Large-scale metabolomic studies are needed to identify and validate biomarkers for their successful translation in emerging population health and precision medicine initiatives. Yet, untargeted mass spectrometry (MS)-based metabolomics remains hampered by low sample throughput, limited coverage, complicated data processing, poor standardization, and high operating costs. These challenges also contribute to a reproducibility crisis, with most reported biomarkers not independently replicated, given variations in study designs, sample workup protocols, instrumental methods, and data pre-processing workflows. This review will focus on new advances in high-throughput MS platforms and computational software with emerging artificial intelligence/machine learning tools that are scalable, faster, and less prone to error. Recent progress to improve data harmonization in population-level metabolomic, lipidomic, and exposomic studies (n > 1000) will also be discussed. This will include strategies to correct for long-term batch effects, improve metabolite identification, and derive biochemical insights into disease mechanisms when integrated with multi-omic studies.
Although ion mobility-mass spectrometry (IM-MS) is no longer a new technology, new developments in instrumentation and resources for structurally informed measurements are enabling the use of IM-MS in emerging metabolomic applications. Once limited by experimental measurements, the growth of machine-learning strategies to predict collision cross-section values is rapidly increasing the coverage of IM-MS information in metabolite databases. IM-MS instrumentation capable of high-resolution separations is bringing new depth to the level of structural annotation that can be achieved, while creative strategies to combine IM-MS with complementary analytical or chemical methods are further leveraging its ability to resolve small molecule isomers and isobars. This brief review highlights the recent developments of IM-MS for metabolomics with a focus on applications to mass spectrometry imaging, rapid multi-omics, and single-cell analyses.
Hybrid electro-biomanufacturing provides an attractive route for converting CO₂ into fuels and chemicals beyond the constraints of natural photosynthesis. However, achieving systems-level high productivity and efficiency while maintaining robust electro-biological (electrobio) operation remains a key challenge. This mini review quantitatively benchmarks electrobio system architectures by evaluating the kinetic and chemical compatibility between electrochemical CO₂ reduction and biological conversion to identify the key determinants of performance and scalability. We demonstrate that carbon intermediate compatibility is the primary requirement for successful integration, while production–consumption rate matching ultimately determines system efficiency and scale-up potential. Together, these insights establish electrobio compatibility as a critical yet underappreciated design principle for guiding the development of next-generation electrobio manufacturing platforms.
Introduction: Mesenchymal stem cells (MSCs) play a significant role in shaping and regulating microenvironments. The factors influencing the glycolytic metabolic reprogramming of MSCs remain unknown. Methods: MSCs were isolated from human umbilical cords and identified using flow cytometry. Glycolysis-related gene expression, glucose consumption, and ATP and lactate production were measured in MSCs with HIF1A-AS3 overexpression or knockdown. The roles of HIF1A-AS3 in the glycolytic pathway and its downstream network were revealed by high-throughput sequencing. Results: HIF1A-AS3 enhanced the glycolytic level of MSCs by increasing glucose consumption, lactate production, ATP levels, and expression of key glycolytic enzymes (GLUT1, HK2, and PKM2). The downstream signaling pathway of HIF1A-AS3 might be associated with glycosylationrelated diseases. Discussion: It was demonstrated that HIF1A-AS3, a hypoxia-induced long non‑coding RNA, acted as a critical regulator of glycolytic reprogramming in MSCs. Additionally, HIF1A-AS3 upregulated a distinct subset of interferon‑stimulated genes, suggesting a potential link between metabolic reprogramming and immunomodulation in MSCs. Further mechanistic studies are warranted to elucidate how HIF1A-AS3 regulates these processes. Conclusion: The study reveals that HIF1A-AS3 is a regulator of the metabolic reprogramming of glycolysis in MSCs. These findings provide new insights into understanding the metabolic regulatory mechanism of MSCs.
Introduction/ Objective: Neutrophils are crucial for an effective innate immune response. However, overactivation is associated with chronic inflammation, as in systemic lupus erythematosus (SLE). Gingival mesenchymal stromal cells (GMSCs) are used as anti-inflammatory therapies because they possess strong immunomodulatory properties, primarily acting through paracrine mechanisms. GMSCs exhibit immunoplasticity in response to their microenvironment and adjust their secretion profile. This study aimed to investigate the effects of conditioned media derived from human gingival mesenchymal stromal cells (hGMSC-CM) or from cells pretreated with IFNγ (hGMSCγ- CM) on neutrophil antimicrobial and proinflammatory functions. METHODS:hGMSCs were isolated to meet the criteria of the International Society for Cell & Gene Therapy (ISCT). Neutrophil intracellular reactive oxygen species (ROS) production; neutrophil elastase (NE), cathepsin G (CG), and myeloperoxidase (MPO) enzymatic activities; induction of lytic and vital neutrophil extracellular traps (NETs); and bacterial uptake and engulfment were analyzed using flow cytometry, photometric methods, and fluorescence and confocal microscopy. RESULTS:Both hGMSC-derived CMs significantly reduced intracellular ROS levels, reduced the enzymatic activities of MPO, CG, and NE by decreasing degranulation, and diminished NET formation (DNA, LL37, and PAD4) through both the lytic and vital pathways, including NET production observed in an inflammatory environment using plasma from SLE patients. DISCUSSION:These inhibitory effects were more pronounced with hGMSCγ-CM. Interestingly, hGMSCγ-CM did not impair bacterial uptake, engulfment, or neutrophil microbicidal activity against Staphylococcus aureus and Escherichia coli, thereby maintaining the functional balance of neutrophils. CONCLUSION:These findings support the use of hGMSCγ-CM as a cell-free biological product for therapies targeting inflammation driven by neutrophil overactivation.
