Changes and Significance of Central Carbon Metabolism before and after Metformin Treatment of Type 2 Diabetes Based on Mass Spectrometry.

BACKGROUND: An imbalance in energy metabolism serves as a causal factor for type 2 diabetes (T2D). Although metformin has been known to ameliorate the overall energy metabolism imbalance, but the direct correlation between metformin and central carbon metabolism (CCM) has not been thoroughly investigated. In this study, we employed a high-performance ion chromatography-tandem mass spectrometry (HPIC-MS/MS) technique to examine the alterations and significance of CCM both before and after metformin treatment for T2D. METHODS: We recruited 29 participants, comprising 10 individuals recently diagnosed with T2D (T2D group). Among these, 10 patients underwent a 4-6-week treatment with metformin (MET group). Additionally, we included 9 healthy subjects (CON group). Employing HPIC-MS/MS, we quantitatively analyzed 56 metabolites across 18 biologically relevant metabolic pathways associated with CCM. Univariate and multivariate statistical analyses were utilized to identify differential metabolites. Subsequently, correlation analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted on the identified differential metabolites. RESULTS: We identified seven distinct metabolites in individuals with T2D (p < 0.05). Notably, cyclic 3',5'-Adenosine MonoPhosphate (AMP), Glucose 6-phosphate, L-lactic acid, Maleic acid, and Malic acid exhibited a reversal to normal levels following metformin treatment. Furthermore, Malic acid demonstrated a positive correlation with L-lactic acid (r = 0.94, p < 0.05), as did succinic acid with malic acid (r = 0.81, p < 0.05), L-lactic acid with succinic acid (r = 0.78, p < 0.05), and L-lactic acid with glucose-6-phosphate (r = 0.72, p < 0.05). These metabolites were notably enriched in pyruvate metabolism (p = 0.005), tricarboxylic acid cycle (TCA) (p = 0.007), propanoate metabolism (p = 0.007), and glycolysis or gluconeogenesis (p = 0.009), respectively. CONCLUSIONS: We employed HPIC-MS/MS to uncover alterations in CCM among individuals recently diagnosed with T2D before and after metformin treatment. The findings suggest that metformin may ameliorate the energy metabolism imbalance in T2D by reducing intermediates within the CCM pathway.

Saccharin Sodium Coupling Fluorinated Solvent Enabled Stable Interface for High-Voltage Li-Metal Batteries.

Optimizing the electrode/electrolyte interface structure is the key to realizing high-voltage Li-metal batteries (LMBs). Herein, a functional electrolyte is introduced to synergetically regulate the interface layer structures on the high-voltage cathode and the Li-metal anode. Saccharin sodium (NaSH) as a multifunctional electrolyte additive is employed in fluorinated solvent-based electrolyte (FBE) for robust interphase layer construction. On the one hand, combining the results of ex-situ techniques and in-situ electrochemical dissipative quartz crystal microbalance (EQCM-D) technique, it can be seen that the solid electrolyte interface (SEI) layer constructed by NaSH-coupled fluoroethylene carbonate (FEC) on Li-metal anode significantly inhibits the growth of lithium dendrites and improves the cyclic stability of the anode. On the other hand, the experimental results also confirm that the cathode-electrolyte interface (CEI) layer induced by NaSH-coupled FEC effectively protects the active materials of LiCoO2 and improves their structural stability under high-voltage cycling, thus avoiding the material rupture. Moreover, theoretical calculation results show that the addition of NaSH alters the desolvation behavior of Li+ and enhances the transport kinetics of Li+ at the electrode/electrolyte interface. In this contribution, the LiCoO2 ǁLi full cell containing FBE+NaSH results in a high capacity retention of 80% after 530 cycles with a coulombic efficiency of 99.8%.

Optimizing the method for removing MSNs templates using an ionic liquid ([C4mim]Cl).

