Search

Simple Summary: tRF-27 has been identified as upregulated in both naïve trastuzumab-resistant HER2-positive breast cancer cells and patient samples, positioning it as a potential biomarker. However, the underlying mechanisms of this upregulation remain unclear. This study proposes that the abnormal transcription of specific tRNA-Cys-GCA isodecoders in naïve trastuzumab-resistant cells might contribute to the accumulation of tRF-27. Additionally, the reduction in H3K27me3 modifications at these tRNA genes, attributed to imbalances in histone modification enzymes, appears to influence tRNA transcription alterations. Building upon these findings, our research demonstrates that the application of a demethylase inhibitor may offer a potential strategy to overcome trastuzumab resistance. tRNA-derived fragments (tRFs) play crucial roles in cancer progression. Among them, tRF-27 has been identified as a key factor in promoting naïve trastuzumab resistance in HER2-positive breast cancer. However, the origin of tRF-27 remains uncertain. In this study, we propose that the upregulated expression of specific cysteine tRNAs may lead to the increased accumulation of tRF-27 in trastuzumab-resistant JIMT1 cells. Mechanistically, the reduced inhibitory H3K27me3 modification at the promoter regions of tRF-27-related tRNA genes in JIMT1 cells, potentially resulting from decreased EZH2 and increased KDM6A activity, may be a critical factor stimulating the transcriptional activity of these tRNA genes. Our research offers fresh insights into the mechanisms underlying elevated tRF-27 levels in trastuzumab-resistant breast cancer cells and suggests potential strategies to mitigate trastuzumab resistance in clinical treatments. [ABSTRACT FROM AUTHOR]

Sharing new energy vehicles is crucial for addressing the issue of traditional vehicles' carbon emissions, reducing urban traffic congestion, safeguarding the environment, and promoting citizens' use of green transportation. However, the parking lot's drawbacks—poor location, challenging parking, and difficulty finding a car—lead to a low popularity rate, few users, and infrequent use. How to scientifically choose parking outlets and maximize the advantages of sharing new energy vehicles has become an important topic in current urban traffic management. This paper constructed a "G-B-U" framework starting with quasi-public goods and stakeholders to analyze the factors influencing the location selection of these vehicles. On this basis, a three-stage location decision method of "market demand prediction—alternative network screening—location model solution" is proposed to optimize the location selection of shared new energy vehicles. The factors are analyzed, and numerical examples are studied, using the districts of Xuzhou City in China as examples: Gulou, Yunlong, and Quanshan. The findings indicate that the main variables influencing how frequently Xuzhou residents use shared new energy cars are network dispersion, rental and return convenience, and usage experience. After site selection optimization, the journey distance is nearly cut in half, saving users a significant amount of travel time. It may meet the travel needs of residents better based on the same number of parking lots. [ABSTRACT FROM AUTHOR]

