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Recurrent events, including cardiovascular events, are commonly observed in biomedical studies. Understanding the effects of various treatments on recurrent events and investigating the underlying mediation mechanisms by which treatments may reduce the frequency of recurrent events are crucial tasks for researchers. Although causal inference methods for recurrent event data have been proposed, they cannot be used to assess mediation. This study proposed a novel methodology of causal mediation analysis that accommodates recurrent outcomes of interest in a given individual. A formal definition of causal estimands (direct and indirect effects) within a counterfactual framework is given, and empirical expressions for these effects are identified. To estimate these effects, a semiparametric estimator with triple robustness against model misspecification was developed. The proposed methodology was demonstrated in a real‐world application. The method was applied to measure the effects of two diabetes drugs on the recurrence of cardiovascular disease and to examine the mediating role of kidney function in this process. [ABSTRACT FROM AUTHOR]

The wavelength-routed optical network on chip (WRONoC) is a promising solution for signal transmission in modern System-on-Chip (SoC) designs. Previous works do not simultaneously handle all the following four main issues for WRONoCs: 1) correlations between the topological structure and physical layout; 2) tradeoffs between the maximum insertion loss and the number of wavelengths; 3) runtime scalability of wavelength assignment scheme; and 4) a fully automated flow to generate predictable designs. As a result, their insertion loss estimation is inaccurate, their wavelength assignment is inefficient, and thus, only suboptimal results are obtained. To remedy these disadvantages, we present a fully automated topological structure and a physical layout co-design flow with improved wavelength assignment schemes to minimize the maximum insertion loss and the laser power simultaneously with a significant speedup. The experimental results show that our co-design flow significantly outperforms state-of-the-art works in the maximum insertion loss, laser power, and runtimes. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As interleukin‐1β (IL‐1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL‐1β‐induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL‐6, inducible nitric oxide synthase, cyclooxygenase‐2, and tumor necrosis factor‐α (TNF‐α) in a concentration‐dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti‐inflammatory effect by inactivating the PI3K/AKT/NF‐κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy. [ABSTRACT FROM AUTHOR]

Objectives. Stroke is a common condition after a transient ischemic attack (TIA) or minor ischemic stroke (IS). Adding clopidogrel to aspirin may yield more beneficial outcomes than aspirin mono-therapy; meanwhile, the risk of bleeding in the acute phase remains poorly understood. Therefore, there is increasing emphasis on the risks and benefits of clopidogrel with aspirin compared with aspirin mono-therapy in an effort to treat TIA/IS. Design. We searched several electronic databases, including PubMed, Cochrane, and Embase, to identify eligible randomized controlled trials (RCTs) based on the index words comparing dual-antiplatelet therapy to aspirin mono-therapy for secondary stroke prevention updated to December, 2018. Results. A total of 11 RCTs met our inclusion criteria. The pooled analysis showed that clopidogrel plus aspirin was associated with a trend toward a reduction in recurrent IS (RR = 0.72, 95%CI = 0.65-0.81, p < .001), but not the recurrent stroke rate (RR = 0.81, 95% CI = 0.63-1.03, p = .09) than aspirin mono-therapy. There were differences in bleeding episodes (RR = 1.81, 95%CI = 1.65-1.99, p < .001), moderate-severe major bleeding (RR = 1.64, 95% CI = 1.24-2.16, p = .0005), or mild bleeding (RR = 2.25, 95%CI = 1.54-3.31, p < .001) between the study groups. Meanwhile, no benefit of reducing the risk of intracranial hemorrhage with dual-antiplatelet therapy was found in TIA/IS patients (RR = 1.44, 95% CI = 0.95-2.19, p = .09). Conclusions. The addition of clopidogrel to aspirin for patients with TIA or IS appeared to significantly reduce the risk of IS recurrence with a possible increase in the risk of bleeding compared with aspirin alone. [ABSTRACT FROM AUTHOR]

Although the small bowel mesentery was slightly bruised, the herniated small bowel was otherwise healthy and viable, and no bowel resection was necessary. Surg. 1964; 159: 382 - 4. 3 Kheok SW, Haja Mohideen SM, Lim JW, Santhosh Raj SR. Intramesosigmoid hernia complicated by strangulated small-bowel obstruction. The clinical suspicion was either a congenital adhesion band or an internal hernia causing the small bowel obstruction. [Extracted from the article]

