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For cross welded joints, the behavior of microscopic short crack nucleation and early propagation of the weld toe was studied. Using the Voronoi method, a representative element（RE） with a side length of 150μm at the weld toe was established. Based on the distribution characteristics of the fatigue indicator parameter（FIP）, the fatigue life between FIP and microscopic short crack was constructed.The nucleation of microscopic short crack and their early propagation life were calculated. The results show that the calculated life of weld toe microscopic short crack nucleation and its early propagation is more consistent with the test life data, indicating the applicability of this calculation method; the calculated life of microscopic short crack nucleation and its early expansion accounted for a larger ratio of the overall fatigue life, so it has a non-negligible impact; affected by the microstructure of the grains, the propagation path of the early cracks presents an obvious tortuous shape.

The reliability of the traction converter, a core component in the power traction system of the CRH380 EMU equipment, is heavily reliant on the performance of its cooling unit. The service life of the cooling unit is primarily impacted by its material performance. In order to investigate the material performance of the cooling unit, an impact model was established by using the finite element method. The stress distribution of the cooling unit, made of different materials, was analysed under various impact loads. The accuracy of the calculation results was verified through experiments. The research results show that stress concentration and cracks were identified in the cooling unit of the initial material when subjected to different impact loads. Consequently, an improvement scheme was proposed, which resulted in reduced deformation of the cooling unit, enhanced damage resistance, and an overall mass reduction of approximately 138 kg. These improvements can effectively increase the service life of the cooling unit. The research findings can serve as a reference for further research and optimisation of cooling unit materials. [ABSTRACT FROM AUTHOR]

Let α ∈ (1 , 2 ] , β ∈ (0 , 1) with α − β > 1. This paper focused on the multiplicity of positive solutions for a singular tempered fractional boundary value problem { − 0 R D t α , λ u (t) = p (t) h (e λ t u (t) , 0 R D t β , λ u (t)) , t ∈ (0 , 1) , 0 R D t β , λ u (0) = 0 , 0 R D t β , λ u (1) = 0 , where h ∈ C ([ 0 , + ∞) × [ 0 , + ∞) , [ 0 , + ∞)) and p ∈ L 1 ([ 0 , 1 ] , (0 , + ∞)). By applying reducing order technique and fixed point theorem, some new results of existence of the multiple positive solutions for the above equation were established. The interesting points were that the nonlinearity contained the lower order tempered fractional derivative and that the weight function can have infinite many singular points in [ 0 , 1 ]. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PCa) is one of the most fatal human malignancies. The enhanced infiltration of stromal tissue into the PCa tumor microenvironment limits the identification of key tumor‐specific transcription factors and epigenomic abnormalities in malignant epithelial cells. Integrated transcriptome and epigenetic multiomics analyses of the paired PCa organoids indicate that the basic helix‐loop‐helix transcription factor 40 (BHLHE40) is significantly upregulated in tumor samples. Increased chromatin accessibility at the promoter region and enhanced mTOR pathway activity contribute to the elevated expression of BHLHE40. Integrated analysis of chromatin immunoprecipitation‐seq, RNA‐seq, and high‐throughput chromosome conformation capture data, together with chromosome conformation capture assays, indicate that BHLHE40 not only regulates sterol regulatory element‐binding factor 1 (SREBF1) transcription as a classic transcription factor but also links the enhancer and promoter regions of SREBF1. It is found that the BHLHE40‐SREBF1‐stearoyl‐CoA desaturase axis protects PCa cells from ferroptosis, resulting in the reduced accumulation of lipid peroxidation. Moreover, fatostatin, an SREBF1 inhibitor, significantly suppresses the growth of PCa tumors with high expressions of BHLHE40. This study highlights the important roles of BHLHE40‐mediated lipid peroxidation in inducing ferroptosis in PCa cells and provides a novel mechanism underlying SREBF1 overexpression in PCa. [ABSTRACT FROM AUTHOR]

Non‐alcoholic fatty liver disease (NAFLD) is a progressive disease that can further evolve towards liver fibrosis and hepatocellular carcinoma in the end stage. Costunolide (Cos) is a natural sesquiterpene lactone that exhibits both anti‐inflammatory and antioxidant properties. However, the therapeutic effect of Cos on NAFLD is not clear. In this study, we explored the potential protective effect and mechanism of Cos on NAFLD. C57BL/6 mice were fed with high‐fat diet (HFD) to induce NAFLD. Cos was administered by gavage to observe the effect of Cos on NAFLD. We demonstrated that oral administration of Cos reduced HFD‐induced hepatic fibrosis and the release of inflammatory cytokines, limiting the generation of reactive oxygen species. In vitro experiments revealed that pretreatment with Cos significantly decreased PA‐induced production of inflammatory cytokines and fibrosis in AML‐12 cells. Mechanism study showed that the effect of Cos was correlated to the induction of Nrf‐2 and inhibition of NF‐κB pathways. Collectively, these findings indicated that Cos exerts hepatoprotective effect against NAFLD through blocking inflammation and oxidative stress. Our study suggested that Cos might be an effective pharmacotherapy for the treatment of NAFLD. [ABSTRACT FROM AUTHOR]

Follicular dendritic cell sarcoma (FDCS) is a rare low-intermediate grade malignant neoplasm. To date, published data on FDCS clinical courses are sparse, and no conditional survival study has been performed. Thus, we retrospectively analyzed 187 patients diagnosed with FDCS from the Surveillance, Epidemiology, and End Results (SEER) database. In this study, the median age at diagnosis was 50 years and 91 (48.7%) patients were male. The most common primary location was the abdomen/pelvis (82, 43.9%). The 1-year, 3-year, and 5-year overall survival (OS) were 88.7%, 69.0%, and 59.8%, respectively. The 5-year conditional overall survival increased from 65.7% at baseline to 83.8% in 5-year survivors. The 3-year FDCS-specific death rate was 26.7% and the rate of death from other reasons was 3.7%. In addition, the annual death hazard was the highest in the first four years after diagnosis and increased again in the 7th and 8th years. Age > 60 years at diagnosis, metastatic disease, and FDCS in thoracic organs were associated with shorter OS and FDCS-specific survival. In addition, FDCS patients, with either local or metastatic disease, could benefit from surgery therapy. In addition, adjuvant radiotherapy or chemotherapy for local disease provided no significant improvement in overall survival or FDCS-specific survival. We hope these findings may guide treatments and surveillance strategies for FDCS patients in clinical practice. [ABSTRACT FROM AUTHOR]