IET Syst Biol. 2025 Jan-Dec;19(1):e70015. doi: 10.1049/syb2.70015.

ABSTRACT

ADAMTS5, a member of the ADAMTS family, exhibits crucial biological roles, including protein shedding, proteolysis, and cell migration. Its relevance in breast cancer (BC) was explored through an integrative approach combining high-throughput analyses, database validations, and experimental confirmation. ADAMTS5 expression was significantly reduced in BC samples, as verified by microarray analysis, qRT-PCR, and public database resources. A protein-protein interaction network revealed five proteins-COL10A1, COL11A1, COMP, MMP1 and SDC1-that interact with ADAMTS5 and are primarily associated with the ECM-receptor interaction pathway. These proteins also engage in cell cycle checkpoint signalling, emphasising their potential role in tumour progression. Survival analysis of BC samples identified a novel prognostic signature based on ADAMTS5-related proteins. The study extended to coding and noncoding RNA interactions, identifying lncRNAs as key regulators. CRNDE acts as a ceRNA for ADAMTS5, modulating its expression via hsa-miR-135b-3p. Meanwhile, BAIAP2-AS1 interacts directly with ADAMTS5, offering another layer of regulatory control and prognostic value. These findings position ADAMTS5 as a vital player in BC biology, with its low expression linked to critical pathways and survival outcomes. The identified lncRNA-mediated regulatory mechanisms add depth to understanding ADAMTS5's role and suggest potential targets for therapeutic development. This study underscores ADAMTS5's potential as a biomarker and its broader implications in unravelling BC molecular mechanisms.

PMID:40472834 | DOI:10.1049/syb2.70015

J Environ Manage. 2025 Jun 4;389:126075. doi: 10.1016/j.jenvman.2025.126075. Online ahead of print.

ABSTRACT

The spread of aquatic invasive species (AIS) presents a pressing challenge for global biodiversity, with freshwater ecosystems being particularly affected. The connection of watersheds throughout Europe by the construction of artificial shipping canals has created novel invasion pathways, but may also provide critical infrastructure to counter range expansion by implementation of different barrier solutions. Here, we critically review the efficacy, applicability and limitations of dispersal barriers against AIS in shipping canals considering fishes, invertebrates, algae, bacteria and fungi. Despite the wide spread of AIS and their known detrimental effects on aquatic ecosystems, research focusing on barriers for AIS in shipping canals is rather limited and predominantly concentrated on a few species of fish. Out of 180 screened studies, only 32 examined the efficacy of technologies such as electric fields, acoustic signals, strobe light, air-bubble curtains, CO2 and pheromones as non-physical barriers. Efficacy and applicability was mostly tested in laboratory setups and strongly species-dependent, requiring a site-specific identification of the most useful barrier technology. Major limitations to barrier implementation include undesired and unknown side effects on non-target species, humans and the environment. To preserve the ecological integrity of freshwater ecosystems across transboundary and inland watersheds, future research should tackle these challenges by increasing the number of studies under realistic field conditions to allow evidence-based decision making on the management of AIS.

PMID:40472533 | DOI:10.1016/j.jenvman.2025.126075

Comput Biol Med. 2025 Jun 3;194:110456. doi: 10.1016/j.compbiomed.2025.110456. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: Coronary heart disease (CHD) is a leading cause of morbidity and mortality globally, frequently accompanied by major depressive disorder (MDD), which exacerbates clinical outcomes. While Guanxinning (GXN) has demonstrated efficacy in improving cardiac function and reducing angina symptoms in CHD patients, its potential role in alleviating MDD symptoms has not been extensively studied. This study aims to explore the potential therapeutic effects of GXN on CHD and MDD through the regulation of S1PR3.

METHODS: We utilized bioinformatics, network pharmacology, and Mendelian randomization to identify S1PR3 as a key therapeutic target for CHD and MDD. Molecular docking simulations were conducted to validate the binding affinity between GXN components and S1PR3.

RESULTS: Our findings indicate that CHD is a risk factor for MDD, and the downregulation of S1PR3 expression in CHD patients is associated with the onset of MDD. Molecular docking analysis demonstrated that GXN can effectively bind to S1PR3, suggesting that GXN may modulate S1PR3 expression levels to prevent MDD in CHD patients.

