Nat Commun. 2025 Feb 1;16(1):1247. doi: 10.1038/s41467-025-56535-0.

ABSTRACT

Recent advances in spatial epigenomic techniques have given rise to spatial assay for transposase-accessible chromatin using sequencing (spATAC-seq) data, enabling the characterization of epigenomic heterogeneity and spatial information simultaneously. Integrative analysis of multiple spATAC-seq samples, for which no method has been developed, allows for effective identification and elimination of unwanted non-biological factors within the data, enabling comprehensive exploration of tissue structures and providing a holistic epigenomic landscape, thereby facilitating the discovery of biological implications and the study of regulatory processes. In this article, we present INSTINCT, a method for multi-sample INtegration of Spatial chromaTIN accessibility sequencing data via stochastiC domain Translation. INSTINCT can efficiently handle the high dimensionality of spATAC-seq data and eliminate the complex noise and batch effects of samples through a stochastic domain translation procedure. We demonstrate the superiority and robustness of INSTINCT in integrating spATAC-seq data across multiple simulated scenarios and real datasets. Additionally, we highlight the advantages of INSTINCT in spatial domain identification, visualization, spot-type annotation, and various downstream analyses, including motif enrichment analysis, expression enrichment analysis, and partitioned heritability analysis.

PMID:39893190 | DOI:10.1038/s41467-025-56535-0

Nat Commun. 2025 Feb 1;16(1):1253. doi: 10.1038/s41467-025-56383-y.

ABSTRACT

We reported that an acquired miR-142 deficit transforms chronic phase (CP) chronic myeloid leukemia (CML) leukemic stem cells (LSCs) into blast crisis (BC) LSCs. Given the role of miR-142 in the development and activity of the immune system, we postulated that this deficit also promotes LSC immune escape. Herein, we report on IL-6-driven miR-142 deficit occurring in T cells during BC transformation. In CML murine models, miR-142 deficit impairs thymic differentiation of lymphoid-primed multipotent progenitors (LMPP) into T cells and prevents T cells' metabolic reprogramming, thereby leading to loss of T cells and leukemia immune escape. Correcting miR-142 deficit with a miR-142 mimic compound (M-miR-142), alone or in combination with immune checkpoint antibodies, restores T cell number and immune activity, leading to LSC elimination and prolonged survival of BC CML murine and patient-derived xenograft models. These observations may open new therapeutic opportunities for BC CML and other myeloid malignancies.

PMID:39893171 | DOI:10.1038/s41467-025-56383-y

J Genet Genomics. 2025 Jan 30:S1673-8527(25)00032-3. doi: 10.1016/j.jgg.2025.01.017. Online ahead of print.

ABSTRACT

The liver performs several vital functions such as metabolism, toxin removal, and glucose storage through the coordination of various cell types. With the recent breakthrough of the single-cell/single-nucleus RNA-seq (sc/snRNA-seq) techniques, there is a great opportunity to establish a reference cell map of the liver at single-cell resolution with transcriptome-wise features. In this study, we build a unified liver cell atlas uniLIVER (http://lifeome.net/database/uniliver) by integrative analysis of a large-scale sc/snRNA-seq data collection of normal human liver with 331,125 cells and 79 samples from 6 datasets. Moreover, we introduce LiverCT, a novel machine learning based method for mapping any query dataset to the liver reference map by introducing the definition of "variant" cellular states analogy to the sequence variants in genomic analysis. Applying LiverCT on liver cancer datasets, we find that the "deviated" states of T cells are highly correlated with the stress pathway activities in hepatocellular carcinoma, and the enrichments of tumor cells with the hepatocyte-cholangiocyte "intermediate" states significantly indicate poor prognosis. Besides, we find the tumor cells of different patients have different zonation tendencies and this zonation tendency is also significantly associated with the prognosis. This reference atlas mapping framework can also be extended to any other tissues.

PMID:39892777 | DOI:10.1016/j.jgg.2025.01.017

Protein Expr Purif. 2025 Jan 30:106678. doi: 10.1016/j.pep.2025.106678. Online ahead of print.

