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Summary Some cyanobacteria can grow photoautotrophically or photomixotrophically by using simultaneously CO2 and glucose. The switch between these trophic modes and the role of glycogen, their main carbon storage macromolecule, was investigated. We analysed the effect of glucose addition on the physiology, metabolic and photosynthetic state of Synechocystis sp. PCC 6803 and mutants lacking phosphoglucomutase and ADP‐glucose pyrophosphorylase, with limitations in glycogen synthesis. Glycogen acted as a metabolic buffer: glucose addition increased growth and glycogen reserves in the wild‐type (WT), but arrested growth in the glycogen synthesis mutants. Already 30 min after glucose addition, metabolites from the Calvin–Benson–Bassham cycle and the oxidative pentose phosphate shunt increased threefold more in the glycogen synthesis mutants than the WT. These alterations substantially affected the photosynthetic performance of the glycogen synthesis mutants, as O2 evolution and CO2 uptake were both impaired. We conclude that glycogen synthesis is essential during transitions to photomixotrophy to avoid metabolic imbalance that induces inhibition of electron transfer from PSII and subsequently accumulation of reactive oxygen species, loss of PSII core proteins, and cell death. Our study lays foundations for optimising photomixotrophy‐based biotechnologies through understanding the coordination of the crosstalk between photosynthetic electron transport and metabolism. [ABSTRACT FROM AUTHOR]

Thiazide and thiazide‐like diuretics (thiazides) belong to the most frequently prescribed drugs worldwide. By virtue of their natriuretic and vasodilating properties, thiazides effectively lower blood pressure and prevent adverse cardiovascular outcomes. In addition, through their unique characteristic of reducing urine calcium, thiazides are also widely employed for the prevention of kidney stone recurrence and reduction of bone fracture risk. Since their introduction into clinical medicine in the early 1960s, thiazides have been recognized for their association with metabolic side effects, particularly impaired glucose tolerance, and new‐onset diabetes mellitus. Numerous hypotheses have been advanced to explain thiazide‐induced glucose intolerance, yet underlying mechanisms remain poorly defined. Regrettably, the lack of understanding and unpredictability of these side effects has prompted numerous physicians to refrain from prescribing these effective, inexpensive, and widely accessible drugs. In this review, we outline the pharmacology and mechanism of action of thiazides, highlight recent advances in the understanding of thiazide‐induced glucose intolerance, and provide an up‐to‐date discussion on the role of thiazides in kidney stone prevention. [ABSTRACT FROM AUTHOR]

Mesenchymal stem cells (MSCs) are a therapeutically efficient type of stem cells validated by their ability to treat many inflammatory and chronic conditions. The biological and therapeutic characteristics of MSCs can be modified depending on the type of microenvironment at the site of transplantation. Diabetes mellitus (DM) is a commonly diagnosed metabolic disease characterized by hyperglycemia, which alters over time the cellular and molecular functions of many cells and causes their damage. Hyperglycemia can also impact the success rate of MSCs transplantation; therefore, it is extremely significant to investigate the effect of high glucose on the biological and therapeutic attributes of MSCs, particularly their immunomodulatory abilities. Thus, in this study, we explored the effect of high glucose on the immunosuppressive characteristics of human adipose tissue‐derived mesenchymal stem cells (hAD‐MSCs). We found that hAD‐MSCs cultured in high glucose lost their immunomodulatory abilities and became detectable by immune cells. The decline in the immunosuppressive capabilities of hAD‐MSCs was mediated by significant decrease in the levels of IDO, IL‐10, and complement factor H and substantial increase in the activity of immunoproteasome. The protein levels of AMP‐activated protein kinase (AMPK) and phosphofructokinase‐1 (PFK‐1), which are integral regulators of glycolysis, revealed a marked decline in high glucose exposed MSCs. The findings of our study indicated the possibility of immunomodulatory shift in MSCs after being cultured in high glucose, which can be translationally employed to explain their poor survival and short‐lived therapeutic outcomes in diabetic patients. [ABSTRACT FROM AUTHOR]

Aim: We investigated whether periodontal measures are cross‐sectionally associated with prediabetes and cardiometabolic biomarkers among non‐diabetic younger adults. Materials and Methods: One thousand seventy‐one participants (mean age = 32.2 years [SE = 0.3]; 73% female) from the Oral Infections, Glucose Intolerance and Insulin Resistance Study were enrolled. Full‐mouth clinical attachment loss (fm‐CAL), probing depth (fm‐PD) and bleeding on probing were ascertained. Interproximal CAL (i‐CAL) and probing depths (i‐PD) served as our primary exposures. Glucose, HbA1c, insulin and insulin resistance (HOMA‐IR) outcomes were assessed from fasting blood. Prediabetes was defined per American Diabetes Association guidelines. Prediabetes prevalence ratios (PR [95% CI]) and mean [SE] cardiometabolic biomarkers were regressed on periodontal variables via multivariable robust variance Poisson regression or multivariable linear regression. Results: Prevalence of prediabetes was 12.5%. Fully adjusted prediabetes PR in Tertiles 3 versus 1 of mean i‐CAL was 2.42 (1.77, 3.08). Fully adjusted fasting glucose estimates across i‐CAL tertiles were 83.29 [0.43], 84.31 [0.37], 86.48 [0.46]; p for trend <.01. Greater percent of sites with i‐PD ≥3 mm showed elevated natural‐log‐HOMA‐IR after adjustment (0%–12% of sites = 0.33 [0.03], 13%–26% of sites = 0.39 [0.03], ≥27% of sites = 0.42 [0.03]; p for trend =.04). Conclusions: i‐CAL (vs. fm‐CAL) was associated with elevated fasting glucose and prediabetes, whereas i‐PD (vs. fm‐PD) was associated with insulin resistance. Future studies are needed to examine periodontal disease and incident prediabetes. [ABSTRACT FROM AUTHOR]

Although the etiology of intervertebral disc degeneration is still unresolved, the nutrient paucity resulting from its avascular nature is suspected of triggering degenerative processes in its core: the nucleus pulposus (NP). While severe hypoxia has no significant effects on NP cells, the impact of glucose depletion, such as found in degenerated discs (0.2–1 mM), is still uncertain. Using a pertinent ex‐vivo model representative of the unique disc microenvironment, the present study aimed, therefore, at determining the effects of "degenerated" (0.3 mM) glucose levels on bovine NP explant homeostasis. The effects of glucose depletion were evaluated on NP cell viability, apoptosis, phenotype, metabolism, senescence, extracellular matrix anabolism and catabolism, and inflammatory mediator production using fluorescent staining, RT‐qPCR, (immuno)histology, ELISA, biochemical, and enzymatic assays. Compared to the "healthy" (2 mM) glucose condition, exposure to the degenerated glucose condition led to a rapid and extensive decrease in NP cell viability associated with increased apoptosis. Although the aggrecan and collagen‐II gene expression was also downregulated, NP cell phenotype, and senescence, matrix catabolism, and inflammatory mediator production were not, or only slightly, affected by glucose depletion. The present study provided evidence for glucose depletion as an essential player in NP cell viability but also suggested that other microenvironment factor(s) may be involved in triggering the typical shift of NP cell phenotype observed during disc degeneration. The present study contributes new information for better understanding disc degeneration at the cellular‐molecular levels and thus helps to develop relevant therapeutical strategies to counteract it. [ABSTRACT FROM AUTHOR]

Aim: Myo‐inositol supplementation from ~13 weeks' gestation reportedly improves glycaemia regulation in metabolically at‐risk women, with speculation that earlier supplementation might bring further improvement. However, the NiPPeR trial of a myo‐inositol‐containing supplement starting preconception did not lower gestational glycaemia in generally healthy women. We postulated that the earlier timing of supplementation influences the maternal metabolic adaptation for gestational glycaemia regulation. Methods: In total, 585 women were recruited from Singapore, UK and New Zealand for the NiPPeR study. We examined associations of plasma myo‐inositol concentrations at 7 and 28 weeks' gestation with 28 weeks plasma glucose (PG; fasting, and 1 h and 2 h in 75 g oral glucose tolerance test) and insulin indices using linear regression adjusting for covariates. Results: Higher 7‐week myo‐inositol, but not 28‐week myo‐inositol, associated with higher 1 h PG [βadj (95% confidence intervals) 0.05 (0.01, 0.09) loge mmol/L per loge μmol/L, p =.022] and 2 h PG [0.08 (0.03, 0.12), p =.001]; equivalent to 0.39 mmol/L increase in 2 h PG for an average 7‐week myo‐inositol increase of 23.4 μmol/L with myo‐inositol supplementation. Higher 7‐week myo‐inositol associated with a lower 28‐week Stumvoll index (first phase), an approximation of insulin secretion [−0.08 (−0.15, −0.01), p =.020] but not with 28‐week Matsuda insulin sensitivity index. However, the clinical significance of a 7‐week myo‐inositol‐related increase in glycaemia was limited as there was no association with gestational diabetes risk, birthweight and cord C‐peptide levels. In‐silico modelling found higher 28‐week myo‐inositol was associated with lower gestational glycaemia in White, but not Asian, women after controlling for 7‐week myo‐inositol effects. Conclusion: To our knowledge, our study provides the first evidence that increasing first trimester plasma myo‐inositol may slightly exacerbate later pregnancy post‐challenge glycaemia, indicating that the optimal timing for starting prenatal myo‐inositol supplementation needs further investigation. [ABSTRACT FROM AUTHOR]