CONCLUSION: This study identifies S1PR3 as a critical therapeutic target for the comorbidity of CHD and MDD. GXN has the potential to treat CHD and MDD by regulating S1PR3 expression levels. Although further validation through animal and cell-based experiments is needed, our findings provide a foundational understanding of the molecular mechanisms and highlight the therapeutic potential of GXN in dual heart therapy.

PMID:40472508 | DOI:10.1016/j.compbiomed.2025.110456

Blood Adv. 2025 Jun 5:bloodadvances.2025016209. doi: 10.1182/bloodadvances.2025016209. Online ahead of print.

ABSTRACT

Platelets fulfill their essential physiological roles sensing the extracellular environment through their membrane proteins. The native membrane environment provides essential regulatory cues that impact the protein structure and mechanism of action. Single-particle cryogenic electron microscopy (cryo-EM) has transformed structural biology by allowing high-resolution structures of membrane proteins to be solved from homogeneous samples. Our recent breakthroughs in data processing now make it feasible to obtain atomic-level-resolution protein structures from crude preparations in their native environments by integrating cryo-EM with the "Build-and-Retrieve" (BaR) data processing methodology. We applied this iterative bottom-up methodology on resting human platelet membranes for an in-depth systems biology approach to uncover how lipids, metal binding, post-translational modifications, and co-factor associations in the native environment regulate platelet function at the molecular level. Here, we report using cryo-EM followed by the BaR method to solve the unmodified integrin αIIbβ3 structure directly from resting human platelet membranes in its inactivated and intermediate states at 2.75Å and 2.67Å, respectively. Further, we also solved a novel dimer conformation of αIIbβ3 at 2.85Å formed by two intermediate-states of αIIbβ3. This may indicate a previously unknown self-regulatory mechanism of αIIbβ3 in its native environment. In conclusion, our data show the power of using cryo-EM with the BaR method to determine three distinct structures including a novel dimer directly from natural sources. This approach allows us to identify unrecognized regulation mechanisms for proteins without artifacts due to purification processes. These data have the potential to enrich our understanding of platelet signaling circuitry.

PMID:40472320 | DOI:10.1182/bloodadvances.2025016209

Elife. 2025 Jun 5;13:RP94586. doi: 10.7554/eLife.94586.

ABSTRACT

A classic problem in metabolism is that fast-proliferating cells use seemingly wasteful fermentation for energy biogenesis in the presence of sufficient oxygen. This counterintuitive phenomenon, known as overflow metabolism or the Warburg effect, is universal across various organisms. Despite extensive research, its origin and function remain unclear. Here, we show that overflow metabolism can be understood through growth optimization combined with cell heterogeneity. A model of optimal protein allocation, coupled with heterogeneity in enzyme catalytic rates among cells, quantitatively explains why and how cells choose between respiration and fermentation under different nutrient conditions. Our model quantitatively illustrates the growth rate dependence of fermentation flux and enzyme allocation under various perturbations and is fully validated by experimental results in Escherichia coli. Our work provides a quantitative explanation for the Crabtree effect in yeast and the Warburg effect in cancer cells and can be broadly used to address heterogeneity-related challenges in metabolism.

PMID:40472190 | DOI:10.7554/eLife.94586

Hum Mol Genet. 2025 Jun 5:ddaf090. doi: 10.1093/hmg/ddaf090. Online ahead of print.

ABSTRACT

Shaker-type potassium channel genes (Kv1) have been linked to human epilepsies, including KCNA1 (Kv1.1), KCNA2 (Kv1.2), and more recently, KCNA3 (Kv1.3) and KCNA6 (Kv1.6). In this study, we report three early-onset epilepsy cases with de novo missense mutations in Shaker-type channel genes, including Kv1.3, KCNA4 (Kv1.4), and Kv1.6, identified through whole exome sequencing trio study. The newly identified Kv1.3-V478M, Kv1.6-T421I, and Kv1.4-V558L mutations are located within the channel selectivity filter or S6 hinge, both critical for channel gating. These variants are in paralogous locations of previously reported pathogenic variant in KCNA2. These mutations do not significantly affect trafficking and plasma membrane localization of the Kv channels. In contrast, our patch-clamp analysis in a cell-based system reveals that all three mutations cause severe loss-of-function channel properties. Additionally, our Drosophila model highlights the detrimental effects of Kv1.3-V478M on neural circuit activity. Current findings suggest that, similar to Kv1.1, Kv1.2, and Kv1.3, both loss-of-function and gain-of-function mutations in Kv1.6 may contribute to the phenotypic variability in epilepsy severity. Our study also extends the list of potassium channel genes implicated in human epilepsy, introducing Kv1.4 as a novel epilepsy-related gene.

