Influence of thickness and strength on plastic instability in tailored steel structures.

A mathematical model was intricately devised to explore the influence of continuous variations in thickness and mechanical properties on the performance of tailor rolled blanks (TRB) and tailor rolled tubes (TRT). Through the integration of analytical and numerical techniques, it was discerned that these variations play a pivotal role in modulating stress distribution and strain localization, thereby inducing a spectrum of plastic instability behaviors within the structures. The introduction of an 'equivalent strength' metric as a novel means to quantify structural performance shed light on strategic material distribution to enhance durability and mechanical efficiency. Moreover, the insights garnered from this research deepen the understanding of the mechanical responses of tailor-rolled constructs under varying loads, offering valuable perspectives for the development and fabrication of engineered materials with bespoke properties. This study not only contributes to bridging a knowledge gap in the realm of tailored material engineering but also fosters the advancement of design methodologies in the construction of high-performance engineered structures.

Apigenin intervenes in liver fibrosis by regulating PKM2-HIF-1α mediated oxidative stress.

Apigenin (API) is a natural flavonoid compound with antioxidant, anti fibrotic, anti-inflammatory and other effects, but there is limited research on the effect of API on liver fibrosis. This study aims to explore the effect and potential mechanism of API on liver fibrosis induced by CCl4 in mice. The results indicate that API reduces oxidative stress levels, inhibits hepatic stellate cell (HSC) activation, and exerts anti liver fibrosis effects by regulating the PKM2-HIF-1α pathway. We observed that API alleviated liver tissue pathological damage and collagen deposition in CCl4 induced mouse liver fibrosis model, promoting the recovery of liver function in mice with liver fibrosis. In addition, the API inhibits the transition of Pyruvate kinase isozyme type M2 (PKM2) from dimer to tetramer formation by regulating the EGFR-MEK1/2-ERK1/2 pathway, thereby preventing dimer from entering the nucleus and blocking PKM2-HIF-1α access. This change leads to a decrease in malondialdehyde (MDA) and Catalase (CAT) levels and an increase in glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) levels, as well as total antioxidant capacity (T-AOC) in the liver of liver fibrosis mice. At the same time, API downregulated the expression of α-smooth muscle actin (α-SMA), Vimentin and Desmin in the liver tissue of mice with liver fibrosis, inhibited the activation of HSC, and reduced collagen deposition. These results indicate that API can inhibit HSC activation and alleviate CCl4 induced liver fibrosis by inhibiting the PKM2-HIF-1α pathway and reducing oxidative stress, laying an important foundation for the development and clinical application of API as a novel drug for treating liver fibrosis.

Analysis of the Asymmetrical Rolling of Ultra-Thin Strips Considering Elastic Deformation of the Strips.

In normal cold rolling, the elastic deformation of the strip is typically ignored because of the dominant plastic deformation. However, this neglect may introduce additional errors when the strip is very thin. The aim of this study is to investigate the characteristics of the deformation region and thickness reduction in the asymmetrical rolling of ultra-thin strips. Mathematical models were developed based on the slab method, with consideration of the elastic deformation of the strips, and employed in the simulation calculation. The percentage of the three zones and the thickness reduction were analyzed using the simulation results. An increase in the speed ratio results in an increase in the reduction ratio, which is influenced by parameters, such as front tension, back tension, friction coefficient, and entry thickness. The elastic deformation of the strip reduces the tension and the roll pressure and causes the reduction ratio to decrease. The findings and conclusions of this study may be helpful to the mill operating in the asymmetrical rolling process of ultra-thin strips.

Forming Characteristics of Tailor Rolled Blank of Aluminum Alloy during Three-Point Bending.