ABSTRACT

SOG1, a transcription factor consisting of a folded NAC (NAM-ATAF-CUC2) domain and an intrinsically disordered C-terminal domain (CTD), co-ordinates the DNA damage response in plants. Here we compare different methods to express and purify recombinant full length Arabidopsis thaliana SOG1. Expression in Sf9 insect cells results in a protein that contains a phosphorylated site that is possibly located on the T423 site in the CTD. This site is reported to be phosphorylated in planta upon aluminium toxicity stress and may affect the transcriptional activity of SOG1 in an yet undetermined way. Expression of SOG1 in E. coli BL21 (DE3) leads to the formation of inclusion bodies, a problem that is resolved by using a cleavable SUMO solubility tag. The resulting protein is not phosphorylated and represents the transcriptional inactive state of SOG1. Both protein preparations show similar CD spectra and melting temperatures. SEC-MALS determined that the proteins, like other NAC transcription factors, form a dimer in solution. Both proteins are also highly non-globular as determined by analytical SEC and are likely stretched out due to their disordered CTD. In electromobility shift assays, both insect and E. coli purified SOG1 proteins bind to a DNA fragment from the promoter region of SMR5, a well established target gene of SOG1, showing the functionality of both purified proteins.

PMID:39892530 | DOI:10.1016/j.pep.2025.106678

Mol Cell. 2025 Jan 28:S1097-2765(25)00003-6. doi: 10.1016/j.molcel.2025.01.003. Online ahead of print.

ABSTRACT

Amplification of chromosomal material derived from 12q13-15 is common in human cancer and believed to result in overexpression of multiple collaborating oncogenes. To define the oncogenes involved, we overexpressed genes recurrently amplified in human liposarcoma using a zebrafish model of the disease. We found several genes whose overexpression collaborated with AKT in sarcomagenesis, including the tRNA methyltransferase METTL1. This was surprising, because AKT phosphorylates METTL1 to inactivate its enzymatic activity. Indeed, phosphomimetic S27D or catalytically dead alleles phenocopied the oncogenic activity of wild-type METTL1. We found that METTL1 binds the multi-tRNA synthetase complex, which contains many of the cellular aminoacyl-tRNA synthetases and promotes tRNA aminoacylation, polysome formation, and protein synthesis independent of its methyltransferase activity. METTL1-amplified liposarcomas were hypersensitive to actinomycin D, a clinical inhibitor of ribosome biogenesis. We propose that METTL1 overexpression promotes sarcomagenesis by stimulating tRNA aminoacylation, protein synthesis, and tumor cell growth independent of its methyltransferase activity.

PMID:39892392 | DOI:10.1016/j.molcel.2025.01.003

Cell Genom. 2025 Jan 30:100764. doi: 10.1016/j.xgen.2025.100764. Online ahead of print.

ABSTRACT

Tumor hypoxia drives metabolic shifts, cancer progression, and therapeutic resistance. Challenges in quantifying hypoxia have hindered the exploitation of this potential "Achilles' heel." While gene expression signatures have shown promise as surrogate measures of hypoxia, signature usage is heterogeneous and debated. Here, we present a systematic pan-cancer evaluation of 70 hypoxia signatures and 14 summary scores in 104 cell lines and 5,407 tumor samples using 472 million length-matched random gene signatures. Signature and score choice strongly influenced the prediction of hypoxia in vitro and in vivo. In cell lines, the Tardon signature was highly accurate in both bulk and single-cell data (94% accuracy, interquartile mean). In tumors, the Buffa and Ragnum signatures demonstrated superior performance, with Buffa/mean and Ragnum/interquartile mean emerging as the most promising for prospective clinical trials. This work delivers recommendations for experimental hypoxia detection and patient stratification for hypoxia-targeting therapies, alongside a generalizable framework for signature evaluation.

PMID:39892389 | DOI:10.1016/j.xgen.2025.100764

Microbiol Res. 2025 Jan 30;293:128087. doi: 10.1016/j.micres.2025.128087. Online ahead of print.