PMID:40472070 | DOI:10.1093/hmg/ddaf090

Proc Natl Acad Sci U S A. 2025 Jun 10;122(23):e2501830122. doi: 10.1073/pnas.2501830122. Epub 2025 Jun 5.

ABSTRACT

Prior studies have indicated that the transcription factor Creb5 is expressed in the joint interzone, which contains the progenitors for all synovial joint tissues in both mouse and human embryos. In the absence of Creb5 function, most synovial joint interzones fail to form and the cartilage templates in the long bones remain fused. This earlier work did not clarify whether Creb5 initiates a cascade of signaling molecules, such as growth and differentiation factor 5 (Gdf5) and Wnt-family members, that in turn induce the formation of the joint interzone, or instead directly activates the expression of joint interzone markers. In the present study, an integrative analysis of the transcriptome, chromatin accessibility, and Creb5-occupancy in joint progenitors revealed that Creb5 directly binds to both its own two promoters and to the regulatory regions of Gdf5 and Sfrp2, each of whose expression in the joint interzone is Creb5-dependent. Functional enhancer analysis indicated that Creb5 binding sites in either the two Creb5 promoters, or in Gdf5 and Sfrp2 regulatory elements are necessary for these sequences to drive transgene expression in the developing synovial joints. While Creb5 directly drives Gdf5 and Sfrp2 expression in the inner joint interzone, Creb5 activates Barx1 expression specifically in the outer joint interzone. Our findings indicate that Creb5 initiates a regulatory network that both promotes the formation of synovial joints, and subsequently activates distinct transcriptional targets in the inner versus the outer regions of the joint interzone, thus regionalizing gene expression in the developing joint.

PMID:40472036 | DOI:10.1073/pnas.2501830122

Eur Heart J. 2025 Jun 5:ehaf370. doi: 10.1093/eurheartj/ehaf370. Online ahead of print.

ABSTRACT

BACKGROUND AND AIMS: Previous studies have highlighted the significance of RNA-binding proteins and alternative splicing (AS) in the progression of complex diseases, but the specific involvement of AS in heart failure (HF) remains unclear. This study aimed to elucidate the role of RNA-binding motif single-stranded interacting protein 1 (RBMS1), an RNA-binding protein, in the development of HF by regulating AS and its effect on cardiac fibrosis.

METHODS: The level of RBMS1 was investigated in the hearts of both HF patients and mice. Fibroblast-specific knockout RBMS1 mice were generated to investigate the role of RBMS1 in cardiac fibrosis and HF. Unbiased RNA sequencing and RNA immunoprecipitation combined with RNA pull-down were conducted to identify the downstream effector of RBMS1 in fibroblasts.

RESULTS: RBMS1 expression was increased in murine hearts following myocardial infarction, as well as in the hearts of patients with ischaemic cardiomyopathy and hypertrophic cardiomyopathy. Moreover, RBMS1 levels in the hearts of HF patients were positively associated with cardiac fibrosis. Furthermore, fibroblast-specific ablation of RBMS1 improved cardiac dysfunction by mitigating myocardial fibrosis. Mechanistically, RBMS1 regulated the alternative splicing of LIM domain 7 (LMO7) by binding to intron 19 and splicing out exon 20, resulting in the formation of the LMO7-Δe20 isoform, which thus activated the transforming growth factor (TGF)-β1 pathway by upregulating activator protein 1. More importantly, overexpression of LMO7-Δe20 in mice resulted in cardiac fibrosis and cardiac dysfunction, which was ablated after treatment with TGF-β1 pathway inhibitor SB431542. In addition, SB431542 attenuated the RBMS1-driven fibrogenesis in human cardiac fibroblasts. Strikingly, pharmacologically inhibiting RBMS1 by low-dose nortriptyline or antisense oligonucleotide-mediated RBMS1 deficiency alleviated myocardial fibrosis and improved cardiac function in HF mice.

