Am J Respir Cell Mol Biol. 2025 May 9. doi: 10.1165/rcmb.2025-0030OC. Online ahead of print.

ABSTRACT

Contractile myofibroblasts immersed in stiffened remodelled extracellular matrix (ECM) characterise fibrotic lesions in idiopathic pulmonary fibrosis (IPF). Lipofibroblasts are lipid-droplet containing interstitial fibroblasts that support functional homeostasis of the developing and adult lung. We show that stiff substrates augment myofibroblast differentiation and ECM production in vitro under basal conditions and following transforming growth factor-β1 (TGF-β1) incubation when cultured on tissue culture plastic, whereas culture in soft microenvironments (as spheroids or on soft collagen-coated substrate) redirects myofibroblast to a lipofibroblast-like phenotype (identified by expression of adipose differentiation-related protein (ADRP) and intracellular lipid droplets), with reduced basal alpha-smooth muscle actin (α-SMA), collagen I, vimentin (VIM) and fibronectin (FN1) expression. The fibrogenic effects of TGF-β1 are prevented in fibroblasts cultured in soft settings. Global proteomics showed similar numbers of TGF-β1-induced differentially expressed proteins in stiff and soft settings (271 and 436, respectively). Of these, only 33 were similarly altered by TGF-β1; 200 were exclusively altered by TGF-β1 in stiff setting; 365 in soft setting, while 38 showed opposite responses. Reductions in YAP/TAZ, beta-catenin and SMAD expression and their limited nuclear levels in soft settings may explain the "afibrogenic" characteristic of these lipofibroblasts. Thus, in spheroids of lipofibroblasts TGF-β1 intracellular signalling is redirected and uncoupled from fibrogenesis, including YAP/TAZ, β-catenin and SMAD. Understanding the proximal causal mechano-transduction signalling networks that are differentially active in soft and stiff microenvironments may reveal novel drug targets for fibrosis treatment.

PMID:40343813 | DOI:10.1165/rcmb.2025-0030OC

Eur Radiol. 2025 May 8. doi: 10.1007/s00330-025-11649-3. Online ahead of print.

ABSTRACT

OBJECTIVES: To develop a new high-resolution (HR)CT abnormalities quantification tool (CVILDES) for interstitial lung diseases (ILDs) based on the nnU-Net network structure and to determine whether the quantitative parameters derived from this new software could offer a reliable and precise assessment in a clinical setting that is in line with expert visual evaluation.

METHODS: HRCT scans from 83 cases of ILDs and 20 cases of other diffuse lung diseases were labeled section by section by multiple radiologists and were used as training data for developing a deep learning model based on nnU-Net, employing a supervised learning approach. For clinical validation, a cohort including 51 cases of interstitial pneumonia with autoimmune features (IPAF) and 14 cases of idiopathic pulmonary fibrosis (IPF) had CT parenchymal patterns evaluated quantitatively with CVILDES and by visual evaluation. Subsequently, we assessed the correlation of the two methodologies for ILD features quantification. Furthermore, the correlation between the quantitative results derived from the two methods and pulmonary function parameters (DLCO%, FVC%, and FEV%) was compared.

RESULTS: All CT data were successfully quantified using CVILDES. CVILDES-quantified results (total ILD extent, ground-glass opacity, consolidation, reticular pattern and honeycombing) showed a strong correlation with visual evaluation and were numerically close to the visual evaluation results (r = 0.64-0.89, p < 0.0001), particularly for the extent of fibrosis (r = 0.82, p < 0.0001). As judged by correlation with pulmonary function parameters, CVILDES quantification was comparable or even superior to visual evaluation.

CONCLUSION: nnU-Net-based CVILDES was comparable to visual evaluation for ILD abnormalities quantification.

KEY POINTS: Question Visual assessment of ILD on HRCT is time-consuming and exhibits poor inter-observer agreement, making it challenging to accurately evaluate the therapeutic efficacy. Findings nnU-Net-based Computer vision-based ILD evaluation system (CVILDES) accurately segmented and quantified the HRCT features of ILD, and results were comparable to visual evaluation. Clinical relevance This study developed a new tool that has the potential to be applied in the quantitative assessment of ILD.

