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COVID-19 is an immune-mediated inflammatory disease caused by SARS-CoV-2 infection, the combination of anti-inflammatory and antiviral therapy is predicted to provide clinical benefits. We recently demonstrated that mast cells (MCs) are an essential mediator of SARS-CoV-2-initiated hyperinflammation. We also showed that spike protein-induced MC degranulation initiates alveolar epithelial inflammation for barrier disruption and suggested an off-label use of antihistamines as MC stabilizers to block degranulation and consequently suppress inflammation and prevent lung injury. In this study, we emphasized the essential role of MCs in SARS-CoV-2-induced lung lesions新冠肺炎（COVID-19）是由新型冠状病毒（SARS-CoV-2）感染导致的炎症相关疾病。抗病毒药物和抗炎药物联用有望在临床治疗取得有益的效果。我们最近证明，肥大细胞（Mast cell，MC）是SARS-CoV-2引发炎症的重要效应细胞。发现SARS-CoV-2刺突蛋白（Spike）通过诱导MC脱颗粒诱发肺泡上皮细胞炎症从而造成组织通透性破坏，并发现临床上治疗过敏性疾病的抗组胺药物可作为MC稳定剂，阻止Spike诱导的MC脱颗粒,进而抑制炎症发生和保护肺损伤。在该研究中，我们进一步阐述MC在SARS-CoV-2引发肺损伤中的作用，并评价抗组胺药物和抗病毒药物联用对病毒复制和炎症损伤的双重抑制效果。证明Spike诱导的MC脱颗粒可导致肺泡毛细血管损伤，而抗组胺药物预处理肺微血管内皮细胞，可防止细胞间紧密连接的破坏；特别重要一点，发现抗组胺药物HR1(histamine receptor)拮抗剂氯雷他定（Loratadine）和抗病毒药物瑞德西韦（Remdesivir）联用，可同时抑制SARS-CoV-2复制和缓解炎症造成的小鼠肺部损伤。该研究再次证明了MC在SARS-CoV-2诱导肺部炎症和导致肺损伤中的重要作用，并提出一种COVID-19抗病毒药物和抗炎药物联用治疗策略。.

In this paper, the content and density of adsorbed water in fine-grained soil are determined. According to the test results, the calculation method of compaction degree of the solid-phase and void ration of soil is improved. Four kinds of fine-grained soils from different regions in China were selected, and the adsorbed water content and density of four kinds of fine-grained soils were determined by thermogravimetry and volumetric flask method. Furthermore, SEM and XRD experiments were used to analyze the differences in the ability of each soil sample to absorb water. In order to study the compression characteristics of adsorbed water, four saturated soil samples were tested by consolidation method. The results show that the desorption temperature range of the adsorbed water and its density were equal to 100–115 °C and 1.30 g/cm3, respectively. Adsorbed water plays a positive role in keeping the compressibility of fine-grained soil at a low rate when it has high water content. Besides, adsorbed water can be a stable parameter and is difficult to discharge during the operation period of subgrade. The settlement of fine-grained soil embankment is predicted by engineering example, and compared with the result of conventional calculation method. The results show that it is more close to the field monitoring results by using the improved void ratio of soil as the parameter.

Mast cells (MCs) are strategically located at the host-environment interface and their non-allergic roles in the immune-surveillance of pathogens have recently gained more attention. However, MC-caused detrimental regulation of immune inflammations can promote viral invasion. Currently, the role of MCs in retroviral infection remains elusive. We have recently proved that human gut MCs could capture and transfer HIV-1 to CD4+ T cells for promoting viral spread; MC-released histamine augments HIV-1-induced functional polarization of dendritic cells to cause immunosuppression via stimulating the differentiation of regulatory T cells. In this study, we used a murine model of MuLV/Friend virus infection to address MC role in acute retroviral infection in vivo. The acute infection of MuLV/Friend virus could be established in C57BL/6 wild type mice, but viral acquisition showed low efficiency in C57BL/6-KitW–sh/W–sh (Sash) mice which lack MCs. In mechanism, we found that MuLV/Friend virus triggered MC activation for degranulation; MC degranulation subsequently activated the granulocyte-like myeloid derived suppressive cells (G-MDSCs) to inhibit CD8+ T cells- and NK cells-mediated antiviral immune responses. The reconstruction of MCs in Sash mice promoted acute retroviral infection by regulating G-MDSCs functions and antiviral immune responses. Importantly, the administration of MC stabilizers to block cell degranulation elevated antiviral immune response and consequently suppressed retrovirus infection. This study uncovers a specific role of MCs in acute retroviral infection and elucidates the underlying immune-mechanisms. Targeting MCs may provide a novel approach for controlling acute infection by retroviruses.