ABSTRACT

Erwinia amylovora (Ea) is a devastating bacterial pathogen that causes fire blight disease in Rosaceae family plants, including apples and pears. The use of bacteriophages is an alternative strategy to antibiotics for managing bacterial pathogens. In this study, the Ea-specific virulent phiEaSP1 phage was characterized, and its biocontrol efficacy against Ea was evaluated in apple seedlings. Genomic analyses revealed that phiEaSP1 belongs to the family Chaseviridae, subfamily Cleopatravirinae, and genus Loessnervirus. Most phiEaSP1 particles bound to the host cell surface within 5 min, and one virion made 68 progenies within 20 min of infection. The phage rapidly lysed Ea cells in vitro and maintained its lytic activity after incubation under different environmental conditions, including temperature, pH, and UV-A, as well as in the soil, with surfactants, and on apple seedlings. Receptor analysis using the Tn5 random mutant library of Ea TS3128 demonstrated that phiEaSP1 recognizes lipopolysaccharide as a receptor, whereas phiEaP-8 and phiEaP-21 recognize cellulose as a receptor. Protective efficacy against fire blight was tested on apple seedlings pretreated with the single phiEaSP1 or a phage cocktail containing phiEaSP1, phiEaP-8, and phiEaP-21. No or only weak symptoms were observed in the phage-treated seedlings. The application of a phage cocktail showed better control efficacy, indicating the potential of the phage cocktail, including phiEaSP1, as a preventive agent. Taken together, these results suggest that the use of a phage cocktail containing phiEaSP1 could be a potential strategy for the biocontrol of fire blight disease in apples.

PMID:39892321 | DOI:10.1016/j.micres.2025.128087

Eur J Med Chem. 2025 Jan 2;287:117234. doi: 10.1016/j.ejmech.2024.117234. Online ahead of print.

ABSTRACT

Despite the significant roles of solute carrier (SLC) and ATP-binding cassette (ABC) transporters in human health and disease, most remain poorly characterized as intrinsic and/or xenobiotic ligands are unknown, rendering them as 'undruggable'. Polypharmacology, defined as the simultaneous engagement of multiple targets by a single ligand, offers a promising avenue for discovering novel lead compounds addressing these emerging pharmacological challenges - a major focus in contemporary medicinal chemistry. While common structural motifs among phylogenetically diverse proteins have been proposed to underlie polypharmacology through the concept of 'multitarget binding sites', a comprehensive analysis of these functional and structural aspects from a medicinal chemistry perspective has yet to be undertaken. In our study, we synthesized 65 distinct indazole derivatives and evaluated their activity across a broad biological assessment platform encompassing 17 specific and polyspecific SLC and ABC transporters. Notably, ten indazoles exhibited cross-target activity against challenging transporter targets associated with neurodegeneration (ABCA1), metabolic reprogramming (MCT4), and cancer multidrug resistance (ABCC10). Furthermore, molecular blind docking experiments and advanced binding site analyses revealed, for the first time, conserved binding motifs across monocarboxylate transporters (MCTs), organic anion transporting polypeptides (OATPs), organic cation transporters (OCTs), and ABC transporters, characterized by specific and recurring residues of tyrosine, phenylalanine, serine, and threonine. These findings highlight not only the potential of polypharmacology in drug discovery but also provide insights into the structural underpinnings of ligand binding across membrane transporters.

PMID:39892094 | DOI:10.1016/j.ejmech.2024.117234

J Thromb Thrombolysis. 2025 Feb 1. doi: 10.1007/s11239-025-03072-8. Online ahead of print.

ABSTRACT

Chronic thromboembolic pulmonary hypertension (CTEPH) and COVID-19 share molecular pathways yet remain poorly understood in their interrelation. Using RNA-seq datasets (GSE130391 and GSE169687), we identified 645, 206, and 1,543 differentially expressed genes (DEGs) for long-COVID (16 and 24 weeks post-infection) and CTEPH, respectively. Weighted Gene Co-Expression Network Analysis (WGCNA) pinpointed 234 intersecting key module genes. Three hub genes-DNAJA1, NDUFA5, and SLC2A14-were identified with robust discriminatory capabilities (AUC ≥ 0.7). Enrichment analyses revealed shared pathways linked to immune modulation, oxidative stress, and metabolic dysfunction. Immune analysis highlighted activated CD8 T cells as critical regulators. Regulatory networks implicated TFs and miRNAs, including STAT1 and hsa-mir-23a-3p. Drug prediction identified potential therapeutic compounds with strong molecular docking interactions. These findings unravel critical molecular linkages, emphasizing shared pathogeneses and guiding experimental validations for improved diagnostic and therapeutic strategies in COVID-19 and CTEPH.

