Ann Clin Microbiol Antimicrob. 2025 Jul 10;24(1):41. doi: 10.1186/s12941-025-00803-w.

NO ABSTRACT

PMID:40640905 | DOI:10.1186/s12941-025-00803-w

Malar J. 2025 Jul 10;24(1):224. doi: 10.1186/s12936-025-05471-x.

ABSTRACT

BACKGROUND: The in vitro cultivation of individual stages of the Plasmodium falciparum mosquito life cycle is notably challenging. The main difficulty is replicating the intricate nutrient and metabolite exchanges necessary for oocyst development and sporozoite (SPZ) formation in the three-dimensional environment of the mosquito midgut. Replicating these conditions is essential for understanding the biological interactions between mosquito and parasite, as well as advancing malaria vaccine development.

METHODS: An in vitro three-dimensional system was developed that closely mimics the mosquito midgut epithelium, basal lamina, and haemolymph, facilitating the production of substantial quantities of haemolymph-like Pf SPZ.

RESULTS: Use of an extracellular matrix-coated Alvetex® Strata scaffold, combined with optimized culture medium, supports efficient oocyst attachment and provides the necessary nutrients for robust production of haemolymph-like SPZ. This system enables full maturation of oocysts, as shown by immunofluorescence assays (IFA), and allows timely release of in vitro SPZ (IVS) between days 11 and 15, comparable to the in vivo mosquito timeline. Haemolymph-like SPZ generated were found to be infectious, as evidenced by successful HC04 infection in in vitro and in vivo studies using FRG-huHep mice. Similar outcomes were observed across different P. falciparum strains.

CONCLUSIONS: Implementation of the Alvetex Strata scaffold, optimized medium, and improved ookinete production consistently enables in vitro generation of large quantities of haemolymph-like SPZ.

PMID:40640876 | DOI:10.1186/s12936-025-05471-x

J Transl Med. 2025 Jul 10;23(1):775. doi: 10.1186/s12967-025-06600-5.

ABSTRACT

BACKGROUND: Chronic Fatigue Syndrome (CFS) is a debilitating condition often follows infections, including influenza. Influenza frequently results in fatigue during the acute stage. However, the data regarding the association of influenza, vaccine and CFS is scarce. Thus, this study aims to investigate whether influenza increases the risk of developing CFS and examine the impact of influenza vaccination and severity of influenza on this risk.

METHODS: We conducted a national, population-based cohort study, using data from the National Health Insurance Research Database (NHIRD) of Taiwan, which identified 309,692 patients aged 20 years or older who were newly diagnosed with influenza between 2000 and 2019. An equal number of participants without influenza were also identified. Both groups were followed up until the end of CFS diagnoses. Cox proportional hazards regression analysis was used to calculate adjusted hazard ratios(aHRs) and 95% confidence intervals (CIs) for CFS as associated with influenza, adjusting for demographic factors and comorbidities. We also evaluated the effects of influenza vaccination and severe influenza.

RESULTS: After propensity matching, each cohort comprised 309,692 patients. Over an average follow-up period of approximately 12 years, influenza patients exhibited a significantly increased risk of developing CFS compared to matched controls (aHR = 1.51; 95% CI: 1.48-1.55; p < 0.001). The increased risk of CFS among patients with influenza was consistent across all age groups and both sexes, with the most pronounced elevation observed in older individuals. Patients who experienced severe influenza, as indicated by the need for mechanical ventilation, exhibited a significantly higher risk of developing CFS compared to those who did not require ventilatory support. In contrast, influenza vaccination was associated with a reduced risk of developing CFS. Patients who received the influenza vaccine-either before or following their influenza episode-exhibited a lower incidence of CFS than those who remained unvaccinated. The protective effect of vaccination was not evident in patients with severe influenza requiring ventilation.

CONCLUSIONS: Influenza infection is associated with an increased risk of developing CFS. These findings suggest that preventing influenza and mitigating its severity, such as through vaccination, could reduce the burden of CFS in at-risk populations.

PMID:40640868 | DOI:10.1186/s12967-025-06600-5

Nature. 2025 Jul 10. doi: 10.1038/s41586-025-09356-6. Online ahead of print.

NO ABSTRACT

PMID:40640568 | DOI:10.1038/s41586-025-09356-6

Nat Commun. 2025 Jul 10;16(1):6365. doi: 10.1038/s41467-025-61625-0.

