Discovery of ()-3-(3-((2-Cyano-4'-dimethylaminobiphenyl-4-ylmethyl)cyclohexanecarbonylamino)-5-fluorophenyl)acrylic Acid Methyl Ester, an Intestine-Specific, FXR Partial Agonist for the Treatment of Nonalcoholic Steatohepatitis.

A series of fexaramine analogs were synthesized and evaluated to develop an intestine-selective/specific FXR partial agonist. Introduction of both a CN substituent at the C-2 in the biphenyl ring and a fluorine at the C-5 in the aniline ring in fexaramine markedly increased FXR agonistic activity. showed 53 ± 3% maximum efficacy relative to GW4064 in an FXR agonist assay.

Physically Detachable and Operationally Stable Cs SnI Photodetector Arrays Integrated with µ-LEDs for Broadband Flexible Optical Systems.

With the surge in perovskite research, practical features for future applications are desired to be secured, but the reliability of the materials and the use of hazardous Pb are longstanding problems. Here, an air-stable Cs SnI (CSI) is prepared via diluted hydriodic acid solvent-based precursor optimization during scalable hydrothermal growth. Materials characterization is performed using various elemental peak analyses and crystallographic identification.

Combinatorial inhibition of BTK, PI3K-AKT and BRD4-MYC as a strategy for treatment of mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a subtype of non-Hodgkin's lymphoma characterized by poor prognosis. The complexity of MCL pathogenesis arises from aberrant activities of diverse signaling pathways, including BTK, PI3K-AKT-mTOR and MYC-BRD4. Here, we report that MCL-related signaling pathways can be altered by a single small molecule inhibitor, SRX3305.

Control of Peptide Amphiphile Supramolecular Nanostructures by Isosteric Replacements.

Supramolecular nanostructures with tunable properties can have applications in medicine, pharmacy, and biotechnology. In this work, we show that the self-assembly behavior of peptide amphiphiles (PAs) can be effectively tuned by replacing the carboxylic acids exposed to the aqueous media with isosteres, functionalities that share key physical or chemical properties with another chemical group. Transmission electron microscopy, atomic force microscopy, and small-angle X-ray scattering studies indicated that the nanostructure's morphologies are responsive to the ionization states of the side chains, which are related to their p values.

Physical and electrical properties of CuCoSnS nanoparticles synthesized by hydrothermal growth at different reaction time and copper concentration.

Herein, the physical properties such as crystal phase, morphology, and chemical composition for CuCoSnS (CCTS) nanoparticles, synthesized by hydrothermal growth at 200 °C, are studied according to the short reaction times from 1 h to 6 h, respectively. The raw data of chemical composition, XPS analysis, and their electrical properties of CCTS nanoparticles prepared at 200 °C for 12 h with different Cu concentrations are presented [1] in the present manuscript. Materials properties of CCTS and their electrical, optical properties were systematically studied, and their correlation between physical properties and materials properties is strongly studied in depth mode.

Protecting Groups in Peptide Synthesis.

The protection of amino acid reactive functionalities including the α-amino group, the side chain (amines, carboxylic acids, alcohols, and thiols), or the carboxylic acid terminus is an essential strategy in peptide chemistry. This is mandatory to prevent polymerization of the amino acids and to minimize undesirable side reactions during the synthetic process. Proper protecting group manipulation strategies can maximize the yield of the desired product or allow the construction of complex peptide-based structures.

Understanding interactions of Citropin 1.1 analogues with model membranes and their influence on biological activity.

The rapid emergence of resistant bacterial strains has made the search for new antibacterial agents an endeavor of paramount importance. Cationic antimicrobial peptides (AMPs) have the ability to kill resistant pathogens while diminishing the development of resistance. Citropin 1.

Cryoprotective role of organic Zn and Cu supplementation in goats (Capra hircus) diet.

The current study focused on cryopreservation and assessment of characters of post-thaw semen of indigenous Osmanabadi bucks maintained with standard diet, supplemented with different concentrations of organic zinc (Zn), copper (Cu) or in combination, for a period of 180 days. The different doses of organic Zn and Cu were fed per kg DM basis, Zn groups (low: Zn20, medium: Zn40 and high: Zn60), Cu groups: (low: Cu12.5, medium: Cu25 and high: Cu37.

Primary Jejunal Adenocarcinoma Presenting as Bilateral Ovarian Metastasis.

Small intestinal tumors are rare with adenocarcinoma of the small intestine accounting for less than 2% of all gastrointestinal cancers. Primary jejunal adenocarcinoma constitutes a minute portion of small intestine adenocarcinomas. Clinically, this cancer presents at latter stages of its progression, mainly due to vague and non-specific symptoms, and the difficulty encountered in accessing the jejunum on upper endoscopy.

Synthesis, biological evaluation, and metabolic stability of phenazine derivatives as antibacterial agents.

Drug-resistant pathogens are a major cause of hospital- and community-associated bacterial infections in the United States and around the world. These infections are increasingly difficult to treat due to the development of antibiotic resistance and the formation of bacterial biofilms. In the paper, a series of phenazines were synthesized and evaluated for their in vitro antimicrobial activity against Gram positive (methicillin resistant staphylococcus aureus, MRSA) and Gram negative (Escherichia coli, E.

Plummer-Vinson Syndrome with Proximal Esophageal Web.

