Dendrobium officinale Polysaccharide Alleviates Type 2 Diabetes Mellitus by Restoring Gut Microbiota and Repairing Intestinal Barrier via the LPS/TLR4/TRIF/NF-kB Axis

Dendrobium officinale polysaccharide (DOP), the main active component, has a variety of bioactivities. In this study, a type 2 diabetes mellitus (T2DM) and antibiotic-induced pseudo-germ-free mouse models were used to investigate the hypoglycemic mechanisms of DOP. The findings showed that DOP ameliorated dysfunctional glucolipid metabolism, lipopolysaccharide (LPS) leakage, and metabolic inflammation levels in T2DM mice. Furthermore, DOP significantly upregulated the mRNA expression of tight junction proteins Claudin-1, Occludin, and ZO-1 and reduced intestinal inflammation and oxidative stress damage through the LPS/TLR4/TRIF/NF-κB axis to repair the intestinal barrier. Interestingly, pseudo-germ-free mouse experiments confirmed that the above beneficial effects of DOP were dependent on gut microbiota. 16S rRNA analysis showed that DOP strongly inhibited the harmful bacterium Helicobacter by 94.57% and facilitated the proliferation of probiotics Allobaculum, Bifidobacterium, and Lactobacillus by 34.96, 139.41, and 88.95%, respectively. Therefore, DOP is capable of rebuilding certain specific intestinal microbiota to restore intestinal barrier injury, which supports the utilization of DOP as a new type of prebiotic in functional foods for T2DM

Two-way ANOVA of pH levels and metal species effects for total amounts of the metals leached from the soil columns.

<p>Note: **significant at 99% probability level, *significant at 95% probability level.</p

Variation of the percentage of metals in different fractions.

<p>Species distribution of Cu, Pb, Cd and Zn extracted with Tessier scheme before and after the column tests.</p

Leaching experimental design.

<p>(A) Schematic diagram of soil column. (B) Schematic analytical setup for the measurement of metal concentrations in the leaching experiment.</p

Total amounts of the metals leached from the soil columns in mg of metal per kg of soil.

<p>Note: The values are means ± standard deviation. Different lower case letters show significant differences in the same treatment (ANOVA/LSD, <i>P</i><0.05).</p

Metal concentrations in leachates as functions of addition of SAR.

<p>The concentrations of Cu and Zn in the leachates as functions of addition of SAR at different pHs. (A) Copper. (B) Zinc.</p

Molecular Dynamic Simulation To Reveal the Mechanism Underlying MGL-3196 Resistance to Thyroxine Receptor Beta

Thyroxine receptor beta (TRβ) is a ligand-dependent nuclear receptor that participates in regulating multiple biological processes, particularly playing an important role in lipid metabolism regulation. TRβ is currently a popular therapeutic target for nonalcoholic steatohepatitis (NASH), while no drugs have been approved to treat this disease. MGL-3196 (Resmetirom) is the first TRβ agonist that has succeeded in phase III clinical trials for the treatment of NASH; therefore, studying its molecular mechanism of action is of great significance. In this study, we employed molecular dynamic simulation to investigate the interaction mode between MGL-3196 and TRβ at the all-atom level. More importantly, by comparing the binding patterns of MGL-3196 in several prevalent TRβ mutants, it was identified that the mutations R243Q and H435R located, respectively, around and within the ligand-binding pocket of TRβ cause TRβ to be insensitive to MGL-3196. This indicates that patients with NASH carrying these two mutations may exhibit resistance to the medication of MGL-3196, thereby highlighting the potential impact of TRβ mutations on TRβ-targeted treatment of NASH and beyond

Dual Lewis Acid- and Base-Responsive Terpyridine-Based Hydrogel: Programmable and Spatiotemporal Regulation of Fluorescence for Chemical-Based Information Security

A huge amount of data inundated in our daily life; there is an ever-increasing need to develop a new strategy of information encryption–decryption–erasing. Herein, a polymeric DCTpy/PAM hydrogel has been fabricated to store information via controllable Eu3+/Zn2+ ionoprinting for hierarchical and multidimensional information decryption. Eu3+ and Zn2+ have a competition and dynamic interaction toward DCTpy under NH3 stimuli in the polymeric DCTpy/PAM hydrogel network. The Eu(III)/Zn(II)@DCTpy/PAM hydrogel exhibits light red fluorescence of Eu3+ due to the antenna effect. Upon the addition of NH3, dissociation of the Eu3+–DCTpy complex takes place, and the Zn(II)/DCTpy/NH3 complex is formed with both ICT (intramolecular charge-transfer) and PET (photo-induced electron-transfer) process characteristics that exhibits yellow emission color. Subsequently, HCl can quench the fluorescence of the resulting hydrogel. By integrating transparency, adhesiveness, and programmable stimuli responsiveness of the hydrogel blocks in to one system, complex, multistage, and time-controlled information storage–encryption–decryption–erasing in sequence with multidimensions is illustrated via the molecule diffusion method. This work provides a novel and representative strategy in fabricating information encryption–decryption-erasing materials with high capacity and complexity by a simple terpyridine-based hydrogel

Weighted bilinear coding model.

Weighted bilinear coding model.</p

Comparison with baseline on QMUL-Shoe.

Comparison with baseline on QMUL-Shoe.</p