Role In Metabolism Research Articles

SIRT2-mediated deacetylation of ACLY promotes the progression of oesophageal squamous cell carcinoma.

ATP citrate lyase (ACLY), as a key enzyme in lipid metabolism, plays an important role in energy metabolism and lipid biosynthesis of a variety of tumours. Many studies have shown that ACLY is highly expressed in various tumours, and its pharmacological or gene inhibition significantly inhibits tumour growth and progression. However, the roles of ACLY in oesophageal squamous cell carcinoma (ESCC) remain unclear. Here, our data showed that ACLY inhibitor significantly attenuated cell proliferation, migration, invasion and lipid synthesis in different ESCC cell lines, whereas the proliferation, migration, invasion and lipid synthesis of ESCC cells were enhanced after ACLY overexpression. Furthermore, ACLY inhibitor dramatically suppressed tumour growth and lipid metabolism in ESCC cells xenografted tumour model, whereas ACLY overexpression displayed the opposite effect. Mechanistically, ACLY protein harboured acetylated modification and interacted with SIRT2 protein in ESCC cells. The SIRT2 inhibitor AGK2 significantly increased the acetylation level of ACLY protein and inhibited the proliferation and migration of ESCC cells, while overexpression of ACLY partially reversed the inhibitory effect of AGK2 on ESCC cells. Overall, these results suggest that targeting the SIRT2/ACLY signalling axis may be a potential therapeutic strategy for ESCC patients.

Mutation in Arabidopsis mitochondrial Pentatricopeptide repeat 40 gene affects tolerance to water deficit

Main ConclusionThe Arabidopsis Pentatricopeptide repeat 40 (PPR40) insertion mutants have increased tolerance to water deficit compared to wild-type plants. Tolerance is likely the consequence of ABA hypersensitivity of the mutants.Plant growth and development depend on multiple environmental factors whose alterations can disrupt plant homeostasis and trigger complex molecular and physiological responses. Water deficit is one of the factors which can seriously restrict plant growth and viability. Mitochondria play an important role in cellular metabolism, energy production, and redox homeostasis. During drought and salinity stress, mitochondrial dysfunction can lead to ROS overproduction and oxidative stress, affecting plant growth and survival. Alternative oxidases (AOXs) and stabilization of mitochondrial electron transport chain help mitigate ROS damage. The mitochondrial Pentatricopeptide repeat 40 (PPR40) protein was implicated in stress regulation as ppr40 mutants were found to be hypersensitive to ABA and high salinity during germination. This study investigated the tolerance of the knockout ppr40-1 and knockdown ppr40-2 mutants to water deprivation. Our results show that these mutants display an enhanced tolerance to water deficit. The mutants had higher relative water content, reduced level of oxidative damage, and better photosynthetic parameters in water-limited conditions compared to wild-type plants. ppr40 mutants had considerable differences in metabolic profiles and expression of a number of stress-related genes, suggesting important metabolic reprogramming. Tolerance to water deficit was also manifested in higher survival rates and alleviated growth reduction when watering was suspended. Enhanced sensitivity to ABA and fast stomata closure was suggested to lead to improved capacity for water conservation in such environment. Overall, this study highlights the importance of mitochondrial functions and in particular PPR40 in plant responses to abiotic stress, particularly drought.

Atherosclerosis: an overview of mouse models and a detailed methodology to quantify lesions in the aortic root.

