Search Results (190)

Background: Soil heavy metal pollution by chromium (Cr) and copper (Cu) is a global environmental concern. Methods: This study evaluated Cr/Cu accumulation in Paulownia fortunei tissues and analyzed its root transcriptome under Cr and Cu stress to elucidate molecular response mechanisms. Results: Findings revealed significantly higher Cr and Cu accumulation capacity in roots compared to stems and leaves. Transcriptome sequencing identified 6017 and 2265 differentially expressed genes (DEGs) under Cr and Cu stress, respectively. These DEGs were primarily involved in redox reactions, stress responses, transcriptional regulation, transmembrane transport, and metabolism. Quantitative PCR of 20 selected genes validated dynamic expression changes under stress. Weighted Gene Co-expression Network Analysis (WGCNA) identified distinct co-expression modules associated with Cr and Cu. Hub gene analysis implicated Pfo_020668 and Pfo_019190 in Cr response, while Pfo_010312 and Pfo_000197 may enhance Cu tolerance via cell wall polysaccharide synthesis regulation. Pathways related to pyruvate metabolism and proteasome were significantly enriched under Cr stress, whereas amino acid metabolism pathways were prominent under Cu stress. Conclusions: Differentially expressed transporter genes suggest potential roles in heavy metal uptake and transport. This transcriptomic analysis provides novel insights into P. fortunei’s molecular responses to Cr and Cu stress, offering a foundation for utilizing this species in soil phytoremediation efforts. Full article

Background: Dietary consumption of insulinogenic amino acids (IAA) is known to contribute to the development of insulin resistance. It remains to be studied whether dietary IAA restriction improves glucose metabolism and insulin sensitivity and whether this improvement is related to alterations in glucose metabolism in peripheral tissues. The objective of this study was to examine the effect of IAA restriction on glucose metabolism in a piglet model. Methods: Following the acclimation period, thirty-two seven-day-old male piglets were randomly assigned into one of three groups for three weeks as follows (n = 10–11/group): (1) NR (control): basal diet without IAA restriction; (2) R50: basal diet with IAA restricted by 50%; (3) R75: basal diet with IAA restricted by 75%. IAA were alanine (Ala), arginine (Arg), isoleucine (Ile), leucine (Leu), lysine (Lys), threonine (Thr), phenylalanine (Phe), and valine (Val) as suggested by previous studies. Thermal images, body weight, and growth parameters were recorded weekly, oral glucose tolerance tests were performed on week 2 of the study, and blood and tissue samples were collected on week 3 after a meal test. Results: R75 improved glucose tolerance and, together with R50, reduced blood insulin concentration and homeostatic model assessment for insulin resistance (HOMA-IR) value, which is suggestive of improved insulin sensitivity following IAA restriction. R75 increased thermal radiation and decreased adipocyte number in white adipose tissue (WAT). R75 had a greater transcript of glucose transporter 1 (GLUT1), phosphofructokinase, liver type (PFKL), and pyruvate kinase, liver, and RBC (PKLR) in the liver and glucokinase (GCK) in WAT indicating a higher uptake of glucose in the liver and greater glycolysis in both liver and WAT. R75 increased the mRNA abundance of insulin receptor substrate 1 (IRS1) and protein kinase B (AKT1) in skeletal muscle suggestive of enhanced insulin signaling. Further, R75 had a higher mRNA of fibroblast growth factor 21 (FGF-21) in both the liver and hypothalamus and its upstream molecules such as activating transcription factor 4 (ATF4) and inhibin subunit beta E (INHBE) which may contribute to increased energy expenditure and improved glucose tolerance during IAA restriction. Conclusions: IAA restriction improves glucose tolerance and insulin sensitivity in piglets while not reducing body weight, likely through improved hepatic glycolysis and insulin signaling in skeletal muscle, and induced FGF-21 signaling in both the liver and hypothalamus. Full article

