Efficacy of therapeutically administered gepotidacin in a rabbit model of inhalational anthrax.

is a Gram-positive Centers for Disease Control and Prevention category "A" biothreat pathogen. Without early treatment, inhalation of anthrax spores with progression to inhalational anthrax disease is associated with high fatality rates. Gepotidacin is a novel first-in-class triazaacenaphthylene antibiotic that inhibits bacterial DNA replication by a distinct mechanism of action and is being evaluated for use against biothreat and conventional pathogens.

Diagnosing Balamuthia mandrillaris amebic meningoencephalitis in a 64-year-old woman from the Southwest of China.

Balamuthia mandrillaris amebic encephalitis (BAE) can cause a fatal condition if diagnosis is delayed or effective treatment is lacking. Patients with BAE have been previously reported in 12 provinces of China, with skin lesions being the primary symptom and encephalitis developing after several years. However, a significantly lower number of cases has been reported in Southwest China.

Efficacy of Intravenously Administered Gepotidacin in Cynomolgus Macaques following a Francisella tularensis Inhalational Challenge.

Francisella tularensis (F. tularensis) is a Centers for Disease Control (CDC) category "A" Gram-negative biothreat pathogen. Inhalation of F.

Ordered Hierarchical Porous Structure of PtSn/3DOMM-AlO Catalyst for Promoting Propane Non-Oxidative Dehydrogenation.

Herein, the hierarchical porous catalyst of 3-dimensional ordered macro-mesoporous (3DOMM) AlO supported active PtSn nanoparticles (NPs) was prepared by the combined synthesized path of evaporation-induced self-assembly with colloid crystal template (EISA-CCT) methods. The hierarchical macro-mesoporous composite structure can markedly increase the specific surface area, accommodate the diffusion of propene, and decrease the number of surface acid sites. In addition, the special surface property and pore structure of 3DOMM-AlO can modify the interaction between metals and substrates, as well as stabilize the metal nanoparticle, which promotes the formation of a highly active and stable PtSn phase.

A Review of Converter Circuits for Ambient Micro Energy Harvesting.

The Internet of Things (IoT) has a great number of sensor nodes distributed in different environments, and the traditional approach uses batteries to power these nodes: however, the resultant huge cost of battery replacement means that the battery-powered approach is not the optimal solution. Micro energy harvesting offers the possibility of self-powered sensor nodes. This paper provides an overview of energy harvesting technology, and describes the methods for extracting energy from various sources, including photovoltaic, thermoelectric, piezoelectric, and RF; in addition, the characteristics of the four types of energy sources and the applicable circuit structures are summarized.

Gepotidacin is efficacious in a nonhuman primate model of pneumonic plague.

Gepotidacin is a first-in-class triazaacenaphthylene antibacterial agent that selectively inhibits bacterial DNA gyrase and topoisomerase IV through a unique binding mode and has the potential to treat a number of bacterial diseases. Development of this new agent to treat pneumonic plague caused by depends on the U.S.

Association of Systolic and Diastolic Blood Pressure With All-Cause Mortality Among Community-Dwelling Older Adults: A Prospective Observational Study.

Objectives: To assess the association of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with mortality among older adults in Singapore.

Methods: Association of SBP and DBP measured in 2009 for 4443 older adults (69.5±7.

The Vancomycin Resistance-Associated Regulatory System VraSR Modulates Biofilm Formation of Staphylococcus epidermidis in an -Dependent Manner.

The two-component system VraSR responds to the cell wall-active antibiotic stress in Staphylococcus epidermidis. To study its regulatory function in biofilm formation, a deletion mutant (Δ) was constructed using S. epidermidis strain 1457 (SE1457) as the parent strain.

Controlled Delivery of Dutasteride Using Dissolvable Microarrays: Initial Formulation and In Vivo Evaluation.

Dutasteride is prescribed as a once-daily oral capsule for the treatment of symptomatic benign prostatic hyperplasia. As an alternative and patient-focused drug product, this laboratory evaluated the potential to deliver dutasteride in a controlled/sustained manner when formulated as a microarray. The low oral dose, low aqueous solubility, and slow rate of elimination of dutasteride were considered ideal properties which may enable a once-weekly microarray option for patients.

Dexmedetomidine Analgesia Effects in Patients Undergoing Dental Implant Surgery and Its Impact on Postoperative Inflammatory and Oxidative Stress.

