Agmatine attenuates the severity of immunometabolic disorders by suppressing macrophage polarization: an in vivo study using an ulcerative colitis mouse model.

Agmatine, an endogenous polyamine generated by the gut microbiota, positively affects host lifespan by regulating mononuclear cell or macrophage function. Although the regulatory pathways governing monocyte/macrophage differentiation have been well studied, the influence of the microbiome and its metabolites on monocyte/macrophage function have not been fully elucidated. To address this, we aimed to investigate the mechanisms whereby agmatine inhibits immunometabolic disorders using the colon of ulcerative colitis (UC) model mice.

Introduction to the themed collection on 'AI in Medicinal Chemistry'.

Jian Zhang, Ola Engkvist and Gerhard Hessler introduce the themed collection on 'AI in Medicinal Chemistry'.

Haplotype-resolved genome assembly and resequencing provide insights into the origin and breeding of modern rose.

Modern rose (Rosa hybrida) is a recently formed interspecific hybrid and has become one of the most important and widely cultivated ornamentals. Here we report the haplotype-resolved chromosome-scale genome assembly of the tetraploid R. hybrida 'Samantha' ('JACmantha') and a genome variation map of 233 Rosa accessions involving various wild species, and old and modern cultivars.

Rfam 15: RNA families database in 2025.

The Rfam database, a widely-used repository of non-coding RNA (ncRNA) families, has undergone significant updates in release 15.0. This paper introduces major improvements, including the expansion of Rfamseq to 26,106 genomes, a 76% increase, incorporating the latest UniProt reference proteomes and additional viral genomes.

Sequence-based analysis of the rice CAMTA family: haplotype and network analyses.

The calmodulin-binding transcription activator (CAMTA) family contributes to stress responses in many plant species. The Oryza sativa ssp. japonica genome harbors seven CAMTA genes; however, intraspecific variation and functional roles of this gene family have not been determined.

Selective ligand recognition and activation of somatostatin receptors SSTR1 and SSTR3.

Somatostatin receptors (SSTRs) exert critical biological functions such as negatively regulating hormone release and cell proliferation, making them popular targets for developing therapeutics to treat endocrine disorders, especially neuroendocrine tumors. Although several panagonists mimicking the endogenous ligand somatostatin are available, the development of more effective and safer somatostatinergic therapies is limited due to a lack of molecular understanding of the ligand recognition and regulation of divergent SSTR subtypes. Here, we report four cryoelectron microscopy structures of G-coupled SSTR1 and SSTR3 activated by distinct agonists, including the FDA-approved panagonist pasireotide as well as their selective small molecule agonists L-797591 and L-796778.

The glutamate receptor antagonist ifenprodil inhibits hepatitis E virus infection.

Infection with hepatitis E virus (HEV) represents a global problem, with over 20 million people infected annually. No specific antiviral drugs are available for treating HEV infection, necessitating the development of novel targeted therapeutics. Here, we report that the N-methyl-D-aspartate receptor (NMDAR) antagonist ifenprodil, a clinically approved drug used to treat idiopathic pulmonary fibrosis (IPF), is an HEV inhibitor in liver-derived cells.

Phenolic content discrimination in Thai holy basil using hyperspectral data analysis and machine learning techniques.

Hyperspectral imaging has emerged as a powerful tool for the non-destructive assessment of plant properties, including the quantification of phytochemical contents. Traditional methods for antioxidant analysis in holy basil (Ocimum tenuiflorum L.) are time-consuming, while hyperspectral imaging has the potential to rapidly observe holy basil.

Proteomic and -glycomic comparison of synthetic and bovine whey proteins and their effect on human gut microbiomes.

Advances in food production systems and customer acceptance have led to the commercial launch of dietary proteins produced via modern biotechnological approaches as alternatives to traditional agricultural sources. At the same time, a deeper understanding of how dietary components interact with the gut microbiome has highlighted the importance of understanding the nuances underpinning diet-microbiome interactions. Novel food proteins with distinct post-translational modifications resulting from their respective production systems have not been characterized, nor how they may differ from their traditionally produced counterparts.

Multiplex PCR Approach for Rapid African Swine Fever Virus Genotyping.

African swine fever virus (ASFV) has been spreading through Europe, Asia, and the Caribbean after its introduction in Georgia in 2007 and, due to its particularly high mortality rate, poses a continuous threat to the pig industry. The golden standard to trace back the ASFV is whole genome sequencing, but it is a cost and time-intensive methodology. A more efficient way of tracing the virus is to amplify only specific genomic regions relevant for genotyping.