PMID:39891865 | DOI:10.1007/s11239-025-03072-8

Eur J Nutr. 2025 Feb 1;64(2):75. doi: 10.1007/s00394-025-03589-x.

ABSTRACT

PURPOSE: During pregnancy, extracellular vesicle and particle microRNAs (EVP miRNA) in maternal circulation have the capacity to cross the placenta and facilitate maternal-fetal communication. Both dysregulation of circulating EVP miRNA during pregnancy and maternal diet quality have been previously associated with pregnancy complications and adverse birth outcomes. However, little is known about how maternal diet influences circulating EVP miRNA during pregnancy. This study assesses associations between maternal diet quality, as measured by the Alternative Healthy Eating Index (2010; AHEI-2010), and EVP miRNA levels in maternal circulation during pregnancy.

METHODS: In a pilot study of 53 pregnant participants in the New Hampshire Birth Cohort Study, maternal diet quality was assessed using AHEI-2010 and plasma (mean gestational age at blood collection: 28.8 weeks) EVP miRNA were profiled using the NanoString nCounter platform which interrogates 798 miRNA transcripts.

RESULTS: In covariate-adjusted models, the AHEI-2010 adherence score was negatively associated (P < 0.05) with the number of unique miRNA transcripts detectable in each sample. In post hoc analyses, greater consumption of red and processed meats was positively associated with levels of 7 miRNA (Q < 0.05), including hsa-miR-512-5p (PBonf < 0.01), a member of the placenta-specific chromosome 19 miRNA cluster.

CONCLUSION: We identified associations between the consumption of red and processed meat and levels of circulating select EVP miRNA during pregnancy, including placenta-specific miRNA and miRNA with target genes overrepresented in pathways involved in placental development. Additional research is needed to assess whether alterations in maternal circulating EVP miRNA may mediate maternal diet quality's impacts on pregnancy and birth outcomes.

PMID:39891736 | DOI:10.1007/s00394-025-03589-x

BMC Cancer. 2025 Jan 31;25(1):182. doi: 10.1186/s12885-025-13580-8.

ABSTRACT

BACKGROUND: Small-molecule compounds that even partially restore the GTPase activity of RASG12V can be used in anticancer therapy. Until now, attempts to obtain such compounds have failed. Compounds with this ability have been defined in our research.

METHODS: The compounds were initially identified through virtual screening, and their optimal binding conformation in the RAS SW-II pocket was determined using the flexible docking technique. Efficacy was verified based on the IC50 determination, GTPase activity, as well as the AKT and ERK phospho WB assays.

RESULTS: The IC50 of the tested compounds was significantly lower against cells with the RASG12V mutation than against selected types of normal cells. The molecular mechanism of action of these compounds was proposed - minimization of the negative impact of the V12 sidechain on GTP hydrolysis of RASG12V. The work also indicates that the model of action of RAS mutants in cell lines is incomplete. The analysed cell line (SW-480) with RAS mutations does not always show increased ERK and AKT activity.

CONCLUSIONS: We have demonstrated molecules that partially restore the GTPase activity of RASG12V. Their mechanism of action is well explained based on current RAS mutant conformation and mechanistic models. These molecules inhibit the RAS-AKT pathway and show higher cytotoxicity against cancer cells with the RASG12V mutation (SW-480 cell line). However, SW-480 cells can switch into the subline proliferating independently of AKT phosphorylation and show partial resistance to the molecules described in this article.

PMID:39891136 | DOI:10.1186/s12885-025-13580-8

Sci Rep. 2025 Jan 31;15(1):3946. doi: 10.1038/s41598-025-87867-y.