The aim of the study was to determine whether or not dexmedetomidine- (DEX-) based intravenous infusion in dental implantation can provide better sedation and postoperative analgesia via suppressing postoperative inflammation and oxidative stress. Sixty patients were randomly assigned to receive either DEX (group D) or midazolam (group M). Recorded variables were vital sign (SBP/HR/RPP/SpO2/RR), visual analogue scale (VAS) pain scores, and observer's assessment of alertness/sedation scale (OAAS) scores.

The Expression, Purification, and Characterization of a Ras Oncogene (Bras2) in Silkworm (Bombyx mori).

The Ras oncogene of silkworm pupae (Bras2) may belong to the Ras superfamily. It shares 77% of its amino acid identity with teratocarcinoma oncogene 21 (TC21) related ras viral oncogene homolog-2 (R-Ras2) and possesses an identical core effector region. The mRNA of Bombyx mori Bras2 has 1412 bp.

A shark liver gene-derived active peptide expressed in the silkworm, Bombyx mori: preliminary studies for oral administration of the recombinant protein.

Active peptide from shark liver (APSL) is a cytokine from Chiloscyllium plagiosum that can stimulate liver regeneration and protects the pancreas. To study the effect of orally administered recombinant APSL (rAPSL) on an animal model of type 2 diabetes mellitus, the APSL gene was cloned, and APSL was expressed in Bombyx mori N cells (BmN cells), silkworm larvae and silkworm pupae using the silkworm baculovirus expression vector system (BEVS). It was demonstrated that rAPSL was able to significantly reduce the blood glucose level in mice with type 2 diabetes induced by streptozotocin.

The cytomorphologic spectrum of small-cell carcinoma and large-cell neuroendocrine carcinoma in body cavity effusions: A study of 68 cases.

Background: Small-cell carcinoma (SCC) and large-cell neuroendocrine carcinoma (LCNEC) are uncommon in serous body cavity effusions. The purpose of this study is to examine the cytomorphological spectrum of SCC and LCNEC in body cavity serous fluids.

Materials And Methods: We have 68 cases from 53 patients who had metastatic SCC or LCNEC diagnoses.

[Alcohol consumption and drug use among middle school students aged 13-15 in 4 cities of China].

Objective: To provide data on alcohol consumption and drug use among middle-school students aged 13-15 in 4 cities of China, and to provide evidence for developing intervention strategies on adolescents alcohol and drug use.

Methods: Standardized sample selection process of two-stage cluster-sampling was used in middle-school students in Beijing, Hangzhou, Wuhan and Urumchi. A self-administered questionnaire survey was conducted in Sept.

Phosphorothioate analogues of alkyl lysophosphatidic acid as LPA3 receptor-selective agonists.

The metabolically stabilized LPA analogue 1-oleoyl-2-O-methyl-rac-glycerophosphorothioate (OMPT) was recently shown to be a potent subtype-selective agonist for LPA3, a G-protein-coupled receptor (GPCR) in the endothelial differentiation gene (EDG) family. Further stabilization was achieved by replacing the sn-1 O-acyl group with an O-alkyl ether. A new synthetic route for the enantiospecific synthesis of the resulting alkyl LPA phosphorothioate analogues is described.

Oxidative activation of thiacetazone by the Mycobacterium tuberculosis flavin monooxygenase EtaA and human FMO1 and FMO3.

Thiacetazone (TAZ) and ethionamide (ETA) are, respectively, thiourea- and thioamide-containing second line antitubercular prodrugs for which there is an extensive clinical history of cross-resistance in Mycobacterium tuberculosis. EtaA, a recently identified flavin-containing monooxygenase (FMO), is responsible for the oxidative activation of ETA in M. tuberculosis.

Lysophosphatidic acid affinity chromatography reveals pyruvate kinase as a specific LPA-binding protein.

Lysophosphatidic acid is a pleiotropic lipid signaling molecule that evokes a broad array of cellular responses including proliferation, tumor cell invasion, neurite retraction, cytoskeletal rearrangements and smooth muscle contraction. Generally, lysophosphatidic acid triggers physiological responses through interaction with specific plasma membrane receptors called LPA 1-4. There is, however, increasing evidence in support of intracellular proteins that interact with LPA.

Structure-activity relationships of fluorinated lysophosphatidic acid analogues.

