Front Toxicol. 2025 Jul 7;7:1619651. doi: 10.3389/ftox.2025.1619651. eCollection 2025.

ABSTRACT

AIMS: In silico methods provide a resourceful toolbox for new approach methodologies (NAMs). They can revolutionize chemical safety assessment by offering more efficient and human-relevant alternatives to traditional animal testing. In this study, we introduce two Liver Physiological Maps (PMs); comprehensive and machine-readable graphical representations of the intricate mechanisms governing two major liver functions.

METHODS: Two PMs were developed through manual literature curation, integrating data from established pathway resources and domain expert knowledge. Cell-type specificity was validated using Human Protein Atlas datasets. An interactive version is available online for exploration. Cross-comparison analysis with existing Adverse Outcome Pathway (AOP) networks was performed to benchmark physiological coverage and identify knowledge gaps.

RESULTS: The LiverLipidPM focuses on liver lipid metabolism, detailing pathways involved in fatty acid synthesis, triglycerides, cholesterol metabolism, and lipid catabolism in hepatocytes. And the LiverBilePM represents bile acid biosynthesis and secretion processes, detailing biosynthesis, transport, and secretion processes between hepatocytes and cholangiocytes. Both maps integrate metabolism with signaling pathways and regulatory networks. The interactive maps enable visualization of molecular pathways, linkage to external ontologies, and overlay of experimental data. Comparative analysis revealed unique mechanisms to each map and overlaps with existing AOP networks. Chemical-target queries identified new potential targets in both PMs, which might represent new molecular initiating events for AOP network extension.

CONCLUSION: The developed liver PMs serve as valuable resources for hepatology research, with a special focus on hepatotoxicity, supporting the refinement of AOP networks and the development of human-oriented in vitro test batteries for chemical toxicity assessment. These maps provide a foundation for creating computational models and mode-of-action ontologies while potentially extending their utility to systems biology and drug discovery applications.

PMID:40692843 | PMC:PMC12277266 | DOI:10.3389/ftox.2025.1619651

ERJ Open Res. 2025 Jul 21;11(4):01231-2024. doi: 10.1183/23120541.01231-2024. eCollection 2025 Jul.

ABSTRACT

BACKGROUND: Individuals with inactive pulmonary tuberculosis (PTB) lesions were found to be high-risk populations for active PTB development. This retrospective study evaluated the association between different types of inactive PTB lesions and the development of active PTB aiming to provide epidemiological evidence for developing precise intervention strategies.

METHODS: Based on a population-based PTB active-case-finding project conducted on the elderly, 154 028 subjects who had participated in the 2020 baseline survey were included in the current analysis.

RESULTS: During the 2-year follow-up, 462 cases developed microbiologically confirmed active PTB with an overall incidence rate of 0.19 per 100 person-years. Among the study population, 15 037 (9.76%) showed chest radiography (CXR) abnormalities suggestive of inactive PTB, which was found to be independently associated with an increased risk of active PTB with an adjusted hazard ratio (aHR) of 6.00 (95% confidence interval (CI) 4.85-7.43) compared with normal CXR. Such a relationship was consistently observed for inactive lesions, including fibrosis, calcification, pleural thickening and nodule lesions with aHRs ranging from 2.94 to 6.55. Inactive PTB lesions alone or a history of anti-tuberculosis (TB) treatment alone were independently associated with the risk of active PTB with aHRs of 6.96 (95% CI 5.59-8.67) and 7.67 (95% CI 4.26-13.78), respectively. A combined effect between inactive PTB lesions and with history of anti-TB treatment was found with an aHR of 10.50 (95% CI 5.93-18.52).

CONCLUSION: Overall, individuals with inactive PTB lesions, regardless of lesion type and history of anti-TB treatment, are at increased risk of developing active PTB and deserve interventions for TB control.

PMID:40692838 | PMC:PMC12278313 | DOI:10.1183/23120541.01231-2024

Health Sci Rep. 2025 Jul 21;8(7):e70910. doi: 10.1002/hsr2.70910. eCollection 2025 Jul.

ABSTRACT

BACKGROUND AND AIM: Despite the variety of screening tests, the number of babies born with Down's syndrome (DS) has not significantly decreased. The aim of this study was systematically review previously published meta-analysis studies to identify the most efficient screening tests for DS during only the first trimester (FT) and only in the second trimester (ST) of pregnancy.