This paper presents an investigation on the forming characteristics of the tailor rolled blank of an aluminum alloy (Al-TRB) during three-point bending at room temperature through experiments and finite element simulations. The strain distribution, spring-back characteristics, and metal flow law of 6000 series Al-TRB during three-point bending are explored. The prepared Al-TRB has good bending properties, and no surface cracks appear in the bending region of the Al-TRB when bent to 180°. Surface roughening occurs on the outside of the bending region. Since the strain in the thick zone is greater than that in the thin zone, the surface roughening in the thick zone is more obvious than that in the thin zone. The spring-back angle in the thin zone is higher than that in the thick zone after three-point bending, and the overall spring-back angle of Al-TRB becomes larger with an increasing bending angle. When the transition zone of Al-TRB is centered and the length of the transition zone is certain, as the length of the equal-thickness zone increases, the spring-back angle of the thin zone is larger, while the spring-back angle of the thick zone is smaller. Under the premise of a certain total length of Al-TRB and the length of the transition zone, the larger the length proportion of the thin zone, the larger the overall spring-back angle of Al-TRB, and the larger the length proportion of the thick zone, the smaller the overall spring-back angle of Al-TRB. In addition, a slight metal flow phenomenon exists during three-point bending, which shows that the metal in the bending region will flow to the thick zone, and the metal at the edge will flow to the thin zone. At the same time, there are localized thickening and thinning phenomena in Al-TRB. This study is helpful because it provides theoretical guidance for designing molds for the actual production of Al-TRB parts for automotives.

Review on Cellular Automata for Microstructure Simulation of Metallic Materials.

The cellular automata (CA) method has played an important role in the research and development of metallic materials. CA can interpret the microstructure changes of materials and obtain more abundant, accurate and intuitive information of microstructure evolution than conventional methods. CA can visually represent the process of grain formation, growth, development and change to us in a graphical way, which can assist us in analysis, thinking and solving problems. In the last five years, the application of CA in materials research has been rapidly developed, and CA has begun to occupy an increasingly important position in the simulation research of metallic materials. After introducing the advantages and limitations of CA compared to other widely used simulation methods, the purpose of this paper is to review the recent application progress on the microstructure simulation of metallic materials using CA, such as solidification, recrystallization, phase transformation and carbide precipitation occurring during forming and heat treatment. Specifically, recent research advances on microstructure simulation by CA in the fields of additive manufacturing, welding, asymmetrical rolling, corrosion prevention, etc., are also elaborated in this paper. Furthermore, this paper points out the future work direction of CA simulation in the research of metallic materials, especially in the simulation of the crystal structure, the prediction of mechanical properties, CA simulation software and rule systems, etc. These are expected to attract wide attention of researchers in the field of metallic materials and promote the development of CA in materials research.

[Research on fault diagnosis of patient monitor based on text mining].

The conventional fault diagnosis of patient monitors heavily relies on manual experience, resulting in low diagnostic efficiency and ineffective utilization of fault maintenance text data. To address these issues, this paper proposes an intelligent fault diagnosis method for patient monitors based on multi-feature text representation, improved bidirectional gate recurrent unit (BiGRU) and attention mechanism. Firstly, the fault text data was preprocessed, and the word vectors containing multiple linguistic features was generated by linguistically-motivated bidirectional encoder representation from Transformer. Then, the bidirectional fault features were extracted and weighted by the improved BiGRU and attention mechanism respectively. Finally, the weighted loss function is used to reduce the impact of class imbalance on the model. To validate the effectiveness of the proposed method, this paper uses the patient monitor fault dataset for verification, and the macro F1 value has achieved 91.11%. The results show that the model built in this study can realize the automatic classification of fault text, and may provide assistant decision support for the intelligent fault diagnosis of the patient monitor in the future.

Microstructure and Mechanical Properties of Ti/Al-SiC/Ti Clad Plates Prepared via the Powder-in-Tube Method.

SiC particle-reinforced Ti/Al/Ti clad plates were successfully fabricated by the powder-in-tube method. The surface micrography, element diffusion, peeling strength and tensile property of clad plates were studied after annealing and cold rolling. The experimental results show that 6 wt.% is optimal. The presence of SiC particles has been seen to significantly enhance the diffusion of Ti and Al elements. Additionally, it has been observed that the diffusion width of the intermetallic compound (IMC) increases as the size of SiC particles grows. However, it is worth noting that the average of Ti/Al-SiC/Ti clad plates initially increases and subsequently falls. The optimized diffusion thickness of the Ti/Al-SiC/Ti clad plate's IMC layer determined via the powder-in-tube method is approximately 4.5 µm. The 1 µm SiC-reinforced Ti/Al/Ti clad plate can obtain the best mechanical properties after annealing at 500 °C and further hot rolling, and the peeling strength, ultimate tensile strength and elongation are 31.5 N/mm, 305 MPa and 26%, respectively. The efficacy of Ti/Al-SiC/Ti clad plates in delivering exceptional performance is substantiated by the analysis of peeling surfaces, peeling tests and tensile testing, which collectively demonstrate the presence of compact and homogenous intermetallic compounds.

