Search Results (2,373)

Background/Objectives: The increase in incidences of multidrug resistance exacerbates tuberculosis-related global health challenges and underscores a call for more efforts for development of new antitubercular drugs, including the use of medicinal plants, especially those that have been used for generations by traditional healers. Despite reports of antimicrobial activity and chemical profiling of Kirkia wilmsii (K. wilmsii) extracts, chemical structures of the bioactive agents have not been elucidated. Here, we used a combination of bioactivity-guided fractionation, mass spectrometry, and nuclear magnetic resonance to purify and elucidate the chemical structure of antimycobacterial agents contained in leaf and twig extracts for K. wilmsii. Results: After overnight extraction with acetone and 90 g of dry twigs and leaves produced 5.38 g (6%) and 4.56 g (5%) of product, which displayed moderate antimycobacterial activity of 0.5 and 1 mg/mL, respectively. The antimycobacterial activity was increased six- and three-fold, respectively, after the crude extracts were subjected to solvent–solvent partitioning. Due to many bioactive fractions being obtained after silica gel chromatography purification, fraction 5 of twig extract was prioritized for further purification due to its low minimum inhibitory concentration (MIC) (0.25 mg/mL) and cytotoxicity (20%, in THP-1 cells). Sequential purification of the fraction 5 (twig extract) extracts through the C18 cartridge and high-performance liquid chromatography (HPLC) produced four fractions, which were subjected to structural elucidation. The high-resolution mass spectrometric analyses revealed that the first two eluting peaks had the same mass ion of 441.0822 m/z (M − H⁻), which corresponded to catechin monogallate, and so were the last two eluting peaks, which had a mass ion of 539.0932 m/z (M − H⁻), corresponding to catechin digallate. Further analyses by ¹H, ¹³C, and 2D NMR confirmed the chemical structures of compounds eluting in the first two peaks on HPLC as structural isomers of catechin 3′-monogallate and catechin 4′-monogallate (MIC not determined). Similarly, compounds eluting in the last two peaks were identified as structural isomers catechin 3′-digallate and catechin 4′-digallate, with an MIC of 250 µg/mL against Mycobacterium smegmatis and Mycobacterium tuberculosis H37Rv and an MBC of 500 μg/mL against M. smegmatis. Conclusions: To the best of our knowledge, this study is the first to report the structure of catechin 3′- and 4′-digallate, their antimycobacterial activity, and the existence of acyl migration involving galloyl 3′ and 4′-hydroxyl groups of catechin ring B. Full article

Apple aroma is an important factor influencing consumers’ preferences. To understand the overall flavor characteristics of apples (Ruixue, Liangzhi, Grystal Fuji, and Guifei), volatile compounds and aroma profiles were investigated by headspace–gas chromatography–ion mobility spectrometry (HS-GC-IMS) combined with stir bar sorptive extraction (SBSE) and gas chromatography–mass spectrometry (GC-MS). The results showed that a total of 56 aroma compounds were identified by SBSE-GC-MS, and 39 aroma-active compounds were screened out using aroma intensity (AI) and odor activity value (OAV). Aroma recombination experiments showed enhanced ‘fruity’ and ‘sweet’ notes, whereas ‘floral’, ‘woody’, and ‘green’ aromas were weaker compared to the Crystal Fuji sample. Additionally, GC-IMS coupled with principal component analysis (PCA) was used to distinguish the apple samples, and partial least squares regression (PLSR) was applied to explore the correlation between sensory attributes and characteristic aroma compounds. The results indicated that Crystal Fuji exhibited the greatest correlation with the “woody” attribute, and Ruixue was highly correlated with “fruity”, “green”, and “sour” attributes, while butanoic acid, β-damascenone, butyl acetate, pentyl acetate, furfuryl alcohol, γ-decalactone, and vanillin had a significant impact on the “flower” and “sweet” attributes of Guifei. This study clarified the characteristic aroma composition of the four apple cultivars, providing data support for apple flavor quality evaluation and cultivar optimization. Full article

