The purpose of this review is to highlight the role of NO in the physiology and pathophysiology of ocular surface and propose suitable techniques to measure NO levels in ocular surface tissues and tears. This will improve the understanding of NO's role in ocular surface biology and the development of new NO-based therapies to treat various ocular surface diseases. Further, this review summarizes the biochemistry underpinning NO's antimicrobial action.The COVID-19 pandemic has piqued interest in spontaneous face-touch as a possible route of microbial infection, with eye-touch of particular importance since the ocular surface is a likely portal of human Coronavirus infection. Spontaneous face-touching is a poorly understood, ingrained habit for humans, who engage in this activity on average between 9 to 162 times per hour. Nearly half of spontaneous face-touches involve mucous membranes, and one third of those involve the eyes. The infective sequelae of self-touch are well documented in ophthalmological conditions such as infectious conjunctivitis, with risks for ocular surface disease beyond primary infection from pathogens such as human papillomavirus. Through tear film conveyance via the nasolacrimal duct, ocular surface pathogens may furthermore have access to the nasopharynx, oropharynx, and respiratory/gastrointestinal systems beyond. Ocular surface and face self-touch therefore represent a concerning possible method of not only local, but also systemic, self-inoculation. Conversely, microbial diversity in the mutualistic microbiome is being increasingly implicated as integral for developing immunity, and protecting against endocrinological and neurodegenerative disease, including those that affect the eye. Spontaneous face-touch brings the hands, the part of the body most in contact with the external world and with the highest temporal diversity, into direct contact with the body's multiple microbiomes.  https://www.selleckchem.com/products/amg-232.html  The authors hypothesise that spontaneous self-touch may represent an important mechanism by which the skin, ocular surface, gastrointestinal, and respiratory tracts maintains microbial diversity and prevents dysbiosis. It may be that whilst the eyes are at risk of infection through self-touch, they may paradoxically benefit through the acquisition of a mutualistic microbiome, protective not only for the eyes, but for the body as a whole.
  Sporulation is a complex cell differentiation programme shared by many members of the Firmicutes, the end result of which is a highly resistant, metabolically inert spore that can survive harsh environmental insults. Clostridioides difficile spores are essential for transmission of disease and are also required for recurrent infection. However, the molecular basis of sporulation is poorly understood, despite parallels with the well-studied Bacillus subtilis system. The spore envelope consists of multiple protective layers, one of which is a specialised layer of peptidoglycan, called the cortex, that is essential for the resistant properties of the spore. We set out to identify the enzymes required for synthesis of cortex peptidoglycan in C.difficile.
 
  Bioinformatic analysis of the C.difficile genome to identify putative homologues of Bacillus subtilis spoVD was combined with directed mutagenesis and microscopy to identify and characterise cortex-specific PBP activity.
 
  Deletion of CDR20291_2544 (SpoVD
  ) abrogated spore formation and this phenotype was completely restored by complementation in cis. Analysis of SpoVD
  revealed a three domain structure, consisting of dimerization, transpeptidase and PASTA domains, very similar to B.subtilis SpoVD. Complementation with SpoVD
  domain mutants demonstrated that the PASTA domain was dispensable for formation of morphologically normal spores. SpoVD
  was also seen to localise to the developing spore by super-resolution confocal microscopy.
 
  We have identified and characterised a cortex specific PBP in C.difficile. This is the first characterisation of a cortex-specific PBP in C.difficile and begins the process of unravelling cortex biogenesis in this important pathogen.
 We have identified and characterised a cortex specific PBP in C. difficile. This is the first characterisation of a cortex-specific PBP in C. difficile and begins the process of unravelling cortex biogenesis in this important pathogen.
  Gastrointestinal (GI) toxicity is still an issue within drug development, especially for novel oncology drugs. The identification of GI mucosal damage at an early stage with high sensitivity and specificity across preclinical species and humans remains difficult. To date, in preclinical studies, no qualified mechanistic, diagnostic or prognostic biomarkers exist for GI mucosal toxicity. l-citrulline is one of the most promising biomarker candidates used in clinical settings to quantify enterocyte integrity in various small intestinal diseases. l-citrulline is an intermediate metabolic amino acid produced mainly by functional enterocytes of the small intestine, whereby enterocyte loss will cause a drop in circulating l-citrulline.
 
  In several repeat-dose toxicity studies, plasma l-citrulline has been evaluated as a potential safety biomarker for intestinal toxicity in beagle dogs and Wistar (Han) rats treated with different oncological drug candidates in drug development. Clinical observations and body weigitrulline as a small intestine biomarker.
 Based on the performed analysis, a longitudinal investigation of l-citrulline plasma levels for individual animals in the control and treatment groups is essential and pretreatment values of l-citrulline levels in rodents would be highly informative. Overall, further cross-species comparison (Cynomolgus monkey, mouse) and implementation in clinical trials as exploratory biomarker is essential to foster the hypothesis and to understand completely the clinical relevance of l-citrulline as a small intestine biomarker.Tau is a microtubule-stabilizing protein that plays an important role in the formation of axonal microtubules in neurons. Phosphorylated tau (p-Tau) has received great attention in the field of Alzheimer's disease (AD) as a potential therapeutic target due to its involvement with synaptic damage and neuronal dysfunction. Mounting evidence suggests that amyloid beta (Aβ)-targeted clinical trials continuously failed; therefore, it is important to consider alternative therapeutic strategies such as p-tau-PROTACs targeted small molecules for AD and other tauopathies. The present article describes the characteristics of tau biology, structure, and function in both healthy and pathological states in AD. It also explains data from studies that have identified the involvement of p-tau in neuronal damage and synaptic and cognitive functions in AD. Current article also covers several aspects, including small molecule inhibitors, and the development of p-tau-PROTACs targeted drug molecules to treat patients with AD and other tauopathies.