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The interaction of two neutral alkoxy bridged binuclear rhenium(I) complexes, 1 and 2 [{Re(CO) 3 (1,4-NVP)} 2 (μ 2 -OR) 2 ] (1, R = C 4 H 9 ; 2, R = C 10 H 21 ; 1,4-NVP = 4-(1-naphthylvinyl)pyridine] with polycyclic aromatic hydrocarbons (PAH) is investigated. UV-vis absorption, emission, 1 H NMR spectral titrations, TCSPC lifetime studies and DFT theoretical calculations were carried out to examine the binding responses of complexes 1 and 2 with various PAHs such as pyrene, naphthalene, anthracene and phenanthrene. The UV-Vis absorption spectra showed an increase in absorbance of the metal-to ligand charge-transfer (MLCT) and ligand centered (LC) bands upon addition of various PAH molecules to 1 and 2, whereas the emission behavior was found to show emission quenching, which might occur through energy transfer pathway. The binding constants (K) of complexes 1 and 2 for various PAHs are found to be in the order of 10 4  M -1 with a 1:1 binding mode, as determined from UV-vis absorption and emission spectral titration studies. 1 H NMR spectral studies show that the chemical shifts of pyrene guest and the 1,4-NVP moiety of 2 are shifted up-field, whilst the alkoxy protons do not show any appreciable change in their chemical shifts. It is believed that the open cavities present in the Re(I) complexes may lead to the recognition of PAHs via CH···π interaction., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Apple is one of the most popular fruit crops world-wide and its skin color is an important quality consideration essential for commercial value. However, the strategy on genetic breeding for red skin apple and the genetic basis of skin color differentiation is very limited and still largely unknown., Results: Here, we reported a bud sport mutant of Fuji apple with red skin color and enhanced anthocyanins accumulation. Quantitative SWATH-MS (sequential window acquisition of all theoretical spectra-mass spectrometry) proteomics investigations revealed proteome changes in the apple red skin bud mutation and a total of 451 differentially expressed proteins were identified in apple skin. The mutant showed significantly increased expression levels of photosynthesis-related proteins, stress-related proteins as well as anthocyanins biosynthesis pathway. On the other hand, substantial downregulation of mitogen-activated protein kinase 4 (MAPK4) and mevalonate kinase (MVK) were detected, indicating a promising role for the red skin color development in the mutant. Furthermore, we also hypothesize that a post-transcriptional regulation of the skin color formation occurs in the mutant through the advanced SWATH-MS analysis., Conclusion: Our work provides important information on the application of proteomic methods for analysing proteomes changes in Fuji apple and highlights a clade of regulatory proteins potentially contributing for the molecular breeding of fruit skin color.

Immune checkpoint receptors with co-stimulatory and co-inhibitory signals are important modulators for the immune system. However, unrestricted co-stimulation and/or inadequate co-inhibition may cause breakdown of self-tolerance, leading to autoimmunity. Systemic lupus erythematosus (SLE) is a complex multi-organ disease with skewed and dysregulated immune responses interacting with genetics and the environment. The close connections between co-signaling pathways and SLE have gradually been established in past research. Also, the recent success of immune checkpoint blockade in cancer therapy illustrates the importance of the co-inhibitory receptors in cancer immunotherapy. Moreover, immune checkpoint blockade could result in substantial immune-related adverse events that mimic autoimmune diseases, including lupus. Together, immune checkpoint regulators represent viable immunotherapeutic targets for the treatment of both autoimmunity and cancer. Therefore, it appears reasonable to treat SLE by restoring the out-of-order co-signaling axis or by manipulating collateral pathways to control the pathogenic immune responses. Here, we review the current state of knowledge regarding the relationships between SLE and the co-signaling pathways of T cells, B cells, dendritic cells, and neutrophils, and highlight their potential clinical implications. Current clinical trials targeting the specific co-signaling axes involved in SLE help to advance such knowledge, but further in-depth exploration is still warranted.