Wearable sweat sensors exhibit significant promise in the realm of smart healthcare. Efficient and non‐contaminating continuous sweat collection, transport, and disposal are crucial for enhancing detection accuracy. In this study, a novel wearable sweat sensor is presented that integrates various biomimetic structures, including cactus‐inspired spine, shorebird‐inspired conical through‐holes, and frog‐foot‐inspired micro‐grooves. These structures facilitate sweat droplets to be automatically transported from the skin to the sensing chamber and discharged without external power. First, theoretical analysis, simulation, and experiments based on self‐driven droplet mechanisms to determine the optimal transport efficiency parameters for biomimetic structures are conducted. Next, a novel sweat transport module is fabricated through ultra‐precision 3D printing according to these optimal parameters. And this module has excellent sweat collection performance contrastively. Finally, the novel biomimetic sweat transport module is integrated with a high‐sensitivity glucose detection electrode, resulting in a wearable sweat glucose detection system. Human experiments monitoring glucose metabolism in sweat verify the correlation between glucose concentrations in blood and sweat, which proves the feasibility of reflecting changes in the body's circulatory system by monitoring changes in sweat composition. [ABSTRACT FROM AUTHOR]

Developing a biphasic catalyst is of great significance for improving reaction efficiency and its industrial application. Herein a novel biphasic catalyst containing three functional groups of chlorophenol, amino and carboxyl was synthesized and used as mimic glucose isomerase to catalyze the isomerization. The mimic enzyme exhibited excellent catalytic performance for isomerization of glucose to fructose under mild conditions. Temperature and pH of solution showed significant influence on the conversion of glucose and the selectivity of fructose. The yield and selectivity of fructose reached 32.4 % and 91.0 % after reacting 2 h, respectively, at pH 9.5 and 90 °C. The solubility of the catalyst exhibited dual sensitivity to both pH and temperature. The catalyst was in a soluble state during the reaction process and could be precipitated by reducing the pH and temperature of the reaction system. The catalyst could be reused and still maintained good catalytic activity after five consecutive cycles. [ABSTRACT FROM AUTHOR]

SUMMARY Sugar beet (Beta vulgaris) is the major sugar‐producing crop in Europe and Northern America, as the taproot stores sucrose at a concentration of around 20%. Genome sequence analysis together with biochemical and electrophysiological approaches led to the identification and characterization of the TST sucrose transporter driving vacuolar sugar accumulation in the taproot. However, the sugar transporters mediating sucrose uptake across the plasma membrane of taproot parenchyma cells remained unknown. As with glucose, sucrose stimulation of taproot parenchyma cells caused inward proton fluxes and plasma membrane depolarization, indicating a sugar/proton symport mechanism. To decipher the nature of the corresponding proton‐driven sugar transporters, we performed taproot transcriptomic profiling and identified the cold‐induced PMT5a and STP13 transporters. When expressed in Xenopus laevis oocytes, BvPMT5a was characterized as a voltage‐ and H+‐driven low‐affinity glucose transporter, which does not transport sucrose. In contrast, BvSTP13 operated as a high‐affinity H+/sugar symporter, transporting glucose better than sucrose, and being more cold‐tolerant than BvPMT5a. Modeling of the BvSTP13 structure with bound mono‐ and disaccharides suggests plasticity of the binding cleft to accommodate the different saccharides. The identification of BvPMT5a and BvSTP13 as taproot sugar transporters could improve breeding of sugar beet to provide a sustainable energy crop. [ABSTRACT FROM AUTHOR]

Biomass–derived feedstocks for hydrogen production are crucial as an alternative to fossil fuel especially in those areas where green electricity and clean water are scarce. In this framework the transformation of simple (formic acid, alcohols) and more complex (polyalcohols, sugars and cellulose) bio–derivatives in pure hydrogen is recognized as a promising approach. Parallel to great effort in heterogeneous catalysis, milder molecular systems represent a more selective eye for alternative solutions and mechanistic insights. In the present review the introduction summarizes the challenges in the catalytic utilization of biomass–derived feedstocks, followed by the advances in homogeneously catalyzed hydrogen production from different substrates which will cover formic acid, with oustanding efficiency with noble metals and promising results with earth abundant ones and alcohols and polyalcohols, with particular emphasis to the development of heterogenized systems, ligand assisted catalysts and bi‐catalytic synergistic solutions which allow to avoid base and to promote catalyst stability and recyclability. In the last part, description of hydrogen production from more complex substrates, such as sugars and cellulose, will show the role of molecular complexes in main and side reactions. Critical comments on the reported advances are provided along the whole discussion. [ABSTRACT FROM AUTHOR]

Many synthetic glucokinase activators (GKAs), modulating glucokinase (GK), an important therapeutic target in diabetes have failed to clear clinical trials. In this study, an in silico structural similarity search with differing scaffolds of reference GKAs have been used to identify derivatives from natural product databases. Ten molecules with good binding score and similar interactions to that in the co‐crystallized GK as well good activation against recombinant human GK experimentally were identified. Tetrahydropalmatine, an alkaloid present in formulations and drugs from medicinal plants, has not been explored as an antidiabetic agent and no information regarding its mechanism of action or GK activation exists. Tetrahydropalmatine activates GK with EC50 value of 71.7 ± 17.9 μM while lowering the S0.5 (7.1 mM) and increasing Vmax (9.22 μM/min) as compared to control without activator (S0.5 = 10.37 mM; Vmax = 4.8 μM/min). Kinetic data (α and β values) suggests it to act as mixed, nonessential type activator. Using microscale thermophoresis, Kd values of 3.8 μM suggests a good affinity for GK. In HepG2 cell line, the compound potentiated the uptake of glucose and maintained glucose homeostasis by increasing the expression of GK, glycogen synthase, and insulin receptor genes and lowering the expression of glucokinase regulatory protein (GKRP) and glucagon. Tetrahydropalmatine at low concentrations could elicit a good response by reducing expression of GKRP, increasing expression of GK while also activating it. Thus, it could be used alone or in combination as therapeutic drug as it could effectively modulate GK and alter glucose homeostasis. [ABSTRACT FROM AUTHOR]

Summary: The present study aimed to evaluate the combined application of edible coatings (alginate or pectin) and the osmotic dehydration process (glucose solution at 40 °Brix and 60 °Brix, solution temperatures of 20 and 40 °C, and process times of 1, 2, 4, 8, and 16 h) on mass transfer kinetics and physicochemical parameters (weight reduction (WR), water loss (WL), solids gain (SG), and optical and mechanical properties) of pear cubes. The best dehydration performance was observed in the coated samples treated at 60 °Brix‐40 °C. At the end of this process, the coated samples showed higher values of WR (77.30% and 75.13%) and WL (77.39%; 74.38%) and lower values of SG (1.69% and 1.24%) than the uncoated samples (WR: 65.97%, WL: 68.38%, and SG: 4.12%). Additionally, optimal retention of optical and mechanical properties was achieved in the coated samples exposed to the 40 °Brix‐40 °C condition. [ABSTRACT FROM AUTHOR]