ABSTRACT

While exome and whole genome sequencing have transformed medicine by elucidating the genetic underpinnings of both rare and common complex disorders, its utility to predict clinical outcomes remains understudied. Here, we use artificial intelligence (AI) technologies to explore the predictive value of whole exome sequencing in forecasting clinical outcomes following surgery for congenital heart defects (CHD). We report results for a prospective observational cohort study of 2,253 CHD patients from the Pediatric Cardiac Genomics Consortium with a broad range of complex heart defects, pre- and post-operative clinical variables and exome sequencing. Damaging genotypes in chromatin-modifying and cilia-related genes are associated with an elevated risk of adverse post-operative outcomes, including mortality, cardiac arrest and prolonged mechanical ventilation. The impact of damaging genotypes is further amplified in the context of specific CHD phenotypes, surgical complexity and extra-cardiac anomalies. The absence of a damaging genotype in chromatin-modifying and cilia-related genes is also informative, reducing the risk for some adverse postoperative outcomes. Thus, genome sequencing enriches the ability to forecast outcomes following congenital cardiac surgery.

PMID:40640177 | DOI:10.1038/s41467-025-61625-0

Nat Commun. 2025 Jul 10;16(1):6396. doi: 10.1038/s41467-025-61774-2.

ABSTRACT

Primary sensory neurons convert external stimuli into electrical signals, yet how heterogeneous neurons encode distinct sensations remains unclear. In vivo dorsal root ganglia (DRG) imaging with genetically-encoded Ca2+ indicators (GECIs) enables mapping of neuronal activity from over 1800 neurons per DRG in live mice, offering high spatial and populational resolution. However, GECIs' slow Ca2+ response kinetics limit the temporal accuracy of neuronal electrical dynamics. Genetically-encoded voltage indicators (GEVIs) provide real-time voltage tracking but often lack the brightness and dynamic range required for in vivo use. Here, we used soma-targeted ASAP4.4-Kv, a bright and fast positively tuned GEVI, to dissect temporal dynamics of DRG neuron responses to mechanical, thermal, or chemical stimulation in live male and female mice. ASAP4.4-Kv revealed previously unrecognized cell-to-cell electrical synchronization and robust dynamic transformations in sensory coding following tissue injury. Combining GEVI and GECI imaging empowers spatiotemporal analysis of sensory signal processing and integration mechanisms in vivo.

PMID:40640176 | DOI:10.1038/s41467-025-61774-2

Nat Commun. 2025 Jul 10;16(1):6366. doi: 10.1038/s41467-025-61530-6.

ABSTRACT

Plants have expanded various biosynthetic enzyme families to produce a wide diversity of natural products; however, most enzymes encoded in plant genomes remain uncharacterized, highlighting the need for new functional genomic approaches. Here, we report a platform enabling the rapid functional characterization of plant family 1 glycosyltransferases, which serve important roles in plant development, defense, and communication. Using substrate-multiplexed reactions, mass spectrometry, and automated analysis, we screen 85 enzymes against a diverse library of 453 natural products, for a total of nearly 40,000 possible reactions. The resulting dataset reveals a widespread promiscuity and a strong preference for planar, hydroxylated aromatic substrates among family 1 glycosyltransferases. We also characterize glycosyltransferases with an unusually wide substrate scope and with a non-canonical Cys-Asp catalytic dyad. This work establishes a widely-applicable enzymatic screening pipeline, reflects the immense glycosylation capability of plants, and has implications in biocatalysis, metabolic engineering, and gene discovery.

PMID:40640145 | DOI:10.1038/s41467-025-61530-6

Nat Commun. 2025 Jul 10;16(1):6364. doi: 10.1038/s41467-025-61779-x.

ABSTRACT

Conserving crop wild relatives (CWR) in their natural environments, together with the complex communities of microorganisms that live with them, could lay the foundation to unlock novel mechanisms for crop resilience and new strategies for achieving food security.

PMID:40640143 | DOI:10.1038/s41467-025-61779-x

Nat Commun. 2025 Jul 11;16(1):6402. doi: 10.1038/s41467-025-61118-0.

ABSTRACT

Single-cell RNA sequencing (scRNA-seq) facilitates the study of transcriptome diversity in individual cells. Yet, many existing methods lack sensitivity and accuracy. Here we introduce SCALPEL, a Nextflow-based tool to quantify and characterize transcript isoforms from standard 3' scRNA-seq data. Using synthetic data, SCALPEL demonstrates higher sensitivity and specificity compared to other tools. In real datasets, SCALPEL predictions have a high agreement with other tools and can be experimentally validated. The use of SCALPEL on real datasets reveals novel cell populations undetectable using single-cell gene expression data, confirms known 3' UTR length changes during cell differentiation, and identifies cell-type specific miRNA signatures regulating isoform expression. Additionally, we show that SCALPEL improves isoform quantification using paired long- and short-read scRNA-seq data. Overall, SCALPEL expands the current scRNA-seq toolkit to explore post-transcriptional gene regulation across species, tissues, and technologies, advancing our understanding of gene regulatory mechanisms at the single-cell level.