CONCLUSIONS: These findings unveil a critical role of RBMS1 in regulating cardiac fibrosis through controlling the splicing of LMO7 to activate the TGF-β1 pathway. Genetic ablation or pharmacological inhibition of RBMS1 improves cardiac function in mice, suggesting its potential as a therapeutic target for HF.

PMID:40471706 | DOI:10.1093/eurheartj/ehaf370

J Am Chem Soc. 2025 Jun 5. doi: 10.1021/jacs.5c03996. Online ahead of print.

ABSTRACT

Ultranarrow crystalline one-dimensional nanostructures formed from soft materials facilitate precise structural control in nanomaterial design, which is essential for biomedicine and nanotechnology applications. Systematic control of their hierarchical structure is challenging due to the complexities of simultaneously manipulating multiple noncovalent interactions at such small scales. We employed a polypeptoid crystal motif as a supramolecular synthon to engineer ultranarrow crystalline nanofibers constrained to a single lattice axis by incorporating a single ionizable side chain into the hydrophobic core of a nanosheet-forming peptoid. Cryogenic transmission electron microscopy of the nanofibers revealed detailed molecular arrangements of a unit-cell cross-section and the presence of distinct pH-dependent lattice isoforms that resulted in morphological transformations. Molecular dynamics simulations demonstrated that the ionizable side chain plays a critical role in changing the local conformation of the unit cell, which further impacts the dimensionality of hierarchical structures. Moreover, these fibers were readily functionalized with biological ligands to afford one-dimensional (1D) protein arrays. This approach for the high-precision bottom-up assembly of ultranarrow 1D nanostructures offers significant potential for developing novel biomimetic nanostructures.

PMID:40471545 | DOI:10.1021/jacs.5c03996

Planta. 2025 Jun 5;262(1):17. doi: 10.1007/s00425-025-04735-9.

ABSTRACT

This review highlights the diverse modeling approaches essential for understanding the dynamics of plant circadian clock genes, which are key to optimizing plant growth, development, and resilience to environmental stress. The circadian clock in plants is a complex system governed by intricate transcriptional regulatory networks that orchestrate gene expression in response to environmental cues. These networks are crucial for understanding plant adaptation to daily changes and optimizing growth. This review provides a comprehensive account of various modeling approaches used to study plants' transcriptional regulatory network of circadian clock genes. Here, we review different computational methodologies like ordinary differential equation-based approaches, stochastic models, and spatial techniques that can be evaluated on their ability to capture the dynamics, variability, and interactions inherent to the circadian clock system. Moreover, the circadian clock's responsiveness to environmental cues, such as light, temperature, and other stressors plays a pivotal role in ensuring plant development. The modeling approaches must consider environmental factors influencing the transcriptional regulatory networks, which potentially alter the clock's phase, amplitude, and photoperiod. These adaptations are critical for plant survival, as they align physiological processes with specific hours of the day, enhancing resource use efficiency, and stress resilience. We highlight the respective strengths and limitations of different models emphasizing the importance of an integrative approach that combines multiple techniques which capture the essence of interactions of circadian clock components and their implications for plant growth, development and survival.

PMID:40471439 | DOI:10.1007/s00425-025-04735-9

J Am Chem Soc. 2025 Jun 5. doi: 10.1021/jacs.5c04942. Online ahead of print.

ABSTRACT

The ortho-nitrobenzyl (ONB) group is one of the most widely utilized photocages for spatiotemporal control of biological processes via the light-triggered activation of small molecules and macromolecules. However, a significant limitation is that ONB photocages typically absorb in the UV/blue light region, which is phototoxic to living systems and exhibits limited tissue penetration. In this study, we present a novel approach for near-infrared (NIR) light-triggered photodecaging of the ONB core using silicon rhodamine (SiR) as a photoredox catalyst. The reaction efficiently uncages ONB substrates under 660 nm light irradiation, achieving high yields across a diverse range of substrates, including amino acids, nucleotides, prodrugs, bioactive small molecules, caged fluorescent dyes, and proteins. Mechanistic studies demonstrate that the uncaging reaction proceeds through nitroreduction via a single electron transfer mechanism, followed by an electron cascade-triggered self-immolation process. The reaction has been successfully applied in both mammalian cells and bacteria. Furthermore, we developed a NIR light-activated prodrug release protocol for antibody-drug conjugates (ADCs) targeting noninternalizable cancer cell surface markers and demonstrated the utility of this approach in a tumor-bearing mouse model.