Cardiovascular disease, the primary cause of human mortality globally, is predominantly caused by a progressive disorder known as atherosclerosis. Atherosclerosis refers to the process of accumulation of cholesterol-enriched lipoproteins and the concomitant initiation of inflammatory processes in the arterial wall, including the recruitment of immune cells. This leads to the formation of atherosclerotic plaques, initially causing a thickening of the arterial wall and narrowing of arteries. However, as plaque formation progresses, atherosclerotic plaques may become unstable and rupture, leading to a blood clot that blocks the affected artery or travels through the blood to block blood flow elsewhere. In the early 1990s, emerging gene editing methods enabled the development of apolipoprotein E knockout (Apoe-/- ) and low-density lipoprotein receptor knockout (Ldlr-/- ) mice. These mice have been instrumental in unraveling the complex pathogenesis of atherosclerosis. Around the same time, human APOE*3-Leiden transgenic mice were generated, which were more recently cross-bred with human cholesteryl ester transfer protein (CETP) transgenic mice to generate APOE*3-Leiden.CETP mice. This model appears to closely mimic human lipoprotein metabolism and responds to classic lipid-lowering interventions due to an intact ApoE-LDLR pathway of lipoprotein remnant clearance. In this review, we describe the role of lipid metabolism and inflammation in atherosclerosis development and highlight the characteristics of the frequently used animal models to study atherosclerosis, with a focus on mouse models, discussing their advantages and limitations. Moreover, we present a detailed methodology to quantify atherosclerotic lesion area within the aortic root region of the murine heart, as well as details required for scoring atherosclerotic lesion severity based on guidelines of the American Heart Association adapted for mice.

Berberine: Pharmacological Features in Health, Disease and Aging.

Berberine is the main active compound of different herbs and is defined as an isoquinoline quaternary botanical alkaloid found in barks and roots of numerous plants. It exhibits a wide range of pharmacological effects, such as anti-obesity and antidiabetic effects. Berberine has antibacterial activity against a variety of microbiota, including many bacterial species, protozoa, plasmodia, fungi, and trypanosomes. This review describes the role of berberine and its metabolic effects. It also discusses how it plays a role in glucose metabolism, fat metabolism, weight loss, how it modulates the gut microbiota, and what are its antimicrobial properties along with its potential side effects with maximal tolerable dosage. Representative studies were considered and analyzed from different scientific databases, including PubMed and Web of Science, for the years 1982-2022. Literature analysis shows that berberine affects many biochemical and pharmacological pathways that theoretically yield a positive effect on health and disease. Berberine exhibits neuroprotective properties in various neurodegenerative and neuropsychological ailments. Despite its low bioavailability after oral administration, berberine is a promising tool for several disorders. A possible hypothesis would be the modulation of the gut microbiome. While the evidence concerning the aging process in humans is more limited, preliminary studies have shown positive effects in several models. Berberine could serve as a potential candidate for the treatment of several diseases. Previous literature has provided a basis for scientists to establish clinical trials in humans. However, for obesity, the evidence appears to be sufficient for hands-on use.

Novel insights into the synergetic degradation of pyrene by microbial communities from mangroves in China

Pyrene is a high molecular weight polycyclic aromatic hydrocarbon (HMW-PAHs). It is a ubiquitous, persistent, and carcinogenic environmental contaminant that has raised concern worldwide. This research explored synergistic bacterial communities for efficient pyrene degradation in seven typical Southern China mangroves. The bacterial communities of seven typical mangroves were enriched by pyrene, and enriched bacterial communities showed an excellent pyrene degradation capacity of > 95% (except for HK mangrove and ZJ mangrove). Devosia, Hyphomicrobium, Flavobacterium, Marinobacter, Algoriphahus, and Youhaiella all have significant positive correlations with pyrene (R>0, p < 0.05) by 16SrRNA gene sequencing and metagenomics analysis, indicated that these genera play a vital role in pyrene metabolism. Meanwhile, the functional genes were involved in pyrene degradation that was enriched in the bacterial communities, including the genes of nagAa, ndoR, pcaG, etc. Furthermore, the analyses of functional genes and binning genomes demonstrated that some bacterial communities as a unique teamwork to cooperatively participate in pyrene degradation. Interestingly, the genes related to biogeochemical cycles were enriched, such as narG , soxA, and cyxJ, suggested that bacterial communities were also helpful in maintaining the stability of the ecological environment. In addition, some novel species with pyrene-degradation potential were identified in the pyrene-degrading bacterial communities, which can enrich the resource pool of pyrene-degrading strains. Overall, this study will help develop further research strategies for pollutant removal.

SULTR2;1 Adjusts the Bolting Timing by Transporting Sulfate from Rosette Leaves to the Primary Stem.