A novel design for T-shaped and Π-shaped transmission lines on dual-band bandpass filters are proposed to efficiently suppress high-frequency harmonic. The dual-band can be designed using stepped-impedance resonators. The harmonic suppression of the proposed dual-band bandpass filter is extended to 12 GHz with a rejection level higher than −20 dB. The measured results concur with the full-wave simulation results. © 2015 Wiley Periodicals, Inc. Microwave Opt Technol Lett 57:547-551, 2015 [ABSTRACT FROM AUTHOR]

Aim: Periodontitis (PD) is the sixth most prevalent disease around the world and is involved in the development and progression of multiple systemic diseases. Previous studies have reported that PD may aggravate liver injuries. The objective of this study was to investigate whether and how PD affects liver fibrosis. Materials and Methods: Ligature‐induced PD (LIP) was induced in male C57/B6J mice, and sub‐gingival plaques (PL) from patients with PD were applied to mouse teeth. Liver fibrosis was induced by carbon tetrachloride (CCl4) injection. The mice were randomly divided into six groups: Oil, Oil+LIP, Oil+LIP+PL, CCl4, CCl4+LIP, and CCl4+LIP+PL. Alveolar bone resorption was evaluated by methylene blue staining. Hepatic function was analysed by serum alanine aminotransferase and hepatic hydroxyproline. Picrosirius red and α‐smooth muscle actin (SMA) staining were used to evaluate the fibrotic area. RNA sequencing and quantitative RT‐PCR were used to measure gene expression. Western blotting was used to measure protein levels. Flow cytometry was used to analyse the accumulation of immune cells. Mouse microbiota were analysed using 16S rRNA gene sequencing. Results: Mice in the CCl4+LIP+PL group displayed higher serum alanine aminotransferase and hepatic hydroxyproline as well as more Picrosirius red‐positive and α‐SMA‐positive areas in liver samples than those of the CCl4 group, suggesting that PD (LIP+PL) aggravated CCl4‐induced hepatic dysfunction and liver fibrosis. Consistently, the expression of fibro‐genic genes and the protein levels of transforming growth factor β were much higher in the CCl4+LIP+PL group than in the CCl4 group. Flow cytometry revealed that PD increased the accumulation of immune cells, including Kupffer cells, B cells, and Th17 cells, in the liver of mice with CCl4 treatment. PD also increased the expression of inflammatory genes and activated pro‐inflammatory nuclear factor‐kappa B pathway in the livers of CCl4‐injected mice. Moreover, PD altered both oral and liver microbiota in CCl4‐injected mice. Conclusions: PD aggravates CCl4‐induced hepatic dysfunction and fibrosis in mice, likely through the increase of inflammation and alteration of microbiota in the liver. [ABSTRACT FROM AUTHOR]

Abstract: Two series of raw materials were adopted to form TiAl/Ti2AlC composites: Ti/Al/TiC and Ti/Al/C. Differential thermal analysis (DTA) of starting powers and X-ray diffraction (XRD) of samples sintered at different temperatures from 600°C to 1300°C by hot pressing were utilized to analyze the phase transformation and the mechanism of synthesis. Scanning electron microscopy (SEM) coupled with energy-dispersive spectroscopy (EDS) was utilized to investigate the morphology characteristics of the products. The experimental results showed that Ti reacted with Al to form TiAl intermetallics below 900°C; and above 900°C, TiAl reacted with TiC to produce dense TiAl/Ti2AlC composites. The products sintered at 1200°C had fine crystals and dense fibres, and the distribution of Ti2AlC particles in TiAl matrix was homogeneous. [Copyright &y& Elsevier]

Background: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. Results: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. Conclusions: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP. [ABSTRACT FROM AUTHOR]

Background: Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. Results: In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs’ stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. Conclusions: PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP. [ABSTRACT FROM AUTHOR]