METHODS: The data sources, including Scopus, Cochrane Library, and PubMed, were reviewed. The effectiveness of tests was investigated and compared by extracting their sensitivity and specificity values from meta-analyses. The heterogeneity of data was investigated by χ 2 and I 2 tests. In addition, publication bias was assessed through Egger's and Begg's tests.

RESULTS: This study investigated 14 eligible and high-quality meta-analyses. Meta-analysis of 13 studies revealed FT and ST as the best stage for conducting serum tests, with a sensitivity of 0.824 (CI: 0.790-0.857) and specificity of 0.956 (CI: 0.947-0.965). Likewise, FT and ST were found as the best stage for conducting ultrasound tests, with a sensitivity of 0.882 (CI: 0.850-0.914) and a specificity of 0.95 (CI: 0.944-0.956). In addition, ST was determined as the best stage for carrying out ultrasound (US) and serum screening (SS) tests, with a sensitivity of 0.93 and a specificity of 0.93, indicating the highest sensitivity and specificity of US + SS tests in the ST than FT and FT & ST stages.

CONCLUSION: The first and second trimesters (FT and ST) is the best stage for carrying out ultrasound and serum screening tests. ST was found to be the best stage for conducting US + SS in DS screening tests. US + SS tests achieved the best results for DS screening during the FT and ST of pregnancy.

PMID:40692565 | PMC:PMC12277661 | DOI:10.1002/hsr2.70910

Mol Nutr Food Res. 2025 Jul 22:e70174. doi: 10.1002/mnfr.70174. Online ahead of print.

ABSTRACT

The postprandial period is an opportunity window to assess metabolic phenotype, and its study is gaining popularity due to the wealth of information that can be uncovered when a dietary challenge is associated with the application of metabolomics approaches. Bile acids (BA) were recently identified as signaling molecules that display major changes in circulating levels following food intake. In this regard, a gap of information remains linking BA postprandial kinetics with their possible metabolic effects. This study aimed to characterizing a murine model for investigating postprandial metabolism and inflammation. Changes in plasma and hepatic markers of metabolism, inflammation and BA levels were assessed in male Sprague-Dawley rats before and after the ingestion of an energy-dense meal. Rats display postprandial alterations in circulating BA levels, with cholic acid constituting the predominant species (36%). These changes are accompanied by shifts in intermediates of energy metabolism and inflammatory markers, as demonstrated by a four-fold increase in hepatic NF-κB protein content, a key inflammatory transcription factor, two hours after food intake. Despite inherent species-specific differences, this murine model represents a promising tool for studying postprandial modulation energy metabolism, establishing a pioneering framework for future investigations into the role of BA in postprandial metabolic responses.

PMID:40692377 | DOI:10.1002/mnfr.70174

Plant Biotechnol J. 2025 Jul 21. doi: 10.1111/pbi.70248. Online ahead of print.

ABSTRACT

Excessive nitrogen use and low nitrogen use efficiency (NUE) in current agroecosystems are disrupting the global nitrogen cycle. Chemical inhibitors offer only temporary relief, while plant-derived biological nitrification inhibitors (BNIs) remain safer but underexplored. Identifying biological nitrification inhibition (BNI) traits in nitrogen-demanding crops like wheat is key to improving sustainability. In this study, a combined GC- and LC-MS platform was used to determine the metabolome of the root exudates of 44 diverse wheat genotypes originating from India and Austria. With more than 6000 metabolic features, a pronounced genotype-specific variation, a clear geographic pattern and an unexpected complexity of the root exudate metabolome were observed. A novel high-throughput assay utilizing diverse ammonia-oxidizing bacteria (AOB) and archaea (AOA) was developed for rapid BNI testing, highlighting distinct inhibition and even growth stimulation capacities between genotypes. Network analysis and advanced machine and deep learning analysis identified combinations of 32 metabolites linked to high BNI activity, including phenylpropanoids sinapinic acid, syringic acid and others, as well as glycosylated flavones isoschaftoside and others. This indicates that the concurrent presence of specific metabolites, rather than a single compound, drives nitrification inhibition in the rhizosphere. Variation in BNI activity among wheat genotypes, classified as either spring or winter types, suggests that root architecture modulates the dynamics of root exudation and the potential for nitrification inhibition. The unique combination of high-throughput metabolomics analysis and the BNI fast-track assay allows for screening of large germplasm collections as an essential requirement to introduce BNI and related NUE traits into modern breeding programmes.