Previous studies have demonstrated that catecholamines, including epinephrine (Epi), norepinephrine (NE), and dopamine (DA), function both as xenosiderophores for bacteria possessing dedicated transport channels and as potential quorum-sensing signaling molecules or regulatory factors. However, current research on the interactions between dopamine and bacteria remains relatively limited. In this study, treatment of Escherichia coli (E. coli) ATCC 11303 with a specific concentration of dopamine resulted in a 33.63% increase in the maximum growth biomass, a 47.32% enhancement in biofilm formation, a 24.60% increase in protease activity, a 68.81% improvement in swimming motility, and increases of 33.77% and 47.67% in chemotaxis and swarming motility, respectively. Transcriptome analysis revealed that dopamine promoted the expression of numerous iron uptake-related genes, while biofilm formation-related genes and virulence genes were concomitantly upregulated. High-performance liquid chromatography–mass spectrometry (HPLC-MS) and isotope ratio mass spectrometry (IRMS) analyses confirmed that E. coli ATCC 11303 can uptake dopamine, suggesting the existence of specific transport pathways. Multi-omics analysis revealed significant regulatory effects on metal ion transport, amino acid metabolism, purine metabolism, environmental adaptation, quorum sensing, two-component systems, and xylene degradation pathways. Dopamine may act as both a xenosiderophore and a signaling molecule, thereby modulating multiple critical physiological and biochemical processes and promoting bacterial growth. These findings provide valuable insights into the development of novel exogenous xenosiderophores and signaling modulators, advancing our understanding of microbial interactions with their host environment and contributing to the field of microbial endocrinology. Full article

Paris polyphylla (Chonglou), a medicinal herb documented in Shennong’s Classic of Materia Medica and a key component of formulas such as Yunnan Baiyao, is a rare and endangered plant prized for its bioactive steroidal saponins, notably polyphyllin I (PPI) and II (PPII). However, its pharmacological potential is hampered by inefficient extraction and unreliable compound identification. Herein, we developed a sustainable and efficient extraction strategy using ultrasound-assisted deep eutectic solvents (DES), optimized via an L₉(3⁴) orthogonal experimental design. Extraction efficiencies across the seven Paris species ranged from 2.04% to 16.51%, achieved by systematically optimizing key parameters such as the choline chloride-to-ethanol molar ratio (1:1.8), material-to-liquid ratio (1:20 g mL⁻¹), and extraction time (100 min). By ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS) analysis, PPI and PPII were quantified using specific retention times and characteristic fragment ions, revealing content ranges of 3.282–21.452 mg g⁻¹ and 4.201–17.975 mg g⁻¹, respectively. This methodology provides a robust platform for quality control and standardization of Paris-derived medicines, while paving the way for sustainable utilization and in-depth study of its steroidal saponins. Full article

Synthesized by expressing natural collagen sequences in specific hosts, recombinant collagen exhibits multiple advantages, encompassing a higher content of bioactive domains, enhanced antioxidant activity, the absence of viral pathogens, favorable hydrophilicity, reproducible production, and low immunogenicity. Consequently, it has found extensive use in applications ranging from biomaterials and pharmaceuticals to skincare. This review systematically explores various expression systems for recombinant collagen, including those utilizing Escherichia coli, Pichia pastoris, plants, insect baculovirus, and mammalian cells. It provides a detailed comparison of their differences and commonalities in terms of production efficiency, post-translational modification capability, and cost-effectiveness. Key separation and purification techniques for recombinant collage-notably precipitation, affinity chromatography, ion-exchange chromatography, and gel filtration chromatography are further introduced, with an in-depth analysis of the applicable scenarios and purification outcomes for each method. Finally, the review comprehensively summarizes the characterization methods for both the physicochemical properties and biological functions of recombinant collagen. For physicochemical properties, techniques covered include scanning electron microscopy, micro-differential thermal analysis, circular dichroism spectroscopy, SDS-PAGE, mass spectrometry, and Fourier-transform infrared spectroscopy. For biological functions, the focus is on its roles and the corresponding assessment methods in processes such as cell proliferation, migration, adhesion, and wound healing. Building upon this comprehensive overview, current challenges facing recombinant collagen are identified, and future directions are proposed, emphasizing the need to reduce R&D costs, refine testing methods for cosmetic products, and improve safety evaluation protocols to advance the field. Full article

