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Background Screw-retained implant crowns are considered more biologically compatible than cemented crowns due to the absence of excess cement. However, traditional screw-retained implant crowns are not viable when the access hole of the screw channel would need to be located in an esthetic area, which would compromise the esthetic outcome of the treatment. Purpose To evaluate the clinical, radiographic, and immunological outcomes of angulated screw-retained and cemented single-implant crowns in the esthetic region. Materials and methods The study was a single-center, open-label, randomized controlled clinical trial. Eligible patients were randomly placed in two groups: angulated screw-retained group (AG) and cemented group (CG). Implant survival rate, bleeding on probing rate (BOP%), probing depth (PD), modified plaque index (mPI), marginal bone loss (MBL), concentrations of pro-inflammatory cytokines (TNF-α, IL-6) in peri-implant crevicular fluid (PICF), mechanical complications, and pink esthetic score/white esthetic score (PES/WES) were evaluated. Results Fifty-six patients (AG: 29, CG: 27) attended the 1-year examination. The drop-out rate was 6.67%. No implant failure was found in both groups during the observation period. BOP% was significantly lower in the AG than that in the CG (mean, 21.84% ± 19.97% vs. 37.04% ± 26.28%, p = 0.018). The concentration of TNF-α in PICF was significantly higher in the AG than that in the CG (median, 13.54 vs. 4.62, p = 0.019). No significant difference of PD, mPI, MBL, IL-6, or mechanical complication rates was found between the two groups. Mean scores for PES/WES were 21.71 and 21.64 in the AG and CG, respectively. Conclusion Based on the present results, both treatment options showed acceptable clinical outcomes in the short term. Angulated screw-retained crowns might benefit the peri-implant soft tissue. However, studies with long-term follow-up are needed to confirm whether the higher concentration of TNF-α will compromise the long-term outcomes of treatment.

Background Intranasal nebulization is an effective treatment for chronic rhinosinusitis and allergic rhinitis; however, terminal inhalation devices have not been fully studied. We compared the sinonasal aerosol distributions and adverse effects of different inhalation units. Methods A mask, double-head nozzle, and single-head nozzle were applied to atomize the methylene blue solution to 3-dimensional printed models of the pediatric nasal cavity, adult nasal cavity with septal deviation, and postsurgical paranasal sinuses, and staining of the different sites was scored. Volunteers received nebulization of normal saline via different devices; thereafter, the adverse effects were assessed using the visual analogue scale (VAS). Results After nebulization, the staining scores for the middle turbinate and middle meatus of the pediatric and adult nasal cavity models and the score for the anterior ethmoid sinus of the sinus model with the single-head nozzle were significantly higher than those with the mask and double-head nozzle (all p 0.05). Conclusion The single-head nozzle was the most effective device in aerosol delivery to the lateral wall of the nasal cavity and sinuses; conversely, the mask yielded limited sinonasal deposition. Intranasal nebulization was well tolerated, and the adverse effects among the devices were comparable. These findings are meaningful for selecting and developing inhalation units.

A goal for human society is to convert organic waste into valuable materials. Herein, 2-(methylthio)-bezothiazole (MTBT), an important organic waste in urban runoff, was catalytically converted into a series of organic semiconductors through carbon-sulfur bond activation. The efficient conversion of various substrates with different aromatic moieties and reacting functional groups (tin and boron) proved the generality of this novel diarylation Liebeskind-Srogl methodology. Moreover, the resulting organic semiconductors showed excellent performance in field effect transistors and cell imaging. This contribution presents an excellent example of converting organic waste into valuable materials and may open a new avenue to utilizing widely available aromatic thioethers.

