Systems Biology

Dual-Signal Electrochemical Aptasensor Based on High-Entropy Alloy Nanosheets for Calprotectin Detection in Inflammatory Bowel Disease

Sat, 2025-06-28 06:00

ACS Appl Mater Interfaces. 2025 Jun 28. doi: 10.1021/acsami.5c08094. Online ahead of print.

ABSTRACT

The development of biofunctional electrochemical aptasensors represents an emerging frontier in diagnostic technology, yet achieving precise and ultrasensitive detection of inflammatory bowel disease (IBD) biomarkers for early stage diagnosis remains a critical challenge. To overcome this, we engineered a novel material-based electrochemical aptasensor by using amino acid-functionalized high-entropy alloy nanosheets (HEANSs@AAs) for calprotectin (CP) detection. The fabricated HEANSs@AAs demonstrate remarkable electrochemical performance through their multielemental composition and mesoporous architecture, featuring abundant active sites enriched with several functional groups, which improve the surface chemistry of the composite for efficient immobilization of NH2-aptamer. The HEANSs@AAs-based platform enables dual signal amplification through accelerated electron transfer kinetics and improved surface reactivity. The developed aptasensor demonstrates an ultrawide dynamic range (5 pg mL-1 to 100 ng mL-1) with a limit of detection (LOD) of 2.02 pg mL-1 (S/N = 3). Significantly, the aptasensor exhibits 5.32% signal retention after 8 days storage at 4 °C and demonstrates an outstanding relative standard deviation (RSD) of 1.92%, revealing remarkable stability and reproducibility. The fabricated sensor revealed acceptable recovery rates in human serum samples between 96.6 and 97.6%, with inter-assay RSD below 2.7%, confirming its efficiency for clinical use. This work establishes a robust platform for early IBD diagnosis through precise CP quantification and introduces a versatile strategy for developing high-performance biosensors based on entropy-stabilized nanomaterials, thereby advancing multiplex biomarker detection in point-of-care diagnostic applications.

PMID:40580097 | DOI:10.1021/acsami.5c08094

Categories: Literature Watch

Advances in seed 'omics

Sat, 2025-06-28 06:00

J Exp Bot. 2025 Jun 28:eraf294. doi: 10.1093/jxb/eraf294. Online ahead of print.

ABSTRACT

Seeds provide 70% of the global food supply, making them crucial for food security. Understanding the molecular mechanisms governing seed development, dormancy, and germination has become increasingly urgent as climate change impacts crop productivity. Over the last three years, 'omics technologies have transformed our understanding of seed biology through comprehensive molecular profiling at unprecedented resolution. This review synthesises recent advances in seed biology enabled by cutting-edge 'omics applications in Arabidopsis and crops. We examine how the integration of epigenomics, genomics, transcriptomics, proteomics, and metabolomics analysis has enabled reconstruction of the complex regulatory networks controlling seed development, dormancy, and germination. The recent emergence of single-cell and spatial technologies has been revolutionary, uncovering previously unknown cell types and tissue-specific regulatory mechanisms. Key discoveries include the identification of critical phosphorylation networks, metabolic transitions, and hormone signalling activity in seeds. Advanced genomic approaches have provided insights into crop domestication and trait control, while proteomics and metabolomics have been used to characterise essential regulatory modules controlling dormancy release and germination. These findings provide valuable molecular frameworks for developing climate-resilient crops and enhanced seed vigour through targeted genetic improvements, as well as optimised agricultural practices for ensuring global food security.

PMID:40580085 | DOI:10.1093/jxb/eraf294

Categories: Literature Watch

Ecological management of the microbiota in patients with cancer

Fri, 2025-06-27 06:00

Nat Rev Clin Oncol. 2025 Jun 27. doi: 10.1038/s41571-025-01049-3. Online ahead of print.