Background: Patients with end-stage renal disease (ESRD) under hemodialysis (HD) are at greater risks of infectious spondylitis (IS), but there is no reliable predictor that facilitate early detection of this relatively rare and insidious disease., Methods: A retrospective review of the medical records from patients with ESRD under HD over a 12-year period was performed at a tertiary teaching hospital, and those with a first-time diagnosis of IS were identified. A 1:4 propensity score-matched case-control study was carried out, and baseline characteristics, underlying diseases, and laboratory data were compared between the study group and the control group, one month before the date of diagnosis or the index date respectively., Results: A total of 16 patients with IS were compared with 64 controls. After adjustment, recent access operation (odds ratio [OR], 13.27; 95% confidence interval [CI], 3.53 to 49.91; p <  0.001), degenerative spinal disease (OR, 12.87; 95% CI, 1.89 to 87.41; p = 0.009), HD through a tunneled cuffed catheter (OR, 6.75; 95% CI, 1.74 to 26.14; p = 0.006), low serum levels of hemoglobin, albumin, as well as high levels of red blood cell volume distribution width (RDW), alkaline phosphatase (ALP), and high sensitivity C-reactive protein were significant predictors for a IS diagnosis one month later. Receiver operating characteristic curves for hemoglobin, RDW, ALP, and albumin all showed good discrimination. The further multivariate models identified both high serum ALP levels and low serum RDW levels following a recent access intervention in patients with relatively short HD vintages may be indicative of the development of IS., Conclusion: Patients under HD with relatively short HD vintages showing either elevated ALP levels or low RDW levels following a recent access intervention should prompt clinical awareness about IS for timely diagnosis.

Objectives: A previous study suggested that colchicine may cause leukopenia and increase the risk of infection, such as pneumonia. Thus, we investigated the potential relationship between colchicine use and risk of developing pneumonia. Methods: Data were collected from Taiwan's National Health Insurance Research Database (NHIRD), a nationwide, population-based database. A 13-year retrospective cohort study was conducted, and all investigated subjects were identified by International Classification of Disease, Ninth Revision, Clinical Modification, codes between 2000 and 2012. Propensity score matching was applied to adjust for potential confounding variables, and then Cox proportional hazard model was used to evaluate the hazard ratio (HR) of pneumonia in gout patients and its associations with colchicine use, colchicine dosage, and days of colchicine use. Results: A total of 24,410 gout patients were enrolled in this study, including 12,205 cases who were treated with colchicine (colchicine group) and 12,205 cases who did not receive colchicine (non-colchicine group). The overall incidence rates of pneumonia in the colchicine group and non-colchicine group were 18.6 and 12.6 per 1,000 person-years, respectively. The colchicine group had a higher risk of pneumonia as compared with the non-colchicine group [adjusted HR, 1.42; 95% confidence interval (CI), 1.32 to 1.53; P < 0.05]. High cumulative dose and days of colchicine use notably increased the risk of contracting pneumonia. Conclusion: This nationwide population-based cohort study reveals that gout patients taking colchicine are at increased risk of developing pneumonia compared with gout patients who do not use colchicine. Therefore, it is crucial that gout patients being treated with colchicine be given the minimally effective dosage for the shortest possible duration to minimize their risk of pneumonia.

This work describes the successful incorporation of a redox active linker, tris(4-(1H-1,2,4-triazol-1-yl)phenyl)amine (TTPA) into Mn(ii)/Cu(ii) based coordination frameworks. Solution state in situ spectroelectrochemistry of EPR and UV/Vis/NIR of the TTPA ligand were measured to gain a deeper understanding of the charge delocalization of the triphenylamine backbone. The assignments of the absorption bands for the radical cations in UV/Vis/NIR spectroelectrochemistry were supported by DFT calculations. For Mn(ii)/Cu(ii) based coordination frameworks, solid state electrochemical and in situ spectroelectrochemical methods were applied to elucidate the accessible redox states and the optical properties of the frameworks. The findings provide a basic comprehension of the interconversion of different redox states and how an electroactive framework can be potentially used in applications of electrochromic and optical devices.

Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) used to share management with similar principles. However, their genetic and epigenetic differences along with different responses to immunotherapy were recently identified, which are reminiscent of their distinct etiologies. Different from the variety of environmental factors relating to UCB, UTUC is best known for its close relationship with exposure to aristolochic acid (AA). AA is believed to cause its carcinogenicity through forming DNA adducts of deoxyadenosine-aristolactam, as well as A:T → T:A transversions in the TP53 tumor suppressor gene. Since recent findings suggested that cancers with higher somatic mutations are associated with better treatment responses upon immune checkpoint blockade, UTUC and AA-related biomarkers reasonably serve as good candidates, as well as a potential prognostic predictor for the flourishing immunotherapy. This review covers the current state of the literature on the clinical response of UTUC and UCB receiving immunotherapy and points out directions for refinement regarding patient selection.

Objectives: The aim of this study is to explore the safety and feasibility of early oral feeding (EOF) on short-term postoperative outcomes. Trial design: A prospective randomized non-inferiority trial. Materials and methods: From August 27, 2015 to March 31, 2017, 100 consecutive patients with gastric cancer in Xijing Hospital were recruited. Patients undergoing total laparoscopic radical gastrectomy (TLRG) received either EOF group or delayed oral feeding (DOF group). The endpoints were anastomotic leakage, the recovery of bowel function, the postoperative complications and costs. The process of randomization used a computer-generated sequence that was kept in a sealed envelope by a nurse that did not participate in the trial. None of the participants, administrators of interventions and those assessing outcomes was blinded. Results: Ultimately, 51 patients were in EOF group and 49 in DOF group, which both are comparable. The postoperative hospital stay in EOF group was significantly lower than DOF group (5.18±1.47 days vs 6.18±2.46 days, P =0.016). Furthermore, there was a trend for a reduction in the time of first flatus (10.3 hrs) and defecation (12.7 hrs) in EOF group compared to DOF group, but it was not statistically significant. Meanwhile, there were no significant differences in postoperative complications between two groups. One patient in the EOF group developed a fistula in the surgical remnant, which was recorded as other leakages; there was no difference between the two groups ( P =0.582). Conclusion: EOF does not seem to be more harmful than DOF, and might significantly improve the short-term outcomes for patients receiving TLRG., Competing Interests: The authors report no conflicts of interest in this work.

The normal microbiota plays a key role in the health of host, but little is known of how the fish immune system recognizes and responds to indigenous bacteria/probiotics. Our previous studies have showed that heat-inactivated indigenous Bacillus pumilus SE5 activate the TLR2 signaling pathways and modulate the intestinal microbiota in grouper (Epinephelus coioides), suggesting microbial-associated molecular patterns (MAMPs) involved. In this study, whole cell wall (CW) and two possible MAMPs, peptidoglycan (PG) and lipoteichoic acid (LTA) have been extracted from B. pumilus SE5 and their effects on intestinal immune related genes expression and microbiota were evaluated in a 60 days feeding trial. Significantly elevated expression of TLR1, TLR2, TLR5 and MyD88 was observed in fish fed the CW, PG and LTA containing diets, and the highest expression was observed in groups PG and LTA. At the same time, significantly upregulated expression of antimicrobial effectors, such as antimicrobial peptides (epinecidin-1, hepcidin-1 and β-defensin), C-type Lectin and IgM was observed in fish fed PG and LTA containing diets. This induced activation of intestinal immunity was consistent with the microbiota data showing that CW, PG and LTA originated from SE5 modulated the overall structure of intestinal microbiota, and the relative abundance of potentially pathogenic Vibrio decreased significantly while beneficial Lactobacillus increased significantly in fish fed PG and LTA. In conclusion, both the PG and LTA originated from B. pumilus SE5 could activate TLRs/MyD88 signaling and expression of wide-ranging antibacterial effectors, and therefore shape the intestinal microbiota in grouper., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Designing highly conducting metal-organic frameworks (MOFs) is currently a subject of great interest for their potential applications in diverse areas encompassing energy storage and generation. Herein, a strategic design in which a metal-sulfur plane is integrated within a MOF to achieve high electrical conductivity, is successfully demonstrated. The MOF {[Cu 2 (6-Hmna)(6-mn)]·NH 4 } n (1, 6-Hmna = 6-mercaptonicotinic acid, 6-mn = 6-mercaptonicotinate), consisting of a two dimensional (-Cu-S-) n plane, is synthesized from the reaction of Cu(NO 3 ) 2 , and 6,6'-dithiodinicotinic acid via the in situ cleavage of an S-S bond under hydrothermal conditions. A single crystal of the MOF is found to have a low activation energy (6 meV), small bandgap (1.34 eV) and a highest electrical conductivity (10.96 S cm -1 ) among MOFs for single crystal measurements. This approach provides an ideal roadmap for producing highly conductive MOFs with great potential for applications in batteries, thermoelectric, supercapacitors and related areas.