Microglia are the primary immune cells in the central nervous system with functional plasticity. They can be activated into M1 and M2 phenotypes when neuroinflammation-related diseases occur. M1 phenotype cells produce pro-inflammatory mediators that cause neuroinflammation and the M2 phenotype can secrete anti-inflammatory cytokines that protect neurons from damage. Therefore, inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for treating neuroinflammation-related diseases. Puerarin has been demonstrated to exert anti-inflammatory and neuroprotective effects. However, the role of puerarin in regulating microglia polarization and its reaction mechanism has not been fully elucidated. In this paper, a metabolomics approach with ultra-performance liquid chromatography-mass spectrometry was performed to investigate the metabolic changes of BV-2 cells in different phenotypes and test the effects of puerarin on polarization. Thirty-nine metabolites were identified as the biomarkers related to the polarization of BV-2 cells and puerarin intervention reverted the content of most of the biomarkers. Our study demonstrated that puerarin could play a key role in M1/M2 polarization of BV-2 cells from a perspective of metabolomics, and it could regulate the balance between promotion and suppression of inflammation.

Background Asthma is an inflammatory disease characterized by airway hyperresponsiveness. Gallic acid is a powerful anti-inflammatory agent. In this study we aimed to investigate the efficacy of gallic acid in asthma treatment and its mechanisms. Methods An ovalbumin-induced asthma mouse model was generated. Pro-inflammatory cell infiltration and T helper (Th2)-associated cytokine release in the bronchoalveolar lavage fluid (BALF) were analyzed to reflect the severity of asthma in mice. An interleukin-33 (IL-33)-induced asthma mouse model was also generated to study the mechanism by which gallic acid could improve asthma. Group 2 lymphoid cells (ILC2s) were identified using flow cytometry. Proteins were detected using Western blotting. Results Ovalbumin significantly increased the infiltration of pro-inflammatory cells, including eosinophils, macrophages, lymphocytes, and neutrophils, accompanied by enhanced airway hyperesponsiveness. Gallic acid reduced pro-inflammatory cell infiltration and improved airway hyperresponsiveness. Meanwhile, gallic acid reduced IL-5 and IL-13 levels in BALF and decreased expression of IL-33 in the lungs. Mechanistically, gallic acid inhibited MyD88 expression and downregulated nuclear factor (NF)-κB signaling to decrease IL-33 expression. Conclusions Gallic acid can mollify ovalbumin-induced asthma in mice, possibly by inhibiting IL-33-mediated ILC2 activation and subsequent Th2 cytokine release via downregulation of the MyD88/NF-κB signaling pathway. ©2018 ARSAAOA, LLC.

Two isomeric 1,4-thiaborin derivatives fused by two thiophene rings (dithieno-1,4-thiaborins, DTTBs) were synthesized in two steps from commercially available materials, and their structures were confirmed by X-ray crystallographic analysis. DTTBs 1 and 2 showed excellent stability towards air and moisture. Theoretical calculations revealed that the fusion of thiophenes enhanced the aromaticity of the centered 1,4-thiaborins compared to their corresponding dibenzothiaborins. Furthermore, DTTBs 1 and 2 could be further functionalized by metalation followed by addition of electrophile. DTTBs are promising platforms upon which it is possible to build the next generation of organoboron π-electron materials.

Three acceptor–acceptor (A–A) type conjugated polymers based on isoindigo and naphthalene diimide/perylene diimide are designed and synthesized to study the effects of building blocks and alkyl chains on the polymer properties and performance of all-polymer photoresponse devices. Variation of the building blocks and alkyl chains can influence the thermal, optical, and electrochemical properties of the polymers, as indicated by thermogravimetric analysis, differential scanning calorimetry, UV–vis, cyclic voltammetry, and density functional theory calculations. Based on the A–A type conjugated polymers, the most efficient all-polymer photovoltaic cells are achieved with an efficiency of 2.68%, and the first all-polymer photodetectors are constructed with high responsivity (0.12 A W−1) and detectivity (1.2 × 1012 Jones), comparable to those of the best fullerene based organic photodetectors and inorganic photodetectors. Photoluminescence spectra, charge transport properties, and morphology of blend films are investigated to elucidate the influence of polymeric structures on device performances. This contribution demonstrates a strategy of systematically tuning the polymeric structures to achieve high performance all-polymer photoresponse devices.