Sweet potatoes (Ipomoea batatas (L.) Lam.) are known for their anti-inflammatory effects, which are attributed to their phytochemical content. Our previous study revealed that ethanol extracts of sweet potato storage roots (SP-EtOH-Ex) inhibit interleukin-6 (IL-6) production in RAW264.7 cells stimulated with lipopolysaccharide (LPS). However, the causative compounds responsible for the anti-inflammatory effect have not yet been identified. This study aims to identify the compounds responsible for the anti-inflammatory effect of SP-EtOH-Ex using liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-Q-TOF-MS). The unknown compounds were measured using the auto MS/MS mode (data-dependent acquisition; DDA) of LC-Q-TOF-MS, and the resulting data were analyzed using MS-DIAL and MS-FINDER and also compared with those of the corresponding reference standards in terms of retention time and fragment ions. As a result, β-sitosterol (2.527–4.850 µg/mL), campesterol (75.74–93.63 ng/mL), and lauroyl diethanolamide (4.568–9.260 ng/mL) were identified and quantified in SP-EtOH-Ex. Moreover, the anti-inflammatory effect of these three compounds against RAW264.7 cells was investigated at varying concentrations of β-sitosterol (1 µg/mL, 5 µg/mL, 10 µg/mL), campesterol (10 ng/mL, 100 ng/mL, 1000 ng/mL), and lauroyl diethanolamide (1 ng/mL, 10 ng/mL, 100 ng/mL). The phytosterols β-sitosterol and campesterol suppressed LPS-induced IL-6 production at concentrations comparable to those present in SP-EtOH-Ex. In contrast, lauroyl diethanolamide did not similarly suppress LPS-induced IL-6 production. These results suggest that β-sitosterol and campesterol in sweet potato storage roots contribute to their anti-inflammatory effects. The lack of activity in lauroyl diethanolamide further supports that phytosterols are the primary anti-inflammatory constituents. The edible portion of sweet potatoes holds promise as a promising raw material with anti-inflammatory properties. Full article

Recent discoveries of fluorite–barite deposits in the Donghai–Linshu area in northern Jiangsu Province, China, underscore the region’s mineral potential, yet detailed geological investigations remain limited. In this study, we examined monzonite and quartz monzonite from drill cores in the Jiashan mining area using petrography, U–Pb zircon dating, zircon trace element geochemistry, whole-rock geochemistry, and zircon Lu–Hf isotopes. Laser ablation inductively coupled plasma mass spectrometry (LA–ICP–MS) zircon U–Pb analyses were conducted to constrain the crystallization ages of the monzonite (127.06 ± 0.54 Ma and 126.83 ± 0.75 Ma) and quartz monzonite (127.2 ± 0.5 Ma and 128.59 ± 0.62 Ma) to the Early Cretaceous, marking a significant magmatic event. Many of the zircons contain inherited Neoproterozoic cores (718–760 Ma and 800–860 Ma), indicating the assimilation of deep crustal materials of this age. The monzonite is metaluminous, with moderate SiO₂ (61.61–62.41 wt.%), high alkalis (Na₂O + K₂O = 7.48–7.92 wt.%), and A/CNK = 0.72–0.91. The quartz monzonite has higher SiO₂ (66.26–68.18 wt.%) and alkalis (8.32–9.33 wt.%). Both rock types exhibit similar trace and rare earth element patterns: enrichment in large-ion lithophile and light rare earth elements, depletions in Nb, Ta, and Ti, no significant Zr-Hf depletion, and weak negative Eu anomalies (δEu ≈ 0.84–1.00). Their low Zr + Nb + Ce + Y contents, Ga/Al ratios, and TFeO/MgO ratios indicate that they have an I-type granite affinity. The Early Cretaceous zircons have highly negative ε_Hf(t) values (−33.7 to −23.5) and ancient two-stage model ages (2622–3247 Ma), which are consistent with derivation from Archean crust. The inherited Neoproterozoic zircons have younger Paleo–Mesoproterozoic T_DM2 ages. The evidence suggests that both intrusions were mainly generated by partial melting of ancient Archean basement, with minor mantle input. The magma generation was likely triggered by crustal anatexis induced by the underplating of mantle-derived magmas in an extensional tectonic regime, coeval with Early Cretaceous magmatism in the Sulu orogen. Full article