Sulfur (S) is an essential macronutrient for plant growth and metabolism. SULTR2;1 is a low-affinity sulfate transporter facilitating the long-distance transport of sulfate in Arabidopsis. The physiological function of SULTR2;1 in the plant life cycle still needs to be determined. Therefore, we analyzed the sulfate transport, S-containing metabolite accumulation and plant growth using Arabidopsis SULTR2;1 disruption lines, sultr2;1-1 and sultr2;1-2, from seedling to mature growth stages to clarify the metabolic and physiological roles of SULTR2;1. We observed that sulfate distribution to the stems was affected in sultr2;1 mutants, resulting in decreased levels of sulfate, cysteine, glutathione (GSH) and total S in the stems, flowers and siliques; however, the GSH levels increased in the rosette leaves. This suggested the essential role of SULTR2;1 in sulfate transport from rosette leaves to the primary stem. In addition, sultr2;1 mutants unexpectedly bolted earlier than the wild-type without affecting the plant biomass. Correlation between GSH levels in rosette leaves and the bolting timing suggested that the rosette leaf GSH levels or limited sulfate transport to the early stem can trigger bolting. Overall, this study demonstrated the critical roles of SULTR2;1 in maintaining the S metabolite levels in the aerial part and transitioning from the vegetative to the reproductive growth phase.

Investigating the alterations of endocannabinoidome signaling in the human small intestine in the context of obesity and type 2 diabetes

BackgroundHuman studies have linked obesity-related diseases, such as type-2 diabetes (T2D), to the modulation of endocannabinoid signaling. Cannabinoid CB1 and CB2 receptor activation by the endocannabinoids (eCBs) 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine (AEA), both derived from arachidonic acid, play a role in homeostatic regulation. Other long chain fatty acid-derived endocannabinoid-like molecules have extended the metabolic role of this signaling system through other receptors. In this study, we aimed to assess in depth the interactions between the circulating and intestinal tone of this extended eCB system, or endocannabinoidome (eCBome), and their involvement in the pathogenesis of diabetes. MethodsPlasma and ileum samples were collected from subjects with obesity and harboring diverse degrees of insulin resistance or T2D, who underwent bariatric surgery. The levels of eCBome mediators and their congeners were then assessed by liquid chromatography coupled to tandem mass spectrometry, while gene expression was screened with qPCR arrays. FindingsIntestinal and circulating levels of eCBome mediators were higher in subjects with T2D. We found an inverse correlation between the intestinal and circulating levels of monoacylglycerols (MAGs). Additionally, we identified genes known to be implicated in both lipid metabolism and intestinal function that are altered by the context of obesity and glucose homeostasis. InterpretationAlthough the impact of glucose metabolism on the eCBome remains poorly understood in subjects with advanced obesity state, our results suggest a strong causative link between altered glucose homeostasis and eCBome signaling in the intestine and the circulation.

Protein lipidation in cancer: mechanisms, dysregulation and emerging drug targets.

Protein lipidation describes a diverse class of post-translational modifications (PTMs) that is regulated by over 40 enzymes, targeting more than 1,000 substrates at over 3,000 sites. Lipidated proteins include more than 150 oncoproteins, including mediators of cancer initiation, progression and immunity, receptor kinases, transcription factors, G protein-coupled receptors and extracellular signalling proteins. Lipidation regulates the physical interactions of its protein substrates with cell membranes, regulating protein signalling and trafficking, and has a key role in metabolism and immunity. Targeting protein lipidation, therefore, offers a unique approach to modulate otherwise undruggable oncoproteins; however, the full spectrum of opportunities to target the dysregulation of these PTMs in cancer remains to be explored. This is attributable in part to the technological challenges of identifying the targets and the roles of protein lipidation. The early stage of drug discovery for many enzymes in the pathway contrasts with efforts for drugging similarly common PTMs such as phosphorylation and acetylation, which are routinely studied and targeted in relevant cancer contexts. Here, we review recent advances in identifying targetable protein lipidation pathways in cancer, the current state-of-the-art in drug discovery, and the status of ongoing clinical trials, which have the potential to deliver novel oncology therapeutics targeting protein lipidation.

Knockdown of ANGPTL4 inhibits adipogenesis of preadipocyte via autophagy.