The title inorganic-organic hybrid material containing a mixed anion, [BzIQl]2[Zn(NCS)2Br2] (1) (BzIQl = benzyl isoquinolinium, NCS− = isothiocyanate), crystallizes with a benzyl isoquinolinium cation and half of a bis(bromo)-bis(isothiocyanate)zinc(II) anion in the asymmetric unit. It was characterized by elemental analysis, Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis), electrospray ionization mass spectrometry (ESI-MS), and powder and single crystal X-ray diffraction (PXRD and SC-XRD). The organic cation exhibits a Λ-shaped configuration in which two aromatic rings form an inclined dihedral angle of 90.12°. The ZnII ion in the anion is coordinated by two Br ions and two isothiocyanate ions, and two contiguous anions forms a dimer through S···Br interactions. The thermal stability of the hybrid crystal analyzed by thermogravimetric-differential thermal analysis (TG-DTA) reveals that the title crystal was stable up to 170 °C. The PXRD study confirms the phase purity of the crystalline sample. The band gap energy between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) explains the eventual charge transfer interaction that take place mainly between the anion and [BzIQl]+ cation, and the low value (0.46 ev) indicates the suitability of the crystal for optical application. The first hyperpolarizability predicted using density functional theory (DFT) is more than 720 times that of the reference potassium dihydrogen phosphate crystal (KDP). [ABSTRACT FROM AUTHOR]

Abstract: Adsorption of ammonia (NH3) onto activated carbons prepared from palm shells impregnated with sulfuric acid (H2SO4) was investigated. The effects of activation temperature and acid concentration on pore surface area development were studied. The relatively large micropore surface areas of the palm-shell activated carbons prepared by H2SO4 activation suggest their potential applications in gas adsorption. Adsorption experiments at a fixed temperature showed that the amounts of NH3 adsorbed onto the chemically activated carbons, unlike those prepared by CO2 thermal activation, were not solely dependent on the specific pore surface areas of the adsorbents. Further adsorption tests for a wide range of temperatures suggested combined physisorption and chemisorption of NH3. Desorption tests at the same temperature as adsorption and at an elevated temperature were carried out to confirm the occurrence of chemisorption due to the interaction between NH3 and some oxygen functional groups via hydrogen bonding. The surface functional groups on the adsorbent surface were detected by Fourier transform infrared spectroscopy. The amounts of NH3 adsorbed by chemisorption were correlated with the contents of elemental oxygen present in the adsorbents. Mechanisms for chemical activation and adsorption processes are proposed based on the observed phenomena. [Copyright &y& Elsevier]

Background: The poor prognosis of patients with ovarian cancer is mainly due to cancer progression. γ-Synuclein (SNCG) has reported as a critical player in cancer metastasis. However, its biological roles and mechanism are yet incompletely understood in ovarian cancer, especially in high-grade serous ovarian cancer (HGSOC). Methods: This is a retrospective study of 312 patients with ovarian cancer at a single center between 2006 and 2016. Ovarian cancer tissues were stained by immunohistochemistry to analyze the relationship between SNCG expression and clinicopathologic factors. The clinical outcomes versus SNCG expression level were evaluated by Kaplan–Meier method and multiple Cox regression analysis. Next, systematical functional experiments were given to examine the proliferation and metastatic abilities of SNCG both in vitro and in vivo using loss- and gain- of function approaches. Furthermore, the mechanisms of SNCG overexpression were examined by human phospho-kinase array kit and western blot analysis. Results: Clinically, the expression of SNCG was significantly upregulated in ovarian cancer compared with the borderline and benign tumor, normal ovary, and fallopian tube. Notably, the high level of SNCG correlated with high-risk clinicopathologic features and showed poor survival for patients with HGSOC, indicating an independent prognostic factor for these patients. Functionally, we observed that overexpression of SNCG promoted cell proliferation, tumor formation, migration, and invasion both in vitro and in vivo. Mechanistically, we identified that SNCG promoted cancer cell metastasis through activating the PI3K/AKT signaling pathway. Conclusions: Our results reveal SNCG up-regulation contributes to the poor clinical outcome of patients with HGSOC and highlight the metastasis-promoting function of SNCG via activating the PI3K/Akt signaling pathway in HGSOC. [ABSTRACT FROM AUTHOR]