ABSTRACT

This paper focuses on the elective surgical scheduling problem with multi-resource constraints, including material resources, such as operating rooms (ORs) and non-operating room (NOR) beds, and human resources (i.e., surgeons, anesthesiologists, and nurses). The objective of multi-resource constrained elective surgical scheduling (MESS) is to simultaneously minimize the average recovery completion time for all patients, the average overtime for medical staffs, and the total medical cost. This problem can be formulated as a mixed integer linear multi-objective optimization model, and the honey badger algorithm based on the Nash equilibrium (HBA-NE) is developed for the MESS. Experimental studies were carried out to test the performance of the proposed approach, and the performance of the proposed surgical scheduling scheme was validated. Finally, to narrow the gap between the optimal surgical scheduling solution and actual hospital operations, digital twin (DT) technology is adopted to build a physical-virtual hospital surgery simulation model. The experimental results show that by introducing a digital twin, the physical and virtual spaces of the smart hospital can be integrated to visually simulate and verify surgical processes.

PMID:39890977 | DOI:10.1038/s41598-025-87867-y

Inflamm Res. 2025 Jan 31;74(1):31. doi: 10.1007/s00011-025-01996-8.

ABSTRACT

OBJECTIVE AND DESIGN: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of inflammatory muscle disorders of unknown etiology. It is postulated that mitochondrial dysfunction and protein aggregation in skeletal muscle contribute to myofiber degeneration. However, molecular pathways that lead to protein aggregation in skeletal muscle are not well defined.

SUBJECTS: Here we have isolated membrane-bound organelles (e.g., nuclei, mitochondria, sarcoplasmic/endoplasmic reticulum, Golgi apparatus, and plasma membrane) from muscle biopsies of normal (n = 3) and muscle disease patients (n = 11). Of the myopathy group, 10 patients displayed mitochondrial abnormalities (IIM (n = 9); mitochondrial myopathy (n = 1)), and one IIM patient did not show mitochondrial abnormalities (polymyositis).

METHODS: Global proteomic analysis was performed using an Orbitrap Fusion mass spectrometer. Upon unsupervised clustering, normal and mitochondrial myopathy muscle samples clustered separately from IIM samples.

RESULTS: We have confirmed previously known protein alterations in IIM and identified several new ones. For example, we found differential expression of (i) nuclear proteins that control cell division, transcription, RNA regulation, and stability, (ii) ER and Golgi proteins involved in protein folding, degradation, and protein trafficking in the cytosol, and (iii) mitochondrial proteins involved in energy production/metabolism and alterations in cytoskeletal and contractile machinery of the muscle.

CONCLUSIONS: Our data demonstrates that molecular alterations are not limited to protein aggregations in the cytosol (inclusions) and occur in nuclear, mitochondrial, and membrane compartments of IIM skeletal muscle.

PMID:39890639 | DOI:10.1007/s00011-025-01996-8

FEMS Microbiol Lett. 2025 Jan 31:fnaf017. doi: 10.1093/femsle/fnaf017. Online ahead of print.

ABSTRACT

Pseudomonas aeruginosa has increasing clinical relevance and commonly occupies the cystic fibrosis (CF) airways. Its ability to colonize and persist in diverse niches is attributed to its large accessory genome, where prophages represent a common feature and may contribute to its fitness and persistence. We focused on the CF airways niche and used 197 longitudinal isolates from 12 patients persistently infected by P. aeruginosa. We computationally predicted intact prophages for each longitudinal group and scored their long-term persistence. We then confirmed prophage inducibility and mapped their location in the host chromosome with lysate sequencing. Using comparative genomics, we evaluated prophage genomic diversity, long-term persistence and level of genomic maintenance. Our findings support previous findings that most P. aeruginosa genomes harbour prophages some of which can self-induce, and that a common CF-treating antibiotic, ciprofloxacin, can induce prophages. Induced prophage genomes displayed high diversity and even genomic novelty. Finally, all induced prophages persisted long-term with their genomes avoiding gene loss and degradation over four years of host replication in the stressful CF airways niche. This and our detection of phage genes which contribute to host competitiveness and adaptation, lends support to our hypothesis that the vast majority of prophages detected as intact and inducible in this study facilitated their host fitness and persistence.

PMID:39890605 | DOI:10.1093/femsle/fnaf017

J Dairy Sci. 2025 Jan 29:S0022-0302(25)00046-3. doi: 10.3168/jds.2024-25812. Online ahead of print.

