Fogpotts6151

The results indicated that ARHGEF39 promoted the viability, migration and invasion of ccRCC cells by regulating the activation of the AKT/ERK signaling pathway. Overall, our research suggested that ARHGEF39 was upregulated in ccRCC and possibly facilitated the malignant development of ccRCC by modulating the AKT/ERK signaling pathway.Breast cancer is the leading cause of death by cancer among women in less developed regions. In Colombia, few published studies have applied next-generation sequencing technologies to evaluate the genetic factors related to breast cancer. R428 This study characterized the exome of three patients with breast cancer from southwestern Colombia to identify likely pathogenic or disease-related DNA sequence variants in tumor cells. For this, the exomes of three tumor tissue samples from patients with breast cancer were sequenced. The bioinformatics analysis identified two pathogenic variants in Fgfr4 and Nf1 genes, which are highly relevant for this type of cancer. Specifically, variant FGFR4-c.1162G>A predisposes individuals to a significantly accelerated progression of this pathology, while NF1-c.1915C>T negatively alters the encoded protein and should be further investigated to clarify the role of this variant in this neoplasia. Moreover, 27 novel likely pathogenic variants were found and 10 genes showed alterations of pathological interest. These results suggest that the novel variants reported here should be further studied to elucidate their role in breast cancer.The clinical performance of the current cancer therapies is still far from satisfactory. The emerging ferroptosis-driven therapy strategies reignite the hope of chemotherapy in tumor treatment due to their incredible tumor suppression. Among ferroptosis-based cancer therapies, metal elements have attracted remarkable attention due to their inherent physicochemical properties in inducing ferroptosis of tumor cells quickly and strongly without complex cellular signal transduction. Although the discovery and applications of ferroptosis for tumor treatment have been discussed in many reviews, the unique advantages of metal-containing nanomaterials interfering ferroptotic cancer therapies (MIFCT) have seldom been mentioned. Here, we outline the latest advances of MIFCT comprehensively. Firstly, the functions of different kinds of metal elements or their ions are introduced to illustrate their advantages in MIFCT. Secondly, the emerging metal-containing nanomaterials that are designed to achieve ferroptosis-driven therapy are overviewed, including their ability to boost the Fenton or Fenton-like reaction for reactive oxygen species generation, act as hydrogen peroxide self-providers, damage the reducing system, and disturb cellular communication. Moreover, metal-containing nanomaterials with external energy conversion features for MIFCT are discussed. Finally, the future expectations and challenges of MIFCT for clinical cancer therapy are spotlighted.β-Glucan, an economical by-product of yeast, has various health-promoting activities. However, the digestion and fermentation characteristics of β-glucan from yeast are still unknown. Thus, simulated digestion under saliva, gastric and small intestinal solutions and fermentation by gut microbiota were studied in this work. The results showed β-glucan could not be hydrolyzed in saliva, gastric and small intestinal conditions. Then, β-glucan reaches the large intestine, where it is degraded and metabolized by gut microbiota. At the same time, β-glucan could modulate the structure and composition of gut microbiota by inhibiting the proliferation of harmful gut microbiota and promoting the growth of health-promoting gut microbiota. At the phylum level, β-glucan significantly decreased the ratio of Firmicutes to Bacteroidetes. Furthermore, both β-glucan and inulin could selectively promote the growth of Bifidobacterium. Unlike inulin, β-glucan was able to better promote the growth of Bifidobacterium_longum. Thus, β-glucan showed a similar probiotic activity to inulin and is expected to be a potential prebiotic for the modulation of gut microbiota.Coarse-grained water models offer opportunities to study the molecular processes in water on spatial and temporal scales inaccessible to conventional atomic-level simulations. Such a model that can accurately describe the structural, electrostatic and thermodynamic properties of liquid water is difficult to derive but invaluable. Here, we present FlexDQ, a flexible three-site coarse-grained model, representing clusters of water molecules. This model was derived using a full bottom-up approach in which atomistic information of water molecules is processed using clustering techniques based on considerations of both energy and geometry and a mapping algorithm that encodes information of dipole and quadrupole moments of water clusters into coarsely grained interaction sites. Parameterization of FlexDQ was conducted consistently and systematically, augmented by these data. The resulting model reproduces not only dipolar and quadrupolar fluctuations of water clusters, but also their local structural correlations in the bulk phase and, to a good extent, pressure-related properties, dielectric permittivity and water-air interfacial properties that were not targeted for parameterization. The ability of our model to reproduce various properties of water has been shown to originate from its explicit treatment of electrostatics. Coupled with the popular MARTINI CG model, FlexDQ captures the entropy-enthalpy balance of hydrophobic interactions and describes the dielectric behavior of water at the water-membrane interface, yielding a positive internal electrostatic potential in membranes, which is otherwise difficult to reproduce using MARTINI alone. Together, the FlexDQ model and its development framework reported here show promise for studies on the biomolecules in water.The effect of the polyanionic polymer of inorganic polyphosphate (polyP) involved in innate immunity on the binding of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein to the cellular ACE2 receptor was studied. The RBD surface comprises a basic amino acid stretch of four arginine residues which interact with the physiological polyP (polyP40) and polyP3. Subsequently, the interaction of RBD with ACE2 is sensitively inhibited. After the chemical modification of arginine, an increased inhibition by polyP, at a 1  1 molar ratio (polyP  RBP), is measured already at 0.1 μg mL-1. Heparin was ineffective. The results suggest a potential therapeutic benefit of polyP against SARS-CoV-2 infection.