PMID:40341974 | DOI:10.1007/s00330-025-11649-3

Biotechnol Bioeng. 2025 May 8. doi: 10.1002/bit.29023. Online ahead of print.

ABSTRACT

Cytochrome P450 enzymes (P450s) are versatile biocatalysts with applications spanning pharmaceutical development and natural product biosynthesis. A critical bottleneck in P450-mediated reactions is the electron transfer process, which often limits catalytic efficiency and promotes uncoupling events leading to reactive oxygen species (ROS) formation. This review comprehensively examines recent protein engineering strategies aimed at enhancing electron transfer efficiency in P450 systems. We explore the design and application of different fusion constructs, which improve proximity between the P450 enzyme and its redox partners (RPs), as well as scaffold-mediated protein assembly, enabling precise spatial organization of P450s and RPs. Furthermore, we discuss targeted modifications at the P450-RP interaction interface and optimization of electron transfer pathways through site-directed mutagenesis and directed evolution. These strategies enhance catalytic activity, improve coupling efficiency, and reduce ROS formation. Finally, we address the remaining challenges in understanding and engineering P450 electron transfer, and discuss the future directions, emphasizing the need for advanced computational modeling, structural characterization, and integration of synthetic and systems biology approaches.

PMID:40344219 | DOI:10.1002/bit.29023

Sci Immunol. 2025 May 9;10(107):eadr4795. doi: 10.1126/sciimmunol.adr4795. Epub 2025 May 9.

ABSTRACT

High-grade serous ovarian cancer (HGSOC) remains an urgent unmet clinical need, with more than 70% of patients presenting with metastatic disease. Many patients develop large volumes of ascites, which promotes metastasis and is associated with poor therapeutic response and survival. Immunotherapy trials have shown limited success, highlighting the need to better understand HGSOC immunology. Here, we analyzed cytotoxic lymphocytes [natural killer (NK), T, and innate T cells] from patients with HGSOC and observed widespread dysfunction across primary and metastatic sites. Although nutrient rich, ascites was immunosuppressive for all lymphocyte subsets. NK cell dysfunction was driven by uptake of polar lipids, with associated dysregulation in lipid storage. Phosphatidylcholine was a key immunosuppressive metabolite, disrupting NK cell membrane order and cytotoxicity. Blocking lipid uptake through SR-B1 protected NK cell antitumor functions in ascites. These findings offer insights into immune suppression in HGSOC and have important implications for the design of future immunotherapies.

PMID:40344087 | DOI:10.1126/sciimmunol.adr4795

Sci Adv. 2025 May 9;11(19):eadu6843. doi: 10.1126/sciadv.adu6843. Epub 2025 May 9.

ABSTRACT

Correct organogenesis depends on the timely coordination of developmental processes, such as cell proliferation, differentiation, and migration. This coordination is particularly critical in crowded tissues, such as pseudostratified epithelia (PSE) that are often found as organ precursors. They are composed of elongated epithelial cells with densely packed nuclei aligned along the apicobasal axis. While cell cycle-dependent nuclear movements in PSE are well studied, less is known about how nuclear packing influences tissue morphogenesis. To investigate this, we analyzed nuclear shapes, sizes, and neighborhood statistics in zebrafish neuroepithelia, focusing on the retinal PSE. We found that nuclei exhibit elongated shapes and biaxial nematic-like orientational order but remain positionally disordered. During retinal development, nuclear packing density increases, approaching theoretical limits. This occurs when the tissue transitions to a laminated structure and nuclear shapes are remodeled. Timely neurogenesis is critical as failure to initiate neurogenesis leads to tissue deformations. These findings highlight the influence of nuclear shape and positioning for organ morphogenesis.

PMID:40344072 | DOI:10.1126/sciadv.adu6843

Cell Rep. 2025 May 7;44(5):115687. doi: 10.1016/j.celrep.2025.115687. Online ahead of print.

