Cancer Cell. 2025 May 2:S1535-6108(25)00162-X. doi: 10.1016/j.ccell.2025.04.003. Online ahead of print.

ABSTRACT

How tumor microenvironment shapes lung adenocarcinoma (LUAD) precancer evolution remains poorly understood. Spatial immune profiling of 114 human LUAD and LUAD precursors reveals a progressive increase of adaptive response and a relative decrease of innate immune response as LUAD precursors progress. The immune evasion features align the immune response patterns at various stages. TIM-3-high features are enriched in LUAD precancers, which decrease in later stages. Furthermore, single-cell RNA sequencing (scRNA-seq) and spatial immune and transcriptomics profiling of LUAD and LUAD precursor specimens from 5 mouse models validate high TIM-3 features in LUAD precancers. In vivo TIM-3 blockade at precancer stage, but not at advanced cancer stage, decreases tumor burden. Anti-TIM-3 treatment is associated with enhanced antigen presentation, T cell activation, and increased M1/M2 macrophage ratio. These results highlight the coordination of innate and adaptive immune response/evasion during LUAD precancer evolution and suggest TIM-3 as a potential target for LUAD precancer interception.

PMID:40345189 | DOI:10.1016/j.ccell.2025.04.003

Biotechnol Bioeng. 2025 May 9. doi: 10.1002/bit.29020. Online ahead of print.

ABSTRACT

Changes in biological pathways provide essential clues about metabolism. Genome-scale metabolic models (GEM) are network-based templates that computationally describe all stoichiometric associations and gene-protein reaction (GPR) relations found in an organism for all its metabolic genes and metabolites. Using reaction stoichiometry as input, GEMs mathematically simulate metabolic reaction fluxes occurring in an organism and predict changes in the metabolic system under the relevant condition. Multiple tools and approaches in the literature can capture fluxes sensitive to a given condition by using GEMs. However, functional enrichment analysis of these reaction lists in a systems biology perspective is not straightforward. Here, we introduce RSEA to annotate given reaction sets to significantly related metabolic pathways: Reaction Set Enrichment Analysis web server tool. RSEA converts given reaction list derived from GEMs into proper reaction identifiers and statistically analyze its enrichment in metabolic pathways. RSEA is designed to provide researchers with a practical and user-friendly platform to explore and interpret sets of reactions in biological pathways and freely available online (https://rseatool.com/).

PMID:40345143 | DOI:10.1002/bit.29020

Cancer Treat Res Commun. 2025 Apr 28;43:100934. doi: 10.1016/j.ctarc.2025.100934. Online ahead of print.

ABSTRACT

BACKGROUND: Malignant ovarian germ cell tumor (MOGCT) is a rare neoplasm predominantly affecting adolescent and young adult females. Establishing personalized permanent tumor cell lines is crucial for understanding tumor behavior and optimizing precision treatment for these patients.

METHODS: We developed a novel procedure for isolating and culturing human MOGCT cells from peritoneal wash cytology using the circulating cell extraction technique (Labyrinthbiotech Co. LLC, LABYRINTHCE01, China).

RESULT: Peripheral blood and peritoneal washings were collected from 15 patients, including those with yolk sac tumor (n = 6), dysgerminoma (n = 2), immature teratoma (n = 5), and mixed germ cell tumor (n = 2). After washing and centrifugation, samples were processed using the labyrinth technique to achieve high-purity cell cultures. The isolated tumor cells were characterized by immunofluorescence microscopy and flow cytometry. Immunohistochemical analysis enabled specific discrimination from primary peritoneal human fibroblasts. Cultures were established from peritoneal cytology with cell densities ranging from 10² to 10⁵ cells per well, with 5 samples showing over 10⁵ cell growth, 3 samples over 10⁴ cell growth, and others at 10³ cell growth. The longest cell culture has been maintained for 18 generations. Short tandem repeat (STR) analysis of cultured cells confirmed their germ cell tumor origin. Preliminary assessments of chemosensitivity in cultured cells have been found to reflect similar clinical responses in the corresponding patients.

CONCLUSION: The MOGCT cell lines derived from peritoneal washings using the circulating tumor cell chip represent the tumor characteristics. This method holds promise for functional studies on rare ovarian tumors and for evaluating chemo-sensitivity for potential therapeutic applications.

PMID:40344740 | DOI:10.1016/j.ctarc.2025.100934

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

Nat Commun. 2025 May 9;16(1):4313. doi: 10.1038/s41467-025-59569-6.

ABSTRACT

The K29/K48-linked ubiquitination generated by the cooperative catalysis of E3 ligase Ufd4 and Ubr1 is an enhanced protein degradation signal, in which Ufd4 is responsible for introducing K29-linked ubiquitination to K48-linked ubiquitin chains to augment polyubiquitination. How HECT-E3 ligase Ufd4 mediates the ubiquitination event remains unclear. Here, we biochemically determine that Ufd4 preferentially catalyses K29-linked ubiquitination on K48-linked ubiquitin chains to generate K29/K48-branched ubiquitin chains and capture structural snapshots of Ub transfer cascades for Ufd4-mediated ubiquitination. The N-terminal ARM region and HECT domain C-lobe of Ufd4 are identified and characterized as key structural elements that together recruit K48-linked diUb and orient Lys29 of its proximal Ub to the active cysteine of Ufd4 for K29-linked branched ubiquitination. These structures not only provide mechanistic insights into the architecture of the Ufd4 complex but also provide structural visualization of branched ubiquitin chain formation by a HECT-type E3 ligase.

PMID:40341121 | DOI:10.1038/s41467-025-59569-6