SARS-CoV-2 infection-induced hyper-inflammation links to the acute lung injury and COVID-19 severity. Identifying the primary mediators that initiate the uncontrolled hypercytokinemia is essential for treatments. Mast cells (MCs) are strategically located at the mucosa and beneficially or detrimentally regulate immune inflammations. Here we showed that SARS-CoV-2-triggeed MC degranulation initiated alveolar epithelial inflammation and lung injury. SARS-CoV-2 challenge induced MC degranulation in ACE-2 humanized mice and rhesus macaques, and a rapid MC degranulation could be recapitulated with Spike-RBD binding to ACE2 in cells; MC degranulation alterred various signaling pathways in alveolar epithelial cells, particularly, led to the production of pro-inflammatory factors and consequential disruption of tight junctions. Importantly, the administration of clinical MC stabilizers for blocking degranulation dampened SARS-CoV-2-induced production of pro-inflammatory factors and prevented lung injury. These findings uncover a novel mechanism for SARS-CoV-2 initiating lung inflammation, and suggest an off-label use of MC stabilizer as immunomodulators for COVID-19 treatments.Graphical abstractIn BriefSARS-CoV-2 triggers an immediate mast cell (MC) degranulation, which initiates the alveolar epithelial inflammation and disrupts the tight junction. MC stabilizers that block degranulation reduce virus-induced lung inflammation and injury.HighlightsThe binding of RBD of Spike protein of SARS-CoV-2-to ACE2 receptor protein triggers an immediate MC degranulationMC degranulation induces transcriptomic changes include an upregulated inflammatory signaling and a downregulated cell-junction signalingMC degranulation leads to alveolar epithelial inflammation and disruption of tight junctionsMC stabilizer that inhibits degranulation reduces SARS-CoV-2-induced lung inflammation and injury in vivo

In preclinical and phase I and II clinical studies, 2'-deoxy-2'-β-fluoro-4'-azidocytidine (FNC) displays a potent and long-lasting inhibition of HIV-1 infection. To investigate its mechanism of action, we compared it with the well-documented lamivudine (3TC). Pharmacokinetic studies revealed that the intracellular retention of FNC triphosphate in peripheral blood mononuclear cells was markedly longer than that of the 3TC triphosphate. FNC selectively enters and is retained in HIV target cells, where it exerts long-lasting prevention of HIV-1 infection. In addition to inhibition of HIV-1 reverse transcription, FNC also restores A3G expression in CD4+ T cells in FNC-treated HIV-1 patients. FNC binds to the Vif-E3 ubiquitin ligase complex, enabling A3G to avoid Vif-induced ubiquitination and degradation. These data reveal the mechanisms underlying the superior anti-HIV potency and long-lasting action of FNC. Our results also suggest a potential clinical application of FNC as a long-lasting pre-exposure prophylactic agent capable of preventing HIV infection.

Two methods are proposed in the paper to reduce the flow and pressure pulsation caused by the reciprocating pump in aircraft deicing system. First, the control algorithm for multiple phases of pumps is used to cut down the pulse energy among the pumps. Then the inflatable accumulator is used in combination with pumps to make the fluid more stable. At last, the simulation results show that the methods can effectively decrease the pulsation in the system.

The theory of aircraft ground deicing processes is studied in this paper. Aiming at the civil aviation airport with a number of parking bays, a model considering multiple constraints is presented. According to the first come first service scheduling, simulation is carried out to get the relationship between the quantity of flights and the delay time, based on the flight plan data of Beijing Capital International Airport. Then, taking into account the cooperation of the airports with airlines, besides the competition between airline companies, priority comparison method is proposed to optimize the airline flight deicing scheme. The result of research shows that the optimization method can effectively reduce the delay time.

Aiming at the flow and pressure pulsation caused by the reciprocating pump in aircraft deicing system, two solutions are presented in the paper. First, based on computational fluid dynamics and finite element analysis theory, the assembled ways of rigid and flexible accumulators are applied to absorb vibration in order to inhibit the pulse. Then, the control algorithm for multiple phases of three pumps is used to offset the pulse energy among the pumps. At last, simulation results show that both methods have effectively reduced the pulsation in the aircraft deicing system.

This paper established a mathematical model for the centralized aircraft ground deicing processes which includes preparation, deicing operations and release after the deicing. To ensure the safety of aircraft, the proposed model has taken into account the constraint that the total time of deicing processes shall be less than the retention time of the deicing fluid so as to avoid secondary icing hazards. The proposed model has been verified through numerical simulations, where a first-come-first-service scheduling scheme is assumed. Simulation results show that the proposed model matches the current status of airport deicing very well.