It has been demonstrated that angiopoietin-like protein 4 (ANGPTL4) plays an important regulatory role in lipid metabolism and backfat deposition appears to vary in different pig breeds. However, the correlation between ANGPTL4 and backfat deposition have not been well characterized and the role of ANGPTL4 in regulating adipogenesis remains unclear. Therefore, this study aimed to investigate correlation between ANGPTL4 and backfat deposition and to explore the effects of ANGPTL4 on preadipocyte differentiation and the underlying mechanism. Our results showed that the backfat thickness and the ANGPTL4 gene expression of Laiwu pigs were significantly higher than those in DLY pigs and the ANGPTL4 gene expression was positively correlated with backfat thickness both in DLY pigs and Laiwu pigs. Moreover, an increase in ANGPTL4 expression and activation of autophagy were observed during the differentiation of stromal vascular fraction cells. In addition, knockdown of ANGPTL4 inhibited the differentiation of 3T3-L1 cells with decreased expression of LC3-II and ATG5 and increased expression of SQSTM1, suggesting the involvement of autophagy in ANGPTL4-mediated adipogenesis. In conclusion, these results suggested that ANGPTL4 is positively correlated with backfat deposition in pigs and knockdown of ANGPTL4 inhibits adipogenesis of preadipocyte via autophagy, providing new insights into the regulation of fat deposition and to improve the carcass quality and meat quality of porcine.

SDF-1 involvement in orthodontic tooth movement after tooth extraction

The stromal cell-derived factor 1 (SDF-1)/chemokine receptor type 4 (CXCR4) axis plays a key role in alveolar bone metabolism during orthodontic tooth movement (OTM). Herein, the effects of the SDF-1/CXCR4 axis on the regional acceleratory phenomenon (RAP) in OTM velocity and on changes in the surrounding periodontium after adjacent tooth extraction in rats were investigated. Six-week-old male Wistar/ST rats underwent left maxillary first molar (M1) extraction and mesial OTM of the left maxillary second molar (M2) with a 10-g force closed-coil spring. Phosphate-buffered saline, immunoglobulin G (IgG) isotype control antibody, or anti-SDF-1 neutralizing monoclonal antibody were injected at the M1 and M2 interproximal areas (10 μg/0.1 mL) for the first three days. Analyses were performed after 1, 3, and 7 days (n = 7). The results demonstrated a significant increase in SDF-1 expression from day 1, which was effectively blocked via anti-SDF-1 neutralizing monoclonal antibody injection. On day 3, the M2 OTM distance and the number of positively stained osteoclasts significantly reduced alongside a reduction in inflammatory markers in the experimental group. Our results demonstrated that serial local injection of the anti-SDF-1 neutralizing monoclonal antibody reduces M2 OTM, osteoclast accumulation, and localized inflammatory responses in an OTM model with tooth extraction-induced RAP.

Cryo-electron microscopy for GPCR research and drug discovery in endocrinology and metabolism.

G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors, with many GPCRs having crucial roles in endocrinology and metabolism. Cryogenic electron microscopy (cryo-EM) has revolutionized the field of structural biology, particularly regarding GPCRs, over the past decade. Since the first pair of GPCR structures resolved by cryo-EM were published in 2017, the number of GPCR structuresresolved by cryo-EM has surpassed the number resolved by X-ray crystallography by 30%, reaching >650, and the number has doubled every ~0.63 years for the past 6 years. At this pace, it is predicted that the structure of 90% of all human GPCRs will be completed within the next 5-7 years. This Review highlights the general structural features and principles that guide GPCR ligand recognition, receptor activation, Gprotein coupling, arrestin recruitment and regulation by GPCR kinases. The Review also highlights the diversity of GPCR allosteric binding sites and how allosteric ligands could dictate biased signalling that is selective for a G protein pathwayor an arrestin pathway. Finally, the authors use the examples of glycoprotein hormone receptors and glucagon-like peptide 1 receptor to illustrate the effect of cryo-EM on understanding GPCR biology in endocrinology and metabolism, as well as on GPCR-related endocrine diseases and drug discovery.

