ACBD3 is up-regulated in gastric cancer and promotes cell cycle G1-to-S transition in an AKT-dependent manner.

It has been reported that ACBD3 is closely related to the malignant process of cells, but its role in gastric cancer has not been elucidated. This study aims to investigate the expression and function of ACBD3 in human gastric cancer. The Cancer Genome Atlas (TCGA) database were selected to analyze mRNA levels of ACBD3 in gastric cancer tissues and normal gastric epithelial tissues. qPCR and Western blot were conducted to detect the expression of ACBD3 in two normal gastric epithelial cell lines and five gastric cancer cell lines which were cultured in our laboratory. To exclude differences in individual background between different patients, we further detected the expression of ACBD3 in 8 pairs of malignant/non-malignant clinical gastric tissues. Through the establishment of stable cells, in vitro cell experiments and in vivo xenotransplantation models in mice, the role of ACBD3 in the proliferation of gastric cancer cells has been further explored. AKT inhibitors were used to deeply explore the molecular regulation mechanism of ACBD3. The results showed that the elevated ACBD3 in gastric cancer tissue were positively correlated with the clinical grade and prognosis of gastric cancer. In terms of molecular function, we found that ACBD3 can enhance the production and growth of gastric cancer cells. At the same time, the activation of AKT kinase played an important role in ACBD3's promotion of G1-to-S transition. The experiments generally indicate that ACBD3 is expected to become a potential diagnostic molecule or therapeutic target for gastric cancer.

Development and validation of a clinical risk model to predict the hospital mortality in ventilated patients with acute respiratory distress syndrome: a population-based study.

BACKGROUND: Large variability in mortality exists in patients of acute respiratory distress syndrome (ARDS), especially those with invasive ventilation. The aim of this study was to develop a model to predict risk of in-hospital death in ventilated ARDS patients. METHODS: Ventilated patients with ARDS from two public databases (MIMIC-III and eICU-CRD) were randomly divided as training cohort and internal validation cohort. Least absolute shrinkage and selection operator (LASSO) and then Logistic regression was used to construct a predictive model with demographic, clinical, laboratory, comorbidities and ventilation variables ascertained at first 24 h of ICU admission and invasive ventilation. Our model was externally validated using data from another database (MIMIC-IV). RESULTS: A total of 1075 adult patients from MIMIC-III and eICU were randomly divided into training cohort (70%, n = 752) and internal validation cohort (30%, n = 323). 521 patients were included from MIMIC-IV. From 176 potential predictors, 9 independent predictive factors were included in the final model. Five variables were ascertained within the first 24 h of ICU admission, including age (OR, 1.02; 95% CI: 1.01-1.03), mean of respiratory rate (OR, 1.04; 95% CI: 1.01-1.08), the maximum of INR (OR, 1.14; 95% CI: 1.03-1.31) and alveolo-arterial oxygen difference (OR, 1.002; 95% CI: 1.001-1.003) and the minimum of RDW (OR, 1.17; 95% CI: 1.09-1.27). And four variables were collected within the first 24 h of invasive ventilation: mean of temperature (OR, 0.70; 95% CI: 0.57-0.86), the maximum of lactate (OR, 1.15; 95% CI: 1.09-1.22), the minimum of blood urea nitrogen (OR, 1.02; 95% CI: 1.01-1.03) and white blood cell counts (OR, 1.03; 95% CI: 1.01-1.06). Our model achieved good discrimination (AUC: 0.77, 95% CI: 0.73-0.80) in training cohort but the performance declined in internal (AUC: 0.75, 95% CI: 0.69-0.80) and external validation cohort (0.70, 95% CI: 0.65-0.74) and showed modest calibration. CONCLUSIONS: A risk score based on routinely collected variables at the start of admission to ICU and invasive ventilation can predict mortality of ventilated ARDS patients, with a moderate performance.

Transition-metal catalyzed oxidative spirocyclization of N-aryl alkynamides with methylarenes under microwave irradiation.

A practical synthetic route to construct a variety of 3-benzyl spiro[4,5]trienones was developed via transition-metal Cu/Ag-catalyzed oxidative ipso-annulation of activated alkynes with unactivated toluenes using TBPB as an oxidant under microwave irradiation. This method allows the formation of two carbon-carbon bonds and one carbon-oxygen bond in a single reaction through a sequence of C-H oxidative coupling, ipso-carbocyclization and dearomatization. The advantages of this protocol are its operational simplicity and broad substrate scope, and the ability to afford the desired products in moderate to good yields.

