Search Results (41)

ZnO nanostructures have attracted attention as transducer materials in optical biosensing platforms due to their wide bandgap, defect-mediated photoluminescence, high surface-to-volume ratio, and tunable morphology. This review examines how the dimensionality of ZnO nanostructures affects biosensor performance, particularly in terms of charge transport, signal transduction, and biomolecule immobilization. The synthesis approaches are discussed, highlighting how they influence crystallinity, defect density, and surface functionalization potential. The impact of immobilization strategies on sensor stability and sensitivity is also assessed. The role of ZnO in various optical detection schemes, including photoluminescence, surface plasmon resonance (SPR), localized (LSPR), fluorescence, and surface-enhanced Raman scattering (SERS), is reviewed, with emphasis on label-free and real-time detection. Representative case studies demonstrate the detection of clinically and environmentally relevant targets, such as glucose, dopamine, cancer biomarkers, and SARS-CoV-2 antigens, with limits of detection in the pico- to femtomolar range. Recent developments in ZnO-based hybrid systems and their integration into fiber-optic and microfluidic platforms are explored as scalable solutions for portable, multiplexed diagnostics. The review concludes by outlining current challenges related to reproducibility, long-term operational stability, and surface modification standardization. This work provides a framework for understanding structure–function relationships in ZnO-based biosensors and highlights future directions for their development in biomedical and environmental monitoring applications. Full article

Background: Abnormal sodium-dependent hexose reabsorption in the proximal tubule, accompanied by a functional decrease in sodium and water reabsorption under conditions of increased volemia, may be attributed to a dysfunction of primary transporters related to a genetic defect in the Na,K-ATPase gamma subunit. Methods: We examined two sisters, aged 6 and 8 years, who presented with hypercalciuria, glucosuria, fructosuria, galactosuria, and atypical proteinuria. Primary diabetes, galactosemia, and fructosemia were excluded, suggesting a defect in cellular hexose transport in the proximal tubule. We conducted tests on the family members to assess the impact of gradually increasing volemia, using a water-loading test, on tubular H⁺ transport and urinary excretion of calcium, citrate, endothelin-1 (ET-1), and atypical proteins. Whole-exome sequencing was performed in the affected patients to identify the genetic basis of this phenotype. Results: Extended investigations revealed a complex defect in tubular H⁺ transport, calcium and citrate handling, and atypical proteinuria, resulting from water load-driven overproduction of endothelin-1 (ET-1). Genetic analysis identified a heterozygous pathogenic variant, c.80G>A, p.(Arg27His), in the FXYD2 gene, which encodes the gamma subunit of sodium/potassium-transporting ATPase. Conclusions: Our findings provide evidence that a defect in FXYD2 (splice form a) leads to functional impairment of proximal tubular hexose reabsorption. This is the first report on the metabolic consequences of a pathogenic FXYD2 variant affecting the gamma subunit of sodium/potassium-transporting ATPase in humans. The genotype–phenotype correlation in two siblings with a sodium-dependent defect in fructose, galactose, and glucose renal reabsorption allowed us to characterize a disease with a distinct clinical course and biochemical profile, not previously reported in the medical literature or genetic databases. Analysis of this condition was crucial for the early introduction of reno-protective treatment aimed at slowing the progression of nephropathy and for risk assessment in family members, which was essential for genetic counseling. Full article

The aim of this study was to determine the effects of loading density and gender on blood welfare indicators, carcass bruises and horsemeat quality. Data were collected from twelve transports of 89 slaughter horses originating from the same collection centre. The transportation of slaughter horses at high loading densities (>200 kg/m²), especially stallions, resulted in increased levels of lactate (p = 0.021), glucose (p < 0.0001), ceruloplasmin (p < 0.0001) and AOPP (p < 0.0001), but lower GSH levels (p < 0.0001). Compared to stallions and mares, geldings subjected to high loading density (>200 kg/m²) during transport had lower levels of the aforementioned blood metabolites. In addition, stallions exposed to a high load density (>200 kg/m²) had the highest frequency of severe (p = 0.0002), large (p < 0.0001) and circular (p = 0.0001) carcass bruises, which were predominantly located on the abdominal (p = 0.0056) and thoracic (p = 0.0004) wall. In contrast, a higher percentage (p < 0.0001) of undamaged carcasses was found in slaughter horses exposed to a low loading density (≤200 kg/m²) during transport. Stallions exposed to high loading densities (>200 kg/m²) during transport had the highest initial pH (p < 0.0001) and ultimate pH (p = 0.005) in terms of m. longissimus lumborum and redness (p = 0.017), but the lowest drip loss (p = 0.050) and lightness (p < 0.0001), which, consequently, led to the highest (p = 0.0045) proportion of DFD-like defects in the meat quality. In conclusion, the results of this study showed that high loading densities (>200 kg/m²), regardless of gender, negatively affect horse welfare during transport. In addition, stallions were more sensitive to poor pre-slaughter conditions and produced the lowest meat quality, while geldings were the most resistant. To determine the optimal transport density, further research is needed to determine the effects of different loading densities on the behaviour, physiology, carcass and meat quality of slaughter horses. Full article

