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The Omicron BA.2 variant has become a dominant infective strain worldwide. Receptor binding studies reveal that the Omicron BA.2 spike trimer have 11-fold and 2-fold higher potency to human ACE2 than the spike trimer from the wildtype (WT) and Omicron BA.1 strains. The structure of the BA.2 spike trimer complexed with human ACE2 reveals that all three receptor-binding domains (RBDs) in the spike trimer are in open conformation, ready for ACE2 binding, thus providing a basis for the increased infectivity of the BA.2 strain. JMB2002, a therapeutic antibody that was shown to have efficient inhibition of Omicron BA.1, also shows potent neutralization activities against Omicron BA.2. In addition, both BA.1 and BA.2 spike trimers are able to bind to mouse ACE2 with high potency. In contrast, the WT spike trimer binds well to cat ACE2 but not to mouse ACE2. The structures of both BA.1 and BA.2 spike trimer bound to mouse ACE2 reveal the basis for their high affinity interactions. Together, these results suggest a possible evolution pathway for Omicron BA.1 and BA.2 variants from human-cat-mouse-human circle, which could have important implications in establishing an effective strategy in combating viral infection.
RESUMO
Objective:To evaluate the effect of perioperative transcutaneous electrical acupoint stimulation (TEAS) on postoperative cellular immune function in the patients undergoing posterior spinal internal fixation.Methods:Ninety patients, aged 40-70 yr, of American Society of Anesthesiologists physical status Ⅰ or Ⅱ, undergoing elective posterior spinal internal fixation in our hospital, were divided into 2 groups ( n=45 each) using a computer-generated table of random numbers: routine group and experiment group.Total intravenous anesthesia was used in routine group, while total intravenous anesthesia combined with TEAS was applied in experiment group.In experiment group, bilateral Zusanli and Sanyinjiao acupoints were stimulated with 2/15 Hz disperse-dense waves at the intensity that could be tolerated by patients at 30 min before induction of anesthesia, maintaining with 2/100 Hz disperse-dense waves from the end of induction until the end of operation at the same stimulation intensity before induction.Bilateral Neiguan and Taichong acupoints were stimulated for 30 min each time with 2/15Hz disperse-dense waves once a day at 1st-4th days after operation.In routine group, the electrodes were connected at the same time period, but no stimulation was given.Venous blood samples were collected before induction of anesthesia, at 1 h after surgery, and on 1st, 3rd, and 5th days after surgery, and the percentage of CD3 + , CD4 + , CD8 + T lymphocytes, CD4 + /CD8 + ratio, WBC count and percentage of neutrophils (NE%) were determined by flow cytometry, and the consumption of intraoperative anesthetics, use of postoperative analgesics, nausea and vomiting, dizziness, infection and length of hospital stay were recorded. Results:Compared with routine group, the total consumption and consumption index of remifentanil were significantly decreased, the percentage of CD3 + T lymphocytes was increased on 3rd and 5th postoperative days, the NE% was decreased on 1st postoperative day, and the incidence of dizziness was decreased ( P<0.05), and no significant change was found in the other indicators in experiment group ( P>0.05). Conclusions:Perioperative TEAS can improve postoperative cellular immune function and has a certain potential value in preventing postoperative infection in the patients undergoing posterior spinal internal fixation.