Three new complexes have been prepared based on the transition metals and zwitterionic dicarboxylate ligand 1,1′-(1,4-phenylene-bis(methylene))-bis(pyridine-3-carboxylic acid) (L), whose formulas are {[Cd4(L)(SO4)]· (Cl)6}n (1), [Zn(L)Cl2]n (2), and [Co(L)Cl2]n (3), respectively. Complexes 1–3 have been characterized by elemental analyses, IR spectroscopy, XRD, thermal analyses and single crystal X-ray (powder) diffraction. 1 crystallizes in monoclinic space group C2/m, displaying a 2-D layer structure with three unique Cd2+ centers. 2 and 3 are isomorphic structures with the orthorhombic Cmca space group. They exhibit a 1-D zigzag chain, which can be linked to generate a 2-D layer via hydrogen bonding interactions (CH···O). Moreover, electrochemical behavior reveals that the redox reaction of 3-CPE is a surface-controlled reaction. And the luminescent properties of the title complexes have been investigated at room temperature.

Various organic nanoagents have been developed for photothermal therapy (PTT) and photodynamic therapy (PDT) under near-infrared (NIR) irradiation. Among them, small molecule-based nanoagents are very attractive due to their advantages of well-defined chemical structures, high purity, good reproducibility, and easy processability. However, only a few small molecule-based nanoagents have been developed for PDT under NIR irradiation. Moreover, the mechanism of PDT under NIR is still elusive. Herein, a semiconducting small molecule (BTA) with donor-acceptor-donor structure and twisted conformation is developed for PDT/PTT under NIR irradiation. A large π-conjugated electron-deficient unit is used as the core to couple with two electron-donating units, ensuring the strong absorption under 808 nm. Moreover, the donor-acceptor structures and twisted conformation can reduce the energy gap between the singlet and triplet states (∆EST ) to afford effective intersystem crossing, beneficial for reactive oxygen species generation. The mechanism is probed by experimental and theoretical evidence. Moreover, the BTA nanoparticles exhibit excellent biocompatibility and PTT/PDT in vitro performance under NIR irradiation. This provides a strategy for designing highly efficient PDT/PTT molecular materials.

High tracking accuracy is a prerequisite of reliable space optical communication links and its effective means is the utilization of coarse and fine compound-axis structure. After an in-depth study of the active laser tracking mechanism of fine tracking assembly, this paper emphasizes the exploration of these methods enabling the improvement of tracking accuracy under the condition of relative movement and platform vibration. Firstly, switching technique using a single beacon between different divergence angles is put forward to improve the signal to noise ratio (SNR) of the focal spot. Secondly, the high-frame rate charge-coupled device is achieved after proposing the pseudo random window readout technique. Thirdly, the unique design of the high resonant frequency of two-dimensional PZT fast steering mirror (FSM) and sub-pixel subdivision technique with adaptive control of integral time is used to achieve high accuracy and fast beam pointing. Fourthly, this paper puts forward a digital servol control method with intelligent variable structure. Finally, after building a hardware-in-loop simulation platform, the tracking accuracy of 3μrad is concluded according to simulation experimental results.

A rapid, simple and sensitive, liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for simultaneous determination of bergenin, chlorogenic acid and four flavonoids in a QingGanSanJie preparation in rat plasma. Puerarin was selected as the internal standard (IS). Plasma samples were precipitated with methanol and separated with a reverse phase Agilent Poroshell 120 EC-C18 column using a gradient mobile phase of methanol-water containing 0.1% formic acid (v/v). A triple quadruple mass spectrometer was used for quantification (limit of detection 0.36-5.55 ng/mL). Intra-day and inter-day precisions were within 15% and the average extraction recoveries ranged from 85 to 115% for each analyte. The method allowed simultaneous quantification for the first time of the pharmacokinetics of bergenin, chlorogenic acid and four flavonoids after intragastric administration of a QingGanSanJie extract in Sprague-Dawley rats. It was found that bergenin and chlorogenic acid had typical extravascular administration concentration-time curves; flavonoids had a bimodal distribution improving bioavailability and extending the pharmacodynamics period.