Appropriate fertilization depth promotes the absorption and transport of nutrients, crop growth and yield. However, little is known about whether deep fertilization improves crude protein synthesis and how to regulate it. A two-year field experiment was conducted with various fertilization depths: (1) conventional fertilization (CF), (2) fertilization application depth at 30 cm (DF), and (3) fertilizer average application at depths of 15 cm and 30 cm (AF). The fertilization rates under all treatments were 300 kg N ha⁻¹ nitrogen fertilizer (urea, 46% N), 150 kg P₂O₅ ha⁻¹ calcium superphosphate (16% P₂O₅), and 135 kg K₂O ha⁻¹ potassium sulfate (51% K₂O). The nitrogen/potassium (N/K) ratio, the activities of nitrate reductase [NR], glutamine synthetase [GS], and glutamic pyruvic transaminase [GPT], crude protein content in leaves, stems, and grains, as well as the relationships among the parameters were explored. The result showed that deep fertilization (DF) significantly improved the N/K ratio. NR activity in DF increased by 26.30%, 35.56%, and 57.30% in leaves, stems, and grains, respectively, when compared to conventional fertilization (CF), and by 54.22%, 43.27%, and 28.44% when compared to average fertilization (AF). GS activity in DF increased by 29.67%, 47.96%, and 47.46% in leaves, stems, and grains when compared to CF, and by 40.05%, 31.51%, and 40.62% when compared to AF. GPT activity in DF was significantly higher than CF and AF in grains, and differences between treatments were significant. Crude protein content was significantly correlated with NR and GS activities in leaves, GPT activity in stems, as well as GS and GPT activities in grains. The crude protein content of leaves and grains in DF was significantly higher than in CF and AF. In conclusion, DF significantly improved crude protein synthesis and increased the crude protein content of forage maize by increasing the whole plant N/K ratio, NR and GS activities in leaves, as well as GS and GPT activities in grains. It is a highly efficient cultivation technology that significantly improves the quality of forage maize. Full article

Waxy sorghum–soybean intercropping is a sustainable and intensive farming system in southwest China. However, there is limited knowledge about the effects of intercropped soybean combined with nitrogen application on nitrogen uptake and utilization in waxy sorghum. A two-year (2023 and 2024) field experiment was carried out using a randomized complete block design with three planting patterns and three nitrogen application rates to explore the responses of grain yield formation and nitrogen uptake, accumulation, transportation, metabolism physiology, and utilization of waxy sorghum for intercropped soybean combined with nitrogen application. Planting patterns included sole cropped waxy sorghum (SCW), sole cropped soybean (SCS), and waxy sorghum intercropped with soybean (WSI), and nitrogen application rates included zero nitrogen (N0), medium nitrogen (N1), and high nitrogen (N2). Results showed that the dry matter accumulation amount, nitrogen content, nitrogen accumulation amount, nitrogen transportation amount, nitrogen transportation rate, contribution rate of nitrogen transportation to grains, nitrogen metabolizing enzymes activities (including nitrate reductase, nitrite reductase, glutamine synthetase, glutamate synthetase, glutamate dehydrogenase, and glutamic-pyruvic transaminase), and active substances contents (including soluble sugar, soluble protein, and free amino acid) in various organs of waxy sorghum among planting patterns and nitrogen application rates were in the order of WSI > SCW and N1 > N2 > N0, respectively. In addition, the nitrogen uptake efficiency, nitrogen agronomy efficiency, nitrogen apparent efficiency, nitrogen recovery efficiency, nitrogen partial factor productivity, and nitrogen contribution rate of waxy sorghum among planting patterns and nitrogen application rates were in the sequence of WSI > SCW and N1 > N2, respectively. The changes in above traits resulted in the WSI-N1 treatment obtaining the highest grain yield (6020.66 kg ha⁻¹ in 2023 and 6159.81 kg ha⁻¹ in 2024), grain weight per spike (65.22 g in 2023 and 64.51 g in 2024), 1000-grain weight (23.14 g in 2023 and 23.18 g in 2024) of waxy sorghum, and land equivalent ratio (1.41 in 2023 and 1.44 in 2024). Overall, waxy sorghum intercropped with soybean combined with medium nitrogen application (220 kg ha⁻¹ for waxy sorghum and 18 kg ha⁻¹ for soybean) can help enhance the nitrogen uptake and utilization of waxy sorghum by improving nitrogen metabolizing enzymes’ activities and active substances’ contents, thereby promoting its productivity. Full article

