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Glycogen, a polysaccharide composed of glucose molecules linked by α-1,4-glycosidic and α-1,6- glycosidic bonds, is one of the primary energy storage forms in human body. Glycogen is primarily stored in the liver (as liver glycogen) and skeletal muscles (as muscle glycogen), with smaller amounts present in tissues such as myocardium, kidneys, and brain. When the body requires energy, liver glycogen can be broken down into glucose, which is then utilized by various tissues and organs. During exercise, muscle glycogen is consumed by skeletal muscles to meet the energy demands of the muscles. Beyond its crucial roles in maintaining blood glucose levels and providing energy, recent research has revealed that glycogen metabolism also regulates biological processes such as cell differentiation, signal transduction, and redox reactions. This review focuses on the latest research advancements in the regulatory mechanisms of glycogen metabolism in metabolic diseases, tumors, and immune cell responses, highlighting new regulatory modes and mechanisms.

The flow and diffusion of high-temperature smoke in mine fires is an important cause of safety accidents. In response to the unclear relationship between fire hazard zones and time in typical mine roadways, a safety zone classification method for T-shaped roadway fire in deep coal mines is proposed. A three-dimensional numerical model is established using Pyrosim software to simulate the high-temperature smoke flow in the T-shaped roadway during the fire development stage under high temperature and humidity conditions. The variation law of temperature field and CO, CO2 concentration field with time and spatial location in the T-shaped roadway during the fire development stage are revealed. Based on the simulated data of the height of the human mouth and nose (i.e. the height of 1.6 meters in the roadway), the relationship between the horizontal length of the roadway and temperature, CO concentration and CO2 concentration is obtained. The airflow mixes high-temperature smoke through the roadway and spreads downwards along the top of the roadway. As the distance from the fire source increases, the temprature gradually decreases, and the longitudinal distribution of CO and CO2 concentration contour lines becomes denser. On this basis, safety zones are classified based on the temperature of the smoke and the harm degree of CO and CO2 concentration to human health. The smoke diffusion area is divided into four categories: safety zone (hazard level 1), mild hazard zone (hazard level 2), moderate hazard zone (hazard level 3), and severe hazard zone (hazard level 4). The analysis results show that in the temperature classification results, the measurement points in roadwayⅠare mainly concentrated in the severe hazard zone. In the toxic gas classification results, the safety zone range of CO2 in roadway Ⅰ is larger than that of CO. The risk factors for CO are greater, mainly concentrated in mild and moderate hazard zones. In roadway Ⅱ, it is mainly concentrated in mild hazard zones. The range of hazard level 1 in roadway Ⅰ gradually decreases over time, while the range of hazard level 4 gradually increases over time, with the maximum change rate occurring at 40 seconds. The rates of change for hazard levels 2 and 3 are very small. The regional range changes of the two classification methods in roadway Ⅱ are similar, with the maximum change rate of hazard levels 2 and 3 occurring at 60 seconds.

Considering the creep characteristics of the rubber bearing material,the infinite line contact model of the water-lubricated bearing is established,based on the Kelvin model and the three-parameter model,the elastohydrodynamic lubrication of water-lubricated rubber bearings is analyzed. The effects of creep of rubber bearing on the pressure and film thickness of the lubricating membrane are obtained. The effects of the central pressure,the central film thickness and the minimum film thickness under the influence of the two models are analyzed and contrasted. The results show that the creep characteristics of the rubber bearing has great influence on the pressure and the thickness of the lubricating membrane. Under the two creep models,the pressure of the lubricating film decreases with the creep time,and the thickness of the lubricating film increases with the creep time,at the same time the contact area is increasing to the end of the constant value. The central pressure increases with the creep time and tends to be stable. The minimum film thickness decreases with the creep time and then decreases to the steady value. After the creep stabilization,the pressure and film thickness of the two models are larger than those of the rubber bearing as the linear elastomer. Compared with the previous work,the three-parameter solid model can describe the lubricating performance of the rubber bearing better than the Kelvin model.