Protein phosphorylation is a crucial post-translational modification that regulates protein activity, cellular signaling, transcriptional regulation, and cell cycle control. However, the analysis of phosphoproteins in biological samples is often compromised by complex sample matrices and interference from high-abundance proteins. While the top-down phosphoproteomics strategy enables comprehensive analysis of post-translational modifications based on intact proteins, its requirement for higher protein purity due to low protein ionization efficiency poses stern challenges. Consequently, developing appropriate enrichment methods for phosphoproteins in practical samples becomes essential. Immobilized metal ion affinity chromatography (IMAC) represents a common strategy for phosphorylated protein separation and enrichment. Among metal ions, Ti⁴⁺ has gained widespread application as IMAC chelating ligands due to its capacity to form multiple coordination networks and its high selectivity for phosphorylated protein enrichment, leveraging the strong chelating ability of phosphate groups toward metal ions. This paper presents the design and preparation of a novel magnetic Ti-IMAC nanocomposite, MNP@MPTMS–VPA–Ti(IV). The material is modified with phosphate groups via facile thiol-ene click chemistry and then immobilizes Ti⁴⁺, enabling selective enrichment of intact phosphoproteins through IMAC affinity. The efficiency of enrichment was evaluated using subsequent matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) for detection and analysis. This Ti-IMAC material-based magnetic solid-phase extraction (MSPE)-MALDI-TOF MS protocol has been successfully applied to enrich intact phosphoproteins in milk and eel mucus with high selectivity, sensitivity, and suitability. Full article

The use of lecithin as an emulsifier in food supplements has increased in recent years. However, successful formation of liposomes or micelles requires an appropriate mixture of phospholipids in lecithin. To evaluate the emulsification properties of lecithin for food supplements, a reliable analytical procedure for characterizing phospholipids is necessary. A liquid chromatography–mass spectrometry method was developed to identify phospholipids in lecithin without standard reference materials. For efficient separation of phospholipids before mass spectrometric analysis, a reverse-phase high-performance liquid chromatography method was optimized using a Waters XBridge Protein BEH C4 column. The optimized chromatographic method demonstrated good linearity and precision. Molecular ions were detected in full scan mode to determine accurate mass-to-charge ratios for individual peaks in the chromatogram. A custom Python program was then used to generate a list of possible phospholipid species for each peak based on the measured mass-to-charge ratios. Tandem mass spectrometry was performed to confirm the identity of specific phospholipids by comparing experimental fragmentation patterns with theoretical predictions. Identification of the phospholipids was also confirmed with four commercially available standard reference compounds, demonstrating the reliability of the proposed approach. The developed method offers a practical and cost-effective strategy for identifying phospholipids in complex matrices, especially when standard reference compounds are unavailable. Additionally, it enables targeted selection of standard compounds for future quantitative analyses, making it a valuable tool for comprehensive lipid profiling. Full article

Fragmentation Resilience Energy Mass Spectrometry (FREMS) builds on the field of energy-resolved mass spectrometry and previously used methods, e.g., Survival Yield. It exploits breakdown energies at near “continuous” ramp (0.2% NCE increments) to offer higher resolution and a reliable method for compound differentiation, contaminant identification and structural elucidation. Implementation of FREMS involves acquiring ion breakdown/formation curves as collision energy is incrementally increased. These curves themselves can be analyzed by several means to give a single metric—Fragmentation Resilience (FR₅₀). This value has been shown to be experimentally interchangeable with the modified-Survival Yield (m-SY₅₀) and the Cross-Intersect (C-I). A full panel of testing on an LTQ-Orbitrap revealed that breakdown energies depend only on three controllable parameters—number of ions inside the ion trap, Maximum Inject time and Activation Time. A fairly linear relationship (R² > 0.95) with proposed FR₅₀, m-SY₅₀ and C-I metrics provides reliable adjustment mechanisms for these variables via calibrations. Consequently, this technique can be applied to ions produced by any atmospheric pressure ionization processes and treated as exclusively in vacuo experiments. Applications of FREMS to 4-chlorobenzylpyridinium ion revealed that under collisional activated dissociation (CAD) conditions, the rate of decomposition of precursor ion is equivalent to the rate of formation of its fragments, i.e., normalized breakdown and formation curves intersect at inflection points. Full article