ABSTRACT

Increasing production and environmental challenges in dairy cattle means that selecting for resilience is becoming more important. This study explored whether data on cows that exit before completing their lactation and those that die during lactation can be used to predict resilience. To identify predictors of resilience, exiting the herd by 60, 120, 180, and 240 d were defined as traits. Additional traits were defined, by including all the cows that died during the entire lactation to the cows that exited at different times up to 240 d of lactation. For all traits, cows that exited the herd or died were coded as 1, otherwise as 0 at the end of the lactation. We used performance and exit data of Holstein (H) and Jersey (J) cows that calved between 1998 and 2023. The data were analyzed using a multi-trait sire model to estimate heritability and correlations with milk yield (MY), somatic cell count (SCC), calving interval (CIN), and selected type traits. The results showed that the proportion of cows that exited by 60 d was 2%, increasing by about 2% every 2 mo until exit by 240 d. The trend over the years in the proportion of exits, taking Exit 180d and Exit 180 + death as an example, showed an undesirable increase from 5.6% in 2000 to 9.4% in 2022. Heritability of all exit traits was low, increasing from below 1% for exit by 60 to 2.8% for exit by 240 d + all deaths over the lactation. The genetic correlation of early exit (i.e., 60 or 120 d) with first test-day MY was positive (unfavorable) and higher at the beginning (0.4), decreasing over time to be favorable in J (-0.2) and near zero in H (0.1) by the end of the lactation. On the other hand, the genetic correlation of exit with first test-day SCC became stronger (favorable) at the end of the lactation (0.3 to 0.4). Exit at any time during the lactation had the strongest genetic correlation with CIN (i.e., fertility). The genetic correlation of exit traits with body condition score (BCS) and angularity showed that the likelihood of cow exit, especially up to 180 d, was higher for thin and more angular cows. The genetic correlation estimates imply that cows with high potential for MY, poor fertility, poor BCS, and high scores for angularity are more likely to exit early due to metabolic stress. The change in genetic correlation between exit and MY early from unfavorable to favorable in J is due to more culling for milk and less for fertility and udder health is leading to an undesirable genetic trend for exit by 180 d as well as exit by 180 d + all death. However, the increasing phenotypic trend of exit rates in both breeds suggests a need for close monitoring. The selective use of exit data can help to develop genetic evaluations for resilience and health traits and validate and complement data collected to improve health and welfare during the transition period.

PMID:39890077 | DOI:10.3168/jds.2024-25812

Cell Rep Med. 2025 Jan 28:101931. doi: 10.1016/j.xcrm.2025.101931. Online ahead of print.

ABSTRACT

Chimeric antigen receptor (CAR) T cell therapy is a promising immunotherapy against cancer. Although there is a growing interest in other cell types, a comparison of CAR immune effector cells in challenging solid tumor contexts is lacking. Here, we compare mouse and human NKG2D-CAR-expressing T cells, natural killer (NK) cells, and macrophages against glioblastoma, the most aggressive primary brain tumor. Invitro we show that T cell cancer killing is CAR dependent, whereas intrinsic cytotoxicity overrules CAR dependence for NK cells, and CAR macrophages reduce glioma cells in co-culture assays. In orthotopic immunocompetent glioma mouse models, systemically administered CAR T cells demonstrate superior accumulation in the tumor, and each immune cell type induces distinct changes in the tumor microenvironment. An otherwise low therapeutic efficacy is significantly enhanced by co-expression of pro-inflammatory cytokines in all CAR immune effector cells, underscoring the necessity for multifaceted cell engineering strategies to overcome the immunosuppressive solid tumor microenvironment.

PMID:39889712 | DOI:10.1016/j.xcrm.2025.101931

Cell Rep Med. 2025 Jan 27:101935. doi: 10.1016/j.xcrm.2025.101935. Online ahead of print.

ABSTRACT

Chronic hepatic injury and inflammation from various causes can lead to fibrosis and cirrhosis, potentially predisposing to hepatocellular carcinoma. The molecular mechanisms underlying fibrosis and its progression remain incompletely understood. Using a proteo-transcriptomics approach, we analyze liver and plasma samples from 330 individuals, including 40 healthy individuals and 290 patients with histologically characterized fibrosis due to chronic viral infection, alcohol consumption, or metabolic dysfunction-associated steatotic liver disease. Our findings reveal dysregulated pathways related to extracellular matrix, immune response, inflammation, and metabolism in advanced fibrosis. We also identify 132 circulating proteins associated with advanced fibrosis, with neurofascin and growth differentiation factor 15 demonstrating superior predictive performance for advanced fibrosis(area under the receiver operating characteristic curve [AUROC] 0.89 [95% confidence interval (CI) 0.81-0.97]) compared to the fibrosis-4 model (AUROC 0.85 [95% CI 0.78-0.93]). These findings provide insights into fibrosis pathogenesis and highlight the potential for more accurate non-invasive diagnosis.

