Hovmandcamacho2789

Moreover, cadmium exposure promoted increased macrophage glycolytic function with enhanced extracellular acidification rate, glycolytic metabolites, and lactate excretion. These observations suggest that cadmium mediates the persistence of classically activated lung macrophages to exacerbate lung injury.Sphingosine has been shown to prevent and eliminate bacterial infections of the respiratory tract, but it is unknown whether sphingosine can be also employed to prevent viral infections. To test this hypothesis, we analyzed whether sphingosine regulates the infection of cultured and freshly isolated ex vivo human epithelial cells with pseudoviral particles expressing SARS-CoV-2 spike (pp-VSV-SARS-CoV-2 spike) that served as a bona fide system mimicking SARS-CoV-2 infection. We demonstrate that exogenously applied sphingosine suspended in 0.9% NaCl prevents cellular infection with pp-SARS-CoV-2 spike. Pretreatment of cultured Vero epithelial cells or freshly isolated human nasal epithelial cells with low concentrations of sphingosine prevented adhesion of and infection with pp-VSV-SARS-CoV-2 spike. Mechanistically, we demonstrate that sphingosine binds to ACE2, the cellular receptor of SARS-CoV-2, and prevents the interaction of the receptor-binding domain of the viral spike protein with ACE2. These data indicate that sphingosine prevents at least some viral infections by interfering with the interaction of the virus with its receptor. Our data also suggest that further preclinical and finally clinical examination of sphingosine is warranted for potential use as a prophylactic or early treatment for coronavirus disease-19.Precise genetic manipulation of specific cell types or tissues to pinpoint gene function requirement is a critical step in studies aimed at unraveling the intricacies of organismal physiology. Drosophila researchers heavily rely on the UAS/Gal4/Gal80 system for tissue-specific manipulations; however, it is often unclear whether the reported Gal4 expression patterns are indeed specific to the tissue of interest such that experimental results are not confounded by secondary sites of Gal4 expression. Here, we surveyed the expression patterns of commonly used Gal4 drivers in adult Drosophila female tissues under optimal conditions and found that multiple drivers have unreported secondary sites of expression beyond their published cell type/tissue expression pattern. These results underscore the importance of thoroughly characterizing Gal4 tools as part of a rigorous experimental design that avoids potential misinterpretation of results as we strive for understanding how the function of a specific gene/pathway in one tissue contributes to whole-body physiology.The wels catfish (Silurus glanis) is one of the largest freshwater fish species in the world. This top predator plays a key role in ecosystem stability, and represents an iconic trophy-fish for recreational fishermen. S. glanis is also a highly valued species for its high-quality boneless flesh, and has been cultivated for over 100 years in Eastern and Central Europe. The interest in rearing S. glanis continues to grow; the aquaculture production of this species has almost doubled during the last decade. However, despite its high ecological, cultural and economic importance, the available genomic resources for S. glanis are very limited. To fulfill this gap we report a de novo assembly and annotation of the whole genome sequence of a female S. glanis The linked-read based technology with 10X Genomics Chromium chemistry and Supernova assembler produced a highly continuous draft genome of S. glanis ∼0.8Gb assembly (scaffold N50 = 3.2 Mb; longest individual scaffold = 13.9 Mb; BUSCO completeness = 84.2%), which included 313.3 Mb of putative repeated sequences. In total, 21,316 protein-coding genes were predicted, of which 96% were annotated functionally from either sequence homology or protein signature searches. The highly continuous genome assembly will be an invaluable resource for aquaculture genomics, genetics, conservation, and breeding research of S. glanis.There is an urgent need to repurpose drugs against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recent computational-experimental screenings have identified several existing drugs that could serve as effective inhibitors of the virus' main protease, Mpro, which is involved in gene expression and replication. Among these, ebselen (2-phenyl-1,2-benzoselenazol-3-one) appears to be particularly promising. Here, we examine, at a molecular level, the potential of ebselen to decrease Mpro activity. We find that it exhibits a distinct affinity for the catalytic region. Our results reveal a higher-affinity, previously unknown binding site localized between the II and III domains of the protein. A detailed strain analysis indicates that, on such a site, ebselen exerts a pronounced allosteric effect that regulates catalytic site access through surface-loop interactions, thereby inducing a reconfiguration of water hotspots. Together, these findings highlight the promise of ebselen as a repurposed drug against SARS-CoV-2.Recent reports suggest that 10 to 30% of severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) infected patients are asymptomatic and that viral shedding may occur before symptom onset. Therefore, there is an urgent need to increase diagnostic testing capabilities to prevent disease spread. We developed P-BEST, a method for Pooling-Based Efficient SARS-CoV-2 Testing, which identifies all positive subjects within a set of samples using a single round of testing. Each sample is assigned into multiple pools using a combinatorial pooling strategy based on compressed sensing. We pooled sets of 384 samples into 48 pools, providing both an eightfold increase in testing efficiency and an