Alzheimer’s disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine- or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas of AD subjects. However, the biological role of GNPDA2 in neurodegeneration remains unknown. Using mass spectrometry, multiple GNPDA2 interactors were identified in human nasal epithelial cells (NECs) mainly involved in intraciliary transport. Moreover, GNPDA2 overexpression induced an increment in NEC proliferation rates, accompanied by transcriptomic alterations in Type II interferon signaling or cellular stress responses. In contrast, the presence of beta-amyloid or mutated Tau-P301L in GNPDA2-overexpressing NECs induced a slowdown in the proliferative capacity in parallel with a disruption in protein processing. The proteomic characterization of Tau-P301L transgenic zebrafish embryos demonstrated that GNPDA2 overexpression interfered with collagen biosynthesis and RNA/protein processing, without inducing additional changes in axonal outgrowth defects or neuronal cell death. In humans, a significant increase in serum GNPDA2 levels was observed across multiple neurological proteinopathies (AD, Lewy body dementia, progressive supranuclear palsy, mixed dementia and amyotrophic lateral sclerosis) (n = 215). These data shed new light on GNPDA2-dependent mechanisms associated with the neurodegenerative process beyond the hexosamine route. Full article

Insulin is a polypeptide hormone synthesized and secreted by pancreatic β-cells. It plays an important role as a metabolic hormone. Insulin influences the metabolism of glucose, regulating plasma glucose levels and stimulating glucose storage in organs such as the liver, muscles and adipose tissue. It is involved in fat metabolism, increasing the storage of triglycerides and decreasing lipolysis. Ketone body metabolism also depends on insulin action, as insulin reduces ketone body concentrations and influences protein metabolism. It increases nitrogen retention, facilitates the transport of amino acids into cells and increases the synthesis of proteins. Insulin also inhibits protein breakdown and is involved in cellular growth and proliferation. On the other hand, defects in the intracellular signaling pathways of insulin may cause several disturbances in human metabolism, resulting in several chronic diseases. Insulin resistance, also known as impaired insulin sensitivity, is due to the decreased reaction of insulin signaling for glucose levels, seen when glucose use in response to an adequate concentration of insulin is impaired. Insulin resistance may cause, for example, increased plasma insulin levels. That state, called hyperinsulinemia, impairs metabolic processes and is observed in patients with type 2 diabetes mellitus and obesity. Hyperinsulinemia may increase the risk of initiation, progression and metastasis of several cancers and may cause poor cancer outcomes. Insulin resistance is a health problem worldwide; therefore, mechanisms of insulin resistance, causes and types of insulin resistance and strategies against insulin resistance are described in this review. Attention is also paid to factors that are associated with the development of insulin resistance, the main and characteristic symptoms of particular syndromes, plus other aspects of severe insulin resistance. This review mainly focuses on the description and analysis of changes in cells due to insulin resistance. Full article

Vacuolar sugar transporters transport sugar across the tonoplast, are major players in maintaining sugar homeostasis, and therefore play vital roles in plant growth, development, and biomass yield. In this study, we analyzed the physiological roles of the tonoplast monosaccharide transporter 2 (TMT2) in Arabidopsis. In contrast to the wild type (WT) that produced uniform seedlings, the tmt2 mutant produced three types of offspring: un-germinated seeds (UnG), seedlings that cannot form true leaves (tmt2-S), and seedlings that develop normally (tmt2-L). Sucrose, glucose, and fructose can substantially, but not completely, rescue the abnormal phenotypes of the tmt2 mutant. Abnormal cotyledon development, arrested true leaf development, and abnormal development of shoot apical meristem (SAM) were observed in tmt2-S seedlings. Cotyledons from the WT and tmt2-L seedlings restored the growth of tmt2-S seedlings through micrografting. Moreover, exogenous sugar sustained normal growth of tmt2-S seedlings with cotyledon removed. Finally, we found that the TMT2 deficiency resulted in growth defects, most likely via changing auxin signaling, target of rapamycin (TOR) pathways, and cellular nutrients. This study unveiled the essential functions of TMT2 for seed germination and initial seedling development, ensuring cotyledon function and mobilizing sugars from cotyledons to seedlings. It also expanded the current knowledge on sugar metabolism and signaling. These findings have fundamental implications for enhancing plant biomass production or seed yield in future agriculture. Full article

