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Objectives: The emergence of new SARS-CoV-2 variants has led to the development of Omicron-targeting bivalent mRNA vaccines. It is crucial to understand how bivalent vaccines may improve antibody responses against new variants., Methods: A total of 107 participants, who had three COVID-19 WT mRNA vaccine doses, were recruited, and given either a monovalent (WT) or a bivalent mRNA vaccination (Pfizer/BioNTech Bivalent (WT and BA.4/BA.5) or Moderna Bivalent (WT and BA.1). Blood samples were taken before booster and at 28 days post-booster., Results: We found significantly lower fold change in serum binding IgA responses against BA.1, BA.5 and EG.5.1 spike in the bivalent booster group, compared with the monovalent (WT) booster group, following vaccination. However, this was only observed in individuals with prior infection. The relative fold change in serum binding IgA response was more skewed towards WT over variant (BA.1, BA.5 or EG.5.1) spike in previously infected bivalent-booster-vaccinees, as compared with previously infected monovalent-(WT)-booster-vaccinees., Conclusion: The findings suggest imprinting of antibody responses that is shaped by the first vaccination (WT spike). Previous infection also affects the boosting effect of follow-up vaccination. Studies are needed to understand how to induce a robust and long-lasting IgA immunity for protection against COVID-19 infection., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with a 382-nucleotide deletion (∆382) in the open reading frame 8 (ORF8) region of the genome have been detected in Singapore and other countries. We investigated the effect of this deletion on the clinical features of infection., Methods: We retrospectively identified patients who had been screened for the ∆382 variant and recruited to the PROTECT study-a prospective observational cohort study conducted at seven public hospitals in Singapore. We collected clinical, laboratory, and radiological data from patients' electronic medical records and serial blood and respiratory samples taken during hospitalisation and after discharge. Individuals infected with the ∆382 variant were compared with those infected with wild-type SARS-CoV-2. Exact logistic regression was used to examine the association between the infection groups and the development of hypoxia requiring supplemental oxygen (an indicator of severe COVID-19, the primary endpoint). Follow-up for the study's primary endpoint is completed., Findings: Between Jan 22 and March 21, 2020, 278 patients with PCR-confirmed SARS-CoV-2 infection were screened for the ∆382 deletion and 131 were enrolled onto the study, of whom 92 (70%) were infected with the wild-type virus, ten (8%) had a mix of wild-type and ∆382-variant viruses, and 29 (22%) had only the ∆382 variant. Development of hypoxia requiring supplemental oxygen was less frequent in the ∆382 variant group (0 [0%] of 29 patients) than in the wild-type only group (26 [28%] of 92; absolute difference 28% [95% CI 14-28]). After adjusting for age and presence of comorbidities, infection with the ∆382 variant only was associated with lower odds of developing hypoxia requiring supplemental oxygen (adjusted odds ratio 0·07 [95% CI 0·00-0·48]) compared with infection with wild-type virus only., Interpretation: The ∆382 variant of SARS-CoV-2 seems to be associated with a milder infection. The observed clinical effects of deletions in ORF8 could have implications for the development of treatments and vaccines., Funding: National Medical Research Council Singapore., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Gap junctional intercellular communication (GJIC) is important for maintaining the pluripotency of mouse embryonic stem cells (mESC). However, human ESC (hESC) have a high level of connexin (Cx) molecules with unknown function. In this study, we found that the major Cx molecule, Cx43, was highly expressed in undifferentiated hESC. It was down-regulated upon spontaneously differentiation by embryoid body formation and induced differentiation along ectoderm, mesoderm and extraembryonic lineages, but up-regulated along endoderm differentiation. The knockdown of Cx43 and GJIC had no effect on the maintenance of hESC, as demonstrated by no morphological changes and similar expression levels of pluripotent markers (OCT4, NANOG, SSEA-3 and SSEA-4) and early differentiation markers (KRT8 and KRT18). Meanwhile, Cx43 knock down had no effect on endodermal markers (SOX17, FOXA2 and CXCR4) expression when hESC were differentiating into definitive endoderm lineage. On the contrary, it led to lower levels of mesodermal markers (CD56, CD34 and PDGFR-α) when cells were undergoing mesoderm differentiation. When compared to control, Cx43 knockdown led to higher attachment rate, HCG secretion and cell invasion of the hESC derived trophoblastic cells. Cx43 knockdown also resulted in up-regulated expressions of placental hormone (β-hCG) and implantation related genes (LIFR, CDH5, LEP, PGF, TGFBR2). Our study suggested that Cx43 and GJIC had no effect on the undifferentiated growth of hESC but affected specific lineage differentiation., (Copyright © 2018 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.)

Introduction: High-intensity focused ultrasound (HIFU) produces collapsing cavitation bubbles. This study aims to investigate the efficacy of collapsing cavitation bubbles to deliver antibacterial nanoparticles into dentinal tubules to improve root canal disinfection., Methods: In stage 1, experiments were performed to characterize the efficacy of collapsing cavitation bubbles to deliver the miniature plaster beads into a tubular channel model. In stage 2, experiments were conducted on root-dentin blocks to test the efficacy of HIFU applied at 27 kHz for 2 minutes to deliver antibacterial nanoparticles into dentinal tubules. After the stage 2 experiment, the samples were sectioned and analyzed using field-emission scanning electron microscopy and energy dispersive X-ray analysis., Results: The stage 1 experiment showed that collapsing cavitation bubbles using HIFU delivered plaster beads along the entire length of the tubular channel. It was observed from the stage 2 experiments that the diffusion of fluids alone was not able to deliver antibacterial nanoparticles into dentinal tubules. The collapsing cavitation bubbles treatment using HIFU resulted in significant penetration up to 1,000 microm of antibacterial nanoparticles into the dentinal tubules. The statistical analysis showed a highly significant difference in the depth of penetration of antibacterial nanoparticles between the two groups (<0.005)., Conclusion: The cavitation bubbles produced using HIFU can be used as a potential method to deliver antibacterial nanoparticles into the dentinal tubules to enhance root canal disinfection.