Mouse pulmonary response following solid surface composite dust inhalation.

: Pulmonary exposure to emissions from manipulating solid surface composite (SSC) materials has been associated with adverse health effects in humans and laboratory animals. Previous and investigations of SSC toxicity have been limited by particle delivery methods that do not fully recapitulate the workplace environment. This study sought to determine the acute SSC-induced pulmonary responses whole-body inhalation exposure.

Characteristics of exopolysaccharides produced by isolates from natural bioflocculant of conglutination mud.

Three novel types of exopolysaccharides (EPS) EPS-S8, EPS-S5, and EPS-F10 were extracted and purified from bacterial isolates sp. GHS8, sp. GHS5 and sp.

Mutational and splicing landscape in a cohort of 43,000 patients tested for hereditary cancer.

DNA germline genetic testing can identify individuals with cancer susceptibility. However, DNA sequencing alone is limited in its detection and classification of mRNA splicing variants, particularly those located far from coding sequences. Here we address the limitations of splicing variant identification and interpretation by pairing DNA and RNA sequencing and describe the mutational and splicing landscape in a clinical cohort of 43,524 individuals undergoing genetic testing for hereditary cancer predisposition.

Simplified Machine Learning Models Can Accurately Identify High-Need High-Cost Patients With Inflammatory Bowel Disease.

Introduction: Hospitalization is the primary driver of inflammatory bowel disease (IBD)-related healthcare costs and morbidity. Traditional prediction models have poor performance at identifying patients at highest risk of unplanned healthcare utilization. Identification of patients who are high-need and high-cost (HNHC) could reduce unplanned healthcare utilization and healthcare costs.

Effect of Novel Biotherapeutic Elevating Angiopoietin 1 on Progression of Diabetic Nephropathy in Diabetic/Obese Mice.

Diabetic nephropathy is a leading cause of end-stage renal disease, characterized by endothelial dysfunction and a compromised glomerular permeability barrier. Dysregulation of the angiopoietin 1 (ANGPT1)/angiopoietin 2 (ANGPT2) signaling axis is implicated in disease progression. We recently described the discovery of an IgG antibody, O010, with therapeutic potential to elevate circulating endogenous ANGPT1, a tyrosine kinase with Ig and epidermal growth factor (EGF) homology domains-2 (TIE2) agonist.

Embedding of Functionalized Coordination Cages and a Molecular Knot in a Polymeric Membrane for Potentiometric Sensing of Environmentally Important Oxyanions and Halides.

Three kinds of coordination cages and a molecular knot with inductively activated P-H, N-H, or C-H hydrogen bond donors anchoring in the functionalized cavities were inspected as ionophores to develop polymeric membrane ISEs for potentiometric sensing of environmentally important oxyanions and halides. The proposed ISEs displayed significant preference for perrhenate, phosphate, or chloride with a selectivity pattern distinctively different from the sequence depending on the Gibbs free energy of hydration owing to the high degree of shape, charge, and size selectivity originating from the rigidity and complementarity of the binding cavities. To gain further insight into the response characters of the proposed ISEs, the binding constants of ionophore-anion complexes in the membrane phase were investigated, and the binding affinity, together with the Hofmeister series, correlates well with the determined selectivity pattern of the proposed ISEs.

MiR-1266 suppresses the growth and metastasis of prostate cancer via targeting PRMT5.

The article "MiR-1266 suppresses the growth and metastasis of prostate cancer via targeting PRMT5, by C.-M. Sun, G.

Circular RNA hsa_circ_0017247 acts as an oncogene in bladder cancer by inducing Wnt/β-catenin signaling pathway.

The article "Circular RNA hsa_circ_0017247 acts as an oncogene in bladder cancer by inducing Wnt/β-catenin signaling pathway, by C.-T. Han, Q.

Hydroxy acids for adhesion to enamel and dentin: Long-term bonding performance and effect on dentin biostability.

Objectives: To test the demineralization potential, bonding performance, and dentin biostability when using hydroxy acids for etching enamel and dentin.