ABSTRACT

In cardiac progenitor cells (CPCs), retinoic acid (RA) signaling induces atrial lineage gene expression and acquisition of an atrial cell fate. To achieve this, RA coordinates a complex regulatory network of downstream effectors that is not fully identified. To address this gap, we applied a functional genomics approach (i.e., scRNA-seq and snATAC-seq) to untreated and RA-treated human embryonic stem cell (hESC)-derived CPCs. Unbiased analysis revealed that the Hippo effectors YAP1 and TEAD4 are integrated with the atrial transcription factor enhancer network and that YAP1 activates RA enhancers in CPCs. Furthermore, Yap1 deletion in mouse embryos compromises the expression of RA-induced genes, such as Nr2f2, in the CPCs of the second heart field. Accordingly, in hESC-derived patterned heart organoids, YAP1 regulates the formation of an atrial chamber but is dispensable for the formation of a ventricle. Overall, our findings revealed that YAP1 cooperates with RA signaling to induce atrial lineages during cardiogenesis.

PMID:40343798 | DOI:10.1016/j.celrep.2025.115687

FEMS Yeast Res. 2025 May 9:foaf024. doi: 10.1093/femsyr/foaf024. Online ahead of print.

ABSTRACT

Yeasts play a vital role in both research and industrial biomanufacturing. Saccharomyces cerevisiae has been extensively utilized as a model system. However, its application is often constrained by limited tolerance to the diverse stress conditions encountered in bioprocesses. These challenges have driven increasing interest in non-conventional, multi-stress tolerant yeasts as alternative biomanufacturing hosts. This review highlights Pichia kudriavzevii as a promising non-conventional yeast for industrial applications. Unlike S. cerevisiae, P. kudriavzevii exhibits exceptional tolerance to high temperatures, elevated concentrations of furanic and phenolic inhibitors, osmotic stress, salinity, and extreme pH. These traits make it an attractive candidate for industrial processes without requiring extensive genetic modifications to enhance stress resistance. As a result, P. kudriavzevii has emerged as a flagship species for advancing bioeconomy. Despite its industrial potential, the molecular mechanisms underlying P. kudriavzevii's superior stress tolerance remain poorly understood. This review compiles current knowledge on P. kudriavzevii and compares its stress tolerance mechanisms with those of S. cerevisiae, providing insights into its innate resilience. By expanding our understanding of non-conventional yeasts, this review aims to facilitate their broader adoption as robust microbial platforms for industrial biomanufacturing.

PMID:40343780 | DOI:10.1093/femsyr/foaf024

Res Sq [Preprint]. 2025 Apr 29:rs.3.rs-5960764. doi: 10.21203/rs.3.rs-5960764/v1.

ABSTRACT

HTLV-1 is an enigmatic retrovirus triggering a debilitating neuroinflammatory disease, HTLV-1-associated myelopathy (HAM), with unknown pathogenesis. Both HTLV-1 infection and HAM predominantly affect women and non-white neglected populations. HAM is lacking disease-modifying treatment, as current treatment is mostly symptomatic and inspired by either HIV-1 or multiple sclerosis therapeutic strategies. We used systems biology analyses of novel and publicly available data comprising (epi)genomics, transcriptomics, metabolomics and proteomics of multi-ancestry cohorts from a total of > 2500 People Living with HTLV-1 from 5 countries (Brazil, Peru, Japan, UK, US). Leveraging an unique admixed Brazilian cohort, genome-wide association study (GWAS) revealed African-specific variants in inflammasome sensor AIM2 with genome-wide significance (p < 5x10 - 8 ). Suggestive loci (p > 5x10 - 8 ) corresponding to metabolic, immune and neuronal genes were validated using published Japanese GWAS. Polygenic risk score and proviral load were independent disease predictors across ancestries. Systems biology analysis revealed neuronal/synaptic signaling, monocyte count, glucose/lipid metabolism, and neurocognition/depression as genetically linked to HAM. In silico drug screening identified estrogen blocker Fulvestrant as the top hit, while also confirming existing (pre)clinical data for HDAC inhibitors and immunosuppressants. Validated GWAS genes were overexpressed in HAM patients' whole blood and CD4 T-cells, as well as in spinal cord astrocytes, oligodendrocytes, and microglia by single-cell RNAseq. We experimentally confirmed decreased ApoA1/lipid/cholesterol levels, higher monocyte levels and lower neurocognitive scores in multi-ancestry cohorts. We found striking biological similarities between retroviral Hbz/Tax overexpression, Hbz interactome and HAM multi-omics findings: enrichment for lipid/cholesterol metabolism, estrogen signaling, neurodegenerative diseases, and viral pathways including EBV, recently identified as the major driver of multiple sclerosis. In conclusion, our data-driven approach uncovers novel disease mechanisms and therapeutic targets, and a validated polygenic risk score allowing targeted surveillance for high-risk individuals. A strong molecular overlap to other neurodegenerative/neuroinflammatory diseases reveals shared neuropathogenic pathways between unrelated viruses.

