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The article discusses the association of myokines with disease progression in primary biliary cholangitis (PBC) patients, building on previous research in alcohol-associated liver disease (ALD). The study found that myostatin levels increased and decorin levels decreased as PBC advanced, similar to findings in ALD patients. These results suggest that myokines could serve as potential biomarkers for monitoring disease progression in chronic liver diseases like PBC. Further research is needed to validate these findings. [Extracted from the article]

Liver diseases, such as viral hepatitis, alcoholic hepatitis and cirrhosis, nonalcoholic steatohepatitis, and hepatocellular carcinoma place a heavy burden on many patients worldwide. However, the treatment of many liver diseases is currently insufficient, and the treatment may be associated with strong side effects. Therapies for liver diseases targeting the molecular and cellular levels that minimize adverse reactions and maximize therapeutic effects are in high demand. Immune cells are intimately involved in the occurrence, development, and prognosis of liver diseases. The immune response in the liver can be suppressed, leading to tolerance in homeostasis. When infection or tissue damage occurs, immunity in the liver is activated rapidly. As small membrane vesicles derived from diverse cells, exosomes carry multiple cargoes to exert their regulatory effects on recipient cells under physiological or pathological conditions. Exosomes from different immune cells exert different effects on liver diseases. This review describes the biology of exosomes and focuses on the effects of exosomes from different immune cells on pathogenesis, diagnosis, and prognosis and their therapeutic potential in liver diseases. [ABSTRACT FROM AUTHOR]

The microstructure changes of steel for large size bearing ring with different Ni contents at different cooling rates under fast heating and short soaking time condition are analyzed by using thermal simulation test, scanning electron microscope (SEM), field emission scanning electron microscope (FESEM), electron-backscattering diffraction (EBSD), and transmission electron microscope (TEM). The hardness is evaluated by Rockwell hardness test and the hardening mechanism is discussed. Full martensite cooling rate can be lowered from 10 to 3 °C s−1 by the addition of 0.59% Ni. At full martensite cooling rate range, the martensitic lath structures are refined by adding 0.59% Ni or increasing the cooling rate. The hardness increases progressively with the cooling rate due to the refinement of martensitic lath structures and the precipitation strengthening of M23C6-type carbides. But the grain boundary strengthening has predominance. The highest hardness values of steel No. 2 with higher Ni is 60 and 2.5 HRC higher than that of steel No. 1 at the cooling rate of 100 °C s−1. This increase of hardness in steel No. 2 can be attributed to the finer martensitic lath structures and the solid solution strengthening. The grain boundary strengthening is the main influencing factor. [ABSTRACT FROM AUTHOR]

The effect of carbide distribution on the grain refinement in the steel for large-size bearing ring is investigated. It is observed that Ni-containing steel has an obvious grain refinement below 1050 °C, whereas its grain growth trend is steeper than that of Ni-free steel above 1050 °C. No evident segregation of Ni is observed, whereas the pinning effect of carbides distributed along grain boundaries is advantageous for the grain refinement. It is found that Ni addition could affect the type of carbides and contribute to decreasing the size of carbides via accelerating the diffusion of carbon. A stronger pinning effect with smaller carbides distributed along grain boundaries could be obtained, which is beneficial to grain refinement with Ni addition in small amounts. [ABSTRACT FROM AUTHOR]

Reverse transformation at 725-800°C × 0-35 s from a ferrite/pearlite to austenite was investigated in spring steel 60Si2MnA with various pearlite fineness obtained by isothermal transformation. Then, its influence on the structure inheritance in the spring steel during heat treatment process was discussed. The results indicated that various pearlite fineness influences clearly start temperature of the reverse transformation. Austenite preferentially nucleates at the ferrite/cementite interface within pearlite, the neighboring pearlite colony boundary and the proeutectoid ferrite/pearlite boundary during the reverse transformation process. And the angle between pearlite lamellae and austenite growth direction has an important influence on austenite growth rate. Besides, the ferrite/pearlitic structure has structure inheritance phenomenon, because various hot-rolled microstructure affect the austenite nucleation and growth during heat treatment process. [ABSTRACT FROM AUTHOR]