Improved polygenic risk prediction in migraine-first patients.

Background: Recent meta-analyses estimated 14.6% and 11.2% SNP-based heritability of migraine, compared to twin-heritability estimates of 30-60%.

Characterizing the Tumor Microenvironment and Its Prognostic Impact in Breast Cancer.

The tumor microenvironment (TME) is crucial in cancer development and therapeutic response. Immunotherapy is increasingly recognized as a critical component of cancer treatment. While immunotherapies have shown efficacy in various cancers, including breast cancer, patient responses vary widely.

Divergent autoantibody and cytokine levels in COVID-19 sepsis patients influence survival.

Studies have pointed to a decisive role of autoantibodies in the context of sepsis and severe Coronavirus disease 2019 (COVID-19), which itself often fulfills the criteria for sepsis, including dysregulated immune responses and organ dysfunction. To directly compare and further analyze the autoantibody profiles of sepsis patients with and without COVID-19, the luciferase immunoprecipitation systems (LIPS) assay was used to measure the levels of autoantibodies against a variety of clinically relevant cytokines, lung-associated proteins, other autoantigens, and antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In addition, cytokine titers were measured with the LEGENDplex™ Human Antivirus Response Panel.

Spatiotemporal dynamics of giant viruses within a deep freshwater lake reveal a distinct dark-water community.

Giant viruses (GVs) significantly regulate the ecological dynamics of diverse ecosystems. Although metagenomics has expanded our understanding of their diversity and ecological roles played in marine environments, little is known about GVs of freshwater ecosystems. Most previous studies have employed short-read sequencing and therefore resulted in fragmented genomes, hampering accurate assessment of genetic diversity.

ENGOT-en11/GOG-3053/KEYNOTE-B21: a randomised, double-blind, phase III study of pembrolizumab or placebo plus adjuvant chemotherapy with or without radiotherapy in patients with newly diagnosed, high-risk endometrial cancer.

Background: Pembrolizumab plus chemotherapy provides clinically meaningful benefit as first-line therapy for advanced (locoregional extension and residual disease after surgery)/metastatic/recurrent mismatch repair-proficient (pMMR) and mismatch repair-deficient (dMMR) endometrial cancer, with greater magnitude of benefit in the dMMR phenotype. We evaluated the addition of pembrolizumab to adjuvant chemotherapy (with/without radiation therapy) among patients with newly diagnosed, high-risk endometrial cancer without any residual macroscopic disease following curative-intent surgery.

Methods: We included patients with histologically confirmed high-risk [International Federation of Gynecology and Obstetrics (FIGO) stage I/II of non-endometrioid histology or endometrioid histology with p53/TP53 abnormality, or stage III/IVA of any histology] endometrial cancer following surgery with curative intent and no evidence of disease postoperatively, with no prior radiotherapy or systemic therapy.

A metabolomic profile of biological aging in 250,341 individuals from the UK Biobank.

The metabolomic profile of aging is complex. Here, we analyse 325 nuclear magnetic resonance (NMR) biomarkers from 250,341 UK Biobank participants, identifying 54 representative aging-related biomarkers associated with all-cause mortality. We conduct genome-wide association studies (GWAS) for these 325 biomarkers using whole-genome sequencing (WGS) data from 95,372 individuals and perform multivariable Mendelian randomization (MVMR) analyses, discovering 439 candidate "biomarker - disease" causal pairs at the nominal significance level.

Proteogenomic reconstruction of organ-specific metabolic networks in an environmental sentinel species, the amphipod Gammarus fossarum.

Metabolic pathways are affected by the impacts of environmental contaminants underlying a large variability of toxic effects across different species. However, the systematic reconstruction of metabolic pathways remains limited in environmental sentinel species due to the lack of available genomic data in many taxa of animal diversity. In this study we used a multi-omics approach to reconstruct the most comprehensive map of metabolic pathways for a crustacean model in biomonitoring, the amphipod Gammarus fossarum in order to improve the knowledge of the metabolism of this sentinel species.

Evaluation of corn fermented protein on the fecal microbiome of cats.

Co-products from the ethanol industry, such as distillers dried grains with solubles (DDGS), can provide alternative protein sources for pet food. Corn fermented protein (CFP) is produced using postfermentation technology to split the protein and yeast from fiber prior to drying. This results in a higher protein ingredient compared to DDGS, increasing its appeal for pet food.