PMID:40692297 | DOI:10.1111/pbi.70248

Am J Bot. 2025 Jul 21:e70076. doi: 10.1002/ajb2.70076. Online ahead of print.

ABSTRACT

PREMISE: Soil salinization is a growing global challenge that significantly reduces agricultural productivity by impairing seed germination, growth, and yield. While conventional crops have limited tolerance to high salinity, halophytes are promising biological models for developing strategies to sustain agriculture in saline environments and support global food security. This review addresses the potential of halophyte-produced allelochemicals and related signaling molecules to mitigate the impacts of salinization, a topic of growing relevance for sustainable agriculture in a changing climate.

METHODS: We surveyed and synthesized current research on halophyte allelochemicals and complementary plant-derived molecules and discussed their roles in enhancing resilience to salt stress. Emphasis was placed on distinguishing true allelochemicals from other biologically active compounds and evaluating their applications in plant stress management.

RESULTS: Conventional allelochemicals that are synthesized and released into the environment by halophytes modulate plant responses and may enhance their salt stress resistance. In addition, phytohormones, polyamines, and microbial metabolites have also demonstrated significant hardening effects by enhancing plant tolerance to salinity. Halophytes also provide additional ecosystem benefits as biofuel, forage, or edible crop sources and play a role in phytoremediation.

CONCLUSIONS: Using halophyte-derived allelochemicals and complementary signaling molecules offers a viable, environmentally friendly way to increase crop production in saline areas, reduce soil salinization, and conserve freshwater. Future research is expected to focus on optimizing application strategies, evaluating environmental risks, and integrating allelopathy-based approaches into sustainable agricultural systems to enhance crop resilience in the face of climate change.

PMID:40692138 | DOI:10.1002/ajb2.70076

Genome Biol. 2025 Jul 21;26(1):215. doi: 10.1186/s13059-025-03666-8.

ABSTRACT

X-chromosome inactivation (XCI) is a crucial mechanism of dosage compensation in female mammals ensuring that genes from only one X chromosome are expressed, initiated through expression of the long noncoding RNA Xist. Recent evidence underscores the significance of molecular crowding-most likely via liquid-liquid phase separation (LLPS)-in forming Xist RNA-driven condensates critical for establishing and sustaining the silenced state. By integrating existing knowledge and emerging ideas, we provide a comprehensive perspective on the molecular underpinnings of XCI and outline how manipulation of LLPS-based mechanisms offers new avenues for novel therapeutic approaches.

PMID:40691806 | DOI:10.1186/s13059-025-03666-8

J Gastroenterol. 2025 Jul 21. doi: 10.1007/s00535-025-02285-1. Online ahead of print.

ABSTRACT

BACKGROUND: Increasing evidence reveals that immune cells significantly contribute to metabolic dysfunction-associated steatotic liver disease (MASLD) progression. The patatin-like phospholipase domain-containing protein 3 (PNPLA3) I148M variant has been linked to hepatic inflammation and fibrosis; however, its role in immune cell infiltration and activation within the liver remains unclear.

METHODS: Seventy patients with MASLD were prospectively enrolled. Genomic DNA was extracted from buccal swabs or liver biopsy samples, followed by single nucleotide polymorphism genotyping to determine the rs738409 SNP genotype at codon 148 of PNPLA3. Immunohistochemistry was conducted using CD3 and CD68 antibodies to quantify T cell and macrophage infiltration, respectively. Total RNA extracted from biopsy specimens was used for quantitative reverse transcription polymerase chain reaction to assess the expression of specific markers associated with immune cell activation.

RESULTS: Among the 70 patients with MASLD, 34 had the GG genotype, whereas 21 and 15 had the GC and CC genotypes, respectively. The GG genotype group showed a higher proportion of advanced fibrosis (F3 or F4) than the GC + CC group (P = 0.051). GG genotype carriers exhibited significantly higher CD3+ and CD68+ cell counts in the periportal region than the GC/CC carriers (P < 0.05). The transcriptomic analysis revealed elevated expression of markers associated with chronic antigen stimulation and immune cell activation (CD8A, GZMB, CCL2, and TIMP1) in GG carriers compared with those of GC and CC (P < 0.05). Furthermore, correlations among various markers, including inflammatory, steatosis-associated, and fibrosis-associated markers, exhibited consistent positive correlations.

