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This report describes a case of a 60-year-old male patient who received the first dose of the AstraZeneca vaccine and presented to the emergency department complaining of left hand pain and paresthesia. Investigations revealed upper limb ischemia; he was hospitalized for further management.Allium cepa L. remains the most cultivated Allium species in Morocco and around the world. With the purpose of making the first biochemical characterization of Moroccan onions, several biochemical components have been measured in eleven onion ecotypes. Onions were collected as seeds from different geographical origins and cultivated in the same environment, to eliminate the influence of the environment on biochemical expression. Moisture, total phenols, flavonoids, antioxidant activity, total and reducing sugars, and sulfur dioxide were the biochemical properties of interest. Except for moisture, the eleven onion ecotypes revealed a highly significant variation in terms of the studied biochemical characters. The total phenol and flavonoid content ranged from 5.94 to 11.22 mg equivalent gallic acid/g dry weight and 0.67 to 1.52 mg equivalent quercetin/g dry weight, respectively. The antioxidant activity of the studied onions showed a strong correlation with the polyphenols (R 2 = 0.7189), especially with the flavonoids (R 2 = 0.8063). The sulfur dioxide content parted from 85.60 to 30.43 ppm when measured using the Monier-Williams distillation method. The current results show that there is no correlation between total sugars and reducing sugars. In conclusion, these findings present a clear biochemical profile of Moroccan onion ecotypes, as well as confirm, for the first time, the presence of a clear variation between the biochemical profiles of Moroccan onion ecotypes, which could be useful for future valorization programs.Here, we describe a reliable approach for targeted DNA integrations in the genome of R. microsporus, one of the main causal agents of mucormycosis. We provide a strategy for stable, targeted integration of DNA templates by homologous recombination (HR) based on the CRISPR-Cas9 technology. This strategy opens a wide range of possibilities for the genetic modification of R. microsporus and will be useful for the study of mucormycosis. For complete details on the use and execution of this protocol, please refer to Lax et al. (2021).Our protocol combines Maximum Parsimony and Phylogenetic Networks approaches to understand the phylogenetic relationships and evolutionary processes of hominin species that might have shared inheritance from multiple ancestors. By addressing the questions of pattern and process in human phylogeny, the protocol can be used to clarify the taxonomic definition(s) of diverse hominin groups and ascertain whether or not the mode of evolution of genus Homo is reticulate. Using high quality and informative phenotypic data sets is necessary to yield meaningful results. For complete details on the use and execution of this protocol, please refer to Caparros and Prat (2021).A family of inositol hexakisphosphate kinases (IP6Ks) catalyzes the production of inositol pyrophosphate IP7 (5-diphosphoinositolpentakisphosphate) which is known to modulate various biological events such as cell growth. While targeting IP6K1 in various cancer cells has been well reported to control cancer cell motility and invasiveness, the role of host IP6K1 in tumor progression remains unknown. By using a syngeneic MC38 murine mouse colon carcinoma model, here we examined how host IP6K1 in the tumor microenvironment influences tumor growth. In IP6K1 knockout (KO) mice, the growth of MC38 tumor cells was markedly accelerated and host survival was significantly shortened compared with wild-type (WT). Our flow cytometric analysis revealed that tumors grown in IP6K1 KO mice had lower immune suppressive myeloid cells and M1 polarized macrophages. Notably, infiltration of both antigen-presenting dendritic cells and CD8+ cytotoxic T lymphocytes into the tumor tissues was remarkably abrogated in IP6K1 KO condition. These studies suggest that enhanced tumor growth in IP6K1 KO mice resulted from reduced anti-tumor immunity due to disturbed immune cell actions in the tumor microenvironment. In conclusion, we demonstrate that host IP6K1 acts as a tumor suppressor, most likely by fine-tuning diverse tumor-immune cell interactions, which might have implications for improving the host response against cancer progression.Human immunodeficiency virus type I (HIV-1) infection of the CNS produces synapse loss which correlates with cognitive decline in patients with HIV-associated neurocognitive disorders (HAND). Lithium is mood stabilizer of unknown mechanism used to treat bipolar disorder and is known to exhibit neuroprotective properties. Here, we studied the effects of lithium on HIV-1 Tat-induced synapses between rat hippocampal neurons. The number of synapses was quantified to detect clusters of the scaffold protein postsynaptic density 95 (PSD95) which is clustered at glutamatergic synapses on cultured rat hippocampal neurons in vitro. Lithium protected synapses from HIV-1 Tat-induced synapse loss and subsequent neuronal death. This synaptic protection was prevented by both the activation of NMDA receptor leading to intracellular signaling and the regulatory pathway of lithium including inositol depletion and glycogen synthase kinase-3β (GSK-3β). These results suggest that mood stabilizers might be effective drugs to treat neurodegenerative disorders including HAND.Although simvastatin has been shown to inhibit vascular permeability, which might be amplified via gap junction intercellular communication (GJIC), the underlying mechanism of action remains unclear. In the present study, we investigated the