Transcription factor Dmrt1 triggers the SPRY1-NF-κB pathway to maintain testicular immune homeostasis and male fertility.

Bacterial or viral infections, such as Brucella, mumps virus, herpes simplex virus, and Zika virus, destroy immune homeostasis of the testes, leading to spermatogenesis disorder and infertility. Of note, recent research shows that SARS-CoV-2 can infect male gonads and destroy Sertoli and Leydig cells, leading to male reproductive dysfunction. Due to the many side effects associated with antibiotic therapy, finding alternative treatments for inflammatory injury remains critical. Here, we found that Dmrt1 plays an important role in regulating testicular immune homeostasis. Knockdown of Dmrt1 in male mice inhibited spermatogenesis with a broad inflammatory response in seminiferous tubules and led to the loss of spermatogenic epithelial cells. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) revealed that Dmrt1 positively regulated the expression of Spry1, an inhibitory protein of the receptor tyrosine kinase (RTK) signaling pathway. Furthermore, immunoprecipitation-mass spectrometry (IP-MS) and co-immunoprecipitation (Co-IP) analysis indicated that SPRY1 binds to nuclear factor kappa B1 (NF-κB1) to prevent nuclear translocation of p65, inhibit activation of NF-κB signaling, prevent excessive inflammatory reaction in the testis, and protect the integrity of the blood-testis barrier. In view of this newly identified Dmrt1- Spry1-NF-κB axis mechanism in the regulation of testicular immune homeostasis, our study opens new avenues for the prevention and treatment of male reproductive diseases in humans and livestock.

A Cascade-SEME network for COVID-19 detection in chest x-ray images.

PURPOSE: The worldwide spread of the SARS-CoV-2 virus poses unprecedented challenges to medical resources and infection prevention and control measures around the world. In this case, a rapid and effective detection method for COVID-19 can not only relieve the pressure of the medical system but find and isolate patients in time, to a certain extent, slow down the development of the epidemic. In this paper, we propose a method that can quickly and accurately diagnose whether pneumonia is viral pneumonia, and classify viral pneumonia in a fine-grained way to diagnose COVID-19. METHODS: We proposed a Cascade Squeeze-Excitation and Moment Exchange (Cascade-SEME) framework that can effectively detect COVID-19 cases by evaluating the chest x-ray images, where SE is the structure we designed in the network which has attention mechanism, and ME is a method for image enhancement from feature dimension. The framework integrates a model for a coarse level detection of virus cases among other forms of lung infection, and a model for fine-grained categorisation of pneumonia types identifying COVID-19 cases. In addition, a Regional Learning approach is proposed to mitigate the impact of non-lesion features on network training. The network output is also visualised, highlighting the likely areas of lesion, to assist experts' assessment and diagnosis of COVID-19. RESULTS: Three datasets were used: a set of Chest x-ray Images for Classification with bacterial pneumonia, viral pneumonia and normal chest x-rays, a COVID chest x-ray dataset with COVID-19, and a Lung Segmentation dataset containing 1000 chest x-rays with masks in the lung region. We evaluated all the models on the test set. The results shows the proposed SEME structure significantly improves the performance of the models: in the task of pneumonia infection type diagnosis, the sensitivity, specificity, accuracy and F1 score of ResNet50 with SEME structure are significantly improved in each category, and the accuracy and AUC of the whole test set are also enhanced; in the detection task of COVID-19, the evaluation results shows that when SEME structure was added to the task, the sensitivities, specificities, accuracy and F1 scores of ResNet50 and DenseNet169 are improved. Although the sensitivities and specificities are not significantly promoted, SEME well balanced these two significant indicators. Regional learning also plays an important role. Experiments show that Regional Learning can effectively correct the impact of non-lesion features on the network, which can be seen in the Grad-CAM method. CONCLUSIONS: Experiments show that after the application of SEME structure in the network, the performance of SEME-ResNet50 and SEME-DenseNet169 in both two datasets show a clear enhancement. And the proposed regional learning method effectively directs the network's attention to focus on relevant pathological regions in the lung radiograph, ensuring the performance of the proposed framework even when a small training set is used. The visual interpretation step using Grad-CAM finds that the region of attention on radiographs of different types of pneumonia are located in different regions of the lungs.