Yaks are an important livestock species on the Tibetan Plateau, but traditional grazing practices cause a sharp drop in their weight during winter, leading to grassland degradation due to overgrazing. Although off-site fattening can improve performance and protect ecology, it often leads to a negative energy balance, liver metabolism disorders, and immune impairment due to stress. However, the effects of rumen-protected glucose (RPG) and rumen-protected taurine (RPT) on yak liver health are not yet clear. The purpose of this study was to evaluate the effects of dietary RPG and RPT levels on the growth performance, serum biochemical parameters, liver antioxidant capacity, and immunity of yaks. Twenty-eight healthy yaks weighing 170 ± 10.4 kg were randomly divided into four treatments: LGLT (RPG: 1%—low RPG [LG]; RPT: 5 g/d—low RPT [LT]), LGHT (RPG: 1%—low RPG [LG]; RPT: 20 g/d—high RPT [HT]), HGLT (RPG: 3%—high RPG [HG]; RPT: 5 g/d—low RPT [LT]), and HGHT (RPG: 3%—high RPG [HG]; RPT: 20 g/d—high RPT [HT]). The results showed that compared with the LTHT treatment group, the HGHT group upregulated the serum concentrations of glucose (p = 0.004) and Interleukin-10 (p = 0.03), the relative mRNA expression of small heterodimer partners (p = 0.01), and the sterol 12-alpha-hydroxylase (p < 0.001), while reducing the serum concentration of gamma-glutamyl transferase (p = 0.048). The serum concentration of hepatic protein carbonyl (p = 0.005) and malondialdehyde (p = 0.03) was lower in the LGHT and HGHT treatment groups than in the LGLT and HGLT groups. The relative mRNA expression of Toll-like receptor 4 (p = 0.02), Interleukin-8 (p < 0.01), and Interleukin-1β (p < 0.01) was lower in the LGHT and HGHT groups than in the LGLT and HGLT groups. Tumor necrosis factor expression was lower (p = 0.04) and glucose transporter 2 expression was higher (p < 0.01) in the HGHT group compared to other treatment groups. The expression of glucokinase, glycogen synthase, pyruvate kinase, and farnesoid X receptor was higher in the HGLT treatment group than in other treatments (p < 0.01). In conclusion, dietary supplementation with 3% PRG and 5 g/d PRT can enhance liver antioxidant capacity and immune function, reduce lipid peroxidation, and promote glucose and bile acid metabolism in yaks. Full article

Smoltification is stressful for salmonids, and cortisol is one of the central endocrine regulators for seawater adaptation. It has been established that cortisol plays both mineralocorticoid and glucocorticoid functions by MR and GR, respectively, since the aldosterone hormone is absent. Recently, investigations have proposed that the 11-deoxycorticosterone (DOC) mineralocorticoid precursor might support cortisol effects, but this mechanism remains unclear. Hence, we assessed the early effects of DOC on rainbow trout pre-smolts, the key smoltification stage, via metabolic and transcriptomic approaches. Thirty-six juveniles (~120 g) were treated for 3 h with DOC (1 mg/kg) and/or mineralocorticoid (eplerenone) or glucocorticoid (mifepristone) receptor antagonists (n = 6 for each group). DOC decreased plasma glucose and pyruvate and increased phosphate and liver glycogen. DOC also downregulated carbohydrate metabolism-related genes in the liver. Finally, gill RNA-seq analysis presented 1660 differentially expressed transcripts in DOC versus vehicle, 1022 for eplerenone + DOC versus DOC and 3324 for mifepristone + DOC versus DOC. The enrichment analysis mainly revealed the upregulation of ion transmembrane transport and carbohydrate metabolism and the downregulation of stress and innate immune responses. This suggests a significant role of DOC in liver carbohydrate metabolism and gill osmoregulation of pre-smolts through both receptors. Hence, this could contribute to improving animal welfare monitoring during smoltification by featuring novel and potential biomarkers. Full article

