Activity

It is concluded that using a Cu-10Ni substrate as opposed to a Cu substrate could achieve sufficient metallurgical bonding within shorter processing time. The results have implications for broadening the application temperatures when using Ga as a low-temperature joining material.Drug resistant pathogens are on the rise and new treatments are needed for bacterial infections. Efforts toward antimicrobial discovery typically identify compounds that prevent bacterial growth in microbiological media. However, the microenvironments to which pathogens are exposed during infection differ from rich media and alter the biology of the pathogen. We and others have therefore developed screening platforms that identify compounds that disrupt pathogen growth within cultured mammalian cells. Our platform focuses on Gram-negative bacterial pathogens, which are of particular clinical concern. We screened a panel of 707 drugs to identify those with efficacy against Salmonella enterica Typhimurium growth within macrophages. One of the drugs identified, clofazimine (CFZ), is an antibiotic used to treat mycobacterial infections that is not recognized for potency against Gram-negative bacteria. We demonstrated that in macrophages CFZ enabled the killing of S. Typhimurium at single digit micromolar concentrations, and in mice CFZ reduced tissue colonization. We confirmed that CFZ does not inhibit the growth of S. Typhimurium and E. coli in standard microbiological media. However, CFZ prevents bacterial replication under conditions consistent with the microenvironment of macrophage phagosomes, in which S. Typhimurium resides during infection low pH, low magnesium and phosphate, and the presence of certain cationic antimicrobial peptides. These observations suggest that in macrophages and mice the efficacy of CFZ against S. Typhimurium is facilitated by multiple aspects of soluble innate immunity. Thus, systematic screens of existing drugs for infection-based potency is likely to identify unexpected opportunities for repurposing drugs to treat difficult pathogens.Little is known about the role of the three Jumonji C (JmjC) enzymes in Plasmodium falciparum (Pf). Here we show that JIB-04 and other established inhibitors of mammalian JmjC histone demethylases kill asexual blood stage parasites and are even more potent at blocking gametocyte development and gamete formation. In late stage parasites, JIB-04 increased levels of tri-methylated lysine residues on histones suggesting inhibition of P. falciparum Jumonji demethylase activity. These epigenetic defects coincide with deregulation of invasion, cell motor, and sexual development gene programs, including gene targets coregulated by the PfAP2-I transcription factor and chromatin-binding factor, PfBDP1. Mechanistically, we demonstrate that PfJmj3 converts 2-oxoglutarate to succinate in an iron-dependent manner consistent with mammalian Jumonji enzymes, and this catalytic activity is inhibited by JIB-04 and other Jumonji inhibitors. Our pharmacological studies of Jumonji activity in the malaria parasite provides evidence that inhibition of these enzymatic activities is detrimental to the parasite.For converting the renewable solar energy to hydrogen (H2) energy by photocatalytic (PC) overall water splitting (OWS), visible-light-driven photocatalysts are especially desired. Herein, a model CdS/g-C3N4 photocatalyst with a type II heterojunction is first demonstrated via a facile coupling of g-C3N4 nanosheets and CdS nanorods. After being combined with in situ photodeposited 3 wt % Pt and 4 wt % MnOx dual cocatalysts simultaneously, the optimal visible-light-driven (λ > 400 nm) composite photocatalyst of Pt-CdS/g-C3N4-MnOx gives a H2 generation rate of 9.244 μmol h-1 (924.4 μmol h-1 g-1) and a O2 evolution rate of 4.6 μmol h-1 (460 μmol h-1 g-1) in pure water, which is over 420 times higher than that of pure CdS nanorods loaded with 0.5 wt % Pt. The apparent quantum efficiency (AQE) reaches about 3.389% (at 400 nm) and 1.745% (at 420 nm), respectively. The combination of a type II heterojunction and simultaneous in situ photodeposition of the dual cocatalysts results in a dramatically improved PC efficiency and a long-term stability of the CdS/g-C3N4 visible-light-driven photocatalyst for OWS.Synchronous gastric cancer and adenomatous colorectal polyp in patients with Klebsiella pneumoniae-induced pyogenic liver abscess (KP-PLA) and bacteremia is a rare presentation. A 58-year-old man with a 6-month history of diabetes mellitus (DM) presented with febrile sensation and dull abdominal pain in the right upper quadrant of the abdomen. Subsequent to laboratory test results and abdominal computed tomography findings, KP-PLA with bacteremia was diagnosed. After intravenous antibiotic administration, his symptoms improved, and upper endoscopy and colonoscopy were performed to evaluate the cause of KP-PLA. Biopsy specimens of the prepyloric anterior wall revealed a moderately differentiated adenocarcinoma. Endoscopic mucosal resection of the colon revealed high-grade dysplasia. Early gastric cancer (EGC) and adenomatous colorectal polyps with high-grade dysplasia concomitant with KP-PLA and bacteremia were diagnosed in our patient who had DM. NSC649890 Intravenous antibiotic treatment for KP-PLA, subtotal gastrectomy for EGC, and colonoscopic mucosal resection for the colon polyp were performed. After 25 days of hospitalization, subtotal gastrectomy with adjacent lymph node dissection was performed. Follow-up ultrasound imaging showed resolution of the abscess 5 weeks post-antibiotic treatment, as well as no tumor metastasis. Upper gastrointestinal endoscopy and colonoscopy should be performed to evaluate gastric cancer in patients with PLA or bacteremia, accompanied with DM or an immunocompromised condition.Background Prophylactic central neck dissection (CND) in clinically node-negative (cN0) papillary thyroid carcinoma (PTC) remains controversial. The purpose of this study was to evaluate the benefits of prophylactic ipsilateral CND compared with bilateral CND in total thyroidectomy for cN0 unilateral PTC. Methods We retrospectively enrolled 174 patients who underwent total thyroidectomies with prophylactic CND for cN0 unilateral PTC between January 2009 and May 2010. The prophylactic CND patients were divided into group 1, the ipsilateral CND group (n=74), and group 2, the bilateral CND group (n=100). The incidence of central lymph node metastasis (CLNM) and postoperative complications, such as hypoparathyroidism, recurrent laryngeal nerve injury, and recurrence were assessed. Results CLNM was found in 22 (29.8%) in group 1 and 69 (69%) in group 2. The incidence of postoperative severe hypocalcemia less than 7.0 was also significantly different (six patients [8.1%] in group 1 and 23 [23%] in group 2; p=0.009).