Pan-phylum genomes of hornworts reveal conserved autosomes but dynamic accessory and sex chromosomes.

Hornworts, one of the three bryophyte phyla, show some of the deepest divergences in extant land plants, with some families separated by more than 300 million years. Previous hornwort genomes represented only one genus, limiting the ability to infer evolution within hornworts and their early land plant ancestors. Here we report ten new chromosome-scale genomes representing all hornwort families and most of the genera.

Blood DNA virome associates with autoimmune diseases and COVID-19.

Aberrant immune responses to viral pathogens contribute to pathogenesis, but our understanding of pathological immune responses caused by viruses within the human virome, especially at a population scale, remains limited. We analyzed whole-genome sequencing datasets of 6,321 Japanese individuals, including patients with autoimmune diseases (psoriasis vulgaris, rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), pulmonary alveolar proteinosis (PAP) or multiple sclerosis) and coronavirus disease 2019 (COVID-19), or healthy controls. We systematically quantified two constituents of the blood DNA virome, endogenous HHV-6 (eHHV-6) and anellovirus.

The highly allo-autopolyploid modern sugarcane genome and very recent allopolyploidization in Saccharum.

Modern sugarcane, a highly allo-autopolyploid organism, has a very complex genome. In the present study, the karyotype and genome architecture of modern sugarcane were investigated, resulting in a genome assembly of 97 chromosomes (8.84 Gb).

Context-dependent effects of CDKN2A and other 9p21 gene losses during the evolution of esophageal cancer.

CDKN2A is a tumor suppressor located in chromosome 9p21 and frequently lost in Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC). How CDKN2A and other 9p21 gene co-deletions affect EAC evolution remains understudied. We explored the effects of 9p21 loss in EACs and cancer progressor and non-progressor BEs with matched genomic, transcriptomic and clinical data.

Long-range organization of intestinal 2D-crypts using exogenous Wnt3a micropatterning.

Intestinal epithelial cells are segregated into proliferative crypts and differentiated regions. This organization relies on specific signals, including Wnt3a, which regulates cell proliferation within crypts, and Eph/Ephrin, which dictates cell positioning along the crypt-villus axis. However, studying how the spatial distributions of these signals influences crypt-villus organization is challenging both in vitro and in vivo.

Localized In Vivo Prodrug Activation Using Radionuclides.

Radionuclides used for imaging and therapy can show high molecular specificity in the body with appropriate targeting ligands. We hypothesized that local energy delivered by molecularly targeted radionuclides could chemically activate prodrugs at disease sites while avoiding activation in off-target sites of toxicity. As proof of principle, we tested whether this strategy of radionuclide-induced drug engagement for release (RAiDER) could locally deliver combined radiation and chemotherapy to maximize tumor cytotoxicity while minimizing off-target exposure to activated chemotherapy.

Classification of non-TCGA cancer samples to TCGA molecular subtypes using compact feature sets.

Molecular subtypes, such as defined by The Cancer Genome Atlas (TCGA), delineate a cancer's underlying biology, bringing hope to inform a patient's prognosis and treatment plan. However, most approaches used in the discovery of subtypes are not suitable for assigning subtype labels to new cancer specimens from other studies or clinical trials. Here, we address this barrier by applying five different machine learning approaches to multi-omic data from 8,791 TCGA tumor samples comprising 106 subtypes from 26 different cancer cohorts to build models based upon small numbers of features that can classify new samples into previously defined TCGA molecular subtypes-a step toward molecular subtype application in the clinic.

Evolutionary study and structural basis of proton sensing by Mus GPR4 and Xenopus GPR4.

Animals have evolved pH-sensing membrane receptors, such as G-protein-coupled receptor 4 (GPR4), to monitor pH changes related to their physiology and generate adaptive reactions. However, the evolutionary trajectory and structural mechanism of proton sensing by GPR4 remain unresolved. Here, we observed a positive correlation between the optimal pH of GPR4 activity and the blood pH range across different species.

A self-assembled fluorescent nanoprobe recognized by FA1 site for specifically selecting HSA: Its applications in hemin detection, cell imaging and fluorescent tracing drug delivery.