Aquaculture jeopardizes the aquatic environment by discharge of the most dietary phosphorus (P) into the water. Reducing the dietary P level is a common approach for decreasing the P discharge but it may result in increased risk of P deficiency leading to vertebral deformities. However, the molecular mechanism of vertebral deformities is poorly understood. We assessed vertebral transcriptome and compared the genes associated with bone metabolism in Japanese seabass (Lateolabrax japonicus) fed three diets containing different P and Ca levels including: diet I (0.4% P, 0.3% Ca), diet II (0.8% P, 0.3% Ca) and diet III (0.8% P, 3% Ca). The results showed that P deficiency reduces the ossification of vertebrae and induces visible vertebral deformities. Moreover, 256 gens were up-regulated and 125 genes were down-regulated in fish fed P deficient diets. Furthermore, administration of the diet with adequate P and Ca excess (diet III) resulted in the significant enhancement in expression of 19 genes and reduced expression of 93 genes. Comparing group II with group III, expression of 109 genes was up-regulated and expression of 1369 genes was down-regulated. Gene ontology enrichment analysis revealed significant alterations in biological functions by P deficiency. In summary, these findings indicated that both dietary P shortage and Ca excess lead to reduced differentiation and proliferation of osteoblast and induce a higher activity of osteoclastogenesis, which could subsequently impair vertebral mineralization and cause skeletal deformities., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Peritoneal dialysis (PD) is a home-based therapy where nurses train patients in its use. There has been no published randomized controlled trial (RCT) evaluating any specific protocol for nurses delivering PD training. A standardized education package based upon the best available evidence and utilizing modern educational practices may lead to improved patient outcomes. The aim is to develop a standardized, evidence-based curriculum for PD trainers and patients aligned with guidelines from the International Society for Peritoneal Dialysis (ISPD), using best practice pedagogy., Methods: A literature search and clinical audit were conducted to identify current practice patterns and best practice. Results were reviewed by a focus group of practitioners comprising PD nurses, nephrologists, consumers, a medical education expert, and an eLearning expert. From this, a training curriculum and modules were developed., Results: A comprehensive PD training curriculum has been developed, which includes modules for training PD nurses (trainers) and patient training manuals. The package comprises 2 introductory modules and 2 clinical case modules. The curriculum is designed for both interactive digital media (trainers) and traditional paper-based teaching with practical demonstrations (patients). Assessment is also addressed., Conclusion: The need for the development of a comprehensive and standardized curriculum for PD nurse trainers and their patients was confirmed. This paper outlines the process of the development of this curriculum. Pilot testing of the modules was launched in late 2017 to examine feasibility, and planning has commenced for a RCT in 2019 to investigate the effect of the modules on clinical outcomes, and their wider application across Australia and New Zealand., (Copyright © 2019 International Society for Peritoneal Dialysis.)

An SHG-active noncentrosymmetric (3,4)-connected Zn(ii)-organic framework, {[Zn2(4-abpt)(3,4-pydc)2]·2DMAc·3MeOH·H2O}n (1-Zn), was synthesized using a mixed-ligand system. The 1-Zn framework undergoes metal metathesis, with the complete exchange of the tetrahedrally coordinated ZnII ions with CuII ions while retaining the integrity of the network.