PMID:40471121 | DOI:10.1021/jacs.5c04942

J Virol. 2025 Jun 5:e0078925. doi: 10.1128/jvi.00789-25. Online ahead of print.

ABSTRACT

Herpesviruses are large DNA viruses that encode homologs of cellular enzymes. The viral ribonucleotide reductase, which consists of large R1 and small R2 subunits, is required for deoxyribonucleotide synthesis. However, herpesviruses have repurposed the R1 subunit for additional non-canonical functions in virus-host interaction and immune evasion. Here, we investigated the R1 proteins of Kaposi's sarcoma-associated herpesvirus (KSHV) and murine gammaherpesvirus 68 (MHV-68), two γ-herpesviruses of the genus Rhadinovirus. We show that the ORF61-encoded viral R1 proteins form elongated cytoplasmic condensates in infected cells, which structurally differ from the previously described R1 condensates of other herpesviruses. Fluorescently labeled ORF61 condensates exhibited the properties of solid aggregates, as determined by fluorescence recovery after photobleaching (FRAP). Correlative light and electron microscopy (CLEM) showed that ORF61 aggregates consist of filamentous bundles. The KSHV ORF61 protein interacted with the cellular cytosine deaminase APOBEC3B in infected cells and translocated it from the nucleus, the site of viral DNA replication, to the cytoplasmic aggregates. Aggregate formation and relocalization of APOBEC3B depended on a conserved Induced Protein Aggregation Motif (IPAM) in the C-terminal part of ORF61. A KSHV ORF61 IPAM mutant was vulnerable to APOBEC3B-mediated deamination and replicated to reduced titers. In contrast, MHV-68 ORF61 did not relocalize human or murine APOBEC3 proteins, suggesting that it engages different target proteins. The results show that rhadinovirus ORF61 proteins form elongated filamentous aggregates in infected cells to sequester and inactivate target proteins, such as APOBEC3B.IMPORTANCEHerpesviruses are large DNA viruses that encode enzymes similar to those in host cells. The R1 subunit of their ribonucleotide reductase is important for DNA synthesis and plays additional roles in immune evasion and virus-host interactions. This study focused on the R1 protein ORF61 of two γ-herpesviruses of the genus Rhadinovirus: KSHV and MHV-68. Unlike their homologs in other herpesviruses, KSHV and MHV-68 R1 proteins form cytoplasmic aggregates consisting of filamentous bundles in infected cells. KSHV ORF61 depletes the mutagenic cellular enzyme APOBEC3B from the nucleus, the site of viral DNA replication, and sequesters it in cytoplasmic aggregates, thereby protecting the viral genome from APOBEC3B-mediated mutations. This process relies on a specific conserved motif in ORF61. However, the MHV-68 ORF61 protein does not redistribute APOBEC3 proteins, suggesting that it binds different targets. These findings reveal how rhadinoviruses use filamentous ORF61 aggregates to manipulate host antiviral defenses.

PMID:40470958 | DOI:10.1128/jvi.00789-25

Elife. 2025 Jun 5;12:RP89170. doi: 10.7554/eLife.89170.

ABSTRACT

The successful integration of engineered gene circuits into host cells remains a significant challenge in synthetic biology due to circuit-host interactions, such as growth feedback, where the circuit influences cell growth and vice versa. Understanding the dynamics of circuit failures and identifying topologies resilient to growth feedback are crucial for both fundamental and applied research. Utilizing transcriptional regulation circuits with adaptation as a paradigm, we systematically study more than 400 topological structures and uncover various categories of failures. Three dynamical mechanisms of circuit failures are identified: continuous deformation of the response curve, strengthened or induced oscillations, and sudden switching to coexisting attractors. Our extensive computations also uncover a scaling law between a circuit robustness measure and the strength of growth feedback. Despite the negative effects of growth feedback on the majority of circuit topologies, we identify several circuits that maintain optimal performance as designed, a feature important for applications.

PMID:40470804 | DOI:10.7554/eLife.89170

Adv Sci (Weinh). 2025 Jun 5:e05075. doi: 10.1002/advs.202505075. Online ahead of print.