Plummer-Vinson Syndrome is a condition where iron deficiency is associated with difficulty swallowing due to the presence of an esophageal web. Deficiency of iron-dependent oxidative enzymes causes gradual degradation of the pharyngeal muscles which lead to mucosal atrophy and formation of webs. Although it is a very rare condition, an increased risk of esophageal squamous cell carcinoma makes its identification very important.

Synthesis and biological evaluation of 5-(fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles as inhibitors of transforming growth factor-β type I receptor kinase.

To further optimize a clinical candidate 5 (EW-7197), a series of 5-(3-, 4-, or 5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles 19a-l have been synthesized and evaluated for their TGF-β type I receptor kinase (ALK5) and p38α MAP kinase inhibitory activity in an enzyme assay. The 5-(5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles 19h-l displayed the similar level of potency to that of 5 against both ALK5 (IC50=7.68-13.

Endoscopic closure of persistent gastrocutaneous fistulae, after percutaneous endoscopic gastrostomy (PEG) tube placement, using the over-the-scope-clip system.

Objectives: The Over-The-Scope-Clip (OTSC) has had an evolving role in endoscopic closure of gastrointestinal wall defects, in hemostasis of primary or postinterventional bleeding, and approximation of postbariatric surgery defects. Rapid and effective closure of gastrocutaneous (GC) fistulae using this device has been recently described in the literature. The aim of this study was to evaluate the technical feasibility, efficacy and safety of OTSC as an effective tool in the management of persistent GC fistulae secondary to a complication of percutaneous endoscopic gastrostomy (PEG) tube placement.

Hemostatic powder spray: a new method for managing gastrointestinal bleeding.

Gastrointestinal bleeding is a leading cause of morbidity and mortality in the United States. The management of gastrointestinal bleeding is often challenging, depending on its location and severity. To date, widely accepted hemostatic treatment options include injection of epinephrine and tissue adhesives such as cyanoacrylate, ablative therapy with contact modalities such as thermal coagulation with heater probe and bipolar hemostatic forceps, noncontact modalities such as photodynamic therapy and argon plasma coagulation, and mechanical hemostasis with band ligation, endoscopic hemoclips, and over-the-scope clips.

Importance of reporting segmental bowel preparation scores during colonoscopy in clinical practice.

Aim: To evaluate the impact of reporting bowel preparation using Boston Bowel Preparation Scale (BBPS) in clinical practice.

Methods: The study was a prospective observational cohort study which enrolled subjects reporting for screening colonoscopy. All subjects received a gallon of polyethylene glycol as bowel preparation regimen.

A rare presentation of metastasis of prostate adenocarcinoma to the stomach and rectum.

Prostate cancer is the second most common cause of cancer death in men in the United States. The most common sites of metastasis include the bone, lymph nodes, lung, liver, pleura, and adrenal glands, whereas metastatic prostate cancer involving the gastrointestinal tract has been rarely reported. A 64-year-old African-American man with a history of prostate cancer presented with anemia.

Role of over the scope clips in the management of iatrogenic gastrointestinal perforations.

Advances in endoscopic and surgical techniques have increased the frequency and complexity of these procedures and associated complications such as gastrointestinal perforation. With the advancements in the field of gastroenterology, the promising use of an over the scope clips (OTSC) has fulfilled the unmet need for a reliable endoscopic devise in approximation of gastrointestinal perforation. This novel approach has raised the level of confidence in endoscopist in dealing with this serious complication during endoscopy.

Prescreening with FOBT Improves Yield and Is Cost-Effective in Colorectal Screening in the Elderly.

Background. Utilization of colonoscopy for routine colorectal cancer (CRC) screening in the elderly (patients over 75) is controversial. This study was designed to evaluate if using fecal occult blood test (FOBT) to select patients for colonoscopy can improve yield and be a cost- effective approach for the elderly.

Impact of bowel preparation on surveillance colonoscopy interval.

Background/aims: Atpresent there are no guidelines for colonoscopy surveillance interval in subjects with unsatisfactory bowel preparation. Study was designed to compare outcomes of repeat colonoscopy at different surveillance intervals in patients with unsatisfactory preparation on index exam.

Methods: Ten thousand nine hundred and eight colonoscopies were done during the study period.

Discovery of N-((4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)-1H-imidazol-2-yl)methyl)-2-fluoroaniline (EW-7197): a highly potent, selective, and orally bioavailable inhibitor of TGF-β type I receptor kinase as cancer immunotherapeutic/antifibrotic agent.

A series of 2-substituted-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)-5-(6-methylpyridin-2-yl)imidazoles was synthesized and evaluated to optimize a prototype inhibitor of TGF-β type I receptor kinase (ALK5), 6. Combination of replacement of a quinoxalin-6-yl moiety of 6 with a [1,2,4]triazolo[1,5-a]pyridin-6-yl moiety, insertion of a methyleneamino linker, and a o-F substituent in the phenyl ring markedly increased ALK5 inhibitory activity, kinase selectivity, and oral bioavailability. The 12b (EW-7197) inhibited ALK5 with IC50 value of 0.

Over the scope clip: technique and expanding clinical applications.

Background: Advances in endoscopic and surgical techniques have increased the frequency and complexity of these procedures, and thus, the incidence of associated complications.

Aims: To describe the use and clinical applications of the Over the Scope Clip (OTSC) system.

Methods: An English language literature search was conducted using the key words "endoscopy" and "over the scope clip" in order to identify human studies evaluating the application of OTSC from January 2001 to August 2012.