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Cisplatin (CDDP) serves as a vital component in the chemotherapeutic approach to treat esophageal squamous cell carcinoma (ESCC). However, prolonged CDDP application frequently culminates in resistance, compromising therapeutic outcomes. Through genome-wide CRISPR library screening, our study elucidates the mechanisms underlying this resistance, pinpointing CYFIP2 as a pivotal mediator. Notably, the involvement CYFIP2 is characterized by pronounced autophagic activity and the modulation of multiple cellular pathways. Empirical validation was achieved by treating ESCC cell lines with CDDP, which resulted in an upsurge of CYFIP2 expression. The functional impact of CYFIP2 was further delineated through knockdown experiments, where a marked suppression in cell proliferation was observed, alongside a discernible decline in reactive oxygen species levels. This was complemented by a suite of assays and microscopic techniques, including GFP-LC3, mRFP-GFP-LC3, electron microscopy and western blot, which collectively affirmed the inhibitory effect of CYFIP2 knockdown on autophagic processes, particularly impeding autophagosome formation and their subsequent fusion with lysosomes. In vivo studies have also confirmed that CYFIP2 knockdown limits tumor progression and increases CDDP efficacy. Conclusively, our findings introduce CYFIP2 as a novel contributor to CDDP resistance in ESCC, underscoring its potential as a therapeutic target. This revelation not only deepens our understanding of resistance mechanisms but also paves the way for novel oncotherapeutic strategies, promising enhanced treatment efficacy against ESCC. [ABSTRACT FROM AUTHOR]

This study aimed to characterize the role of female sex in the pathogenesis of diabetic retinopathy. In the retinae of female Ins2Akita-diabetic mice (F-IA), ovariectomized female Ins2Akita-diabetic mice (F-IA/OVX), male Ins2Akita-diabetic mice (M-IA), and female STZ-diabetic mice (F-STZ), the formation of reactive metabolites and post-translational modifications, damage to the neurovascular unit, and expression of cellular stress response genes were analyzed. Compared to the male diabetic retina, the concentrations of the glycation adduct fructosyl-lysine, the Maillard product 3-deoxyglucosone, and the reactive metabolite methylglyoxal were significantly reduced in females. In females, there was also less evidence of diabetic damage to the neurovascular unit, as shown by decreased pericyte loss and reduced microglial activation. In the male diabetic retina, the expression of several members of the crystallin gene family (Cryab, Cryaa, Crybb2, Crybb1, and Cryba4) was increased. Clinical data from type 1 diabetic females showed that premenopausal women had a significantly lower prevalence of diabetic retinopathy compared to postmenopausal women stratified for disease duration and glycemic control. These data emphasize the importance of estradiol in protecting the diabetic retina and highlight the pathogenic relevance of sex in diabetic retinopathy., (© 2024. The Author(s).)

In order to improve the real-time performance of gesture recognition by a micro-Doppler map of mmWave radar, the point cloud based gesture recognition for mmWave radar is proposed in this paper. Two steps are carried out for mmWave radar-based gesture recognition. The first step is to estimate the point cloud of the gestures by 3D-FFT and the peak grouping. The second step is to train the TRANS-CNN model by combining the multi-head self-attention and the 1D-convolutional network so as to extract the features in the point cloud data at a deeper level to categorize the gestures. In the experiments, TI mmWave radar sensor IWR1642 is used as a benchmark to evaluate the feasibility of the proposed approach. The results show that the accuracy of the gesture recognition reaches 98.5%. In order to prove the effectiveness of our approach, a simply 2Tx2Rx radar sensor is developed in our lab, and the accuracy of recognition reaches 97.1%. The results show that our proposed gesture recognition approach achieves the best performance in real time with limited training data in comparison with the existing methods.

Basal progenitor cells serve as a stem cell pool to maintain the homeostasis of the epithelium of the foregut, including the esophagus and the forestomach. Aberrant genetic regulation in these cells can lead to carcinogenesis, such as squamous cell carcinoma (SCC). However, the underlying molecular mechanisms regulating the function of basal progenitor cells remain largely unknown. Here, we use mouse models to reveal that Hippo signaling is required for maintaining the homeostasis of the foregut epithelium and cooperates with p53 to repress the initiation of foregut SCC. Deletion of Mst1/2 in mice leads to epithelial overgrowth in both the esophagus and forestomach. Further molecular studies find that Mst1/2 -deficiency promotes epithelial growth by enhancing basal cell proliferation in a Yes-associated protein (Yap)-dependent manner. Moreover, Mst1/2 deficiency accelerates the onset of foregut SCC in a carcinogen-induced foregut SCC mouse model, depending on Yap. Significantly, a combined deletion of Mst1/2 and p53 in basal progenitor cells sufficiently drives the initiation of foregut SCC. Therefore, our studies shed light on the collaborative role of Hippo signaling and p53 in maintaining squamous epithelial homeostasis while suppressing malignant transformation of basal stem cells within the foregut., Competing Interests: Competing interests statement:The authors declare no competing interest.