Search Results (661)

Diabetes mellitus remains a major global health burden, and many patients do not achieve durable glycemic control despite modern pharmacotherapy. This narrative review synthesizes evidence on plant-derived strategies that may complement standard care, focusing on two clinically aligned domains: glucose-lowering medicinal plants and plant-based sugar substitutes that reduce dietary glycemic load. We summarize key mechanistic pathways, including inhibition of α-amylase/α-glucosidase, reduced intestinal glucose entry and absorption kinetics, glucose-dependent insulinotropic effects, improved insulin signaling, suppression of hepatic gluconeogenesis, and microbiota-linked effects. We critically appraise human evidence for selected botanicals (cinnamon, fenugreek, mulberry, gymnema, gynura, rosehip, and Jerusalem artichoke) and plant sweeteners (stevia and monk fruit). Overall, clinical effects are modest and heterogeneous; the most reproducible signals are observed for mulberry leaf in blunting postprandial glucose excursions, and for cinnamon, fenugreek, and gymnema, where meta-analyses suggest modest improvements in glycemic markers. Stevia and monk fruit are best supported as glycemically neutral sucrose substitutes, while inulin-type fructans show small-to-moderate benefits with sustained intake, limited by gastrointestinal tolerability at higher doses. Key gaps include a shortage of long-term randomized trials using standardized preparations and durable endpoints such as glycated hemoglobin. Plant-derived interventions are therefore best positioned as adjuncts within individualized, evidence-based glycemic management. Full article

Background: Thyroid hormones regulate energy homeostasis, lipid/glucose metabolism, and protein turnover. Chronic Hepatitis C Virus (HCV) infection is highly associated with autoimmune hypothyroidism, which may have profound metabolic implications. This study evaluates thyroid dysfunction and anti-thyroid peroxidase (anti-TPO) autoimmunity in HCV patients and explores its potential metabolic implications in a high-prevalence region. Methods: In this comparative cross-sectional study adhering to STROBE guidelines, we enrolled 100 PCR-confirmed chronic HCV patients and 100 age/gender-matched controls from District Peshawar, Pakistan. Serum TSH, fT3, fT4, and anti-TPO antibodies were quantified. Multivariable logistic regression, adjusted for age, gender, and viral load, was used to compute adjusted odds ratios (aOR) with 95% confidence intervals (CI). Results: Thyroid dysfunction affected 41% of HCV patients vs. 12% of controls (aOR 5.2, 95% CI 2.8–9.6, p < 0.001), predominantly hypothyroidism (29% overall; 18% overt, 11% subclinical). Anti-TPO positivity was 38% in HCV vs. 8% in controls (aOR 6.7, 95% CI 3.1–14.5, p < 0.001). Anti-TPO titers correlated positively with TSH (r = +0.62, p < 0.001) and inversely with fT3/fT4. Subgroup analysis showed higher dysfunction in patients aged ≥40 years (52% vs. 28%, p = 0.012) and viral load ≥ 10⁶ IU/mL (48% vs. 32%, p = 0.041). We hypothesize that these findings may have significant metabolic implications, including impaired mitochondrial β-oxidation and insulin resistance. Conclusions: HCV infection is strongly associated with autoimmune hypothyroidism, which may amplify cardiometabolic risk. The paper has not explicitly identified metabolic parameters, including lipid profiles, indices of insulin resistance, and metabolomic signatures, and, therefore, any metabolic inferences are speculative and based on established thyroid and HCV pathophysiology. Routine thyroid screening pre- and post-DAA therapy is recommended, alongside metabolomic profiling to validate these proposed metabolic pathways. Full article

