Melanoma is the most aggressive type of skin cancer, exhibiting extensive local invasion and early distant metastasis. Aberrant expression of ubiquitin-protein ligase E3C (UBE3C) plays a key role in tumor development and progression. In the present study, we analyzed UBE3C expression in samples of cancerous and normal skin tissue. Levels of UBE3C expression were much higher in primary and metastatic melanoma tissues than in normal skin, cutaneous squamous cell carcinoma or basal cell carcinoma. Melanoma cells overexpressing UBE3C frequently exhibited a mesenchymal phenotype, including reduced expression of the epithelial marker E-cadherin and expression of the mesenchymal marker vimentin. Knockdown of UBE3C expression in melanoma cells significantly suppressed melanoma growth and progression. Furthermore, silencing UBE3C led to increased E-cadherin expression and decreased vimentin and Snail1 expression. Thus UBE3C promotes melanoma progression, possibly by inducing epithelial-mesenchymal transition in melanoma cells. Inhibiting UBE3C activity may suppress melanoma invasion and metastasis and may represent a targeted therapeutic approach.
Urban transportation issues continue to emerge and evolve as a result of rapid urbanization, and the systematic and scientific assessment of urban mobility is becoming increasingly essential. In this work, a Pressure-State-Response (PSR) model with 25 indicators was established to reflect the status of urban mobility. Then, the importance of indicators was determined with the interval-valued intuitionistic fuzzy analytic hierarchy process (IVIF-AHP) method, and the fuzzy comprehensive evaluation (FCE) method was applied to assess the overall status of urban mobility. The validity of the proposed model was demonstrated using the mobility system of Beijing as a case study, and the pressure, state, and response scores were calculated. The proposed assessment model can help to improve urban transportation monitoring and can also provide a scientific foundation for future urban transportation policymaking, planning, and traffic management, thereby further ensuring the sustainable development of urban transportation systems.
An efficient method for transient analysis of onchip coupled interconnects is presented considering nonuniform temperature profiles of the underlying substrate. The parametric macromodeling technique is performed to take into account the effects of substrate temperature. The waveform relaxation with transverse partitioning algorithm is employed for fast transient simulation of large coupled interconnects. With the proposed method, the impact of typical substrate thermal profiles on the performance of on-chip global interconnects is investigated. The efficiency and accuracy of the proposed method is demonstrated by a numerical example.Index Terms -Nonuniform substrate temperature effects, parametric macromodel, transient analysis, interconnect.
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