Summary: Visualizing genes’ structure and annotated features helps biologists to investigate their function and evolution intuitively. The Gene Structure Display Server (GSDS) has been widely used by more than 60 000 users since its first publication in 2007. Here, we reported the upgraded GSDS 2.0 with a newly designed interface, supports for more types of annotation features and formats, as well as an integrated visual editor for editing the generated figure. Moreover, a user-specified phylogenetic tree can be added to facilitate further evolutionary analysis. The full source code is also available for downloading.Availability and implementation: Web server and source code are freely available at http://gsds.cbi.pku.edu.cn.Contact: gaog@mail.cbi.pku.edu.cn or gsds@mail.cbi.pku.edu.cnSupplementary information: Supplementary data are available at Bioinformatics online.

Modern research has provided new insights into the biological mechanisms of noise-induced hearing loss, and with these new insights comes hope for possible prevention or treatment. Underlying the classic set of cochlear pathologies that occur as a result of noise exposure are increased levels of reactive oxygen species (ROS) that play a significant role in noise-induced hair cell death. Both necrotic and apoptotic cell death have been identified in the cochlea. Included in the current review is a brief review of ROS, along with a description of sources of cochlear ROS generation and how ROS can damage cochlear tissue. The pathways of necrotic and apoptotic cell death are also reviewed. Interventions are discussed that target the prevention of noise-induced hair cell death: the use of antioxidants to scavenge and eliminate the damaging ROS, pharmacological interventions to limit the damage resulting from ROS, and new techniques aimed at interrupting the apoptotic biochemical cascade that results in the death of irreplaceable hair cells.

Background In December 2019, Coronavirus Disease 2019 (COVID-19) outbreak was reported from Wuhan, China. Information on the clinical course and prognosis of COVID-19 was not thoroughly described. We described the clinical courses and prognosis in COVID-19 patients. Methods Retrospective case series of COVID-19 patients from Zhongnan Hospital of Wuhan University in Wuhan, and Xi-shui Hospital, Hubei Province, China, up to February 10, 2020. Epidemiological, demographic and clinical data were collected. Clinical course of survivors and non-survivors were compared. Risk factors for death were analyzed. Results A total of 107 discharged patients with COVID-19 were enrolled. The clinical course of COVID-19 presented as a tri-phasic pattern. Week 1 after illness onset was characterized by fever, cough, dyspnea, lymphopenia and radiological multilobar pulmonary infiltrates. In severe cases, thrombocytopenia, acute kidney injury, acute myocardial injury or adult respiratory distress syndrome were observed. During week 2, in mild cases, fever, cough and systemic symptoms began to resolve and platelet count rose to normal range, but lymphopenia persisted. In severe cases, leukocytosis, neutrophilia and deteriorating multi-organ dysfunction were dominant. By week 3, mild cases had clinically resolved except for lymphopenia. However, severe cases showed persistent lymphopenia, severe acute respiratory dyspnea syndrome , refractory shock, anuric acute kidney injury, coagulopathy, thrombocytopenia and death. Older age and male sex were independent risk factors for poor outcome of the illness. Conclusions A period of 7–13 days after illness onset is the critical stage in COVID-19 course. Age and male gender were independent risk factors for death of COVID-19.

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The immune response is an important component of the cochlear response to stress. As an important player in the cochlear immune system, the basilar membrane immune cells reside on the surface of the scala tympani side of the basilar membrane. At present, the immune cell properties in this region and their responses to stress are not well understood. Here, we investigated the functional role of these immune cells in the immune response to acoustic overstimulation. This study reveals that tissue macrophages are present in the entire length of the basilar membrane under steady-state conditions. Notably, these cells in the apical and the basal sections of the basilar membrane display distinct morphologies and immune protein expression patterns. Following acoustic trauma, monocytes infiltrate into the region of the basilar membrane, and the infiltrated cells transform into macrophages. While monocyte infiltration and transformation occur in both the apical and the basal sections of the basilar membrane, only the basal monocytes and macrophages display a marked increase in the expression of MHC II and CIITA, a MHC II production cofactor, suggesting the site-dependent activation of antigen-presenting function. Consistent with the increased expression of the antigen-presenting proteins, CD4+ T cells, the antigen-presenting partner, infiltrate into the region of the basilar membrane where antigen-presenting proteins are upregulated. Further pathological analyses revealed that the basal section of the cochlea displays a greater level of sensory cell damage, which is spatially correlated with the region of antigen-presenting activity. Together, these results suggest that the antigen-presenting function of the mononuclear phagocyte population is activated in response to acoustic trauma, which could bridge the innate immune response to adaptive immunity.