HPLC with diode array detection and ESI-TOF-MS was used for the study of the constituents in Apocynum venetum L. extracts and the metabolites in rat urine after oral administration of A. venetum L. extracts. A formula database of the known constituents in A. venetum L. was established, and 21 constituents were rapidly identified by accurately matching their molecular masses with the formulae of the compounds in the database. Furthermore, 34 metabolites were detected and elucidated in the rat urine. The scientific and plausible biotransformation pathways of the flavonoid components in A. venetum L. were also proposed together with the presentation of clues for potential mechanisms of bioactivity. This specific and sensitive HPLC–ESI-TOF-MS method can be used to identify the chemical components in the extracts of A. venetum L. and their metabolites in rat urine. This method can also be used to reveal the possible metabolic mechanisms of action of the extract components in vivo.

Large-scale group performance animation has been an important research topic because of its diverse range of applications including virtual rehearsal and film production. Animating hundreds of virtual actors as what the director wishes is a tough task. In this paper, we address this challenge by introducing an optimization method that generates large-scale group performance by deducing a small-scale one with fewer actors. We introduced group motion bigraph technique and transformed the motion-deducing problem into a constrained optimization problem. A solving process is then presented to automatically obtain the motion of the large group with velocity constraints. Moreover, an interactive system of constructing the group motion bigraph has been implemented, which provides flexible edit and control on deducing group motion. The animation results show that our method is competent for deducing large-scale group performance from only several motion clips performed by small groups. Copyright © 2013 John Wiley & Sons, Ltd.

Type 2 diabetes (T2D) is associated with accelerated restenosis rates after angioplasty. We have previously proved that Pin1 played an important role in vascular smooth muscle cell (VSMC) cycle and apoptosis. But neither the role of Pin1 in restenosis by T2D, nor the molecular mechanism of Pin1 in these processes has been elucidated. A mouse model of T2D was generated by the combination of high-fat diet (HFD) and streptozotocin (STZ) injections. Both Immunohistochemistry and Western blot revealed that Pin1 expression was up-regulated in the arterial wall in T2D mice and in VSMCs in culture conditions mimicking T2D. Next, increased activity of Pin1 was observed in neointimal hyperplasia after arterial injury in T2D mice. Further analysis confirmed that 10% serum of T2D mice and Pin1-forced expression stimulated proliferation, inhibited apoptosis, enhanced cell cycle progression and migration of VSMCs, whereas Pin1 knockdown resulted in the converse effects. We demonstrated that STAT3 signalling and mitochondria-dependent pathways played critical roles in the involvement of Pin1 in cell cycle regulation and apoptosis of VSMCs in T2D. In addition, VEGF expression was stimulated by Pin1, which unveiled part of the mechanism of Pin1 in regulating VSMC migration in T2D. Finally, the administration of juglone via pluronic gel onto injured common femoral artery resulted in a significant inhibition of the neointima/media ratio. Our findings demonstrated the vital effect of Pin1 on the VSMC proliferation, cell cycle progression, apoptosis and migration that underlie neointima formation in T2D and implicated Pin1 as a potential therapeutic target to prevent restenosis in T2D.

We present a rigid-motion-inspired method for animating liquid characters in this paper. Our method allows an animator to control the motion of liquid characters with motion capture data that is widely used in rigid body animation. It animates the most visual interesting part of liquid character, that is, to preserve character's shape as well as produce enough liquid details. To this end, we build a two-layer model to represent the character by two coaxial layers: the rigid kernel and the liquid shell. Different control paradigms are used for the two layers instead of applying homogeneous force that is common in previous approaches. By embedding the control algorithm to the Navier–Stokes equations, we compute the fluid velocity that drives the motion of the liquid character. Results show that the method is easy and intuitive to use while incurring little additional cost.Copyright © 2013 John Wiley & Sons, Ltd.

