BMC Pregnancy Childbirth. 2025 May 29;25(1):629. doi: 10.1186/s12884-025-07752-4.

ABSTRACT

BACKGROUND: Cesarean scar pregnancy (CSP) is a life-threatening condition with a rising incidence in China. The pathogenesis of CSP remains poorly understood, partly due to the limited availability of comprehensive datasets constrained by spatiotemporal factors.

OBJECTIVE: This study aimed to explore key regulatory molecules and mechanisms involved in CSP through a multi-omics approach.

METHODS: Proteomic analysis was performed on decidual and villous tissues from clinical patients (n = 6, including 3 CSP cases and 3 controls). Gene expression datasets (n = 9) were obtained from the GEO and SRA databases. Bioinformatics analyses were conducted using DAVID, Metascape, and STRING, with transcription factor prediction performed via the JASPAR database. Data analysis was conducted using SPSS 27, with a significance threshold set at P < 0.05.

RESULTS: CSP shared differentially expressed genes (DEGs) with cesarean delivery (CD) and embryo implantation (EI). Enrichment analysis revealed that biological processes and KEGG pathways related to adhesion, with Integrin Subunit Beta 3 (ITGB3), Integrin Subunit Alpha 2b (ITGA2B), and Vitronectin (VTN) playing significant roles. ITGB3 expression was significantly downregulated following CD compared to spontaneous delivery, followed by upregulation in subsequent pregnancies. The transcription factor GATA4 was identified as a key regulator of ITGB3, potentially contributing to CSP pathogenesis.

CONCLUSION: Our findings suggest that CSP development is closely associated with CD and EI, with ITGB3 and its regulatory network playing a crucial role. GATA4-mediated regulation of ITGB3 may represent an important molecular mechanism contributing to CSP formation.

PMID:40442657 | DOI:10.1186/s12884-025-07752-4

J Assist Reprod Genet. 2025 May 29. doi: 10.1007/s10815-025-03518-1. Online ahead of print.

ABSTRACT

The intersection of aging and reproductive decline presents a significant challenge in human health, with fertility rates decreasing sharply in later life for both sexes. This review delves into the intricate relationship between germ cells, the fundamental units of reproduction, and their surrounding microenvironment, known as the niche. Emphasizing that reproductive longevity is not solely determined by the intrinsic properties of germ cells, but rather by the complex interplay with their niche, a dynamic system that changes with age. We highlight evidence from model organisms like Drosophila and C. elegans demonstrating how age-related changes in niche signaling impact germ cell function. A systems biology approach, integrating multi-omics data (genetics, epigenetics, cellular behavior), is crucial to fully understanding this complex interaction. Specifically, we discuss the role of epigenetic modifications, such as DNA methylation and histone acetylation, in modulating niche-germ cell communication. This approach offers a comprehensive view of the aging reproductive system and opens up avenues for therapeutic interventions aimed at modulating the niche and potentially extending reproductive lifespan. Future research focused on unraveling the specific molecular mechanisms underlying the niche-germ cell interaction will be pivotal in developing strategies to combat age-related reproductive decline.

PMID:40442411 | DOI:10.1007/s10815-025-03518-1

J Thromb Haemost. 2025 May 27:S1538-7836(25)00339-3. doi: 10.1016/j.jtha.2025.05.020. Online ahead of print.

ABSTRACT

BACKGROUND: Increased body mass index (BMI) is associated with an increased risk of venous thrombosis. However, recent data has highlighted that visceral adipose tissue (VAT) volume may be a better marker of cardiometabolic risk.

OBJECTIVES: To investigate the relationship between VAT volume and VTE risk and explore whether increased VAT volumes is associated with VTE risk.

METHODS: We performed a cross-sectional study utilising MRI imaging data from the UK Biobank (UKB). The association between VTE incidence and VAT measured by MRI imaging from 39,144 UKB patients was analysed by ridge regression accounting for covariates including age and sex.

RESULTS: VAT volume, as measured by MRI, was demonstrated to be associated with an increased risk of VTE [OR 4.020 (95%CI: 3.752 - 4.287) per dm3]. Moreover, we observed a significant association of VAT volume with VTE risk in both those who were overweight [VAT high; OR 1.589 (95%CI: 1.317 - 1.860), VAT medium; OR 1.303 (95%CI:1.054 -1.552)] and obese [VAT high; OR 3.222 (95%CI: 2.971 - 3.473)]. Notably, the strongest association of VAT was observed in those with obesity.

