BackgroundIL-1β is a pleiotropic pro-inflammatory cytokine and its up-regulation is closely associated with various cancers including gastrointestinal tumors. However, it remains unclear how IL-1β may contribute to the initiation and development of these inflammation-associated cancers. Here we investigated the role of IL-1β in colon cancer stem cell (CSC) development.MethodsUsing self-renewal assay, soft-agar assay, invasion assay, real-time PCR analysis, immunoblot assay and shRNA knockdown, we determined the effects of IL-1β on cancer stem cell development and epithelial-mesenchymal transition (EMT) in human primary colon cancer cells and colon cancer cell line HCT-116.ResultsWe found that IL-1β can increase sphere-forming capability of colon cancer cells in serum-free medium. IL-1β-induced spheres displayed an up-regulation of stemness factor genes (Bmi1 and Nestin) and increased drug resistance, hallmarks of CSCs. Importantly, expression of EMT activator Zeb1 was increased in IL-1β-induced spheres, indicating that there might be a close association between EMT and IL-1β-induced CSC self-renewal. Indeed, IL-1β treatment led to EMT of colon cancer cells with loss of E-cadherin, up-regulation of Zeb1, and gain of the mesenchymal phenotype. Furthermore, shRNA-mediated knockdown of Zeb1 in HCT-116 cells reversed IL-1β-induced EMT and stem cell formation.ConclusionOur findings indicate that IL-1β may promote colon tumor growth and invasion through activation of CSC self-renewal and EMT, and Zeb1 plays a critical role in these two processes. Thus, IL-1β and Zeb1 might be new therapeutic targets against colon cancer stem cells.

Many compounds containing a five-membered heterocyclic ring display exceptional chemical properties and versatile biological activities. In this Minireview, thiadiazoles are summarized according to their therapeutic potential, highlighting the versatility of this scaffold in medicinal chemistry. The unique properties of thiadiazoles are also discussed in relation to their potential effect on activity. Thiadiazole is a bioisostere of pyrimidine and oxadiazole, and given the prevalence of pyrimidine in nature it is unsurprising that thiadiazoles exhibit significant therapeutic potential. The sulfur atom of the thiadiazole imparts improved liposolubility, and the mesoionic nature of thiadiazoles makes these compounds better able to cross cellular membranes. By summarizing the thiadiazole-containing compounds reported in recent decades, we aim to give a brief introduction to their synthesis and diverse biological activities, such as anti-inflammatory, anticancer, antibacterial, antifungal, antiviral, antiparasitic, anticonvulsant, anticoagulant, antidiabetic, and to show the significant utility of the thiadiazole scaffolds in medicinal chemistry.

No abstract

No abstract

Despite the advances in defining Enterocytozoon bieneusi genotypes worldwide, rare genotypic surveys have been documented on this ubiquitous pathogenic protozoan in mammals in China, especially the role of pigs in zoonotic transmission of microsporidiosis remains unclear. In this study, the distribution of E. bieneusi genotypes in 113 duodenal mucosal specimens of pigs with acute diarrhea from 15 cities in northeast China was determined by PCR and DNA sequence analysis of the ribosomal internal transcribed spacer. The organism was detected in 51 (45.1%) pigs from 12 cities, with infection rates of the nursery pigs (21/33, 63.6%) significantly higher than the preweaned (25/61, 41.0%; P < 0.05) and the growing (5/19, 26.3%; P < 0.01) ones. E. bieneusi belongs to nine known human-pathogenic genotypes (D, EbpA, EbpC, EbpD, H, Henan-I, Henan-III, Henan-IV, and O) and eight new genotypes (CS-1 to CS-8). Genotypes D, EbpA, EbpC, EbpD, Henan-I, Henan-III, and Henan-IV have been found in human infections and D, EbpA, EbpC, and EbpD in wastewater in central China. The new genotypes were genetically clustered into a group of existing E. bieneusi genotypes with zoonotic potential. Considering the discovery of a high prevalence and wide genetic diversity of E. bieneusi zoonotic strains in pigs in northeast China and the co-occurrence of seven known genotypes in pigs and humans and four in pigs and wastewater, pigs probably served as a reservoir for human microsporidiosis and an important source of water contamination in China.

IMPORTANCE Although hospitalizations for injection drug use-associated infective endocarditis (IDU-IE) have increased during the opioid crisis, utilization of and mortality associated with receipt of medication for opioid use disorder (MOUD) after discharge from the hospital among patients with IDU-IE are unknown. OBJECTIVE To assess the proportion of patients receiving MOUD after hospitalization for IDU-IE and the association of MOUD receipt with mortality. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used a population registry with person-level medical claims, prescription monitoring program, mortality, and substance use

We demonstrate an interactive method to create heterogeneous continuous deformable materials on complex three-dimensional meshes. The user specifies displacements and internal elastic forces at a chosen set of mesh vertices. Our system then rapidly solves an optimization problem to compute a corresponding heterogeneous spatial distribution of material properties using the Finite Element Method (FEM) analysis. We apply our method to linear and nonlinear isotropic deformable materials. We demonstrate that solving the problem interactively in the full-dimensional space of individual tetrahedron material values is not practical. Instead, we propose a new model reduction method that projects the material space to a low-dimensional space of material modes. Our model reduction accelerates optimization by two orders of magnitude and makes the convergence much more robust, making it possible to interactively design material distributions on complex meshes. We apply our method to precise control of contact forces and control of pressure over large contact areas between rigid and deformable objects for ergonomics. Our tetrahedron-based dithering method can efficiently convert continuous material distributions into discrete ones and we demonstrate its precision via FEM simulation. We physically display our distributions using haptics, as well as demonstrate how haptics can aid in the material design. The produced heterogeneous material distributions can also be used in computer animation applications.

Open-mouthed, yolk–shell Au@AgPd nanoparticles are successfully produced via galvanic replacement reaction in water at room temperature.