The pathogen Alternaria alternata infects a variety of plants and crops, notably poplars, and results in large financial losses. Using twelve chemical fungicides for fungicide sensitivity tests (FSTs) on A. alternata, the result showed that prochloraz (PCZ), mancozeb (MZ), and fludioxonil (FLU) have potent inhibitory effects against the pathogen through different mechanisms. To investigate how the pathogen responded to fungicide-induced stress, transcriptome and physiological investigations were carried out after treatments with three fungicides at their corresponding 50% effective concentration (EC₅₀) doses. The MZ treatment produced a distinct genetic response; FLU treatment produced the greatest number of differentially expressed genes (DEGs), followed by PCZ. DEGs from FLU treatment were mostly engaged in ribosome biosynthesis, those from MZ treatment in lipid and carbohydrate metabolism, and those from PCZ treatment in carbohydrate metabolism, according to Gene Ontology (GO) analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that FLU and PCZ treatments were associated with ribosome biogenesis, whereas MZ treatment was linked to the pyruvate metabolic pathway. Collinear trend analysis indicates that MZ exhibits a unique pattern, with FLU treatment causing the most significant overexpression of genes, followed by PCZ. The six categories of 88 elevated DEGs associated with fungal resistance include tyrosinase, ATP-binding cassette (ABC) transporters, major facilitator superfamily (MFS) transporters, antioxidant and cellular resilience genes, as well as genes involved in cell wall and membrane biosynthesis. Notably, the pathways involved in the synthesis of melanin and ergosterol exhibited the strongest response to FLU. The results of a correlation analysis between physiological indices and resistance-related genes indicated that melanin content, malondialdehyde (MDA) content, and tyrosinase activity were positively correlated with the majority of resistance-related DEGs, whereas soluble protein content, superoxide dismutase (SOD) activity, and catalase (CAT) activity were negatively correlated, which is consistent with the observed trends in the measured physiological indicators. Taken together, this study provides a theoretical basis for developing more effective fungicides and chemical control strategies against A. alternata. Full article

The present study aimed to investigate the effects of exogenous carnitine treatments on maize seed germination by stimulating lipid metabolism and regulating the mitochondrial respiratory pathway. Maize seeds were grown as control, 5, 7.5, and 10 μM carnitine treatment groups in a germination chamber at 25 °C under dark conditions for 5 d. It was determined that carnitine treatments increased the germination rate (GR), germination index (GI), germination potential (GP), vigor index (VI), root and hypocotyl length, fresh weight (FW), and content of total soluble protein but decreased the total carbohydrate content. It was also found that it increased the activities of α-amylase, isocitrate lyase (ICL), and malate synthase (MS) enzymes, which are critical in the germination process, and upregulated the expression of ICL and MS genes. To clarify the potential of carnitine treatments to promote the participation of lipids in respiration in roots and hypocotyls, lipase, carnitine acyltransferases (CATI and CATII), and citrate synthase (CS) enzyme activities were examined, and significant increases in these activities were detected. It was also found that gene levels of respiratory enzymes cytochrome oxidase (COX), pyruvate dehydrogenase (PDH), and Atp synthase, lipase, and CS proteins were upregulated by carnitine treatment. In support of the enzyme and gene change findings, significant changes were determined in fatty acid contents, free carnitine, and long-chain acylcarnitine levels in seeds, roots, and hypocotyls depending on carnitine application. In roots and hypocotyls, carnitine treatments significantly increased glutamine synthase (GS) and glutamate dehydrogenase (NADH-GDH) activities and gene expression levels, which are closely related to the tricarboxylic acid cycle (TCA). It was also noted that all proteins analyzed at the gene expression level were upregulated by carnitine applications in seeds. In addition, significant increases were recorded in antioxidant enzyme ascorbate peroxidase (APX) and superoxide dismutase (SOD) activities and total ascorbate (AsA) and glutathione (GSH) contents in roots and hypocotyls, while decreases were determined in guaiacol peroxidase (GPX) and catalase activities. Significant changes were recorded in all parameters examined, especially with 7.5 µM carnitine application. The findings suggest that carnitine may promote the transport of fatty acids to mitochondrial respiration by accelerating lipid catabolism in five-day-old maize and contribute to seed germination and growth and development processes by activating other metabolic pathways associated with respiration in this process. Full article