Lysophosphatidic acid (LPA, 1- or 2-acyl-sn-glycerol 3-phosphate) displays an intriguing cell biology that is mediated via interactions with seven-transmembrane G-protein-coupled receptors (GPCRs) and the nuclear hormone receptor PPARgamma. To identify receptor-selective LPA analogues, we describe a series of fluorinated LPA analogues in which either the sn-1 or sn-2 hydroxyl group was replaced by a fluoro or fluoromethyl substituent. We also describe stabilized phosphonate analogues in which the bridging oxygen of the monophosphate was replaced by an alpha-monofluoromethylene (-CHF-) or alpha-difluoromethylene (-CF(2)-) moiety.

Renal cell carcinoma metastatic to Hurthle cell adenoma of thyroid.

Metastases to the thyroid gland are a common finding at autopsy in patients who died of malignancy and are often misdiagnosed as primary thyroid neoplasms clinically. We present a patient with a rare, unusual case of renal cell carcinoma (RCC) metastatic to a Hurthle cell adenoma of the thyroid. A 53-year-old woman was admitted to a University of Texas Medical Branch Hospital (Galveston, TX) for a large right thyroid mass that was present for 3 months.

Enantioselective responses to a phosphorothioate analogue of lysophosphatidic acid with LPA3 receptor-selective agonist activity.

The metabolically stabilized LPA analogue, 1-oleoyl-2-O-methyl-rac-glycerophosphothioate (OMPT), is a potent agonist for the LPA(3) G-protein-coupled receptor. A new enantiospecific synthesis of both (2R)-OMPT and (2S)-OMPT is described. Calcium release assays in both LPA(3)-transfected insect Sf9 and rat hepatoma Rh7777 cells showed that (2S)-OMPT was 5- to 20-fold more active than (2R)-OMPT.

Synthesis of migration-resistant hydroxyethoxy analogues of lysophosphatidic acid.

[reaction: see text] The susceptibility of lysophosphatidic acid (LPA) to intramolecular acyl migration impedes the determination of specific receptor activation by the sn-1 and sn-2 LPA regioisomers. An efficient enantioselective synthesis of hydroxyethoxy (HE)-substituted analogues of sn-1-acyl and 2-acyl LPA derivatives that possess palmitoyl and oleoyl chains is described. While the palmitoyl derivatives fail to activate calcium release in cells transfected with LPA(2) or LPA(3) G-protein-coupled receptors, the LPA(3) receptor is activated by both 1-HE and 2-HE oleoyl LPA analogues with a potency 10-fold lower than that of the parent oleoyl LPA.

Synthesis of monofluorinated analogues of lysophosphatidic acid.

Lysophosphatidic acid (LPA, 1- or 2-acyl-sn-glycerol 3-phosphate) displays an intriguing cell biology that is mediated via interactions both with G-protein coupled seven transmembrane receptors and with the nuclear hormone receptor PPARgamma. Synthesis and biological activities of fluorinated analogues of LPA are still relatively unknown. In an effort to identify receptor-selective LPA analogues and to document in detail the structure-activity relationships of fluorinated LPA isosteres, we describe a series of monofluorinated LPA analogues in which either the sn-1 or the sn-2 hydroxy group was replaced by fluorine, or the bridging oxygen in the monophosphate was replaced by an alpha-monofluoromethylene (-CHF-) moiety.

Synthesis of alpha-fluorinated phosphonates from alpha-fluorovinylphosphonates: a new route to analogues of lysophosphatidic acid.

A versatile, efficient method for the preparation of alpha-monofluoromethylene (-CHF-) phosphonates from alpha-fluorovinylphosphonate provides access to a class of lysophosphatidic acid (LPA) receptor-subtype agonists. In addition, sn-2 O-methylation of alpha-monofluoromethylene phosphonates using trimethylsilyldiazomethane generated sn-1-acyl, 2-O-methyl alpha-monofluoromethylene derivatives. Finally, a novel method for the selective etherification of 1,2-diols was developed and a new class of sn-1 O-methyl, 2-acyl alpha-monofluoromethylene LPA analogues was prepared.

Congenital transcobalamin II deficiency due to errors in RNA editing.

Transcobalamin II (TCII) is a plasma protein essential for the transport and cellular uptake of vitamin B12 (B12; cobalamin, Cbl). Congenital deficiency of functional TCII is an autosomal recessive genetic disorder that results in clinical B12 deficiency usually within several months following birth. In this report, we describe the molecular basis for TCII deficiency in two patients who developed a megaloblastic anemia in early infancy.