The relationship between transformation conditions, microstructures and mechanical properties were investigated on a 0.60%C hypoeutectoid steel, which has predominantly pearlitic microstructure. The steel had been austenized at 850-1050 °C and then isothermally transformed at 570-660 °C. Afterwards, the microstructures were analyzed by optical microscope, scanning electron microscope, and quantitative metallography. And the mechanical properties were determined. The results indicated that the interlamellar spacing, the pearlitic colony size and the proeutectoid ferrite content follow a linear relationship with the reciprocal of the undercooling, and the strength, the hardness and the toughness follow a Hall-Petch type of relationship with the inverse of the square root of the interlamellar spacing. Besides, the stress condition should be taken into account during analyzing the effect of the interlamellar spacing on the mechanical properties. The results have been explained on the basis of transformation conditions - microsturctures - mechanical properties ralationship. [ABSTRACT FROM AUTHOR]

A combination of simulation and experimental approaches to optimize the vacuum carburizing process is necessary to replace the costly experimental trial-and-error method in time and resources. In order to accurately predict the microstructure evolution and mechanical properties of the vacuum carburizing process, a multi-field multi-scale coupled model considering the interaction of temperature, diffusion, phase transformation, and stress was established. Meanwhile, the improved model is combined with the heat treatment software COSMAP to realize the simulation of the low-pressure vacuum carburizing process. The low-pressure vacuum carburizing process of 20CrMo gear steel was simulated by COSMAP and compared with the experimental results to verify the model. The results indicated that the model could quantitatively obtain the carbon concentration distribution, Fe-C phase fraction, and hardness distribution. It can be found that the carbon content gradually decreased from the surface to the center. The surface carbon concentration is relatively high only after the carburizing stage. With the increase in diffusion time, the surface carbon concentration decreases, and the carburized layer depth increases. The simulated surface carbon concentration results and experimental results are in good agreement. However, there is an error between calculations and observations for the depth of the carburized layer. The error between simulation and experiment of the depth of carburized layer is less than 6%. The simulated surface hardness is 34 HV lower than the experimental surface hardness. The error of surface hardness is less than 5%, which indicates that the simulation results are reliable. Furthermore, vacuum carburizing processes with different diffusion times were simulated to achieve the carburizing target under specific requirements. The results demonstrated that the optimum process parameters are a carburizing time of 42 min and a diffusion time of 105 min. This provides reference and guidance for the development and optimization of the vacuum carburizing process. [ABSTRACT FROM AUTHOR]

Laser surface hardening is a promising surface technology to enhance the properties of surfaces. This technology was used on the 42CrMo press brake die. Its hardening behavior was investigated by using scanning electron microscopy and electron backscattering diffraction. The results indicated that the martensite in the hardening zone was significantly finer than that in the substrate. There were many low-angle grain boundaries in the martensite of the hardening zone, and the kernel average misorientation and grain orientation spread in the hardening zone grains were obviously greater, which further improved the hardness of the hardening zone, especially near the substrate. The microstructure and the properties of the blade maintained excellent uniformity with treatment by single-pass laser surface hardening with a spot size of 2 mm, scanning speed of 1800 mm/min, and power of 2200 W. The hardness of the hardening zone was 1.6 times higher than that of the base material, and the thickness of the hardening zone reached 1.05 mm. [ABSTRACT FROM AUTHOR]