Based on ANSYS finite element static analysis,the mechanical properties of the water lubricated spiral stepped rubber stern bearings are obtained by orthogonal design and control variable method. Based on the results,the influence of structural parameters on the mechanical properties of the stern bearings is obtained based on Minitab. Finally,the surface structure of the stern bearings is analyzed by Design Exploration module and the multi-objective optimization is used to improve the mechanical property.

The high-frequency excitation generated by the wheel polygon seriously affects the safety of the train. In order to explore the evolution mechanism of wheel polygonisation, a long-term prediction model of wheel circumferential wear on both sides of the wheelset is proposed. Based on a new updating strategy, the model is implemented by combining the coupled vehicle/track dynamic model and the wheel circumferential wear model. The wheel circumferential wear model is implemented by local tangential contact model FaStrip and USFD (a wear model proposed by The University of Sheffield). By analysing the measured data, five wheel circumferential states are summarised, which are employed as wheel non-circular excitations to analyse the evolution of the wheel polygons on both sides of the wheelset. The results show that the same order of the polygonal wheels on both sides of the wheelset is the main reason for the evolution of the order of polygonal wheels in integer multiples. When the circumferences of the wheels on both sides are in an asymmetric state, the wheels on both sides will interact with each other, and the final circumferences of the wheels will gradually evolve into mixed polygonal circumferences related to the initial orders. [ABSTRACT FROM AUTHOR]

The dynamical performance of vehicles on railway tracks is significantly influenced by wheel‐rail interactions, which makes the wheel‐rail force be a safety indicator of vehicle systems. Owing to the high cost of direct measurement, inversion models are widely used to measure the wheel‐rail force. This study proposes a model called the Lightweight Wheel‐Rail Force Inversion Model (LFIM) to calculate the wheel‐rail force by using vibration signals collected from the vehicle system. The model can extract the relevant features, and outperforms prevalent models. It is also resource efficient and small in size, which makes it suitable for edge computing environment. The basic LFIM yielded a correlation coefficient of 0.99 in experiments, significantly higher than the value recorded by the traditional dynamic methods. The compressed LFIM yielded a 91% reduction in floating‐point operations (FLOPs) and had an R2 score of 90%, which satisfies the demands for vehicle monitoring. By balancing accuracy and size, LFIM is a feasible model to deploy on edge devices to monitor the wheel‐rail force in real‐time and assess the safety of railway vehicles. [ABSTRACT FROM AUTHOR]

Weak immunogenicity of tumor cells is a root cause for the ultimate failure of immunosurveillance and immunotherapy. Although tumor evolution can be shaped by immunoediting toward a less immunogenic phenotype, mechanisms governing the initial immunogenicity of primordial tumor cells or original cancer stem cells remain obscure. Here, using a single tumor-repopulating cell (TRC) to form tumors in immunodeficient or immunocompetent mice, we demonstrated that immunogenic heterogeneity is an inherent trait of tumorigenic cells defined by the activation status of signal transducer and activator of transcription 1 (STAT1) protein in the absence of immune pressure. Subsequent investigation identified that the RNA binding protein cold shock domain–containing protein E1 (CSDE1) can promote STAT1 dephosphorylation by stabilizing T cell protein tyrosine phosphatase (TCPTP). A methyltransferase SET and MYN domain–containing 3 (SMYD3) was further identified to mediate H3K4 trimethylation of CSDE1 locus, which was under the regulation of mechanotransduction by cell-matrix and cell-cell contacts. Thus, owing to the differential epigenetic modification and subsequent differential expression of CSDE1, nascent tumorigenic cells may exhibit either a high or low immunogenicity. This identified SMYD3-CSDE1 pathway represents a potential prognostic marker for cancer immunotherapy effectiveness that requires further investigation. Shocking the immune system: One way tumors overcome immunosurveillance and immunotherapy is through their inherent lack of immunogenicity, however, the mechanisms underlying this are not well understood. Here, Lv et al. have utilized a single tumor-repopulating cell model in mice to demonstrate that immunogenic heterogeneity is regulated by signal transducer and activator of transcription 1 (STAT1) and cold shock domain containing protein E1 (CSDE1). CSDE1 is additionally regulated epigenetically by mechanotransduction and has the propensity to exhibit either high or low immunogenicity. Thus, CSDE1 expression could be a potential marker for cancer immunotherapy response that requires further investigation. — DH [ABSTRACT FROM AUTHOR]

