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Ovarian cancer is the leading cause of death among gynecological malignancies. Checkpoint blockade immunotherapy has so far only shown modest efficacy in ovarian cancer and platinum-based chemotherapy remains the front-line treatment. Development of platinum resistance is one of the most important factors contributing to ovarian cancer recurrence and mortality. Through kinome-wide synthetic lethal RNAi screening combined with unbiased datamining of cell line platinum response in CCLE and GDSC databases, here we report that Src-Related Kinase Lacking C-Terminal Regulatory Tyrosine And N-Terminal Myristylation Sites (SRMS), a non-receptor tyrosine kinase, is a novel negative regulator of MKK4-JNK signaling under platinum treatment and plays an important role in dictating platinum efficacy in ovarian cancer. Suppressing SRMS specifically sensitizes p53-deficient ovarian cancer cells to platinum in vitro and in vivo. Mechanistically, SRMS serves as a sensor for platinum-induced ROS. Platinum treatment-induced ROS activates SRMS, which inhibits MKK4 kinase activity by directly phosphorylating MKK4 at Y269 and Y307, and consequently attenuates MKK4-JNK activation. Suppressing SRMS leads to enhanced MKK4-JNK-mediated apoptosis by inhibiting MCL1 transcription, thereby boosting platinum efficacy. Importantly, through a drug repurposing strategy, we uncovered that PLX4720, a small molecular selective inhibitor of B-RafV600E, is a novel SRMS inhibitor that can potently boost platinum efficacy in ovarian cancer in vitro and in vivo. Therefore, targeting SRMS with PLX4720 holds the promise to improve the efficacy of platinum-based chemotherapy and overcome chemoresistance in ovarian cancer.

The knowledge of the distribution of residual stresses in milling planes is of paramount importance to understand the surface qualities of engineering components, research on manufacturing processes and improve the assembly qualities of machines. For this purpose, a prediction method for the residual stress fields was proposed. Residual stresses of some surface discrete points of a rectangular specimen were measured. Based on the measurements, the residual stress field was predicted by establishing bivariate mathematical models. The obtained results are close to the experimental technique and superior to the previous average method. The predicted stress fields are almost symmetrical along the length or width. The proposed method avoids simulating the process of residual stresses generation and has a unique potential application for engineering components of which the generation process of residual stresses can hardly be simulated in detail.

The bioactive components of chrysanthemum tea are an essential indicator in evaluating its nutritive and commercial values. Combining hyperspectral imaging (HSI) with key wavelength selection and pattern recognition methods, this study developed a novel approach to estimating the content of bioactive components in chrysanthemums, including the total flavonoids (TFs) and chlorogenic acids (TCAs). To determine the informative wavelengths of hyperspectral images, we introduced a variable similarity regularization term into particle swarm optimization (denoted as VSPSO), which can focus on improving the combinatorial performance of key wavelengths and filtering out the features with higher collinearity simultaneously. Moreover, considering the underlying relevance of the phytochemical content and the exterior morphology characteristics, the spatial image features were also extracted. Finally, an ensemble learning model, LightGBM, was established to estimate the TF and TCA contents using the fused features. Experimental results indicated that the proposed VSPSO achieved a superior accuracy, with R2 scores of 0.9280 and 0.8882 for TF and TCA prediction. Furthermore, after the involvement of spatial image information, the fused spectral–spatial features achieved the optimal model accuracy on LightGBM. The R2 scores reached 0.9541 and 0.9137, increasing by 0.0308–0.1404 and 0.0181–0.1066 in comparison with classical wavelength-related methods and models. Overall, our research provides a novel method for estimating the bioactive components in chrysanthemum tea accurately and efficiently. These discoveries revealed the potential effectiveness for constructing feature fusion in HSI-based practical applications, such as nutritive value evaluation and heavy metal pollution detection, which will also facilitate the development of quality detection in the food industry. [ABSTRACT FROM AUTHOR]