PMID:40343334 | PMC:PMC12060986 | DOI:10.21203/rs.3.rs-5960764/v1

Iran J Basic Med Sci. 2025;28(6):746-754. doi: 10.22038/ijbms.2025.82718.17878.

ABSTRACT

OBJECTIVES: Sleep impacts the well-being and quality of life of millions. Given conventional pharmacotherapy's limitations and side effects, the quest for adequate and proper sleep promotion is imperative. This study aims to identify a suitable and effective compound for sleep by examining qualified herbal compounds in the PubChem database using in silico methods. Ultimately, the extracted compound (ginkgetin, a bioactive flavonoid from Ginkgo biloba) through molecular docking by considering the GABAA receptors will be evaluated through the in vivo method in an animal model to serve as proof for the findings from the molecular docking process.

MATERIALS AND METHODS: Utilizing a comprehensive approach, this research employed molecular docking to screen 2299 phytochemicals for their affinity towards the GABAA receptor, focusing on the GABA, benzodiazepine, and steroid-binding sites. Ginkgetin emerged as a top candidate due to its high binding affinity. Subsequent in vivo electrophysiological assessments in rats treated with G. biloba extract containing ginkgetin evaluated alterations in sleep architecture, REM, and NREM sleep phases.

RESULTS: Molecular docking identified ginkgetin as possessing the highest binding affinity among the screened phytochemicals. In vivo studies corroborated these findings, demonstrating that rats treated with Ginkgo biloba extract significantly enhanced REM and NREM sleep compared to controls.

CONCLUSION: Ginkgetin, derived from G. biloba, shows promising potential as a novel therapeutic agent for sleep disorders, supported by its strong affinity to key receptor sites and its efficacy in modulating sleep architecture in vivo. These findings contribute to the expanding evidence base for the therapeutic use of G. biloba in sleep promotion and underscore the need for further research to elucidate the mechanisms and clinical applicability of ginkgetin in sleep disorder treatment.

PMID:40343295 | PMC:PMC12057750 | DOI:10.22038/ijbms.2025.82718.17878

Front Neurol. 2025 Apr 24;16:1488890. doi: 10.3389/fneur.2025.1488890. eCollection 2025.

ABSTRACT

Attachment style shapes one's connections with important figures in their life. One such unique relationship is the connection to God (CTG), which may be shaped by attachment style. Stronger CTG has been associated with secure attachment, yet the neural mechanisms underlying this relationship remain unclear. While previous research has implicated the prefrontal cortex (PFC) in CTG, findings have been mixed and may depend on attachment style-an idea that has yet to be directly tested. This study aimed to (1) examine whether individuals with a secure attachment style report higher levels of CTG compared to those with a non-secure attachment style, and (2) identify the brain regions associated with CTG in individuals with secure vs. non-secure attachment. We assessed attachment style and CTG in a sample of male combat veterans (N = 150), the majority of whom had focal traumatic brain injuries (pTBI; N = 119). Brain imaging (CT scans) was also obtained. Behaviorally, after controlling for age, years of education, and brain volume loss, individuals with a secure attachment style reported stronger CTG. Voxel-based lesion-symptom mapping revealed that damage to the right orbitofrontal cortex was associated with stronger CTG in individuals with secure-but not insecure-attachment. These findings suggest that attachment style shapes CTG at both behavioral and neural levels. Moreover, they highlight the potential role of attachment style in TBI recovery, offering insights that could inform spiritually integrated therapeutic interventions and support strategies.