The central role of mitochondrial metabolism in hepatic steatosis

Mitochondria are present in all mammalian cells except matured red blood cells. Mitochondria consist of several metabolic pathways for glucose, fatty acids, amino acids, and bioenergetic pathways for ATP synthesis, membrane potential, and reactive oxygen production. In the liver, hepatic mitochondria play a key role in hepatic steatosis because mitochondrial metabolism produces acetyl-CoA which is the building block for synthesis of lipids and cholesterol. Mitochondria inner membrane is impermeable of metabolites, reducing equivalents, and small molecules such as phosphate, and sulfate. Thus, mitochondrial shuttles and carriers function as the routes of influx and efflux of these metabolites and molecules across the inner membrane. The signal regulation of these shuttles and mitochondrial enzymes could play a key role in coordinating the mitochondrial metabolism to adapt the cytosolic part of metabolic pathways in liver metabolic stress. Intriguingly, the interaction of mitochondria protein SH3 domain-binding protein 5 (SAB/SH3BP5) and c-Jun N-terminal kinase (JNK) was found as a pivotal role in sustained activation of JNK and phosphorylated-JNK (P-JNK) mediated activation of lipogenic pathway in nutritional excess. Knockout or knockdown of SAB prevented or reversed the hepatic steatosis, inflammation, and fibrosis, and improved metabolic intolerance and energy expenditure. Moreover, blocking the SAB peptide prevents palmitic acid-induced P-JNK interaction with SAB and inhibition of mitochondrial bioenergetics, implying the P-JNK effect on mitochondrial metabolism. This review focuses on the flow of mitochondrial metabolites in metabolic stress conditions and the contribution of mitochondria and mitochondrial stress signals in hepatic steatosis.

The effect of Vitamin D deficiency on the occurrence of enamel hypoplasia in babies: A review article

Background: Vitamin D is a steroid prohormone that can be obtained primarily from exposure to sunlight and can also be obtained from food or supplements. Vitamin D has an important role in various metabolisms and developments in the human body, including in the process of odontogenesis or tooth development. Vitamin D deficiency can be associated with various problems in the oral cavity, in this case it has the potential to trigger enamel hypoplasia. Enamel hypoplasia is a quantitative defect in enamel, which appears as pits, grooves, missing enamel or smaller teeth. This literature study will discuss the relationship between Vitamin D concentration and dental development in early childhood. Method: The method used is an article review that was conducted by analyzing various articles on related themes on virtual platforms such as PubMed, Google Scholar, ProQuest, and Science Direct. Results: Vitamin D significantly affects the development of teeth in fetuses to babies. Conclusion: Vitamin D plays an important role in various metabolisms and development of the human body. Vitamin D deficiency can cause developmental disorders and various diseases of the oral cavity such as enamel hypoplasia.

Verification of the analytical performance of the serum Folate assay on the Abbott Alinity ci®

In the evolving landscape of clinical diagnostics, the significance of folate takes center stage as precision and innovation shape advancements in analytical methodologies. Folate, a pivotal element in cellular metabolism, governs physiological processes and serves as an indicator for various medical conditions. This study employs the Chemiluminescent Microparticle Immunoassay (CMIA), known for its accuracy, to assess the reproducibility and repeatability of serum folate levels. Folate's role in cellular metabolism influences diverse physiological functions, making its precise quantification crucial for identifying and monitoring conditions such as folate deficiency. The CMIA method emerges as a robust approach, leveraging immunological specificity for high precision and reliability. Utilizing the Abbott Alinity ci® Analyzer, a technologically advanced clinical chemistry instrument, this study incorporates a systematic analytical method verification procedure. This involves quantification through a standardized protocol and a comparative analysis against criteria set by esteemed societies (RICOS and FSCB), ensuring comprehensive insights into analysis techniques. The reproducibility test, evaluating the impact of various factors on assay results, reveals low Coefficient of Variation (CV) values (CV1: 10.25%, CV2: 8.58%, CV3: 9.13%) across different levels. The results align with quality control limits, emphasizing the method's reliability. Repeatability assessment demonstrates exceptionally low CV values (CV1: 4.84%, CV2: 3.41%, CV3: 1.89%), highlighting the method's stability and precision under controlled conditions.

