[This corrects the article DOI: 10.1016/j.apsb.2021.07.004.].

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.

The oxytocin receptor (OXTR) has garnered increasing attention for its role in regulating both mature behaviors and brain development. It has been established that OXTR mediates a range of effects that are region-specific or period-specific. However, the current studies of OXTR expression patterns in mice only provide limited help due to limitations in resolution. Therefore, our objective was to generate a comprehensive, high-resolution spatiotemporal expression map of Oxtr mRNA across the entire developing mouse brain. We applied RNAscope in situ hybridization to investigate the spatiotemporal expression pattern of Oxtr in the brains of male mice at six distinct postnatal developmental stages (P7, P14, P21, P28, P42, P56). We provide detailed descriptions of Oxtr expression patterns in key brain regions, including the cortex, basal forebrain, hippocampus, and amygdaloid complex, with a focus on the precise localization of Oxtr⁺ cells and the variance of expression between different neurons. Furthermore, we identified some neuronal populations with high Oxtr expression levels that have been little studied, including glutamatergic neurons in the ventral dentate gyrus, Vgat⁺Oxtr⁺ cells in the basal forebrain, and GABAergic neurons in layers 4/5 of the cortex. Our study provides a novel perspective for understanding the distribution of Oxtr and encourages further investigations into its functions.
Animals ; Receptors, Oxytocin/metabolism* ; Male ; Brain/growth & development* ; Mice ; Mice, Inbred C57BL ; Neurons/metabolism* ; Single-Cell Analysis ; Gene Expression Regulation, Developmental ; RNA, Messenger/metabolism* ; Animals, Newborn

ObjectiveTo understand the prevalence of tobacco use among residents aged 15 years old and above in Jiading District of Shanghai, and to provide a scientific basis for formulating effective regional tobacco control policies. MethodsThe Probability Proportional to Size (PPS) sampling method was employed to select one neighborhood committee (village) from each of Jiading District’s 11 subdistricts as survey monitoring sites. From the household registry of each selected neighborhood committee (village), 50 residential households were randomly sampled, resulting in a total of 550 households surveyed. Within each selected household, one permanent resident aged 15 years old or above was randomly chosen to complete the questionnaire. The content covered general information, exposure to secondhand smoke, awareness of tobacco related health hazards, etc. Statistical analyses were performed using SPSS 27.0 software. ResultsA total of 550 questionnaires were distributed, with 549 valid responses collected, and the effective response rate was 99.82%. The survey findings revealed that in 2023, the current smoking rate among individuals aged 15 years old and above in Jiading District of Shanghai was 18.76%, with males accounting for 38.93% and females accounting for 2.62%. Male gender was identified as a relative factor for smoking (OR=34.108, 95%CI: 14.440‒80.722), whereas higher education attainment emerged as a protective factor against smoking (OR=0.388, 95%CI: 0.184‒0.820). Among non-smokers aged 15 years old and above in Jiading District, the secondhand smoke exposure rate was 46.86%, with statistically significant differences observed across different age groups and occupations (P<0.001). Restaurants exhibited the highest secondhand smoke exposure rate of 42.14%, followed by households bearing (36.79%). The overall awareness rate among individuals aged 15 years old and above in Jiading District regarding four smoking-related diseases, namely stroke, heart disease, lung cancer, and impotence, was 48.45%, while the awareness rate for three secondhand smoke-induced diseases, namely adult heart disease, pediatric pulmonary disease, and adult lung cancer, was 64.29%. ConclusionThere is still room for reduction in the prevalence of tobacco use among individuals aged 15 yeas old and above in Jiading District. The exposure to secondhand smoke is severe, and residents have low awareness of the harm of tobacco. Tobacco control law enforcement should be strengthened, smoke-free-home health education should be included in tobacco control efforts, and targeted health education should be carried out.