Analysis of Mechanical Parameters in Multi-Pass Asymmetrical Rolling of Strip by Slab Method.

Mechanical parameters, time consumption and energy consumption are important considerations in the application of a certain rolling process. This study aims to investigate characteristics of the roll force, roll torque, roll power, rolling time and total work in multi-pass asymmetrical rolling of strip. Mathematic models were built using the slab method to calculate parameters in the asymmetrical rolling process, and the characteristics of these parameters were analyzed on the basis of simulation results. Mechanical parameters are affected by the change of deformation region type. When the speed ratio is less than the critical speed ratio, the roll force, absolute values of roll torque and roll power are found to increase with the increase in the speed ratio. After the speed ratio reaches the critical speed ratio, the roll force, roll torque and lower roll power keep constant, but the upper roll power continues increasing. The upper roll torque and upper roll power required by asymmetrical rolling are much greater than that by symmetrical rolling, which indicates that stronger drive shafts and more powerful drive motors are required by asymmetrical rolling. Compared with symmetrical rolling, asymmetrical rolling requires less roll force to obtain the same thickness reduction, especially for thin and hard strips. Rolling time can be saved at the cost of more energy consumption by using asymmetrical rolling with the same roll force to attain the same final thickness. The results and conclusions of this study can provide a reference for mill design and application of asymmetrical rolling in strip manufacturing.

A bibliometric analysis of metastatic breast cancer: two-decade report (2002-2022).

Background: MBC is a lethal form of breast cancer that arises when cancer cells invade other organs or tissues. The treatment of MBC needs personalized approaches based on the tumor and patient characteristics. The purpose of this paper is to analyze MBC studies from 2002 to 2022 using bibliometrics and to investigate its current situation, main contributors, core journals, highly cited papers, and topic evolution. Materials and methods: We retrieved data from Web of Science Core Collection (WOSCC). Bibliometric analysis of the included literatures mainly used the following tools: the function of "analyze results" and "citation report" in WoS, Microsoft excel 2021, CiteSpace v.6.1. R6, VOSviewer v.1.6.18, BICOMB v.2.04 and gCLUTO v.1.0. Results: We found 12,653 articles on MBC research published in 1, 802 journals by 69, 753 authors from 118 countries. The annual output and citation of MBC articles showed a rising trend over time. The United States was the most influential country in MBC research. The most cited journal in this field was The Journal of Clinical Oncology. And the most cited article was by Slamon DJ. The co-word analysis of keywords divides MBC into six research clusters. The hormone receptor-positive MBC and liquid biopsy of MBC are the frontiers research trends. "CDK4/6 inhibitor" had the highest burst strength. Conclusion: Our bibliometric analysis offers a comprehensive overview of MBC research in the past two decades. It shows the current situation, main contributors, core journals, highly cited papers, and topic evolution of this field. Our study can assist researchers and practitioners to comprehend the development and trends of MBC research and to discover potential directions for future research.

Exploring the mechanism of Chaihujia Longgu Muli decoction in the treatment of epilepsy in rats based on the RhoA/ROCK signaling pathway.