CONCLUSIONS: Our findings revealed that the PNPLA3 I148M variant and increased immune cell infiltration and activation were significantly correlated within the MASLD liver. Further studies are needed to elucidate the mechanistic links between this genetic variant and liver inflammation.

PMID:40691355 | DOI:10.1007/s00535-025-02285-1

J Neurointerv Surg. 2025 Jul 21:jnis-2025-023364. doi: 10.1136/jnis-2025-023364. Online ahead of print.

ABSTRACT

OBJECTIVE: Intracranial atherosclerotic disease (ICAD) is a leading cause of ischemic stroke worldwide. The objective of this study is to evaluate the association of three-dimensional high-resolution MRI (3D HR-MRI) characteristics related to intracranial plaques with the risk of vascular events in ICAD patients.

METHODS: A comparison of demographics and intracranial plaque characteristics was conducted on intracranial atherosclerotic plaques in 43 asymptomatic ICAD patients, 31 patients with transient ischemic attack (TIA), and 113 patients with acute ischemic stroke (AIS). Univariate and multivariate logistic regression analyses were employed to identify specific plaque characteristics associated with these vascular events. Receiver operating characteristic curves were generated to illustrate the discriminatory performance of these plaque features.

RESULTS: Significant differences in irregular surface, grade 2 enhancement, signal intensity (SI), wall contrast ratio (CR), remodeling index, normalized wall index, 3D average normalized wall index, plaque length, and volume were observed between the asymptomatic group and the AIS group (P<0.05). When comparing the asymptomatic group to the TIA group, statistically significant disparities were noted in plaque irregularity, plaque length, and plaque volume (P<0.05). Conversely, comparing TIA and AIS groups, only plaque wall CR demonstrated a statistically meaningful difference (P<0.05). Multivariable logistic regression analysis identified increased plaque volume as an independent risk factor for ICAD-related vascular events leading to TIA (OR 1.01, 95% CI 1.00 to 1.03, P=0.02). The efficacy of plaque volume in differentiating between asymptomatic patients and those presenting with TIA was substantial, yielding an area under the curve (AUC) value of 0.74 (95% CI 0.59 to 0.89). Moreover, plaque grade 2 enhancement (OR 6.31, 95% CI 1.70 to 31.63, P=0.011), remodeling index (OR 15.64, 95% CI 2.25 to 148, P=0.009), and plaque volume (OR 1.01, 95% CI 1.00 to 1.02, P=0.003) emerged as independent predictors for the occurrence of AIS linked to ICAD. A comprehensive model that integrates these features achieved a remarkable predictive capability (AUC 0.83, 95% CI 0.76 to 0.91).

CONCLUSION: The 3D HR-MRI characteristics of atherosclerotic plaques exhibited notable variations across different vascular events and can be identified through distinct imaging markers, serving as a basis for studying the pathogenesis of ICAD.

PMID:40691056 | DOI:10.1136/jnis-2025-023364

Tissue Eng Part C Methods. 2025 Jul;31(7):248-260. doi: 10.1177/19373341251360742.

