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Background Low-frequency intrahost single-nucleotide variants of SARS-CoV-2 have been recognized as predictive indicators of selection. However, the impact of vaccination on the intrahost evolution of SARS-CoV-2 remains uncertain at present. Methods We investigated the genetic variation of SARS-CoV-2 in individuals who were unvaccinated, partially vaccinated, or fully vaccinated during Shanghai's Omicron BA.2.2 wave. We substantiated the connection between particular amino acid substitutions and immune-mediated selection through a pseudovirus neutralization assay or by cross-verification with the human leukocyte antigen–associated T-cell epitopes. Results In contrast to those with immunologic naivety or partial vaccination, participants who were fully vaccinated had intrahost variant spectra characterized by reduced diversity. Nevertheless, the distribution of mutations in the fully vaccinated group was enriched in the spike protein. The distribution of intrahost single-nucleotide variants in individuals who were immunocompetent did not demonstrate notable signs of positive selection, in contrast to the observed adaptation in 2 participants who were immunocompromised who had an extended period of viral shedding. Conclusions In SARS-CoV-2 infections, vaccine-induced immunity was associated with decreased diversity of within-host variant spectra, with milder inflammatory pathophysiology. The enrichment of mutations in the spike protein gene indicates selection pressure exerted by vaccination on the evolution of SARS-CoV-2. [ABSTRACT FROM AUTHOR]

The easy‐going oxidation of silicon nitride (Si3N4) at high temperature greatly hampers its potential applications. Here, we explored the reaction mechanism between β‐Si3N4 and O2 via density functional theory (DFT) calculation, which discloses that O atoms are preferentially adsorbed on the top of Si atoms and N2 starts to be generated as the dominant gas product at 2/3 monolayer (ML) O coverage. The vacancies formed by N2 removal attract the O adatoms to transfer to the site of the N vacancy, which accelerates the adsorption of O and the formation of Si–O bonds toward the growth of SiO2 product. The surface oxidation of β‐Si3N4 (0001) has been clarified by the unambiguous evolution of [SiN4‐nOn] (n = 0‐4) tetrahedrons going through from [SiN4] tetrahedron to [SiO4] tetrahedron, providing a deep insight into intrinsic oxidation process of Si3N4 ceramic. [ABSTRACT FROM AUTHOR]

Data on reinfection in large Asian populations are limited. In this study, we aimed to evaluate the reinfection rate, disease severity, and time interval between the infections in the symptomatic and asymptomatic populations which are firstl infected with BA.2 Omicron Variant. We retrospectively included adult patients with COVID-19 discharged from four designated hospitals between 27 April 2021 and 30 November 2022, who were interviewed via telephone from 29 January to 1 March 2023. Univariable and multivariable analyses were used to explore risk factors associated with reinfection. A total of 16,558 patients were followed up, during the telephone survey of an average of 310.0 days, 1610 (9.72%) participants self-reported reinfection. The mean time range of reinfection was 257.9 days. The risks for reinfection were analysed using multivariable logistic regression. Patients with severe first infection were at higher risk for reinfection (aORs, 2.50; P  < 0.001). The male (aORs,0.82; P  < 0.001), the elderly (aORs, 0.44; P  < 0.001), and patients with full vaccination (aORs, 0.67; P  < 0.001) or booster (aORs, 0.63; P  < 0.001) had the lower risk of reinfection. Patients over 60 years of age (aORs,9.02; P  = 0.006) and those with ≥2 comorbidities (aORs,11.51; P  = 0.016). were at higher risk for severe reinfection. The number of clinical manifestations of reinfection increases in people with severe first infection (aORs, 2.82; P  = 0.023). The overall reinfection rate was 9.72%, and the reinfection rate of Omicron-to-Omicron subvariants was 9.50% at one year. The severity of Omicron-Omicron reinfection decreased. Data from our clinical study may provide clinical evidence and bolster response preparedness for future COVID-19 reinfection waves.