This study investigates Metal–Organic Vapor Phase Epitaxy (MOVPE)-grown AlGaN/GaN and AlN/GaN heterostructures using high-temperature thermal annealing and Secondary Ion Mass Spectrometry (SIMS). By fitting experimental diffusion coefficients (DAl) to the Arrhenius equation, two crucial kinetic parameters were found: the activation energy (E_a) and the pre-factor (D₀). In the AlGaN/GaN structure, the dominating out-diffusion of Al has a large D₀ = 4.03 × 10⁻⁵ cm² s⁻¹ and a low activation energy in the range of [2.1–2.4 eV]. A substitutional diffusion mechanism in the crystal lattice mediated by defects is closely linked to the low E_a. Significantly higher activation energies (E_a) of 3.66 and 4.59 eV, respectively, control both in- and out-diffusion processes in the AlN/GaN structure. The better intrinsic thermal stability of the pure AlN layer, whose stability is attained by a strong energy barrier, is confirmed by the increase of more than 1.2 eV in E_a. Full article

Hawk tea (Litsea coreana Levl. var. lanuginosa), a naturally caffeine-free herbal beverage widely consumed in Southwest China, is characterized by a pronounced camphoraceous note that often deters first-time consumers. In this study, hawk tea leaves were subjected to solid-state fermentation with four microbial strains—Monascus purpureus, Aspergillus cristatus, Bacillus subtilis, and Blastobotrys adeninivorans. The volatile compounds of unfermented and fermented hawk teas were identified by ultra-fast gas chromatography electronic nose (ultra-fast GC e-nose), gas chromatography–mass spectrometry (GC-MS) and gas chromatography–ion mobility spectrometry (GC-IMS) analyses, respectively. Furthermore, the calculation of odor activity values (OAVs) and relative odor activity value (ROAV) revealed that 6 and 25 volatile chemicals, including perillaldehyde (OAV 3.692) and linalool (ROAV 100), were the main contributors to the floral, fruity, and woody aroma of fermented hawk tea. Sensory evaluation confirmed that fermentation generally enhanced woody notes while significantly reducing the characteristic camphoraceous and oil oxidation odors. Notably, the Blastobotrys adeninivorans-fermented sample exhibited the most pronounced floral and fruity nuances, accompanied by significantly elevated aroma complexity and acceptability. Consequently, Blastobotrys adeninivorans represents a promising starter culture for the improvement of hawk tea flavor. Full article

Background: Triple-negative breast cancer (TNBC) remains primarily treated with chemotherapy due to the lack of effective therapeutic targets, but this approach carries significant systemic toxicity and a high risk of drug resistance. Curcumin (Cur), despite its multifaceted antitumor activity, faces limitations in clinical application due to poor water solubility and weak targeting properties. This study aims to develop a folate/mitochondria dual-targeted curcumin–copper chelate liposome (Cu-Cur DTLPs) formulation that enables copper accumulation within tumor cells and induces copper-mediated cell death, thereby providing an effective and relatively low-toxicity therapeutic strategy for triple-negative breast cancer. Methods: Curcumin–copper chelates (Cu-Cur) were first synthesized and characterized using mass spectrometry, NMR, and infrared spectroscopy. Subsequently, dual-targeted liposomes (Cu-Cur DTLPs) were prepared via the thin-film dispersion method, with systematic evaluation of particle size, zeta potential, encapsulation efficiency, and in vitro release profiles. In vitro cytotoxicity was assessed against 4T-1 and MDA-MB-231 cells using the MTT assay. In a 4T-1 tumor-bearing BALB/c mouse model, comprehensive evaluation of targeting efficiency, antitumor efficacy, and mechanisms of action was conducted via in vivo imaging, tumor volume monitoring, immunohistochemistry (detecting FDX1 and DLAT proteins), and TUNEL staining. Results: Cu-Cur DTLPs with a uniform particle size of approximately 104.4 nm were successfully synthesized. In vitro and in vivo studies demonstrated that compared to free curcumin and conventional liposomes, Cu-Cur DTLPs significantly enhanced drug accumulation in tumor tissues and exhibited effective tumor growth inhibition. Mechanistic studies confirmed that this formulation specifically accumulates copper ions within tumor cells, upregulates FDX1, promotes DLAT oligomerization, and induces mitochondrial dysfunction, thereby driving copper death. TUNEL staining ruled out apoptosis as the primary mechanism. Safety evaluation revealed no significant toxicity in major organs. Conclusions: The Cu-Cur DTLPs developed in this study effectively induce copper-mediated death in TNBC through a dual-targeted delivery system, significantly enhancing antitumor activity with favorable safety profiles. This establishes a highly promising novel nanotherapeutic strategy for TNBC treatment. Full article