Purpose: To investigate the anatomical and biomechanical feasibility of the unilateral C1 double screw [pedicle screw (PS) + lateral mass screw (LMS)] and ipsilateral C2 PS combined with contralateral C2 laminar screw (LS)-rod fixation for atlantoaxial instability by comparison with traditional posterior fixation methods., Methods: Fifteen sets of complete dry bony specimens of atlas were used for morphometric analysis. The working length, width and thickness of the C1 PSs and LMSs were manually measured. Ten fresh-frozen cervical spines (C0-C7) were used to complete the range of motion (ROM) testing in their intact condition, under destabilization and after stabilization by the following procedures: unilateral C1-C2 PS rod fixation (Group A), bilateral C1-C2 PS rod fixation (Group B), and unilateral C1 double screw and ipsilateral C2 PS combined with contralateral C2 LS rod fixation (Group C)., Results: The working thickness of the C1 PS was ≤ 3.5 mm in only one (1/15 = 6.7%) specimen. The other parameters were > 3.5 mm in all specimens. In the ROM test, all fixation groups showed significantly reduced flexibility in all directions compared with both the intact and destabilization groups. Further, Groups B and C showed better stability in all directions than Group A. However, no significant differences were observed between Groups B and C., Conclusion: The C1 unilateral lateral mass could mostly contain two screws(PS + LMS) with diameters ≤ 3.5 mm. The novel technique of unilateral C1 double screw and ipsilateral C2 PS combined with contralateral C2 LS rod fixation provided better stability than unilateral PS rod fixation and similar as bilateral PS rod fixation. Therefore, it is a feasible salvage method that provides a new insight into atlantoaxial instability. These slides can be retrieved under Electronic Supplementary Material.

During the last two decades, spectacular development of light-emitting diodes (LEDs) has been achieved owing to their widespread application possibilities. However, traditional LEDs suffer from unavoidable energy loss because of the down conversion of photons, toxicity due to the involvement of rare-earth materials in their production, higher manufacturing cost, and reduced thermal stability that prevent them from all-inclusive applications. To address the existing challenges associated with current commercially available white LEDs, herein, we report a broad-band emission originating from an intrinsic lanthanide-free single-molecule-based LED. Self-assembly of a butterfly-shaped strontium-based compound {[Sr(H 2 btc) 2 (MeOH)(H 2 O) 2 ]·2H 2 O} (1) was achieved through the reaction of Sr(NO 3 ) 2 with 1,2,3-benzenetricarboxylic acid hydrate (1,2,3-H 3 btc) under hydrothermal conditions. A white LED based on this single molecule exhibited a remarkable broad-band luminescence spectrum with Commission Internationale de l'Eclairage (CIE) coordinates at (0.33, 0.32) under 30 mA current injection. Such a broad luminescence spectrum can be attributed to the simultaneous existence of several emission lines originating from the intramolecular interactions within the structure. To further examine the nature of the observed transitions, density functional theory (DFT) calculations were carried out to explore the geometric and electronic properties of the complex. Our study thus paves the way toward a key step for developing a basic understanding and the development of high performance broad-band light-emitting devices with environment-friendly characteristics based on organic-inorganic supramolecular materials.

Controlling the polymerization of aniline in the presence of zirconium-based metal-organic frameworks (Zr-MOFs) using polystyrene sulfonic acid as a dopant resulted in the formation of a new type of free-standing thermoelectric composite film. Polyaniline chains interpenetrate into the Zr-MOFs to enhance the crystallinity of polyaniline, resulting in an improved degree of electrical conductivity. In addition, the inherent porosity of the Zr-MOFs functions to suppress the increase in thermal conductivity, thus dramatically promoting a negative Seebeck coefficient. When 20 wt % Zr-MOF was used, a power factor of up to 664 μW/(m K 2 ) was obtained, which was accompanied by a surprisingly large, negative Seebeck coefficient. The new class of MOF-based composites offers a new direction for developing new types of efficient thermoelectric materials.