African swine fever(ASF),caused by the African swine fever virus(ASFV),is a highly contagious infectious disease of pigs.This disease has been spread rapidly in China since 2018,po-sing a huge threat to China's pig farming industry.To rapid detect the ASFV,a loop-mediated iso-thermal amplification(LAMP)combined with the disposable nucleic acid visualization test strip was established for visual detection of the nucleic acid of ASFV B646L gene.The method was easy to operate without special instruments and equipment,while it effectively avoided the disadvantage of false positives caused by aerosol contamination.The method was able to detect 1.16 copies/μL of the recombinant plasmid in 50 min at 65 ℃.In addition,the method was specific with no cross-re-action with classical swine fever virus,porcine reproductive and respiratory syndrome virus,por-cine parvovirus,transmissible gastroenteritis virus.The results in this study provides a rapid,con-venient,sensitive and reliable method for early diagnosis and screening for ASFV suspected infec-tion cases.

Objective:To summarize the clinical and electrophysiological characteristics of epilepsy patients with fixation-off sensitivity (FOS).Methods:Using "fixation-off sensitivity" and "epilepsy" as search terms, data were retrieved from the Electroencephalogram Monitoring Center Database of Xijing Hospital, Air Force Military Medical University. Information was collected on epilepsy patients with FOS who were seen at the Xijing Hospital Electroencephalogram Monitoring Center from March 2019 to May 2023. A retrospective analysis of video electroencephalograms and clinical information was conducted, along with follow-up. Single factor analysis and multi-factor Logistic regression analysis were used to analyze the risk factors affecting the prognosis of the patients.Results:A total of 78 patients met the inclusion criteria, including 43 females and 35 males; the age at first epilepsy onset was 12.00 (8.00, 15.25) years. Among these 78 patients, 46 were diagnosed with genetic generalized epilepsy, 11 with self-limited focal epilepy, 9 with familial cortical myoclonic tremor with epilepsy, 7 with developmental and epileptic encephalopathy, 3 with symptomatic epilepsy, and 2 with progressive myoclonic epilepsy. The fixation-off induction trial most commonly triggered seizures in epilepsy with eyelid myoclonia (EEM) patients, with eyelid myoclonia being the most common type of seizure. Twenty-five epilepsy patients with FOS showed a positive photoparoxysmal response, of whom 6 experienced photo-convulsive response. Sixty-eight patients completed follow-up with comprehensive clinical data. At the last follow-up, 45 patients had been free from tonic-clonic seizures for at least one year. A history of febrile seizures ( OR=20.559, 95% CI 2.179-193.997, P=0.008) and cognitive decline ( OR=3.752, 95% CI 1.118-12.588, P=0.032) were identified as risk factors for poor prognosis in epilepsy patients with FOS. The age of first epilepsy onset, the number of anti-seizure medications, and the intermittent photo stimulation trial results had no correlation with prognosis. Conclusions:FOS is more common in female epilepsy patients and can be observed in both generalized and focal epilepsy syndromes. EEM patients are prone to seizures during fixation-off induction trial, and the most common type of seizures is eyelid myoclonus seizure. Patients with epilepsy with FOS who have a history of febrile seizures and cognitive impairment tend to have poor prognosis.

Objective To construct a model for predicting the benign and malignant risk of the patients with gastric diseases using con-ventional laboratory indicators such as tumor markers,blood routine,and coagulation indicators,and validate its predictive value.Methods The medical records of patients with gastric diseases who visited the First Affiliated Hospital of Guangzhou Medical Univer-sity from January 2018 to January 2023 were analyzed retrospectively.According to the pathological results,the patients were divided into the gastric cancer(GC)group(n=134)and chronic non-atrophic gastritis(CNAG)group(n=298).Their routine test data such as serum and whole blood tests were collected.The statistical analysis was conducted using the R 4.2.3 software,and a model for pre-dicting the risk of GC was constructed and validated.Results A model for predicting the risk of GC was constructed successfully using the Logistic regression analysis,which included D-dimer,carcinoembryonic antigen(CEA),carbohydrate antigen 72-4(CA72-4)and hemoglobin(Hb).A visual nomogram was plotted as the final prediction model.The areas under the receiver operating characteristic(ROC)curve(AUCROC)of the model in the training and testing sets were 0.809(95%CI:0.754-0.864)and 0.808(95%CI:0.724-0.892),respectively.The sensitivity and specificity of the model were 58.5%and 93.3%,respectively,indicating that it had good pre-dictive ability.Conclusion The model for predicting the malignant risk of patients with gastric diseases constructed using routine tes-ting indicators has good accuracy and can effectively predict the risk of gastric disease transforming into gastric cancer.It helps to find early gastric cancer patients in clinical practice and take targeted prevention and intervention measures.