ABSTRACT

The synthesis of cellulose pellicles by bacteria offers an enticing strategy for the biofabrication of sustainable materials and biomedical devices. To leverage this potential, bacterial strains that overproduce cellulose are identified through directed evolution technology. While cellulose overproduction is linked with a specific genetic mutation, the effect of such mutation on the intracellular protein landscape and on the structure and mechanical properties of the cellulose pellicles is not yet understood. Here, the proteome of bacteria evolved to overproduce cellulose is studied and its effect on the structure and mechanics of the resulting cellulose pellicles is investigated. Proteomic analysis reveals that the protein landscape of the evolved bacteria shows pronounced differences from that of native microorganisms. Thanks to concerted changes in the proteome, the evolved bacteria can generate cellulose pellicles with exquisite structure and improved mechanical properties for applications in textiles, packaging, and medical implants.

PMID:40470676 | DOI:10.1002/advs.202505075

Insect Mol Biol. 2025 Jun 5. doi: 10.1111/imb.13006. Online ahead of print.

ABSTRACT

Cyantraniliprole (Cya), a diamide insecticide, is widely utilised for the management of Lepidoptera pests owing to its potent insecticidal efficacy and broad spectrum of activity. The extensive use and prolonged environmental persistence of this insecticide pose a significant threat to the sustainable development of sericulture. This study firstly assessed the lethal toxicity of cyantraniliprole to the 5th instar larvae of Bombyx mori. Exposure to cyantraniliprole (LC5, LC10 and LC20) resulted in a concentration-dependent reduction in larval weight, pupal weight and survival rate and a prolongation of larval development time. Moreover, cyantraniliprole LC10 resulted in substantial structural damage to the epithelial cells, suppressed the mRNA levels of oxidative phosphorylation genes, perturbed ATP synthesis and led to an imbalance of intracellular reactive oxygen species. Meanwhile, the starvation treatment suggested that the impacts of cyantraniliprole on silkworms cannot be solely ascribed to nutritional deficiencies. Additionally, the results revealed that cytochrome P450s might serve as a pivotal factor in the detoxification metabolism of cyantraniliprole in the midgut of silkworms. The findings of this study offer evidence for the ecological risk posed by environmental residues of cyantraniliprole to non-target organisms and are also of great significance for sericulture production.

PMID:40470600 | DOI:10.1111/imb.13006

Front Med (Lausanne). 2025 May 21;12:1597844. doi: 10.3389/fmed.2025.1597844. eCollection 2025.

ABSTRACT

INTRODUCTION: Total-body PET is a recent development in clinical imaging that produces large datasets involving multiple tissues, enabling the use of new analytical methods for multi-organ assessments, such as network analysis-a well-developed method in neuroimaging. The skeletal system provides a good model for applying network analysis to total-body PET, as bone serves many classical whole-body functions as well as being an endocrine regulator of metabolism. Previous reports have suggested an association between the expression of bone-specific phosphatase, orphan 1 and disorders of altered energy metabolism such as obesity and diabetes. Here, we explore how lacking phosphatase, orphan 1 affects the skeletal metabolic networks of mice as a test approach for deploying network analysis in total-body PET.

METHODS: We retrospectively analysed [18F]fluorodeoxyglucose total-body PET/CT images from six 13-week-old wild type mice, three 22-week-old wild type mice, and three 22-week-old Phospho1 -/- mice. Pearson correlation networks were created using the dynamic data from seven bone regions, with a Pearson threshold of r>0.6 (significant at p < 0.005).

RESULTS: The bone metabolic networks of 13-week-old wild type mice were found to robustly resist changes to the data from different PET measurements, increased noise, and shortened scan length. Key features were repeatedly observed, namely that all bones except the spine are highly inter-correlated, while the spine has minimal correlation to other bones. When network analysis was used to compare the three cohorts, the older wild type network had similar features to the young mouse, whereas the Phospho1 -/- network had increased correlations across all bones. An all-cohort network separated the data into one part including only bones from the wild type mice (13 nodes) and one part only bones from the Phospho1 -/- mice (8 nodes, 95% separation purity). Within the wild type section, the same bone from each young and old mouse were correlated.

DISCUSSION: We demonstrated network analysis is a promising method for studying whole-body PET, sensitive to dynamic details in the data without relying on assumptions or modelling. The proposed method could be applied to other total-body PET data-of healthy and diseased subjects, with different radiotracers, and more-to further elucidate tissue interactions at a systems level.

