COVID-19: Attacks Immune Cells and Interferences With Antigen Presentation Through MHC-Like Decoy System.

The high mortality of coronavirus disease 2019 is related to poor antigen presentation and lymphopenia. Cytomegalovirus and the herpes family encode a series of major histocompatibility complex (MHC)-like molecules required for targeted immune responses to achieve immune escape. In this present study, domain search results showed that many proteins of the severe acute respiratory syndrome coronavirus 2 virus had MHC-like domains, which were similar to decoys for the human immune system. MHC-like structures could bind to MHC receptors of immune cells (such as CD4 + T-cell, CD8 + T-cell, and natural killer-cell), interfering with antigen presentation. Then the oxygen free radicals generated by E protein destroyed immune cells after MHC-like of S protein could bind to them. Mutations in the MHC-like region of the viral proteins such as S promoted weaker immune resistance and more robust transmission. S 127-194 were the primary reason for the robust transmission of delta variants. The S 144-162 regulated the formation of S trimer. The mutations of RdRP: G671S and N: D63G of delta variant caused high viral load. S 62-80 of alpha, beta, lambda variants were the important factor for fast-spreading. S 616-676 and 1014-1114 were causes of high mortality for gamma variants infections. These sites were in the MHC-like structure regions.

Current Status and Correlation of Physical Activity and Tendency to Problematic Mobile Phone Use in College Students.

OBJECTIVE: To explore the effect of problematic mobile phone use on college students' physical activity and their relationships. METHODS: A cross-sectional study was conducted among 3980 college students from three universities in Jiangsu province by random cluster sampling. The International Physical Activity Questionnaire Short (IPAQ-SF) measured college students' physical activity. The Mobile Phone Addiction Tendency Scale for College Students (MPATS) measured problematic mobile phone use tendencies. College students' physical activity was measured by the International Physical Activity Questionnaire Short (IPAQ-SF), and the Mobile Phone Addiction Tendency Scale measured their mobile phone addiction tendency for College Students (MPATS). RESULTS: (1) The proportions of the low-, medium-, and high-intensity physical activity were 83.5%, 10.7%, and 5.8%, respectively, with gender differences; The score of problematic mobile phone use tendency was 38.725 ± 15.139. (2) There were significant differences in problematic mobile phone use tendency among college students with different physical activity intensity (F = 11.839, p < 0.001, η2 = 0.007). (3) The level of physical activity was significantly correlated with the tendency of problematic mobile phone use (r = -0.173, p < 0.001). (4) Physical activity of college students could significantly predict the tendency of problematic mobile phone use (F (3,3605) = 11.296, p < 0.001). CONCLUSIONS: The physical activity of college students was mainly moderate to low intensity, while the tendency of problematic mobile phone use was high. College students' physical activity level was one of the important constraints of problematic mobile phone use tendency.

Predicting the structure of unexplored novel fentanyl analogues by deep learning model.

Fentanyl and its analogues are psychoactive substances and the concern of fentanyl abuse has been existed in decades. Because the structure of fentanyl is easy to be modified, criminals may synthesize new fentanyl analogues to avoid supervision. The drug supervision is based on the structure matching to the database and too few kinds of fentanyl analogues are included in the database, so it is necessary to find out more potential fentanyl analogues and expand the sample space of fentanyl analogues. In this study, we introduced two deep generative models (SeqGAN and MolGPT) to generate potential fentanyl analogues, and a total of 11 041 valid molecules were obtained. The results showed that not only can we generate molecules with similar property distribution of original data, but the generated molecules also contain potential fentanyl analogues that are not pretty similar to any of original data. Ten molecules based on the rules of fentanyl analogues were selected for NMR, MS and IR validation. The results indicated that these molecules are all unreported fentanyl analogues. Furthermore, this study is the first to apply the deep learning to the generation of fentanyl analogues, greatly expands the exploring space of fentanyl analogues and provides help for the supervision of fentanyl.

Expression and Clinical Significance of ERCC1 and XPF in Human Hepatocellular Carcinoma.

