The continuous emergence of SARS-CoV-2 variants as well as other potential future coronavirus has challenged the effectiveness of current COVID-19 vaccines. Therefore, there remains a need for alternative antivirals that target processes less susceptible to mutations, such as the formation of six-helix bundle (6-HB) during the viral fusion step of host cell entry. In this study, a novel high-throughput screening (HTS) assay employing a yeast-two-hybrid (Y2H) system was established to identify inhibitors of HR1/HR2 interaction. The compound IMB-9C, which achieved single-digit micromolar inhibition of SARS-CoV-2 and its Omicron variants with low cytotoxicity, was selected. IMB-9C effectively blocks the HR1/HR2 interaction in vitro and inhibits SARS-CoV-2-S-mediated cell-cell fusion. It binds to both HR1 and HR2 through non-covalent interaction and influences the secondary structure of HR1/HR2 complex. In addition, virtual docking and site-mutagenesis results suggest that amino acid residues A930, I931, K933, T941, and L945 are critical for IMB-9C binding to HR1. Collectively, in this study, we have developed a novel screening method for HR1/HR2 interaction inhibitors and identified IMB-9C as a potential antiviral small molecule against COVID-19 and its variants.

Objective:To investigate whether repeated tirofiban injections can continuously inhibit platelet aggregation in the arterial duct and affect its closure in neonatal canines.Methods:Four 24-month-old pregnant beagles underwent cesarean sections in two batches (two dogs per batch) 1-2 days before the expected delivery date at the Xuzhou Medical University Animal Experiment Center. The first litter of 21 neonates served as the control group (receiving 10 ml/kg normal saline) and were randomly divided into 1-h ( n=7, injected immediately after birth), 4-h ( n=7, injected at 0 h and 2 h after birth), and 12-h subgroups ( n=7, injected at 0 h, 2 h, 4 h, 6 h, 8 h, and 10 h after birth). The second litter of 18 neonates served as the experimental group (receiving 10 ml/kg tirofiban) with identical subgroup assignments ( n=6 per subgroup). Echocardiography was performed at 1 h, 4 h, and 12 h after birth to measure arterial duct inner diameter, maximum shunt velocity, and left atrial diameter/aortic root diameter (LA/Ao) ratio. Plasma platelet-derived growth factor (PDGF) was detected by enzyme-linked immunosorbent assay, while platelet membrane glycoprotein Ⅱb-Ⅲa in the arterial duct was assessed by Western blot and immunohistochemistry. Data were analyzed using t-tests, one-way ANOVA, Chi square tests, or Fisher's exact test. Results:No significant bleeding tendency occurred in either group. Two control neonates (one each in the 4-h and 12-h subgroups) died. In both control and experimental 1-h subgroups, all arterial ducts remained open, with no significant differences in ductal diameter, shunt velocity, or LA/Ao between groups (all P>0.05). In the 4-h subgroups, all experimental neonates had patent ducts arteriosus, while two controls exhibited closure; the experimental group had larger ductal diameters [(1.05±0.05) vs. (0.55±0.44) mm, t=－2.75, P<0.05)] and higher LA/Ao ratios (1.31±0.09 vs. 1.14±0.03, t=－4.90, P<0.05), but lower maximum shunt velocities [(107.06±17.47) vs. (153.74±12.78) cm/s, t=4.54, P=0.002). In the 12-h subgroups, all the controls had closed arterial ducts, while four of six experimental neonates exhibited closure, though the difference in closure rate was not statistically significant (6/6 vs. 4/6, Fisher's exact test, P=0.455). Plasma PDGF and glycoprotein Ⅱb-Ⅲa levels did not differ between two 1-h subgroups (all P>0.05). However, the 4-h and 12-h experimental subgroups showed lower PDGF levels [(373.5±13.1) vs. (880.3±80.2) pg/ml, t=10.81; (356.7±35.0) vs. (1 111.2±125.3) pg/ml, t=9.74; both P<0.05] and reduced glycoprotein Ⅱb-Ⅲa expression (0.32±0.07 vs. 0.80±0.23, t=3.29; 0.42±0.07 vs. 0.92±0.26, t=3.24; both P<0.05) compared to controls. Conclusion:Repeated tirofiban injections sustainably inhibit platelet aggregation in the arterial duct of neonatal canines and delay ductal closure, suggesting that intraductal platelet aggregation may be one factor influencing this process.