ABSTRACT

The composition of the intestinal microbiota influences the outcomes of patients receiving cancer treatment, although the best way to use this knowledge to improve cancer care remains unclear. In this Review, I synthesize the current understanding of host-microbiota dynamics in patients with cancer, and propose the integration of microbiota management guided by ecological principles in cancer care. Ecological management of the microbiota emphasizes the preservation of microbial populations - and the benefits they provide to the host - from the disruption caused by treatments such as chemotherapy and prophylactic antibiotics. The microbiota can be routinely and longitudinally monitored in patients using proven non-invasive methods, such as 16S ribosomal RNA amplicon sequencing. Longitudinal microbiome data can be processed with innovative computational tools based on principles of mathematical ecology to predict the risk of microbiota-related complications, guide treatment choices that minimize disturbance to the microbiota and restore microbial populations damaged by cancer treatment. Routine microbiome monitoring could also generate extensive datasets for human-based research, which could inform new microbiota-targeted interventions that improve responses to cancer treatments, including immune-checkpoint inhibitors. Applying ecological approaches to manage microbiota could enhance cancer care and improve patient outcomes.

PMID:40579430 | DOI:10.1038/s41571-025-01049-3

Categories: Literature Watch

Role of stem-like cells in chemotherapy resistance and relapse in pediatric T-cell acute lymphoblastic leukemia

Fri, 2025-06-27 06:00

Nat Commun. 2025 Jun 27;16(1):5413. doi: 10.1038/s41467-025-61222-1.

ABSTRACT

T-ALL relapses are characterized by chemotherapy resistance, cellular diversity and dismal outcome. To gain a deeper understanding of the mechanisms underlying relapses, we conduct single-cell RNA sequencing on 13 matched pediatric T-ALL patient-derived samples at diagnosis and relapse, along with samples derived from 5 non-relapsing patients collected at diagnosis. This comprehensive longitudinal single-cell study in T-ALL reveals significant transcriptomic diversity. Notably, 11 out of 18 samples exhibit a subpopulation of T-ALL cells with stem-like features characterized by a common set of active regulons, expression patterns and splice isoforms. This subpopulation, accounting for a small proportion of leukemia cells at diagnosis, expands substantially at relapse, indicating resistance to therapy. Strikingly, increased stemness at diagnosis is associated with higher risk of treatment induction failure. Chemotherapy resistance is validated through in-vitro and in-vivo drug testing. Thus, we report the discovery of treatment-resistant stem-like cells in T-ALL, underscoring the potential for devising future therapeutic strategies targeting stemness-related pathways.

PMID:40579412 | DOI:10.1038/s41467-025-61222-1

Categories: Literature Watch

Circular RNA circIGF1R controls cardiac fibroblast proliferation through regulation of carbohydrate metabolism

Fri, 2025-06-27 06:00

Sci Rep. 2025 Jun 27;15(1):20331. doi: 10.1038/s41598-025-07167-3.

ABSTRACT

Excessive fibroblast proliferation and metabolic reprogramming are hallmarks of pathological cardiac remodeling, contributing significantly to impaired cardiac function. This study investigates the role of circular RNAs (circRNAs) in fibroblast metabolic reprogramming, an unexplored area with potential therapeutic implications. Through deep circRNA sequencing of cardiac tissue from heart failure (HF) patients and healthy individuals, we identified circIGF1R (hsa_circ_0005035), which exhibited dysregulation specifically in isolated cardiac fibroblasts derived from failing hearts. Silencing circIGF1R in patient-derived human cardiac fibroblasts (HCFs) led to accelerated proliferation, enhanced glycolytic activity, altered glucose trafficking, and increased glucose import. Conversely, administering recombinant circIGF1R inhibited the accelerated proliferation and enhanced glycolytic activity observed in HCFs from HF patients. Mechanistically, RNA pulldown assays and in silico analyses identified AZGP1 as a potential interaction partner facilitating the glycolysis-inhibitory and anti-proliferative functions of circIGF1R. Our findings identify circIGF1R as a pivotal regulator of fibroblast proliferation via metabolic reprogramming, particularly by glycolysis inhibition. Overexpression of circIGF1R demonstrated significant anti-fibrotic effects in cardiac fibroblasts derived from heart failure patients. These results underscore the therapeutic potential of circIGF1R in attenuating cardiac fibrosis by directly targeting fibroblast metabolism in the context of pathological cardiac remodeling.

PMID:40579400 | DOI:10.1038/s41598-025-07167-3

Categories: Literature Watch

Natural variation of the holobiont for sustainable agroecosystems

Fri, 2025-06-27 06:00

Trends Plant Sci. 2025 Jun 27:S1360-1385(25)00134-7. doi: 10.1016/j.tplants.2025.05.006. Online ahead of print.