ABSTRACT

Fibrosis causes altered tissue structure and function in multiple organs due to a complex interplay between inflammatory cells, myofibroblasts, and extracellular matrix (ECM) components. While it is known that T cells play a role in tissue fibrosis, it remains unclear how they modulate cellular interactions to activate fibrogenesis. Since conventional monolayer cell cultures do not mimic the tissue complexity and cellular heterogeneity in the fibrotic tissue environment, there is a need to bridge the gap between monolayer cultures and in vivo animal studies of fibrosis by providing a more predictive 3D model for preclinical drug screening and mechanistic studies of fibrotic diseases. We have developed 3D skin-like tissues harboring blood-derived human T cells that offer a model to better understand the role these cells play in the pathogenesis of tissue fibrosis. In the current study, we constructed skin-like tissues harboring T cells, fibroblasts, macrophages, and keratinocytes and analyzed them using tissue analysis and single-cell RNA sequencing (scRNA-seq). Skin-like tissues constructed with fully autologous cells (donor-matched fibroblasts and T cells) or nonautologous cells (mismatched fibroblasts and T cells) derived from patients with scleroderma (SSc) demonstrated normal distribution of tissue markers of epithelial differentiation and proliferation. T cells in these tissues were viable and functional as seen by elevated IL-6 production by enzyme-linked immunosorbent assay, expression of alpha smooth muscle actin in fibroblasts, and scRNA-seq. We used scRNA-seq to identify five distinct T cell subpopulations: CD8 T cells (identified by KLRK1 and CD8A), proliferating CD4 T cells (identified by PCNA, MKI67, and CD4), activated CD4 T cells (identified by IL2RA, RORA, and CD4), naïve CD4 T cells (identified by CCR7 and CD4), and Th17 CD4 T cells (identified by KLRB1, RORA, IL2RA, and CD4). Fabrication of complex 3D tissues are an important step toward establishing tissue engineering approaches to study fibrosis in multiple diseases, including SSc, idiopathic pulmonary fibrosis, as well as liver and kidney fibrosis. Understanding the roles of T cells in the ECM environment and their interactions with fibroblasts will support the development of novel treatments to reverse fibrosis and restore normal tissue and organ function.

PMID:40690724 | DOI:10.1177/19373341251360742

PLoS Comput Biol. 2025 Jul 21;21(7):e1013296. doi: 10.1371/journal.pcbi.1013296. Online ahead of print.

ABSTRACT

For unicellular organisms, the reproduction rate and growth are crucial fitness determinants and functional manifestations of the organism genotype. Using the budding yeast Saccharomyces cerevisiae as a model organism, we integrated metabolism, which provides energy and building blocks for growth, with cell mass growth and cell cycle progression into a low-granularity, multiscale (from cell to population) computational model. This model predicted that cells with constitutive respiration do not modulate cell size according to the growth conditions. We experimentally validated the model predictions using mutants with defects in the upper part of glycolysis or glucose transport. Plugging in molecular details of cellular subsystems allowed us to refine predictions from the cellular to the molecular level. Our hybrid multiscale modeling approach provides a framework for structuring molecular knowledge and predicting cell phenotypes under various genetic and environmental conditions.

PMID:40690530 | DOI:10.1371/journal.pcbi.1013296

PLoS Biol. 2025 Jul 21;23(7):e3003298. doi: 10.1371/journal.pbio.3003298. Online ahead of print.

ABSTRACT

The biogenesis of mitochondria relies on the import of hundreds of different precursor proteins from the cytosol. Most of these proteins are synthesized with N-terminal presequences which serve as mitochondrial targeting signals. Presequences consistently form amphipathic helices, but they considerably differ with respect to their primary structure and length. Here we show that presequences can be classified into seven different groups based on their specific features. Using a test set of different presequences, we observed that group A presequences endow precursor proteins with improved in vitro import characteristics. We developed IQ-Compete (for Import and de-Quenching Competition assay), a novel assay based on fluorescence de-quenching, to monitor the import efficiencies of mitochondrial precursors in vivo. With this assay, we confirmed the increased import competence of group A presequences. Using mass spectrometry, we found that the presequence of the group A protein Oxa1 specifically recruits the tetratricopeptide repeat (TPR)-containing protein TOMM34 to the cytosolic precursor protein. TOMM34, and the structurally related yeast co-chaperone Cns1, apparently serve as a presequence-specific targeting factor which increases the import efficiency of a specific subset of mitochondrial precursor proteins. Our results suggest that presequences contain a protein-specific priority code that encrypts the targeting mechanism of individual mitochondrial precursor proteins.

PMID:40690527 | DOI:10.1371/journal.pbio.3003298

J Vis Exp. 2025 Jul 3;(221). doi: 10.3791/68379.