CONCLUSION: These data demonstrate for the first time that VAT volume is associated with an increased risk of VTE and importantly has a stronger association with VTE risk as compared to BMI.

PMID:40441356 | DOI:10.1016/j.jtha.2025.05.020

Nat Methods. 2025 May 29. doi: 10.1038/s41592-025-02707-1. Online ahead of print.

ABSTRACT

Artificial intelligence has revolutionized computational biology. Recent developments in omics technologies, including single-cell RNA sequencing and spatial transcriptomics, provide detailed genomic data alongside tissue histology. However, current computational models focus on either omics or image analysis, lacking their integration. To address this, we developed OmiCLIP, a visual-omics foundation model linking hematoxylin and eosin images and transcriptomics using tissue patches from Visium data. We transformed transcriptomic data into 'sentences' by concatenating top-expressed gene symbols from each patch. We curated a dataset of 2.2 million paired tissue images and transcriptomic data across 32 organs to train OmiCLIP integrating histology and transcriptomics. Building on OmiCLIP, our Loki platform offers five key functions: tissue alignment, annotation via bulk RNA sequencing or marker genes, cell-type decomposition, image-transcriptomics retrieval and spatial transcriptomics gene expression prediction from hematoxylin and eosin-stained images. Compared with 22 state-of-the-art models on 5 simulations, and 19 public and 4 in-house experimental datasets, Loki demonstrated consistent accuracy and robustness.

PMID:40442373 | DOI:10.1038/s41592-025-02707-1

Sci Bull (Beijing). 2025 May 12:S2095-9273(25)00519-5. doi: 10.1016/j.scib.2025.05.016. Online ahead of print.

NO ABSTRACT

PMID:40441974 | DOI:10.1016/j.scib.2025.05.016

Nature. 2025 May 29. doi: 10.1038/s41586-025-09183-9. Online ahead of print.

ABSTRACT

Modelling liver disease requires in vitro systems that replicate disease progression1,2. Current tissue-derived organoids fail to reproduce the complex cellular composition and tissue architecture observed in vivo3. Here, we describe a multicellular organoid system composed of adult hepatocytes, cholangiocytes and mesenchymal cells that recapitulates the architecture of the liver periportal region and, when manipulated, models aspects of cholestatic injury and biliary fibrosis. We first generate reproducible hepatocyte organoids with functional bile canaliculi network that retain morphological features of in vivo tissue. By combining these with cholangiocytes and portal fibroblasts, we generate assembloids that mimic the cellular interactions of the periportal region. Assembloids are functional, consistently draining bile from bile canaliculi into the bile duct. Strikingly, manipulating the relative number of portal mesenchymal cells is sufficient to induce a fibrotic-like state, independently of an immune compartment. By generating chimeric assembloids of mutant and wild-type cells, or after gene knockdown, we show proof-of-concept that our system is amenable to investigating gene function and cell-autonomous mechanisms. Taken together, we demonstrate that liver assembloids represent a suitable in vitro system to study bile canaliculi formation, bile drainage, and how different cell types contribute to cholestatic disease and biliary fibrosis, in an all-in-one model.

PMID:40441268 | DOI:10.1038/s41586-025-09183-9

Mol Cell. 2025 May 21:S1097-2765(25)00412-5. doi: 10.1016/j.molcel.2025.05.007. Online ahead of print.

ABSTRACT

Coordination of adaptive metabolism through signaling networks is essential for cellular bioenergetics and homeostasis. Phosphorylation of metabolic enzymes provides a rapid, efficient, and dynamic mechanism to regulate metabolic networks. Our structural analysis stratified phosphosites on metabolic enzymes based on proximity to functional and dimerization domains. Most phosphosites occur on oxidoreductases and are enriched near substrate, cofactor, active sites, or dimer interfaces. Despite low stoichiometry, phosphotyrosine (pY) is overrepresented in functional domains. Using high-fat diet (HFD)-induced obesity in C57BL/6J mice and multiomics, we measured HFD-induced sex-specific dysregulation of pY and metabolites, which was reversible with the antioxidant butylated hydroxyanisole (BHA). Computational modeling revealed predictive pY sites for HFD- or BHA-induced metabolite changes. We characterized functional roles for predictive pY sites on glutathione S-transferase pi 1 (GSTP1), isocitrate dehydrogenase 1 (IDH1), and uridine monophosphate synthase (UMPS) using CRISPR interference (CRISPRi) rescue and stable isotope tracing. Our findings reveal mechanisms whereby cellular signaling fine-tunes enzyme activity and metabolism.