ABSTRACT

Plant evolution is largely driven by plant-microbe interactions, yet the ecology of the plant holobiont is not well understood at a molecular level. However, these relationships hold diverse benefits for sustainable agriculture as nature-based solutions (NbS). We propose a workflow to enhance understanding of natural variation in the plant-soil microbiome holobiont, addressing key challenges like growth promotion, stress resilience, nitrogen use efficiency (NUE), biological nitrification inhibition (BNI), healthy soils, and improving fertilization practices towards a more natural agroecosystem. We discuss a panome-wide association study (PWAS) approach to discover and incorporate novel genetic diversity from exotic germplasm into breeding populations. Ultimately, understanding natural variation of the holobiont in agroecosystems will contribute to the development of novel climate-resilient crop varieties for food security.

PMID:40579258 | DOI:10.1016/j.tplants.2025.05.006

Categories: Literature Watch

KIL transcription factors facilitate embryo growth in maize by promoting endosperm elimination via lytic cell death

Fri, 2025-06-27 06:00

Plant Cell. 2025 Jun 20:koaf162. doi: 10.1093/plcell/koaf162. Online ahead of print.

ABSTRACT

The endosperm is a transient nutritive tissue in plant seeds. During maize (Zea mays) grain development, two distinct endosperm cell death processes occur: in one process, the endosperm adjacent to the embryo scutellum (EAS) is completely dismantled; in the other, the starchy endosperm (SE) retains nutrient-packed cell corpses after grain filling. Here, we show that SE cell death degrades some organelles including the mitochondria and the endoplasmic reticulum, while preserving protein bodies, starch granules, and chromatin. In contrast, EAS cells undergo lytic cell death to remobilize stored nutrients through a complex corpse clearance process. Using single-cell transcriptome analysis, we identified two NAC transcription factors, KIRA-LIKE 1 (KIL1) and 2 (KIL2), as specifically upregulated in the EAS. Analyses using dominant and recessive loss-of-function kil mutants demonstrate that these genes redundantly promote cell death and corpse clearance in the EAS, but are not required for SE cell death. Reduced EAS cell death in kil loss-of-function mutants strongly impeded embryo growth, indicating that EAS elimination is crucial for optimal embryo development. Notably, kil1 and kil2 expression is regulated by DOSAGE-EFFECT DEFECTIVE1, an imprinted paternally expressed endosperm transcription factor. Our findings suggest paternal control over EAS cell death and the embryo-endosperm size ratio in maize, providing new leads to modulate this agronomically important trait.

PMID:40579219 | DOI:10.1093/plcell/koaf162

Categories: Literature Watch

The significance of protein N-glycosylation in the pathogenesis of lung cancer and its clinical implications

Fri, 2025-06-27 06:00

Cancer Lett. 2025 Jun 25:217849. doi: 10.1016/j.canlet.2025.217849. Online ahead of print.

ABSTRACT

This comprehensive review systematically elucidates the multifaceted roles of protein N-glycosylation in lung cancer pathogenesis, including its contributions to accelerated cell proliferation, enhanced metastatic potential, promotion of epithelial‒mesenchymal transition (EMT), maintenance of stem cell characteristics, facilitation of immune evasion, preservation of angiogenesis, and diminished drug sensitivity. Additionally, the potential clinical utility of aberrant N-glycosylation is examined as a novel biomarker for early diagnosis, prognostic evaluation, and treatment monitoring in lung cancer. The analysis highlights the critical involvement of N-glycosylation in chemotherapy resistance, targeted therapy, and immunotherapy, offering new perspectives for the development of innovative therapeutic strategies. Furthermore, this review highlights promising applications of antibody-enzyme engineering technology in achieving more precise lung cancer treatments, introducing new opportunities for the field. These findings provide a significant theoretical basis and experimental evidence to support progress in lung cancer research and treatment advancements.

PMID:40578752 | DOI:10.1016/j.canlet.2025.217849

Categories: Literature Watch

Baeyer-Villiger monooxygenase immobilized on magnetic nanoparticles: reusable biocatalytic system for drug metabolite synthesis

Fri, 2025-06-27 06:00

Int J Biol Macromol. 2025 Jun 25:145588. doi: 10.1016/j.ijbiomac.2025.145588. Online ahead of print.