ABSTRACT

Environmental sampling of photosynthetic microorganisms and their viruses plays a critical role in understanding contemporary marine and freshwater biodiversity and ecosystem dynamics as well as the impacts of climate change-related factors (e.g., rising temperatures and acidification) on evolutionary trajectories of species and community composition. Unfortunately, the diversity of the virosphere does not support a single universal sampling and experimental workflow. Indeed, each virus system has unique features, which require modifications to standard protocols in virology to accomplish research goals. Although virus discovery and characterization require approaches that are specific to the target system, for all viruses, the research aims are similar: isolate the virus; determine host range; confirm productive infection; and characterize the virus, the host, and virus-host dynamics. Robust descriptions of virus-host systems consist minimally of elucidating morphology, physiology, biochemistry, and omics profiles. Further information may be obtained by manipulating the system by changing factors such as multiplicity of infection, temperature, pH, host-switch, directed evolution, or applying drugs to observe virus-host system response. Our laboratory studies viruses across domains of life (Archaea, Bacteria, and Eukarya). In this report, we detail methods for sampling photosynthetic microbes from the euphotic zone of freshwater and marine environments with focus on isolating bacteriophage (i.e., cyanophage) of cyanobacteria. Cyanobacteria are keystone species critical to primary production and nutrient cycling in these aquatic ecosystems. The described workflow extends from sampling waters at different depths to characterizing virus-host system features using liquid and solid media culture, advanced molecular/genetic methods, and analytical approaches. The methods described are adaptable to bacteriophage and virus discovery in virus-host systems across domains of life.

PMID:40690404 | DOI:10.3791/68379

Pediatr Nephrol. 2025 Jul 21. doi: 10.1007/s00467-025-06872-5. Online ahead of print.

ABSTRACT

BACKGROUND: Data on the relevance of tacrolimus intrapatient variability (TacIPV) and concentration-to-dose ratio (C/D ratio) as an approximation of tacrolimus metabolism for predicting outcomes in pediatric kidney transplant (pKTx) recipients are scarce.

METHODS: We conducted a multicenter retrospective study of 255 pKTx recipients from the CERTAIN registry. TacIPV was quantified as the coefficient of variation (CV%) during months 6-12 post-transplant. In addition, the C/D ratio, corrected for body surface area, was calculated for the first 6 months post-transplant. Cutoffs were determined by minimization of log-rank P values: 23% for TacIPV and 1.0 for C/D ratio. Rejection episodes were classified according to the Banff criteria in the period following marker quantification.

RESULTS: A total of 13,159 tacrolimus trough blood levels were analyzed, with a median of 52 (IQR, 41-63) measurements per patient. High TacIPV (> 23%) during months 6-12 post-transplant was associated with an increased risk of rejection beyond 12 months post-transplant (hazard ratio (HR) 1.04, 95% CI 1.01-1.06, P = 0.002; Kaplan-Meier analysis P = 0.002). Similarly, a low C/D ratio (< 1.0), i.e., rapid tacrolimus metabolism, during the first 6 months was associated with a higher risk of rejection between months 6 and 12 (inverse HR 3.13, 95% CI 1.01-9.09, P = 0.04; Kaplan-Meier analysis P = 0.011).

CONCLUSIONS: This largest to date multicenter study determines pediatric-specific cutoff values for TacIPV and tacrolimus C/D ratio as a predictive marker for graft rejection. Patients with these risk factors should be closely monitored and their immunosuppressive therapy adjusted accordingly.

PMID:40689947 | DOI:10.1007/s00467-025-06872-5

Infect Dis Model. 2025 Jul 7;10(4):1252-1269. doi: 10.1016/j.idm.2025.07.005. eCollection 2025 Dec.

ABSTRACT

In the present article we propose a Partial Integro-Differential Equation (PIDE) model to approximate a stochastic SIS compartmental model for viral infection spread. First, an appropriate set of reactions is considered, and the corresponding Chemical Master Equation (CME) that describes the evolution of the reaction network as a stochastic process is posed. In this way, the inherent stochastic behaviour of the infection spread is incorporated in the modelling approach. More precisely, by considering that infection is propagated in bursts we obtain the PIDE model as the continuous counterpart to approximate the CME. In this way, the model takes into account that one infectious individual can be in contact with more than one susceptible person at a given time. Moreover, an appropriate semi-Lagrangian numerical method is proposed to efficiently solve the PIDE model. Numerical results and computational times for CME and PIDE models are compared and discussed. We also include a comparison of the main statistics of the PIDE model with the deterministic ODE model. Moreover, we obtain an analytical expression for the stationary solution of the proposed PIDE model, which also allows us to study the disease persistence. The methodology presented in this work is also applied to a real scenario as the COVID-19 pandemic.

PMID:40689269 | PMC:PMC12274815 | DOI:10.1016/j.idm.2025.07.005

IMA Fungus. 2025 Jul 10;16:e157337. doi: 10.3897/imafungus.16.157337. eCollection 2025.

