Role of liver sinusoidal endothelial cell in metabolic dysfunction-associated fatty liver disease.

Liver sinusoidal endothelial cells (LSECs) are highly specialized endothelial cells that represent the interface between blood cells on one side and hepatocytes on the other side. LSECs not only form a barrier within the hepatic sinus, but also play important physiological functions such as regulating hepatic vascular pressure, anti-inflammatory and anti-fibrotic. Pathologically, pathogenic factors can induce LSECs capillarization, that is, loss of fenestra and dysfunction, which are conducive to early steatosis, lay the foundation for the progression of metabolic dysfunction-associated fatty liver disease (MAFLD), and accelerate metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. The unique localization, phenotype, and function of LSECs make them potential candidates for reducing liver injury, inflammation, and preventing or reversing fibrosis in the future.

Modified Hu-lu-ba-wan protects diabetic glomerular podocytes via promoting PKM2-mediated mitochondrial dynamic homeostasis.

BACKGROUND: Mitochondrial dysfunction is implicated in the progression of diabetic kidney disease (DKD). Damaged mitochondria produce excessive reactive oxygen species (ROS) that can cause apoptosis. Mitochondrial dynamics control the quality and function of mitochondria. Targeting mitochondrial dynamics may reduce ROS-induced apoptosis and improve renal injury in DKD. Modified Hu-lu-ba-wan (MHLBW) shows distinct clinical effects on DKD patients, which are related to its role in antioxidant stress modulation. However, the relevant mechanisms of MHLBW have not been clearly explored. PURPOSE: This study was aimed to evaluate the therapeutic effects of MHLBW on spontaneous DKD mice and clarify the potential mechanisms. METHODS: The main components of MHLBW were identified by HPLC. Using db/db mice as DKD models, we evaluated the therapeutic effects of MHLBW on mice after an 8-week administration. We investigated the molecular mechanism of MHLBW in regulating mitochondrial dynamic homeostasis, podocyte apoptosis, and glomerular damage. After that, computational docking analysis and in vitro experiments were conducted for further mechanism verification. RESULTS: Intragastric administration of MHLBW for 8 weeks in db/db mice significantly improved glucose metabolism, basement membrane thickening, mesangial expansion, glomerular fibrosis, and podocyte injury. MHLBW can reverse podocyte apoptosis via promoting mitochondrial dynamic homeostasis, which was related to regulating the PKM2/ PGC-1α/Opa1 pathway. Berberine (BBR), one of the components of MHLBW, exhibited preeminent affinity with PKM2 as reflected by computational docking analysis. In cultured podocytes, BBR can also prevent apoptosis by promoting PKM2-mediated mitochondrial dynamic homeostasis. CONCLUSION: Our study demonstrates that MHLBW can treat DKD by inhibiting glomerular damage and podocyte apoptosis through positive regulation of PKM2-mediated mitochondrial dynamic homeostasis. These results may provide a potential strategy against DKD.

3D microscopy at the nanoscale reveals unexpected lattice rotations in deformed nickel.

In polycrystalline metals, plastic deformation is accompanied by lattice rotations resulting from dislocation glide. Following these rotations in three dimensions requires nondestructive methods that so far have been limited to grain sizes at the micrometer scale. We tracked the rotations of individual grains in nanograined nickel by using three-dimensional orientation mapping in a transmission electron microscope before and after in situ nanomechanical testing. Many of the larger-size grains underwent unexpected lattice rotations, which we attributed to a reversal of rotation during unloading. This inherent reversible rotation originated from a back stress-driven dislocation slip process that was more active for larger grains. These results provide insights into the fundamental deformation mechanisms of nanograined metals and will help to guide strategies for material design and engineering applications.

Multi-target regulation of intestinal microbiota by berberine to improve type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) and its complications are major public health problems that seriously affect the quality of human life. The modification of intestinal microbiota has been widely recognized for the management of diabetes. The relationship between T2DM, intestinal microbiota, and active ingredient berberine (BBR) in intestinal microbiota was reviewed in this paper. First of all, the richness and functional changes of intestinal microbiota disrupt the intestinal environment through the destruction of the intestinal barrier and fermentation/degradation of pathogenic/protective metabolites, targeting the liver, pancreas, visceral adipose tissue (VAT), etc., to affect intestinal health, blood glucose, and lipids, insulin resistance and inflammation. Then, we focus on BBR, which protects the composition of intestinal microbiota, the changes of intestinal metabolites, and immune regulation disorder of the intestinal environment as the therapeutic mechanism as well as its current clinical trials. Further research can analyze the mechanism network of BBR to exert its therapeutic effect according to its multi-target compound action, to provide a theoretical basis for the use of different phytochemical components alone or in combination to prevent and treat T2DM or other metabolic diseases by regulating intestinal microbiota.

New Therapeutic Horizon of Graves' Hyperthyroidism: Treatment Regimens Based on Immunology and Ingredients From Traditional Chinese Medicine.