Background/Objectives: Insulin resistance and ambulatory blood pressure monitoring (ABPM) abnormalities represent distinct but interrelated pathways contributing to cardiovascular risk. The triglyceride–glucose (TyG) index reflects metabolic burden, whereas arterial load—captured through arterial stiffness, blood pressure variability, and morning surge—reflects hemodynamic instability. Whether the coexistence of these domains identifies a particularly high-risk ambulatory phenotype remains unclear. To evaluate the independent and combined effects of metabolic burden (TyG) and arterial load on circadian blood pressure pattern and short-term systolic blood pressure variability. Methods: This retrospective cross-sectional study included 294 adults who underwent 24 h ABPM. Arterial load was defined using three ABPM-derived indices (high AASI, high SBP-ARV, high morning surge). High metabolic burden was defined as TyG in the upper quartile. The “double-high” phenotype was classified as high TyG plus high arterial load. Primary and secondary outcomes were non-dipping pattern and high SBP variability. Multivariable logistic regression and Firth penalized models were used to assess independent associations. Predictive performance was evaluated using ROC analysis. Results: The double-high phenotype (n = 15) demonstrated significantly higher nighttime SBP, reduced nocturnal dipping, and markedly elevated BP variability. It was the strongest independent predictor of non-dipping (adjusted OR = 42.0; Firth OR = 11.73; both p < 0.001) and high SBP variability (adjusted OR = 41.7; Firth OR = 26.29; both p < 0.001). Arterial load substantially improved model discrimination (AUC = 0.819 for non-dipping; 0.979 for SBP variability), whereas adding TyG to arterial load produced minimal incremental benefit. Conclusions: The coexistence of elevated TyG and increased arterial load defines a distinct hemodynamic endotype characterized by severe circadian blood pressure disruption and exaggerated short-term variability. While arterial load emerged as the principal determinant of adverse ambulatory blood pressure phenotypes, TyG alone demonstrated limited discriminative capacity. These findings suggest that TyG primarily acts as a metabolic modifier, amplifying adverse ambulatory blood pressure phenotypes predominantly in the presence of underlying arterial instability rather than serving as an independent discriminator. Integrating metabolic and hemodynamic domains may therefore improve risk stratification and help identify a small but clinically meaningful subgroup of patients with extreme ambulatory blood pressure dysregulation. Full article

Lactoferrin (LF) is an iron-binding immunoprotein of the mammary gland whose levels increase during mastitis and may be influenced by the metabolic status of the cow. During early lactation, dairy cows are exposed to a negative energy balance (NEB) and the associated increase in susceptibility to mastitis. However, the extent to which the metabolic profile influences LF secretion in milk during the postpartum period remains unclear. The objective of this study was to assess the associations between metabolic status and milk LF contents in Holstein cows (n = 122) in the first twenty days of lactation. Based on the milk LF contents, the cows were categorized into two groups: LF-LOW (≤123 mg/L; n = 81) and LF-HIGH (>123 mg/L; n = 41). Serum indicators of energy and nitrogen metabolism, hepatic function, and selected macro-/microelements were measured; urine electrolytes and net acid–base excretion (U-ABB) were assessed; and milk composition, including somatic cell count (SCC), was determined. LF-HIGH cows showed higher SCC (p = 0.0516) and serum glucose (p < 0.001), together with lower serum triglycerides (p = 0.0101) versus LF-LOW cows. Milk beta-hydroxybutyric acid (BHB) content was lower in the LF-HIGH group (trend, p ≈ 0.062). LF-HIGH also exhibited significantly greater natriuresis (p = 0.0078) and a more negative U-ABB (p < 0.001), indicating higher acid–base load. In conclusion, elevated LF contents during the postpartum period were associated with the activation of local mammary gland immune defence and concurrent compensatory metabolic processes related to NEB, rather than with pronounced alterations in basic milk composition. Milk LF content may therefore be considered as a specific indicator of immunometabolic compensation during the early postpartum period, rather than as a general marker of overall cow health. Full article