Methods: Surface microhardness, roughness and depth of demineralization were investigated after etching enamel and dentin with 35 % glycolic acid (Gly), tartaric acid (Ta), gluconic acid (Glu), gluconolactone (Gln), or phosphoric acid (Pa) (n = 5/group). Dentin microtensile bond strength (μTBS) after 24 h or 1 year of bonding (n = 8 teeth/group) and enamel shear bond strength (SBS) after 24 h (n = 10 teeth/group) were obtained.

Crystal structures, thermal stabilities, and dissolution behaviours of tinidazole and the tinidazole-vanillic acid cocrystal: insights from energy frameworks.

The crystal structures of the antimicrobial drug tinidazole [TNZ; systematic name: 1-(2-ethylsulfonylethyl)-2-methyl-5-nitroimidazole, CHNOS] and the 1:1 cocrystal of TNZ with the naturally occurring compound vanillic acid (VA; systematic name: 4-hydroxy-3-methoxybenzoic acid, CHO), namely, the TNZ-VA cocrystal, were determined by single-crystal X-ray analysis at 100 K. The supramolecular structure of the TNZ-VA cocrystal is composed of a carboxylic acid dimer and an O-H..

Electrocatalytic Intermolecular C(sp)-H/N-H Coupling of Methyl N-Heteroaromatics with Amines and Amino Acids: Access to Imidazo-Fused N-Heterocycles.

An efficient NHI-mediated intermolecular annulation of methyl N-heteroaromatics with amines/amino acids was developed by virtue of anodic oxidation, providing a variety of functionalized imidazo-fused N-heterocycles with good to excellent yields. The practicality of this protocol was demonstrated by the readily available starting materials, broad substrate scope, water tolerance, scalability, and the diverse transformations of the electrolysis product.

Electrocatalytic C-H/N-H Coupling of 2'-Aminoacetophenones for the Synthesis of Isatins.

2'-Aminoacetophenones undergo a C(sp)-H oxidation followed by intramolecular C-N bond formation by virtue of a simple electrochemical oxidation in the presence of n-BuNI, providing various isatins with moderate to good yields. The reaction intermediates were detected, and a radical-based pathway was proposed.

Using brain organoids to understand Zika virus-induced microcephaly.

Technologies to differentiate human pluripotent stem cells into three-dimensional organized structures that resemble organs are pushing the frontiers of human disease modeling and drug development. In response to the global health emergency posed by the Zika virus (ZIKV) outbreak, brain organoids engineered to mimic the developing human fetal brain have been employed to model ZIKV-induced microcephaly. Here, we discuss the advantages of brain organoids over other model systems to study development and highlight recent advances in understanding ZIKV pathophysiology and its underlying pathogenesis mechanisms.

Melittin induces human gastric cancer cell apoptosis via activation of mitochondrial pathway.

Aim: To investigate the apoptotic effects of melittin on SGC-7901 cells via activation of the mitochondrial signaling pathway in vitro.

Methods: SGC-7901 cells were stimulated by melittin, and its effect on proliferation and apoptosis of was investigated by methyl thiazolyl tetrazolium assay, morphologic structure with transmission electron microscopy, annexin-V/propidium iodide double-staining assay, measuring mitochondrial membrane potential (MMP) levels, and analyzing reactive oxygen species (ROS) concentrations were analyzed by flow cytometry. Cytochrome C (Cyt C), apoptosis-inducing factor (AIF), endonuclease G (Endo G), second mitochondria-derived activator of caspases (Smac)/direct IAP binding protein with low isoelectric point (Diablo), and FAS were analyzed by western blot.

New primary mechanisms for the synthesis of rare 9Be in early supernovae.

We present two new primary mechanisms for the synthesis of the rare nucleus (9)Be, both triggered by ν-induced production of (3)H followed by (4)He((3)H,γ)(7)Li in the He shells of core-collapse supernovae. For progenitors of ∼ 8M(⊙), (7)Li((3)H,n(0))(9)Be occurs during the rapid expansion of the shocked He shell. Alternatively, for ultra-metal-poor progenitors of ∼ 11-15 M(⊙), (7)Li(n,γ)(8)Li(n,γ)(9)Li(e(-)ν(e))(9)Be occurs with neutrons produced by (4)He(ν(e),e(+)n)(3)H, assuming a hard effective ν(e) spectrum from oscillations (which also leads to heavy element production through rapid neutron capture) and a weak explosion (so the (9)Be survives shock passage).

