Search Results (45)

Undifferentiated sarcomas (USs), including undifferentiated pleomorphic sarcoma (UPS), are aggressive mesenchymal malignancies with limited molecular biomarkers for prognostic assessment and therapeutic stratification. Expression-based markers may provide insight into tumor aggressiveness and clinical outcomes. Here, we performed integrative transcriptomic and spatial analyses to identify differentially expressed genes (DEGs). By comparing normal tissues with sarcoma tumors and sarcoma tumors with cell lines. Intersection and clustering analyses were conducted to define shared expression programs, which revealed a subset of DEGs enriched in epithelial-mesenchymal transition (EMT)-related pathways. CosMx spatial transcriptomics was applied to xenograft tumors derived from two UPS cell lines to resolve tumor-intrinsic signatures. The National Cancer Center Cohort samples were used for validation, and immunohistochemistry confirmed the expression in thirty US tissues. Spatial transcriptomic profiling identified mesenchymal tissue–driven gene expression programs in UPS xenografts. Across bulk RNA-seq and spatial data, epithelial membrane protein 3 (EMP3) consistently emerged as highly expressed in US tissues and cell lines. EMP3 is a robust mesenchymal-associated biomarker linked to EMT, tumor progression, and clinical outcomes in USs, supporting its potential utility as a prognostic indicator and therapeutic target. Full article

Background: Osteoarthritis (OA) is a multifactorial disease, including inflammation, autophagy and senescence. Published work has indicated that empagliflozin (EMP) exhibits robust anti-inflammatory and anti-senescence effects, while its role in autophagy appears paradoxical. Here, we aim to identify the chondroprotective effect of EMP on OA. Methods: An OA model was established both in vitro, by stimulating primary chondrocytes (isolated from C57BL/6J mice) with IL-1β, and in vivo, by performing (Destabilized medial meniscus) DMM surgery on C57BL/6J mice. (Western blot) WB and (quantitative real-time polymerase chain reaction) qRT-PCR analysis were employed to detect the gene expression. (Immunofluorescence) IF staining was employed to detect the expression and location of target protein. SA-β-gal staining was employed to evaluate cellular senescence. Autophagic flux was assessed using a GFP-RFP-LC3 adenoviral vector. Network pharmacology was applied to identify potential pathways for experimental validation. The effects of EMP in vivo were evaluated by μ-CT, histological and (Immunohistochemistry) IHC staining. Results: EMP promoted anabolism, inhibited the inflammatory response and catabolism in IL-1β stimulated chondrocytes. EMP enhanced autophagic activity and attenuated senescent phenotype in vitro. Mechanistically, EMP regulated the PI3K/Akt/mTOR and AMPK pathways. The chondroprotective effects of EMP were reversed by (3-methyladenine) 3-MA. EMP also ameliorated OA-related phenotype in DMM models. Compared with (Kartogenin) KGN, EMP showed more pronounced suppression of inflammatory and catabolic markers, while both compounds similarly promoted anabolic marker expression. Conclusions: These in vitro and in vivo data collectively indicates that EMP can alleviate OA both in IL-1β stimulated chondrocytes and DMM induced models. Beyond its established role in diabetes management, EMP is evaluated in the context of OA, emerging as a novel and promising therapeutic agent for OA. Full article

This study utilized network pharmacology, bioinformatics, along with machine learning to investigate the multi-target synergistic anti-cancer mechanisms of three edible medicinal plants (EMPs)—mulberry leaf, lotus leaf, and sea buckthorn—against oral and esophageal squamous cell carcinomas (OSCC and ESCC). We identified potential active constituents and their targets through mining Traditional Chinese Medicine Systems Pharmacology (TCMSP) and Swiss Target Prediction databases. Concurrently, integration with differential expression profiles and co-expression modules identified crucial intersection targets between the EMPs and these two cancers. Subsequent machine learning algorithms and cross-cancer analysis consistently identified Matrix Metalloproteinase-1 (MMP1) as a critical hub gene. Its overexpression is closely associated with tumor invasion and metastasis. Molecular simulations revealed stable binding interactions between active constituents from three EMPs and hub proteins. Furthermore, research on immune cell infiltration suggested that the active components of three EMPs may impact the tumor immune microenvironment in both OSCC and ESCC through the regulation of pivotal gene expression. Collectively, this work systematically elucidates the molecular basis underlying the multi-target, multi-pathway synergistic anti-cancer effects of these EMPs, providing a theoretical foundation for developing natural drugs against these squamous cell carcinomas. Full article