PMID:40343178 | PMC:PMC12058672 | DOI:10.3389/fneur.2025.1488890

Immune Netw. 2025 Apr 9;25(2):e17. doi: 10.4110/in.2025.25.e17. eCollection 2025 Apr.

ABSTRACT

NK cell adoptive cell therapy (ACT) has emerged as a promising strategy for cancer immunotherapy, offering advantages in scalability, accessibility, efficacy, and safety. Ex vivo activation and expansion protocols, incorporating feeder cells and cytokine cocktails, have enabled the production of highly functional NK cells in clinically relevant quantities. Advances in NK cell engineering, including CRISPR-mediated gene editing and chimeric Ag receptor technologies, have further enhanced cytotoxicity, persistence, and tumor targeting. Cytokine support post-adoptive transfer, particularly with IL-2 and IL-15, remains critical for promoting NK cell survival, proliferation, and anti-tumor activity despite persistent challenges such as regulatory T cell expansion and cytokine-related toxicities. This review explores the evolving roles of IL-2 and IL-15 in NK cell-based ACT, evaluating their potential and limitations, and highlights strategies to optimize these cytokines for effective cancer immunotherapy.

PMID:40342841 | PMC:PMC12056295 | DOI:10.4110/in.2025.25.e17

JAC Antimicrob Resist. 2025 May 8;7(3):dlaf064. doi: 10.1093/jacamr/dlaf064. eCollection 2025 Jun.

ABSTRACT

OBJECTIVES: Whole-genome sequencing (WGS) was employed to investigate antibiotic resistance, virulence and transmission profiles of multidrug-resistant tuberculosis (MDR-TB) isolates from Shanghai, China.

METHODS: A total of 306 MDR-TB clinical isolates were collected from Shanghai Pulmonary Hospital and underwent phenotypic drug susceptibility testing (DST) for common anti-TB drugs and WGS. Combined 778 published bacterial sequences, we performed phylogenetic analysis, resistance and virulence gene identification to understand the genetic relationships and resistance mechanisms among those strains.

RESULTS: WGS determination, supported by DST, revealed high resistance rates for isoniazid (83.66%) and rifampicin (90.20%) among the MDR-TB isolates. Key resistance-associated mutations included katG Ser315Thr for isoniazid, rpoB mutations for rifampicin, and embB Met306Val for ethambutol. WGS demonstrated >90% concordance with culture-based DST for most drugs, except ethambutol that showed a 76.80% concordance. Analyses of virulence factors and phylogenetics revealed the genetically homogeneous, endemic MDR-TB population in Shanghai, with no evidence of recent transmission.

CONCLUSIONS: This study highlights the genetic homogeneity and endemic nature of MDR-TB in Shanghai, providing insights into key resistance mechanisms of TB.

PMID:40342723 | PMC:PMC12059630 | DOI:10.1093/jacamr/dlaf064

Ecol Evol. 2025 May 7;15(5):e71326. doi: 10.1002/ece3.71326. eCollection 2025 May.

