Uncovering the metabolic and molecular mechanisms involved in plant responses to drought and subsequent recovery, is essential to identify drought tolerance mechanisms that can be used to improve crop plants. Here we combine plant physiology and biochemistry, with gene expression, quantitative proteomics and metabolite profiling to identify the genetic and metabolic networks that operate in plants experiencing and recovering from drought. Network analysis of transcripts, proteins and metabolites revealed that certain biological processes such as the tricarboxylic acid cycle and lipid metabolism had a strong impact on the overall control of leaf responses to drought and recovery. The stimulation of carbohydrate oxidation pathways is demonstrated to be a key node in the generation of energy and precursors required to support diverse survival pathways of defence.

Purine metabolism in tumorigenesis and its clinical implications.

Xylazine abuse is emerging as a global problem, whereas the toxic mechanisms of xylazine poisoning are seldom studied. The present study aims to assess the heart injury in xylazine poisoning and uncover the underlying mechanism. Forty male SD rats were randomly dived into four groups: control (saline), low dose (10 mg/kg xylazine), median dose (20 mg/kg xylazine) and high dose (40 mg/kg xylazine). The rats were injected with the drug intraperitoneally for 28 consecutive days, and then cardiac ultrasound examination was performed and serum and heart tissues were collected. Genomic, proteomic, and metabolic omics analyses were conducted. ELISA, RNA sequencing, histopathology examination, RT-qPCR, and Western blot were performed. Repeated injection of xylazine led to a decrease in the expression of cardiac output (CO), ventricular systole (VS), and ventricular diastole (VD), while concurrently elevating the levels of lactate dehydrogenase (LDH), creatine kinase myocardial band (CK-MB), and cardiac troponin T (c-TNT) in the serum. HE staining analysis showed evidence of contraction band necrosis, interstitial fibrosis, and infiltration by inflammatory cells in animals with xylazine poisoning. The modified genes, proteins, and metabolites were gathered, and the integration of transcriptomic, proteomic, and metabolic networks identified 25 overlapping pathways between the differentially expressed genes and metabolites (DEGs-DEMs) and the differentially expressed proteins and metabolites (DEPs-DEMs) joint pathways. The majority of these pathways pertained to the metabolism of sugars, amino acids, and fats. The proteins associated with fructose and mannose metabolism, as well as cholesterol metabolism, were validated, thereby substantiating their pivotal role in the development of xylazine-induced cardiac injury. Repeated injection of xylazine impaired heart function and the metabolism of fructose and mannose. Cholesterol metabolism pathways were critical in the process of xylazine-induced heart injury.

Trimetallic Pt-Pd-Au alloy nanozymes for multimodal synergistic therapy to overcome deep-seated drug-resistant infections via ROS cascade.

Dynamic remodeling of amino acid metabolism in tumor-associated macrophages: Fueling immunosuppression, reshaping tumor niches, and unlocking metabolic checkpoints.

Unraveling principles of thermodynamics for genome-scale metabolic networks using graph neural networks.

Metabolic reprogramming induced by the glutamine/glutamate (Gln/Glu) metabolic pathway is a key mechanism in ATP production, precursor biosynthesis, and redox homeostasis, promoting prostate cancer (PCa) growth and proliferation. This evolutionarily acquired hallmark of cancers enables malignant cells to adapt their bioenergetic and biosynthetic pathways in response to microenvironmental stresses. Therefore, Gln/Glu metabolism orchestrates epigenetic regulation, metastatic capacity, and oxidative homeostasis in PCa, supporting the survival of PCa tumors. Fluctuations in Glu metabolite levels and oxygen tension shape the PCa epigenome by facilitating Glu-derived α-ketoglutarate (α-KG) activation of TET and KDM enzymes, which drive histone and DNA demethylation. Furthermore, tumor progression toward metastatic castration-resistant PCa is characterized by heightened Gln/Glu dependency and increased Gln uptake. Within the tumor microenvironment (TME), a dynamic tug-of-war occurs between tumor and immune cells, competing for Gln metabolites. Gln/Glu converges on critical oncogenic signaling axes, including NF-κB/Nrf2, c-Myc/androgen receptor, MAPK/ERK, and PI3K/AKT/mTOR. Additionally, extracellular Glu release via SLC7A11 and PSMA triggers metabotropic glutamate receptor (mGluR) signaling, further potentiating oncogenic programs. Targeting this Gln/Glu metabolic network thus presents a promising therapeutic approach against PCa. In this review, we summarize the role of Gln/Glu in PCa progression based on the compartmentalization of the Gln/Glu metabolic pathway to elucidate why PCa cells manifest dependence on Gln/Glu. Eventually, we highlight potential therapeutic targets that can be exploited for PCa treatment.

