The global coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a positive-sense RNA virus. How the host immune system senses and responds to SARS-CoV-2 infection remain largely unresolved. Here, we report that SARS-CoV-2 infection activates the innate immune response through the cytosolic DNA sensing cGAS-STING pathway. SARS-CoV-2 infection induces the cellular level of 2′3′-cGAMP associated with STING activation. cGAS recognizes chromatin DNA shuttled from the nucleus as a result of cell-to-cell fusion upon SARS-CoV-2 infection. We further demonstrate that the expression of spike protein from SARS-CoV-2 and ACE2 from host cells is sufficient to trigger cytoplasmic chromatin upon cell fusion. Furthermore, cytoplasmic chromatin-cGAS-STING pathway, but not MAVS-mediated viral RNA sensing pathway, contributes to interferon and pro-inflammatory gene expression upon cell fusion. Finally, we show that cGAS is required for host antiviral responses against SARS-CoV-2, and a STING-activating compound potently inhibits viral replication. Together, our study reported a previously unappreciated mechanism by which the host innate immune system responds to SARS-CoV-2 infection, mediated by cytoplasmic chromatin from the infected cells. Targeting the cytoplasmic chromatin-cGAS-STING pathway may offer novel therapeutic opportunities in treating COVID-19. In addition, these findings extend our knowledge in host defense against viral infection by showing that host cells’ self-nucleic acids can be employed as a “danger signal” to alarm the immune system.

The tunneled central venous catheter (CVC) plays an important role for hemodialysis patients, but CVC-related thrombosis in the central veins remain problematic. This study is the first try to numerically find out what hemodynamic parameters are predisposed to the initiation and formation of thrombus after CVC insertion. And the potential relationship between hemodynamic parameters and the incidence rates of thrombosis occurrence was explored. The results revealed that the CVC insertion led to a significant increase of hydraulic resistance, wide-ranging abnormally high wall shear stress (WSS), and a great loss of flow rotation in the vein. Moreover, the clinical data showed that thrombosis mainly occurred at sections where most blood flow lost spiral rotation after the CVC insertion, but no corresponding match was observed between the occurrence of thrombosis and the flow velocity or WSS. We speculate that the destruction of the flow rotation in the central vein is a precursor to the thrombus formation around CVC, and an introduction of spiral flow with the CVC insertion may possibly help to protect the central vein from thrombosis. Further animal and clinical experiments should be carried out to test and verify this speculation.

The rupture of an abdominal aortic aneurysm (AAA) is generally an unexpected event. Up to now, there is no agreement on an accurate criteria to predict the rupture risk of AAAs. This paper aims to numerically investigate the hemodynamics of three ruptured and one non-ruptured patient-specific AAA models to correlate local hemodynamic parameters with the rupture sites, and for the first time, this study introduced helicity as a potential index for the rupture potential of AAAs.3D reconstructions from CT scans were done. The simulation revealed that all the rupture sites were in regions of stagnation with near zero wall shear stress (WSS) but large WSS gradient (WSSG), which may explain the observation by the former researchers that the rupture site in the ruptured AAA has the lowest recorded wall thickness compared to other non-ruptured regions. Moreover, all the ruptures occurred at regions of zero helicity which represents a purely axial or circumferential flow. In addition, this study revealed that the double low region for the non-ruptured AAA was present with a thick layer of plaques, it suggests that the AAA rupture and the formation of atherosclerotic plaques may share a lot common physiological features. However, the fact that there are no plaques present in the walls of three RAAAs also indicates that AAA is not always a result of atherosclerosis. The current computational study may complement the maximum diameter, peak wall stress and other clinically relevant factors in AAA ruptures to identify the rupture sites of AAAs.

Preliminary studies on an individual helical graft indicated that its hemodynamics might be improved while pressure drop increased compared with a traditional graft. Aiming to investigate whether the benefits of a helical graft to hemodynamics dominate its deficits, this study numerically carried out comparative study of helical-type artery bypass graft (ABG) and traditional-type ABG under both steady and pulsatile flow conditions. The results showed that a helical-type ABG resulted in reduced oscillating shear index, improved wall shear stress, enhanced flow mixing and three-dimensionality, and improved flow behavior at the distal anastomosis and occluded section of the host vessel compared with traditional-type ABG. More important, although a helical-type ABG did increase the pressure drop compared with a traditional one, its maximum percentage increase during a cardiac cycle was <21% which is still within physiological sense. Therefore, we believe that the adoption of helical bypass could help to prevent intimal hyperplasia (IH) and thrombosis at the distal anastomosis and improve the graft patency while keeping clinical maintenance. This investigation provided an important basis for the clinical applications and theory support of helical graft.

The guideline for the treatment of interrupted aortic arch (IAA) in adults has not been established although most centers tend to propose surgery. There is no clear evidence for the preferred selection of surgical repair versus conservatively medical treatment for the uncertain effects of both treatments. However, reports of sporadic aortic dissection (AD) of descending aorta (DAo) in IAA in adults before surgery drew our attention. It is quite perplexing because there seems to be no risk factors for the development of AD at DAo such as long-term uncontrolled hypertension, atherosclerosis, aortic aneurysm or genetic disorder. In this paper, we carried out the numerical investigation on the hemodynamics in a patient-specific IAA model, which was reconstructed from computed tomography images. Hemodynamic parameters including the flow pattern, pressure distribution, and wall shear stress (WSS) indicators were obtained. The simulation revealed that the jet flows from the collateral arteries (CAs) induced risk hemodynamic forces on the lumen wall including high time-averaged wall shear stress (TAWSS), high pressure and rapid change of WSS direction throughout the cardiac cycle. Moreover, it is found that only a jet flow which circumferentially washes out the aortic wall might cause tears on the wall. It is concluded that the specific geometrical features of the extensive major CAs might result in the risky hemodynamics leading to the initiation and development of AD in this particular IAA patient. CFD analysis in IAA can provide a clinical reference, and the results should be further studied in depth in the future.