Silver-catalyzed direct C-H oxidative carbamoylation of quinolines with oxamic acids.

A silver-catalyzed efficient and direct C-H carbamoylation of quinolines with oxamic acids to access carbamoylated quinolines has been developed through oxidative decarboxylation reaction. The reaction proceeds smoothly over a broad range of substrates with excellent functional group tolerance and excellent yields under mild conditions.

Tunable dielectric polarization and breakdown behavior for high energy storage capability in P(VDF-TrFE-CFE)/PVDF polymer blended composite films.

Polymer dielectrics with high dielectric performances and superior discharge energy capability are highly desirable for advanced electrostatic capacitor applications. However, the paradoxical relationship between dielectric polarization and electric breakdown behavior generally hinder their further enhancement in energy storage performances. Herein, polymer blended composite films with high energy storage capability were successfully fabricated by blending together poly(vinylidene fluoride) (PVDF) polymer and poly(vinylidene fluoride-trifluoroethylene-chlorofluoroethylene) (P(VDF-TrFE-CFE)) terpolymer. The P(VDF-TrFE-CFE) terpolymer has a high dielectric constant to provide a large electric displacement under an applied electric field far below its breakdown field, which is anticipated to modulate the dielectric polarization behavior of PVDF polymer when blended in different proportions. Consequently, the polymer blended composite film consisting of 20 wt% (P(VDF-TrFE-CFE)) terpolymer exhibits a high discharge energy density of 13.63 J cm-3 at an enhanced breakdown strength of 480 MV m-1. This obtained high discharge energy density is 84% higher than the pure PVDF film and 582% higher than a commercialized biaxially oriented polypropylene (BOPP). Large interfacial polarization and strong interaction of polymer chains between the PVDF polymer and P(VDF-TrFE-CFE) terpolymer may contribute to the tunable dielectric constant and electric breakdown strength, thus promoting the energy storage capability. This work establishes a facile, but effective approach to achieve the high energy storage capability of PVDF polymer-based flexible composite films for capacitive energy storage applications.

Fluorination-triggered tandem cyclization of styrene-type carboxylic acids to access 3-aryl isocoumarin derivatives under microwave irradiation.

A practical and straightforward synthetic route through a fluorination-triggered tandem cyclization of styrene-type carboxylic acids was developed to construct a variety of 4-fluoro-3-aryl-3,4-dihydroisocoumarins and 3-arylisocoumarins under microwave irradiation. This novel protocol features mild reaction conditions and operational simplicity, with good yields.

Palladium-catalyzed oxidative amidation of quinoxalin-2(1H)-ones with acetonitrile: a highly efficient strategy toward 3-amidated quinoxalin-2(1H)-ones.

A novel and convenient palladium-catalyzed direct oxidative amidation of quinoxalin-2(1H)-ones with acetonitrile was developed to synthesize 3-amidated quinoxalin-2(1H)-ones. A series of 3-acetamino quinoxalin-2(1H)-one derivatives were constructed with good to excellent yields. This methodology provided a practical approach to various 3-acetamino quinoxalin-2(1H)-ones from the readily available starting material acetonitrile.

Transition-metal free C3-amidation of quinoxalin-2(1H)-ones using Selectfluor as a mild oxidant.

A practical and efficient synthetic route to construct a variety of 3-amidated quinoxalin-2(1H)-ones was developed via transition-metal free direct oxidative amidation of quinoxalin-2(1H)-ones with amidates using Selectfluor reagent as a mild oxidant. This protocol features mild reaction conditions, operational simplicity, broad substrate scope, and good to excellent yields.

Room Temperature Chemoselective Deoxygenation of Aromatic Ketones and Aldehydes Promoted by a Tandem Pd/TiO2 + FeCl3 Catalyst.

A rapid and practical protocol for the chemoselective deoxygenation of various aromatic ketones and aldehydes was described, which used a tandem catalyst composed of heterogeneous Pd/TiO2 + homogeneous FeCl3 with the green hydrogen source, polymethylhydrosiloxane (PMHS). The developed catalytic system was robust and scalable, as exemplified by the deoxygenation of acetophenone, which was performed on a gram scale in an atmospheric environment utilizing only 0.4 mol % Pd/TiO2 + 10 mol % FeCl3 catalyst to give the corresponding ethylbenzene in 96% yield within 10 min at room temperature. Furthermore, the Pd/TiO2 catalyst was shown to be recyclable up to three times without an observable decrease in efficiency and it exhibited low metal leaching under the reaction conditions. Insights toward the reaction mechanism of Pd-catalyzed reductive deoxygenation for aromatic ketones and aldehydes were investigated through operando IR, NMR, and GC-MS techniques.