eightfold reduction in test costs, while identifying up to five positive carriers. We then used P-BEST to screen 1115 health care workers using 144 tests. P- BEST provides an efficient and easy-to-implement solution for increasing testing capacity that can be easily integrated into diagnostic laboratories.Hepatic steatosis is a widespread metabolic disease characterized by excessive accumulation of triglyceride (TG) in liver. So far, effective approved drugs for hepatic steatosis are still in development, and removing the unnecessary TG from the hepatocytes is an enormous challenge. Here, we explore a promising anti-hepatic steatosis strategy by boosting hepatocellular TG transport using β-alanine-modified gadofullerene (GF-Ala) nanoparticles. We confirm that GF-Ala could reverse hepatic steatosis in oleic acid-induced hepatocytes, fructose-induced mice, and obesity-associated transgenic ob/ob mice. Observably, GF-Ala improves hepatomegaly and hepatic lipid accumulation, reduces lipid peroxidation, and repairs abnormal mitochondria. Of note, we demonstrate that GF-Ala markedly inhibits the posttranslational degradation of apolipoprotein B100 (ApoB100) and boosts hepatocellular TG transport based on their superior antioxidant property. Together, we conclude that GF-Ala could potently ameliorate hepatic TG transport and maintain hepatic metabolic homeostasis without apparent toxicity, being beneficial for treatments of hepatic steatosis and other fatty liver diseases.Metasurfaces provide a compact, flexible, and efficient platform to manipulate the electromagnetic waves. However, chromatic aberration imposes severe restrictions on their applications in broadband polarization control. Here, we propose a broadband achromatic methodology to implement polarization-controlled multifunctional metadevices in mid-wavelength infrared with birefringent meta-atoms. We demonstrate the generation of polarization-controlled and achromatically on-axis focused optical vortex beams with diffraction-limited focal spots and switchable topological charge (L∥ = 0 and L⊥ = 2). Besides, we further implement broadband achromatic polarization beamsplitter with high polarization isolation (extinction ratio up to 21). The adoption of all-silicon configuration not only facilitates the integration with CMOS technology but also endows the polarization multiplexing meta-atoms with broad phase dispersion coverage, ensuring the large size and high performance of the metadevices. Compared with the state-of-the-art chromatic aberration-restricted polarization-controlled metadevices, our work represents a substantial advance and a step toward practical applications.Intestinal epithelial homeostasis is maintained by adult intestinal stem cells, which, alongside Paneth cells, appear after birth in the neonatal period. We aimed to identify regulators of neonatal intestinal epithelial development by testing a small library of epigenetic modifier inhibitors in Paneth cell-skewed organoid cultures. We found that lysine-specific demethylase 1A (Kdm1a/Lsd1) is absolutely required for Paneth cell differentiation. Lsd1-deficient crypts, devoid of Paneth cells, are still able to form organoids without a requirement of exogenous or endogenous Wnt. Mechanistically, we find that LSD1 enzymatically represses genes that are normally expressed only in fetal and neonatal epithelium. This gene profile is similar to what is seen in repairing epithelium, and we find that Lsd1-deficient epithelium has superior regenerative capacities after irradiation injury. In summary, we found an important regulator of neonatal intestinal development and identified a druggable target to reprogram intestinal epithelium toward a reparative state.A comprehensive 13C nuclear magnetic resonance (NMR) approach for characterizing the location of chain ends of polyethers and polyesters, at the crystallite surface or in the amorphous layers, is presented. The OH chain ends of polyoxymethylene are labeled with 13COO-acetyl groups and their dynamics probed by 13C NMR with chemical shift anisotropy (CSA) recoupling. At least three-quarters of the chain ends are not mobile dangling cilia but are immobilized, exhibiting a powder pattern characteristic of the crystalline environment and fast CSA dephasing. The location and clustering of the immobilized chain ends are analyzed by spin diffusion. Fast 1H spin diffusion from the amorphous regions shows confinement of chain ends to the crystallite surface, corroborated by fast 13C spin exchange between chain ends. These observations confirm the principle of avoidance of density anomalies, which requires that chains terminate at the crystallite surface to stay out of the crowded interfacial layer.Agonist-induced phosphorylation of G protein-coupled receptors (GPCRs) is a key determinant for their interaction with β-arrestins (βarrs) and subsequent functional responses. Therefore, it is important to decipher the contribution and interplay of different receptor phosphorylation sites in governing βarr interaction and functional outcomes. Here, we find that several phosphorylation sites in the human vasopressin receptor (V2R), positioned either individually or in clusters, differentially contribute to βarr recruitment, trafficking, and ERK1/2 activation. Even a single phosphorylation site in V2R, suitably positioned to cross-talk with a key residue in βarrs, has a decisive contribution in βarr recruitment, and its mutation results in strong G-protein bias. Molecular dynamics simulation provides mechanistic insights into the pivotal role of this key phosphorylation site in governing the stability of βarr interaction and regulating the interdomain rotation in βarrs. Our findings uncover important structural aspects to better understand the framework of GPCR-βarr interaction and biased signaling.