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, underscoring the need to elucidate molecular mechanisms that regulate tumor cell state and behavior. Leucine zipper–like post-translational regulator 1 (LZTR1) regulates RAS/mitogen-activated protein kinase (MAPK) signaling, yet LZTR1-dependent transcriptional alterations in HCC cells remain poorly defined. To address this gap and determine how LZTR1 loss reshapes signaling, transcriptional programs, and cellular phenotypes, we established a LZTR1 knockout (KO) Hep3B model and combined pathway profiling with transcriptomic and functional analyses. Immunoblotting revealed increased phosphorylation across the RAF–MEK–ERK–RSK cascade in LZTR1 KO cells. Transcriptome-wide RNA sequencing (RNA-Seq) identified differentially expressed genes, and selected findings were validated by qRT-PCR. Gene set enrichment analysis indicated that the epithelial–mesenchymal transition (EMT) gene set was enriched in control cells. At the protein level, LZTR1 loss remodeled EMT-associated markers in a hybrid epithelial–mesenchymal pattern consistent with epithelial–mesenchymal plasticity (EMP). Vimentin was suppressed at transcript and protein levels. Functionally, LZTR1 KO cells exhibited impaired wound closure and reduced transwell migration and invasion. Collectively, these findings define an EMP-related molecular and phenotypic state associated with LZTR1 deficiency in Hep3B cells, providing insight into how LZTR1 loss reshapes tumor cell behavior in HCC. Full article

Fermentation remains central to food manufacturing and to the bio-based production of organic acids, solvents, and functional metabolites. This review integrates the biochemical pathways, key microorganisms, and application space of five major industrial fermentations—alcoholic, acetic, butyric, lactic, and propionic. We summarize the principal metabolic routes (EMP/ED glycolysis; oxidative ethanol metabolism; butyrate-forming pathways; and the Wood–Werkman, acrylate, and 1,2-propanediol routes to propionate) and relate them to the dominant microbial groups involved, including yeasts, acetic acid bacteria, lactic acid bacteria, clostridia, and propionibacteria. We highlight how the resulting metabolite spectra—ethanol, acetic acid, butyrate, lactate, propionate, and associated secondary metabolites—underpin product quality and safety in fermented foods and beverages and enable the industrial synthesis of platform chemicals, polymers, and biofuels. Finally, we discuss current challenges and opportunities for sustainable fermentation, including waste stream valorization, process intensification, and the integration of systems biology and metabolic engineering within circular economy frameworks. Full article

Erythro-myeloid progenitors (EMPs) originate from the haemogenic endothelium in the yolk sac via an endothelial-to-haematopoietic transition (EHT) to generate blood and immune cells that support embryo development. Yet, the transitory nature of EHT and the limited availability of molecular markers have constrained our understanding of the origin, identity, and differentiation dynamics of EMPs. Here, we have refined the annotation of yolk sac haemato-vascular populations in publicly available single-cell RNA sequencing (scRNAseq) datasets from mouse embryos to identify novel molecular markers of haemogenic endothelium and EMPs. By sub-clustering key cell populations followed by pseudotime analysis, we refined cluster annotations and then reconstructed differentiation trajectories. Subsequent differential gene expression analysis between clusters identified novel cell surface markers for haemogenic endothelial cells (Fxyd5 and Scarf1) and EMPs (Fcer1g, Tyrobp, and Mctp1). Further, we have identified candidate signalling and metabolic pathways that may regulate yolk sac haematopoietic emergence and differentiation. The specificity of FXYD5, SCARF1, and FCER1G for haemogenic endothelium and EMPs was validated by immunostaining of the mouse yolk sac. These insights into the transcriptional dynamics in the yolk sac should support future investigation of EHT and haematopoietic differentiation during early mammalian development. Full article