ABSTRACT

Drug metabolites are critical for assessing drug efficacy, pharmacokinetics, and safety. Biocatalysis offers a selective and sustainable route to their synthesis. In this study, a Baeyer-Villiger monooxygenase from Acinetobacter radioresistens (Ar-BVMO) was immobilized onto bare iron oxide nanoparticles (BIONs), producing a reusable biocatalytic system (BVMO@BION) for drug metabolite production. The magnetic properties of BIONs facilitated easy recovery and reuse of the biocatalyst, making the system practical for repeated use. High loading efficiency (0.14 mg enzyme per mg of BIONs) was achieved through histidine-tag-mediated binding. The immobilized enzyme exhibited enhanced thermostability, increasing its melting temperature from 46.3 °C to 54.9 °C, and reduced nanoparticle aggregation. The system demonstrated robust activity for Baeyer-Villiger and S/N-oxidation reactions. Notably, BVMO@BION achieved over 95 % conversion efficiency for the N-oxidation of tozasertib (an anti-cancer drug) across nine reaction cycles (2 h each) over 3 days, while activity recovery values ranged from 81 % to 127 %. For S-oxidation of ethionamide (an antibiotic used in multidrug-resistant tuberculosis) approximately 26 % conversion was consistently achieved across eight 1-hour cycles. This work demonstrates that BVMO@BION is a robust, magnetically recoverable platform for repeated and selective drug metabolite synthesis, supporting greener and more efficient pharmaceutical development.

PMID:40578651 | DOI:10.1016/j.ijbiomac.2025.145588

Categories: Literature Watch

Diet-derived LPS determines intestinal IgA induction and repertoire characteristics independently of the microbiota

Fri, 2025-06-27 06:00

Immunity. 2025 Jun 24:S1074-7613(25)00245-6. doi: 10.1016/j.immuni.2025.05.024. Online ahead of print.

ABSTRACT

A hallmark of the main secreted antibody immunoglobulin A (IgA) is its mutational load that accumulates throughout life. Although this is mainly interpreted in terms of continuing microbial induction, we show that dietary composition during early life can promote IgA induction, its repertoire, and mutational diversification independently of microbial exposure. Using germ-free and colonized mice fed different diets formulated with proprietary grain-based processing or from purified chemicals with different principal macronutrient calorie sources, we found that dietary lipopolysaccharide contamination led to Toll-like receptor (TLR) 4 signaling and promoted germinal center activity in the intestinal immune compartment. The effects of lipopolysaccharide on mucosal immune induction were phenocopied only when presented within colloidal liposomes rather than in dispersed solution. These findings indicate that dietary composition and its formulation can leave a durable impression on the resultant IgA repertoire.

PMID:40578363 | DOI:10.1016/j.immuni.2025.05.024

Categories: Literature Watch

A CXCR4 partial agonist improves immunotherapy by targeting immunosuppressive neutrophils and cancer-driven granulopoiesis

Fri, 2025-06-27 06:00

Cancer Cell. 2025 Jun 21:S1535-6108(25)00256-9. doi: 10.1016/j.ccell.2025.06.006. Online ahead of print.

ABSTRACT

Pathologically activated immunosuppressive neutrophils impair cancer immunotherapy efficacy. The chemokine receptor CXCR4, a central regulator of hematopoiesis and neutrophil biology, represents an attractive target. Here, we fuse a secreted CXCR4 partial agonist, trefoil factor 2 (TFF2), to mouse serum albumin (MSA) and demonstrate that TFF2-MSA peptide synergizes with anti-PD-1 to inhibit primary tumor growth and distant metastases and prolongs survival in gastric cancer (GC) mouse models. Using histidine decarboxylase (Hdc)-GFP transgenic mice to track polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) in vivo, we find that TFF2-MSA selectively reduces the Hdc-GFP+CXCR4high immunosuppressive neutrophils, thereby boosting CD8+ T cell-mediated tumor killing with anti-PD-1. Importantly, TFF2-MSA reduces bone marrow granulopoiesis, contrasting with CXCR4 antagonism, which fails to confer therapeutic benefits. In GC patients, elevated CXCR4+LOX-1+ low-density neutrophils correlate with lower circulating TFF2 levels. Collectively, our studies introduce a strategy that utilizes CXCR4 partial agonism to restore anti-PD-1 sensitivity by targeting immunosuppressive neutrophils and granulopoiesis.