ABSTRACT

Ants occupy a great variety of habitats, perform essential ecological roles, and interact with a wide variety of other organisms. However, the interaction between ants and mollusks is a lesser-explored relationship that can be categorized into (a) ant predation on mollusks, (b) shell collection as hoarding behavior, (c) the use of shells for nesting, and (d) myrmecophilic relationships. This study reports new data about several interactions from accidental field observations, a quantitative analysis of the snail shells found in 16 Messor ant nest cleanings, and a qualitative analysis of 51 additional nests of different species. We found 1127 snail shells from 20 species, most of them belonging to juveniles of the Geomitridae and Helicidae families. Notably, Granopupa granum was the only species found alive in the collected material. Furthermore, in our qualitative assessment, we found 86.8% of the analyzed nests with shell remains in the nest cleanings of at least nine ant species. Additional observations revealed ants transporting both empty shells and live snails to the nest, some living snail species around the nest entries, and additional interactions. Our results may support cases of (a) predation of snails of certain species by ants, as many shells were found with perforations compatible with ant attacks and we have recorded direct predation, (b) the collection of empty shells to gather the body remains of snails as a trophic resource or for other purposes, and (c) the potential existence of more myrmecophilous snail species than currently known, capable of living in ant nests without being attacked, like Cecilioides acicula, Ferrussacia folliculum, or G. granum. Although more studies are necessary to understand the intriguing relationship between ants and snails, the study of ant nest wastes can also become a valuable tool for detecting rare native micromollusc, as well as invasive, non-native, and aquatic species.

PMID:40342693 | PMC:PMC12058647 | DOI:10.1002/ece3.71326

J Sci Food Agric. 2025 May 8. doi: 10.1002/jsfa.14339. Online ahead of print.

ABSTRACT

BACKGROUND: Phytochemicals have long been utilized as active ingredients in the developing of novel functional foods or drugs due to their diverse biological and pharmacological effects. Many studies have demonstrated that polyphenols exhibit low absorption rates and are extensively metabolized into various metabolites, resulting in significantly reduced bioavailability.

RESULTS: Puerarin and diosmin exhibited the highest transport from the apical (AP) to basolateral (BL) direction, while diosmin and silybin showed the highest BL to AP transport. Most polyphenols demonstrated well-absorbed characteristics based on their apparent permeability coefficients (Papp), except for flavokawain A, phloretin, chrysin and dicoumarol, which displayed incomplete bidirectional absorption. Hesperetin exhibited a notable efflux ratio (ER) of 5.45, suggesting increased efflux compared to other compounds. A strong positive correlation was observed for Papp in both directions (Pearson correlation coefficient (PCC) = 0.53, P < 0.001), with a moderate correlation between ER and Papp(BL→AP) (PCC = 0.49, P < 0.001). Principal component analysis highlighted Papp(BL→AP) as the most influential indicator for polyphenol permeability, explaining a relatively wide portion of the data variance. Polyphenol compounds with a higher number of functional groups, such as -OH and -CH3, exhibited enhanced absorption due to increased binding affinity with intestinal cells and interactions with intracellular proteins.

CONCLUSION: These findings offer valuable insights for expressing polyphenol permeability via Caco-2 cells and may contribute to strategies aimed at enhancing the biological activities of polyphenols. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

PMID:40342091 | DOI:10.1002/jsfa.14339

Am J Biol Anthropol. 2025 May;187(1):e70061. doi: 10.1002/ajpa.70061.

ABSTRACT

OBJECTIVE: Play Face (PF) and Full Play Face (FPF) in the great apes-homologous to human smile and laugh-face-have been considered a single phenomenon. However, if natural selection has preserved two expressions, probably their adaptive value differs.

MATERIALS AND METHODS: We collected video data on play interactions in two lowland gorilla groups (N = 21; Gorilla gorilla gorilla) housed at La Vallée des Singes and the ZooParc de Beauval (France). Lacking a tool tailored for gorillas during this study, we analyzed facial action-unit activation via chimpFACS and OpenFace.

RESULTS: We found that PF and FPF activated partly different action units as it occurs for chimpanzees and humans' PF/FPF. We detected the rapid replication (Rapid Facial Mimicry [RFM]) of either PF or FPF that was associated with longer play sessions. Not-mimicked PF was linked to increased play session variability (different types of play patterns) measured via the Shannon Index, whereas not-mimicked FPF was associated with increased play asymmetry (imbalance between offensive/defensive patterns) measured via the Play Asymmetry Index.