The key step in preparing mesoporous silica is to remove the organic template agent, and the most common method used to achieve this goal is high-temperature calcination. However, this method has many disadvantages, one of which is that it reduces the silanol density on the surface of mesoporous silica, which affects its subsequent modification. Ionic liquids (ILs) are often used as extractants. In this work, the 1-butyl-3-methylimidazolium chloride ([C4mim]Cl) IL is considered, and the effects of its concentration, reaction temperature, and reaction time as well as HCl concentration on the extraction rate and silanol density were investigated using an IL extraction template agent (cetyl trimethyl ammonium bromide (CTAB)). The results show that an IL concentration of 10%, a reaction temperature of 120 °C, a reaction time of 12 h, and an HCl concentration of 1% are the best reaction parameters; with these parameters, the extraction rate and the silanol density were found to be 93.19% and 2.23%, respectively. The silanol density of mesoporous silica treated by calcination is only 0.81%. A higher silanol density provides more reaction sites, so that the modified mesoporous silica treated with the IL can be loaded with more Zn ions.

Berberine influences multiple diseases by modifying gut microbiota.

Berberine (BBR) is an isoquinoline alkaloid that is widely distributed in the plant kingdom and is commonly found in Coptis chinensis Franch. It has low bioavailability, but it can interact with gut microbiota and affect a variety of diseases. The effects of BBR in diabetes, hyperlipidemia, atherosclerosis, liver diseases, intestinal diseases, mental disorders, autoimmune diseases, and other diseases are all thought to be related to gut microbiota. This review systematically and comprehensively summarize these interactions and their effects, and describes the changes of gut microbiota after the intervention of different doses of berberine and its potential clinical consequences, in order to provide a basis for the rational application of BBR in the future clinical treatment.

A Mixed Protonic-Electronic Conductor Base on the Host-Guest Architecture of 2D Metal-Organic Layers and Inorganic Layers.

The key to designing and fabricating highly efficient mixed protonic-electronic conductors materials (MPECs) is to integrate the mixed conductive active sites into a single structure, to break through the shortcomings of traditional physical blending. Herein, based on the host-guest interaction, an MPEC is consisted of 2D metal-organic layers and hydrogen-bonded inorganic layers by the assembly methods of layered intercalation. Noticeably, the 2D intercalated materials (≈1.3 nm) exhibit the proton conductivity and electron conductivity, which are 2.02 × 10-5 and 3.84 × 10-4 S cm-1 at 100 °C and 99% relative humidity, much higher than these of pure 2D metal-organic layers (>>1.0 × 10-10 and 2.01×10-8 S cm-1 ), respectively. Furthermore, combining accurate structural information and theoretical calculations reveals that the inserted hydrogen-bonded inorganic layers provide the proton source and a networks of hydrogen-bonds leading to efficient proton transport, meanwhile reducing the bandgap of hybrid architecture and increasing the band electron delocalization of the metal-organic layer to greatly elevate the electron transport of intrinsic 2D metal-organic frameworks.

Correlation between gut bacteria Phascolarctobacterium and exogenous metabolite α-linolenic acid in T2DM: a case-control study.