Summary: Objective: Rising prevalence of obesity has led to increased rates of prediabetes and diabetes mellitus (DM) in children. This study compares rates of prediabetes and diabetes using two recommended screening tests (fasting plasma glucose [FPG] and haemoglobin A1c [HbA1c]). Study Design: Data were collected prospectively from 37 multi‐component paediatric weight management programs in POWER (Paediatric Obesity Weight Evaluation Registry). Results: For this study, 3962 children with obesity without a known diagnosis of DM at presentation and for whom concurrent measurement of FPG and HbA1c were available were evaluated (median age 12.0 years [interquartile range, IQR 9.8, 14.6]; 48% males; median body mass index 95th percentile [%BMIp95] 134% [IQR 120, 151]). Notably, 10.7% had prediabetes based on FPG criteria (100–125 mg/dL), 18.6% had prediabetes based on HbA1c criteria (5.7%–6.4%), 0.9% had DM by FPG abnormality (≥126 mg/dL) and 1.1% had DM by HbA1c abnormality (≥6.5%). Discordance between the tests was observed for youth in both age groups (10–18 years [n = 2915] and age 2–9 years [n = 1047]). Conclusion: There is discordance between FPG and HbA1c for the diagnosis of prediabetes and DM in youth with obesity. Further studies are needed to understand the predictive capability of these tests for development of DM (in those diagnosed with prediabetes) and cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Aim: Hypoglycaemic events are linked to microvascular and macrovascular complications in people with type 1 diabetes. We aimed to evaluate the efficacy of glucose sensor [real‐time continuous glucose monitoring (RT‐CGM)] with predictive alarm (PA) in reducing the time spent below the range (%TBR <70 mg/dl) in a group of adolescents with type 1 diabetes (AwD). Materials and Methods: This was a crossover, monocentric and randomized study. RT‐CGM was set with Alarm on Threshold (AoT) at 70 mg/dl) or PA for hypoglycaemia (20 m before threshold). Twenty AwD were enrolled and randomized to either a PA/AoT or AoT/PA treatment sequence, in a 1:1 ratio. The two groups (PA vs. AoT) were compared using two‐way repeated measures ANOVA taking account of the carryover effect. Results: AwD using PA for hypoglycaemia spent less time in severe hypoglycaemia (%TBR2 <54 mg/dl; 0.32 ± 0.31 vs. 0.91 ± 0.90; p <.02) and hypoglycaemia (%TBR <70 mg/dl; 1.68 ± 1.06 vs. 2.90 ± 2.05; p <.02), with better glycaemia risk index (51.3 ± 11.0 vs. 61.5 ± 12.6; p ≤.01). Conclusion: The use of RT‐CGM with PA for hypoglycaemia technology in AwD using multiple daily insulin injection treatment could significantly reduce the risk of having hypoglycaemic events resulting in an improved quality of glucose control. Clinical Trial Registration number: NCT05574023. [ABSTRACT FROM AUTHOR]

Aim: We aimed to investigate the long‐term influence of a diet and/or exercise intervention on long‐term mortality and cardiovascular disease (CVD) events. Methods: The Da Qing Diabetes Prevention Study had 576 participants with impaired glucose tolerance (IGT) randomized to diet‐only, exercise‐only and diet‐plus‐exercise intervention group and control group. The participants underwent lifestyle interventions for 6 years. The subsequent Da Qing Diabetes Prevention Outcome Study was a prospective cohort study to follow‐up the participants for up to 24 years after the end of 6‐year intervention. In total, 540 participants completed the follow‐up, while 36 subjects lost in follow‐up. Cox proportional hazards analysis was applied to assess the influence of lifestyle interventions on targeted outcomes. Results: Compared with controls, the diet‐only intervention in people with IGT was significantly associated with a reduced risk of all‐cause death [hazard ratio (HR) 0.77, 95% confidence interval (CI) (0.61‐0.97)], CVD death [HR 0.67, 95% CI (0.46‐0.97)] and CVD events [HR 0.72, 95% CI (0.54‐0.96)]. The diet‐plus‐exercise intervention was significantly associated with a decreased risk of all‐cause death [HR 0.64, 95% CI (0.48‐0.84)], CVD death [HR 0.54, 95% CI (0.30‐0.97)] and CVD events [HR 0.68, 95% CI (0.52‐0.90)]. Unexpectedly, the exercise‐only intervention was not significantly associated with the reduction of any of these outcomes, although there was a consistent trend towards reduction. Conclusions: A diet‐only intervention and a diet‐plus‐exercise intervention in people with IGT were significantly associated with a reduced risk of all‐cause death, CVD death and CVD events, while an exercise‐only intervention was not. It suggests that diet‐related interventions may have a potentially more reliable influence on long‐term vascular complications and mortality. [ABSTRACT FROM AUTHOR]

The kinetics of total organic carbon (TOC) destruction during supercritical water gasification (SCWG) of glucose were studied at 400–500°C and 25 MPa in a 600 mL batch reactor. Both TOC and water concentrations are critical for the conversion of TOC in supercritical water, especially at longer residence times. Initially, it was assumed that the TOC destruction reaction followed first‐order kinetics ignoring the water concentration. However, experimental results showed that the feed‐to‐water ratio had a significant effect on TOC decomposition. Considering the water concentration in the reaction, the reaction orders of TOC (2.35) and water (1.45) were calculated using nonlinear regression analysis (the Runge‐Kutta method). The estimated pre‐exponential factor (k’) and activation energy (E) were calculated to be 8.1 ± 2/min and 90.37 ± 9.38 kJ/mol respectively. [ABSTRACT FROM AUTHOR]

Nanoparticles that catalyze biochemically relevant reactions are promoted as alternative enzymes. The application of such artificial enzymes is severely restricted by poor selectivity in biological fluids; mainly because the reactions occur at active sites on the exterior surface of the nanoparticle. Enzymes in contrast typically have their active sites down a nanoconfined substrate channel where the reaction occurs in different solution conditions to bulk solution which aids in achieving selectivity for the substrate. Herein the same 3D structure of enzymes is mimicked in nanoparticles to allow selective reactions in biological fluids. This is achieved using a gold nanoparticle coated in a conducting mesoporous carbon shell where isolated nanochannels lead to the gold surface. It can detect glucose in whole blood with no interference from other species. This is achieved by electrochemically pulsing the artificial enzymes to generate the locally required alkalinity for an effective electrocatalytic reaction in the nanochannels, as well as expelling fouling agents that will otherwise passivate the electrocatalytic reaction. The artificial enzymes are shown to be capable of detecting glucose in biological fluids, without loss of signal, for several months. This study shows how nanoconfinement in nanoparticles can be exploited to potentially allow a broad range of species to be selectively detected in biological fluids with stability that can exceed that of enzymes. [ABSTRACT FROM AUTHOR]

The erratic, intermittent, and unpredictable nature of sweat production, resulting from physiological or psychological fluctuations, poses intricacies to consistently and accurately sample and evaluate sweat biomarkers. Skin‐interfaced microfluidic devices that rely on colorimetric mechanisms for semi‐quantitative detection are particularly susceptible to these inaccuracies due to variations in sweat secretion rate or instantaneous volume. This work introduces a skin‐interfaced colorimetric bifluidic sweat device with two synchronous channels to quantify sweat rate and biomarkers in real‐time, even during uncertain sweat activities. In the proposed bifluidic‐distance metric approach, with one channel to measure sweat rate and quantify collected sweat volume, the other channel can provide an accurate analysis of the biomarkers based on the collected sweat volume. The closed channel design also reduces evaporation and resists contamination from the external environment. The feasibility of the device is highlighted in a proof‐of‐the‐concept demonstration to analyze sweat chloride for evaluating hydration status and sweat glucose for assessing glucose levels. The low‐cost yet highly accurate device provides opportunities for clinical sweat analysis and disease screening in remote and low‐resource settings. The developed device platform can be facilely adapted for the other biomarkers when corresponding colorimetric reagents are exploited. [ABSTRACT FROM AUTHOR]

Catalytic conversion of glucose to lactic acid is a green promising strategy for the effective utilization of biomass‐derived carbohydrates to generate valuable chemicals. The generation of lactic acid would also be distinguishing in different reaction atmospheres. In this work, we firstly investigated the decomposition of lactic acid and glucose transformation to lactic acid in H2. No obvious decomposition of lactic acid was observed in H2. The activity testing results showed that glucose could be completely converted over the selected hydroxides, while the formation of lactic acid was closely related to the alkalinity of hydroxide. The yield of lactic acid was remarkably obtained to be 87 % over Ca(OH)2 at 220 °C for 3 h. Stronger alkalinity of the catalyst would facilitate glucose isomerization to fructose, and then easily be transformed into dihydroxyacetone or glyceraldehyde intermediates through reverse aldol condensation, which is beneficial to the generation of lactic acid. [ABSTRACT FROM AUTHOR]

Generally, two‐dimensional gold nanomaterials have unique properties and functions that offer exciting application prospects. However, the crystal phases of these materials tend to be limited to the thermodynamically stable crystal structure. Herein, we report a DNA framework‐templated approach for the ambient aqueous synthesis of freestanding and microscale amorphous gold nanosheets with ultrathin sub‐nanometer thickness. We observe that extended single‐stranded DNA on DNA nanosheets can induce site‐specific metallization and enable precise modification of the metalized nanostructures at predefined positions. More importantly, the as‐prepared gold nanosheets can serve as an electrocatalyst for glucose oxidase‐catalyzed aerobic oxidation, exhibiting enhanced electrocatalytic activity (~3‐fold) relative to discrete gold nanoclusters owing to a larger electrochemical active area and wider band gap. The proposed DNA framework‐templated metallization strategy is expected to be applicable in a broad range of fields, from catalysis to new energy materials. [ABSTRACT FROM AUTHOR]