BACKGROUND: The Chinese herbal formula Chaihujia Longgu Muli Decoction (CD) has a good antiepileptic effect, but its mechanisms remain unclear. Therefore, in this study we explored the molecular mechanisms of CD against epilepsy. METHODS: Twelve-day-old SD rats were randomly divided into a normal group, model group, valproic acid group, and CD high, medium, and low groups. Except for the normal group, the other groups were given an intraperitoneal injection of pentylenetetrazol (PTZ) to establish epilepsy models, and the Racine score was applied for model judgment. After 14 consecutive days of dosing, the Morris water maze test was performed. Then, hippocampal Nissl staining and immunofluorescence staining were performed, and synaptic ultrastructure was observed by transmission electron microscopy (TEM). RhoA/ROCK signaling pathway proteins were detected. RESULTS: In PTZ model rats, the passing times were reduced, and the escape latency was prolonged in the Morris water maze test. Nissl staining showed that some hippocampal neurons swelled and ruptured, Nissl bodies in the cytoplasm were significantly reduced, and neurons were lost. Immunofluorescence detection revealed that the expression of PSD95 and SYP was significantly reduced. Electron microscopy results revealed that the number of synapses in hippocampal neurons was significantly reduced and the postsynaptic membrane length was significantly reduced. Western blot analysis showed that the RhoA/ROCK signaling pathway was activated, while SYP, SPD95, and PTEN expression was significantly decreased. After treatment with CD, neurobehavioral abnormalities and neuronal damage caused by epileptic seizures were improved. CONCLUSION: CD exerted an antiepileptic effect by inhibiting the activation of the RhoA/ROCK signaling pathway.

Melatonin Ameliorates Cisplatin-Induced Renal Tubular Epithelial Cell Damage through PPARα/FAO Regulation.

Previous studies revealed that melatonin ameliorated acute renal injury induced by cisplatin, but the mechanisms remain unclear. Peroxidase proliferative receptor α (PPARα) is considered the major regulator of fatty acid oxidation (FAO), which is an important source of energy for renal tubular epithelial cells. In this study, the aim was to investigate the role of melatonin in cisplatin-induced NRK-52E (rat renal tubular epithelial cell line) cell damage and the underlying mechanisms. We established a cisplatin-stimulated NRK-52E model in vitro. We assessed the levels of apoptotic proteins, including caspase-3, caspase-9, and B-cell lymphoma 2-associated X protein (Bax), as well as PPARα and FAO-related genes (Acadm, Acat1, Acsm2, Acsm3, PGC-1α, Pecr, Bdh2, and Echs1). Furthermore, we detected the effects of miR-21 and PPARα antagonist on the above indicators. We found that melatonin reduced the protein expression levels of caspase-3, caspase-9, and Bax, and increased the expression levels of the PPARα gene and protein and PPARα activity, as well as FAO-related genes, in NRK-52E cells. However, miR-21 mimics and PPARα antagonists partially antagonized the above effects of melatonin. Our data indicated that melatonin could alleviate cisplatin-induced cell damage through the upregulation of PPARα/FAO.

Melatonin attenuates cisplatin-induced acute kidney injury in mice: Involvement of PPARα and fatty acid oxidation.

The present study focused on the protective effects of melatonin against cisplatin-induced acute kidney injury in mice and its possible mechanism of action in relation to the major regulator of fatty acid oxidation (FAO), peroxidase proliferative receptor α (PPARα). The experiment consisted of the following four groups: vehicle control, cisplatin (15 mg/kg), cisplatin & melatonin (20 mg/kg/day), and melatonin (20 mg/kg/day). Concomitant administration of melatonin significantly ameliorated cisplatin-induced acute kidney injury in mice by decreasing serum levels of triglyceride, blood urea nitrogen and creatinine, reducing the number and size of lipid droplets in tubular epithelial cells, and decreasing the incidence of histopathological changes including tubular cell apoptosis. Moreover, melatonin administration protected kidney tissue by significantly upregulating the levels of PPARα reduced by cisplatin injection, resulting in increased FAO pathway-associated genes (PGC-1a, Acadm, Acat1, Acsm2, Acsm3, Bdh2, Echs and Pecr) as well as reducing protein levels of caspase-3, -9 and Bax. Melatonin not only partially modulated FAO via PPARα signaling, but also decreased cisplatin-induced apoptosis by inhibiting the caspase-3, -9 and Bax pathways. Our findings suggest that melatonin prevents cisplatin-induced acute kidney injury in mice, possibly by upregulating the expression of PPARα, resulting in enhanced FAO and anti-apoptotic properties.

Vitamin E Enhances Cancer Immunotherapy by Reinvigorating Dendritic Cells via Targeting Checkpoint SHP1.

