Patients with Coronavirus disease 2019 exhibit low expression of interferon-stimulated genes, contributing to a limited antiviral response. Uncovering the underlying mechanism of innate immune suppression and rescuing the innate antiviral response remain urgent issues in the current pandemic. Here we identified that the dimerization domain of the SARS-CoV-2 nucleocapsid protein (SARS2-NP) is required for SARS2-NP to undergo liquid-liquid phase separation with RNA, which inhibits Lys63-linked poly-ubiquitination and aggregation of MAVS and thereby suppresses the innate antiviral immune response. Mice infected with an RNA virus carrying SARS2-NP exhibited reduced innate immunity, an increased viral load and high morbidity. Notably, we identified SARS2-NP acetylation at Lys375 by host acetyltransferase and reported frequently occurring acetylation-mimicking mutations of Lys375, all of which impaired SARS2-NP liquid-liquid phase separation with RNA. Importantly, a peptide targeting the dimerization domain was screened out to disrupt the SARS2-NP liquid-liquid phase separation and demonstrated to inhibit SARS-CoV-2 replication and rescue innate antiviral immunity both in vitro and in vivo.Inflammatory bowel diseases present with elevated levels of intestinal epithelial cell (IEC) death, which compromises the gut barrier, activating immune cells and triggering more IEC death. The endogenous signals that prevent IEC death and break this vicious cycle, allowing resolution of intestinal inflammation, remain largely unknown. Here we show that prostaglandin E2 signalling via the E-type prostanoid receptor 4 (EP4) on IECs represses epithelial necroptosis and induces resolution of colitis. We found that EP4 expression correlates with an improved IBD outcome and that EP4 activation induces a transcriptional signature consistent with resolution of intestinal inflammation. We further show that dysregulated necroptosis prevents resolution, and EP4 agonism suppresses necroptosis in human and mouse IECs. Mechanistically, EP4 signalling on IECs converges on receptor-interacting protein kinase 1 to suppress tumour necrosis factor-induced activation and membrane translocation of the necroptosis effector mixed-lineage kinase domain-like pseudokinase. In summary, our study indicates that EP4 promotes the resolution of colitis by suppressing IEC necroptosis.Tissue turnover requires activation and lineage commitment of tissue-resident stem cells (SCs). These processes are impacted by ageing, but the mechanisms remain unclear. Here, we addressed the mechanisms of ageing in murine hair follicle SCs (HFSCs) and observed a widespread reduction in chromatin accessibility in aged HFSCs, particularly at key self-renewal and differentiation genes, characterized by bivalent promoters occupied by active and repressive chromatin marks. GI254023X research buy Consistent with this, aged HFSCs showed reduced ability to activate bivalent genes for efficient self-renewal and differentiation. These defects were niche dependent as the transplantation of aged HFSCs into young recipients or synthetic niches restored SC functions. Mechanistically, the aged HFSC niche displayed widespread alterations in extracellular matrix composition and mechanics, resulting in mechanical stress and concomitant transcriptional repression to silence promoters. As a consequence, increasing basement membrane stiffness recapitulated age-related SC changes. These data identify niche mechanics as a central regulator of chromatin state, which, when altered, leads to age-dependent SC exhaustion.Aim To determine if a single pre-operative dose of oral corticosteroids would be effective in reducing pain, trismus and oedema following lower third molar surgical extraction. Secondary outcomes of interest were post-operative complications such as infections.Methods Searching was conducted using Embase, Medline, DOSS, CINAHL and CENTRAL for randomised controlled trials. Four studies which compared pre-operative oral corticosteroids to placebo before lower third molar surgical extractions were eligible for inclusion.Results All studies were judged to be at unclear risk of bias. All studies tested the efficacy of 8 mg dexamethasone 60-90 minutes before surgical extractions. While three studies showed improvement in pain visual analogue scale (VAS) scores in the dexamethasone groups, two were not statistically significant. One study found no improvement in pain scores on VAS. One study found no difference in either trismus or oedema. One study reported one occurrence of post-operative alveolar infection in the dexamethasone group and one occurrence of alveolar osteitis in the placebo group.Conclusion While there seems to be an improvement in pain scores on VAS, these results are not clinically significant. Post-operative analgesia plays a more important role clinically.Introduction Nursing home residents with cognitive and physical disabilities often depend on assistance from caregivers to perform personal hygiene tasks including toothbrushing. Only a minority receives the care needed and toothbrushing compliance levels are not registered.Aims To describe toothbrushing compliance levels in a nursing home setting and investigate the relevance and practicality of using telemonitoring-enabled powered toothbrushes for automated compliance tracking. Furthermore, to investigate changes in plaque and bleeding scores.Materials and methods Nursing home residents were provided with powered toothbrushes and telemonitoring gateways. Toothbrushing frequency and duration were automatically recorded by the telemonitoring gateways, and an email report was sent once a week to the nursing home manager. Plaque index and bleeding index were assessed by dentists at baseline, at the end of the intervention and at three months post-intervention.Results Data from 20 participants for 100 days (3,920 measurements) were collected and used to evaluate toothbrushing compliance. A minority of toothbrushings (5%) were in compliance with the two-minute toothbrushing duration recommendation, while around 30% achieved the one-minute toothbrushing minimum duration recommendation. Around 25% of participants would get only one toothbrushing per day, while 40% would get none. Both plaque and bleeding scores improved significantly during the project, but all progress was lost three months after the project's end.Conclusions It is relevant and practical to monitor toothbrushing compliance in the nursing home setting using telemonitoring-enabled powered toothbrushes. Despite finding limited compliance levels, a significant improvement in the plaque and bleeding index was found after the intervention, which was lost again three months after the telemonitoring gateways had been removed.