Background: The use of two or more drugs carries the potential risk of drug–drug interactions (DDIs), which may result in adverse reactions. Some human immunodeficiency virus (HIV)‐infected patients who receive antiretroviral therapy (ART) may require general anesthesia with propofol (PRL) before undergoing surgical treatment. Both PRL and ART drugs may lead to neuronal dysfunction, which can be accompanied by energy metabolism disorders. Neurons take in glucose mainly through glucose transporter 3 (Glut3) which is specifically expressed on the cell membranes of neurons. However, to date, no study has examined whether the DDIs of PRL and ART drugs interfere with glucose metabolism and Glut3 expression in neurons. Methods: An in vitro model was constructed using the primary cultures of neurons. PRL and ART drugs (EFV, AZT, and 3TC), were added at different concentrations (low, medium, and high). The neurons were exposed to the drugs for 1, 4, 8, and 12 h. The optimal drug concentration and exposure time were selected. The cellular survival rate, glucose concentration, electrophysiology, and the expression of Glut3 were detected. Results: There were no significant changes in the cellular survival rates of the neurons that were exposed to both PRL and ART drugs at low concentrations for 1 h. However, the survival rates of the neurons decreased significantly as the drug concentrations and durations increased. The glucose concentration of the neurons that were exposed to both PRL and the ART drugs was significantly decreased. The glucose concentration of the neurons was not affected by any individual drug. The amplitude of the action potential and the expression of Glut3 were decreased in the neurons that were exposed to both PRL and ART drugs. Conclusions: The main adverse reactions induced by the DDIs between PRL and the ART drugs were decreased glucose metabolism and neuronal damage, which were caused by inhibiting the expression of Glut3. More importantly, we found that decreases in glucose metabolism predated neuronal damage. [ABSTRACT FROM AUTHOR]

Many of the cancer cells produce energy with accelerated glycolysis and perform lactic acid production even under normoxic conditions called the "Warburg effect". Metabolism can directly or indirectly regulate the apoptotic mechanism so that cancer cells take advantage of reprogrammed metabolism to avoid apoptosis. The aim of this study is to examine the mechanism of apoptosis by incubating human lung carcinoma cells (A549) under different metabolic conditions in hypoxia or normoxia environments. A549 cells were incubated in the normoxic or hypoxic condition that contained 5 mM glucose (Glc 5), 25 mM glucose (Glc 25), or 10 mM galactose (OXPHOS/aglycemic), and the mechanism of apoptosis was investigated. In the hypoxia condition, the rate of early apoptosis in aglycemic OXPHOS cells was increased (15.5% ±7.1). In addition, the activity of caspase‐3 (6.1% ± 0.9), caspase‐9 (30.4% ± 0.9), and cytochrome c expression level increased; however, the mitochondrial membrane potential (51.9% ± 0.4) was found to be decreased. Changing the amount of oxygen in glycolytic cells had no effect on apoptosis. However, it has been determined that apoptosis is stimulated under hypoxia conditions in aglycemic cells in which galactose is used instead of glucose. Considering that the majority of cancer cells are hypoxic, these data are important in determining targets in therapeutic intervention. Significance statement: Hypoxia, a common feature of solid tumors, greatly hinders the efficacy of conventional cancer treatments such as chemo‐, radio‐, and immunotherapy. Metabolism can directly or indirectly regulate the apoptotic mechanism so that cancer cells take advantage of reprogrammed metabolism to avoid apoptosis. In this article, the link between metabolism and apoptosis pathway under hypoxic conditıon was evaluated in A549 cells. [ABSTRACT FROM AUTHOR]

This study presents an innovative refractive index (RI) sensor that measures glucose concentration by utilizing the photonic spin Hall effect (SHE) in a resonant optical tunneling effect (ROTE) structure. The ROTE structure consists of three InP layers with the high RI and two analyte layers (with a high‐low‐high‐low‐high RI distribution), in which glucose solution samples with the low RI are injected. By subjecting the InP layers to external bias‐assisted light, the photonic SHE can be flexibly manipulated, enabling the modulation of the sensing performance accordingly. It is found that the transverse shift of photonic SHE presents a large variation in response to the tiny change in glucose concentrations. By optimizing the parameters (i.e., intensity or wavelength) of bias light, the sensitivity of this sensor can reach as high as 735.7 µm RIU−1. Compared to traditional glucose sensors, this original work implements the novel photonic SHE with the superior sensing performance. Therefore, the proposed design shows promising potential for biomedical applications, such as medical diagnoses and drug discovery. [ABSTRACT FROM AUTHOR]

Ethanol metabolism is relatively understudied in neurons, even though changes in neuronal metabolism are known to affect their activity. Recent work demonstrates that ethanol is preferentially metabolized over glucose as a source of carbon and energy, and it reprograms neurons to a state of reduced energy potential and diminished capacity to utilize glucose once ethanol is exhausted. Ethanol intake has been associated with changes in neuronal firing and specific brain activity (EEG) patterns have been linked with risk for alcohol use disorder (AUD). Furthermore, a haplotype of the inwardly rectifying potassium channel subunit, GIRK2, which plays a critical role in regulating excitability of neurons, has been linked with AUD and shown to be directly regulated by ethanol. At the same time, overexpression of GIRK2 prevents ethanol‐induced metabolic changes. Based on the available evidence, we conclude that the mechanisms underlying the effects of ethanol on neuronal metabolism are a novel target for developing therapies for AUD. [ABSTRACT FROM AUTHOR]

5‐hydroxymethylfurfural (5‐HMF) has been considered as an important biomass‐based platform chemical for its wide applications. Currently, the production of 5‐HMF from the catalytic dehydration of glucose is preferred, in which the Brønsted and Lewis acids in catalysts play an important role. Here, it was found that MIL‐53(Al) modified with tin was an active, selective, and reusable catalyst for the transformation of glucose to 5‐HMF in dimethyl sulfoxide (DMSO) solvent. Around 42.3% yield of 5‐HMF with 93% glucose conversion was achieved, when the prepared metal‐organic frameworks (MOFs) was used as the catalyst, showing superior catalytic performance compared with most of other MOFs. Moreover, the catalyst possessed inert catalytic properties in water with almost no any influence on the conversion of glucose, suggesting a compelling opportunity to act as a support material. [ABSTRACT FROM AUTHOR]

Objectives: Despite the growing rates of global obesity and the known positive associations between brown adipose tissue (BAT) and cardiovascular health, little is known about the metabolic effects of BAT activity in Samoans, a population at high risk of obesity and type II diabetes. Here we assessed the potential effects of inferred BAT activity on metabolic health markers in Samoan adults exposed to mild cold. Methods: Using point‐of‐care finger prick technology we measured fasting glucose, total cholesterol, high‐density lipoprotein (HDL), and low‐density lipoprotein (LDL) levels before and after 30 min of cold exposure among 61 individuals (38 females, 23 males, ages 31–54) from 'Upolu Island, Samoa. Respiratory quotient was measured by indirect calorimetry to determine substrate metabolism at room temperature and cold exposure. Results: Fasting glucose levels decreased significantly (p <.001) after cold exposure while neither total cholesterol (p =.88), HDL (p =.312), nor LDL (p =.089) changed. Respiratory quotient decreased significantly (p =.009) between exposures, suggesting an increased preference for lipid metabolism as a response to cold. Conclusions: The observed effects of inferred BAT activity on biomarkers suggest BAT activity utilizes both glucose and lipid‐derived fatty acids as fuel for thermogenesis. Our work provides evidence for the beneficial metabolic effects of BAT and emphasizes the need for the population‐specific development of metabolic treatments involving BAT to ensure the successful and equitable minimization of extreme consequences of obesity and metabolic health. [ABSTRACT FROM AUTHOR]