PMID:40578360 | DOI:10.1016/j.ccell.2025.06.006

Categories: Literature Watch

A Drosophila single-cell 3D spatiotemporal multi-omics atlas unveils panoramic key regulators of cell-type differentiation

Fri, 2025-06-27 06:00

Cell. 2025 Jun 24:S0092-8674(25)00629-4. doi: 10.1016/j.cell.2025.05.047. Online ahead of print.

ABSTRACT

The development of a multicellular organism is a highly intricate process tightly regulated by numerous genes and pathways in both spatial and temporal manners. Here, we present Flysta3D-v2, a comprehensive multi-omics atlas of the model organism Drosophila spanning its developmental lifespan from embryo to pupa. Our datasets encompass 3D single-cell spatial transcriptomic, single-cell transcriptomic, and single-cell chromatin accessibility information. Through the integration of multimodal data, we generated developmentally continuous in silico 3D models of the entire organism. We further constructed tissue development trajectories that uncover the detailed profiles of cell-type differentiation. With a focus on the midgut, we identified transcription factors involved in midgut cell-type regulation and validated exex as a key regulator of copper cell development. This extensive atlas provides a rich resource and serves as a systematic platform for studying Drosophila development with integrated single-cell data at ultra-high spatiotemporal resolution.

PMID:40578340 | DOI:10.1016/j.cell.2025.05.047

Categories: Literature Watch

Molecular hybridization-driven FAK inhibitors: N-2,4-diarylaminopyrimidine-3-sulfamoyl-benzamide derivatives with improved antitumor potency

Fri, 2025-06-27 06:00

Eur J Med Chem. 2025 Jun 20;296:117885. doi: 10.1016/j.ejmech.2025.117885. Online ahead of print.

ABSTRACT

A series of novel 2,4-diarylaminopyrimidine derivatives incorporating a 3-sulfamoylbenzamide moiety were designed and synthesized as potent focal adhesion kinase (FAK) inhibitors. Three compounds (5f, 10b, and 10c) demonstrated FAK inhibitory activities comparable to the reference inhibitor TAE226. In cellular assays, most analogues exhibited significant antiproliferative effects against four FAK-overexpressing tumor cell lines (HCT116, HeLa, MDA-MB-231, and A375), with IC50 values below 1 μM. Notably, compound 10c displayed superior potency, showing IC50 values ranging from 0.08 to 0.31 μM across the tested cell lines, and exhibited approximately 2-fold enhanced activity over TAE226 in inhibiting HCT116, MDA-MB-231, and A375 cell proliferation. Further mechanistic studies revealed that 10c effectively suppressed colony formation, migration, and adhesion of HCT116 cells, while inducing apoptosis via ROS elevation. Molecular docking analysis suggested that the enhanced activity of 10c may arise from an additional hydrogen bond interaction with the Arg426 residue of FAK, leading to stronger binding affinity compared to TAE226. In vivo, 10c showed good oral bioavailability and significantly inhibited HCT116 xenograft tumor growth (TGI = 62.22 % at 50 mg/kg), outperforming TAE226 (50.98 %) without inducing weight loss or hepatorenal toxicity. These results highlight 10c as a promising FAK-targeted candidate worthy of further preclinical investigation.

PMID:40578255 | DOI:10.1016/j.ejmech.2025.117885

Categories: Literature Watch

Enzymatic depolymerization of polyethylene using a small laccase and its potential for bio-upcycling

Fri, 2025-06-27 06:00

J Hazard Mater. 2025 Jun 21;495:139021. doi: 10.1016/j.jhazmat.2025.139021. Online ahead of print.