Objective:To investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics (PS-NPs) on lipid metabolism in mice liver.Methods:An animal experimental model was designed, which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed. After exposure 7 d, serum was collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and air flow assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis were used to analyze the mRNA levels of fatty acid esterification related genes ( Dgat1 and Dgat2) and lipid transport related genes ( ApoB, Cd36, ApoE and Mttp) and metabolites′ spatial changes in liver tissue. In vivo imaging system (IVIS) and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs. t-test or one-way ANOVA was used to explore the difference between groups. Results:The serum ALT levels were (83.97±4.58), (91.17±13.69) and (142.43±6.09) U/L in the control group, 1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively ( F=37.281, P<0.05). The relative mRNA levels of Dgat1, Dgat2, ApoB, Cd36 and ApoE were (1.49±0.63, 2.53±0.32, 2.45±0.54), (1.07±0.38, 1.86±0.83, 2.23±0.73), (1.01±0.13, 1.58±0.43, 2.03±0.52), (1.01±0.14, 1.55±0.37, 1.52±0.51), (1.01±0.17, 2.11±0.27, 2.39±0.93) in these three groups respectively. The differences were statistically significant ( F=11.54, 6.95, 14.90, 5.98 and 14.68, P<0.05). AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine ( t=4.12 and 3.35, P<0.05), which were associated with lipid beta oxidation. The content of triglycerides (TG) (m/z 921.726 4, t=8.69, P<0.05; m/z 919.711 4, t=3.20, P<0.05), phosphatidylic acid (PA) (m/z 895.712 3, t=3.60, P<0.05; m/z 821.526 6, t=3.36, P<0.05), lysophosphatidylcholine (LysoPC) (m/z 560.310 6, t=3.35, P<0.05; m/z 582.295 3, t=6.28, P<0.05), phosphatidylcholine (PC) (m/z 778.533 9, t=3.53, P<0.05; m/z 804.549 6, t=3.60, P<0.05; m/z 820.523 1, t=3.37, P<0.05), phosphatidylethanolamine (PE) (m/z 772.523 3, t=3.08, P<0.05) showed a significant increase in the PS-NPs exposure group. In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Conclusion:Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.

Objective To study the accuracy and safety of oral mucosal exfoliated cell specimens used in the bedside rapid detection of MTHFR C677T genotype by using the fluorescent probe method.Methods The outpatients and inpatients with hypertension visited and admitted in the department of cardiovascular medicine of this hospital from January 2019 to September 2020 were selected.The plasma homocysteine (Hcy) level in all patients was detected in the laboratory,a total of 482 hypertensive patients with Hcy≥10 μmol/L were se-lected,and the oral mucosal cells and whole blood sample were collected in all patients,and the genotypes of the above specimens were detected by the oral mucosal exfoliative cell fluorescent probe method and whole blood sample contrast reagents.If the two test results were inconsistent,the "gold standard" Sanger sequen-cing method was used to detect the whole blood sample for the final determination of MTHFR C677T geno-type.The coincidence rate was compared between the two detection methods,and the probability of adverse e-vents during the samples collection was observed and recorded.The accuracy and safety of fluorescence probe method for detecting MTHFR C677T genotype in the patients with oral mucosa exfoliation was evaluated.Re-sults The oral mucosal exfoliated cell samples and whole blood samples from 482 hypertensive patients were successfully collected,and no obvious adverse reactions occurred during the sampling process.The incidence rate of total mutation of MTHFR C677T gene detected by the fluorescence probe method and contrast reagent all were 73.23％ (353/482),the coincidence rate of homozygous wild type (CC type) in MTHFR C677T gene detected by the two methods was 100.00％ (95％CI:97.11-100.00),which of heterozygous mutant type (CT type) was 99.14％ (95％CI:96.91-99.76),which of homozygous mutant type (TT type) was 99.17％(95％CI:95.47-99.85),the total coincident rate of MTHFR C677T genotype was 99.38％ (95％CI:98.19-99.79)and the detection results consistency Kappa value was 0.9902.Conclusion The detection of MTHFR C677T gene mutation in oral mucosal exfoliated cells by fluorescent probe method is simple with less invasion,moreover which is rapid,safe and accurate.