PMID:40441152 | DOI:10.1016/j.molcel.2025.05.007

Plant Physiol Biochem. 2025 May 23;226:110066. doi: 10.1016/j.plaphy.2025.110066. Online ahead of print.

ABSTRACT

The BBX family of transcription factors regulate several physiological processes during plant vegetative and reproductive development, bridging light signaling to hormones metabolism. Here, we do an in-depth functional characterization of the tomato SlBBX26 (Solyc10g006750) gene by generating and phenotyping CRISPR/Cas9-mediated genome-edited and RNAi-mediated knockdown lines. We demonstrate that SlBBX26 regulates the negative factor of light signaling, PHYTOCHROME INTERACTING PROTEIN 4 (PIF4), which in turn modulates vegetative growth and flowering by controlling gibberellins (GAs) biosynthetic genes expression and signaling, respectively. Moreover, SlBBX26 regulates fruit growth modulating the expression of cell division- and expansion-related genes. SlBBX26 also influences fruit chloroplast ultrastructure and metabolism in an SlPIF4-mediated manner, leading to alterations in thylakoid stacking, plastoglobuli size, and chlorophyll content, through the regulation of genes involved in chloroplast differentiation and chlorophyll degradation. Finally, SlBBX26-SlPIF4 heterodimer is required to control GA and auxin signaling cascades, triggering the onset of fruit ripening. As such, our findings unveil how BBX proteins contribute to the regulation of main agronomic traits.

PMID:40441101 | DOI:10.1016/j.plaphy.2025.110066

Science. 2025 May 29:eadq7408. doi: 10.1126/science.adq7408. Online ahead of print.

ABSTRACT

The maintenance of H3K9me3 involves the recognition of pre-existing modifications by HP1, which recruits methyltransferase SUV39H1 to methylate the adjacent newly incorporated histones, thereby establishing a positive feedback loop. However, how this positive feedback is restricted to maintain H3K9me3 homeostasis remains largely unknown. Here, we performed an unbiased genome-scale CRISPR-Cas9 screen and identified CUL5ASB7 E3 ubiquitin ligase as a negative regulator of H3K9me3. ASB7 is recruited to heterochromatin by HP1 and promotes SUV39H1 degradation. During mitosis, CDK1 phosphorylates ASB7, preventing its interaction with SUV39H1, leading to SUV39H1 stabilization and H3K9me3 restoration. Our findings reveal a dynamic circuit involving HP1, SUV39H1, and ASB7 that governs H3K9me3 homeostasis, thereby ensuring faithful epigenetic inheritance and preventing excessive heterochromatin formation.

PMID:40440427 | DOI:10.1126/science.adq7408

Cell Rep. 2025 May 28;44(6):115769. doi: 10.1016/j.celrep.2025.115769. Online ahead of print.

ABSTRACT

The ribonuclease DIS3 interacts through its PIN domain with the nuclear exosome and degrades linear RNA substrates using its exoribonuclease domain. However, the PIN domain is also an active endoribonuclease, but cellular substrates are largely unknown. Here, we use a biochemical strategy to find ribonucleases that could degrade circular RNAs (circRNAs). Due to the lack of accessible ends, circRNAs are resistant to exonucleolytic cleavage and are thus more stable than linear RNAs. Using biochemical assays, we identify DIS3 as a candidate for circRNA degradation and demonstrate that it partially resides in the cytoplasm, where circRNAs are degraded. DIS3 shows cleavage activity toward a number of circRNAs and functions independently of the exosome core in vitro. Upon knockdown of DIS3 in cell lines, selected circRNAs are moderately stabilized. We thus propose that cytoplasmic DIS3 functions as a stand-alone enzyme independently of the exosome core and may contribute to circRNA turnover.