Two Co(II)-based coordination polymers: [Co 2 (L) 2 (bib) 2 ] n (1) and {[Co 2 (L) 2 (bimb) 2 ]·2H 2 O·DMA)} n (DMA = N,N-dimethylacetamide) (2) using 4,4′-bis(thiomethylene) dibenzoic acid (H 2 L) as the first ligand, 1,4-bis(imidazol)-butane (bib) and 1,4-bis(imidazol-1-ylmethyl)benzene) (bimb) as the second ligands, were synthesized under the condition of solvothermal and characterized by X-ray single-crystal diffraction, elemental analysis, IR spectra and thermogravimetric analysis (TGA). X-ray single-crystal diffraction analysis exhibits that 1 and 2 belong to the triclinic crystal system, space group P -1. The central Co(II) ions exhibit a regular spatial tetrahedral structure which are coordinated by two O atoms from two L2− ligands and two N atoms from two N-donor ligands. Furthermore, the photocatalytic degradation properties and mechanism of 1 and 2 for methylene blue (MB) were investigated. The results show that the band gap (E g) of 1 and 2 is 3.78 eV and 3.82 eV, and the equipotential point (pH pzc) of 1 is 4.25. Both 1 and 2 show excellent photocatalytic degradation for MB. •OH is the main active substance causing MB degradation. The photocatalytic degradation for MB of 1 and 2 is in line with the first order kinetics equation. The pH pzc of complex 1 is 4.25. When pH < 4.25, 1 has a positive charge on the surface, and will generate electrostatic repulsion with MBH2+, inhibiting the adsorption of 1 to MB, so the degradation rate of MB is greatly reduced. When pH > 4.25, complex 1 has a negative charge on the surface and generates electrostatic attraction with MBH2+, which promotes the adsorption of 1 to MB, so the degradation rate of MB is greatly increased. Image 1 [ABSTRACT FROM AUTHOR]

An amendment to this paper has been published and can be accessed via the original article. [ABSTRACT FROM AUTHOR]

The epithelial-mesenchymal transition (EMT) plays a crucial role in pancreatic ductal adenocarcinoma (PDAC) development and progression. TWIST activated by intra-tumoral hypoxia functions to promote the EMT. We hypothesized that TWIST and the downstream gene pathway could mediate PDAC progression under hypoxia. Therefore, 90 PDAC tissue specimens were immunostained for TWIST and other proteins. Pancreatic cancer cell lines were used for in vitro experiments and nude mice were used to confirm the in vivo data. Expression of TWIST and HIF-1α proteins was significantly upregulated, whereas expression of E-cadherin and p16 was down-regulated in PDAC tissues compared to that of non-tumor tissues and in tumor tissues obtained from patients with tumor involving splenic artery than those without splenic artery involvement. Up-regulated TWIST in tumor tissues were associated with worse prognosis in PDAC patients. The in vitro data showed that HIF-1α-induced TWIST overexpression promoted tumor cell growth and EMT under a hypoxic condition via TWIST interaction with Ring1B and EZH2. In vivo data showed that TWIST overexpression or a hypoxic condition induce xenograft growth, abdominal metastasis and low mouse survival, whereas knockdown of either Ring1B or EZH2 expression suppressed tumor xenograft growth and metastasis and prolonged survival of nude mice. TWIST was the key player in promotion of pancreatic cancer development and metastasis under a hypoxic condition through interaction with Ring1B and EZH2 to regulate expression of E-cadherin and p16 proteins in pancreatic cancer cells. [ABSTRACT FROM AUTHOR]