PMID:40640129 | DOI:10.1038/s41467-025-61118-0

Int J Biol Macromol. 2025 Jul 8:145756. doi: 10.1016/j.ijbiomac.2025.145756. Online ahead of print.

ABSTRACT

Enterovirus 71 (EV71) is a major causative agent of hand, foot, and mouth disease, yet specific antiviral therapies remain unavailable. This study aimed to elucidate the molecular mechanisms of (-)-Epigallocatechin-3-gallate (EGCG) against EV71 and assess its therapeutic translational potential through integrated systems biology analyses, computational modeling, and experimental validation. EGCG was prioritized over other polyphenols due to the unique structural contribution of its galloyl groups, which conferred a 2.7-fold increase in stability when binding to EV71 3C protease compared to reference ligands. Multi-omics analyses identified 2799 EGCG-related targets converging on the NF-κB pathway, with CXCR4 and CXCL10 highlighted as key regulatory hubs. Molecular dynamics revealed stable conformations (RMSD <2 Å), and in vitro studies demonstrated dose-dependent viral inhibition (IC50 = 12.3 μM) via NF-κB suppression, with preventive administration achieving 87 % cell viability. In vivo results confirmed modulation of the TLR2/p65 axis, although optimal clinical bioavailability remains a major challenge. Notably, unresolved questions persist regarding the dynamic binding plasticity of EGCG to EV71 capsid rearrangements and effective oral delivery. These findings collectively establish preclinical proof of concept for an EGCG-based intervention against EV71 while highlighting critical gaps and underscoring the need for formulation strategies to facilitate clinical translation.

PMID:40639510 | DOI:10.1016/j.ijbiomac.2025.145756

Cell Host Microbe. 2025 Jul 9;33(7):1052-1056. doi: 10.1016/j.chom.2025.05.001.

ABSTRACT

Growing insight into microbial symbioses highlights the need to model these systems mathematically. We discuss three areas requiring theoretical advancement: nested ecology within a host or holobiont, holobiont population dynamics, and symbiont-mediated speciation. Developing the proposed frameworks will bridge theory and empirical findings, accelerating our understanding of host-microbe symbioses.

PMID:40639335 | DOI:10.1016/j.chom.2025.05.001

Comput Biol Chem. 2025 Jul 4;119:108589. doi: 10.1016/j.compbiolchem.2025.108589. Online ahead of print.

ABSTRACT

Whole slide imaging (WSI) captures high-resolution histopathological details, enabling the prediction of clinical outcomes such as tumor classification, disease progression, and patient prognosis. However, existing methods often focus on single-tumor prediction, lack pan-cancer analysis, oversimplify clinical data into categorical labels, and down-sample WSIs, leading to a loss of cellular details, and reduced accuracy. Here, we collected ∼18 K WSIs and 12 clinical features from ∼13 K patients across 32 tumor types in the TCGA database. To enhance histology-clinical associations, WSIs were divided into 512 × 512 patches, and paired with clinical features, generating 190 K histology-clinical feature pairs. We developed histology-language image pretraining (HLIP), a transformer-based model that learns embeddings from clinical paragraph descriptions and histological patches using contrastive learning. HLIP achieved F1@10 (0.886), F1@50 (0.856), and F1@100 (0.915) for zero-shot classification on external datasets, outperforming competing models by 0.6, demonstrating its strong generalization capability. Additionally, HLIP facilitates bidirectional retrieval between histology and 12 clinical features and identifies high-malignant regions in histology, highlighting its strong clinical potential.

PMID:40639100 | DOI:10.1016/j.compbiolchem.2025.108589

Plant Physiol. 2025 Jul 10:kiaf217. doi: 10.1093/plphys/kiaf217. Online ahead of print.