PMID:40440169 | DOI:10.1016/j.celrep.2025.115769

Gigascience. 2025 Jan 6;14:giaf052. doi: 10.1093/gigascience/giaf052.

ABSTRACT

Unsupervised clustering is a powerful machine-learning technique widely used to analyze high-dimensional biological data. It plays a crucial role in uncovering patterns, structures, and inherent relationships within complex datasets without relying on predefined labels. In the context of biology, high-dimensional data may include transcriptomics, proteomics, and a variety of single-cell omics data. Most existing clustering algorithms operate directly in the high-dimensional space, and their performance may be negatively affected by the phenomenon known as the curse of dimensionality. Here, we show an alternative clustering approach that alleviates the curse by sequentially projecting high-dimensional data into a low-dimensional representation. We validated the effectiveness of our approach, named automated projection pursuit (APP), across various biological data modalities, including flow and mass cytometry data, scRNA-seq, multiplex imaging data, and T-cell receptor repertoire data. APP efficiently recapitulated experimentally validated cell-type definitions and revealed new biologically meaningful patterns.

PMID:40440093 | DOI:10.1093/gigascience/giaf052

Mol Biol Rep. 2025 May 29;52(1):514. doi: 10.1007/s11033-025-10607-y.

ABSTRACT

BACKGROUND: Gallbladder cancer (GBC) is a rare and aggressive cancer of the biliary tract with a very low survival rate. The availability of diagnostic biomarkers and targeted therapies for its management is limited. The study identifies potential genetic biomarkers of GBC by analyzing differentially expressed genes (DEGs) through microarray profiling and constructing regulatory networks using systems biology techniques.

METHODS: We used Clariom™ D Array in gallbladder cancer, cholelithiasis, and normal tissues (10 cases in each group), identifying DEGs and key biological pathways. Functional analysis via Metascape, DisGeNET, and KEGG-SIGNOR network mapping revealed gene-disease relationships and protein interactions.

RESULTS: There were 3,898 significant DEGs (|Fold Change| > 2.0, p < 0.05) identified in GBC compared to normal gallbladder tissue, with 2,575 genes upregulated and 1,323 downregulated. On comparison with cholelithiasis, 2523 DEGs (|Fold Change|>2.0, p < 0.05) were upregulated and 1451 downregulated. The functional analyses have shown that these DEGs were mainly involved in anatomical structure maturation and cell-cycle regulation. Top ten identified hub genes were XAB2, XPA, RPA1, RAD51B, RPS27A, BRCA2, ATR, PDS5B, CCNB2 and RANBP2. The top 3 related pathways were mismatch repair pathway, nucleotide excision repair and homologous recombination.

CONCLUSION: A significantly high differential gene expression was identified in gallbladder cancer compared to control groups. For the first time, we identified key genes-XAB2, XPA, RPA1, RAD51B, RPS27A, BRCA2, ATR, PDS5B, CCNB2, and RANBP2-as crucial players in homologous recombination, mismatch repair, DNA damage repair, and DNA replication processes that contribute to gallbladder carcinogenesis.

PMID:40439781 | DOI:10.1007/s11033-025-10607-y

Philos Trans R Soc Lond B Biol Sci. 2025 May 29;380(1927):20240234. doi: 10.1098/rstb.2024.0234. Epub 2025 May 29.

ABSTRACT

Rising temperatures and heat waves pose a substantial threat to crop productivity by disrupting essential physiological and reproductive processes. While plants have a genetically inherited capacity to acclimate to high temperatures, the thermotolerance capacity of many crops remains limited. This limitation leads to yield losses, which are further intensified by the increasing intensity of climate change. In this review, we explore how thermopriming enhances plant resilience by preparing plants for future heat stress (HS) events and summarize the mechanisms underlying the memory of HS (thermomemory) in different plant tissues and organs. We also discuss recent advances in priming agents, including chemical, microbial and physiological interventions, and their application strategies to extend thermotolerance beyond inherent genetic capacity. Additionally, this review examines how integrating priming strategies with genetic improvements, such as breeding and genome editing for thermotolerance traits, provides a holistic solution to mitigate the impact of climate change on agriculture. By combining these approaches, we propose a framework for developing climate-resilient crops and ensuring global food security in the face of escalating environmental challenges.This article is part of the theme issue 'Crops under stress: can we mitigate the impacts of climate change on agriculture and launch the 'Resilience Revolution'?'.