OBJECTIVE: To investigate the correlation between the ERCC1 and XPF expression and the clinicopathological parameters of hepatocellular carcinoma (HCC) patients through assessment of the expression of the DNA repair genes ERCC1 and XPF. METHODS: ERCC1 and XPF mRNA expression in HCC (n= 177) and adjacent para-cancer tissues (n=21) were assessed by RT-PCR. The correlation between ERCC1 and XPF expression, clinicopathological features and HCC prognosis were compared. RESULTS: ERCC1 expression in liver cancer tissues was significantly lower than that of adjacent tissues (9.5% (2/21) vs 38.1% (8/21); P<0.05). The positive expression rates of XPF in liver cancer tissues was lower than that of adjacent tissues (14.3% (3/21) vs 71.4% (15/21); P<0.05). ERCC1 and XPF expression were associated with hepatic capsular invasion and microvascular invasion. HCC patients with hepatic capsular invasion and microvascular tumor embolus formation had significantly lower levels of ERCC1 and XPF mRNA than those without hepatic capsular invasion and microvascular tumor embolus formation (P<0.05). In addition, ERCC1 expression was associated with TNM staging of HCC. The expression of ERCC1 mRNA in patients with stage II and III HCC were lower than that of patients with stage I HCC (P<0.05). The low levels of ERCC1 and XPF mRNA significantly correlated with relapse-free survival times (RFS) in HCC patients. The median RFS of the low ERCC1 expression group and low XPF expression group were shorter than those of the high expression group (15.0 months vs 32.0 months, P<0.05) and (19.0 months vs 33.0 months, P<0.05). The decrease in XPF mRNA expression was significantly associated with the overall survival (OS) of HCC patients. The median OS in the low XPF expression group was shorter than that of the high expression group (46.0 months vs 78.0 months, P<0.05). However, no significant difference in OS between the low ERCC1 expression group and the high ERCC1 expression groups were observed (63.0 months vs 64.0 months, P>0.05). Multivariate analysis showed that tumor size and the extent of differentiation were independent factors affecting the RFS in HCC patients (P<0.05). The extent of differentiation and XPF were independent factors affecting the OS in HCC (P<0.05). CONCLUSION: The expression in ERCC1 and XPF were low in HCC and associated with early relapse after HCC surgery. Low XPF expression may be a potential indicator of a high risk of death.

Clinical efficacy and safety of apatinib in patients with advanced colorectal cancer as the late-line treatment.

There is currently no standard therapeutic regimen available for patients with advanced colorectal cancer in whom the disease continues to progress after 2 or more lines of chemotherapy. The purpose of this study is to investigate the efficacy and safety of apatinib in patients with advanced colorectal cancer for whom at least two lines of prior chemotherapy had failed.Twenty seven patients with advanced colorectal cancer who had failed at least 2 lines chemotherapy were treated with apatinib (500 mg/day). As a comparison control, 26 advanced colorectal cancer patients with comparable clinical baseline characteristics including age, sex, Eastern Cooperative Oncology Group (ECOG) score, pathological type, carcinoembryonic antigen (CEA) level, tumor location, number and location(s) of metastasis, and previous chemotherapies were subject to observation. Survival analyses were performed via the Kaplan-Meier method. The toxicity were evaluated in all patients this study according to the National Cancer Institute Common Toxicity Criteria 4 (NCI CTC version 4.0).A total of 53 well-matched patients with advanced colorectal cancer were retrospectively analyzed. The median follow-up time was 6.0 months (2.0-16.0 months). The median PFS was significantly longer for apatinib group than for observation group (2.0 vs. 1.1 months; HR = 3.88; 95% confidence interval [CI], 1.91-7.88; P < .001). However, there was no significant difference between the 2 groups for median OS (5.0 vs. 4.0 months; HR = 1.03; 95% CI, 0.56-1.90; P = .914). The disease control rate of the apatinib group was significantly better than that of the observation group (70.4% vs 26.9%, P = .002). There was no significant difference in the overall remission rate between the 2 groups (3.7% vs 0%, P = .322). Advanced colorectal cancer patients with 2 or fewer metastatic sites experienced longer PFS than those with more than 2 sites. High ECOG scores, cancer localization to the right side of colon and lymph node metastasis were associated with increased risk of death and all remained independent factors affecting OS. The most common grade 3/4 treatment-related adverse events were hypertension and hand-foot skin syndrome.Apatinib treatment for patients with advanced colorectal cancer who had failed chemotherapy achieved better disease control and prolonged PFS relative to untreated controls. The toxicity was manageable.