RESUMO
Objective:To investigate the expressions of nuclear factor of activated T cell 5 (NFAT5) in lung adenocarcinoma tissues and cells, and the effects of NFAT5 on the proliferation, invasion, migration and apoptosis of lung adenocarcinoma cells.Methods:The clinical pathological specimens and paracancerous tissues of 61 patients with lung adenocarcinoma diagnosed and treated in 904th Hospital of Joint Logistic Support Force of People′s Liberation Army from June 2017 to June 2019 were collected. The expression levels of NFAT5 in lung adenocarcinoma tissues and paracancerous tissues were detected by quantitative real-time PCR (qRT-PCR), and the relationships between the expression of NFAT5 and clinicopathological features of patients were analyzed. H1975 cells were divided into control group (no treatment), NC group (transfecting siRNA-NC) and si-NFAT5 group (transfecting siRNA-NFAT5) . qRT-PCR was used to detect the expression level of NFAT5 in cell line. MTT and clone formation assay were used to detect cell proliferation. Transwell and scratch test were used to detect cell invasion and migration ability. Flow cytometry was used to detect cell apoptosis. The expressions of mitogen-activated protein kinase (MAPK) signaling pathway related proteins were detected by Western blotting.Results:The expression level of NFAT5 mRNA in lung adenocarcinoma (3.22±0.20) was significantly higher than that in paracancerous tissues (1.00±0.12), and there was a statistically significant difference ( t=75.662, P<0.001). The expression level of NFAT5 in lung adenocarcinoma tissue was associated with TNM stage ( χ2=10.357, P=0.001) and lymph node metastasis ( χ2=18.268, P<0.001). The expression levels of NFAT5 in the control group, NC group and si-NFAT5 group were 1.00±0.06, 1.01±0.05 and 0.31±0.06, and there was a statistically significant difference ( F=140.498, P<0.001). The absorbance ( A) values in the control group, NC group and si-NFAT5 group were 0.70±0.01, 0.55±0.01 and 0.35±0.01 at 24 h after transfection, 0.92±0.03, 0.87±0.06 and 0.57±0.06 at 48 h after transfection, 1.05±0.01, 0.90±0.01 and 0.66±0.01 at 72 h after transfection, and there were statistically significant differences ( F=9.815, P=0.013; F=45.977, P<0.001; F=129.494, P<0.001). Further pairwise comparison showed that the proliferation abilities of the si-NFAT5 group at 24, 48 and 72 h were significantly lower than those of the control group and NC group (all P<0.001). The cell clone numbers in the three groups were 452.33±31.50, 421.00±17.35 and 129.00±17.35 respectively, with a statistically significant difference ( F=128.200, P<0.001). The cell clone number in the si-NFAT5 group was significantly lower than that in the control group and NC group (both P<0.001). The invasion numbers of cells in the three groups were 262.67±28.02, 278.00±27.50 and 46.00±12.00 respectively, and there was a statistically significant difference ( F=89.896, P<0.001). The cell invasive ability in the si-NFAT5 group was significantly lower than that in the control group and NC group (both P<0.001). The relative scratch widths in the three groups were 0.28±0.04, 0.32±0.04 and 0.54±0.04 respectively, and there was a statistically significant difference ( F=42.889, P<0.001). The relative scratch width in the si-NFAT5 group was significantly increased than that in the control group and NC group (both P<0.001). The apoptosis rates in the three groups were (3.38±0.56)%, (3.14±0.62)% and (13.82±0.75)% respectively, and there was a statistically significant difference ( F=264.705, P<0.001). The apoptosis rate in the si-NFAT5 group was significantly higher than that in the control group and NC group (both P<0.001). The differences of protein expressions of NFAT5, p-P38/P38, p-ERK1/2/ERK1/2, p-JNK/JNK among the three groups were statistically significant ( F=91.245, P<0.001; F=132.896, P<0.001; F=243.332, P<0.001; F=118.358, P<0.001). The protein expressions of NFAT5, p-P38/P38, p-ERK1/2/ERK1/2, p-JNK/JNK in the si-NFAT5 group were all significantly lower than those in the control group and NC group, and there were statistically significant differences (all P<0.001). Conclusion:The expression of NFAT5 is increased in lung adenocarcinoma tissues and cells. Inhibition of NFAT5 can inhibit proliferation, invasion and migration of lung adenocarcinoma H1975 cells, and promote apoptosis of H1975 cells. The mechanism may be related to the inhibition of MAPK signal pathway by NFAT5.