As naturally essential biomacromolecule, HSA has become diagnostic indicators for various diseases and universal carriers for anticancer drug delivery, therefore, fluorescence detection and labeling for HSA possess significant application value in the biomedical field. In this paper, hydrazide Schiff base fluorescent probe NDQC was designed and synthesized, which self-assembled into nanoparticles in aqueous solution system and demonstrated excellent selectivity and sensitivity towards HSA. Through displacement assay and molecular docking simulation, the binding of NDQC with HSA in FA1 site was demonstrated, thereby no obvious fluorescence signal presented for homologous protein BSA due to their structural differences in binding site.

The potential role of viruses in antibiotic resistance gene dissemination in activated sludge viromes.

The dissemination of antibiotic resistance genes (ARGs) in activated sludge (AS) systems poses significant environmental and public health challenges. The role of viruses, primarily bacteriophages, in storing and spreading ARGs in AS systems remains largely unexplored. This study characterized the viral community, virus-associated ARGs (vir_ARGs), and mobile genetic elements (MGEs) of aerobic AS viromes from eight wastewater treatment plants (WWTPs) in eastern China.

Novel antimalarial 3-substituted quinolones isosteres with improved pharmacokinetic properties.

Aryl quinolone derivatives can target the cytochrome bc complex of Plasmodium falciparum, exhibiting excellent in vitro and in vivo antimalarial activity. However, their clinical development has been hindered due to their poor aqueous solubility profiles. In this study, a series of bioisosteres containing saturated heterocycles fused to a 4-pyridone ring were designed to replace the inherently poorly soluble quinolone core in antimalarial quinolones with the aim to reduce π-π stacking interactions in the crystal packing solid state, and a synthetic route was developed to prepare these alternative core derivatives.

RpH-ILV: Probe for lysosomal pH and acute LLOMe-induced membrane permeabilization in cell lines and .

Lysosomal pH dysregulation is a critical element of the pathophysiology of neurodegenerative diseases, cancers, and lysosomal storage disorders (LSDs). To study the role of lysosomes in pathophysiology, probes to analyze lysosomal size, positioning, and pH are indispensable tools. Here, we developed and characterized a ratiometric genetically encoded lysosomal pH probe, RpH-ILV, targeted to a subpopulation of lysosomal intraluminal vesicles.

Treating myocardial infarction via a nano-ultrasonic contrast agent-mediated high-efficiency drug delivery system targeting macrophages.

Following myocardial infarction (MI), the accumulation of CD86-positive macrophages in the ischemic injury zone leads to secondary myocardial damage. Precise pharmacological intervention targeting this process remains challenging. This study engineered a nanotherapeutic delivery system with CD86-positive macrophage-specific targeting and ultrasound-responsive release capabilities.

De novo transcriptome assembly and discovery of drought-responsive genes in white spruce (Picea glauca).

Forests face an escalating threat from the increasing frequency of extreme drought events driven by climate change. To address this challenge, it is crucial to understand how widely distributed species of economic or ecological importance may respond to drought stress. In this study, we examined the transcriptome of white spruce (Picea glauca (Moench) Voss) to identify key genes and metabolic pathways involved in the species' response to water stress.

Putative biomarkers of hepatic dysfunction in critically ill sepsis patients.

Sepsis is a major cause of morbidity and mortality worldwide. Among the various types of end-organ damage associated with sepsis, hepatic injury is linked to significantly higher mortality rates compared to dysfunction in other organ systems. This study aimed to investigate potential biomarkers of hepatic injury in sepsis patients through a multi-center, case-control approach.

Integrated Analysis of Methylome and Transcriptome Responses to Exercise Training in Children with Overweight/Obesity.

We examined the effects of a 20-week exercise intervention on whole-blood genome-wide DNA methylation signature and its association with the exercise-induced changes in gene expression profiles in boys and girls with overweight/obesity (OW/OB). Twenty-three children (10.05 ± 1.

Versatile Stimuli-Responsive Controlled Release of Pinanediol-Caged Boronic Esters for Spatiotemporal and Nitroreductase-Selective Glucose Bioimaging.

Boronic acids have been widely applied in various biological fields, particularly achieving significant practical progress in boronic acid-based glucose sensing. However, boronic acids exhibit nonspecific binding to other nucleophiles, and the inherent lability of boronic esters in biological systems limits their further applications. Herein, we developed a stimuli-responsive controllable caging strategy to achieve photoresponsive spatiotemporally and nitroreductase-responsive cancer cell-selective glucose sensing.

