No abstract

DBHB promoted functional recovery and relieved pain hypersensitivity in mice with SCI, possibly through inhibition of histone deacetylation and NLRP3 inflammasome activation and preservation of mitochondrial function. DBHB could thus be envisaged as a potential use of interventions for SCI but remains to be tested in humans.

SARS-CoV-2 is the coronavirus responsible for the COVID-19 pandemic. Proteases are central to the infection process of SARS-CoV-2. Cleavage of the spike protein on the virus's capsid causes the conformational change that leads to membrane fusion and viral entry into the target cell. Since inhibition of one protease, even the dominant protease like TMPRSS2, may not be sufficient to block SARS-CoV-2 entry into cells, other proteases that may play an activating role and hydrolyze the spike protein must be identified. We identified amino acid sequences in all regions of spike protein, including the S1/S2 region critical for activation and viral entry, that are susceptible to cleavage by furin and cathepsins B, K, L, S, and V using PACMANS, a computational platform that identifies and ranks preferred sites of proteolytic cleavage on substrates, and verified with molecular docking analysis and immunoblotting to determine if binding of these proteases can occur on the spike protein that were identified as possible cleavage sites. Together, this study highlights cathepsins B, K, L, S, and V for consideration in SARS-CoV-2 infection and presents methodologies by which other proteases can be screened to determine a role in viral entry. This highlights additional proteases to be considered in COVID-19 studies, particularly regarding exacerbated damage in inflammatory preconditions where these proteases are generally upregulated.

Liver trauma, the main cause of death in patients suffering abdominal injury, remains an unresolved problem, especially in its most severe forms. The objective of this study was to probe effective surgical procedures and improve the outcome for patients with severe hepatic injury. A retrospective study of 348 patients with hepatic trauma seen in our institution during the past 12 years was carried out. Of these 348 patients, 259 (74.4%) underwent surgery. To manage severe liver trauma (American Association for the Surgery of Trauma grade III to grade V), procedures such as packing of the laceration with omentum, hepatectomy or direct control of bleeding vessels within the liver substance by means of the Pringle maneuver, selective hepatic artery ligation, retrohepatic caval repair with total hepatic vascular occlusion, and perihepatic packing were selected and combined based on the specific injury. In the 259 patients treated operatively, the survival rate was 86.9% (225/259); and 15 of 40 with retrohepatic venous injury (RHVI) were cured with the maximum blood transfusion of 60 units. In 42 patients treated by perihepatic packing, the bleeding was stopped in 20 of 25 (80%) with RHVI and in 14 of 17 (82%) without such injury ( p > 0.75). The percentage of failure of nonoperative management was 17.2% (17/99); and it was 46.7% (14/30) in patients with grade III-V injury. Death occurred in 3 (50%) of 6 failures of grade IV-V injury. The overall mortality rate was 11.8% (41/348), and 51% of the deaths were due to exsanguination. The results suggest that severe hepatic injuries, especially grade IV-V injuries, usually require surgical intervention; reasonable surgical procedures based on classification of liver trauma and combined application of techniques can increase the survival rate; and perihepatic packing is effective in dealing with RHVI.