Background: Autoimmune hepatitis (AIH) is a serious liver disease characterized by immune disorders, particularly effector T-cell overactivation. This study aimed to explore the therapeutic effect and underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) treatment on CD4 + T-cell overactivation and liver injury in AIH., Methods: The metabolic changes of CD4 + T cells were assayed in human AIH and mouse hepatitis models. The liver protective effect of MSC-EVs was evaluated by transaminase levels, liver histopathology and inflammation. The effect of MSC-EVs on the metabolic state of CD4 + T cells was also explored., Results: Enhanced glycolysis (eg, ~1.5-fold increase in hexokinase 2 levels) was detected in the CD4 + T cells of AIH patient samples and mouse hepatitis models, whereas the inhibition of glycolysis decreased CD4 + T-cell activation (~1.8-fold decrease in CD69 levels) and AIH liver injury (~6-fold decrease in aminotransferase levels). MSC-EV treatment reduced CD4 + T-cell activation (~1.5-fold decrease in CD69 levels) and cytokine release (~5-fold decrease in IFN-γ levels) by reducing glycolysis (~3-fold decrease) while enhancing mitochondrial oxidative phosphorylation (~2-fold increase in maximal respiration) in such cells. The degree of liver damage in AIH mice was ameliorated after MSC-EV treatment (~5-fold decrease in aminotransferase levels). MSC-EVs carried abundant mitochondrial proteins and might transfer them to metabolically reprogram CD4 + T cells, whereas disrupting mitochondrial transfer impaired the therapeutic potency of MSC-EVs in activated CD4 + T cells., Conclusion: Disordered glucose metabolism promotes CD4 + T-cell activation and associated inflammatory liver injury in AIH models, which can be reversed by MSC-EV therapy, and this effect is at least partially dependent on EV-mediated mitochondrial protein transfer between cells. This study highlights that MSC-EV therapy may represent a new avenue for treating autoimmune diseases such as AIH., Competing Interests: The authors declare that they have no competing interests in this work., (© 2024 Shen et al.)

Rationale: Dysregulated T-cell immune response-mediated inflammation plays critical roles in the pathology of diverse liver diseases, but the underlying mechanism of liver immune homeostasis control and the specific therapies for limiting T-cell overactivation remain unclear. Methods: The metabolic changes in concanavalin A (ConA) mice and autoimmune hepatitis (AIH) patients and their associations with liver injury were analyzed. The expression of purine catabolism nucleases (e.g., CD39 and CD73) on liver cells and immune cells was assessed. The effects of MCregs and their extracellular vesicles (EVs) on CD4 + T-cell overactivation and the underlying mechanism were also explored. Results: Our findings revealed significant alterations in purine metabolism in ConA mice and AIH patients, which correlated with liver injury severity and therapeutic response. CD39 and CD73 were markedly upregulated on CD11b + Gr-1 + MCs under liver injury conditions. The naturally expanded CD39 + CD73 + Gr-1 high CD11b + MCreg subset during early liver injury effectively suppressed CD4 + T-cell hyperactivation and liver injury both in vitro and in vivo. Mechanistically, MCregs released CD73 high EVs, which converted extracellular AMP to immunosuppressive metabolites (e.g., adenosine and inosine), activating the cAMP pathway and inhibiting glycolysis and cytokine secretion in activated CD4 + T cells. Conclusions: This study provides insights into the mechanism controlling immune homeostasis during the early liver injury phase and highlights that MCreg or MCreg-EV therapy may be a specific strategy for preventing diverse liver diseases induced by T-cell overactivation., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Autoimmune hepatitis (AIH) is an autoimmune disease caused by disruption of liver immune homeostasis. Genetic studies have revealed the predisposition of AIH with the human leukocyte antigen (HLA) region. Recently, metabolomics integrated with genomics has identified many genetic loci of biomedical interest. However, there is no related report in AIH. In the present study, we found that HLA-DRB1*04:05 was linked to the clinical features and prognosis of AIH in Chinese patients. Furthermore, our patients were divided into DRB1*04:05 positive and DRB1*04:05 negative groups and the metabolic profiling was done by HPLC/MS. We chose inosine, one of the highly altered metabolites, to explore the effect on an acute severe hepatitis murine model. The results showed that inosine treatment attenuated hepatocyte apoptosis, enhanced antioxidant ability and inhibited the activation and glycolysis of CD4 + T cell. We propose that inosine participates in the regulation of AIH through its protective effect on hepatocytes and inhibition of overactivated immune cells, which might provide a potential novel approach in treating acute form of AIH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yang, Zhou, Shen, Zhao, Zheng, Men, Fan and Yang.)