Background: The relationship between gut microbiota and metabolites play an important role in the occurrence and development of type 2 diabetes mellitus (T2DM). However, the interaction between intestinal flora abundance and metabolites is still unclear. The purpose of this study was to investigate the correlation of the interaction network between intestinal flora and fecal metabolites in regulating the occurrence of T2DM. Methods: This a case-control study. T2DM patients with different glucose levels and healthy people were divided into case group and normal controls (NC) group. Fasting plasma and fecal samples were collected from the subjects. Ultra-performance liquid chromatography-tandem mass spectrometry (LC-MS) untargeted fecal metabolomics was used to detect small molecular metabolites within 1,500 Da in two groups. The diversity and richness of intestinal flora were analyzed by the 16SrRNA third-generation full-length sequencing technique and the correlation between intestinal microflora and different metabolites was evaluated. Results: A total of 30 patients with T2DM and 21 NC were included for analysis, glycated hemoglobin (HbAlc) (P<0.001), fasting blood glucose (FBG) (P<0.001), total triglycerides (TG) (P=0.002), and fasting serum insulin (FINS) (P=0.026) were significantly higher in the T2DM group compared with the NC group. The fecal metabolomics profiles of the T2DM group and NC group were significantly different, and 355 different metabolites were identified among the two. Compared with the NC group, the levels of ornithine (P=0.04), L-lysine (P=0.03), glutamate (P=0.01), alpha-linolenic acid (P=0.004), traumatin (P=0.05), and erucic acid (P=0.004) in the T2DM group decreased significantly, while PC[18:3(6Z,9Z,12Z)/24:1(15Z)] (P<0.001) levels increased. Compared with the NC group, the richness of Megamonas and Escherichia increased in T2DM patients, while that of Bacteroidota and Phascolarctobacterium were lower. Pearson correlation analysis revealed associations between gut microbiota and faecal metabolites, and Phascolarctobacterium was positively correlated with alpha-linolenic acid (r=0.72, P<0.001). Conclusions: There may be a mutual regulatory network between intestinal bacteria and fecal metabolites in T2DM. The increased abundance of Phascolarctobacterium may increase alpha-linolenic acid uptake, and alpha-linolenic acid may also increase the abundance of intestinal Phascolarctobacterium in vivo after metabolic transformation. The combination of the two may play an important role in the treatment of diabetes.

High-Content Lithium Aluminum Titanium Phosphate-Based Composite Solid Electrolyte with Poly(ionic liquid) Binder.

Solid electrolytes have been regarded as the most promising electrolyte materials for the next generation of flexible electronic devices due to their excellent safety and machinability. Herein, composite solid electrolytes (CSE) with "polymer in ceramic" are prepared by using lithium aluminum titanium phosphate (LATP) as a matrix and modified poly(ionic liquid) as a binder. The results revealed that adding a poly(ionic liquid)-based binder not only endowed good flexibility for solid electrolytes, but also significantly improved the ionic conductivity of the electrolytes. When the content of LATP in the CSE was 50 wt.%, the electrolyte obtained the highest ionic conductivity (1.2 × 10-3 S·cm-1), which was one order of magnitude higher than that of the pristine LATP. Finally, this study also characterized the compression resistance of the composite solid-state electrolyte by testing the Vickers hardness, and the results showed that the hardness of the composite solid-state electrolyte can reach 0.9 ± 0.1 gf/mm2 at a LATP content of 50 wt.%.

Preparation and characterization of vanillin-chitosan Schiff base zinc complex for a novel Zn2+ sustained released system.

In this work, a novel sustained released system (VCSB-Zn(II)) for zinc supplements was built by vanillin-chitosan Schiff base (VCSB) chelated with Zn2+ to improve the zinc trace element utilization ratio. Samples were characterized by FT-IR, 1H NMR, XRD, SEM, and TGA. The results showed that VCSB exhibited a more excellent chelation capacity of Zn2+ than chitosan. The chelation capacity of VCSB was about 1.7 times more than that of chitosan, corresponding to 50.96 mg/g and 29.91 mg/g, respectively. Furthermore, VCSB-Zn(II) showed excellent sustained released performance at simulated gastric fluid because of the acid slow-dissolving ability. And the higher the CN content of VCSB, the higher the cumulative release rate (Ri) of Zn2+, the highest Ri reached 77.81%. The sustained released curves were described by the first-order and Korsmeyer-Peppas equation, which described the Zn2+ sustained released performance caused by the dissolution of VCSB-Zn(II) and Fick diffusion. This Zn2+ sustained released system shows great potential in the application in the field of trace elements supplements for animals.

Enhancing the activity of metal-organic nanosheets for oxygen evolution reaction by substituent effects.