PMID:39889710 | DOI:10.1016/j.xcrm.2025.101935

Semin Cell Dev Biol. 2025 Jan 30;167:22-39. doi: 10.1016/j.semcdb.2025.01.002. Online ahead of print.

ABSTRACT

Embryonic development is a complex and intricately regulated process that encompasses precise control over cell differentiation, morphogenesis, and the underlying gene expression changes. Recent years have witnessed a remarkable acceleration in the development of single-cell and spatial omic technologies, enabling high-throughput profiling of transcriptomic and other multi-omic information at the individual cell level. These innovations offer fresh and multifaceted perspectives for investigating the intricate cellular and molecular mechanisms that govern embryonic development. In this review, we provide an in-depth exploration of the latest technical advancements in single-cell and spatial multi-omic methodologies and compile a systematic catalog of their applications in the field of embryonic development. We deconstruct the research strategies employed by recent studies that leverage single-cell sequencing techniques and underscore the unique advantages of spatial transcriptomics. Furthermore, we delve into both the current applications, data analysis algorithms and the untapped potential of these technologies in advancing our understanding of embryonic development. With the continuous evolution of multi-omic technologies, we anticipate their widespread adoption and profound contributions to unraveling the intricate molecular foundations underpinning embryo development in the foreseeable future.

PMID:39889540 | DOI:10.1016/j.semcdb.2025.01.002

Phytomedicine. 2025 Jan 20;138:156412. doi: 10.1016/j.phymed.2025.156412. Online ahead of print.

ABSTRACT

BACKGROUND: Vascular dementia (VaD), a significant cognitive disorder, is caused by reduced cerebral blood flow. Unraveling the metabolic heterogeneity and reprogramming in VaD is essential for understanding its molecular pathology and developing targeted therapies. However, the in situ metabolic regulation within the specific brain regions affected by VaD has not been thoroughly investigated, and the therapeutic mechanisms of Erigeron breviscapus injection (EBI), a traditional Chinese medicine, require further elucidation.

PURPOSE: To investigate the region-specific metabolic alterations in a VaD rat model, explore the therapeutic effects of EBI at a microregional level, identify the key metabolic pathways and metabolites involved in VaD, and elucidate how EBI modulates these pathways to exert its therapeutic effects.

METHODS: Air-flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI), a novel technique, was employed to investigate the metabolic changes in the brain microregions. We used a bilateral common carotid artery occlusion model to induce VaD in rats. Network analysis and network pharmacology were used to assess the local metabolic effects of the EBI treatment (3.6 mL/kg/day for 2 weeks).

RESULTS: The EBI treatment significantly ameliorated the neurological deficits in VaD rats. AFADESI-MSI revealed 31 key metabolites with significant alterations in the VaD model, particularly within the pathways related to neurotransmitter metabolism, redox homeostasis, and osmoregulation. The metabolic disturbances were primarily observed in the striatum (ST), pyriform cortex (PCT), hippocampus (HP), and other critical brain regions. The EBI treatment effectively reversed these metabolic imbalances, especially in neurotransmitter metabolism, suggesting its potential in mitigating VaD-related cognitive decline.

CONCLUSION: Our findings not only shed light on the molecular underpinnings of VaD but also highlight the potential of EBI as a therapeutic agent in neurodegenerative disorders. Moreover, this study demonstrates the power of advanced mass spectrometry imaging techniques in phytomedicine, offering new insights into the spatial metabolic changes induced by botanical treatments.

PMID:39889490 | DOI:10.1016/j.phymed.2025.156412

Proteomics. 2025 Jan 31:e202400109. doi: 10.1002/pmic.202400109. Online ahead of print.

NO ABSTRACT

PMID:39888210 | DOI:10.1002/pmic.202400109