DISCUSSION: Lowland gorillas may use PF to manage sessions that are more complex in terms of pattern types and FPF-a more salient signal-to prevent misunderstandings when the session is imbalanced. RFM of both expressions may favor the prolongation of play sessions by increasing player synchronization and possibly emotional sharing. Our study opens the door to further comparative studies on playful expressions in humans and other primates as a way to fine-tune possible emotional communication and delineate potential evolutionary roots of Hominidae facial communication.

PMID:40341893 | DOI:10.1002/ajpa.70061

Sci Rep. 2025 May 8;15(1):16081. doi: 10.1038/s41598-025-99277-1.

ABSTRACT

This work presents a multifaceted mechanism of the anticancer action of a 2-styrylquinazoline derivative. Extensive analysis of various aspects related to tyrosine kinase inhibition and effects on cellular targets at both the gene and protein levels revealed the potential of this IS20 compound for future research. This study presents a detailed analysis of the relationship between ABL and SRC kinase affecting the inhibition of the EGFR/mTOR signaling pathway in a non-obvious manner. The study was supported by experiments using various molecular biology techniques to confirm the induction of oxidative stress, inhibition of the cell cycle in the G2/M phase and the triggering of cell death via both the apoptosis and autophagy pathways. The cell models included those with different p53 protein status, which affected the cellular response in the form of altered Ndrg1 expression. Finally, the appropriate physicochemical properties of IS20 for adequate bioavailability and toxicity to the body were observed in an in vivo model.

PMID:40341822 | DOI:10.1038/s41598-025-99277-1

Clin Transl Med. 2025 May;15(5):e70331. doi: 10.1002/ctm2.70331.

ABSTRACT

Analysing the genome, epigenome, transcriptome, proteome, and metabolome within the spatial context of cells has transformed our understanding of tumour spatiotemporal heterogeneity. Advances in spatial multi-omics technologies now reveal complex molecular interactions shaping cellular behaviour and tissue dynamics. This review highlights key technologies and computational methods that have advanced spatial domain identification and their pseudo-relations, as well as inference of intra- and inter-cellular molecular networks that drive disease progression. We also discuss strategies to address major challenges, including data sparsity, high-dimensionality, scalability, and heterogeneity. Furthermore, we outline how spatial multi-omics enables novel insights into disease mechanisms, advancing precision medicine and informing targeted therapies. KEY POINTS: Advancements in spatial multi-omics facilitate our understanding of tumour spatiotemporal heterogeneity. AI-driven multimodal models uncover complex molecular interactions that underlie cellular behaviours and tissue dynamics. Combining multi-omics technologies and AI-enabled bioinformatics tools helps predict critical disease stages, such as pre-cancer, advancing precision medicine, and informing targeted therapeutic strategies.

PMID:40341789 | DOI:10.1002/ctm2.70331

Sci Rep. 2025 May 8;15(1):16057. doi: 10.1038/s41598-025-01300-y.

ABSTRACT

The success of the Nile tilapia (Oreochromis niloticus) as an aquaculture species is partly the result of continuous selective breeding leading to high performing strains. These elite strains have been derived from breeding populations of diverse origins and crosses with other Oreochromis species. Owing to the complex and unique evolutionary histories of each strain, existing reference genomes of wild populations are unsuitable to implement genomic selection for beneficial traits such as growth or environmental resilience in aquaculture programmes. Here we generated a high-quality genome assembly and annotation of the WorldFish Genetically Improved Abbassa Nile tilapia (GIANT) elite strain using a combination of PacBio HiFi, and Omni-C Illumina sequencing. As a male Abbassa Nile tilapia was used for the generation of the genome assembly, we reconstructed both X and Y haplotypes, identifying both amhY and amhΔy on LG23 indicating that Abbassa likely shares the same sex determination system as GIFT, and thereby differs from the existing reference genome, whose sex determination loci are located on LG1.

