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Mounting clinical evidence has revealed that the vitamin D receptor (VDR) is associated with cholestatic liver injury, although the functions of VDR in this condition remain largely unexplored. Here, we investigated the effects of VDR activation on bile duct ligation (BDL) mice, and the underlying mechanisms were further investigated. A low-calcemic VDR agonist, paricalcitol (PAL, 200 ng/kg), was intraperitoneally injected into BDL mice every other day for 5 days or 28 days. Liver histology, liver function indicators, cholangiocyte proliferation, fibrosis scores, and inflammation were evaluated. Mice treated with PAL were rescued from the decreased survival rate induced by BDL and liver damage was reduced. Mechanistically, PAL promoted cholangiocyte proliferation, which was likely conducive to proliferating bile duct maturation and increased branching of bile ducts. PAL treatment also increased the expression of Yes-associated protein (YAP) and its target protein epithelial cell adhesion molecule (EpCam) and decreased the level of inactive cytoplasmic phosphorylated YAP. YAP knockdown abrogated PAL-induced primary bile duct epithelial cell proliferation, confirmed with YAP inhibitor administration. In addition, BDL-induced liver fibrosis and inflammatory cell infiltration were reduced by PAL treatment at both day 5 and day 28 post-BDL. In conclusion, VDR activation mitigates cholestatic liver injury by promoting adaptive bile duct remodeling through cholangiocytic YAP upregulation. Because PAL is an approved clinical drug, it may be useful for treatment of cholestatic liver disease. © 2021 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

One evolutionary path from hermaphroditism to dioecy is via a gynodioecious intermediate. The evolution of dioecy may also coincide with the formation of sex chromosomes that possess sex-determining loci that are physically linked in a region of suppressed recombination. Dioecious papaya (Carica papaya) has an XY chromosome system, where the presence of a Y chromosome determines maleness. However, in cultivation, papaya is gynodioecious, due to the conversion of the male Y chromosome to a hermaphroditic Y

chromosome during its domestication.

We investigated gene expression linked to the X, Y, and Y

chromosomes at different floral developmental stages to identify differentially expressed genes that may be involved in the sexual transition of males to hermaphrodites.

We identified 309 sex-biased genes found on the sex chromosomes, most of which are found in the pseudoautosomal regions. Female (XX) expression in the sex-determining region was almost double that of X-linked expression in males (XY) and hermaphrodites (XY

), which rules out dosage compensation for most sex-linked genes; although, an analysis of hemizygous X-linked loci found evidence of partial dosage compensation. Furthermore, we identified a candidate gene associated with sex determination and the transition to hermaphroditism, a homolog of the MADS-box protein SHORT VEGETATIVE PHASE.

We identified a pattern of partial dosage compensation for hemizygous genes located in the papaya sex-determining region. Furthermore, we propose that loss-of-expression of the Y-linked SHORT VEGETATIVE PHASE homolog facilitated the transition from males to hermaphrodites in papaya.

We identified a pattern of partial dosage compensation for hemizygous genes located in the papaya sex-determining region. Furthermore, we propose that loss-of-expression of the Y-linked SHORT VEGETATIVE PHASE homolog facilitated the transition from males to hermaphrodites in papaya.Currently, the COVID-19 pandemic, caused by the novel SARS-CoV-2 coronavirus, represents the greatest global health threat. Most people infected by the virus present mild to moderate respiratory symptoms and recover with supportive treatments. However, certain susceptible hosts develop an acute respiratory distress syndrome (ARDS), associated with an inflammatory “cytokine storm”, leading to lung damage. Despite the current availability of different COVID-19 vaccines, the new emerging SARS-CoV-2 genetic variants represent a major concern worldwide, due to their increased transmissibility and rapid spread. Indeed, it seems that some mutations or combinations of mutations might confer selective advantages to the virus, such as the ability to evade the host immune responses elicited by COVID-19 vaccines. Several therapeutic approaches have been investigated but, to date, a unique and fully effective therapeutic protocol has not yet been achieved. In addition, steroid-based therapies, aimed to reduce inflammationent opportunistic infections in critically ill COVID-19 patients.

As a beta-coronavirus, Coronavirus disease-2019 (COVID-19) has caused one of the most significant historical pandemics, as well as various health and medical challenges. Our purpose in this report is to collect, summarize, and articulate all essential information about antiviral drugs that may or may not be efficient for treating COVID-19. Clinical evidence about these drugs and their possible mechanisms of action are also discussed.

To conduct a comprehensive review, different keywords in various databases, including Web of Science, Scopus, Medline, PubMed, and Google Scholar, were searched relevant articles, especially the most recent ones, were selected and studied. These selected original research articles, review papers, systematic reviews, and even letters to the editors were then carefully reviewed for data collection.

SARS-CoV-2 is the newest member of the coronavirus family, and there are still no promising therapies or particular antiviral compounds to fight it. AlizarinRedS After entering the body, SARS-Catients or preventing the virus from spreading further. However, other drugs have to be investigated to reach a reliable conclusion about their effectiveness or ineffectiveness.

Approximately 30% of patients with confirmed COVID-19 report persistent smell or taste disorders as long-term sequalae of infection. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is associated with inflammatory changes to the olfactory bulb, and treatments with anti-inflammatory properties are hypothesized to attenuate viral injury and promote recovery of olfaction after infection. Our study investigated the efficacy of a supplement with Palmitoylethanolamide (PEA) and Luteolin to support recovery of olfaction in COVID-19 patients.

We conducted a randomized-controlled pilot study in outpatients with history of confirmed COVID-19 with post-infection olfactory impairment that persisted ≥ 90 days after SARS-CoV-2 negative testing. Patients were randomized to two times a day olfactory rehabilitation alone or weekly olfactory rehabilitation plus daily oral supplement with PEA and Luteolin. Subjects with preexisting olfactory disorders were excluded. Sniffin’ Sticks assessments were performed at baseline and 30 days after treatment.