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The in situ formation of a tribolayer composed of oxide nanoparticles on the wear surface is an important method for suppressing wear in metals with lamellar structures. However, the complex interaction between microstructure evolution and oxidation in a tribolayer obscures the formation mechanisms of nanolamellar oxidation and transformation. In this paper, samples of tribolayers at different oxidation stages were prepared by a focused ion beam (FIB) lift-out method. The dynamic evolution process and distribution of oxides in tribolayers during the dry sliding process were analyzed by characterization and molecular dynamics simulation. The nanolamellar oxidation processes and the effects of oxide nanoparticles on self-lubricating behavior were investigated. The results showed that oxygen diffused into the nanolamellae, resulting in continuous oxidation and the formation of an oxide/metal interface. The nanolamellar oxides were broken and refined in the further friction process and eventually transformed into oxide nanoparticles. The oxidation process was influenced by frictional shear, and the growth of oxides proceeded along the direction parallel to the nanolamellae with high-density dislocations. The above results provide a theoretical basis for the next step to improve the wear resistance and corrosion inhibition of metals by designing lamellar structures.

Ibrutinib exerts promising anticancer effects in chronic lymphocytic leukaemia (CLL). However, acquired resistance occurs during treatment, necessitating the exploration of underlying mechanisms. Although three‐dimensional genome organization has been identified as a major player in the development and progression of cancer, including drug resistance, little is known regarding its role in CLL. Therefore, we investigated the molecular mechanisms underlying ibrutinib resistance through multi‐omics analysis, including high‐throughput chromosome conformation capture (Hi‐C) technology. We demonstrated that the therapeutic response to ibrutinib is associated with the expression of p21‐activated kinase 1 (PAK1). PAK1, which was up‐regulated in CLL and associated with patients' survival, was involved in cell proliferation, glycolysis and oxidative phosphorylation. Furthermore, the PAK1 inhibitor IPA‐3 exerted an anti‐tumour effect and its combination with ibrutinib exhibited a synergistic effect in ibrutinib‐sensitive and ‐resistant cells. These findings suggest the oncogenic role of PAK1 in CLL progression and drug resistance, highlighting PAK1 as a potential diagnostic marker and therapeutic target in CLL including ibrutinib‐resistant CLL.

BackgroundChronic lymphocytic leukemia (CLL) is the most common leukemia in the western world. Although the treatment landscape for CLL is rapidly evolving, there are still some patients who develop drug resistance or disease refractory. Ferroptosis is a type of lipid peroxidation–induced cell death and has been suggested to have prognostic value in several cancers. Our research aims to build a prognostic model to improve risk stratification in CLL patients and facilitate more accurate assessment for clinical management.MethodsThe differentially expressed ferroptosis-related genes (FRGs) in CLL were filtered through univariate Cox regression analysis based on public databases. Least absolute shrinkage and selection operator (LASSO) Cox algorithms were performed to construct a prognostic risk model. CIBERSORT and single-sample gene set enrichment analysis (ssGSEA) were performed to estimate the immune infiltration score and immune-related pathways. A total of 36 CLL patients in our center were enrolled in this study as a validation cohort. Moreover, a nomogram model was established to predict the prognosis.ResultsA total of 15 differentially expressed FRGs with prognostic significance were screened out. After minimizing the potential risk of overfitting, we constructed a novel ferroptosis-related prognostic score (FPS) model with nine FRGs (AKR1C3, BECN1, CAV1, CDKN2A, CXCL2, JDP2, SIRT1, SLC1A5, and SP1) and stratified patients into low- and high-risk groups. Kaplan–Meier analysis showed that patients with high FPS had worse overall survival (OS) (P

Hypocholesterolaemia is associated with elevated cancer risk and mortality, yet the relation between chronic lymphocytic leukaemia (CLL) and serum lipid profile remains unclear. Our study aims to evaluate the prognostic value of cholesterol levels in CLL and develop a prognostic nomogram that incorporates lipid metabolism. We enrolled 761 newly diagnosed CLL patients and separated them into either derivation (n = 507) or validation (n = 254) cohorts. The prognostic nomogram was constructed through multivariate Cox regression analyses, with performance evaluated using C-index, the area under the curve, calibration, and decision curve analyses. Decreased total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) at diagnosis were significantly associated with worse time to first treatment (TTFT) and cancer-specific survival (CSS), and simultaneously, low HDL-C with low LDL-C was identified as an independent prognostic indicator for both TTFT and CSS. CLL patients achieving complete or partial remission post-chemotherapy had significantly increased TC, HDL-C, and LDL-C levels compared with the baseline, and post-therapeutic HDL-C and LDL-C elevation correlated with favourable survival. The prognostic nomogram augmenting the CLL international prognostic index with low cholesterol levels yielded higher predictive accuracy and discrimination capacity for both 3-year and 5-year CSS. In conclusion, cholesterol profiles can be used as a cheap and readily accessible tool for predicting prognosis in CLL practice.

A three-dimensional thermofluidic coupling transport model is proposed to investigate the influences of different spatial laser intensity profiles (SLIPs), including circular super-Gaussian profile (C-SGP), transverse elliptical Gaussian profile (TE-GP) and longitudinal elliptical Gaussian profile (LE-GP), on the thermofluidic transport characteristics within the melt pool. The results demonstrate that the SLIPs dramatically influence the melt pool geometries, temperature gradient (both in magnitude and direction) at the solidification interface, and fluid flow dynamics. Under the TE-GP strategy, the highest average temperature gradients are observed at the solidification interface. The LE-GP strategy yields the smallest magnitudes and narrowest variation range of the temperature gradient direction angles. The heat transport of the melt pool under the C-SGP and TE-GP strategies are jointly dominated by convective and conductive heat transfer, while those under the LE-GP strategy are dominated by convective heat transfer. Marangoni convection is strongest in the LE-GP strategy and weakest in the TE-GP strategy. [ABSTRACT FROM AUTHOR]