The Sar-e-Sang lapis lazuli deposit has a mining history exceeding 5000 years, producing the world’s finest lapis lazuli. Recently, gem-quality forsterite has been discovered in the marble containing spinel, dolomite, and phlogopite at the periphery of the lapis lazuli ore body at the Pitawak mine, located east of the Sar-e-Sang deposit. The mineral assemblage indicates that the protolith of this marble is dolomite with aluminous and siliceous components. These forsterite crystals occur as colorless, transparent anhedral grains, exhibiting distinct red fluorescence under 365 nm ultraviolet light. To investigate the gemological and spectroscopic characteristics of the Pitawak mine forsterite, this study conducted and analyzed data from basic gemological analysis, electron probe microanalysis (EPMA), Laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS), ultraviolet–visible absorption spectroscopy (UV-VIS), Fourier-transform infrared spectroscopy (FTIR), laser Raman spectroscopy (RAMAN), and photoluminescence spectroscopy (PL) on four forsterite samples from the Pitawak mine. The analysis results reveal that the samples indicate a composition close to ideal forsterite with a crystal chemical formula of (Mg_2.00Fe_0.02)_Σ2.02Si_0.99O₄. The trace elements present include Fe, Mn, Ca, and minor amounts of Cr and Ni. The UV-VIS spectroscopy results show that the samples possess high transmittance across the visible light range with very weak absorption bands, contributing to the colorless and transparent appearance of Pitawak mine forsterite. This phenomenon is attributed to the extremely low content of chromophoric elements, which have a negligible effect on the forsterite’s color. PL spectroscopy indicates that the red fluorescence of the samples is caused by an emission peak near 642 nm. This emission peak arises from the spin-forbidden ⁴T₁ → ⁶A₁ transition of Mn²⁺ ions situated in octahedral sites within the forsterite structure. Full article

Background: Uncontrolled diabetes is characterised by a loss of blood glucose control and increased oxidation of fatty acids to produce ATP. Use of metabolic inhibitors to blunt fatty acid oxidation and restore glucose metabolism is a poorly studied intervention for diabetes. Methods: Steptozotocin-induced diabetes was developed in Wistar male rats. A subset was supplemented with mildronate (100 mg/kg—14 days). Exploiting liquid chromatography-mass spectrometry for workflows including ion exchange-, C18-reverse phase- and HILIC-based chromatography methods, metabolite levels were quantified in plasma liver and brain tissue. Using both untargeted and targeted metabolomic analysis changes to the global tissue metabolome and individual metabolic pathways were estimated. Results: We document that an inhibitor of carnitine synthesis, mildronate, decreased plasma (50% p < 0.01) carnitine abundance and decreased plasma glucose concentration by one-third compared to streptozotocin (STZ)-treated rats (p < 0.001). Targeted metabolomic analysis of the liver showed decreased alpha-ketoglutarate abundance (35% p < 0.05) by STZ diabetes that was further decreased following mildronate treatment (50% p < 0.05). For both beta-hydroxybutyrate and succinate levels, STZ diabetes increased hepatic abundance by 50% (p < 0.05 for both), which was restored to control levels by mildronate (p < 0.05 for both). In contrast, brain TCA intermediate abundances were unaffected by either STZ diabetes or mildronate (NS for all). STZ diabetes also decreased abundance of pentose phosphate pathway (PPP) metabolites in the liver (glucose-6-phosphate, 6-phosphogluconolactone, 6-phosphogluconate 50% for all; p < 0.05), which was not restored by mildronate treatment. However, brain PPP metabolite abundance was unchanged by STZ diabetes or mildronate (NS for all). However, mildronate treatment did not affect the increased abundance of brain sorbitol, sorbitol-6-phosphate and glucose-6-phosphate as a result of STZ diabetes. Conclusions: Together, these observations highlight the potential role that metabolic inhibitors, like mildronate, may play in restoring blood glucose for diabetic patients, without a direct effect of tissues that represent obligate consumers of glucose (e.g., brain) whilst manipulating fat oxidation in tissues such as the liver. Full article