The mTOR signaling pathway integrates signaling inputs from nutrients, including glucose and amino acids, which are precisely regulated by transporters depending on nutrient levels. The L-type amino acid transporter 1 (LAT1) affects the activity of mTORC1 through upstream regulators that sense intracellular amino acid levels. While mTORC1 activation by LAT1 has been thoroughly investigated in cultured cells, the effects of LAT1 expression on the activity of mTORC2 has scarcely been studied. Here, we provide evidence that LAT1 recruits and activates mTORC2 on the lysosome for PMA-induced cell migration. LAT1 is translocated to the lysosomes in cells treated with PMA in a dose- and time-dependent manner. Lysosomal LAT1 interacted with mTORC2 through a direct interaction with Rictor, leading to the lysosomal localization of mTORC2. Furthermore, the depletion of LAT1 reduced PMA-induced cell migration in a wound-healing assay. Consistent with these results, the LAT1 N3KR mutant, which is defective in PMA-induced endocytosis and lysosomal localization, did not induce mTORC2 recruitment to the lysosome, with the activation of mTORC2 determined via Akt phosphorylation or the LAT1-mediated promotion of cell migration. Taken together, lysosomal LAT1 recruits and activates the mTORC2 complex and downstream Akt for PMA-mediated cell migration. These results provide insights into the development of therapeutic drugs targeting the LAT1 amino acid transporter to block metastasis, as well as disease progression in various types of cancer. Full article

Sugar transport from the source leaf to the sink organ is critical for seed development and crop yield, as well as for responding to abiotic stress. SWEETs (sugar will eventually be exported transporters) mediate sugar efflux into the reproductive sink and are therefore considered key candidate proteins for sugar unloading during seed development. However, the specific mechanism underlying the sugar unloading to seeds in Camellia oleifera remains elusive. Here, we identified a SWEET gene named CoSWEET10, which belongs to Clade III and has high expression levels in the seeds of C. oleifera. CoSWEET10 is a plasma membrane-localized protein. The complementation assay of CoSWEET10 in SUSY7/ura3 and EBY.VW4000 yeast strains showed that CoSWEET10 has the ability to transport sucrose, glucose, and fructose. Through the C. oleifera seeds in vitro culture, we found that the expression of CoSWEET10 can be induced by hexose and sucrose, and especially glucose. By generating the restoration lines of CoSWEET10 in Arabidopsis atsweet10, we found that CoSWEET10 restored the seed defect phenotype of the mutant by regulating soluble sugar accumulation and increased plant drought tolerance. Collectively, our study demonstrates that CoSWEET10 plays a dual role in promoting seed development and enhancing plant drought resistance as a sucrose and hexose transporter. Full article

Osteoarthritis (OA) is the most common form of arthritis and joint disorder worldwide. Metabolic reprogramming of osteoarthritic chondrocytes from oxidative phosphorylation to glycolysis results in the accumulation of lactate from glycolytic metabolite pyruvate by lactate dehydrogenase A (LDHA), leading to cartilage degeneration. In the present study, we investigated the protective effects of the intra-articular administration of oxamate (LDHA inhibitor) against OA development and glycolysis-related protein expression in experimental OA rats. The animals were randomly allocated into four groups: Sham, anterior cruciate ligament transection (ACLT), ACLT + oxamate (0.25 and 2.5 mg/kg). Oxamate-treated groups received an intra-articular injection of oxamate once a week for 5 weeks. Intra-articular oxamate significantly reduced the weight-bearing defects and knee width in ACLT rats. Histopathological analyses showed that oxamate caused significantly less cartilage degeneration in the ACLT rats. Oxamate exerts hypertrophic effects in articular cartilage chondrocytes by inhibiting glucose transporter 1, glucose transporter 3, hexokinase II, pyruvate kinase M2, pyruvate dehydrogenase kinases 1 and 2, pyruvate dehydrogenase kinase 2, and LHDA. Further analysis revealed that oxamate significantly reduced chondrocyte apoptosis in articular cartilage. Oxamate attenuates nociception, inflammation, cartilage degradation, and chondrocyte apoptosis and possibly attenuates glycolysis-related protein expression in ACLT-induced OA rats. The present findings will facilitate future research on LDHA inhibitors in prevention strategies for OA progression. Full article