Utilization of glucose and fructose in bovine embryos assessed by metabolic flux analysis.

ADP-ribose is a competitive inhibitor of methanol dehydrogenases from Bacillus methanolicus.

Multi-omics analysis reveals lipid metabolism profiles and regulatory networks in meibomian glands aging.

ABSTRACTThe introduction of nitisinone (NTBC) and newborn screening for Tyrosinemia type 1 (TT1) enabled preemptive treatment of patients, thereby significantly improving outcomes by preventing liver, kidney, and neurological issues. Treatment goals have shifted from emergency treatment to long‐term care. To evaluate the risk of developing complications with aging, due to TT1 itself or its treatment, long‐term follow‐up is essential. In 2014, an overview of TT1 management practices in Europe was published. Within the Metabolic European Reference Network's subnetwork on amino‐and‐organic acidurias (MetabERN‐AOA), we considered it important to give an update on current TT1 management practices in Europe. An online survey study was performed among members of the MetabERN‐AOA subnetwork, and participants of a workshop on TT1 at the European Metabolic Group Meeting of Nutricia. Findings were compared to existing data from the aforementioned publication from 2014 and previously published recommendations. Thirty‐two centers (16 European countries) completed the survey. Both consistencies and inconsistencies in TT1 management were seen. Inconsistencies were observed in the frequency and methods of follow‐up, dosing of NTBC, and target ranges of biochemical markers. Compared to 2014, key differences included an increased number of patients detected by newborn screening, lower NTBC dosing, and a shift from interest in mainly hepatic to hepatic and neurocognitive outcomes. These results align with trends seen in TT1 recommendations over the years. In addition to numerous consistencies, many aspects in TT1 management still differ widely across Europe, suggesting the need for uniform guidance in clinical management beyond existing recommendations.

Lymph node metastasis is crucial for esophageal squamous cell carcinoma (ESCC) malignancy. However, the molecular drivers and related mechanisms of lymph node metastasis in ESCC cells are unclear. In the present study, we found that the tyrosine kinase complex-focal adhesion kinase (FAK)/Src family kinase (SFK) axis specifically contributes to metabolic reprogramming by inducing the phosphorylation of ATP-citrate synthase (ACLY) Tyr542, Tyr652, and fructose-bisphosphate aldolase A (ALDOA) Tyr174, Tyr302, or Tyr328 sites in both primary and metastatic ESCC cells. Mechanistically, activated ACLY and ALDOA and their metabolites drive a transcriptional program in primary tumors that induces cyclin-dependent kinase 7/9 (CDK7/9) complex-mediated expression of DNA replication- and cell proliferation-related molecules. This process functions as an enabler of tumor malignancy. In metastatic tumor cells, metabolic enzymes and their products facilitate the transcriptional activity of Yamanaka factors to induce the activation of downstream plasticity-related molecules, fueling ESCC cell survival within metastatic lymph nodes. FAK/SFK axis-controlled ACLY and ALDOA tyrosine phosphorylation and downstream transcription factors and effectors in primary and metastatic ESCC cells are strongly associated with poor patient outcomes. We discovered a lead compound, quercetagitrin, that inhibits the phosphorylation of ALDOA at Tyr174, 302, and 328. Moreover, it has been shown to have antitumor effects alone or in combination with FAK/SFK inhibitors both in vivo and in vitro. The inhibition of tyrosine kinase-regulated metabolic enzyme activities and related signaling networks may be a potential strategy for the treatment and diagnosis of metastatic ESCC.

Integrated transcriptome and metabolome analyses reveal regulatory mechanisms governing carbohydrate biosynthesis in Panax ginseng.

Jiangtang Tiaozhi formula ameliorates MASLD by regulating liver ABCD2/PEX2/ATGL axis-mediated fatty acid metabolic reprogramming.