Exposure to stressful stimuli promotes multi‐system biological responses to restore homeostasis. Catecholaminergic neurons in the rostral ventrolateral medulla (RVLM) facilitate sympathetic activity and promote physiological adaptations, including glycaemic mobilization and corticosterone release. While it is unclear how brain regions involved in the cognitive appraisal of stress regulate RVLM neural activity, recent studies found that the rodent ventromedial prefrontal cortex (vmPFC) mediates stress appraisal and physiological stress responses. Thus, a vmPFC–RVLM connection could represent a circuit mechanism linking stress appraisal and physiological reactivity. The current study investigated a direct vmPFC–RVLM circuit utilizing genetically encoded anterograde and retrograde tract tracers. Together, these studies found that stress‐activated vmPFC neurons project to catecholaminergic neurons throughout the ventrolateral medulla in male and female rats. Next, we utilized optogenetic terminal stimulation to evoke vmPFC synaptic glutamate release in the RVLM. Photostimulating the vmPFC–RVLM circuit during restraint stress suppressed glycaemic stress responses in males, without altering the female response. However, circuit stimulation decreased corticosterone responses to stress in both sexes. Circuit stimulation did not modulate affective behaviour in either sex. Further analysis indicated that circuit stimulation preferentially activated non‐catecholaminergic medullary neurons in both sexes. Additionally, vmPFC terminals targeted medullary inhibitory neurons. Thus, both male and female rats have a direct vmPFC projection to the RVLM that reduces endocrine stress responses, likely by recruiting local RVLM inhibitory neurons. Ultimately, the excitatory/inhibitory balance of vmPFC synapses in the RVLM may regulate stress reactivity and stress‐related health outcomes. Key points: Glutamatergic efferents from the ventromedial prefrontal cortex target catecholaminergic neurons throughout the ventrolateral medulla.Partially segregated, stress‐activated ventromedial prefrontal cortex populations innervate the rostral and caudal ventrolateral medulla.Stimulating ventromedial prefrontal cortex synapses in the rostral ventrolateral medulla decreases stress‐induced glucocorticoid release in males and females.Stimulating ventromedial prefrontal cortex terminals in the rostral ventrolateral medulla preferentially activates non‐catecholaminergic neurons.Ventromedial prefrontal cortex terminals target medullary inhibitory neurons. [ABSTRACT FROM AUTHOR]

Nanosecond laser patterning of Copper Metal–Organic Framework (Cu‐MOF) coated substrates is performed to fabricate non‐enzymatic glucose sensing electrodes. The Cu‐MOF coated glass substrate with a cover glass is subjected to a laser patterning process; the amount of MOF, laser fluence, and scan speeds mainly influenced the patterning process. The electrodes are fabricated on coated and covered glass with varying electrical conductivity due to the high laser energy absorptivity. The patterned electrodes consist of graphitic carbon incorporated with nano‐Cu and show a stable electrical conductivity on the coated substrates. The electrodes are chemically active in the Fe2+/Fe3+ redox system; however, their activity varies with patterning conditions. The electrochemical studies in alkaline electrolytes reveal that the as‐fabricated electrodes can sense the glucose molecule in the linear concentration range of 0.025–1.0 and 1.0–10.0 mm, with a maximum sensitivity of 3260.3 µA mM−1 cm−2 and a response time of no more than 5 s, and a limit of detection (LOD) of 0.25 µm. The current recovery rate is higher (> 80%) when adding glucose molecules than when adding other interference molecules, confirming that the electrode is selective toward glucose sensing. The results reveal that the fabricated electrodes act as stable, reusable, non‐enzymatic glucose‐sensing electrodes. [ABSTRACT FROM AUTHOR]

Objective: This study aims to clarify the effects of diabetes mellitus (DM) on inflammatory profile during orthodontic tooth movement (OTM) and explore potential mechanisms. Methods: OTM models were established in healthy (Ctrl) and DM rats for 0, 3, 7 or 14 days. The tooth movement distance and bone structural parameters were analyzed through micro‐CT. The bone resorption activity and periodontal inflammation status were evaluated through histological staining. RNA sequencing was performed to detect differentially expressed genes in force loading‐treated periodontal ligament fibroblasts (PDLFs) with or without high glucose. The differential expression of inflammatory genes associated with NOD‐like receptor family pyrin domain containing 3 (NLRP3) between groups was tested in vitro and in vivo. Results: DM caused remarkable reduction of alveolar bone height and density around the moved tooth, corresponding with the higher bone resorption activity and inflammatory scores of DM group. For force loading‐treated PDLFs, high glucose induced the activation of inflammatory pathways, including NLRP3. Elevated expression of NLRP3 and cascade molecules (Caspase‐1, GSDMD, and IL‐1β) were validated by RT‐qPCR, Western blot, and immunohistochemistry staining. Conclusions: DM alters the inflammatory status of periodontium and affects tissue reconstruction during OTM. NLRP3 inflammasome may involve in diabetes‐induced periodontal changes. [ABSTRACT FROM AUTHOR]

SUMMARY: The composition and abundance of soluble sugars in mature pear (Pyrus) fruit are important for its acceptance by consumers. However, our understanding of the genes responsible for soluble sugar accumulation remains limited. In this study, a S1‐group member of bZIP gene family, PbrbZIP15, was characterized from pear genome through the combined analyses of metabolite and transcriptome data followed by experimental validation. PbrbZIP15, located in nucleus, was found to function in fructose, sucrose, and total soluble sugar accumulation in pear fruit and calli. After analyzing the expression profiles of sugar‐metabolism‐related genes and the distribution of cis‐acting elements in their promoters, the glucose isomerase 1 gene (PbrXylA1), whose corresponding protein catalyzed the isomerization of glucose and fructose in vitro, was identified as a downstream target gene of PbrbZIP15. PbrbZIP15 could directly bind to the G‐box element in PbrXylA1 promoter and activate its transcription, as evidenced by chromatin immunoprecipitation‐quantitative PCR, yeast one‐hybrid, electrophoretic mobility shift assay, and dual‐luciferase assay. PbrXylA1, featuring a leucine‐rich signal peptide in its N‐terminal, was localized to the endoplasmic reticulum. It was validated to play a significant role in fructose, sucrose, and total soluble sugar accumulation in pear fruit and calli, which was associated with the upregulated fructose/glucose ratio. Further studies revealed a positive correlation between the sucrose content and the expression levels of several sucrose‐biosynthesis‐related genes (PbrFRK3/8, PbrSPS1/3/4/8, and PbrSPP1) in PbrbZIP15‐/PbrXylA1‐transgenic fruit/calli. In conclusion, our results suggest that PbrbZIP15‐induced soluble sugar accumulation during pear development is at least partly attributed to the activation of PbrXylA1 transcription. Significance Statement: The composition and abundance of soluble sugars in mature pear fruit are important for its acceptance by consumers, but our understanding of the molecular mechanism underlying soluble sugar accumulation remains limited. Our findings suggest that PbrbZIP15 and its target gene PbrXylA1 participate in glucose isomerization and thus alter the composition and abundance of soluble sugars, ultimately resulting in the sweetness improvement in pear, making them potential targets for molecular breeding. [ABSTRACT FROM AUTHOR]

Aim: To examine the impact of increased hepatic glucose production (HGP) on the decrease in plasma glucose concentration caused by empagliflozin in individuals living with diabetes and in nondiabetic individuals. Methods: A total of 36 individuals living with diabetes and 34 nondiabetic individuals were randomized to receive, in double‐blind fashion, empagliflozin or matching placebo in a 2:1 treatment ratio. Following an overnight fast, HGP was measured with 3‐3H‐glucose infusion before, at the start of, and 3 months after therapy with empagliflozin. Results: On Day 1 of empagliflozin administration, the increase in urinary glucose excretion (UGE) in individuals with normal glucose tolerance was smaller than in those with impaired glucose tolerance and those living with diabetes, and was accompanied by an increase in HGP in all three groups. The amount of glucose returned to the systemic circulation as a result of the increase in HGP was smaller than that excreted by the kidney during the first 3 h after empagliflozin administration, resulting in a decrease in fasting plasma glucose (FPG) concentration. After 3 h, the increase in HGP was in excess of UGE, leading to a small increase in plasma glucose concentration, which reached a new steady state. After 12 weeks, the amount of glucose returned to the circulation due to the empagliflozin‐induced increase in HGP was comparable with that excreted by the kidney in all three groups. Conclusion: The balance between UGE and increase in HGP immediately after sodium‐glucose cotransporter‐2 (SGLT2) inhibition determined the magnitude of decrease in FPG and the new steady state which was achieved. After 12 weeks, the increase in HGP caused by empagliflozin closely matched the amount of glucose excreted by the kidneys; thus, FPG level remained stable despite the continuous urinary excretion of glucose caused by SGLT2 inhibition. [ABSTRACT FROM AUTHOR]

The adoption of hydrogels in most applications is hampered by their high free water content, which limits their mechanical performance and environmental resilience. Herein, this issue is simultaneously addressed by modulating the state of water and the intermolecular interactions in polyacrylamide (PAM) hydrogels. Specifically, PAM hydrogels are toughened by sugaring‐out using a monosaccharide (glucose, G). Glucose is found to facilitate PAM hydrogen bonding and interchain interactions. Meanwhile, the high hygroscopicity of glucose converts some of the free water to bound state, endowing the hydrogels with remarkable resilience to extreme environmental conditions. The PAM‐G hydrogels are demonstrated as multimodal sensors for soft robotics. Moreover, PAM‐G alcogels produced by solvent exchanging with ethanol are shown as effective opto‐mechanical sensors. Notably, all these properties are obtained by the inclusion of glucose, a green additive showing no negative health and environmental effect. [ABSTRACT FROM AUTHOR]