Metal-free oxidative coupling of quinoxalin-2(1H)-ones with arylaldehydes leading to 3-acylated quinoxalin-2(1H)-ones.

A facile TBHP-mediated direct oxidative coupling of quinoxalin-2(1H)-ones with arylaldehydes has been developed under metal-free conditions. This method provided a convenient and efficient approach to various 3-acylated quinoxalin-2(1H)-ones from readily available starting materials with excellent regioselectivity. This reaction proceeded efficiently under mild conditions over a broad range of substrates and with functional group tolerance.

Cytomegalovirus infection and outcome in immunocompetent patients in the intensive care unit: a systematic review and meta-analysis.

BACKGROUND: Cytomegalovirus (CMV) infection is common in immunocompetent patients in intensive care units (ICUs). However, whether CMV infection or CMV reactivation contributes to mortality of immunocompetent patients remains unclear. METHODS: A literature search was conducted for relevant studies published before May 30, 2016. Studies reporting on CMV infection in immunocompetent patients in ICUs and containing 2 × 2 tables on CMV results and all-cause mortality were included. RESULTS: Eighteen studies involving 2398 immunocompetent patients admitted to ICUs were included in the meta-analysis. The overall rate of CMV infection was 27% (95%CI 22-34%, I2 = 89%, n = 2398) and the CMV reactivation was 31% (95%CI 24-39%, I2 = 74%, n = 666). The odds ratio (OR) for all-cause mortality among patients with CMV infection, compared with those without infection, was 2.16 (95%CI 1.70-2.74, I2 = 10%, n = 2239). Moreover, upon exclusion of studies in which antiviral treatment was possibly or definitely provided to some patients, the association of mortality rate with CMV infection was also statistically significant (OR: 1.69, 95%CI 1.01-2.83, I2 = 37%, n = 912,). For CMV seropositive patients, the OR for mortality in patients with CMV reactivation as compared with patients without CMV reactivation was 1.72 (95%CI 1.04-2.85, I2 = 29%, n = 664). Patients with CMV infection required significantly longer mechanical ventilation (mean difference (MD): 9 days (95% CI 5-14, I2 = 81%, n = 875)) and longer duration of ICU stay (MD: 12 days (95% CI 7-17, I2 = 70%, n = 949)) than patients without CMV infection. When analysis was limited to detection in blood, CMV infection without antiviral drug treatment or reactivation was not significantly associated with higher mortality (OR: 1.69, 95%CI 0.81-3.54, I2 = 52%, n = 722; OR: 1.49, I2 = 63%, n = 469). CONCLUSION: Critically ill patients without immunosuppression admitted to ICUs show a high rate of CMV infection. CMV infection during the natural unaltered course or reactivation in critically ill patients is associated with increased mortality, but have no effect on mortality when CMV in blood. More studies are needed to clarify the impact of CMV infection on clinical outcomes in those patients.

MicroRNA-19b Mediates Lung Epithelial-Mesenchymal Transition via Phosphatidylinositol-3,4,5-Trisphosphate 3-Phosphatase in Response to Mechanical Stretch.

Lung epithelial-mesenchymal transition (EMT) plays an important role in ventilation-associated lung fibrosis, which may contribute to the poor outcome of patients with acute respiratory distress syndrome. Because microRNAs control and modulate normal physiological and pathophysiological processes, we investigated the role of microRNAs in the development of acute respiratory distress syndrome-associated EMT in response to mechanical stress. In the current study, primary human alveolar epithelial type II (AEII) cells were subjected to cyclic stretch that resulted in EMT profiles with decreased gene expression of cytokeratin-8, E-cadherin, and surfactant protein B, and increased expression of vimentin, α-smooth muscle actin, and N-cadherin. Microarray analysis revealed that the expression of microRNA-19b (miR-19b) was up-regulated in the AEII cells, and real-time polymerase chain reaction showed that the expression of miR-19b increased in both the AEII cells and the primary human small-airway epithelial cells. Overexpression of miR-19b in small-airway epithelial cells promoted the mechanical stretch-induced EMT phenotypes, whereas inhibition of miR-19b attenuated it. The inhibitory effect of miR-19b was attributed to enhanced signaling of phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase (PTEN), leading to inactivation of the AKT pathway. Restoration of PTEN expression or inhibition of AKT phosphorylation suppressed the mechanical stretch-induced EMT phenotypes. We further demonstrated that the mechanical stretch-induced miR19 expression was regulated by the focal adhesion kinase-Rho pathway. In conclusion, we found that miR-19b plays a key role in the development of the EMT phenotype through down-regulation of PTEN in human lung epithelial cells in response to mechanical stretch. The miR-19b-PTEN signaling pathway may serve as a novel therapeutic target in the context of ventilator-associated lung fibrosis.