In this study, the probability integral method, Synthetic Aperture Radar Interferometry (InSAR), and the Okada dislocation model were collaboratively used to analyze deformation in the Alhada Pb-Zn mine. The predicted deformation values of the subsidence centers in three subsidence areas were 107 mm, 120 mm, and 83 mm, respectively, as predicted using the probability integral method. The coherent scatterer InSAR technique was used to analyze the time-series deformation of the mining area, and the same subsidence center locations and similar deformation values were observed. The Okada dislocation model was used to invert the optimal parameters of the underground-mining ore body causing the surface subsidence, indicating that the surface subsidence is mainly caused by the mining of ore bodies in the 888 and 848 middle sections. We further simulated ground deformation using the multi-source Okada model. The results showed that the predicted and modeled deformations are highly correlated with the observed deformation. Through the analysis and comparison of the InSAR results, it was concluded that the three subsidence areas do not threaten the stability of the main buildings in the mining area. Using theoretical, observational, and modeling methods, the development and evolution of the subsidence area in mines can be established, which could provide basic data for subsidence control work and guarantee mine production safety. [ABSTRACT FROM AUTHOR]

A long-term tracking test was performed on a newly designed high-speed train with the nominal speed of 250 km/h. The wheel roughness and structural vibration were both recorded during two re-profiling cycles. The 3rd order polygonal wear was observed in the early stage. The vibration of the axlebox can be aggravated even at lower speed when the passing frequency of polygonal wear approaches the P2 resonance frequency. Subsequently, the 22nd–25th and 14th–15th order developed. The trend analysis suggests that the development of high-order polygonal wear is exponential-like. Moreover, a localised decline is explored during the development progress due to the change of route, which indicates the polygonal wear can be suppressed by reducing the proportion of constant-speed operation. It is also found that the acceleration amplitude of 550–650 Hz shows the most remarkable rise with the mileage, following the 300–400 Hz. However, there is a slight difference of characteristic frequency between the initially dominant peak and the finally developed order. The high-frequency vibration induced by high-order polygonal wear can be noticed on the entire vehicle, and it transmits between the adjacent wheels through the rail. [ABSTRACT FROM AUTHOR]

Aims. Metformin is an oral antidiabetic agent that has been widely prescribed for the treatment of type II diabetes. In recent years, anticancer properties of metformin have been revealed for numerous human malignancies. However, there are few indications available regarding the feasibility and safety of these studies in an advanced extrahepatic cholangiocarcinoma (EHCC) population. This study is aimed at evaluating the feasibility, safety, and value of metformin use and survival in patients with advanced EHCC. Methods. All patients with advanced EHCC observed at Fuyang People's Hospital between January 2015 and November 2020 were included in the study. Case data, clinical information, and imaging results were abstracted from the self-administered questionnaire and electronic medical record. All patients were divided into study subjects and control subjects, and the study subjects were given metformin, 0.5 g, three times a day, while control subjects were without metformin. The metformin use and survival time of the subjects were asked by telephone, out-patient, or door-to-door visit, after they left the hospital. Results. One hundred and thirty-three study cases and 589 controls were included in the analysis. This study showed that metformin use cannot improve the overall survival rate of patients with advanced EHCC ([95% CI]: -17.05-0.375, t = − 1.889 , P value = 0.061), but the survival time of patients with drainage treatment from control group (n = 496) was significantly shorter than that of patients with drainage treatment from the study group (n = 113), and the difference was statistically significant (z = − 2.230 , P value = 0.026). There were significant differences between metformin used before or after the diagnosis of advanced EHCC (OR[95% CI], 3.432[2.617-4.502]; P value = 0.001) in survival time. And there was significant difference between the duration of metformin use and survival prognosis (OR[95% CI], 2.967[1.383-6.368]; P = 0.005). Conclusion. Metformin can improve the survival of advanced EHCC patients who underwent drainage treatment, especially for metformin use after diagnosis of advanced EHCC and long duration of metformin. [ABSTRACT FROM AUTHOR]