Canagliflozin (CFZ), a sodium–glucose cotransporter 2 (SGLT2) inhibitor, is extensively utilized in the management of type 2 diabetes. Among its various polymorphic forms, the hemi-hydrate (Hemi-CFZ) has been selected as the active pharmaceutical ingredient (API) for CFZ tablets due to its superior solubility. However, during the production, storage, and transportation of CFZ tablets, Hemi-CFZ can undergo transformations into anhydrous (An-CFZ) and monohydrate (Mono-CFZ) forms under the influence of environmental factors such as temperature, humidity, and pressure, which may adversely impact the bioavailability and clinical efficacy of CFZ tablets. Therefore, it is imperative to develop rapid, accurate, non-destructive, and non-contact methods for quantifying An-CFZ and Mono-CFZ content in CFZ tablets to control polymorphic impurity levels and ensure product quality. This research evaluated the feasibility and reliability of using near-infrared spectroscopy (NIR) combined with partial least squares regression (PLSR) for simultaneous quantitative analysis of An-CFZ and Mono-CFZ in CFZ tablets, elucidating the quantifying mechanisms of the quantitative analysis model. Orthogonal experiments were designed to investigate the effects of different pretreatment methods and ant colony optimization (ACO) algorithms on the performance of quantitative models. An optimal PLSR model for simultaneous quantification of An-CFZ and Mono-CFZ in CFZ tablets was established and validated over a concentration range of 0.0000 to 10.0000 w/w%. The resulting model, Y_{An-CFZ/Mono-CFZ} = 0.0207 + 0.9919 X, achieved an R² value of 0.9919. By analyzing the relationship between the NIR spectral signals selected by the ACO algorithm and the molecular structure information of An-CFZ and Mono-CFZ, we demonstrated the feasibility and reliability of the NIR-PLSR approach for quantifying these polymorphic forms. Additionally, the mechanism of PLSR quantitative analysis was further explained through the variance contribution rates of latent variables (LVs), the correlations between LVs loadings and tablets composition, and the relationships between LV scores and An-CFZ/Mono-CFZ content. This study not only provides a robust method and theoretical foundation for monitoring An-CFZ and Mono-CFZ content in CFZ tablets throughout production, processing, storage, and transportation, but also offers a reliable methodological reference for the simultaneous quantitative analysis and quality control of multiple polymorphic impurities in other similar drugs. Full article

Allostatic load is a physiological measure of chronic stress, and stress is implicated in disrupting appetite regulation. Individuals with obesity and type 2 diabetes have higher allostatic load compared to lean counterparts. However, whether allostatic load differs across prediabetes phenotypes and relates to appetite is unknown. Purpose: Test whether prediabetes phenotypes differ in allostatic load in relation to altered appetite regulation. Methods: Individuals with obesity were recruited, and prediabetes was determined using American Diabetes Association (ADA) criteria (75 g OGTT) for this cross-sectional study. After an overnight fast, appetite hormones (ghrelin and PYY), insulin, and glucose were measured every 30 min up to 120 min of the OGTT. Perception of hunger and fullness as well as desire for sweet and fatty foods were assessed using a visual analog scale. Allostatic load was calculated from physiologic markers. Aerobic fitness (VO₂max), body composition (DXA), clinical labs, and quality-of-life questionnaires were also collected. Results: Participants with impaired fasting glucose (IFG) + impaired glucose tolerance (IGT) had a higher allostatic load, obesity, and insulin resistance compared with IFG or IGT (all p < 0.05), independent of fitness. IFG + IGT also had lower fasting ghrelin (p < 0.05) and no difference in fasting PYY. Hunger, fullness, and sweet ratings were comparable across groups, but fatty food ratings tended to be higher in IFG + IGT than NGT. Conclusions: Allostatic load was associated with altered fasting ghrelin levels in individuals with IFG + IGT, along with elevated body weight and insulin resistance. These findings suggest stress is a potential mechanism underlying appetite dysregulation in different forms of prediabetes. Full article

This study details the design, fabrication, and experimental validation of a wearable, non-invasive microwave sensor for continuous blood glucose monitoring. It incorporates a crescent-loaded elliptical patch antenna with a complementary split-ring resonator (CSRR) tag unit to greatly improve sensing sensitivity. The sensor operates across multiple resonant frequencies, enabling broadband dielectric characterization of glucose-dependent blood permittivity. Incorporation of the CSRR tag unit leads to a marked improvement in electromagnetic coupling and field confinement, resulting in a substantial increase in sensitivity, achieving 1.14 MHz/mg/dL in resonant frequency shift and 0.015 dB/mg/dL in reflection coefficient sensitivity compared to conventional designs. The sensor was fabricated on an FR-4 substrate and experimentally characterized using a vector network analyzer (VNA), showing strong agreement between simulated and measured S11 responses, with minimal frequency deviations and consistent resonance behavior. Experimental results confirmed improved sensitivity in response to glucose concentration variations over the range of 0–500 mg/dL, validating the sensor’s performance under realistic conditions. Furthermore, a physics-informed deep learning (PI-DL) model was developed to predict glucose concentration directly from measured S11 data. The model achieved enhanced prediction accuracy, with a mean absolute error below 1 mg/dL and a strong generalization across unseen samples, demonstrating the power of combining physical modeling with data-driven approaches. These results confirm that the proposed sensor, enhanced with the CSRR tag unit and supported by a PI-DL framework, offers a promising pathway toward next-generation non-invasive, accurate, and wearable glucose monitoring solutions. Full article