Household contacts (HHCs) of patients with active tuberculosis (ATB) are at higher risk of Mycobacterium tuberculosis ( M. tuberculosis ) infection. However, the immune factors responsible for different defense responses in HHCs are unknown. Hence, we aimed to evaluate transcriptome signatures in human peripheral blood mononuclear cells (PBMCs) of HHCs to aid risk stratification. We recruited 112 HHCs of ATB patients and followed them for 6 years. Among the HHCs, only 2 developed ATB, while the remaining HHCs were classified into three groups: (1) HHC-1 group ( n  = 23): HHCs with consistently positive T-SPOT.TB test, negative chest radiograph, and no clinical symptoms or evidence of ATB during the 6-year follow-up period; (2) HHC-2 group ( n  = 15): HHCs with an initial positive T-SPOT result that later became negative without evidence of ATB; (3) HHC-3 group ( n  = 14): HHCs with a consistently negative T-SPOT.TB test and no clinical or radiological evidence of ATB. HHC-2 and HHC-3 were combined as HHC-23 group for analysis. RNA sequencing (RNA-seq) in PBMCs, with and without purified protein derivative (PPD) stimulation, identified significant differences in gene signatures between HHC-1 and HHC-23. Gene ontology analysis revealed functions related to bacterial pathogens, leukocyte chemotaxis, and inflammatory and cytokine responses. Modules associated with clinical features in the HHC-23 group were linked to the IL-17 signaling pathway, ferroptosis, complement and coagulation cascades, and the TNF signaling pathway. Validation using real-time PCR confirmed key genes like ATG-7, CXCL-3, and TNFRSF1B associated with infection outcomes in HHCs. Our research enhances understanding of disease mechanisms in HHCs. HHCs with persistent latent tuberculosis infection (HHC-1) showed significantly different gene expression compared to HHCs with no M. tuberculosis infection (HHC-23). These findings can help identify HHCs at risk of developing ATB and guide targeted public health interventions.

Introduction: Baloxavir Marboxil is a per oral small-molecule antiviral for the treatment of influenza. While the efficacy and safety of Baloxavir Marboxil have been thoroughly characterized across an extensive clinical trial, studies on the effectiveness of Baloxavir Marboxil in a real-world setting are still scarce., Methods: We conducted an ambispective, observational, multi-center study that enrolled uncomplicated in-fluenza outpatients treated with Baloxavir Marboxil or Oseltamivir in East China. The primary endpoint was time from treatment to alleviation of all influenza symptoms (TTAIS). The secondary endpoints included time from treatment to alleviation of fever (TTAF) and household transmission during the duration of influenza., Results: A total of 509 patients were enrolled. The median TTAIS in the Baloxavir Marboxil group and the Oseltamivir group was 28.0  h (IQR, 20.0 to 50.0) and 48.0  h (IQR, 30.0 to 67.0), respectively. The median TTAF in the Baloxavir Marboxil group and the Oseltamivir group was 18  h (IQR, 10.0-24.0) and 30.0  h (IQR, 19.0-48.0). In the COX multivariable analysis, Baloxavir Marboxil reduced the duration of influenza symptoms (HR  =  1.36 [95%CI:1.12-1.64], p =  0.002) and the duration of fever (HR  =  1.93 [95%CI:1.48-2.52], p  < 0.001) compared to Oseltamivir. When antiviral drugs were given within 12-48  h after symptom onset, the Baloxavir Marboxil group had a significantly shorter TTAIS compared to the Oseltamivir group. There was no significant difference in the rate of adverse events between the two group ( p  = 0.555)., Discussion: Baloxavir Marboxil was superior to Oseltamivir in alleviating influenza symptoms in outpatients with uncomplicated influenza. Our findings suggested that compared to Oseltamivir, Baloxavir Marboxil might be more appropriate for patients with influenza 12- 48 h after symptom onset., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Cai, Wang, Ye, Lu, Tan, Li, Lin, Qian, Lu, Wan, Wang, Ai, Pu, Qu and Wang.)