Recent studies support that hematopoietic stem cell (HSC)-derived myeloid dendritic cells, monocytes/macrophages (Mo/Mϕ), and osteoclast precursors (OCps) share common progenitor(s) during development. This occurs mainly through receptor activator of NF-κB ligand (RANKL) signaling via its cytoplasmic adaptor protein complex (TRAF6) to subsequent osteoclastogenesis for bone loss and/or remodeling. Presently, mounting new evidence suggests that erythro-myeloid progenitor (EMP)-derived macrophages (Mϕ) and HSC-derived monocytes (Mo) produce embryonic, fetal, and postnatal OCp pools (i.e., primitive OCp), pinpointing a complex network of multiple OCp developmental origins. However, their ontogenic developments, lineage interactions, and contributions to the alternative osteoclastogenesis—in contrast to overall bone remodeling or loss—remain elusive. Interestingly, studies have also elucidated the contributions of immature CD11c⁺ myeloid DC-like OCps to osteoclastogenesis, with or without the classical so-called Mo/Mϕ-derived OCp subsets, and described that CD11c⁺ myeloid DCs (mDCs) develop into functionally active OCs; meanwhile, the cytokine TGF-β mediates a stepwise regulation of de novo immature mDCs/OCps through distinct crosstalk(s) with IL-17, an unrecognized interaction featuring TRAF6^(−/−)CD11c⁺ mDDOCps that coexist and proficiently colocalize in the local environment to drive a bona fide route for alternative osteoclastogenesis in vivo. Collectively, new findings—critically hinged on progenitor osteoclastogenic pathways (primitive OCps, mDCs/OCps, osteomorphs, etc.) and involving classical and/or alternative routes to inflammation-induced bone loss—are discussed via the illustrated schemes. This review highlights plausible ontogenic vs. principal or alternative developmental paths and their consequential downstream effects. Full article

Background/Objectives: Overactivation of the HGF/c-MET pathway is implicated in various cancers, making its inhibition a promising therapeutic strategy. While several MET-targeting agents are currently approved or in advanced clinical development, patient selection often relies on invasive tissue-based assays. The development of a specific c-MET radioligand for PET imaging and radioligand therapy represents a non-invasive alternative, enabling real-time monitoring of target expression and offering a pathway to personalized treatment. Methods: Radiosynthesis of [⁶⁸Ga]Ga-DOTA-EMP100 was performed using a GMP-certified ⁶⁸Ge/⁶⁸Ga generator connected to an automated synthesis module. The radiopharmaceutical production was optimized by scaling down the amount of DOTA-EMP-100 from 50 to 20 μg. Synthesis efficiency and release criteria were assessed according to Ph. Eur. for all the final products by evaluating radiochemical yield (RY%), radiochemical purity, presence of free gallium (by Radio-UV-HPLC) and gallium colloids (by Radio-TLC), molar activity (Am), chemical purity, pH, and LAL test results. Results: An optimized formulation of [⁶⁸Ga]Ga-DOTA-EMP-100, using 40 μg of precursor, provided the best outcome in terms of radiochemical performance. Process validation across three independent productions confirmed a consistent radiochemical yield of 64.5% ± 0.5, high radiochemical purity (>99.99%), and a molar activity of 53.41 GBq/µmol ± 0.8. Conclusions: [⁶⁸Ga]Ga-DOTA-EMP-100 was successfully synthesized with high purity and reproducibility, supporting its potential for multi-dose application in clinical PET imaging and targeted radioligand therapy. Full article

The sulfo-Embden–Meyerhof–Parnas (sulfo-EMP) pathway enables Escherichia coli to utilize sulfoquinovose, (SQ) a sulfonated sugar derived from plant sulfolipids, as a carbon source. This pathway is encoded by the yih gene cassette. However, structural and functional diversity of this cassette across E. coli strains has not been fully characterized. We identified two structural variants of the yih cassette across E. coli and Shigella strains: a long form (ompL-yihOPQRSTUVW) and a truncated short form (yihTUVW). Both forms occupy the same genomic location but differ in orientation and are scattered across the phylogenetic tree, suggesting frequent recombination events. Transcriptome analyses revealed that only the long cassette, as found in E. coli K-12 MG1655, is transcriptionally induced during growth on sulfoquinovose. The short cassette, found in E. coli Nissle 1917 and other host-adapted strains, showed no differential expression. Despite this, both strains grew comparably on sulfoquinovose, indicating different metabolic adaptation strategies. Gene expression profiling revealed shared stress responses but distinct central metabolic patterns. Electrophoretic mobility shift assays further demonstrated that the transcription factor YihW from Nissle 1917 binds its DNA targets with lower affinity than the homolog from K-12 and shows weaker sulfoquinovose-dependent dissociation. Full article