PMID:40439313 | DOI:10.1098/rstb.2024.0234

Philos Trans R Soc Lond B Biol Sci. 2025 May 29;380(1927):20240241. doi: 10.1098/rstb.2024.0241. Epub 2025 May 29.

ABSTRACT

An increase in the frequency and intensity of heat waves, floods, droughts and other environmental stresses, resulting from climate change, is threatening agricultural food production worldwide. Heat waves are especially problematic to grain yields, as the reproductive processes of almost all our main grain crops are highly sensitive to heat. At times, heat waves can occur together with drought, high ozone levels, pathogen infection and/or waterlogging stress that suppress the overall process of plant cooling by transpiration. We recently reported that under conditions of heat and water-deficit stress combination, the stomata on sepals and pods of soybean (Glycine max) remain open, while the stomata on leaves close. This process, termed 'differential transpiration', enabled the cooling of reproductive organs, while leaf temperature increased owing to suppressed transpiration. In this review article, we focus on the impacts on crops of heat waves occurring in isolation and of heat waves combined with drought or waterlogging stress, address the main processes impacted in plants by these stresses and discuss ways to mitigate the negative effects of isolated heat waves and of heat waves that occur together with other stresses (i.e. stress combination), on crops, with a focus on the process of differential transpiration.This article is part of the theme issue 'Crops under stress: can we mitigate the impacts of climate change on agriculture and launch the 'Resilience Revolution'?'.

PMID:40439306 | DOI:10.1098/rstb.2024.0241

J Exp Bot. 2025 May 29:eraf236. doi: 10.1093/jxb/eraf236. Online ahead of print.

ABSTRACT

Already in the 19th Century it was proposed that ecophysiology could be best studied in regions with extreme climatic conditions. In the present perspective, we argue that perhaps this is timelier than ever. The main reason is the need to improve crops to be simultaneously more productive - due to increased population - and more stress-tolerant - due to climate change. Climate change induces plants to face not just the harsh but also the 'unexpected' (unpredictable) climatic conditions. In this sense, we hypothesize that 'sherplants', i.e. plants living in the extremes of plant life (e.g. hot deserts, Arctic and Antarctica, or high elevations) can provide cues on how to break the trade-off between productivity and stress tolerance, as they need to produce fast due to the very short growing period while being stress tolerant due to the harsh and unpredictable climate endured during most of the year. We present glimpses of results from three consecutive projects developed for the last 10 years, in which hundreds of species from different regions of the world have been studied. In particular, we propose a path for developing 'shercrops' learning from 'sherplants', debate whether some of the already studied species may have really broken the aforementioned trade-off, and present a number of interesting 'side' findings achieved when studying plants from extreme climates.

PMID:40439080 | DOI:10.1093/jxb/eraf236

New Phytol. 2025 May 29. doi: 10.1111/nph.70269. Online ahead of print.

NO ABSTRACT

PMID:40439021 | DOI:10.1111/nph.70269

Microb Genom. 2025 May;11(5). doi: 10.1099/mgen.0.001414.

ABSTRACT

Micro-organisms can survive and thrive in unusual and extreme environments. Here, we present a metagenomic analysis of living bacteria found in highly pure, deleterious heavy water (>99% D2O), stored in sealed plastic containers for more than 30 years, without any external supply. Deep DNA sequencing analyses have revealed that the most abundant genetic signatures were primarily associated with Pseudomonadota and Bacteroidota. These bacteria exhibited shorter gene lengths and depletion of polar and metabolically costly amino acids compared to the related species from light water environments. Genes related to DNA transposition, repair and modification were notably abundant, particularly mutant forms of the IS3 transposable elements family. We also explore potential carbon and energy sources and discuss the evolutionary implications of bacteria capable of surviving in such an extreme human-made environment.

PMID:40438915 | DOI:10.1099/mgen.0.001414

Front Plant Sci. 2025 May 14;16:1538566. doi: 10.3389/fpls.2025.1538566. eCollection 2025.