Gasdermin E as troublemaker: Cytokine release syndrome (CRS) is a complication associated with chimeric antigen receptor (CAR) T cell therapy in cancer patients. The mechanisms that trigger CRS are not clear, but Liu et al. describe a role for the pore-forming protein gasdermin E (GSDME) during tumor cell pyroptosis, which contributes to CRS. CAR T cells release granzyme B, which activates caspase 3 and cleaves GSDME in target tumor cells and causes pyroptosis. Pyroptosis by GSDME leads to activation of caspase 1 and GSDMD in macrophages, which is critical for triggering CRS. Elevated levels of GSDME in cancer patients positively correlated to CRS severity. In addition, the ability of CAR T cells to induce pyroptosis is associated with the levels of perforin and granzyme B released. Cytokine release syndrome (CRS) counteracts the effectiveness of chimeric antigen receptor (CAR) T cell therapy in cancer patients, but the mechanism underlying CRS remains unclear. Here, we show that tumor cell pyroptosis triggers CRS during CAR T cell therapy. We find that CAR T cells rapidly activate caspase 3 in target cells through release of granzyme B. The latter cleaves gasdermin E (GSDME), a pore-forming protein highly expressed in B leukemic and other target cells, which results in extensive pyroptosis. Consequently, pyroptosis-released factors activate caspase 1 for GSDMD cleavage in macrophages, which results in the release of cytokines and subsequent CRS. Knocking out GSDME, depleting macrophages, or inhibiting caspase 1 eliminates CRS occurrence in mouse models. In patients, GSDME and lactate dehydrogenase levels are correlated with the severity of CRS. Notably, we find that the quantity of perforin/granzyme B used by CAR T cells rather than existing CD8+ T cells is critical for CAR T cells to induce target cell pyroptosis. [ABSTRACT FROM AUTHOR]

Objective Construction of mouse liver senescence model induced rapidly in vitro by 3D organoid culture. Methods Mouse hepatocytes were collected by two-step perfusion method and cultured in 3D. Organoids were preliminarily identified by morphology, qPCR and immunofluorescence. The function of hepatocyte organoid was evaluated by their uptake of LDL. The hepatocyte organoids were treated with oleic acid, and their clonal growth, senescence related secretory phenotype, LDL uptake and ROS level of liver cells were detected. The hepatocytes were further treated with N-acetylcysteine (NAC) to detect the above phenotypic and functional changes. Results A large number of active primary mouse hepatocytes were obtained by two-step perfusion method. The hepatocyte organoid with self-reproduction ability was collected by 3D culture in the matrix gel. The expression of liver marker genes in hepatocyte organoid and primary hepatocytes was shown by qPCR detection. The immunofluorescence results showed that it highly expressed ALB protein. Moreover, hepatocyte organoid had normal uptake function of LDL. After treatment with oleic acid, the growth of hepatocyte organoid was slowed down, the expression of senescence related secretory phenotype genes was up-regulated(P＜0.001), the uptake of LDL was reduced(P＜0.001), and ROS was significantly increased(P＜0.001). The above phenotypes were alleviated by NAC treatment(P＜0.01 or P＜0.001). Conclusions Oleic acid treatment can successfully construct the aging model of mouse liver in vitro. Adding NAC can clear ROS and alleviate the occurrence of aging.

Objective The study focuses on the prognostic value of SMYD3 in pan cancer, and analyze the influence of SMYD3 on tumor tissue immune infiltration. Methods The gene expression and protein density data were collected from TCGA, GTEx and HPA databases. Kaplan-Meier(KM) algorithm was used to evaluate the impact of SMYD3 on the prognosis of patients with different kinds of tumor. The ESTIMATE algorithm and Timer database were applied to investigate the relationship between SMYD3 and immune microenvironment. And the results were verified in B16 cell line by knockout SMYD3. Results Higher expression of SMYD3 was observed in tumor tissue than normal tissue in both mRNA and protein level. And SMYD3 was thought to be associated with worse outcomes of patients(PPSmyd3 in B16 cell line increased the expression of antigen present genes(PConclusions Smyd3 is an important gene related to the prognosis of patients and the antigen presentation function of tumor cells. Smyd3 can inhibit the infiltration of immune cell by down-regulation of antigen-present genes, which induces the immune escape.