Viral infections can alter host transcriptomes by manipulating host splicing machinery. Despite intensive transcriptomic studies on SARS-CoV-2, a systematic analysis of alternative splicing (AS) in severe COVID-19 patients remains largely elusive. Here we integrated proteomic and transcriptomic sequencing data to study AS changes in COVID-19 patients. We discovered that RNA splicing is among the major down-regulated proteomic signatures in COVID-19 patients. The transcriptome analysis showed that SARS-CoV-2 infection induces widespread dysregulation of transcript usage and expression, affecting blood coagulation, neutrophil activation, and cytokine production. Notably, CD74 and LRRFIP1 had increased skipping of an exon in COVID-19 patients that disrupts a functional domain, which correlated with reduced antiviral immunity. Furthermore, the dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity. In summary, our data highlight that a better understanding of the AS landscape may aid in COVID-19 diagnosis and therapy.

Background:Tanshinone IIA is a key active ingredient of danshen, which is derived from the dried root or rhizome of Salviae miltiorrhizae Bge. The tanshinone IIA has protective effects against the focal cerebral ischemic injury. However, the underlying mechanisms remain unclear.Methods:An in vitro model of cerebral ischemia was established by subjecting cultures of hippocampal neuronal cells to oxygen-glucose deprivation followed by reperfusion (OGD/R). The probes of 5-(and-6)-chloromethyl-2’,7’-dichlorodihydrofluorescein diacetate, acetyl ester (CM-H2DCFDA) and 5’,6,6’-tetrachloro-1,1’,3,3’-tetraethylbenzimidazolylcarbocyanine,iodide (JC-1) were used to determine the mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) production. Western-blot was used to detect the expression of proteins in HT-22 cells.Results:The results of cell proliferative assays showed that the tanshinone IIA attenuated OGD/R-mediated neuronal cell death, with the evidence of increased cell viability. In addition, OGD/R exposure led to increase the levels of intracellular reactive oxygen species (ROS), which were significantly suppressed by tanshinone IIA treatment. Furthermore, tanshinone IIA treatment inhibited elevations in MMP and autophagy following exposure to OGD/R. Additionally, OGD/R promoted cell death with concomitant inhibiting phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/ mammalian target of Rapamycin (mTOR) pathway, which was reversed by tanshinone IIA.Conclusion:These results suggest that the tanshinone IIA protects against OGD/R-mediated cell death in HT-22 cells, in part, due to activating PI3K/Akt/mTOR pathway.

FBDs do not increase the risk of death. The incidence of colonic cancer in patients with FBDs may be increased, especially in those with functional constipation and in the elderly.

Figure 1: Clothbone benchmark: a piece of cloth (108K) drops onto a bone of dinosaur (47K) causing large number of self-collision and contact with the bone. The scene consists of 90 frames. We test self-collision of the cloth and collision between cloth and dinosaur. Our method removes 99% of redundant elementary tests and gains almost 6.3x speedup compared with previous approaches on the elementary tests. AbstractIn this paper, we present a novel fast Continuous Collision Detection (CCD) method using SIMD capacity of CPU and idea of dimension reduction. We apply a parallel linear filter culling performed in one-dimensional subspace followed by a parallel planar filter culling performed in two-dimensional subspace before each elementary test, which simultaneously and conservatively tests the relative motion of each primitive pairs in various selected subspace. CPU's SIMD capacity is utilized for parallelizing the projection and filtering process in each subspace. Parallel filter culling in subspace removes a large amount of redundant elementary tests with low cost, and improves the overall performance of collision query. We demonstrate the advantages of our approach when comparing with previous alternatives in various dynamic scenes as benchmarks. In experiments, we observe up to 99% removal of false positives, and a huge magnitude of speed improvement on elementary tests (over 3x). Since our method only correlates the elementary test, it is scalable and can be easily integrated with various available single or multicore CPU based CCD algorithm. In addition, the performance of our method is less sensitive to varying step time.