Despite the popular use of dietary supplements during conventional cancer treatments, their impacts on the efficacies of prevalent immunotherapies, including immune-checkpoint therapy (ICT), are unknown. Surprisingly, our analyses of electronic health records revealed that ICT-treated patients with cancer who took vitamin E (VitE) had significantly improved survival. In mouse models, VitE increased ICT antitumor efficacy, which depended on dendritic cells (DC). VitE entered DCs via the SCARB1 receptor and restored tumor-associated DC functionality by directly binding to and inhibiting protein tyrosine phosphatase SHP1, a DC-intrinsic checkpoint. SHP1 inhibition, genetically or by VitE treatment, enhanced tumor antigen cross-presentation by DCs and DC-derived extracellular vesicles (DC-EV), triggering systemic antigen-specific T-cell antitumor immunity. Combining VitE with DC-recruiting cancer vaccines or immunogenic chemotherapies greatly boosted ICT efficacy in animals. Therefore, combining VitE supplement or SHP1-inhibited DCs/DC-EVs with DC-enrichment therapies could substantially augment T-cell antitumor immunity and enhance the efficacy of cancer immunotherapies. SIGNIFICANCE: The impacts of nutritional supplements on responses to immunotherapies remain unexplored. Our study revealed that dietary vitamin E binds to and inhibits DC checkpoint SHP1 to increase antigen presentation, prime antitumor T-cell immunity, and enhance immunotherapy efficacy. VitE-treated or SHP1-silenced DCs/DC-EVs could be developed as potent immunotherapies. This article is highlighted in the In This Issue feature, p. 1599.

Analysis of Mechanical Parameters of Asymmetrical Rolling Dealing with Three Region Percentages in Deformation Zones.

A series of mathematical models were proposed to calculate the roll force, torque and power for cold strip asymmetrical rolling by means of the slab method, taking the percentages of the forward-slip, backward-slip and cross-shear zones into account. The friction power, plastic work and total energy consumption can be obtained by the models. The effects of variable rolling parameters-such as the speed ratio, entry thickness, friction coefficient and front and back tension-on the process of asymmetrical rolling are analyzed. In all cases, an increase in speed ratio leads to an increase in friction work and its proportions. The increase in entry thickness and deformation resistance causes both friction work and plastic deformation work to increase. The proportion of friction work decreases with increasing deformation resistance, entry thickness, front tension and back tension. In the circumstances of a thin strip being rolled with a large speed ratio, the proportion of friction work could exceed that of plastic deformation work. The concept of a threshold point of friction work was proposed to explain this phenomenon. As an example, threshold points T1, T2, T3 with the effect of the entry thickness and S1, S2, S3 with the effect of the friction coefficient have been obtained by computation. Finally, the experiment of the strip asymmetrical rolling was conducted, and a maximum error of 9.7% and an RMS error of 5.9% were found in the comparison of roll forces between experimental measurement values and calculated ones.

The lncRNA ZFAS1 regulates lipogenesis in colorectal cancer by binding polyadenylate-binding protein 2 to stabilize SREBP1 mRNA.

Colorectal cancer (CRC) is the fourth leading cause of cancer-related mortality globally. Therefore, a better understanding of the early molecular events of this disease is needed. Long noncoding RNAs (lncRNAs) play a critical role in the regulation of tumorigenesis and cancer progression. In this study, we investigated the characteristics of ZFAS1 in CRC. We analyzed three independent microarray datasets of CRC tissues from GEO and found that ZFAS1 expression was remarkably upregulated in all three datasets. Moreover, we validated the overexpression of ZFAS1 in CRC tissues compared with normal tissues and found that ZFAS1 was positively correlated with tumor size and metastasis in CRC. Knockdown of ZFAS1 significantly suppressed the malignant phenotype and lipogenesis of CRC cells. Mechanistically, ZFAS1 binds polyadenylate-binding protein 2 (PABP2) to stabilize SREBP1 mRNA, thereby increasing the expression of SREBP1 and its target genes stearoyl-CoA desaturase (SCD1) and fatty acid synthase (FASN), thus promoting CRC lipid accumulation. These data demonstrated that ZFAS1 could act as an oncogene for CRC and that ZFAS1 reprograms lipid metabolism by binding with PABP2 to stabilize SREBP1 mRNA accumulation, implicating it as a novel and potent target for the treatment of CRC.

