ABSTRACT
Objective To explore the effects of four extralevator abdominoperineal excision (ELAPE) procedures on the biomechanics of female pelvic floor through finite element analysis. Methods Six finite element models of the female pelvic floor were established, including a normal model, an ELAPE model, and four individual models. The maximum stress in each model was measured under the same pressure, and the stress distribution was observed. Results The maximum stress of non-levator ani muscle tissues on the partially reserved side and totally removed side of the levator ani muscle were 3.101±0.133 and 4.868±0.123 MPa in individual model 1, respectively, which were lower than the maximum stress in the ELAPE model (5.111±0.081 MPa; both P<0.01). The maximum stress in the non-levator ani muscle tissue were 5.138±0.091 MPa on both sides in individual model 2, which were not significantly different from that in the ELAPE model (P>0.05). The maximum stress of non-levator ani muscle tissues were 4.700±0.105 and 3.653±0.156 MPa in individual models 3 and 4, respectively, which were lower than the maximum stress in the ELAPE model (both P<0.01). Conclusion Three ELAPE procedures, including ELAPE with unilateral levator ani muscle resection plane close to the rectum, and the bilateral pubococcygeal muscle lateral resection of levator ani muscle and levator ani muscle in front of the rectum preserved could decrease stress in the non-levator ani muscle tissue on both sides. The effect is evident on the levator ani muscle partially reserved side of ELAPE with unilateral levator ani muscle resection plane close to the rectum. ELAPE with unilateral levator ani muscle resection plane close to the pelvic wall has no significant reduction effect on the non-levator ani muscle tissue on either side.
ABSTRACT
Objective:To elucidate the change of whole genome expression profile for the effect of melatonin on radiation-induced intestinal injury in mice.Methods:C57BL/6J male mice were administrated with melatonin at 10 mg/kg body weight by intraperitoneal injection once a day for five consecutive days before abdominal irradiation with 14 Gy of γ-rays. Small intestines were harvested 3 d after radiation. GO annotation and KEGG pathway of the differential genes involved in small intestine were explored by DNA microarray analysis.Results:Compared with the control group, 584 differential genes were up-regulated and 538 differential genes were down-regulated for administration group pre-irradiation. The overlapping differential genes were selected from the irradiated mice and the administrated mice pre-irradiation. There were 324 up-regulated genes and 246 down-regulated genes unique to the administrated mice pre-irradiation. GO annotation analysis of the differential genes indicated that the top 15 significantly enriched biological processes for the administrated mice pre-irradiation mainly included autophagosome assembly (GO: 0000045), autophagosome organization (GO: 1905037) and regulation of acute inflammatory response (GO: 0002673). The genes ATG12, ATG16L2 and AMBRA1 were involved in autophagosome assembly and autophagosome organization. The genes C3, CPN1, CD55, CFP, CNR1, C1QA, C2 and CREB3L3 were involved in the regulation of acute inflammation response. KEGG pathway analysis of the differential genes involved indicated that the top 15 significantly enriched pathways for the administrated mice pre-irradiation mainly included O-glycan biosynthesis (hsa00512), glycosphingolipid biosynthesis (hsa00603), ECM-receptor interaction (hsa04512) and biosynthesis of unsaturated fatty acids (hsa01040). qRT-PCR verification showed that the expressions of ATG12 and ATG16L2 genes involved in autophagy for the administrated mice pre-irradiation increased significantly compared with the irradiated mice ( t=2.40, 4.35, P<0.05). Conclusions:The differential genes related with the biological process of autophagy, acute inflammatory response and the pathway of unsaturated fatty acid biosynthesis might be involved in the effect of melatonin on radiation-induced intestinal injury.
ABSTRACT
RNA viruses are critically dependent upon virally encoded proteases that cleave the viral polyproteins into functional mature proteins. Many of these proteases are structurally conserved with an essential catalytic cysteine and this offers the opportunity to irreversibly inhibit these enzymes with electrophilic small molecules. Here we describe the successful application of quantitative irreversible tethering (qIT) to identify acrylamide fragments that selectively target the active site cysteine of the 3C protease (3Cpro) of Enterovirus 71, the causative agent of hand, foot and mouth disease in humans, altering the substrate binding region. Further, we effectively re-purpose these hits towards the main protease (Mpro) of SARS-CoV-2 which shares the 3C-like fold as well as similar catalytic-triad. We demonstrate that the hit fragments covalently link to the catalytic cysteine of Mpro to inhibit its activity. In addition, we provide the first demonstration that targeting the active site cysteine of Mpro can also have profound allosteric effects, distorting secondary structures required for formation of the active dimeric unit of Mpro. These new data provide novel mechanistic insights into the design of EV71 3Cpro and SARS-CoV-2 Mpro inhibitors and identify acrylamide-tagged pharmacophores for elaboration into more selective agents of therapeutic potential.
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Objective: To investigate the mechanism of scorpion venom active peptides(SVAPs) on platelet aggregation. Methods: Platelet aggregation in vivo and vitro was determined by turbidimetry. Carotid thrombosis model was induced by electrostimulation. The determination of 6 keto PGF 1 and TXB 2 were performed by radioimmunoassay. Results: SVAPs 0.125,0.25,0.5mg?ml -1 significantly inhibited the rabbit platelet aggregation triggered by thrombase 0.03u.ml -1 , ADP 10u.ml -1 in vitro( P