Rational designing and synthesizing highly efficient oxygen evolution reaction (OER) electrocatalyst plays a key role in energy conversion. However, due to the numerous factors affecting the activity of electrocatalysis, the understanding of their catalytic mechanism is insufficient, and challenges still exist. Herein, the organic group of the metal-organic nanosheets electrocatalyst was replaced by NH2 to CH3 to controllable regulate the catalytic performance of OER, corresponding to the overpotential of OER reducing from 385 mV to 318 mV at 10 mA cm-2, superior to the commercial precious metal based catalyst RuO2. Furthermore, combining the density functional theory (DFT) and electron localization function (ELF) indicates that the type of ligands group can indirectly modulate the electronic structure of metal catalytic center and the degree of electronic localization of the metal-organic nanosheets catalysts, resulting in the change in electrocatalytic activity. This simple catalytic model is more favorable to investigate the catalytic mechanism, providing a new strategy for the development of efficient electrocatalyst.

Mechanism research on the interaction regulation of Escherichia and IFN-γ for the occurrence of T2DM.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major social and public health problem which may be induced by intestinal flora imbalance through inflammatory response, and the specific mechanism remains unclear. In this study, we aim to explore the interaction network of intestinal flora and cell inflammation in T2DM. METHODS: This a case-control study. Patients with T2DM was the case group and healthy people as control. The differences of cytokine expression levels between patients with T2DM and healthy controls were assessed by using flow cytometry. The diversity and abundance of intestinal flora were evaluated by using 16S rRNA three-generation full-length sequencing technology. RESULTS: A total of 29 patients with T2DM and 28 healthy controls were included for analysis. Compared with the healthy control group, the expression levels of plasma cytokine interleukin-2 (IL-2) (P=0.0000006), IL-6 (P=0.000193), tumor necrosis factor α (TNF-α) (P=0.016), interferon-γ (IFN-γ) (P=0.000036) and interleukin-17 (IL-17) (P=0.004) were significantly up-regulated in T2DM patients, and the abundance of Megamonas_funiformis (P=0.0016) and Escherichia (P=0.049) in the intestine were significantly increased. In contrast, the abundance of Bacteroides_stercoris (P=0.0068), Bacteroides_uniformis (P=0.033), and Phascolarctobacterium_faecium (P=0.033) were decreased in T2DM patients. Further, differentially expressed Escherichia had a positive correlation with IFN-γ (r=0.73) by Pearson correlation analysis. CONCLUSIONS: The interaction network between the intestinal bacteria Escherichia and the cytokine IFN-γ may drive inflammation in visceral adipose tissue (VAT), indicating insulin signal transduction can be inhibited in adipocytes to induce insulin resistance.

Synthesis, Characterization, Immune Regulation, and Antioxidative Assessment of Yeast-Derived Selenium Nanoparticles in Cyclophosphamide-Induced Rats.

This article introduces an environmentally friendly and more economical method for preparing red selenium nanoparticles (Se-NPs) with high stability, good biocompatibility, and narrow size using yeast as a bio-reducing agent with high antioxidant, immune regulation, and low toxicity than inorganic and organic Se. The yeast-derived Se-NPs were characterized by scanning electron microscopy, transmission electron microscopy, energy dispersive spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. The results revealed spherical-shaped particles of Se-NPs with an average diameter of 71.14 ± 18.17 nm, an amorphous structure, and surface enhancement with an organic shell layer, that provide precise geometry and stability in the formation of bio-inert gray or black Se-NPs instead of red Se-NPs. Furthermore, the addition of 0.3-0.8 mg/kg Se-NPs in the feed significantly improved the health of mice. As Se-NPs stimulated the oxidative state of mice, it significantly increased the level of GSH-Px, SOD, and AOC, and decreased the level of MDA. The yeast-derived Se-NPs alleviated the immunosuppression induced by cyclophosphamide, whereas protected the liver, spleen, and kidney of mice, stimulated the humoral immune potential of the mice, and significantly increased the levels of I g M, IgA, and I g G. These results indicated that the yeast-derived Se-NPs, as a trace element feed additive, increased the defense of the animal against oxidative stress and infectious diseases and therefore Se-NPs can be used as a potential antibiotic substitute for animal husbandry.