Objective:To investigate the effect and potential mechanism of exposure to 20 nm polystyrene nanoplastics (PS-NPs) on lipid metabolism in mice liver.Methods:An animal experimental model was designed, which was completed from September 2022 to July 2023 on the exposure omics platform of the School of Public Health at Capital Medical University and the Key Laboratory of Environment and Population Health at the Chinese Center for Disease Control and Prevention.1 mg/kg and 10 mg/kg PS-NPs tail vein mice exposure models were constructed. After exposure 7 d, serum was collected to measure the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) and air flow assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) analysis were used to analyze the mRNA levels of fatty acid esterification related genes ( Dgat1 and Dgat2) and lipid transport related genes ( ApoB, Cd36, ApoE and Mttp) and metabolites′ spatial changes in liver tissue. In vivo imaging system (IVIS) and tissue shake sections were employed to observe the fluorescence biological distribution of PS-NPs. t-test or one-way ANOVA was used to explore the difference between groups. Results:The serum ALT levels were (83.97±4.58), (91.17±13.69) and (142.43±6.09) U/L in the control group, 1 mg/kg PS-NPs exposure group and 10 mg/kg PS-NPs exposure group respectively ( F=37.281, P<0.05). The relative mRNA levels of Dgat1, Dgat2, ApoB, Cd36 and ApoE were (1.49±0.63, 2.53±0.32, 2.45±0.54), (1.07±0.38, 1.86±0.83, 2.23±0.73), (1.01±0.13, 1.58±0.43, 2.03±0.52), (1.01±0.14, 1.55±0.37, 1.52±0.51), (1.01±0.17, 2.11±0.27, 2.39±0.93) in these three groups respectively. The differences were statistically significant ( F=11.54, 6.95, 14.90, 5.98 and 14.68, P<0.05). AFADESI-MSI analysis found that PS-NPs exposure led to a significant decrease in the levels of glutarylcarnitine and O-Linoleoylcarnitine ( t=4.12 and 3.35, P<0.05), which were associated with lipid beta oxidation. The content of triglycerides (TG) (m/z 921.726 4, t=8.69, P<0.05; m/z 919.711 4, t=3.20, P<0.05), phosphatidylic acid (PA) (m/z 895.712 3, t=3.60, P<0.05; m/z 821.526 6, t=3.36, P<0.05), lysophosphatidylcholine (LysoPC) (m/z 560.310 6, t=3.35, P<0.05; m/z 582.295 3, t=6.28, P<0.05), phosphatidylcholine (PC) (m/z 778.533 9, t=3.53, P<0.05; m/z 804.549 6, t=3.60, P<0.05; m/z 820.523 1, t=3.37, P<0.05), phosphatidylethanolamine (PE) (m/z 772.523 3, t=3.08, P<0.05) showed a significant increase in the PS-NPs exposure group. In vivo and in vitro imaging and in situ cell localization revealed that PS-NPs were mainly enriched in hepatic stellate cells and hepatic Kupffer cells in liver tissue. Conclusion:Exposure to PS-NPs induces disorder of liver lipid metabolism, which may be related to the accumulation of PS-NPs in hepatic stellate cells and hepatic Kupffer cells, providing basis for searching early biomarkers of PS-NPs exposure and further mechanism research.