The mesenchymal–epithelial transition/plasticity (MET/EMP) axis is a key regulator of tumor development, cancer progression, and resistance to therapy, making it an attractive target for intervention. This review highlights strategies to modulate MET/EMP using three representative agents—capmatinib, bemcentinib, and galunisertib—each acting on distinct signaling pathways. Capmatinib is a selective MET tyrosine kinase inhibitor with notable efficacy in non-small cell lung cancer harboring MET exon 14 skipping mutations. Bemcentinib blocks AXL receptor tyrosine kinase, interfering with AXL/GAS6 signaling that promotes tumor survival, metastasis, and therapeutic resistance. Galunisertib inhibits TGF-β signaling, reducing epithelial–mesenchymal transition (EMT), immune evasion, and metastatic potential. We discuss their mechanisms of action, therapeutic applications, and current clinical progress. Although these targeted therapies show potential to overcome resistance and improve patient outcomes, challenges remain due to the complex regulation of EMP. Future directions focus on refining combination strategies and advancing personalized approaches to enhance efficacy across multiple cancer types. Full article

Lactic acid (LA) is a versatile, optically active compound with applications across the food, cosmetics, pharmaceutical, and chemical industries, largely driven by its role in producing biodegradable polylactic acid (PLA). Due to its abundance, lignocellulosic biomass is a promising and sustainable resource for LA production, although media derived from these matrices are often rich in xylose and contain growth inhibitors. This study investigates LA production using a xylose-rich medium derived from Cynara cardunculus L. altilis DC stalks treated through steam explosion and enzymatic hydrolysis. The lactic acid bacteria strains Lacticaseibacillus casei, Paucilactobacillus vaccinostercus, and Pediococcus pentosaceus were grown on natural media, achieving yields of 0.59, 0.57, and 0.58 g LA/g total carbon consumed, respectively. Remarkably, on xylose-rich media, all supplied sugar was consumed, with LA yields comparable to those on complex media. These findings highlight the adaptability of these strains in the presence of inhibitors and support the potential of lignocellulosic biomass as a low-cost and sustainable substrate for effective PLA production. Full article

Weathering products of sphalerite-bearing ores play an important role in controlling the fate of Zn in the environment. In this framework, the relative stability of Zn carbonates is of special relevance for the common case of ore weathering by carbonated groundwater in the presence of calcium carbonates. We investigated the experimental (co)nucleation and growth of Zn and Ca carbonates at 25 °C in finite double diffusion silica hydrogel media with the purpose of deciphering the system’s reactive pathway and unraveling the major governing factors behind the obtained mineral assemblages. The crystallized solids were carefully extracted two months post-nucleation and studied with micro-Raman spectroscopy, micro X-ray diffraction (XRD), scanning electron microscopy, and electron microprobe (EMP) methods. The obtained results indicate that the grown Zn-bearing phases corresponded to smithsonite and/or Zn hydroxyl carbonate, while CaCO₃ polymorphs aragonite and calcite were also crystallized. Moreover, the observed mineral textural relationships reflected the interplay between supersaturation with respect to CaCO₃/pCO₂ and the grown Zn-bearing carbonate. Experiments conducted in more supersaturated conditions with respect to CaCO₃ polymorphs (higher pCO₂) favored the precipitation of smithsonite, while the opposite was true for the obtained Zn hydroxyl carbonate phase. The gathered Raman, XRD, and EMP data indicate that the latter phase corresponded to a non-stoichiometric, poorly crystalline solid. Full article