Soda lakes are extreme saline–alkaline environments that harbor metabolically versatile microbial communities with significant biotechnological potential. This study employed shotgun metagenomics (NovaSeq PE150) to investigate the functional diversity and metabolic potential of microbial communities in Ethiopia’s Chitu and Shala Lakes. An analysis of gene content revealed 554,609 and 525,097 unique genes in Chitu and Shala, respectively, in addition to a substantial fraction (1,253,334 genes) shared between the two, underscoring significant functional overlap. Taxonomic analysis revealed a diverse phylogenetic composition, with bacteria (89% in Chitu Lake, 92% in Shala Lake) and archaea (4% in Chitu Lake, 0.8% in Shala Lake) as the dominant domains, alongside eukaryotes and viruses. Predominant bacterial phyla included Pseudomonadota, Actinomycetota, and Gemmatimonadota, while Euryarchaeota and Nitrososphaerota were prominent among archaea. Key genera identified in both lakes were Nitriliruptor, Halomonas, Wenzhouxiangella, Thioalkalivibrio, Aliidiomarina, Aquisalimonas, and Alkalicoccus. Functional annotation using the KEGG, eggNOG, and CAZy databases revealed that the identified unigenes were associated with various functions. Notably, genes related to amino acid, carbohydrate, and energy metabolism (KEGG levels 1–2) were predominant, indicating that conserved core metabolic functions are essential for microbial survival in extreme conditions. Higher-level pathways included quorum sensing, two-component signal transduction, and ABC transporters (KEGG level 3), facilitating environmental adaptation, stress response, and nutrient acquisition. The eggNOG annotation revealed that 13% of identified genes remain uncharacterized, representing a vast untapped reservoir of novel enzymes and biochemical pathways with potential applications in biofuels, bioremediation, and synthetic biology. This study identified 375 unique metabolic pathways, including those involved in pyruvate metabolism, xenobiotic degradation, lipid metabolism, and oxidative stress resistance, underscoring the microbial communities’ ability to thrive under fluctuating salinity and alkalinity. The presence of carbohydrate-active enzymes (CAZymes), such as glycoside hydrolases, polysaccharide lyases, and oxidoreductases, highlights their role in biomass degradation and carbon cycling. Enzymes such as alkaline proteases (Apr), lipases (Lip), and cellulases further support the lakes’ potential as sources of extremophilic biocatalysts. These findings position soda lakes as reservoirs of microbial innovation for extremophile biotechnology. Future research on unannotated genes and enzyme optimization promises sustainable solutions in bioenergy, agriculture, and environmental management. Full article

Drug-resistant epilepsy (DRE) affects 20–30% of patients with epilepsy who fail to achieve seizure control with antiseizure medications, posing a significant therapeutic challenge. In this narrative review, we examine the clinical efficacy and safety of the classic ketogenic diet (cKD) and its variants, including the modified Atkins diet (MAD), medium-chain triglyceride diet (MCTD), and low glycemic index treatment (LGIT), in patients with genetically confirmed drug-resistant epilepsy. These diets induce a metabolic shift from glucose to ketones, enhance mitochondrial function, modulate neurotransmitter balance, and exert anti-inflammatory effects. However, genetic factors strongly influence the efficacy and safety of the cKD, with absolute indications including glucose transporter type 1 deficiency syndrome (GLUT1DS) and pyruvate dehydrogenase complex deficiency (PDCD). Preferred adjunctive applications of the KD include genetic epilepsies, such as SCN1A-related Dravet syndrome, TSC1/TSC2-related tuberous sclerosis complex, and UBE3A-related Angelman syndrome. However, because of the risk of metabolic decompensation, the cKD is contraindicated in patients with pathogenic variants of pyruvate carboxylase and SLC22A5. Recent advancements in precision medicine suggest that genetic and microbiome profiling may refine patient selection and optimize KD-based dietary interventions. Genome-wide association studies and multiomics approaches have identified key metabolic pathways influencing the response to the cKD, and these pave the way for individualized treatment strategies. Future research should integrate genomic, metabolomic, and microbiome data to develop biomarker-driven dietary protocols with improved efficacy and safety. As dietary therapies continue to evolve, a personalized medical approach is essential to maximize their clinical utility for genetic epilepsy and refractory epilepsy syndromes. Full article