• Two substituted benzyl triphenylphosphinium picrate salts were synthesized and characterized. • The FT-IR and Raman spectra have been discussed and assigned. • The HOMO-LUMO energy gap explains the charge transfer interactions in the molecules. • The nonlinear optical properties were studies using DFT calculations. • The title crystals exhibit violet and green fluorescence emissions in solid state at room temperature. Two new organic hybrid materials, namely, 4-chlorobenzyl triphenylphosphinium picrate and 4-iodobenzyl triphenylphosphinium picrate [4ClBzTPP][PIC](1) and [4IBzTPP][PIC](2), have been grown by slow evaporation solution growth technique and characterized by elemental analysis, spectroscopy, thermal analysis, powder and single crystal XRD. Two new picrates crystallize in triclinic space group P −1 and consist of a pair of [4ClBzTPP]+/[4IBzTPP]+ cations and picrate anions. The one-dimensional anionic chain are constructed by the non-bonded O···O and N···O interactions. Experimental vibrational bands (IR and Raman) have been discussed and assigned. The HOMO-LUMO energy gap explains the charge transfer interactions in the molecules. TG-TDA technique reveals that two materials were stable up to 215 °C and 253 °C, respectively. Excited by 250 nm ultraviolet light, two materials emit main luminescent emissions bands at about 374 nm and 524 nm in solid state at room temperature. In addition, two picrates show good antibacterial activities against Escherichia coli and Staphylococcus aureus. The results of DFT calculations based on the structures of 1 and 2 indicate that the first hyperpolarizability value (β tot) of two crystals are 5.8 and 32.3 times that of KDP, respectively, which show good nonlinear optical properties. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Adsorption of hydrogen sulphide (H2S) onto activated carbons derived from oil palm shell, an abundant solid waste from palm oil processing mills, by thermal or chemical activation method was investigated in this paper. Dynamic adsorption in a fixed bed configuration showed that the palm-shell activated carbons prepared by chemical activation (KOH or H2SO4 impregnation) performed better than the palm-shell activated carbon by thermal activation and a coconut-shell-based commercial activated carbon. Static equilibrium adsorption studies confirmed this experimental result. An intra-particle Knudsen diffusion model based on a Freundlich isotherm was developed for predicting the amount of H2S adsorbed. Desorption tests at the same temperature as adsorption (298K) and at an elevated temperature (473K) were carried out to confirm the occurrence of chemisorption and oxidation of H2S on the activated carbon. Surface chemistries of the palm-shell activated carbons were characterized by Fourier transform infrared spectroscopy and Boehm titration. It was found that uptaking H2S onto the palm-shell activated carbons was due to different mechanisms, e.g. physisorption, chemisorption and/or H2S oxidation, depending on the activation agent and activation method. [Copyright &y& Elsevier]

We report here the fabrication of BHPB loaded free-standing multilayered film via alternately depositing HA and PLL-BHPB complex and explore the underlying mechanism for its enhancing wound repair process. Of note, pre-assemble PLL with BHPB amplify PLL/HA film growth via accelerating the diffusion coefficient of PLL inside the film. [Display omitted] • LBL exponential growth is amplified by precursor assembly with charge-switchable BHPB. • BHPB neutralizes excess ROS and activates intracellular ROS scavenging mechanism. • BHPB incorporated PEM can stimulate Keap1/Nrf2/HO-1 axis to combat oxidative stress. The local oxidizing microenvironment and bacterial infection, as crucial internal and external factors that hinder the healing of diabetic wounds, are two main issues to be addressed in the design of novel wound dressing materials. As an attempt to provide optimal solution to the aforementioned problems, free-standing (FS) polyelectrolyte multilayer films (PEMs) loaded with bis[2-(4-hydroxyphenyl) benzimidazole] (BHPB) were constructed by layer-by-layer (LBL) self-assembly method. The exponential growth of LBL deposition as well as the film degradation were extensively studied, our results revealed that by pre-assembling polycation with the pH-sensitive BHPB molecule, the polycation diffusivity was largely accelerated thus greatly amplified LBL film growth, ensuring the facile detachment of the PEMs from the substrates to achieve FS films. The increase in BHPB content leaded to faster film growth and slower film degradation and more sustainable BHPB release. In terms of multifunctionality, which was ideal for the design of wound dressing material, the obtained FS films exhibited effective antimicrobial and antioxidant properties thanks to the addition of bioactive BHPB. Notably, unlike traditional antioxidant materials that only neutralize reactive oxygen species (ROS), the BHPB-loaded films stimulated the Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) axis, which is a vital intercellular ROS scavenging system blocked by hyperglycemia. Moreover, the wound treated by BHPB-incorporated PEMs exhibited faster healing with increased collagen deposition, enhanced angiogenesis, and rapid re-epithelialization in rat diabetic cutaneous defect models. Overall, in the perspective of cost-effectiveness and simple fabrication, the composite BHPB incorporated FS films reported in the current study showed rather promising potential in the application of diabetic wound healing. [ABSTRACT FROM AUTHOR]