Graves' disease is an autoimmune disease characterized by goiter and hyperthyroidism, and 25% patients develop GO. Traditional treatment options, such as antithyroid drugs, radioiodine or thyroidectomy, have remained largely unchanged over the past 70 years. For many patients, there is a high rate of recurrence after antithyroid drugs and lifelong hypothyroidism after ablation and thyroidectomy. The symptoms and quality of life of some patients have not been effectively improved. The clinical demand for new therapeutic regimens, coupled with a deeper understanding of the pathophysiology and immunobiology of Graves' disease, has led to the emergence of several new therapeutic ideas, including biologics, small molecule peptides, immunomodulators and teprotumumab, a specific antibody targeting IGF-1R. Besides, the elements of TCM have attracted more and more interests in modern medicine, because some effective components have been successfully used in the treatment of autoimmune diseases. Based on the pathophysiology and efficacy of clinical management and treatment in Graves' hyperthyroidism, here we review the new strategies under investigation and summarize the effective components of traditional Chinese medicine used for Graves' hyperthyroidism, and explore their mechanisms. These therapies have opened a new window for the treatment of Graves' disease, but the exact mechanism and the research direction still need to be further explored.

Effect of Annealing on Microstructure and Corrosion Behavior of Interstitial Free Steel.

Interstitial free steels with various grain sizes and textures were prepared by cold-rolling followed by an annealing process. The effect of grain size, crystallographic orientations and stored energy on corrosion behavior of interstitial free steel was investigated. It was found that the deformed microstructure and dislocation boundaries were consumed by recrystallizing grains during annealing. The average grain size increase ranging from 0.61 µm to 11 µm and the volume fraction of recrystallized grains was about 96% after annealing for 64 h; meanwhile, the γ fiber was the dominated recrystallized texture component. The stored energy gradually decreased due to the reduction in dislocation density by annealing. The potentiodynamic polarization and Nyquist plots show that the corrosion potential exhibits a more positive shift and depressed capacitive semicircle radius increase with rising annealing time. The 64 h annealed specimens had the biggest depressed semicircle in the Nyquist plots and the highest positive corrosion potential, which indicates the enhancement of corrosion resistance. Such an improvement of corrosion resistance is attributed to the increase in the volume fraction of the γ fiber and decrease in the stored energy.

Simultaneous Enhancement of Mechanical and Magnetic Properties in Extremely-Fine Nanograined Ni-P Alloys.

Exploring structural effects that influence both the mechanics and magnetism in nanocrystalline materials, particularly extremely-fine nanograined ones with grain sizes down to several nanometers, is of high interest for developing multifunctional materials combining superior mechanical and magnetic performances. We found in this work that electrodeposited extremely-fine nanograined Ni-P alloys exhibit a significant enhancement of magnetization, simultaneously along with an increase in hardness, after low-temperature annealing. The relaxation of non-equilibrium structures, precipitation of the second phase and the segregation of P atoms to grain boundaries (GBs) during annealing have then been sequentially evidenced. By systematically comparing the variations in macroscopic and microstructural investigation results among several Ni-P alloys with different P contents, we suggest that the second phase has little effect on magnetization enhancement, and essentially both the structural relaxation and GB segregation can play important roles in hardening by governing GB stability, and in the improvement of magnetization by enhancing Ni⁻Ni atom exchange interactions.

Evolution of Oxyhalide Crystals under Electron Beam Irradiation: An in Situ Method To Understand the Origin of Structural Instability.

The oxyhalides have attracted growing interest because of their excellent photocatalytic performance. However, their structural instability hampers further development toward practical applications, a major challenge of current concerns. It is appealing to figure out the origin of structural instability and guide the design of advanced oxyhalide crystals for efficient photocatalysis. In this study, the decomposition of BiOCl crystals, a typical oxyhalide, is triggered by electron beam irradiation and investigated in situ by transmission electron microscopy. The results indicate that the instability originates from the unique layered structure of BiOCl crystals; the interlayer van der Waals bonds are easily broken under electron beam irradiation via the assistance of hydroxyl groups. This facilitates the formation of O/Cl-deficient BiO1- xCl1- y species, Bi metal nanoparticles, and nanobubbles (gaseous substance) that are confined between the adjacent layers. Surface reconstruction would be an effective way to stabilize the oxyhalide crystals.

Effect of Recrystallization Annealing on Corrosion Behavior of Ta-4%W Alloy.

The effect of recrystallization annealing on corrosion behavior of Ta-4%W alloy was studied. It is found that the deformed sample contains high dense dislocations and dislocation boundaries. During annealing, these dislocations and dislocation boundaries are replaced by recrystallizing grains until the alloy is fully recrystallized. Both the anodic dissolution and the cathodic activity is much more blocked. The corrosion potential gradual shift towards negative values and corrosion current density decrease, while polarization resistance increases after annealing, indicating enhanced corrosion resistance of the alloy. Such an enhancement is caused by the increase of low-Σ coincide site lattice boundaries and decrease of dislocations and dislocation boundaries.