ABSTRACT

Polyethylene (PE) plastics present significant environmental challenges due to their recalcitrant nature and widespread usage. This study explores the biological degradation of PE using a novel enzyme, small laccase from Amycolatopsis sp. ATCC 39116 (ASLAC). Among four selected laccases, ASLAC demonstrated the highest biomass production using PE as a carbon source when expressed by Yarrowia lipolytica. Surface analysis of PE films treated with purified ASLAC, using scanning electron microscopy (SEM) and atomic force microscopy (AFM), revealed substantial degradation of the material. The degradation products were successfully utilized by Y. lipolytica, underscoring its potential for converting PE into bioenergy. Structural analysis and molecular docking simulations revealed that the substrate binding site of ASLAC, characterized by a hydrophobic planner configuration, is highly optimized for binding and cleaving PE polymers. This unique structure distinguishes it from other laccases with narrower or obstructed binding sites. Phylogenetic analysis of 311 small laccase sequences classified ASLAC into the Type-Ia subgroup, which exhibited superior potential for PE degradation. This study establishes ASLAC as a promising biocatalyst for sustainable PE management, providing a foundation for future applications in bioremediation and polymer upcycling.

PMID:40578201 | DOI:10.1016/j.jhazmat.2025.139021

Categories: Literature Watch

CSGL: Chemical Synthesis Graph Learning for Molecule Representation

Fri, 2025-06-27 06:00

Bioinformatics. 2025 Jun 19:btaf355. doi: 10.1093/bioinformatics/btaf355. Online ahead of print.

ABSTRACT

MOTIVATION: Molecule Representation Learning (MRL) translates molecules into a real vector space, serving as input to downstream tasks in biology, chemistry, and computer science. This paper introduces a Chemical Synthesis Graph Learning (CSGL) framework, which enhances MRL by considering both the atomic structures of molecules and their roles in chemical reactions through a hierarchical graph representation. Specifically, molecules are first modeled based on their molecular graphs, which capture atomic-level structural information. They are then further refined using a Chemical Synthesis Graph, where nodes represent reactant and product molecule sets, and edges encode chemical transformations between reactants and products (e.g., changes in molecular structures). CSGL optimizes molecular embeddings of reactant and product nodes in a fashion that ensures the embeddings conform to a chemical balance constraint.

RESULTS: Experimental results show that our method CSGL achieves strong performance on a variety of tasks, including product prediction, reaction classification, and molecular property prediction.

AVAILABILITY: https://github.com/li-2023/CSGL.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:40577789 | DOI:10.1093/bioinformatics/btaf355

Categories: Literature Watch

Nonlinear Spontaneous Flow Instability in Active Nematics

Fri, 2025-06-27 06:00

Phys Rev Lett. 2025 Jun 13;134(23):238301. doi: 10.1103/PhysRevLett.134.238301.

ABSTRACT

Active nematics exhibit spontaneous flows through a well-known linear instability of the uniformly aligned quiescent state. Here, we show that even a linearly stable uniform state can experience a nonlinear instability, resulting in a discontinuous transition to spontaneous flows. In this case, quiescent and flowing states may coexist. Through a weakly nonlinear analysis and a numerical study, we trace the bifurcation diagram of striped patterns and show that the underlying pitchfork bifurcation switches from supercritical (continuous) to subcritical (discontinuous) by varying the flow-alignment parameter. We predict that the discontinuous spontaneous flow transition occurs for a wide range of parameters, including systems of contractile flow-aligning rods. Our predictions are relevant to active nematic turbulence and can potentially be tested in experiments on either cell layers or active cytoskeletal suspensions.

PMID:40577773 | DOI:10.1103/PhysRevLett.134.238301

Categories: Literature Watch

Matrix-Weighted Networks for Modeling Multidimensional Dynamics: Theoretical Foundations and Applications to Network Coherence

Fri, 2025-06-27 06:00

Phys Rev Lett. 2025 Jun 13;134(23):237401. doi: 10.1103/jw1k-6s7w.

ABSTRACT

Networks are powerful tools for modeling interactions in complex systems. While traditional networks use scalar edge weights, many real-world systems involve multidimensional interactions. For example, in social networks, individuals often have multiple interconnected opinions that can affect different opinions of other individuals, which can be better characterized by matrices. We propose a general framework for modeling such multidimensional interacting dynamics: matrix-weighted networks (MWNs). We present the mathematical foundations of MWNs and examine consensus dynamics and random walks within this context. Our results reveal that the coherence of MWNs gives rise to nontrivial steady states that generalize the notions of communities and structural balance in traditional networks.