The design of an "H"‐shaped reactor has been studied to satisfy the possibility of using a triphasic medium to transform d‐glucose into 5‐hydroxymethylfurfural (HMF) by a hybrid catalytic process using an immobilized glucose isomerase, allowing the isomerization of D‐glucose to d‐fructose, and a heterogeneous chemical catalyst to catalyze the dehydration of d‐fructose to HMF. The various parameters influencing the transport of d‐fructose within the reactor were studied, namely the difference in pH between the two aqueous phases, the agitation and the quantity of 3,4‐DCPBA/Aliquat336® used to extract and transport continuously the d‐fructose. The pH discrepancy, which must be between 5.0 and 5.5, turns out to be the real driving force behind the extraction of D‐fructose. The D‐Fru/3,4‐DCPBA molar ratio of 1/0.25 allowed the transport of more than 80 % of the D‐fructose initially present and shows that the same molecule of 3,4‐DCPBA is involved at least twice in the transport of D‐fructose and that the 3,4‐DCPBA/Aliquat336® couple performs a turnover within the organic phase. Finally, a HMF production yield of 30.9 % and an isomerization yield of 79.1 % were obtained, illustrating the shift in the isomerization equilibrium made possible by a D‐fructose extraction yield of 96.8 %. [ABSTRACT FROM AUTHOR]

Continuous monitoring of bio/physiological signals will play an essential role in personalized, patient‐centric medicine in the future healthcare industry. One of the challenges involves providing a sustainable, energy‐efficient operation for long‐term monitoring devices. The current technology based on power sources requires periodic replacement. Here, a hybrid film composed of a layer of piezoelectric nanowire (PVDFHFP) and a layer of microgel (pNIPAM‐APBA) is presented that continuously monitors glucose, does not rely on enzymes, is self‐charging, and decouples changes in read‐out signals due to glucose detection from the force is applied to activate self‐charging. By characterizing self‐charging/discharging properties, the operation and sensing mechanism for the nanowire/microgel hybrid film are proposed. A reasonable sensitivity of 70 mV mm−1 with a high linearity value of R2 = 0.9956 is observed. This work demonstrates the potential for use in a self‐charging wearable platform that enables continuous monitoring of bio/physiological signals. [ABSTRACT FROM AUTHOR]

Excessive CO2 and food shortage are two grand challenges of human society. Directly converting CO2 into food materials can simultaneously alleviate both, like what green crops do in nature. Nevertheless, natural photosynthesis has a limited energy efficiency due to low activity and specificity of key enzyme D‐ribulose‐1,5‐bisphosphate carboxylase/oxygenase (RuBisCO). To enhance the efficiency, many prior studies focused on engineering the enzymes, but this study chooses to learn from the nature to design more efficient reactors. This work is original in mimicking the stacked structure of thylakoids in chloroplasts to immobilize RuBisCO in a microreactor using the layer‐by‐layer strategy, obtaining the continuous conversion of CO2 into glucose precursor at 1.9 nmol min−1 with enhanced activity (1.5 times), stability (≈8 times), and reusability (96% after 10 reuses) relative to the free RuBisCO. The microreactors are further scaled out from one to six in parallel and achieve the production at 15.8 nmol min−1 with an energy conversion efficiency of 3.3 times of rice, showing better performance of this artificial synthesis than NPS in terms of energy conversion efficiency. The exploration of the potential of mass production would benefit both food supply and carbon neutralization. [ABSTRACT FROM AUTHOR]

A series of nickel hydroxyapatite catalysts were synthesized by the co‐precipitation method followed by calcination and reduction. These catalysts were employed for the aqueous phase hydrogenation of glucose to sorbitol. The Ni‐HAP catalyst with comparatively high surface area and acid‐base strength gave high sorbitol selectivity in 1 h. Ni‐HAP‐4 catalyst with moderate Ni (3.5 wt. %) content having smaller and highly dispersed nickel particles gives an excellent yield of sorbitol, 97 % in 1 h. The Ni‐HAP‐4 catalyst works well with other polar protic solvents. Different characterization techniques like XRD, TEM, SEM‐EDS, BET, NH3‐TPD, and CO2‐TPD were employed to analyze the Ni‐HAP‐4 catalyst. [ABSTRACT FROM AUTHOR]

Aims/Introduction: Gastric cancer, one of the most common malignant tumors worldwide, is affected by insulin resistance. The triglyceride glucose (TYG) index is considered a surrogate indicator of insulin resistance; however, its prognostic value in patients with gastric cancer remains obscure. This study aimed to determine whether the TYG index could predict the long‐term prognosis of patients with gastric cancer after radical resection gastrectomy. Materials and Methods: We retrospectively analyzed patients with gastric cancer who underwent radical resection gastrectomy. The preoperative TYG index was calculated using the patients' laboratory data. Patients were divided into two groups based on a high or low TYG index. We observed overall survival and evaluated the clinical application value of the index using Cox proportional hazards regression to calculate independent parameters. A prediction model was also established. Results: In total, 822 patients with gastric cancer were included. The high and low TYG index groups comprised 353 and 469 patients, respectively. The overall survival time was significantly longer in the high‐index group than in the low‐index group. In the multivariate analysis, TYG index, preoperative age, surgical procedure, tumor node metastasis (TNM) stage, N stage, and postoperative complications (all p < 0.01) were considered independent prognostic predictors. Based on the multivariate analysis, the riglyceride glucose (TYG) index hazard ratio was 0.70 (95% confidence interval, 0.54–0.89, p = 0.004). Conclusions: We established a model with a high clinical application value and clinical practice relevance to predict the prognosis of gastric cancer. In this model, TYG was an independent protective factor for gastric cancer prognosis. [ABSTRACT FROM AUTHOR]

Corn straw is an abundant and renewable alternative for microbial biopolymer production. In this paper, an engineered Sphingomonas sanxanigenens NXG‐P916 capable of co‐utilising glucose and xylose from corn straw total hydrolysate to produce xanthan gum was constructed. This strain was obtained by introducing the xanthan gum synthetic operon gum as a module into the genome of the constructed chassis strain NXdPE that could mass produce activated precursors of polysaccharide, and in which the transcriptional levels of gum genes were optimised by screening for a more appropriate promoter, P916. As a result, strain NXG‐P916 produced 9.48 ± 0.34 g of xanthan gum per kg of fermentation broth (g/kg) when glucose was used as a carbon source, which was 2.1 times improved over the original engineering strain NXdPE::gum. Furthermore, in batch fermentation, 12.72 ± 0.75 g/kg xanthan gum was produced from the corn straw total hydrolysate containing both glucose and xylose, and the producing xanthan gum showed an ultrahigh molecular weight (UHMW) of 6.04 × 107 Da, which was increased by 15.8 times. Therefore, the great potential of producing UHMW xanthan gum by Sphingomonas sanxanigenens was proved, and the chassis NXdPE has the prospect of becoming an attractive platform organism producing polysaccharides derived from biomass hydrolysates. [ABSTRACT FROM AUTHOR]

Aim: To determine whether glucose volume of distribution (VdGLUCOSE) affects the diagnosis of impaired insulin sensitivity (IS) when using an intravenous glucose tolerance test (IVGTT). Methods: Individuals with distinct levels of IS underwent IVGTT after an overnight fast. The prediabetic group (Prediab; n = 33) differed from the healthy group (Healthy; n = 14) in their larger glycosylated hemoglobin (HbA1c of 5.9 ± 0.3 vs. 5.4 ± 0.1%; 41 ± 4 vs. 36 ± 1 mmol/mol; p < 0.001), percent body fat (37 ± 6 vs. 24 ± 3%; p < 0.001) and cardiovascular fitness level (VO2MAX 22 ± 5 vs. 44 ± 5 mL of O2·kg−1·min−1; p < 0.001). Ten minutes after intravenous infusion of the glucose bolus (i.e., 35 g in a 30% solution), VdGLUCOSE was assessed from the increases in plasma glucose concentration. IS was calculated during the next 50 min using the slope of glucose disappearance and the insulin time‐response curve. Results: VdGLUCOSE was higher in Healthy than in Prediab (230 ± 49 vs. 185 ± 21 mL·kg−1; p < 0.001). VdGLUCOSE was a strong predictor of IS (β standardized coefficient 0.362; p = 0.004). VO2MAX was associated with VdGLUCOSE and IS (Pearson r = 0.582 and 0.704, respectively; p < 0.001). However, body fat was inversely associated with VdGLUCOSE and IS (r = −0.548 and −0.555, respectively; p < 0.001). Conclusions: Since fat mass is inversely related to VdGLUCOSE and in turn, VdGLUCOSE affects the calculations of IS, the IV glucose bolus dose should be calculated based on fat‐free mass rather than body weight for a more accurate diagnosis of impaired IS. [ABSTRACT FROM AUTHOR]