This paper presents a high-sensitivity microwave sensor based on a modified Complementary Split Ring Resonator (CSRR) architecture, integrated with inductive stubs, for non-invasive blood glucose monitoring. The proposed sensor is designed to enhance the electric field localization and coupling efficiency by introducing inductive elements that strengthen the perturbation effect caused by glucose concentration changes in the blood. Numerical simulations were conducted using a multilayer finger model to evaluate the sensor’s performance under various glucose levels ranging from 0 to 500 mg/dL. The modified sensor exhibits dual-resonance characteristics and outperforms the conventional CSRR in both frequency and amplitude sensitivity. At an optimized stub gap of 2 mm, which effectively minimizes the capacitive coupling effect of the transmission line and thereby improves the quality factor, the sensor achieves a frequency shift sensitivity of 0.086 MHz/mg/dL and an amplitude sensitivity of 0.02 dB/mg/dL, compared to 0.032 MHz/mg/dL and 0.0116 dB/mg/dL observed in the standard CSRR structure. This confirms a significant enhancement in sensing performance and field confinement due to the optimized inductive loading. These results represent significant enhancements of approximately 168% and 72%, respectively. With its compact design, increased sensitivity, and potential for wearable implementation, the proposed sensor offers a promising platform for continuous, real-time, and non-invasive glucose monitoring in biomedical applications. Full article

Glucagon-like peptide-1 receptor agonists and lifestyle interventions effectively treat overt obesity, but the benefits/risks of their combined early intervention during middle age remain unclear. This study investigated whether submaximal-dose liraglutide combined with strength–endurance training improves metabolic and liver health, focusing on hepatic oxidative stress and lipid metabolism. Male Wistar rats (16 months old) received liraglutide (L; 0.186 mg/kg/day, s.c.), training (ladder climbing with weights, 3 times/week), both (L+E) or saline for control middle-aged (C) and young adults (CY; 3–4 months old) for 7 weeks (n = 8/group). Middle-aged rats exhibited age-related changes including higher body and visceral fat, increased hepatic and serum cholesterol, hepatic ALT and glutathione imbalance, and decreased soleus muscle (p < 0.05, vs. CY). Exercise increased hepatic glycogen and oxidative stress markers and downregulated lipogenic genes, consistent with liver adaptation to training. L+E synergistically reduced body and visceral fat, hepatic and serum triglycerides, and the triglyceride–glucose index, while reducing oxidative stress (p < 0.05 vs. E, C) and lipogenic gene expression (p < 0.05 vs. C), without affecting pancreas histopathology and function parameters, muscle mass or exercise load volume. In conclusion, submaximal liraglutide safely synergized with training to enhance metabolic health, improve hepatic redox balance and triglyceride metabolism in middle-aged rats, without mitigating cholesterol rise. Full article

ITIC’s superior electron-accepting capacity and efficient oxygen reduction motivated the design of a sensor to enhance sensitivity, selectivity, and stability over conventional oxygen-dependent or fullerene-based systems. As oxygen acts as the terminal reagent in enzymatic glucose oxidation, we developed an ITIC-mediated glucose oxidase (GOx) biosensor on glassy carbon (GCE) and screen-printed carbon electrodes (SPCE). ITIC, a non-fullerene organic semiconductor, was drop-cast onto the electrode to catalyze oxygen reduction, followed by GOx immobilization in a chitosan matrix. Scanning electron microscopy (SEM) confirmed uniform, ultrathin coatings without significant morphological changes upon ITIC and GOx deposition. Electrochemical studies (cyclic (CV) and differential pulse voltammetry (DPV)) revealed a distinct ITIC reduction peak at –0.7 V (vs. Ag/AgCl) and a glucose-dependent current decrease, consistent with mediated electron transfer during enzymatic oxidation. Under optimized conditions, the GCE-based biosensor showed a sensitivity of 10.7 μA L mmol⁻¹, a linear dynamic range (LDR) of 0.10–1.00 mmol L⁻¹, and detection (LOD)/quantification (LOQ) limits of 0.02 and 0.06 mmol L⁻¹, respectively. The SPCE device displayed sensitivity (3.8 μA L mmol⁻¹) and maintained excellent linearity (R² > 0.99) with LOD and LOQ of 0.05 and 0.16 mmol L⁻¹. Both platforms showed good precision (RSD < 5%) and reliable recovery in deproteinized plasma and artificial tears (90–104%). The superior performance of the GCE is attributed to higher ITIC loading, faster electron transfer, and reduced background current, while the SPCE offers a low-cost, disposable format with sufficient analytical performance for point-of-care glucose monitoring. Full article