Cocaine dependence involves in the brain's reward circuit as well as nucleus accumbens (NAc), a key region of the mesolimbic dopamine pathway. Many studies have documented altered expression of genes and identified transcription factor networks and epigenetic processes that are fundamental to cocaine addiction. However, all these investigations have focused on mRNA of encoding genes, which may not always reflect the involvement of long non-coding RNAs (lncRNAs), which has been implied in a broad range of biological processes and complex diseases including brain development and neuropathological process. To explore the potential involvement of lncRNAs in drug addiction, which is viewed as a form of aberrant neuroplasticity, we used a custom-designed microarray to examine the expression profiles of mRNAs and lncRNAs in brain NAc of cocaine-conditioned mice and identified 764 mRNAs, and 603 lncRNAs were differentially expressed. Candidate lncRNAs were identified for further genomic context characterization as sense-overlap, antisense-overlap, intergenic, bidirection, and ultra-conserved region encoding lncRNAs. We found that 410 candidate lncRNAs which have been reported to act in cis or trans to their targeted loci, providing 48 pair mRNA-lncRNAs. These results suggest that the modification of mRNAs expression by cocaine may be associated with the actions of lncRNAs. Taken together, our results show that cocaine can cause the genome-wide alterations of lncRNAs expressed in NAc, and some of these modified RNA transcripts may to play a role in cocaine-induced neural plasticity and addiction.

Rationale Timosaponin B-II (TB-II) is one of the major bioactive steroid glycosides isolated from Anemarrhena asphodeloides Bge. (Fam. Liliaceae). It has been regarded as a potential lead compound, which may be further developed into a promising new drug for preventing dementia. To fully understand the action mechanism of TB-II, it is important to study the metabolism profile of this compound in vivo. Methods Herein, a rapid and sensitive method based on ultrahigh-performance liquid chromatography (UHPLC)/quadrupole-time-of-flight mass spectrometry (QTOFMS) was established to comprehensively investigate the metabolism of TB-II in Sprague-Dawley rat urine following oral administration of a single dose of TB-II at 500.4 mg·kg(-1). Results A total of twelve metabolites were detected and identified by means of comparing molecular mass, retention time and spectral pattern of the analytes with those of the parent drug. A possible metabolic pathway on the biotransformation of TB-II was also investigated and proposed. Conclusions Oxidation, deglycosylation and E-ring cleavage were found to be the major metabolic processes of the compound in rat. It is the first report on a mammalian metabolism study of timosaponin, a common member of steroid glycosides, in rat urine.

1. The aim of the present study was to determine whether ligustrazine (2,3,5,6-tetramethylpyrazine; TMP) exerts a cardioprotective effect during myocardial ischaemia reperfusion (IR), and to investigate the underlying mechanisms and the role of endothelial nitric oxide synthase (eNOS) in cardioprotection. 2. Sprague-Dawley rats were divided into a sham group and five IR groups: IR control, TMP pretreated, TMP + wortmannin (a phosphatidylinositol 3-kinase (PI3K) inhibitor), N(G) -nitro-L-arginine methyl ester (L-NAME; a NOS inhibitor) and TMP + L-NAME. IR was produced by 35 min of regional ischaemia followed by 120 min of reperfusion. Myocardial infarct size, oxidative stress, myocardial apoptosis, nitric oxide (NO) production, and expression of phosphorylated protein kinase B (Akt) and eNOS were measured. 3. TMP markedly decreased infarct size and attenuated myocardial apoptosis, as evidenced by a decrease in the apoptotic index and reduced caspase-3 activity. TMP treatment caused a marked increase in NO production. Cotreatment with wortmannin or L-NAME completely blocked the TMP-induced NO increase. TMP induced phosphorylation of Akt at Ser 473 (1.61 ± 0.18 vs 0.79 ± 0.10 in the IR control group) and phosphorylation of eNOS at Ser1177 (1.87 ± 0.33 vs 0.94 ± 0.22 in the IR control group). Wortmannin abrogated the phosphorylation of Akt and eNOS induced by TMP. 4. These data suggest that ligustrazine has anti-apoptotic and cardioprotective effects against myocardial IR injury and that it acts through the PI3K/Akt pathway. In addition, the phosphorylation of eNOS with subsequent NO production was found to be an important downstream effector that contributes significantly to the cardioprotective effect of TMP.