High levels of inflammation and insulin resistance in obstructive sleep apnea patients with hypertension.

Hypertension induced by obstructive sleep apnea (OSA) may be multifactorial in origin, and systemic inflammation is one of the major factors. However, OSA patients do not always have the identical probability with hypertension even in patients with the same history and degree of OSA. The aim of this study was to compare the levels of inflammation and insulin resistance in two groups of patients who had the same degree as well as the same long history of OSA, but with/without hypertension.

Theoretical studies on pyrimidine substituent derivatives as dual inhibitors of AP-1 and NF-kappaB.

Theoretical studies on the three-dimensional (3D) quantitative structure-activity relationship (QSAR) and mechanisms of action of a series of pyrimidine substituent derivatives as dual inhibitors of AP-1 and NF-kappaB were carried out using comparative molecular field analysis (CoMFA) and docking methods. The established 3D-QSAR model exhibits a satisfying statistical quality and prediction ability. Docking results show somewhat lower average values of the flexible and rigid energy scores in the chosen binding sites.

Hypothermic protection of the ischemic heart via alterations in apoptotic pathways as assessed by gene array analysis.

Hypothermia improves resistance to ischemia in the cardioplegia-arrested heart. This adaptive process produces changes in specific signaling pathways for mitochondrial proteins and heat-shock response. To further test for hypothermic modulation of other signaling pathways such as apoptosis, we used various molecular techniques, including cDNA arrays.

Dissociation of heat shock proteins expression with ischemic tolerance by whole body hyperthermia in rat heart.

Heat shock (HS) results in the expression of heat shock proteins (hsp) and confers tolerance against subsequent ischemic injury. We examined the extent of myocardial protection in vivo, and determined the level of hsp expression induced by HS as a function of time. Anesthetized rats were subjected to HS by raising core temperature to 42 degrees C for 15 min and they were then allowed to recover from 2 to 30 h (n = 8-11 for each time point).

Both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for inhibition of oncogenic K-Ras prenylation but each alone is sufficient to suppress human tumor growth in nude mouse xenografts.

The ability of Ras oncoproteins to cause malignant transformation requires their post-translational modifications by prenyl groups. Because K-Ras can be both farnesylated and geranylgeranylated it is not known whether both farnesyltransferase and geranylgeranyltransferase I inhibitors are required for suppressing human tumor growth in whole animals. In this paper we report that oncogenic Ras processing, MAP kinase activation and growth in nude mice are inhibited by the farnesyltransferase inhibitor FTI-276 in H- and N-Ras transformed NIH3T3 cells; whereas in KB-Ras transformed NIH3T3 cells both FTI-276 and the geranylgeranyltransferase I inhibitor GGTI-297 are required for inhibition.

The role of CD11b/CD18 mediated neutrophil adhesion in complement deficient xenograft recipients.

Hyperacute rejection (HAR) of discordant xenografts is dependent on local complement activation. The formation of a functional complex of the complement components C5b-9 (membrane attack complex, MAC) causes endothelial injury and activation leading to coagulation and inflammation. In PVG rats which selectively lack the C6 component of complement, the MAC complex is not formed, whereas early split products of the complement cascade are produced normally.

Inhibition of the prenylation of K-Ras, but not H- or N-Ras, is highly resistant to CAAX peptidomimetics and requires both a farnesyltransferase and a geranylgeranyltransferase I inhibitor in human tumor cell lines.

The farnesyltransferase (FTase) inhibitor FTI-277 is highly effective at blocking oncogenic H-Ras but not K-Ras4B processing and signaling. While inhibition of processing and signaling of oncogenic K-Ras4B is more sensitive to the geranylgeranyltransferase I (GGTase I) inhibitor GGTI-286 than it is to FTI-277 in K-Ras4B-transformed NIH3T3 cells, the sensitivity of K-Ras as well as H- and N-Ras to the CAAX peptidomimetics in human tumor cell lines is not known. Here, we report that a panel of five human carcinoma cell lines from pancreatic, pulmonary, and bladder origins all express H-, N-, and K-Ras, and their respective prenylation sensitivities to the FTase and GGTase I inhibitors is variable.