The appearance of cancer progresses through a multistep process that includes genetic, epigenetic, mutational, inflammatory and metabolic disturbances to signaling pathways within an organ. The combined influence of these changes will dictate the growth properties of the cells; the direction of further malignancy depends on the severity of these “disturbances”. The molecular mechanisms driving abnormal inflammation and metabolism are beginning to be identified and, in some cases, are quite prominent in pre-condition states of cancer and are significant drivers of the malignant phenotype. As such, utilizing signaling pathways linked to inflammation and metabolism as biomarkers of cancer is an emerging method and includes pathways beyond those well characterized to drive metabolism or inflammation. In this review, we will discuss several emerging elements influencing proliferation, inflammation and metabolism that may play a part as drivers of the cancer phenotype. These include AMPK and leptin (linked to metabolism), NOD2/RIPK2, TAK1 (linked to inflammation), lactate and pyruvate transporters (monocarboxylate transporter [MCT], linked to mitochondrial biogenesis and metabolism) and RASSF1A (linked to proliferation, cell death, cell cycle control, inflammation and epigenetics). We speculate that the aforementioned elements are important drivers of carcinogenesis that should be collectively referenced as being involved in “ImmunoMET Oncogenesis”, a new tripartite description of the role of elements in driving cancer. This term would suggest that for a better understanding of cancer, we need to understand how proliferation, inflammation and metabolic pathways are impacted and how they influence classical drivers of malignant transformation in order to drive ImmunoMET oncogenesis and the malignant state. Full article

Background: Early and accurate grading of renal cell carcinoma (RCC) improves patient risk stratification and has implications for clinical management and mortality. However, current diagnostic approaches using imaging and renal mass biopsy have limited specificity and may lead to undergrading. Methods: This study explored the use of hyperpolarised [1-¹³C]pyruvate MRI (HP ¹³C-MRI) to identify the most aggressive areas within the tumour of patients with clear cell renal cell carcinoma (ccRCC) as a method to guide biopsy targeting and to reduce undergrading. Six patients with ccRCC underwent presurgical HP ¹³C-MRI and conventional contrast-enhanced MRI. From the imaging data, three k-means clusters were computed by combining the k_PL as a marker of metabolic activity, and the ¹³C-pyruvate signal-to-noise ratio (SNR_Pyr) as a perfusion surrogate. The combined clusters were compared to those derived from individual parameters and to those derived from the percentage of enhancement on the nephrographic phase (%NG). The diagnostic performance of each cluster was assessed based on its ability to predict the highest histological tumour grade in postsurgical tissue samples. The postsurgical tissue samples underwent immunohistochemical staining for the pyruvate transporter (monocarboxylate transporter 1, MCT1), as well as RNA and whole-exome sequencing. Results: The clustering approach combining SNR_Pyr and k_PL demonstrated the best performance for predicting the highest tumour grade: specificity 85%; sensitivity 64%; positive predictive value 82%; and negative predictive value 68%. Epithelial MCT1 was identified as the major determinant of the HP ¹³C-MRI signal. The perfusion/metabolism mismatch cluster showed an increased expression of metabolic genes and markers of aggressiveness. Conclusions: This study demonstrates the potential of using HP ¹³C-MRI-derived metabolic clusters to identify intratumoral variations in tumour grade with high specificity. This work supports the use of metabolic imaging to guide biopsies to the most aggressive tumour regions and could potentially reduce sampling error. Full article

Interactions between carbon and nitrogen metabolism are essential for balancing source–sink dynamics in plants. Frequent cold stress disrupts these metabolic processes in rice and reduces grain yield. Two rice cultivars (DN428: cold-tolerant; SJ10: cold-sensitive) were subjected to 19 °C low-temperature stress at full-heading for varying lengths of time to analyze the effects on leaf and grain metabolism. The objective was to track carbon–nitrogen flow and identify factors affecting grain yield. Low-temperature stress significantly reduced the activity of nitrate reductase (NR), glutamine synthetase (GS), glutamate synthase (GOGAT), glutamate dehydrogenase (GDH), glutamic oxaloacetic transaminase (GOT), and glutamic pyruvic transaminase (GPT), in functional leaves compared to the control. This reduction decreased nitrogen accumulation, inhibited chlorophyll synthesis, and slowed photosynthesis. To preserve intracellular osmotic balance and lessen the effects of low temperatures, sucrose, fructose, and total soluble sugar levels, as well as sucrose synthase (SS) and sucrose phosphate synthase (SPS) activities, surged in response to low-temperature stress. However, low-temperature stress significantly reduced the activity of adenosine diphosphate glucose pyrophosphorylase (AGPase), granule-bound starch synthase (GBSS), soluble starch synthase (SSS), and starch branching enzyme (SBE). At the same time, low-temperature stress reduced the area of vascular bundles and phloem, making it difficult to transport carbon and nitrogen metabolites to grains on time. The response of grains to low-temperature stress differs from that of leaves, with prolonged low-temperature exposure causing a gradual decrease in carbon and nitrogen metabolism-related enzyme activities and product accumulation within the grains. The insufficient synthesis of starch precursors and carbon skeletons results in significantly lower thousand-grain weight and seed-setting rates, ultimately contributing to grain yield loss. This decline was more pronounced in inferior grains compared to superior grains. Compared to SJ10, DN428 exhibited higher values across various indicators and smaller declines under low-temperature stress, suggesting enhanced cold-tolerance and a greater capacity to maintain grain yield stability. Full article