ABSTRACT

Climate change has significantly impacted the distribution patterns of medicinal plants, highlighting the need for accurate models to predict future habitat shifts. In this study, the Maximum Entropy model to analyze the habitat distribution of Pulsatilla chinensis (Bunge) Regel under current conditions and two future climate scenarios (SSP245 and SSP585). Based on 105 occurrence records and 12 environmental variables, precipitation of the wettest quarter, isothermality, average November temperature, and the standard deviation of temperature seasonality were identified as key factors influencing the habitat suitability for P. chinensis. The reliability of the model was supported by a mean area under the curve (AUC) value of 0.916 and a True Skill Statistic (TSS) value of 0.608. The results indicated that although the total suitable habitat for P. chinensis expanded under both scenarios, the highly suitable area contracted significantly under SSP585 compared to SSP245. This suggests the importance of incorporating climate change considerations into P. chinensis management strategies to address potential challenges arising from future ecosystem dynamics.

PMID:40438736 | PMC:PMC12116669 | DOI:10.3389/fpls.2025.1538566

Biomater Res. 2025 May 28;29:0211. doi: 10.34133/bmr.0211. eCollection 2025.

ABSTRACT

While fluorescent labeling has been the standard for visualizing fibers within fibrillar scaffold models of the extracellular matrix (ECM), the use of fluorescent dyes can compromise cell viability and photobleach prematurely. The intricate fibrillar composition of ECM is crucial for its viscoelastic properties, which regulate intracellular signaling and provide structural support for cells. Naturally derived biomaterials such as fibrin and collagen replicate these fibrillar structures, but longitudinal confocal imaging of fibers using fluorescent dyes may impact cell function and photobleach the sample long before termination of the experiment. An alternative technique is reflection confocal microscopy (RCM) that provides high-resolution images of fibers. However, RCM is sensitive to fiber orientation relative to the optical axis, and consequently, many fibers are not detected. We aim to recover these fibers. Here, we propose a deep learning tool for predicting fluorescently labeled optical sections from unlabeled image stacks. Specifically, our model is conditioned to reproduce fluorescent labeling using RCM images at 3 laser wavelengths and a single laser transmission image. The model is implemented using a fully convolutional image-to-image mapping architecture with a hybrid loss function that includes both low-dimensional statistical and high-dimensional structural components. Upon convergence, the proposed method accurately recovers 3-dimensional fibrous architecture without substantial differences in fiber length or fiber count. However, the predicted fibers were slightly wider than original fluorescent labels (0.213 ± 0.009 μm). The model can be implemented on any commercial laser scanning microscope, providing wide use in the study of ECM biology.

PMID:40438124 | PMC:PMC12117218 | DOI:10.34133/bmr.0211

Adv Mater. 2025 May 29:e2502322. doi: 10.1002/adma.202502322. Online ahead of print.

ABSTRACT

Nanozymes hold great potential in protecting human health. However, constructing new and efficient nanozymes is a significant challenge. Developing atomic-level nanozymes is a promising approach. Despite their potential, atomic-level high-entropy nanozymes have not been reported due to thermodynamic instability. Therefore, developing atomic-level high-entropy nanozymes are of great significance. What's more, further exploring their biomedical applications can open up new horizons for nanozymology. Here, the atomic-level high-entropy nanozyme system capable of remarkable endogenous targeted catalysis and enhancing tumor photothermal therapy is successfully constructed. The system is prepared by reduction-diffusion and grafting methods. The RuRhPtIrMo sub-nanometer high-entropy nanozyme (snHEAzyme) with about 8-10 atoms thickness is first prepared. Then, they are grafted by targeting agent DSPE-PEG2000-cRGD and imaging agent Cy7 to obtain the snHEAzyme@DSPE-PEG2000-cRGD@Cy7 nanozyme system. The synthesized snHEAzyme@DSPE-PEG2000-cRGD@Cy7 system exhibits excellent peroxidase-like activity and high absorbance in the near-infrared (NIR) range. Under NIR irradiation, the nanozyme shows efficient photothermal conversion and reactive oxygen species generation effects. In vitro and in vivo experiments demonstrated that the snHEAzyme@DSPE-PEG2000-cRGD@Cy7 system can be effectively targeted to penetrate tumor cell membranes and treat tumors. This work offers a new perspective on snHEAzyme fabrication and its biomedical applications.

PMID:40437935 | DOI:10.1002/adma.202502322