The Gα subunit RGA1, a crucial component of heterotrimeric G proteins, has been well-documented to enhance drought resistance in rice seedlings. However, its role during the reproductive stages has remained unexplored. This study aimed to investigate the function of RGA1 in mitigating drought-induced defects in anther and pollen development during pollen mother cell meiosis with Zhonghua 11 (WT), a Gα-deficient mutant (d1), and an RGA1-overexpressing line (OE-1). Under severe drought stress, the three genotypes exhibited significantly decreased spikelet fertility, kernel weight, and grain yield. Concurrently, decreased pollen viability, photosynthetic efficiency, and plant water content were observed, while levels of hydrogen peroxide and malondialdehyde were elevated. Notably, the d1 mutants showed the strongest drought resistance by exhibiting the least physiological disturbances, outperforming both the WT and OE-1 lines. Compared with the d1 mutant, the anthers of drought-stressed WT and OE-1 lines showed significantly more pronounced decreases in carbohydrate contents, ATP levels, ATPase activity, energy charge, and indole acetic acid (IAA) levels. These results demonstrate that the deficiency of RGA1 enhances carbohydrate and energy metabolism, as well as the IAA levels, in anther tissues under drought stress. This enhancement leads to an improvement in the antioxidant capacity of rice plants to suppress the accumulation of peroxides, which ultimately alleviates drought-induced pollen sterility. Findings of this study indicate that RGA1 modulates drought resilience by coordinating hormones, sugars, and energy metabolism.

Integrating widely targeted metabolomics and network pharmacology to provide insights into the mechanism of nutrition changes in walnut kernel under different drying methods.

Adding value to botanical resources: Metabolic network analysis along with high-resolution bioassays screening and UHPLC-qToF-high-resolution MS/MS profiling detail the pharmacological potential of underexplored Latin-American plants.

Application of nanopore long-read sequencing and metabolomics in an in vitro dynamic intestinal digestion model: A genome-centric metatranscriptomic approach to investigating microbial TMA and SCFA metabolism.

ε-Poly-lysine (ε-PL) is a naturally occurring antimicrobial polypeptide that has been approved as a food preservative in several major global markets, including Japan, China, and the United States, where it is classified as Generally Recognized as Safe (GRAS). It exhibits efficacy against Gram-positive and select Gram-negative bacteria, indicating its broad potential for application in both industrial and medical sectors. The mature fermentation process of Streptomyces albulus has established it as the primary production strain for ε-PL. This article provides a comprehensive overview of the biosynthetic and antibacterial mechanisms of ε-PL and reviews the strategies for strain selection and breeding aimed at developing high-yield ε-PL-producing strains. Furthermore, it examines approaches to enhance ε-PL production through pathway-specific regulation and global metabolic engineering, while also identifying future research directions. This review aims to serve as a theoretical reference for future researchers focusing on high-yield strain breeding and metabolic engineering strategies to optimize ε-PL production. SUMMARY: The biosynthesis and antimicrobial mechanism of ε-PL are described, along with strategies for the selection of high-yielding strains. Regulatory mechanisms within the complex biosynthetic metabolism network are revealed. Strategies to improve the production of ε-PL through pathway-specific and global regulation are discussed.

In this study, we used stable isotope labeling coupled with reversed-phase HPLC-MS to annotate the origin of metabolite features in Arabidopsis (Arabidopsis thaliana) (Columbia-0) seedling rosettes and stems. Using this strategy, a total of 1,240 metabolite features were shown to be derived from 15 amino acids, and these represented 10% to 30% of the total ion counts detected by untargeted LC-MS. The amino acid-derived metabolomes (AADMs) of rosettes and stems exhibited differing patterns of accumulation. Precursor-of-origin annotations (POA) revealed that some metabolites were generated solely from individual amino acids, whereas others were derived from multiple sources. Amino acid feeding altered the abundance of their corresponding AADMs as well as the levels of features derived from other amino acids. These data suggest that the accumulation of amino acid-derived features (AADFs) is restricted by availability of their amino acid precursors and that perturbation of amino acid metabolic networks can lead to long distance changes in end-product accumulation. The alignment of annotated AADFs with features from a previous metabolic genome-wide association study (mGWAS) led to the identification of 87,820 and 61,618 metabolite feature-single nucleotide polymorphism (SNP) associations (P < 10-4) in leaves and stems, respectively. Genes associated with AADF accumulation, including METHYLTHIOALKYLMALATE SYNTHASE 1 (MAM1) and ᴅ-AMINO ACID RACEMASE 1 (DAAR1), were retrieved from this analysis, demonstrating that the integration of isotope labeling and mGWAS can contribute to the identification of genes involved in plant metabolite accumulation.