Flavuside B exhibits antioxidant and anti-inflammatory properties in Staphylococcus aureus infected skin wound and affect the expression of genes controlling bacterial quorum sensing.

Aims: The aim of this study was to evaluate the antioxidant and anti-inflammatory effects of marine fungal cerebroside flavuside B (FlaB) on Staphylococcus aureus-infected keratinocytes in in vitro skin wounds and to identify FlaB targets in bacterial and human cells.

Methods And Results: A combination of enzyme-linked immunosorbent assay (ELISA), plate spectrofluorimetry, and flow cytometry with fluorescence dye staining, scratch assay, and real-time cell imaging techniques was used to investigate the effects of FlaB on S. aureus-infected HaCaT keratinocytes.

MVA-based SARS-CoV-2 vaccine candidates encoding different spike protein conformations induce distinct early transcriptional responses which may impact subsequent adaptive immunity.

Introduction: Vaccine platforms such as viral vectors and mRNA can accelerate vaccine development in response to newly emerging pathogens, as demonstrated during the COVID-19 pandemic. However, the differential effects of platform and antigen insert on vaccine immunogenicity remain incompletely understood. Innate immune responses induced by viral vector vaccines are suggested to have an adjuvant effect for subsequent adaptive immunity.

ABC transporter activity is affected by the size of lipid nanodiscs.

Lipid nanodiscs have become a widely used approach for studying membrane proteins thanks to several advantages they offer. They have been especially useful for studying ABC transporters, despite the growing concern about the possible restriction of the conformational changes of the transporters due to the small size of the discs. Here, we performed a systematic study to determine the effect of the nanodisc size on the ATPase activity of model ABC transporters from human, plant, and bacteria.

PD-L1 and IFN-γ modulate Non-Small Cell Lung Cancer (NSCLC) cell plasticity associated to immune checkpoint inhibitor (ICI)-mediated hyperprogressive disease (HPD).

Background: Non-Small Cell Lung Cancer (NSCLC) is the leading cause of cancer death worldwide. Although immune checkpoint inhibitors (ICIs) have shown remarkable clinical efficacy, they can also induce a paradoxical cancer acceleration, known as hyperprogressive disease (HPD), whose causative mechanisms are still unclear.

Methods: This study investigated the mechanisms of ICI resistance in an HPD-NSCLC model.

Can a plant biologist fix a thermostat?

The shift to reductionist biology at the dawn of the genome era yielded a 'parts list' of plant genes and a nascent understanding of complex biological processes. Today, with the genomics era in full swing, advances in high-definition genomics enabled precise temporal and spatial analyses of biological systems down to the single-cell level. These insights, coupled with artificial intelligence-driven in silico design, are propelling the development of the first synthetic plants.

The β Common Cytokine Receptor Family Reveals New Functional Paradigms From Structural Complexities.

Cytokines are small proteins that are critical for controlling the growth and activity of hematopoietic cells by binding to cell surface receptors and transmitting signals across membranes. The β common (βc) cytokine receptor family, consisting of the granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 cytokine receptors, is an architype of the heterodimeric cytokine receptor systems. We now know that signaling by cytokine receptors is not always an "all or none" phenomenon.

High order expression dependencies finely resolve cryptic states and subtypes in single cell data.

Single cells are typically typed by clustering into discrete locations in reduced dimensional transcriptome space. Here we introduce Stator, a data-driven method that identifies cell (sub)types and states without relying on cells' local proximity in transcriptome space. Stator labels the same single cell multiply, not just by type and subtype, but also by state such as activation, maturity or cell cycle sub-phase, through deriving higher-order gene expression dependencies from a sparse gene-by-cell expression matrix.

Metabolic mutations reduce antibiotic susceptibility of E. coli by pathway-specific bottlenecks.

Metabolic variation across pathogenic bacterial strains can impact their susceptibility to antibiotics and promote the evolution of antimicrobial resistance (AMR). However, little is known about how metabolic mutations influence metabolism and which pathways contribute to antibiotic susceptibility. Here, we measured the antibiotic susceptibility of 15,120 Escherichia coli mutants, each with a single amino acid change in one of 346 essential proteins.