The Berberis nummularia fruit is rich in polyphenols and which are associated with the inhibition of carbohydrate-digesting enzymes. However, the phytochemical compositions, antioxidant strength, and the ability of the fruits on the inhibition of α-amylase to control postprandial blood glucose remained elusive. In this study, therefore, different concentrations of ethanol were used in ultrasound processing at 70 °C for 1 h to obtain the crude polyphenol of B. nummularia fruit (CPB) and obtain the purified polyphenol (PPB) using AB-8 macroporous resin. After this, the polyphenolic constituents within PPB were identified using LC-MS/QTOF and investigated for anti-hyperglycemic properties by sucrose loading test. The results showed that the optimal extraction yield (44.32 ± 2.08%) of CPB was achieved with 30% ethanol and the PPB from CPB was reached at 71.88 ± 2.74%. A total of 30 polyphenols including 13 phenolic acids, 13 flavonoids, 3 benzaldehyde derivatives, and 1 aromatic acid were identified, in which the caffeic acid had the highest content (426.20 ± 0.18 ng/mg). The PPB displayed potent α-amylase inhibitory activity with an IC₅₀ value of 69.91 μg/mL and kinetic analysis via Lineweaver–Burk double reciprocal plots confirmed a non-competitive inhibition mechanism. Moreover, at an administration dose of 100 mg/kg body weight (BW), PPB significantly reduced blood glucose levels by 13.75 ± 0.87% and exerted a marked ameliorative effect on postprandial hyperglycemia in vivo. Therefore, these findings provide a foundation for considering PPB as a beneficial functional food ingredient and a potential dietary supplement for the management of postprandial hyperglycemia. Full article

Background/Objectives: The glycemic index (GI) is a critical factor in managing blood sugar levels and related diseases. Grains, as staple foods consumed worldwide, are primary sources of carbohydrates, starch, and dietary fiber (DF). The carbohydrate composition of grains can significantly influence postprandial blood glucose levels. Therefore, understanding how different carbohydrate components affect blood glucose is essential. Methods: This study retrospectively examined the relationship between carbohydrate composition and GI in various grains, cereals, and legumes. Data on grain and cereal components were obtained from reputable public databases, including PubMed, the U.S. Department of Agriculture (USDA), FooDB, and published studies. Results: Analysis of the GI and glycemic load (GL) across grain components revealed several key findings. In addition to total carbohydrate (TC), both dietary starch (DS) and dietary fiber (DF) had substantial effects on GI. Interestingly, total sugar (TS), often considered a primary concern, showed no significant association with GI. Multiple regression and linear regression analyses demonstrated strong correlations between GI and both TC and DS. Among ratio metrics, the TC-to-DF ratio displayed significant correlation with GI (R = 0.48, p = 0.0003), followed by the DS-to-DF ratio (R = 0.33, p = 0.0159). The TS-to-DF ratio, however, showed no significant correlation (R = 0.04, p = 0.7544). Conclusions: These findings suggest that carbohydrate-to-fiber ratios, especially TC-to-DF, may play an important role in determining GI. Other dietary components, such as dietary fiber and dietary starch, might also affect these results. Additional studies are needed to examine how factors beyond carbohydrates influence GI. These observations may help guide future work aimed at better understanding dietary effects on health. Further, our results offer valuable insights for making healthier nutritional choices and improving the management of chronic diseases. Full article