ABSTRACT

Dermoloma is traditionally known as a small genus of agarics classified in the family Tricholomataceae. This study implemented a multilocus phylogeny of six DNA regions to recognize phylogenetic species within the genus. The species concept is reinforced by observations of well-defined morphological characters enhanced by long term sampling effort in Europe and North America. Thirty European Dermoloma species are described, including 16 new species from Europe and three from North American. These species are classified into two subgenera morphologically distinguished by spores with positive or negative amyloid reaction. A new genus Neodermoloma is introduced for the Dermoloma-like species N.campestre. Localized or continental-scale species endemicity was confirmed based on studied material, but more inclusive phylogenetic clustering supported a mixture of North American species among the European clades. Of the 22 names validly published from Europe prior to this study, 11 could be assigned to well-defined Dermoloma species recognized here. Of the remaining 11 names, two were considered representing Dermoloma species not recorded since their description, and nine were established as later synonyms of other species. Morphological studies of Dermoloma are challenging due to the relatively low number of characters suitable for identification of species. The majority of morphological characters showed continuous variation with high overlap throughout the genus. For this reason, species identification requires an awareness of morphological variability within species, and multiple distinguishing characters need to be combined, and furthermore, often a barcode sequence is needed for a certain identification. Stable isotope analysis in Dermoloma of δ13C and δ15N revealed an ecological signature similar to known CHEGD fungi, i.e. Clavariaceae and Hygrocybe s.l. This indicates that Dermoloma species are biotrophic but neither ectomycorrhizal nor saprotrophic and may form mutualistic root endophytic associations with vascular plants.

PMID:40689223 | PMC:PMC12272084 | DOI:10.3897/imafungus.16.157337

Lancet Reg Health Southeast Asia. 2025 Jul 4;39:100621. doi: 10.1016/j.lansea.2025.100621. eCollection 2025 Aug.

ABSTRACT

BACKGROUND: South Asians are considered to be at higher risk of dyslipidaemia, a modifiable risk factor for cardiovascular diseases (CVDs). We aimed to identify protein targets for dyslipidaemia and CVDs among people with South Asian ancestry.

METHODS: We used a two-sample mendelian randomisation (MR) approach, supplemented with MR-Egger, weighted median, colocalisation, and generalised MR (GMR), to evaluate the effect of 2800 plasma proteins on high/low/non-high-density lipoprotein cholesterol (HDL-C/LDL-C/non-HDL-C), total cholesterol, and triglycerides. Observational analyses were conducted on MR findings with strong colocalisation (posterior probability ≥ 80%) and GMR evidence. Univariate MR assessed lipid-associated proteins' effect on CVDs. Finally, we compared the effects of plasma proteins on lipids between South Asian and European populations.

FINDINGS: We identified 29 genetically proxied proteins potentially causal to at least one lipid measure, 12 of which showed strong colocalisation and GMR evidence, including angiopoietin-related protein 3 (ANGPTL3), proprotein convertase subtilisin/kexin type 9 (PCSK9), and cadherin EGF LAG seven-pass G-type receptor 2 (CELSR2). Notably, PCSK9 demonstrated a stronger association with LDL-C in Europeans compared to South Asians (βEuropean = 0.37; 95% CI 0.36, 0.38, βSouth Asian = 0.16; 95% CI 0.11, 0.21). Observational analysis suggested statistically significant interaction between PCSK9 levels with LDL-C levels in South Asians with South Asians having a significantly lower effect compared to other ethnicities (PCSK9∗South Asian; β = -0.14; 95% CI -0.174, -0.107). Additionally, we showed that CELSR2 is also linked with coronary artery disease in South Asians.

INTERPRETATION: Our study highlighted potential causal links between plasma proteins, dyslipidaemia, and CVDs in South Asians and highlighted protein targets, including CELSR2, PCSK9, ANGPTL3, and Apolipoprotein(a) (LPA). Notably, our study indicated that PCSK9 has a significantly weaker effect on LDL-C in South Asians than Europeans.

FUNDING: This work is supported by the British Heart Foundation Research Excellence Award (4) (RE/24/130023). IT and AR are supported by NIHR01 HL162300-02.