Objective: Enzyme cascade reaction typically involves the synergistic action of two or more enzymes. It is an efficient tool in the field of biosensing. In this research, with the combination of natural enzyme and nanozyme, a high‐performance enzyme cascade bio‐platform is constructed for sensing of H2O2 and glucose. Methods: The enzyme cascade bio‐platform consisting of natural enzyme glucose oxidase (GOX) and nanozyme (hemin@ZIF‐8) was constructed through one‐step co‐precipitation method. The morphology and structure of the composites were characterized by using scanning electron microscopy, x‐ray diffraction and Fourier transform infrared spectrometer. UV‐vis spectrophotometer was used to research the catalytic activity and sensing performances of enzyme cascade bio‐platform. Results: The synergistic catalysis between hemin and ZIF‐8 in hemin@ZIF‐8 nanozyme resulted in highly efficient peroxidase‐like activity, which could be used for H2O2 sensing. The porous structure of the metal‐organic framework provided a good microenvironment for loading the natural enzyme, guaranteeing the enzyme activity and spatial proximity of enzymes. The bio‐platform achieved the sensitive detection of glucose with low detection limit of 7.15 μM. Due to the color change in the catalytic reaction, this bio‐platform can be used for detecting glucose qualitatively and semi‐quantitatively with the naked eye. Conclusions: The constructed efficient enzyme cascade bio‐platform combined the advantages of natural enzyme and nanozyme. This research not only expanded the application possibilities of nanozyme‐based enzyme cascade system, but also offered an effective strategy for the development of simple, rapid and reliable sensing methods for real application. [ABSTRACT FROM AUTHOR]

Truncation of the C‐terminal tail of the β2‐AR, transfection of βARKct or over‐expression of a kinase‐dead GRK mutant reduces isoprenaline‐stimulated glucose uptake, indicating that GRK is important for this response. We explored whether phosphorylation of the β2‐AR by GRK2 has a role in glucose uptake or if this response is related to the role of GRK2 as a scaffolding protein. CHO‐GLUT4myc cells expressing wild‐type and mutant β2‐ARs were generated and receptor affinity for [3H]‐CGP12177A and density of binding sites determined together with the affinity of isoprenaline and BRL37344. Following receptor activation by β2‐AR agonists, cAMP accumulation, GLUT4 translocation, [3H]‐2‐deoxyglucose uptake, and β2‐AR internalization were measured. Bioluminescence resonance energy transfer was used to investigate interactions between β2‐AR and β‐arrestin2 or between β2‐AR and GRK2. Glucose uptake after siRNA knockdown or GRK inhibitors was measured in response to β2‐AR agonists. BRL37344 was a poor partial agonist for cAMP generation but displayed similar potency and efficacy to isoprenaline for glucose uptake and GLUT4 translocation. These responses to β2‐AR agonists occurred in CHO‐GLUT4myc cells expressing β2‐ARs lacking GRK or GRK/PKA phosphorylation sites as well as in cells expressing the wild‐type β2‐AR. However, β2‐ARs lacking phosphorylation sites failed to recruit β‐arrestin2 and did not internalize. GRK2 knock‐down or GRK2 inhibitors decreased isoprenaline‐stimulated glucose uptake in rat L6 skeletal muscle cells. Thus, GRK phosphorylation of the β2‐AR is not associated with isoprenaline‐ or BRL37344‐stimulated glucose uptake. However, GRKs acting as scaffold proteins are important for glucose uptake as GRK2 knock‐down or GRK2 inhibition reduces isoprenaline‐stimulated glucose uptake. [ABSTRACT FROM AUTHOR]

Obesity and metabolic disorders caused by alterations in lipid metabolism are major health issues in developed, affluent societies. Adipose tissue is the only organ that stores lipids and prevents lipotoxicity in other organs. Mature adipocytes can affect themselves and distant metabolism‐related tissues by producing various adipokines, including adiponectin and leptin. The engulfment adaptor phosphotyrosine‐binding domain‐containing 1 (GULP1) regulates intracellular trafficking of glycosphingolipids and cholesterol, suggesting its close association with lipid metabolism. However, the role of GULP1 in adipocytes remains unknown. Therefore, this study aimed to investigate the function of GULP1 in adipogenesis, glucose uptake, and the insulin signaling pathway in adipocytes. A 3T3‐L1 cell line with Gulp1 knockdown (shGulp1) and a 3T3‐L1 control group (U6) were established. Changes in shGulp1 cells due to GULP1 deficiency were examined and compared to those in U6 cells using microarray analysis. Glucose uptake was monitored via insulin stimulation in shGulp1 and U6 cells using a 2‐NBDG glucose uptake assay, and the insulin signaling pathway was investigated by western blot analysis. Adipogenesis was significantly delayed, lipid metabolism was altered, and several adipogenesis‐related genes were downregulated in shGulp1 cells compared to those in U6 cells. Microarray analysis revealed significant inhibition of peroxisome proliferator‐activated receptor signaling in shGulp1 cells compared with U6 cells. The production and secretion of adiponectin as well as the expression of adiponectin receptor were decreased in shGulp1 cells. In particular, compared with U6 cells, glucose uptake via insulin stimulation was significantly decreased in shGulp1 cells through the disturbance of ERK1/2 phosphorylation. This is the first study to identify the role of GULP1 in adipogenesis and insulin‐stimulated glucose uptake by adipocytes, thereby providing new insights into the differentiation and functions of adipocytes and the metabolism of lipids and glucose, which can help better understand metabolic diseases. [ABSTRACT FROM AUTHOR]

In the past several decades, Photoelectrochemical (PEC) sensing still remains a great challenge to design highly‐efficient semiconductor photocatalysts via a facile method. It is of much importance to design and synthesize various novel nanostructured sensing materials for further improving the response performance. Herein, we present an In2O3/In2S3 heterostructure obtained by combining microwave assisted hydrothermal method with S‐induced phase change, whose energy band and electronic structure could be adjusted by changing the S content. Combining theoretical calculation and spectroscopic techniques, the introduction of sulfur was proved to produce multifunctional interfaces, inducing the change of phase, oxygen vacancies and band gap, which accelerates the separation of photoexcited carriers and reduces their recombination, improving the electronic injection efficiency around the interface of In2O3/In2S3. As anticipated, an enhanced glucose response performance with a photocurrent of 0.6 mA cm−2, a linear range of 0.1–1 mM and a detection limit as low as 14.5 μM has been achieved based on the In2O3/In2S3 heterostructure, which is significant superior over its pure In2O3 and S‐doped In2O3 counterparts. This efficient interfacial strategy may open a new route to manipulate the electrical structure, and energy band structure regulation of sensing material to improve the performance of photoelectrodes for PEC. [ABSTRACT FROM AUTHOR]

To explore the relationship between mealtime delays of up to 3 h and subsequent glucose fluctuations, healthy young adults were allocated to three delayed dinnertimes in randomized order. Participants consumed test meals for lunch and dinner. After assessing the glucose responses using intermittently scanned continuous glucose monitoring devices (isCGM), the peak glucose elevation, and incremental area under the curve (iAUC) of postprandial glucose during certain intervals increased significantly when the time between lunch and dinner was delayed by 1 h or more. Our results support the importance of improving irregular mealtime habits, such as late eating. [ABSTRACT FROM AUTHOR]

Summary: Background: Cord blood (CB) leptin is positively associated with adiposity at birth, but the association with child adiposity is unclear. Objectives: We hypothesized that CB leptin is positively associated with adiposity in peripubertal children and with childhood leptin. Methods: Leptin was measured in 986 CB and 931 childhood stored samples from a prospective birth cohort. Adiposity measures were collected at birth and mean age 11.5 years. Linear and logistic regression analyses were used to evaluate associations between log‐transformed CB leptin and neonatal and childhood adiposity measures as continuous and categorical variables, respectively. Results: CB leptin was positively associated with neonatal and childhood adiposity. Childhood associations were attenuated when adjusted for maternal body mass index (BMI) and glucose, but remained statistically significant for childhood body fat percentage (β = 1.15%, confidence interval [CI] = 0.46–1.84), body fat mass (β = 0.69 kg, 95% CI = 0.16–1.23), sum of skin‐folds (β = 1.77 mm, 95% CI = 0.31–3.24), log‐transformed child serum leptin (β = 0.13, 95% CI = 0.06–0.20), overweight/obesity (OR = 1.21, 95% CI = 1.03–1.42), obesity (OR = 1.31, 95% CI = 1.04–1.66) and body fat percentage >85th percentile (OR = 1.38, 95% CI = 1.12–1.73). Positive associations between newborn adiposity measures and CB leptin confirmed previous reports. Conclusion: CB leptin is positively associated with neonatal and childhood adiposity and child leptin levels, independent of maternal BMI and maternal hyperglycemia. CB leptin may be a biomarker of future adiposity risk. [ABSTRACT FROM AUTHOR]