Two new coordination polymers, {[Cd2(btc)(2,2′-bpy)2]·H2O}n (1) and [Zn2(btc)(2,2′-bpy)(H2O)]n (2) (H4btc = biphenyl-2,2′,4,4′-tetracarboxylic acid, 2,2′-bpy = 2,2′-bipyridine), were synthesized hydrothermally under similar conditions and characterized by elemental analysis, IR spectra, TGA, and single-crystal X-ray diffraction analysis. In complexes 1 and 2, the (btc)4– ligand acts as connectors to link metal ions to give a 2D bilayer network of 1 and a 3D metal-organic framework of 2, respectively. The differences in the structures are induced by diverging coordination modes of the (btc)4– ligand, which can be attributed to the difference metal ions in sizes. The results indicate that metal ions have significant effects on the formation and structures of the final complexes. Additionally, the fluorescent properties of the two complexes were also studied in the solid state at room temperature.

A high-performance liquid chromatography with diode-array detection coupled to time-of-flight mass spectrometry (HPLC/DAD/TOFMS) method was established to clarify the chemical composition of Sini decoction (SND) and rat plasma after oral administration of SND. With dynamic adjustment of fragmentor voltage in TOFMS, an efficient transmission of the ions was achieved to obtain the best sensitivity for providing the molecular formula for each analyte and abundant fragment ions for structural information. By accurate mass measurements within 5 ppm error for each molecular ion and subsequent fragment ions, 53 compounds including diterpenoid alkaloids, flavonoids, triterpenoids and gingerol-related compounds were identified in SND. Major compounds identified from SND were further assigned in the three individual herbs. After oral administration of SND, 33 compounds and five metabolites in rat plasma were detected and identified by comparing and contrasting the compounds measured in SND with those in the plasma samples by HPLC/DAD/TOFMS. The results provided helpful chemical information for further pharmacology and active mechanism research on SND. Copyright © 2010 John Wiley & Sons, Ltd.

Stellera chamaejasme L. has been used as a traditional Chinese medicine for the treatment of scabies, tinea, stubborn skin ulcers, chronic tracheitis, cancer and tuberculosis. A sensitive and selective ultra-high liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the simultaneous determination of five flavonoids (stelleranol, chamaechromone, neochamaejasmin A, chamaejasmine and isochamaejasmin) of S. chamaejasme L. in rat plasma. Chromatographic separation was accomplished on an Agilent Poroshell 120 EC-C18 column (2.1 × 100 mm, 2.7 μm) with gradient elution at a flow rate of 0.4 mL/min and the total analysis time was 7 min. The analytes were detected using multiple reaction monitoring in positive ionization mode. The samples were prepared by liquid-liquid extraction with ethyl acetate. The UPLC-MS/MS method was validated for specificity, linearity, sensitivity, accuracy and precision, recovery, matrix effect and stability. The validated method exhibited good linearity (r ≥ 0.9956), and the lower limits of quantification ranged from 0.51 to 0.64 ng/mL for five flavonoids. The intra- and inter-day precision were both

An efficient method for the ultrasound-assisted N-arylation of indoles with haloarenes in an air atmosphere mediated by Cs 2 CO 3 without any catalyst is reported. N-arylindoles are obtained in moderate to good yields while indoles cross-coupling with activated aryl halides (X = F or Cl).

Eight simple N-arylindoles were designed, synthesized and evaluated as human immunodeficiency virus (HIV)-1 integrase inhibitors in vitro for the first time. Among these compounds, 3b, 3e and 3g demonstrated significant anti-HIV-1 integrase activity. Especially 3b showed the highest anti-HIV-1 integrase activity with EC50 value of 7.88 microg/ml and TI value of 24.61. Meantime, some structure-activity relationships were also observed and will provide a new lead for design and discovery of more potent N-arylindoles as HIV-1 integrase inhibitors.