Mechanical Stress and the Induction of Lung Fibrosis via the Midkine Signaling Pathway.

RATIONALE: Lung-protective ventilatory strategies have been widely used in patients with acute respiratory distress syndrome (ARDS), but the ARDS mortality rate remains unacceptably high and there is no proven pharmacologic therapy. OBJECTIVES: Mechanical ventilation can induce oxidative stress and lung fibrosis, which may contribute to high dependency on ventilator support and increased ARDS mortality. We hypothesized that the novel cytokine, midkine (MK), which can be up-regulated in oxidative stress, plays a key role in the pathogenesis of ARDS-associated lung fibrosis. METHODS: Blood samples were collected from 17 patients with ARDS and 10 healthy donors. Human lung epithelial cells were challenged with hydrogen chloride followed by mechanical stretch for 72 hours. Wild-type and MK gene-deficient (MK(-/-)) mice received two-hit injury of acid aspiration and mechanical ventilation, and were monitored for 14 days. MEASUREMENTS AND MAIN RESULTS: Plasma concentrations of MK were higher in patients with ARDS than in healthy volunteers. Exposure to mechanical stretch of lung epithelial cells led to an epithelial-mesenchymal transition profile associated with increased expression of angiotensin-converting enzyme, which was attenuated by silencing MK, its receptor Notch2, or NADP reduced oxidase 1. An increase in collagen deposition and hydroxyproline level and a decrease in lung tissue compliance seen in wild-type mice were largely attenuated in MK(-/-) mice. CONCLUSIONS: Mechanical stretch can induce an epithelial-mesenchymal transition phenotype mediated by the MK-Notch2-angiotensin-converting enzyme signaling pathway, contributing to lung remodeling. The MK pathway is a potential therapeutic target in the context of ARDS-associated lung fibrosis.

Silver catalysed decarboxylative alkylation and acylation of pyrimidines in aqueous media.

Decarboxylative alkylation or acylation reactions of simple pyrimidines have been developed in aqueous media. Using aliphatic carboxylic acids or 2-oxocarboxylic acids and pyrimidines as substrates and silver as the catalyst, the 4-substituted alkyl or acyl pyrimidines were isolated in moderate to good yields.

A gloves-associated outbreak of imipenem-resistant Acinetobacter baumannii in an intensive care unit in Guangdong, China.

BACKGROUND: Imipenem-resistant Acinetobacter baumannii (IRAB) is an important cause of hospital-acquired infection. We aimed to describe an outbreak of IRAB infection and to investigate its possible source in an intensive care unit. METHODS: An environmental investigation was undertaken. Antimicrobial susceptibility testing was performed by microdilution. These isolates were genotyped by use of repetitive extragenic palindromic polymerase chain reaction (rep-PCR; DiversiLab). The study included 11 patients infected with IRAB and 14 control patients free of IRAB. Case and control patients were compared for possible predisposing factors. A multifaceted intervention was implemented to control the outbreak. RESULTS: Thirty-nine IRABs were isolated from patients and the environmental surveillance culture in August, November, and December 2011. All isolates were resistant to imipenem. The IRAB strains belonged to seven clones (A-G) by the use of rep-PCR. There were four epidemic clones (D-G) in the outbreak, and Clone D was predominant. For the case-control study, patients with chronic obstructive pulmonary disease were susceptible to infection with IRAB. The hospital mortality of the case group was significantly higher than that of the control group. CONCLUSIONS: The outbreak strains were transmitted among infected patients and equipment by inappropriate use of gloves. A combination of aggressive infection control measures is essential for preventing recurrent nosocomial outbreaks of IRAB.

Sepsis and ARDS: The Dark Side of Histones.