We previously reported that intense noise exposure causes outer hair cell (OHC) death primarily through apoptosis. Here we investigated the intracellular signal pathways associated with apoptotic OHC death. Chinchillas were exposed to a 4 kHz narrowband noise at 110 dB SPL for 1 h. After the noise exposure, the cochleas were examined for the activity of each of three caspases, including caspase-3, -8, or -9 with carboxyfluorescein-labeled fluoromethyl ketone (FMK)-peptide inhibitors. The cochleas were further examined for cytochrome c release from mitochondria by immunohistology and for DNA degradation by the TUNEL method. The results showed that the noise exposure triggered activation of caspase-3, an important mediator of apoptosis. The noise exposure also caused the activation of caspase-8 and caspase-9, each of which is associated with a distinct signaling pathway that leads to activation of caspase-3. Caspase activation occurred only in the apoptotic OHCs and not in the necrotic OHCs. These results indicate that multiple signaling pathways leading to caspase-3 activation take place simultaneously in the apoptotic OHCs. In addition to caspase activation, noise exposure caused the release of cytochrome c from mitochondria, resulting in a punctate fluorescence in the cytosol. In contrast to activation of caspases, the release of cytochrome c took place in both apoptotic and necrotic OHCs. Moreover, the release of cytochrome c in a subpopulation of OHCs took place early in the cell death process, prior to any outward signs of necrosis or apoptosis. These data suggest that in this subpopulation there exists a common step that is shared by cell death pathways before entering either necrosis or apoptosis. Lastly, use of the TUNEL assay in combination with PI labeling provides a more accurate discrimination between apoptosis and necrosis.

We study the stability properties of switched systems consisting of both Hurwitz stable and unstable linear time-invariant subsystems using an average dwell time approach. We propose a class of switching laws so that the entire switched system is exponentially stable with a desired stability margin. In the switching laws, the average dwell time is required to be suYciently large, and the total activation time ratio between Hurwitz stable subsystems and unstable subsystems is required to be no less than a speci® ed constant. We also apply the result to perturbed switched systems where nonlinear vanishing or non-vanishing norm-bounde d perturbations exist in the subsystems, and we show quantitatively that, when norms of the perturbations are small, the solutions of the switched systems converge to the origin exponentially under the same switching laws.

Background: Accurate glioma grading before surgery is of the utmost importance in treatment planning and prognosis prediction. But previous studies on magnetic resonance imaging (MRI) images were not effective enough. According to the remarkable performance of convolutional neural network (CNN) in medical domain, we hypothesized that a deep learning algorithm can achieve high accuracy in distinguishing the World Health Organization (WHO) low grade and high grade gliomas.Methods: One hundred and thirteen glioma patients were retrospectively included. Tumor images were segmented with a rectangular region of interest (ROI), which contained about 80% of the tumor. Then, 20% data were randomly selected and leaved out at patient-level as test dataset. AlexNet and GoogLeNet were both trained from scratch and fine-tuned from models that pre-trained on the large scale natural image database, ImageNet, to magnetic resonance images. The classification task was evaluated with five-fold cross-validation (CV) on patient-level split.Results: The performance measures, including validation accuracy, test accuracy and test area under curve (AUC), averaged from five-fold CV of GoogLeNet which trained from scratch were 0.867, 0.909, and 0.939, respectively. With transfer learning and fine-tuning, better performances were obtained for both AlexNet and GoogLeNet, especially for AlexNet. Meanwhile, GoogLeNet performed better than AlexNet no matter trained from scratch or learned from pre-trained model.Conclusion: In conclusion, we demonstrated that the application of CNN, especially trained with transfer learning and fine-tuning, to preoperative glioma grading improves the performance, compared with either the performance of traditional machine learning method based on hand-crafted features, or even the CNNs trained from scratch.