Background: Equine spermatozoa appear to differ from spermatozoa of other species in using oxidative phosphorylation preferentially over glycolysis. However, there is little information regarding effects of different energy sources on measured parameters in equine spermatozoa. Objective: To determine the effect of three individual energy substrates, glucose, pyruvate, and lactate, on motion characteristics, membrane integrity, and acrosomal status of stallion spermatozoa. Materials and methods: Freshly ejaculated stallion spermatozoa were incubated with combinations of glucose (5 mm), pyruvate (10 mm), and lactate (10 mm) for 0.5 to 4 h. Response to calcium ionophore A23187 (5 μm) was used to evaluate capacitation status. Motility was evaluated using computer‐assisted sperm analysis, and plasma membrane and acrosomal integrity were evaluated by flow cytometry. Results: Incubation with lactate alone for 2 h increased acrosomal sensitivity to A23187. Notably, incubation with lactate alone for 4 h induced a significant spontaneous increase in acrosome‐reacted, membrane‐intact (viable) spermatozoa, to approximately 50% of the live population, whereas no increase was seen with incubation in glucose or pyruvate alone. This acrosomal effect was observed in spermatozoa incubated at physiological pH as well as under alkaline conditions (medium pH approximately 8.5). Sperm motility declined concomitantly with the increase in acrosome‐reacted spermatozoa. Sperm motility was significantly higher in pyruvate‐only medium than in glucose or lactate. The addition of pyruvate to lactate‐containing medium increased sperm motility but reduced the proportion of live acrosome‐reacted spermatozoa in a dose‐dependent fashion. Discussion: This is the first study to demonstrate that incubation with a specific energy substrate, lactate, is associated with spontaneous acrosome reaction in spermatozoa. The proportion of live, acrosome‐reacted spermatozoa obtained is among the highest reported for equine spermatozoa. Conclusion: These findings highlight the delicate control of key sperm functions, and may serve as a basis to increase our understanding of stallion sperm physiology. [ABSTRACT FROM AUTHOR]

Aim: To develop a new coculture system that allows exposure of dental pulp cells (DPCs) to Streptococcus mutans and dentine matrix proteins (eDMP) to study cellular interactions in dentine caries. Methodology: Dental pulp cells and S. mutans were cocultured with or without eDMP for 72 h. Cell proliferation and viability were assessed by cell counting and MTT assays, while bacterial growth and viability were determined by CFU and LIVE/DEAD staining. Glucose catabolism and lactate excretion were measured photometrically as metabolic indicators. To evaluate the inflammatory response, the release of cytokines and growth factors (IL‐6, IL‐8, TGF‐β1, VEGF) was determined by ELISA. Non‐parametric statistical analyses were performed to compare all groups and time points (Mann–Whitney U test or Kruskal–Wallis test; α =.05). Results: While eDMP and especially S. mutans reduced the number and viability of DPCs (p ≤.0462), neither DPCs nor eDMP affected the growth and viability of S. mutans during coculture (p >.0546). The growth of S. mutans followed a common curve, but the death phase was not reached within 72 h. S. mutans consumed medium glucose in only 30 h, whereas in the absence of S. mutans, cells were able to catabolize glucose throughout 72 h, resulting in the corresponding amount of l‐lactate. No change in medium pH was observed. S. mutans induced IL‐6 production in DPCs (p ≤.0011), whereas eDMP had no discernible effect (p >.7509). No significant changes in IL‐8 were observed (p >.198). TGF‐β1, available from eDMP supplementation, was reduced by DPCs over time. VEGF, on the other hand, was increased in all groups during coculture. Conclusions: The results show that the coculture of DPCs and S. mutans is possible without functional impairment. The bacterially induced stimulation of proinflammatory and regenerative cytokines provides a basis for future investigations and the elucidation of molecular biological relationships in pulp defence against caries. [ABSTRACT FROM AUTHOR]

Aim: To examine the association between 1‐hour plasma glucose (PG) concentration and markers of non‐alcoholic fatty liver disease (NAFLD) assessed by transient elastography (TE). Methods: We performed TE in 107 metabolically well‐characterized non‐diabetic White individuals. Controlled attenuation parameter (CAP) was used to quantify liver steatosis, while liver stiffness marker (LS) was used to evaluate fibrosis. Results: Controlled attenuation parameter correlated significantly with 1‐hour PG (r = 0.301, P < 0.01), fasting insulin (r = 0.285, P < 0.01), 2‐hour insulin (r = 0.257, P < 0.02), homeostasis model assessment index of insulin resistance (r = 0.252, P < 0.01), high‐density lipoprotein cholesterol (r = −0.252, P < 0.02), body mass index (BMI; r = 0.248, P < 0.02) and age (r = 0.212, P < 0.03), after correction for age, sex and BMI. In a multivariable linear regression analysis, 1‐hour PG (β = 0.274, P = 0.008) and fasting insulin levels (β = 0.225, P = 0.029) were found to be independent predictors of CAP. After excluding subjects with prediabetes, 1‐hour PG was the sole predictor of CAP variation (β = 0.442, P < 0.001). In a logistic regression model, we observed that the group with 1‐hour PG ≥ 8.6 mmol/L (155 mg/dL) had a significantly higher risk of steatosis (odds ratio 3.98, 95% confidence interval 1.43‐11.13; P = 0.008) than individuals with 1‐hour PG < 8.6 mmol/L, after correction for potential confounders. No association was observed between 1‐hour PG and LS. Conclusion: Our data confirm that 1‐hour PG ≥ 8.6 mmol/L is associated with higher signs of NAFLD, even among individuals with normal glucose tolerance, categorized as low risk by canonical diagnostic standards. TE is a safe low‐impact approach that could be employed for stratifying the risk profile in these patients, with a high level of accuracy. [ABSTRACT FROM AUTHOR]

Summary: Strigolactones (SLs) are carotenoid‐derived phytohormones that regulate plant growth and development. While root‐secreted SLs are well‐known to facilitate plant symbiosis with beneficial microbes, the role of SLs in plant interactions with pathogenic microbes remains largely unexplored.Using genetic and biochemical approaches, we demonstrate a negative role of SLs in rice (Oryza sativa) defense against the blast fungus Pyricularia oryzae (syn. Magnaporthe oryzae).We found that SL biosynthesis and perception mutants, and wild‐type (WT) plants after chemical inhibition of SLs, were less susceptible to P. oryzae. Strigolactone deficiency also resulted in a higher accumulation of jasmonates, soluble sugars and flavonoid phytoalexins in rice leaves. Likewise, in response to P. oryzae infection, SL signaling was downregulated, while jasmonate and sugar content increased markedly. The jar1 mutant unable to synthesize jasmonoyl‐l‐isoleucine, and the coi1‐18 RNAi line perturbed in jasmonate signaling, both accumulated lower levels of sugars. However, when WT seedlings were sprayed with glucose or sucrose, jasmonate accumulation increased, suggesting a reciprocal positive interplay between jasmonates and sugars. Finally, we showed that functional jasmonate signaling is necessary for SL deficiency to induce rice defense against P. oryzae.We conclude that a reduction in rice SL content reduces P. oryzae susceptibility by activating jasmonate and sugar signaling pathways, and flavonoid phytoalexin accumulation. [ABSTRACT FROM AUTHOR]

Detection and quantification of glucose and urea are fundamental in medical analysis, real‐time monitoring, and point of care analysis. However, such analyses generally require sophisticated instrumentation and specialized personnel. Furthermore, discriminative detection of multiple analytes is often necessary for treatment and diagnosis. To address this challenge, this study describes a proof‐of‐concept for discriminative sensitive amperometric detection of both analytes. This was achieved by the fabrication of a polymer‐MWCNTs composite nanofiber matrix upon which glucose oxidase (GOD) and urease were co‐immobilized to allow detection of the corresponding substrates (glucose and urea). The (PAN(−MWCNTs)/Urease‐GOD) biosensor showed good performance in: (i) glucose biosensing with sensitivity of 31±5 μAmM−2cm−2 within an extended linear range (0.1–5.0 mM) and a limit of detection of 3.7 μM, and (ii) urea detection at very low concentration (4–30 and 30–90 μM) with sensitivity up to 350±19 μAmM−2cm−2 and very low LOD (0.1 μM). The analogous mono‐enzyme platform for urea detection (PAN(−MWCNTs)/Urease) showed very similar performance as the bi‐enzyme sensor, suggesting little to no influence of co‐immobilization on Urease activity, thus confirming that the two catalytic processes are independent of each other. The biosensors exhibited high accuracy in the detection of both analytes (at normal and pathological levels) in human serum, thus proving that the biosensor described herein can have practical applications in healthcare and remote patient monitoring. [ABSTRACT FROM AUTHOR]