Glycogen storage disease type Ib (GSD1b) is due to a defect in the glucose-6-phosphate transporter (G6PT) of the endoplasmic reticulum, which is encoded by the SLC37A4 gene. This transporter allows the glucose-6-phosphate that is made in the cytosol to cross the endoplasmic reticulum (ER) membrane and be hydrolyzed by glucose-6-phosphatase (G6PC1), a membrane enzyme whose catalytic site faces the lumen of the ER. Logically, G6PT deficiency causes the same metabolic symptoms (hepatorenal glycogenosis, lactic acidosis, hypoglycemia) as deficiency in G6PC1 (GSD1a). Unlike GSD1a, GSD1b is accompanied by low neutrophil counts and impaired neutrophil function, which is also observed, independently of any metabolic problem, in G6PC3 deficiency. Neutrophil dysfunction is, in both diseases, due to the accumulation of 1,5-anhydroglucitol-6-phosphate (1,5-AG6P), a potent inhibitor of hexokinases, which is slowly formed in the cells from 1,5-anhydroglucitol (1,5-AG), a glucose analog that is normally present in blood. Healthy neutrophils prevent the accumulation of 1,5-AG6P due to its hydrolysis by G6PC3 following transport into the ER by G6PT. An understanding of this mechanism has led to a treatment aimed at lowering the concentration of 1,5-AG in blood by treating patients with inhibitors of SGLT2, which inhibits renal glucose reabsorption. The enhanced urinary excretion of glucose inhibits the 1,5-AG transporter, SGLT5, causing a substantial decrease in the concentration of this polyol in blood, an increase in neutrophil counts and function and a remarkable improvement in neutropenia-associated clinical signs and symptoms. Full article

Cognitive decline frequently occurs with increasing age, but mechanisms contributing to age-associated cognitive decline (ACD) are not well understood and solutions are lacking. Understanding and reversing mechanisms contributing to ACD are important because increased age is identified as the single most important risk factor for dementia. We reported earlier that ACD in older humans is associated with glutathione (GSH) deficiency, oxidative stress (OxS), mitochondrial dysfunction, glucose dysmetabolism and inflammation, and that supplementing GlyNAC (glycine and N-acetylcysteine) improved these defects. To test whether these defects occur in the brain in association with ACD, and could be improved/reversed with GlyNAC supplementation, we studied young (20-week) and old (90-week) C57BL/6J mice. Old mice received either regular or GlyNAC supplemented diets for 8 weeks, while young mice received the regular diet. Cognition and brain outcomes (GSH, OxS, mitochondrial energetics, autophagy/mitophagy, glucose transporters, inflammation, genomic damage and neurotrophic factors) were measured. Compared to young mice, the old-control mice had significant cognitive impairment and multiple brain defects. GlyNAC supplementation improved/corrected the brain defects and reversed ACD. This study finds that naturally-occurring ACD is associated with multiple abnormalities in the brain, and provides proof-of-concept that GlyNAC supplementation corrects these defects and improves cognitive function in aging. Full article

Nicotinamide mononucleotide (NMN) is a key precursor of nicotinamide adenine dinucleotide and an important source of cellular energy. It can prevent neuronal mitochondrial defects and alleviate heart fibrosis. Strategies to improve NMN production have important implications for human health. Through plasmid expression technology and CRISPR/Cas9 technology, we engineered Escherichia coli for efficient NMN production. First, we upregulated the expression of genes encoding key enzymes in the NMN synthesis pathway, enabling E. coli to directly produce NMN, and established the important role of the nicotinamide mononucleotide transporter in the transport of NMN from cells. The content of NMN was 0.24 g·L⁻¹ at 24 h. Second, we strengthened the adenosine triphosphate (ATP) cycle, and the concentration of NMN was 0.49 g·L⁻¹ at 24 h. Third, we increased the synthesis of the NMN precursor 5-phosphate ribose-1-phosphate and obtained an NMN content of 0.49 g·L⁻¹ at 12 h and 1.11 g·L⁻¹ at 24 h. Fourth, we introduced nicotinamide riboside kinase (NRK) and found that it was effective only for a period of time. The content of NMN was 0.54 g·L⁻¹ at 12 h but only 1.05 g·L⁻¹ at 24 h. Finally, we combined these strategies to regulate the whole metabolic flow, revealing that integrating multiple pathways promoted NMN production. During fermentation, we added 1 g·L⁻¹ nicotinamide and 10 g·L⁻¹ glucose, yielding an extracellular NMN concentration of 1.11 g·L⁻¹. Full article