Genus Pseudomonas bacteria mainly consume glucose through the Entner–Doudoroff (ED) route due to a lack of a functional Embden–Meyerhof–Parnas (EMP) pathway. In the present study, a 6-phosphogluconate dehydratase (edd) operon in the ED route was well investigated to find its structural characteristics and roles in the regulation of glucose consumption and 2-ketogluconic acid (2KGA) metabolism in the industrial 2KGA-producer P. plecoglossicida JUIM01. The edd operon contained four structural genes of edd, glk, gltR, and gtrS, encoding 6-PG dehydratase Edd, glucokinase Glk, response regulatory factor GltR, and histidine kinase GtrS, respectively. A promoter region was observed in the 5′-upstream of the edd gene, with a transcriptional start site located 129 bp upstream of the edd gene and in a pseudo-palindromic sequence of 5′-TTGTN₇ACAA-3′ specifically binding to the transcription factor HexR. The knockout of the edd gene showed a remarkably negative effect on cell growth and re-growth using 2KGA as a substrate, beneficial to 2KGA production, with an increase of 8%. The deletion of glk had no significant effect on the cell growth or glucose metabolism, while showing an adverse impact on the 2KGA production, with a decrease of 5%. The outputs of the present study would provide a theoretical basis for 2KGA-producer improvement with metabolic engineering strategies and the development and optimization of P. plecoglossicida as the chassis cells. Full article

Inner Mongolia, a major region in China for growing sugar beet, faces challenges caused by unscientific water and fertilizer management. This mismanagement restricts the improvement of sugar beet yield and quality and exacerbates water waste and environmental pollution. This study aims to evaluate the effects of reduced water and fertilizer on the growth and physiological metabolism of sugar beet taproot. Field experiments were conducted in Ulanqab, Inner Mongolia, in 2022 and 2023, using a split-plot design with three levels each of fertilization and irrigation. The study analyzed the effects of reduced water and fertilizer treatments on fresh taproot weight, respiration rate, energy metabolism, respiratory enzyme activity, and gene expression in sugar beet taproot. It was found that a 10% reduction in fertilizer significantly increased the beet taproot fresh weight. Further research revealed that during the rapid leaf growth phase and the taproot and sugar growth period, a 10% reduction in fertilizer upregulated HK and IDH gene expression and downregulated G6PDH gene expression in the beet taproot. This increased HK and IDH activities, decreased G6PDH activity, enhanced the activity of the EMP-TCA pathway, and inhibited the PPP. Taproot weight was positively correlated with the respiration rate, ATP content, EC, and ATPase, HK, and IDH activities, thereby increasing the taproot growth rate and taproot fresh weight, with an average increase of 4.0% over two years. These findings introduce a novel method for optimizing fertilizer use, particularly beneficial in water-scarce regions. Implementing this strategy could help farmers in western Inner Mongolia and similar areas improve crop yield and sustainability. This study offers new insights into resource-efficient agricultural practices, highlighting the importance of customized fertilization strategies tailored to local environmental conditions. Full article

Pseudomonas fragi (P. fragi) is usually detected in low-temperature meat products, and seriously threatens food safety and human health. Therefore, the study investigated the antibacterial mechanism of linalool against P. fragi from membrane damage and metabolic disruption. Results from field-emission transmission electron microscopy (FETEM) and atomic force microscopy (AFM) showed that linalool damage membrane integrity increases surface shrinkage and roughness. According to Fourier transform infrared (FTIR) spectra results, the components in the membrane underwent significant changes, including nucleic acid leakage, carbohydrate production, protein denaturation and modification, and fatty acid content reduction. The data obtained from amino acid metabolomics indicated that linalool caused excessive synthesis and metabolism of specific amino acids, particularly tryptophan metabolism and arginine biosynthesis. The reduced activities of glucose 6-phosphate dehydrogenase (G6PDH), malate dehydrogenase (MDH), and phosphofructokinase (PFK) suggested that linalool impair the respiratory chain and energy metabolism. Meanwhile, genes encoding the above enzymes were differentially expressed, with pfkB overexpression and zwf and mqo downregulation. Furthermore, molecular docking revealed that linalool can interact with the amino acid residues of G6DPH, MDH and PFK through hydrogen bonds. Therefore, it is hypothesized that the mechanism of linalool against P. fragi may involve cell membrane damage (structure and morphology), disturbance of energy metabolism (TCA cycle, EMP and HMP pathway) and amino acid metabolism (cysteine, glutamic acid and citrulline). These findings contribute to the development of linalool as a promising antibacterial agent in response to the food security challenge. Full article