Objective:To investigate whether repeated tirofiban injections can continuously inhibit platelet aggregation in the arterial duct and affect its closure in neonatal canines.Methods:Four 24-month-old pregnant beagles underwent cesarean sections in two batches (two dogs per batch) 1-2 days before the expected delivery date at the Xuzhou Medical University Animal Experiment Center. The first litter of 21 neonates served as the control group (receiving 10 ml/kg normal saline) and were randomly divided into 1-h ( n=7, injected immediately after birth), 4-h ( n=7, injected at 0 h and 2 h after birth), and 12-h subgroups ( n=7, injected at 0 h, 2 h, 4 h, 6 h, 8 h, and 10 h after birth). The second litter of 18 neonates served as the experimental group (receiving 10 ml/kg tirofiban) with identical subgroup assignments ( n=6 per subgroup). Echocardiography was performed at 1 h, 4 h, and 12 h after birth to measure arterial duct inner diameter, maximum shunt velocity, and left atrial diameter/aortic root diameter (LA/Ao) ratio. Plasma platelet-derived growth factor (PDGF) was detected by enzyme-linked immunosorbent assay, while platelet membrane glycoprotein Ⅱb-Ⅲa in the arterial duct was assessed by Western blot and immunohistochemistry. Data were analyzed using t-tests, one-way ANOVA, Chi square tests, or Fisher's exact test. Results:No significant bleeding tendency occurred in either group. Two control neonates (one each in the 4-h and 12-h subgroups) died. In both control and experimental 1-h subgroups, all arterial ducts remained open, with no significant differences in ductal diameter, shunt velocity, or LA/Ao between groups (all P>0.05). In the 4-h subgroups, all experimental neonates had patent ducts arteriosus, while two controls exhibited closure; the experimental group had larger ductal diameters [(1.05±0.05) vs. (0.55±0.44) mm, t=－2.75, P<0.05)] and higher LA/Ao ratios (1.31±0.09 vs. 1.14±0.03, t=－4.90, P<0.05), but lower maximum shunt velocities [(107.06±17.47) vs. (153.74±12.78) cm/s, t=4.54, P=0.002). In the 12-h subgroups, all the controls had closed arterial ducts, while four of six experimental neonates exhibited closure, though the difference in closure rate was not statistically significant (6/6 vs. 4/6, Fisher's exact test, P=0.455). Plasma PDGF and glycoprotein Ⅱb-Ⅲa levels did not differ between two 1-h subgroups (all P>0.05). However, the 4-h and 12-h experimental subgroups showed lower PDGF levels [(373.5±13.1) vs. (880.3±80.2) pg/ml, t=10.81; (356.7±35.0) vs. (1 111.2±125.3) pg/ml, t=9.74; both P<0.05] and reduced glycoprotein Ⅱb-Ⅲa expression (0.32±0.07 vs. 0.80±0.23, t=3.29; 0.42±0.07 vs. 0.92±0.26, t=3.24; both P<0.05) compared to controls. Conclusion:Repeated tirofiban injections sustainably inhibit platelet aggregation in the arterial duct of neonatal canines and delay ductal closure, suggesting that intraductal platelet aggregation may be one factor influencing this process.

Objective: To observe the effect of infiltration resin combined with cold light whitening in the treatment of dental fluorosis. Methods: According to the distance between teeth and the long axis of each tooth, 18 anterior teeth were divided equally and randomly between group A and B. Samples in group A underwent cold light whitening, while samples in group B were treated with infiltration resin combined with cold light whitening. The color was measured before and after the treatment. Then, 6 teeth (the first subgroup) were randomly selected from the 18 anterior teeth after measurement for scanning electron microscopy (SEM) to observe the surface microstructure of the teeth. Then, another 6 teeth (the second subgroup) were selected from the remaining 12 teeth for the measurement of the color level and ΔE after being dyed with tea. Results: After treatment, the color level changed significantly in group A and B (P < 0.05), ΔE in group A and B was 13.75, 14.98. There was no significant difference in the color level change between group B and group A, there was a significant difference in the ΔE between the two groups (t = -3.58, P < 0.05). SEM showed that the enamel surface was intact and that the enamel space was filled in group B. In group A, the enamel surface was reduced and uneven, and the characteristic badminton racquet shape of the enamel was not obvious. The color level was lower in both groups after staining, and these differences were significant (P < 0.05), ΔE in group A and B was 19.69, 18.95. There was no significant difference in the color level (t = 1.00, P > 0.05) and ΔE (t = 0.02, P > 0.05) between two groups. Conclusion Cold light whitening combined with infiltration resin is better for treating dental fluorosis than cold light whitening alone.

Objective To investigate radiation risk perception and nuclear acceptance after the 60Co stuck source incident in June 2009 in Qixian County,Henan Province.Methods From March to April 2010,23 hamlets and 2 schools from 5 towns in Qixian County were selected,while 3 hamlets and 2 schools from 3 towns were used as control in Huixian County,1 35 km away where no any impact of the incident was found.Face-to-face questionnaire survey was conducted among three groups including mass public,elite public(representatives of public opinion,such as physicians,teachers,govemmental officials,administrative personnel,private entrepreneurs),and middie school students(the third grade students in junior middle schools and the first grade students in senior middle schools).Results A total of 1 340 valid questionnaires were collected.The public knowledge levels about radiation and nuclear power were low among all groups in two areas and public knowledge levels in Qixian County were higher than those in Huixian County.In both areas.the knowledge levels of the students were higher tIIan those among the elite public,and that among the general public were the lowest.The knowledge levels of males and those with higher educational levels were higher than those of females and those with lower educational levels.More than 40.0% of the respondents supported the idea to build nuclear power plants in China.but only a small part of them supported to build nuclear power plants in their own areas.The percentages of opponents against local nuclear power plant construction were especially higher among the students and those with higher educational levels.More than 60% of the mass public and elite public believed the explanation of the government.More than 80% of the respondents held negative attitudes towards the performance of the Qixian County Government in dealing with this incident.The student gave the lowest evaluation of the credibility and the specific performance of the local government,whereas the elite public placed themselves between the students and the mass public.The reasons why the local people left their homes to evade risk included rumors(67.2%),lack of radiation knowledge(61.9%),group psychology(59.2%),and failure of the government to inform the truth to the public in time(42.3%).Conclusions The public still fails to know enough about radiation and nuclear power.Although they trust the government,they are dissatisfied with the performance of the local government in dealing with the incident.The negative evaluation of the students is worth concerning.

Seventy-three patients with type 2 diabetes mellitus were divided into atheroselerosis(AS) group and non-AS group according to the intima-media thickness(IMT)of the carotid artery.The plasma visfatin level in AS group was higher than that in non-As group[(44.95±10.14 vs 34.52±9.08)μg/L,P<0.05],and both of them were higher than that of the control [(24.46±7.18)μg/L,both P<0.05 ].The visfatin level Was positively correlated with IMT,waist-to-hip ratio,visceral fat thickness,fasting insulin,and HOMA insulin resistance index.Age,duration of diabetes,HbA_(1C),and visfatin level were the major risk factors for IMT of the carotid artery.