Development of a promising PPAR signaling pathway-related prognostic prediction model for hepatocellular carcinoma

The peroxisome proliferator-activated receptor (PPAR) signaling pathway plays a crucial role in systemic cell metabolism, energy homeostasis and immune response inhibition. However, its significance in hepatocellular carcinoma (HCC) has not been well documented. In our study, based on the RNA sequencing data of HCC, consensus clustering analyses were performed to identify PPAR signaling pathway-related molecular subtypes, each of which displaying varying survival probabilities and immune infiltration status. Following, a prognostic prediction model of HCC was developed by using the random survival forest method and Cox regression analysis. Significant difference in survival outcome, immune landscape, drug sensitivity and pathological features were observed between patients with different prognosis. Additionally, decision tree and nomogram models were adopted to optimize the prognostic prediction model. Furthermore, the robustness of the model was verified through single-cell RNA-sequencing data. Collectively, this study systematically elucidated that the PPAR signaling pathway-related prognostic model has good predictive efficacy for patients with HCC. These findings provide valuable insights for further research on personalized treatment approaches for HCC.

Multiomics Evaluation of Human iPSCs and iPSC-Derived Neurons.

Human induced pluripotent stem cells (iPSCs) can be differentiated into neurons, providing living human neurons to model brain diseases. However, it is unclear how different types of molecules work together to regulate stem cell and neuron biology in healthy and disease states. In this study, we conducted integrated proteomics, lipidomics, and metabolomics analyses with confident identification, accurate quantification, and reproducible measurements to compare the molecular profiles of human iPSCs and iPSC-derived neurons. Proteins, lipids, and metabolites related to mitosis, DNA replication, pluripotency, glycosphingolipids, and energy metabolism were highly enriched in iPSCs, whereas synaptic proteins, neurotransmitters, polyunsaturated fatty acids, cardiolipins, and axon guidance pathways were highly enriched in neurons. Mutations in the GRN gene lead to the deficiency of the progranulin (PGRN) protein, which has been associated with various neurodegenerative diseases. Using this multiomics platform, we evaluated the impact of PGRN deficiency on iPSCs and neurons at the whole-cell level. Proteomics, lipidomics, and metabolomics analyses implicated PGRN's roles in neuroinflammation, purine metabolism, and neurite outgrowth, revealing commonly altered pathways related to neuron projection, synaptic dysfunction, and brain metabolism. Multiomics data sets also pointed toward the same hypothesis that neurons seem to be more susceptible to PGRN loss compared to iPSCs, consistent with the neurological symptoms and cognitive impairment from patients carrying inherited GRN mutations.

Preventive Vitamin D Supplementation and Risk for COVID-19 Infection: A Systematic Review and Meta-Analysis.

Over the past few decades, vitamin D has been found to play a crucial role in bone homeostasis, muscle function, oncogenesis, immune response and metabolism. In the context of the COVID-19 pandemic, numerous researchers have tried to determine the role vitamin D might play in the immune response to the virus. The aim of this systematic review and meta-analysis is to demonstrate that preventive vitamin D supplementation can play a protective role in the incidence of COVID-19, mortality and admission to intensive care units (ICUs). A comprehensive search on the PubMed/MEDLINE, Scopus, Cochrane and Google Scholar databases was performed on 15 May 2023, and two of the authors independently screened the literature. As effect measures, we calculated the Odds Ratios with their corresponding 95% confidence intervals (ICs). The assessment of potential bias and the evaluation of study quality will be conducted independently by two researchers. Sixteen publications were selected for inclusion in the meta-analysis. Our findings indicate that vitamin D supplementation has a protective effect against the incidence of COVID-19 in RCT studies (OR 0.403, 95% IC 0.218, 0.747), in the incidence of COVID-19 in analytical studies (OR = 0.592, 95% IC 0.476-0.736) and in ICU admission (OR 0.317, 95% IC 0.147-0.680). Subsequent analyses were conducted by type of subject treated (patient/healthcare workers) and type of supplementation (vitamin D vs. placebo/no treatment or high dose vs. low dose). Our meta-analysis suggests a definitive and significant association between the protective role of vitamin D and COVID-19 incidence and ICU admission.