Mitochondria are semiautonomous doubly membraned intracellular components of cells. The organelle comprises of an external membrane, followed by coiled structures within the membrane called cristae, which are further surrounded by the matrix spaces followed by the space between the external and internal membrane of the organelle. A typical eukaryotic cell contains thousands of mitochondria within it, which make up 25% of the cytoplasm present in the cell. The organelle acts as a common point for the metabolism of glucose, lipids, and glutamine. Mitochondria chiefly regulate oxidative phosphorylation-mediated aerobic respiration and the TCA cycle and generate energy in the form of ATP to fulfil the cellular energy needs. The organelle possesses a unique supercoiled doubly stranded mitochondrial DNA (mtDNA) which encodes several proteins, including rRNA and tRNA crucial for the transport of electrons, oxidative phosphorylation, and initiating genetic repair processors. Defects in the components of mitochondria act as the principal factor for several chronic cellular diseases. The dysfunction of mitochondria can cause a malfunction in the TCA cycle and cause the leakage of the electron respiratory chain, leading to an increase in reactive oxygen species and the signaling of aberrant oncogenic and tumor suppressor proteins, which further alter the pathways involved in metabolism, disrupt redox balance, and induce endurance towards apoptosis and several treatments which play a major role in developing several chronic metabolic conditions. The current review presents the knowledge on the aspects of mitochondrial dysfunction and its role in cancer, diabetes mellitus, infections, and obesity. Full article

Human ageing is accompanied by poor responses to infection and decreased vaccine efficacy. While the causes of this can be attributed to defects in the immune system that increase with age, it is unknown whether mitochondrial dysfunction may also contribute to these phenomena. This study aims to assess mitochondrial dysfunction in CD4+ terminal effector memory T cells re-expressing CD45RA (TEMRA) cells and other CD4+ memory T cell subtypes, which are increased in number in the elderly population, with respect to how their metabolic responses to stimulation are altered compared to CD4+ naïve T cells. In this study, we show that CD4+ TEMRA cells exhibit altered mitochondrial dynamics compared to CD4+ naïve cells and CD4+ central and effector memory cells, with a 25% reduction in OPA1 expression. CD4+ TEMRA and memory cells show increased upregulation of Glucose transporter 1 following stimulation and higher levels of mitochondrial mass compared to CD4+ naïve T cells. Additionally, TEMRA cells exhibit a decrease in mitochondrial membrane potential compared to other CD4+ memory cell subsets by up to 50%. By comparing young to aged individuals, more significant mitochondria mass and lower membrane potential were observed in CD4+ TEMRA of young individuals. In conclusion, we suggest that CD4+ TEMRA cells may be impaired with respect to their metabolic response to stimulation, possibly contributing to impaired responses to infection and vaccination. Full article

Zymomonas mobilis is a natural ethanologen with many desirable characteristics, which makes it an ideal industrial microbial biocatalyst for the commercial production of desirable bioproducts. Sugar transporters are responsible for the import of substrate sugars and the conversion of ethanol and other products. Glucose-facilitated diffusion protein Glf is responsible for facilitating the diffusion of glucose uptake in Z. mobilis. However, another sugar transporter-encoded gene, ZMO0293, is poorly characterized. We employed gene deletion and heterologous expression mediated by the CRISPR/Cas method to investigate the role of ZMO0293. The results showed that deletion of the ZMO0293 gene slowed growth and reduced ethanol production and the activities of key enzymes involved in glucose metabolism in the presence of high concentrations of glucose. Moreover, ZMO0293 deletion caused different transcriptional changes in some genes of the Entner Doudoroff (ED) pathway in the ZM4-ΔZM0293 strain but not in ZM4 cells. The integrated expression of ZMO0293 restored the growth of the glucose uptake-defective strain Escherichia coli BL21(DE3)-ΔptsG. This study reveals the function of the ZMO0293 gene in Z. mobilis in response to high concentrations of glucose and provides a new biological part for synthetic biology. Full article