Autophagosomes fuse to phagosomes and facilitate the degradation of apoptotic cells in Caenorhabditis elegans.

Autophagosomes are double-membrane intracellular vesicles that degrade protein aggregates, intracellular organelles, and other cellular components. During the development of the nematode Caenorhabditis elegans, many somatic and germ cells undergo apoptosis. These cells are engulfed and degraded by their neighboring cells. We discovered a novel role of autophagosomes in facilitating the degradation of apoptotic cells using a real-time imaging technique. Specifically, the double-membrane autophagosomes in engulfing cells are recruited to the surfaces of phagosomes containing apoptotic cells and subsequently fuse to phagosomes, allowing the inner vesicle to enter the phagosomal lumen. Mutants defective in the production of autophagosomes display significant defects in the degradation of apoptotic cells, demonstrating the importance of autophagosomes to this process. The signaling pathway led by the phagocytic receptor CED-1, the adaptor protein CED-6, and the large GTPase dynamin (DYN-1) promotes the recruitment of autophagosomes to phagosomes. Moreover, the subsequent fusion of autophagosomes with phagosomes requires the functions of the small GTPase RAB-7 and the HOPS complex components. Further observations suggest that autophagosomes provide apoptotic cell-degradation activities in addition to and in parallel of lysosomes. Our findings reveal that, unlike the single-membrane, LC3-associated phagocytosis (LAP) vesicles reported for mammalian phagocytes, the canonical double-membrane autophagosomes facilitate the clearance of C. elegans apoptotic cells. These findings add autophagosomes to the collection of intracellular organelles that contribute to phagosome maturation, identify novel crosstalk between the autophagy and phagosome maturation pathways, and discover the upstream signaling molecules that initiate this crosstalk.

Idiopathic Granulomatous Mastitis: Etiology, Clinical Manifestation, Diagnosis and Treatment.

Idiopathic granulomatous mastitis (IGM) is a rare form of chronic inflammatory breast disease. Although it is a benign breast lesion, it may be sometimes difficult to distinguish from breast cancer. The cause of IGM is unknown, but may be associated with autoimmunity, abnormal hormone levels and infection. While the clinical manifestations of IGM involve various manifestations of inflammation, the diagnosis is principally established by histopathology, characterized by non-caseating granulomas and microabscess formation centered on the breast lobules. Therapeutic options for IGM range from observation to various medical treatments, such as steroids, immunosuppressants, and antibiotics, to surgical intervention, particularly if secondarily infected. Given that the controversy on etiology and treatment choices, we accomplished the present review through reviewing IGM-related literature published in 'Pubmed' and 'Web of science' databases during 1997 to 2020, aiming to provide the basis for rational clinical diagnosis and treatment.

Effects of Cold Rolling Reduction on Microstructure, Thickness, Adhesive Force of Al-Si Coating and on Bending Toughness of Al-Si Coated Press-Hardened Steel.

Al-Si coated press-hardened steel (PHS) is widely used along with the development of light-weight vehicles, and the tailor-rolled blank parts based on Al-Si coated PHS have attracted much attention. The preparation process includes cold rolling, austenitization, hot-stamping, and quenching. The most widely used AS60/60 coating will change after cold rolling and austenitization, which has been little-studied. Herein, the effects of cold rolling reduction on the microstructure, thickness, adhesive force of AS60/60 coating and on bending toughness of AS60/60 coated PHS were studied. As the cold rolling reduction ratio increased from 0% to 50%, the coatings were gradually thinned, but the overall continuity was unchanged. When the reduction ratio was 40% or above, rapid diffusion channels were formed. The adhesive force of coatings was 21.50-22.15 MPa. After austenitization, the coating thickness gradually decreased as the cold rolling reduction ratio rose from 0% to 50%, but the structure and overall continuity were both unchanged, and the adhesive force was 21.60-22.40 MPa. The rapid diffusion channels promoted the transition from brittle Fe2Al5 to tough FeAl during austenitization, leading to a rapid increment in bending toughness after Al-Si coated PHS was quenched. When the reduction ratio was 50%, the bending angle was improved by 23%.