effects and mechanisms of simvastatin on endothelial cells GJIC. Specifically, human umbilical vein endothelial cells (HUVECs) were stimulated with TNF-α (10 ng/mL) alone or in combination with simvastatin (5 µM), and their effects on vascular endothelial cell GJIC tested via the scrape loading/dye transfer (SL/DT) assay. Next, we performed immunofluorescence, real-time PCR and western blot assays to analyze expression of Cx37, Cx40 and Cx43 in HUVECs. Results showed that GJIC activity in HUVECs was markedly elevated in HUVECs treated with TNF-α in combination with simvastatin. In addition, simvastatin treatment significantly upregulated expression of Cx37 and Cx40 but downregulated Cx43 mRNAs and proteins. Taken together, these marked changes indicated that simvastatin exerts its regulatory effects on gap junction function by upregulating Cx37 and Cx40 and downregulating Cx43 expression.Autophagy modulators are considered putative therapeutic targets because of the role of autophagy in cancer progression. Kazinol C, a 1,3-diphenylpropane from the plant Broussonetia kazinoki, has been shown to induce apoptosis in colon cancer cells through the activation of AMPK at high concentrations. In the present study, we found that Kazinol C induced autophagy through endoplasmic reticulum stress-mediated unfolded protein response signaling in several normal and cancer cell lines at low concentrations of Kazinol C that did not induce apoptosis. Kazinol C activated the transducers of unfolded protein response signaling, leading to target gene expression, LC3-II conversion, and TFEB nuclear translocation. Chemical inhibition of endoplasmic reticulum stress reduced LC3-II conversion. In addition, blockade of autophagy by knockout of Atg5 or treatment with 3-MA enhanced Kazinol C-induced apoptosis. In summary, we have uncovered Kazinol C as a novel autophagy inducer and confirmed the role of autophagy as a cellular stress protector.Black garlic (BG) is a newly explored food stuff obtained via fermentation of raw, healthy garlic, especially in Asian countries. Interstitial cells of Cajal (ICC) are the pacemaker cells of gastrointestinal (GI) motility. The purpose of this study was to investigate the effects of BG extract on the pacemaker potentials of the ICC in the small intestines of mice and the possibility of controlling GI motility. The antioxidant activity of BG extract was also investigated. The whole-cell electrophysiological method was used to measure pacemaker potentials of the ICC in vitro, whereas GI motility was measured using the intestinal transit rate (ITR) in vivo. BG extract depolarized the pacemaker potentials of the ICC. Y25130 and RS39604 5-HT receptor antagonists could not inhibit the effect of BG extract on the pacemaker potentials of the ICC, whereas the 5-HT receptor antagonist SB269970 could. Pre-treatment with external Na+ (5 mM) or Ca2+-free solution inhibited the BG extract-induced depolarization of the ICC. selleck chemical With SB203580, PD98059, or c-jun NH2-terminal kinase II inhibitor pre-treatment, BG extract did not induce pacemaker potential depolarization. Moreover, the ITR values were increased by BG extract. Elevation of the ITR due to BG extract was related with increased protein expression of the 5-HT7 receptors. In addition, BG extract showed antioxidant activity. Collectively, these results highlight the ability of BG extract to regulate GI motility and the possibility of using it to develop GI motility modulators in the future. Moreover, BG showed immense potential as an antioxidant.Laser-induced incandescence (LII) is a widely used combustion diagnostic for in situ measurements of soot primary particle sizes and volume fractions in flames, exhaust gases, and the atmosphere. Increasingly, however, it is applied to characterize engineered nanomaterials, driven by the increasing industrial relevance of these materials and the fundamental scientific insights that may be obtained from these measurements. This review describes the state of the art as well as open research challenges and new opportunities that arise from LII measurements on non-soot nanoparticles. An overview of the basic LII model, along with statistical techniques for inferring quantities-of-interest and associated uncertainties is provided, with a review of the application of LII to various classes of materials, including elemental particles, oxide and nitride materials, and non-soot carbonaceous materials, and core-shell particles. The paper concludes with a discussion of combined and complementary diagnostics, and an outlook of future research.The demand for large cell numbers for cellular therapies and drug screening applications requires the development of scalable platforms capable of generating high-quality populations of tissue-specific cells derived from human pluripotent stem cells (hPSCs). Here, we studied the ability of Gibco StemScale PSC Suspension Medium to promote the efficient expansion of hPSC cultures as aggregates grown in suspension. We tested human induced pluripotent stem cell (hiPSC) growth in 6-well plates (on orbital shaker platforms) and single-use vertical-wheel bioreactors for a total of three consecutive passages. Up to a 9-fold increase in cell number was observed over 5 days per passage, with a cumulative fold change up to 600 in 15 days. Additionally, we compared neural induction of hiPSCs by using a dual SMAD inhibition protocol with a commercially available neural induction medium, which can potentially yield more than a 30-fold change, including neural progenitor induction and expansion. This system can also be adapted toward the generation of floor plate progenitors, which yields up to an 80-fold change in cell number and generates FOXA2-positive populations.

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