ABSTRACT

Evergreen conifers rely on photoperiod and temperature cues to regulate autumn phenology. Climate change delays autumn cooling, whereas photoperiod remains unaffected, and this mismatch might have consequences for the timing of autumn phenology. Climatic stresses, such as drought and heat during summer, might also impact the timing of phenological events, including photosynthetic downregulation and growth cessation. We investigated the single and combined impacts of summer drought and autumn warming on photosynthetic downregulation and growth cessation in a northern and southern family of white spruce (Picea glauca). In a Temperature Free-Air Controlled Experiment (T-FACE) combined with rainout structures, we exposed white spruce seedlings to ambient temperature and rainfall, summer drought, autumn warming, or a combination of summer drought followed by autumn warming. Warming delayed the downregulation of photosynthesis in both families compared to the control seedlings, with the southern family showing increased photosynthetic activity compared to the northern family. Despite extended photosynthetic activity, secondary growth cessation was not delayed by warming and did not vary between families. Warming affected latewood xylem development, an important component of secondary growth, by increasing and decreasing lumen area in the northern family and southern family, respectively, indicating the northern family may have been more cold-limited under past selective pressures. Summer drought had minimal impacts on photosynthetic downregulation and growth cessation in either family. We conclude that warming-induced extension of photosynthetic activity in autumn may not translate into increased growth and carbon sequestration due to strong photoperiodic and genetic constraints on growth cessation in white spruce.

PMID:40638778 | DOI:10.1093/plphys/kiaf217

Science. 2025 Jul 10;389(6756):157-162. doi: 10.1126/science.adn2804. Epub 2025 Jul 10.

ABSTRACT

Maintenance of mitochondrial redox homeostasis is of fundamental importance to cellular health. Mitochondria harbor a host of intrinsic antioxidant defenses, but the contribution of extrinsic, nonmitochondrial antioxidant mechanisms is less well understood. We found a direct role for peroxisomes in maintaining mitochondrial redox homeostasis through contact-mediated reactive oxygen species (ROS) transfer. We found that ACBD5 and PTPIP51 form a contact between peroxisomes and mitochondria. The percentage of these contacts increased during mitochondrial oxidative stress and helped to maintain mitochondrial health through the transfer of mitochondrial ROS to the peroxisome lumen. Our findings reveal a multiorganelle layer of mitochondrial antioxidant defense-suggesting a direct mechanism by which peroxisomes contribute to mitochondrial health-and broaden the scope of known membrane contact site functions.

PMID:40638754 | DOI:10.1126/science.adn2804

PLoS One. 2025 Jul 10;20(7):e0327648. doi: 10.1371/journal.pone.0327648. eCollection 2025.

ABSTRACT

Alcohol-induced fatty liver disease is a significant contributor to global mortality, primarily resulting from excessive alcohol consumption and subsequent hepatic damage. This study investigated the therapeutic potential of MF001, an aldehyde-reducing compound derived from the yeast Saccharomyces cerevisiae in alcohol-induced liver damage. Using a Lieber-DeCarli ethanol diet-induced live disease model, we assessed the effects of MF001 on lipogenesis, oxidative stress, and inflammation. MF001 treatment significantly reduced lipid accumulation, as indicated by decreased expression of lipogenic genes. Moreover, MF001 suppresses reactive oxygen species (ROS) production indicated by reduced malondialdehyde levels and ROS-associated inflammatory markers, including Tnf-α, Il-6, and Mcp-1. Histological analysis revealed decreased hepatic lipid deposition and inflammation following MF001 administration. Furthermore, MF001 modulated alcohol metabolism by downregulating Cyp2e1 and Adh1, thereby decreasing acetaldehyde accumulation and improving liver function, as evidenced by normalized ALT and AST levels. Our findings suggest that MF001 alleviates alcohol-induced liver damage through its anti-inflammatory, antioxidant, and lipid-lowering properties, highlighting its potential as a function agent for preventing and treating alcohol-induced fatty liver disease.

PMID:40638641 | DOI:10.1371/journal.pone.0327648

Cell Rep. 2025 Jul 9;44(7):115962. doi: 10.1016/j.celrep.2025.115962. Online ahead of print.

ABSTRACT

Fructose metabolism is linked to metabolic dysfunction-associated steatotic liver disease (MASLD), but the regulatory mechanisms governing fructose uptake remain poorly understood. Here, we demonstrate that MASLD livers exhibit increased uptake of fructose-derived carbons compared to healthy livers and identify that the MASLD hepatocyte secretome can increase fructose metabolism. By performing fractionation and untargeted proteomics, we uncover a role for Angiopoietin-like 3 (ANGPTL3) as a regulator of hepatic fructose metabolism, independent of its role as a lipoprotein lipase (LPL) inhibitor. Circulating ANGPTL3 levels increase in response to fructose exposure, consistent with an action as a fructose sensor. Angptl3 knockdown in the liver resulted in a significant reduction in the uptake of hepatic fructose metabolites in vivo and downregulation of the facilitative hepatic fructose transporter slc2a8 (GLUT8) and fructolysis enzymes. This work demonstrates the existence of extracellular control of hepatic fructose metabolism through ANGPTL3.

