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The hit compounds are therefore promising candidates for further development as novel combination agents to restore β-lactam efficacy against MRSA.Cells have evolved a complex molecular network, collectively called the protein homeostasis (proteostasis) network, to produce and maintain proteins in the appropriate conformation, concentration and subcellular localization. Loss of proteostasis leads to a reduction in cell viability, which occurs to some degree during healthy ageing, but is also the root cause of a group of diverse human pathologies. The accumulation of proteins in aberrant conformations and their aggregation into specific beta-rich assemblies are particularly detrimental to cell viability and challenging to the protein homeostasis network. This is especially true for bacteria; it can be argued that the need to adapt to their changing environments and their high protein turnover rates render bacteria particularly vulnerable to the disruption of protein homeostasis in general, as well as protein misfolding and aggregation. Targeting bacterial proteostasis could therefore be an attractive strategy for the development of novel antibacterial therapeutics. This review highlights advances with an antibacterial strategy that is based on deliberately inducing aggregation of target proteins in bacterial cells aiming to induce a lethal collapse of protein homeostasis. The approach exploits the intrinsic aggregation propensity of regions residing in the hydrophobic core regions of the polypeptide sequence of proteins, which are genetically conserved because of their essential role in protein folding and stability. Moreover, the molecules were designed to target multiple proteins, to slow down the build-up of resistance. Although more research is required, results thus far allow the hope that this strategy may one day contribute to the arsenal to combat multidrug-resistant bacterial infections.The prevalence of pulmonary fibrosis is increasing with an aging population and its burden is likely to increase following COVID-19, with large financial and medical implications. As approved therapies in pulmonary fibrosis only slow disease progression, there is a significant unmet medical need. Hyperbaric oxygen (HBO) is the inhaling of pure oxygen, under the pressure of greater than one atmosphere absolute, and it has been reported to improve pulmonary function in patients with pulmonary fibrosis. Our recent study suggested that repetitive HBO exposure may affect biological processes in mice lungs such as response to wounding and extracellular matrix. To extend these findings, a bleomycin-induced pulmonary fibrosis mouse model was used to evaluate the effect of repetitive HBO exposure on pulmonary fibrosis. Building on our previous findings, we provide evidence that HBO exposure attenuates bleomycin-induced pulmonary fibrosis in mice. In vitro, HBO exposure could reverse, at least partially, transforming growth factor (TGF)-β-induced fibroblast activation, and this effect may be mediated by downregulating TGF-β-induced expression of hypoxia inducible factor (HIF)-1α. These findings support HBO as a potentially life-changing therapy for patients with pulmonary fibrosis, although further research is needed to fully evaluate this.As immuno-oncology (I/O) emerges as an effective approach in the fight against cancer, multispectral imaging of multiplex immunofluorescence (mIF) is maturing as an analytical platform. CC-930 cost The timing is fortuitous. Due to health economic considerations surrounding the use of I/O, there is an urgent need for tests that accurately predict response to the growing list of available therapies. Multispectral mIF provides several advantages over other biomarker modalities by enabling deeper interrogation of the intricate biology within the tumor microenvironment, including detection of cell-to-cell spatial interactions that correlate with clinical outcomes. It also provides a practical path for generating reliable and reproducible results in a clinically suitable, high-throughput workflow. In this article, we (1) describe the principles behind multispectral mIF; (2) provide advice and recommendations on assay development and optimization and highlight characteristics of a well-performing assay; and (3) discuss the requirements for translating this approach into clinical practice.Reactive oxygen species (ROS) generated under oxidative stress (OS) cause oxidative damage to RNA. Recent studies have suggested a role for oxidized RNA in several human disorders. Under the conditions of oxidative stress, mRNAs released from polysome dissociation accumulate and initiate stress granule (SG) assembly. SGs are highly enriched in mRNAs, containing inverted repeat (IR) Alus in 3′ UTRs, AU-rich elements, and RNA-binding proteins. SGs and processing bodies (P-bodies) transiently interact through a docking mechanism to allow the exchange of RNA species. However, the types of RNA species exchanged, and the mechanisms and outcomes of exchange are still unknown. Specialized RNA-binding proteins, including adenosine deaminase acting on RNA (ADAR1-p150), with an affinity toward inverted repeat Alus, and Tudor staphylococcal nuclease (Tudor-SN) are specifically recruited to SGs under OS along with an RNA transport protein, Staufen1 (STAU1), but their precise biochemical roles in SGs and SG/P-body docking are uncertain. Here, we critically review relevant literature and propose a hypothetical mechanism for the processing and decay of oxidized-RNA in SGs/P-bodies, as well as the role of ADAR1-p150, Tudor-SN, and STAU1.The COVID-19 pandemic, caused by SARS-CoV-2 infection, remains a dramatic threat to human life and economic well-being worldwide. Significant heterogeneity in the severity of disease was observed for patients infected with SARS-CoV-2 ranging from asymptomatic to severe cases. Moreover, male patients had a higher probability of suffering from high mortality and severe symptoms linked to cytokine storm and excessive inflammation. The NLRP3 inflammasome is presumably critical to this process. Sex differences may directly affect the activation of NLRP3 inflammasome, impacting the severity of observed COVID-19 symptoms. To elucidate the potential mechanisms underlying sex based differences in NLRP3 activation during SARS-CoV-2 infection, this review summarizes the reported mechanisms and identifies potential therapeutic targets.