PMID:40470038 | PMC:PMC12133898 | DOI:10.3389/fmed.2025.1597844

Imeta. 2025 Apr 13;4(3):e70028. doi: 10.1002/imt2.70028. eCollection 2025 Jun.

ABSTRACT

The microbiota, comprising all the microorganisms within the body, plays a critical role in maintaining good health. Dysbiosis represents a condition resulting from an imbalance or alteration of the microbiota. This study comprehensively investigates the patent literature on dysbiosis over the past 20 years.

PMID:40469512 | PMC:PMC12130569 | DOI:10.1002/imt2.70028

Environ Microbiome. 2025 Jun 4;20(1):60. doi: 10.1186/s40793-025-00727-0.

ABSTRACT

BACKGROUND: Intercropping systems enhance agricultural sustainability by promoting ecosystem multifunctionality (EMF). This study examined the impact of adding pigeon pea (M + PG + PP) into a maize-palisade grass (M + PG) intercropping system under a no-till system (NTS) on soil microbial communities and ecosystem services. After five consecutive growing seasons, bulk soil samples from a soybean-based crop-livestock system were analyzed using metagenomics.

RESULTS: The inclusion of pigeon pea significantly improved the EMF index, with higher plant productivity and slightly enhanced outcomes in soil health, lamb meat productivity, and climate protection. The M + PG + PP treatment enriched Bradyrhizobium spp., which were positively correlated with soil health, plant productivity, and EMF index. Functional analysis indicated that M + PG + PP treatment enhanced nitrogen metabolism, biofilm formation, and exopolysaccharide (EPS) biosynthesis, improving soil fertility and microbial activity. Similarly, functional analysis of microbial plant growth-promoting traits revealed that the M + PG + PP treatment promoted microbial functions related to nitrogen and iron acquisition, sulfur assimilation, and plant colonization, all essential for plant growth and nutrient cycling. In contrast, the M + PG treatment primarily enhanced pathways related to competitive exclusion and phytohormone production.

CONCLUSIONS: These findings highlight the importance of incorporating legumes such as pigeon pea into intercropping systems to optimize ecosystem services, enhance soil health, and promote long-term agricultural productivity and sustainability.

PMID:40468430 | DOI:10.1186/s40793-025-00727-0

Nature. 2025 Jun 4. doi: 10.1038/s41586-025-09093-w. Online ahead of print.

ABSTRACT

RNA polymerase III (Pol III) transcribes highly demanded RNAs grouped into three types of classical promoters, including type 1 (5S rRNA), type 2 (tRNA) and type 3 (short non-coding RNAs, such as U6, 7SK and RNase H1) promoters1-7. While structures of the Pol III preinitiation complex (PIC)8-11 and elongation complex (EC)12-16 have been determined, the mechanism underlying the transition from initiation to elongation remains unclear. Here we reconstituted seven human Pol III transcribing complexes (TC4, TC5, TC6, TC8, TC10, TC12 and TC13) halted on U6 promoters with nascent RNAs of 4-13 nucleotides. Cryo-electron microscopy structures captured initially transcribing complexes (ITCs; TC4 and TC5) and ECs (TC6-13). Together with KMnO4 footprinting, the data reveal extensive modular rearrangements: the transcription bubble expands from PIC to TC5, followed by general transcription factor (GTF) dissociation and abrupt bubble collapse from TC5 to TC6, marking the ITC-EC transition. In TC5, SNAPc and TFIIIB remain bound to the promoter and Pol III, while the RNA-DNA hybrid adopts a tilted conformation with template DNA blocked by BRF2, a TFIIIB subunit. Hybrid forward translocation during ITC-EC transition triggers BRF2-finger retraction, GTF release and transcription-bubble collapse. Pol III then escapes the promoter while GTFs stay bound upstream, potentially enabling reinitiation. These findings reveal molecular insights into Pol III dynamics and reinitiation mechanisms on type 3 promoters of highly demanded small RNAs, with the earliest documented initiation-elongation transition for an RNA polymerase.

PMID:40468065 | DOI:10.1038/s41586-025-09093-w

Cell Res. 2025 Jun 4. doi: 10.1038/s41422-025-01132-5. Online ahead of print.

NO ABSTRACT

PMID:40467773 | DOI:10.1038/s41422-025-01132-5