PMID:40638391 | DOI:10.1016/j.celrep.2025.115962

Cell Rep. 2025 Jul 9;44(7):115988. doi: 10.1016/j.celrep.2025.115988. Online ahead of print.

ABSTRACT

L-DOPA-induced dyskinesia (LID) is a debilitating complication of dopamine replacement therapy in Parkinson's disease and the most common hyperkinetic disorder of basal ganglia origin. Abnormal activity of striatal D1 and D2 spiny projection neurons (SPNs) is critical for LID, yet the link between SPN activity patterns and specific dyskinetic movements remains unknown. To explore this, we implemented a data-driven method for clustering movements based on high-resolution motion sensors and video recordings. In a mouse model of LID, this method identified two main dyskinesia types and pathological rotations, all absent during normal behavior. Using single-cell-resolution imaging, we found that specific sets of both D1- and D2-SPNs were abnormally active during these pathological movements. Under baseline conditions, these SPN sets were active during behaviors sharing physical features with LID movements. These findings indicate that ensembles of behavior-encoding D1- and D2-SPNs form new combinations of hyperactive neurons mediating specific dyskinetic features.

PMID:40638389 | DOI:10.1016/j.celrep.2025.115988

Proc Natl Acad Sci U S A. 2025 Jul 15;122(28):e2414331122. doi: 10.1073/pnas.2414331122. Epub 2025 Jul 10.

ABSTRACT

Excessive degradation of the colonic mucin layer by Bacteroides within the human gut microbiota drives inflammatory bowel disease (IBD) in mice. Bacterial carbohydrate sulfatases are key enzymes in gut colonization, and they are elevated in human IBD and correlate with disease severity. Selective inhibitors of carbohydrate sulfatases could function as sulfatase-selective drugs, allowing precise control of sulfatase activity while preserving these otherwise beneficial bacteria. Arylsulfamates are covalent inhibitors that target a catalytic formylglycine residue of steroid sulfatases, a residue that is also conserved in carbohydrate sulfatases. Here, we find that a library of aryl- and carbohydrate sulfamates is ineffective against carbohydrate sulfatases, yet can inhibit human gut microbiota (HGM) species grown on sulfated glycans. Leveraging thermal proteome profiling (TPP), we identify a lipid kinase as the target responsible for these effects. This work highlights the imperative for developing specific inhibitors targeting carbohydrate sulfatases and reveals the adverse effects that arylsulfamates have on Bacteroides species of the HGM.

PMID:40638084 | DOI:10.1073/pnas.2414331122

Methods Mol Biol. 2025;2953:167-187. doi: 10.1007/978-1-0716-4694-6_11.

ABSTRACT

A wide range of technologies have been developed to study protein-protein interactions and to map comprehensive protein interaction networks. In recent years, advances in proximity labeling methods, coupled to protein identification by mass spectrometry, have led to exponential growth in the popularity of these methods. In this chapter, we present a detailed protocol using TurboID in Arabidopsis thaliana seedlings, using membrane-bound transcription factors as a case study. Additionally, we outline the workflow for analyzing mass spectrometry data to identify putative protein interactors.

PMID:40638048 | DOI:10.1007/978-1-0716-4694-6_11

J Cardiovasc Transl Res. 2025 Jul 10. doi: 10.1007/s12265-025-10658-3. Online ahead of print.

ABSTRACT

Cachexia, often seen in chronic heart failure (CHF), worsens patient outcomes and survival. Early detection is crucial, and circulating miRNAs offer potential as biomarkers linking heart function, inflammation, and cachexia. This study aimed to identify plasma miRNAs associated with cachexia in CHF and assess their diagnostic and prognostic value. Plasma samples from 150 newly diagnosed CHF patients were analyzed using next-generation sequencing (NGS) and validated by qRT-PCR. A signature of elevated miRNA-628 and reduced miRNA-6803 (↑miRNA-628+↓miRNA-6803) was associated with poor nutritional status, abnormal lab results, and higher cachexia risk. Combining this signature with inflammatory markers perfectly distinguished cachectic from non-cachectic patients (AUC=1.0). This profile increased cachexia risk 19-fold and was linked to significantly shorter survival (median 14 vs. 41 months). Thus, the identified miRNA signature offers strong predictive and diagnostic potential and could complement clinical assessments of CHF patients' nutritional status.

PMID:40637997 | DOI:10.1007/s12265-025-10658-3