Metabolomics combined with physiology and transcriptomics reveal how Nicotiana tabacum leaves respond to cold stress

Low temperature-induced cold stress is a major threat to plant growth, development and distribution. Unraveling the responses of temperature-sensitive crops to cold stress and the mechanisms of cold acclimation are critical for food demand. In this study, combined physiological, transcriptomic, and metabolomic analyses were conducted on Nicotiana tabacum suffering short-term 4 °C cold stress. Our results showed that cold stress destroyed cellular membrane stability, decreased the chlorophyll (Chl) and carotenoid contents, and closed stomata, resulting in lipid peroxidation and photosynthesis restriction. Chl fluorescence measurements revealed that primary photochemistry, photoelectrochemical quenching and photosynthetic electron transport in Nicotiana tabacum leaves were seriously suppressed upon exposer to cold stress. Enzymatic and nonenzymatic antioxidants, including superoxide dismutase, catalase, peroxidase, reduced glutathione, proline, and soluble sugar, were all profoundly increased to trigger the cold acclimation defense against oxidative damage. A total of 178 metabolites and 16,204 genes were differentially expressed in cold-stressed Nicotiana tabacum leaves. MEturquoise and MEblue modules identified by WGCNA were highly correlated with physiological indices, and the corresponding hub genes were significantly enriched in pathways related to photosynthesis - antenna proteins and flavonoid biosynthesis. Untargeted metabolomic analysis identified specific metabolites, including sucrose, phenylalanine, glutamine, glutamate, and proline, that enhance plant cold acclimation. Combined transcriptomics and metabolomic analysis highlight the vital roles of carbohydrate and amino acid metabolism in enhancing the cold tolerance of Nicotiana tabacum. Our comprehensive investigation provides novel insights for efforts to alleviate low temperature-induced oxidative damage to Nicotiana tabacum plants and proposes a breeding target for cold stress-tolerant cultivars.

Aging-Induced Reduction in Safflower Seed Germination via Impaired Energy Metabolism and Genetic Integrity Is Partially Restored by Sucrose and DA-6 Treatment.

Seed storage underpins global agriculture and the seed trade and revealing the mechanisms of seed aging is essential for enhancing seed longevity management. Safflower is a multipurpose oil crop, rich in unsaturated fatty acids that are at high risk of peroxidation as a contributory factor to seed aging. However, the molecular mechanisms responsible for safflower seed viability loss are not yet elucidated. We used controlled deterioration (CDT) conditions of 60% relative humidity and 50 °C to reduce germination in freshly harvested safflower seeds and analyzed aged seeds using biochemical and molecular techniques. While seed malondialdehyde (MDA) and fatty acid content increased significantly during CDT, catalase activity and soluble sugar content decreased. KEGG analysis of gene function and qPCR validation indicated that aging severely impaired several key functional and biosynthetic pathways including glycolysis, fatty acid metabolism, antioxidant activity, and DNA replication and repair. Furthermore, exogenous sucrose and diethyl aminoethyl hexanoate (DA-6) treatment partially promoted germination in aged seeds, further demonstrating the vital role of impaired sugar and fatty acid metabolism during the aging and recovery processes. We concluded that energy metabolism and genetic integrity are impaired during aging, which contributes to the loss of seed vigor. Such energy metabolic pathways as glycolysis, fatty acid degradation, and the tricarboxylic acid cycle (TCA) are impaired, especially fatty acids produced by the hydrolysis of triacylglycerols during aging, as they are not efficiently converted to sucrose via the glyoxylate cycle to provide energy supply for safflower seed germination and seedling growth. At the same time, the reduced capacity for nucleotide synthesis capacity and the deterioration of DNA repair ability further aggravate the damage to DNA, reducing seed vitality.

Dynamic changes and clinical value of lipocalin 2 in liver diseases caused by microbial infections.

Lipocalin 2 (LCN2) plays a pivotal role in iron metabolism, particularly in the context of microbial infection resistance (e.g., viruses, bacteria, parasites, etc.). LCN2 combats microbial infection by directly assisting the body in competing with microorganisms for iron, inducing immune cells to secrete various cytokines to enhance systemic immune responses, or recruiting neutrophils to infectious sites. The liver serves as the primary organ for LCN2 secretion during microbial infections. This review encapsulates recent advances in dynamic changes, clinical values, and the effects of LCN2 in infectious liver diseases caused by various microbial microorganisms.