Despite advances in management over the last several decades, sepsis and acute respiratory distress syndrome (ARDS) still remain major clinical challenges and the leading causes of death for patients in intensive care units (ICUs) due to insufficient understanding of the pathophysiological mechanisms of these diseases. However, recent studies have shown that histones, also known as chromatin-basic structure proteins, could be released into the extracellular space during severe stress and physical challenges to the body (e.g., sepsis and ARDS). Due to their cytotoxic and proinflammatory effects, extracellular histones can lead to excessive and overwhelming cell damage and death, thus contributing to the pathogenesis of both sepsis and ARDS. In addition, antihistone-based treatments (e.g., neutralizing antibodies, activated protein C, and heparin) have shown protective effects and have significantly improved the outcomes of mice suffering from sepsis and ARDS. Here, we review researches related to the pathological role of histone in context of sepsis and ARDS and evaluate the potential value of histones as biomarkers and therapeutic targets of these diseases.

Silver-catalyzed radical tandem cyclization: an approach to direct synthesis of 3-acyl-4-arylquinolin-2(1H)-ones.

A silver-catalyzed efficient and practical synthesis of 3-acyl-4-arylquinolin-2(1H)-ones or 3-acyl-4-aryldihydroquinolin-2(1H)-ones through intermolecular radical addition/cyclization in aqueous solution is reported. This method provides a novel, highly efficient, and straightforward route to substituted quinolin-2-ones or 3,4-dihydroquinolin-2-ones in one step. A possible mechanism for the formation of quinolin-2-ones is proposed.

Proteomic analysis of lung tissue in a rat acute lung injury model: identification of PRDX1 as a promoter of inflammation.

Acute respiratory distress syndrome (ARDS) remains a high morbidity and mortality disease entity in critically ill patients, despite decades of numerous investigations into its pathogenesis. To obtain global protein expression changes in acute lung injury (ALI) lung tissues, we employed a high-throughput proteomics method to identify key components which may be involved in the pathogenesis of ALI. In the present study, we analyzed lung tissue proteomes of Pseudomonas aeruginosa-induced ALI rats and identified eighteen proteins whose expression levels changed more than twofold as compared to normal controls. In particular, we found that PRDX1 expression in culture medium was elevated by a lipopolysaccharide (LPS) challenge in airway epithelial cells in vitro. Furthermore, overexpression of PRDX1 increased the expression of proinflammatory cytokines interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α), whereas knockdown of PRDX1 led to downregulated expression of cytokines induced by LPS. In conclusion, our findings provide a global alteration in the proteome of lung tissues in the ALI rat model and indicate that PRDX1 may play a critical role in the pathogenesis of ARDS by promoting inflammation and represent a novel strategy for the development of new therapies against ALI.

2-[2-(2-Nitro-phen-yl)-4,5-diphenyl-1H-imidazol-1-yl]-3-phenyl-propan-1-ol.

In the title compound, C30H25N3O3, the central imidazole ring forms dihedral angles of 77.34 (6), 12.56 (6) and 87.04 (6)°, respectively, with the o-nitro-benzene ring and the phenyl substituents in the 5- and 4-positions. The mol-ecular conformation is stabilized by weak intra-molecular C-H⋯π inter-actions. In the crystal, mol-ecules are linked by O-H⋯N hydrogen bonds, forming chains running parallel to the b-axis direction.

1,1'-Methyl-enebis[3-(2,6-diiso-propyl-phen-yl)-3,4,5,6-tetra-hydro-pyrimidin-1-ium] dibromide ethanol monosolvate monohydrate.

In the title methyl-ene-bridged di(tetra-hydro-pyrimidinium) salt, C33H50N4 (2+)·2Br(-)·C2H5OH·H2O, the two tetra-hydro-pyrimidinium rings have envelope conformations with the central CH2 C atom as the flap. Their mean planes are inclined to one another by 73.31 (13)° and the attached benzene rings are inclined to one another by 67.39 (15)°. The methylene-C-N bond lengths in the tetra-hydro-pyrimidinium rings are 1.314 (3) and 1.304 (3) Å, values typical for C=N double bonds. The distances between the methyl-ene-bridge C atom and the linked tetra-hydro-pyrimidinium N atom are 1.457 (3) and 1.465 (3) Å, values typical for C-N single bonds. The mol-ecules co-crystallized with H2O and EtOH mol-ecules from the solvent. In the crystal, there is a zigzag chain along [010] of water mol-ecules linked by one of the Br(-) anions via O-H⋯Br hydrogen bonds. The second Br(-) anion is hydrogen bonded (O-H⋯Br) to the ethanol solvent mol-ecule. There are also a number of C-H⋯Br and C-H⋯O hydrogen bonds present, leading to the formation of a two-dimensional network lying parallel to the bc plane.