Background: Enteropathogenic Escherichia coli (EPEC) disrupts intestinal barrier integrity by adhering to epithelial cells, leading to diarrhea, impaired nutrient absorption, oxidative stress, and intestinal inflammation in young animals. This study aimed to isolate and characterize a neutral exopolysaccharide (EPS-T1) from Enterococcus faecium HDRsEf1, evaluate its functional activities in vitro, and assess its protective effects against EPEC-induced enteritis in vivo. Results: EPS-T1, with a molecular weight of 81.21 ± 1.28 kDa, was mainly composed of glucose, galactose, rhamnose, and mannose, and exhibited a porous, sheet structure with relatively high thermal stability. In vitro, EPS-T1 (200 μg/mL) significantly inhibited EPEC growth and biofilm formation, reduced bacterial adhesion to intestinal epithelial cells, and exhibited broad-spectrum free radical scavenging activity. In vivo, EPS-T1 treatment alleviated EPEC-induced weight loss and intestinal tissue damage, reduced the intestinal EPEC load, downregulated pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), upregulated the anti-inflammatory cytokine IL-10, and improved serum antioxidant indices (T-AOC, SOD, and GSH-PX) while decreasing MDA levels. Conclusions: These results demonstrate that EPS-T1 derived from Enterococcus effectively mitigates EPEC-induced intestinal inflammation and oxidative stress, highlighting its potential as an immunobiotic functional candidate. Full article

Background/Objectives: High-altitude hypoxia may affect ECG readings, but it is unclear whether the “live-low–train-high” approach prevents these changes in winter sports athletes. Methods: This cross-sectional study assessed cardiovascular parameters in 102 winter-sport athletes (mean age 20 ± 4 y; 57% women), divided by training altitude into a high-altitude (HA) group (2500–3300 m, n = 70; skiers/snowboarders) and a low-altitude (LA) group (738 m, n = 32; ice hockey/figure skaters). Mid-season assessments included resting ECG, blood pressure, blood biochemistry, and three 24 h dietary recalls. Results: All ECG parameters were physiological, and no significant differences (p < 0.05) were observed in heart rate, PR interval, or QTc between groups. However, HA group exhibited higher systolic blood pressure and a short QT interval. Lactate was significantly higher in HA (p = 0.028). The HA diet contained more saturated fat (p < 0.001), cholesterol (p = 0.013), magnesium (p = 0.003) and potassium (p = 0.001), whereas LA athletes consumed more glucose (p = 0.024). In HA, total energy expenditure correlated positively (p ≥ 0.05) with QRS (ρ = 0.52) and QT (ρ = 0.56), while heart rate correlated inversely with vitamin D (ρ = −0.59). In LA, QTc showed strong inverse correlations with zinc (ρ = −0.62) and selenium (ρ = −0.85). Conclusions: This finding suggests that intermittent high-altitude training did not alter ECG patterns when nutrient intake was adequate. High lactate level and specific nutrient correlations point to a residual physiological load and a modulatory role of electrolytes, B-vitamins, and vitamin D on cardiac repolarisation. Full article

The application of water-tolerant bifunctional solid acids with high kinetic performance in converting glucose to 5-hydroxymethylfurfural (HMF) presents a number of challenges. In this study, the effect of doping a hierarchically porous tantalum phosphate monolith with transition metal ions (Nb⁵⁺, V⁵⁺, Zr⁴⁺, Ni²⁺, and Zn²⁺) was explored in delivering superior glucose dehydration kinetics and stability. Doping with Nb⁵⁺ (x%Nb-TaP) resulted in the best catalytic performance with enhanced tantalum phosphate stability. The incorporation of Nb⁵⁺ ions inhibited tantalum phosphate crystallization, increased the density of Lewis acid and Brønsted acid sites and average mesopore size, with consequently enhanced kinetics, enabling the reaction kinetics of fructose to approach a steady state. Application of a 25% mol/mol Nb (25%Nb-TaP) activated at 600 °C to convert 1.0 wt.% glucose in a water/methyl isobutyl ketone (MIBK) biphasic system delivered an HMF yield and selectivity of 72.6% and 95.6%, respectively. Moreover, an HMF productivity of 0.11 mol·h⁻¹·kg-solution⁻¹ was achieved by treating a 15.0 wt.% glucose feed at 170 °C in a water/MIBK biphasic system at a catalyst loading of 10.0 wt.%. The 25%Nb-TaP catalyst largely retained its initial activity after three recycles in the water/MIBK biphasic system, generating an HMF yield of 54.1% and selectivity of 87.0%. The results of this study demonstrate the significant potential of Nb-TaP for industrial-scale HMF production. Full article