Simple Summary: While the prognosis of hormone receptor-positive (HR+) breast cancer has been significantly improved, tamoxifen resistance remains a challenge in the treatment of HR+ breast cancer. This study identified that tRF-16-K8J7K1B, a novel small ncRNA derived from the 3′-end of tRNAAla-TGC, was highly expressed in tamoxifen-resistant cells compared to parental cells. Moreover, extracellular tRF-16-K8J7K1B confers tamoxifen resistance via incorporation into exosomes and then degrades the expression of apoptosis-related proteins, reducing the proportion of drug-induced cell apoptosis. Therefore, we propose that exosomal tRF-16-K8J7K1B could be a potential predictive biomarker and therapeutic target for overcoming tamoxifen resistance. Tamoxifen resistance remains a challenge in hormone receptor-positive (HR+) breast cancer. Recent evidence suggests that transfer ribonucleic acid (tRNA)-derived fragments play pivotal roles in the occurrence and development of various tumors. However, the relationship between tRNA-derived fragments and tamoxifen resistance remains unclear. In this study, we found that the expression of tRF-16-K8J7K1B was upregulated in tamoxifen-resistant cells in comparison with tamoxifen-sensitive cells. Higher levels of tRF-16-K8J7K1B were associated with shorter disease-free survival in HR+ breast cancer. Overexpression of tRF-16-K8J7K1B promotes tamoxifen resistance. Moreover, extracellular tRF-16-K8J7K1B could be packaged into exosomes and could disseminate tamoxifen resistance to recipient cells. Mechanistically, exosomal tRF-16-K8J7K1B downregulates the expression of apoptosis-related proteins, such as caspase 3 and poly (ADP-ribose) polymerase, by targeting tumor necrosis factor-related apoptosis-inducing ligand in receptor cells, thereby reducing drug-induced cell apoptosis. Therapeutically, the inhibition of exosomal tRF-16-K8J7K1B increases the sensitivity of breast cancer cells to tamoxifen in vivo. These data demonstrate that exosomal tRF-16-K8J7K1B may be a novel therapeutic target to overcome tamoxifen resistance in HR+ breast cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: There are limited treatments for patients with HER2-negative breast cancer, especially for patients with metastatic breast cancer. This study aimed to observe the efficacy and safety of low-dose apatinib combined with chemotherapy in real-world clinical diagnosis and treatment of HER2-negative metastatic breast cancer. A total of 128 patients were treated with 250 mg apatinib, and we observed the median progression-free survival (PFS) and overall survival (OS) were 4.7 months and 15.3 months, respectively. This observation also indicated that the breast cancer susceptibility gene (BRCA) mutation predicted a better response to apatinib and that combination of immunotherapy or paclitaxel-platinum regimens might be an optimal treatment option. Importantly, a lower dose of apatinib showed mild side effects that improved the patients' life quality. Treatment options for human epidermal growth factor receptor (HER2)-negative breast cancer patients are limited in comparison to the HER2-positive patients, particularly for metastatic breast cancer patients. Apatinib is a small-molecule tyrosine kinase inhibitor that targets the vascular endothelial growth factor receptor 2 (VEGFR-2). Here, we reported the apatinib-based therapy data in HER2-negative metastatic breast cancer. Apatinib was taken at a dose of 250 mg orally once per day and combined with standard chemotherapy regimens. The PFS and OS of 128 patients were 4.7 months and 15.3 months, respectively. The objective response rate (ORR) and the disease control rate (DCR) were 22.7% and 80.5%, respectively. Patients with breast cancer susceptibility gene (BRCA) mutations were found to have a longer PFS and OS. Moreover, combination immunotherapy or paclitaxel-platinum regimens shared an improved response to other regimens. Most of the adverse effects (hypertension, anaemia, and hand-foot syndrome) were grade 1 to 2. Metastatic breast cancer patients could benefit from apatinib therapy at a low dosage, and the adverse effects are mild in real-world clinical practice. Furthermore, BRCA may be a putative biomarker for apatinib in HER2-negative breast cancer. Immunotherapy or paclitaxel-platinum regimens may be recommended to combine with apatinib therapy. [ABSTRACT FROM AUTHOR]

A batch of Sn oxides was fabricated by pulse direct current reactive magnetron sputtering (pDC−RMS) using different Ar/O2 flow ratios at 0.3 Pa; the influence of stoichiometry on the physical and electrochemical properties of the films was evaluated by the characterization of scanning electron microscope (SEM), X-ray diffraction (XRD), X-ray reflection (XRR), X-ray photoelectron spectroscopy (XPS) and more. The results were as follows. First, the film surface transitioned from a particle morphology (roughness of 50.0 nm) to a smooth state (roughness of 3.7 nm) when Ar/O2 flow ratios changed from 30/0 to 23/7; second, all SnOx films were in an amorphous state, some samples deposited with low O2 flow ratios (≤2 sccm) still included metallic Sn grains. Therefore, the stoichiometry of SnOx calculated by XPS spectra increased linearly from SnO0.0.08 to SnO1.71 as the O2 flow ratios increased, and the oxidation degree was further calibrated by the average valence method and SnO2 standard material. Finally, the electrochemical performance was confirmed to be improved with the increase in oxidation degree (x) in SnOx, and the SnO1.71 film deposited with Ar/O2 = 23/7 possessed the best cycle performance, reversible capacity of 396.1 mAh/g and a capacity retention ratio of 75.4% after 50 cycles at a constant current density of 44 μA/cm2. [ABSTRACT FROM AUTHOR]

This paper proposes a demagnetization fault detection, mode recognition, magnetic pole positioning, and degree evaluation method for permanent magnet synchronous motors. First, the analytical model of the single-coil no-load back electromotive force (EMF) of demagnetization fault for Permanent magnet synchronous motor (PMSM) arbitrary magnetic poles is established. In the analytical model, the single-coil no-load back EMF residual of the health state and the single magnetic pole sequential demagnetization fault are calculated and normalized. Model results are used as the fault sample database. Second, the energy interval database of the single-coil no-load back EMF residual with different numbers of magnetic pole demagnetization is established. Demagnetization fault detection and degree evaluation are performed by the real-time acquired amplitudes of the single-coil no-load back EMF residual. The number of demagnetization poles is determined by comparing the energy of the single-coil no-load back EMF residual with the energy interval database. Demagnetization mode recognition and magnetic pole positioning are realized by analyzing the correlation coefficients between normalized the single-coil no-load back EMF residual and the fault sample database. Finally, results of analysis of the finite element simulation validate the feasibility and effectiveness of the proposed method. [ABSTRACT FROM AUTHOR]