PMID:40689090 | PMC:PMC12271078 | DOI:10.1016/j.lansea.2025.100621

J Magn Reson Open. 2025 Sep;24:100205. doi: 10.1016/j.jmro.2025.100205. Epub 2025 Jun 30.

ABSTRACT

We evaluated altered cardiac metabolism in Zucker Spontaneously Hypertensive Fatty (ZSF1) rats fed an isocaloric high-fat diet versus normal chow using hyperpolarized (HP) [1-13C]pyruvate MR spectroscopic imaging (MRSI). This technique exploits remarkable signal enhancement to track the metabolic fate of injected HP [1-13C]pyruvate in vivo, allowing a simultaneous assessment of multiple metabolic pathways. The conversion of [1-13C]pyruvate to [1-13C]lactate (Lac) reflects anaerobic glycolysis activity, while the detection of 13C-bicarbonate (Bic) indicates glucose oxidation. Our findings show that ZSF1 rats fed a high-fat diet exhibit a greater reliance on anaerobic glycolysis relative to glucose oxidation, and this metabolic shift can be detected in vivo in real time. This study demonstrates the feasibility of HP [1-13C]pyruvate MRSI for assessing diet-dependent metabolic shifts in the myocardium of ZSF1 obese rats, a widely used preclinical model for heart failure with preserved ejection fraction (HFpEF).

PMID:40689081 | PMC:PMC12273856 | DOI:10.1016/j.jmro.2025.100205

PNAS Nexus. 2025 Jul 2;4(7):pgaf208. doi: 10.1093/pnasnexus/pgaf208. eCollection 2025 Jul.

ABSTRACT

To complete the genome-to-phenome map, transcriptome-wide association studies (TWAS) are performed to correlate genetically predicted gene expression with observed phenotypic measurements. However, the relatively small training population assayed with gene expression could limit the accuracy of TWAS. We propose genetic score omics regression (GSOR) correlating observed gene expression with genetically predicted phenotype, i.e. estimated breeding values (EBVs) in agriculture or polygenic score (PGS) in medicine. The score, calculated using variants near genes with assayed expression (cis-EBV or cis-PGS), provides a powerful association test between cis-effects on gene expression and the trait. In simulated and real data, GSOR outperforms TWAS in detecting causal/informative genes. We applied GSOR to transcriptomes of 16 tissues (N ∼ 5,000) and 37 traits in ∼120,000 cattle and conducted multitrait meta-analyses of omics-associations (MTAO). We found that, on average, each significant gene expression and splicing mediates cis-genetic effects on 8-10 traits. Many prioritized genes by GSOR and MTAO can be verified by Mendelian randomization analysis and show significantly reduced dN/dS, suggesting elevated evolutionary constraint for these genes. Using multiple methods, we detect expression levels of genes and/or RNA splicing events underlying previously thought single-gene loci to influence multiple traits. For example, the expression and RNA splicing of DGAT1 from multiple tissues regulated milk production, mastitis, gestation length, temperament, and stature. Also, gene expression and splicing of ABO (Histo-blood group) and ACHE (acetylcholinesterase, Cartwright blood group) affected protein concentration and mastitis, respectively. Taken together, our work provides new methods and biological insights for prioritizing informative omics-phenotype associations in mammals.

PMID:40688095 | PMC:PMC12275098 | DOI:10.1093/pnasnexus/pgaf208

Comput Struct Biotechnol J. 2025 Jul 5;27:3036-3044. doi: 10.1016/j.csbj.2025.07.006. eCollection 2025.

ABSTRACT

Proteins work in coordination to catalyze and regulate all biological activities and drive cellular functions. The collective behavior of proteins is studied through protein-protein interaction (PPI) networks, which provide a system-level understanding of their regulatory behavior. konnect2prot (k2p) is a web application that generates a context-specific directional PPI network from a list of proteins as input. It identifies influential spreaders in the generated network and detects their biological and topological importance. Here, we report the features added to k2p since its first release. Building on the foundation of its predecessor, k2p 2.0 now integrates differential gene expression analysis, thereby bridging the gap between gene-level regulation and protein-level activity, providing a holistic view of how transcriptional changes fuel cellular behavior. konnect2prot 2.0 is freely accessible at: https://konnect2prot_v2.thsti.in.

PMID:40687990 | PMC:PMC12275489 | DOI:10.1016/j.csbj.2025.07.006