The mitochondrial pyruvate carrier (MPC) is a transmembrane protein complex critical for cellular energy metabolism, enabling the transport of pyruvate from the cytosol into the mitochondria, where it fuels the citric acid cycle. By regulating this essential entry point of carbon into mitochondrial metabolism, MPC is pivotal for maintaining cellular energy balance and metabolic flexibility. Dysregulation of MPC activity has been implicated in several metabolic disorders, including type 2 diabetes, obesity, and cancer, underscoring its potential as a therapeutic target. This review provides an overview of the MPC complex, examining its structural components, regulatory mechanisms, and biological functions. We explore the current understanding of transcriptional, translational, and post-translational modifications that modulate MPC function and highlight the clinical relevance of MPC dysfunction in metabolic and neurodegenerative diseases. Progress in the development of MPC-targeting therapeutics is discussed, with a focus on challenges in designing selective and potent inhibitors. Emphasis is placed on modern approaches for identifying novel inhibitors, particularly virtual screening and computational strategies. This review establishes a foundation for further research into the medicinal chemistry of MPC inhibitors, promoting advances in structure-based drug design to develop therapeutics for metabolic and neurodegenerative diseases. Full article

Blast trauma presents a unique challenge due to its complex mechanism of injury, which impacts the brain and other vital organs through overpressure waves and internal bleeding. Severe blood loss leads to an inadequate oxygen supply and insufficient fuel delivery to cells, impairing ATP production by mitochondria—essential for cell survival. While clinical symptoms of metabolic disruption are evident soon after injury, the molecular, cellular, and systemic damage persists for days to years post-injury. Current challenges in treating traumatic brain injury (TBI) stem from (1) the lack of early blood-based biomarkers for detecting metabolic failure and mitochondrial damage and (2) the limited success of mitochondrial-targeted therapeutic strategies. Objectives: To identify blood-based mitochondrial biomarkers for evaluating the severity of brain injuries and to investigate therapeutic strategies targeting mitochondria. Methods: A preclinical rat model subjected to blast exposure, with or without hemorrhagic shock (HS), followed by resuscitation was utilized. Blood samples were obtained at baseline (T0), post-injury (T60), and at the conclusion of the experiment (T180), and analyzed using a validated dipstick assay to measure mitochondrial enzyme activity. Results: Blast and HS injuries led to a significant decrease in the activity of mitochondrial enzymes, including complex I, complex IV, and the pyruvate dehydrogenase complex (PDH), compared to baseline (p < 0.05). Concurrently, blood lactate concentrations were significantly elevated (p < 0.001). An inverse correlation was observed between mitochondrial enzyme dysfunction and blood lactate levels (p < 0.05). Treatment with sodium pyruvate post-injury restored complex I, complex IV, and PDH activity to near-baseline levels, corrected hyperlactatemia, and reduced reactive oxygen species (ROS) production by mitochondria. Conclusions: Serial monitoring of blood mitochondrial enzyme activity, such as complex I, complex IV, and PDH, may serve as a valuable tool for prognostication and guiding the use of mitochondrial-targeted therapies. Additionally, mitochondrial enzyme assays in blood samples can provide insights into the global redox status, potentially paving the way for novel therapeutic interventions in TBI. Full article