Background: Brominated flame retardants (BFRs) are a type of widespread pollutant that can be transmitted through particulate matter, such as dust in the air, and have been associated with various adverse health effects, such as diabetes, metabolic syndrome, and cardiovascular disease. However, there is limited research on the link between exposure to mixtures of BFRs and depression in the general population. Methods: To analyze the association between exposure to BFRs and depression in the population, nationally representative data from the National Health and Nutrition Examination Survey (NHANES; 2005–2016) were used. In the final analysis, a total of 8138 adults aged 20 years and older were included. To investigate the potential relationship between BFRs and outcomes, we used binary logistic regression, restricted cubic spline (RCS), quantile-based g computation (QGC), and weighted quantile sum (WQS) regression. Results: The findings showed that serum BFR concentrations were associated with depressive symptoms over a broad spectrum. Binary logistic regression and RCS analysis showed that certain BFRs, particularly PBB153, were significantly and positively associated with the incidence of depression, even after adjustment for various confounders (p < 0.05). Mixed exposure to BFRs was also found to be associated with depression in the population, with a stronger association in men. The two most influential BFRs, PBB153 and PBDE85, were identified in both mixed exposure models and are potential risk factors of concern. Conclusion: Our study identified new insights into the relationship between BFRs and depression, but sizable population-based cohort studies and toxicology mechanism studies will be needed to establish causality. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the impacts of different middle-ear mucosal conditions on the outcomes of type I tympanoplasty. Methods: A retrospective analysis of 164 patients with chronic otitis media was carried out. The patients were divided into 4 groups according to their mucosal condition. Preoperative hearing levels and air-bone gap (ABG) before and after surgery were compared via the Kruskal‒Wallis H test. The chi-squared test and Fisher's exact test were used to assess the postoperative complications and impact factors of functional success. Results: Preoperatively, neither the air conduction nor bone conduction values differed significantly among groups with different mucosal conditions. All of the ABG closed dramatically after type I tympanoplasty (P <.05) regardless of the mucosal conditions. The functional success rates were lower when the intratympanic mucosa was moderately or severely edematous compared with mildly edematous or normal (P <.05). The disease course, perforation site, and perforation size, as well as the status of the opposite ear, were not related to the auditory functional outcome. The differences in postoperative reotorrhea and reperforation among the 4 groups were not statistically significant. Conclusion: Preoperative hearing levels were not affected by middle-ear mucosal conditions. The functional success rate was influenced by mucosal conditions, but hearing levels were significantly enhanced after surgical intervention regardless of the mucosal status. Postoperative complications were not related to the mucosal conditions. Thus, type I tympanoplasty is adoptable for mucosal abnormalities when pharmacotherapy cannot result in a healthy tympanum. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Atrial fibrillation is closely associated with thrombotic events. In non‐valvular atrial fibrillation, 90% of thrombi are formed by the left atrial appendage. Left atrial appendage occlusion (LAAC) can effectively prevent the detachment of left atrial appendage thrombus during atrial fibrillation, thereby reducing the risk of long‐term disability or death caused by thromboembolic events. However, the identification and management of complications in LAAC are also very important. The efficacy and safety of left atrial appendage occlusion (LAAC) in preventing non‐valvular atrial fibrillation stroke have been confirmed by multiple randomized controlled and registered studies, and have been recommended by several guidelines for stroke prevention in patients with atrial fibrillation at high‐risk of stroke. We reported an 80‐year‐old male patient with persistent atrial fibrillation. The patient underwent left atrial appendage closure surgery due to high risk of embolism and bleeding. On the second day after surgery, echocardiography showed displacement of the left atrial appendage occluder. Immediately perform removal of left atrial appendage occlude and left atrial appendage occlusion on the same day, and the patient was discharged on the fifth day after surgery without any special circumstances. This case demonstrates the feasibility and important clinical significance of using interventional surgery to remove the left atrial appendage occluder after displacement in clinical practice. [ABSTRACT FROM AUTHOR]