PMID:40577745 | DOI:10.1103/jw1k-6s7w

Categories: Literature Watch

Structural characterization and dynamics of AdhE ultrastructures from <em>Clostridium thermocellum</em> show a containment strategy for toxic intermediates

Fri, 2025-06-27 06:00

Elife. 2025 Jun 27;13:RP96966. doi: 10.7554/eLife.96966.

ABSTRACT

Clostridium thermocellum, a cellulolytic thermophilic anaerobe, is considered by many to be a prime candidate for the realization of consolidated bioprocessing (CBP) and is known as an industry standard for biofuel production. C. thermocellum is among the best biomass degraders identified to date in nature and produces ethanol as one of its main products. Many studies have helped increase ethanol titers in this microbe; however, ethanol production using C. thermocellum is still not economically viable. Therefore, a better understanding of its ethanol synthesis pathway is required. The main pathway for ethanol production in C. thermocellum involves the bifunctional aldehyde-alcohol dehydrogenase (AdhE). To better understand the function of the C. thermocellum AdhE, we used cryo-electron microscopy (cryo-EM) to obtain a 3.28 Å structure of the AdhE complex. This high-resolution structure, in combination with molecular dynamics simulations, provides insight into the substrate channeling of the toxic intermediate acetaldehyde, indicates the potential role of C. thermocellum AdhE to regulate activity and cofactor pools, and establishes a basis for future engineering studies. The containment strategy found in this enzyme offers a template that could be replicated in other systems where toxic intermediates need to be sequestered to increase the production of valuable biochemicals.

PMID:40577193 | DOI:10.7554/eLife.96966

Categories: Literature Watch

RAP proteins regulate apicoplast noncoding RNA processing in Plasmodium falciparum

Fri, 2025-06-27 06:00

Cell Rep. 2025 Jun 25;44(7):115928. doi: 10.1016/j.celrep.2025.115928. Online ahead of print.

ABSTRACT

The human malaria parasite, Plasmodium falciparum, contains a non-photosynthetic and essential plastid called the apicoplast. This organelle is of major interest for its unique biology and potential as an attractive drug target. In this study, we characterize PfRAP03 and PfRAP08, two members of the RAP (RNA-binding domain abundant in apicomplexans) protein family. We generate inducible knockdown lines in P. falciparum to validate that both RAP proteins are essential for parasite survival and localize to the apicoplast. Transcriptomic analysis demonstrates that PfRAP03 and PfRAP08 depletion significantly affect apicoplast gene expression. Using enhanced crosslinking immunoprecipitation sequencing (eCLIP-seq) method, we show that apicoplast ribosomal RNAs and transfer RNAs are the targets of PfRAP03 and PfRAP08, respectively. Collectively, our results establish the role of these RAP proteins in controlling apicoplast gene expression in P. falciparum, revealing parasite-specific organellar pathways with biomedical significance.

PMID:40577132 | DOI:10.1016/j.celrep.2025.115928

Categories: Literature Watch

Genetic tools for imaging microcirculation via plasma labeling

Fri, 2025-06-27 06:00

Anat Sci Int. 2025 Jun 27. doi: 10.1007/s12565-025-00858-x. Online ahead of print.

ABSTRACT

Cerebral microcirculation is a critical infrastructure for brain function, delivering energy substrates and clearing metabolic byproducts. Disruptions in vascular dynamics contribute to neurodegenerative diseases, stroke, and cognitive impairments. Traditional blood labeling methods for fluorescence imaging, such as fluorescent dextran injection, have advanced our understanding of microcirculation but are limited for long-term imaging. In this mini review, we introduce two recently developed molecular genetic techniques, achieved by recombinant adeno-associated virus (AAV)-mediated plasma label expression or genomic knock-in that enable stable, long-term microcirculation imaging. These AAV-mediated methods require only a single systemic injection, facilitating longitudinal imaging of microcirculation in mouse models of disease. We discuss the fundamental design concepts of these approaches and explore their potential applications in systems biology.

PMID:40576868 | DOI:10.1007/s12565-025-00858-x

Categories: Literature Watch

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