patient videos, aimed at improving the mental status examination (MSE) skills of fifth-year medical students during their psychiatric rotation.

Methods: A randomized controlled trial (RCT) was conducted with 290 students, assigned to either an experimental group, the full e-learning group (Full), or an active comparator group, the limited e-learning group (Limited). The Limited group received a base e-module on MSE, while the Full group received both the base e-module and an additional module with 23 authentic patient videos.