PMID:40341759 | DOI:10.1038/s41598-025-01300-y

Front Vet Sci. 2025 Apr 24;12:1558222. doi: 10.3389/fvets.2025.1558222. eCollection 2025.

ABSTRACT

INTRODUCTION: Continuous product monitoring post approval builds on the knowledge gained during clinical studies to aid in understanding a product's safety and efficacy profile. Pharmacovigilance reporting of a medicinal product might be influenced by several factors including duration in the market, geographical region and veterinary practices. The goals of this report are to present the global data accrued for bedinvetmab, the first monoclonal antibody for canine osteoarthritis, and to explore reporting patterns globally and across major markets.

METHODS: Adverse event reports from the Zoetis Global Pharmacovigilance database (from first introduction on 01 February 2021 through 30 June 2024) were collected irrespective of suspected causality or off-label use. Each adverse event was coded using the Veterinary Dictionary for Drug Related Affairs (VeDDRA) terminology. The top 20 most reported VeDDRA terms were identified. Countries were ranked by number of doses distributed and frequency of adverse events.

RESULTS: Globally, 18,102,535 doses of bedinvetmab were sold during the study period with a total of 17,162 adverse events reported in dogs (9.48 events/10,000 treated animals (doses)). Eight clinical signs were considered rare (1-10 events/10,000 treated animals (doses)) with lack of efficacy having the highest rate (1.70) followed by polydipsia, ataxia, polyuria/pollakiuria, anorexia, lethargy, death, and emesis. All other clinical signs were considered very rare (< 1 event/10,000 treated animals (doses)). Median (interquartile range) of dogs' age and body weight were 12 (10-13) years and 26 (16-34.6) kg, respectively. The top eight countries by market size were United States (US), United Kingdom (UK), Germany, Spain, France, Italy, Canada, and Australia; from these, the top five by frequency of adverse events were Canada, US, UK, Australia and Germany. The most reported adverse events following bedinvetmab are considered rare or very rare.

DISCUSSION: The reported clinical signs generally aligned with expected adverse events or were anticipated within the population receiving bedinvetmab. Reporting rates and patterns in general and for specific VeDDRA terms greatly varied between countries and were not related to market size. Most dogs for which adverse events were reported were considered older and in fair clinical condition. Reporting to pharmacovigilance contributes to the understanding of the safety profile of a medicinal product.

PMID:40343372 | PMC:PMC12061024 | DOI:10.3389/fvets.2025.1558222

Front Pharmacol. 2025 Apr 24;16:1498191. doi: 10.3389/fphar.2025.1498191. eCollection 2025.

ABSTRACT

OBJECTIVE: Although numerous drugs have been associated with cataracts, the risk for most drugs remains unclear. This study aimed to investigate the risk factors for drug-induced cataracts by analyzing large-scale data from the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS).

METHODS: We used the reporting odds ratio (ROR) to evaluate reports of drug-induced cataracts in FAERS from the first quarter of 2004 to the third quarter of 2024. A univariate analysis, LASSO (least absolute shrinkage and selection operator) regression, and a multivariate regression analysis were performed to identify drug-related risk factors for cataracts, and Bonferroni correction was applied for multiple comparisons.

RESULTS: Multivariate logistic regression ultimately identified 15 drugs as independent risk factors, including immunomodulators (6/15), antineoplastic drugs (3/15), psychotropic drugs (1/15), respiratory drugs (1/15), gastrointestinal drugs (1/15), orthopedic drugs (1/15), metabolic regulators (1/15), and ophthalmic drugs (1/15). The median time to onset of drug-induced cataracts was 449 days (interquartile range [IQR]: 150-901 days), with approximately 75% of adverse events occurring within 747 days.

CONCLUSION: These findings may help clinicians detect drug-related cataracts at an early stage and provide valuable insights for future research on the mechanisms of drug-induced cataracts.

PMID:40343006 | PMC:PMC12058479 | DOI:10.3389/fphar.2025.1498191