p38 mitogen-activated protein kinase (MAPK) is an important protein which plays a key role in regulating the innate immunity, so exploring its molecular characterization is helpful in understanding the resistance against microbial infections in cultured fish. Here, a full-length cDNA of p38 MAPK was cloned from liver of blunt snout bream (Megalobrama amblycephala) which covered 2419 bp with an open reading frame of 1086 bp encoding 361 amino acids. p38 MAPK contained the characteristic structures of Thr-Gly-Tyr (TGY) motif and substrate binding site Ala-Thr-Arg-Trp (ATRW), which are conserved in MAPK family. To investigate p38 MAPK functions, two in vivo experiments were carried out to examine its expression following ammonia exposure and bacterial challenge. Also, an in vitro experiment was conducted to assess the role of p38 MAPK in inflammation of primary hepatocytes induced by lipopolysaccharide (LPS). The results showed the ubiquitous expression of p38 MAPK in all the tested tissues with varying levels. p38 MAPK mRNA expression was significantly up-regulated by ammonia stress and Aeromonas hydrophila challenge, and altered in a time-dependent manner. Moreover, the results indicated that the inflammatory response induced by LPS in hepatocytes is p38 MAPK dependent as knockdown of p38 MAPK using siRNA technology depressed the expression of IL-1β and IL-6. The findings in this study showed that p38 MAPK has anti-stress property, and plays key role in protection against bacterial infection and inflammation in blunt snout bream., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Four Zn metal⁻organic frameworks (MOFs), {[Zn₂(2,6-ndc)₂(2-Pn)]·DMF} n ( 1 ), {[Zn₂(cca)₂(2-Pn)]·DMF} n ( 2 ), {[Zn₂(thdc)₂(2-Pn)]·3DMF} n ( 3 ), and {[Zn₂(1,4-ndc)₂(2-Pn)]·1.5DMF} n ( 4 ), were synthesized from zinc nitrate and N , N '-bis(pyridin-2-yl)benzene-1,4-diamine (2-Pn) with naphthalene-2,6-dicarboxylic acid (2,6-H₂ndc), 4-carboxycinnamic acid (H₂cca), 2,5-thiophenedicarboxylic acid (H₂thdc), and naphthalene-1,4-dicarboxylic acid (1,4-H₂ndc), respectively. MOFs 1 ⁻ 4 were all constructed from similar dinuclear paddlewheel {Zn₂(COO)₄} clusters and resulted in the formation of three kinds of uninodal 6-connected non-interpenetrated frameworks. MOFs 1 and 2 suit a topologic 4⁸·6⁷-net with 17.6% and 16.8% extra-framework voids, respectively, 3 adopts a pillared-layer open framework of 4⁸·6⁶·8-topology with sufficient free voids of 39.9%, and 4 features a pcu -type pillared-layer framework of 4 12 ·6³-topology with sufficient free voids of 30.9%. CO₂ sorption studies exhibited typical reversible type I isotherms with CO₂ uptakes of 55.1, 84.6, and 64.3 cm³ g -1 at 195 K and P / P ₀ =1 for the activated materials 1' , 2' , and 4' , respectively. The coverage-dependent isosteric heat of CO₂ adsorption ( Q st ) gave commonly decreased Q st traces with increasing CO₂ uptake for all the three materials and showed an adsorption enthalpy of 32.5 kJ mol -1 for 1' , 38.3 kJ mol -1 for 2' , and 23.5 kJ mol -1 for 4' at zero coverage.

Objective: To investigate esophageal motility and reflux characteristics in gastroesophageal reflux disease (GERD) with and without extra-esophageal symptoms by high-resolution manometry and 24 h esophageal multichannel intraluminal impedance combined pH (MII-pH) monitoring. Methods: From February 2016 to June 2017, GERD patients with and without extra-esophageal symptoms were enrolled in this prospective controlled study. Esophageal HRM and 24 h MII-pH monitoring were performed. The differences in esophageal motility and reflux parameters were further analyzed between 30 GERD patients with extra-esophageal symptoms and 30 simple GERD patients. Results: The GERD symptom scores didn't show statistical difference between two groups. The GERD symptom scores didn't show statistical difference between two groups. The relaxation pressure of lower esophageal sphincter(LES), the integrated relaxation pressure, and the recovery time of upper esophageal sphincter(UES) of GERD patients with extra-esophageal symptoms were all lower than those of patients without extra-esophageal symptoms [(15±7) vs (21±11)mmHg, (8±3) vs (10±5)mmHg, (388±168) vs (492±170)ms, 1 mmHg=0.133 kPa], and the differences were statistically significant(all P <0.05). The main classification of esophageal motility type of GERD patients with extra-esophageal symptoms was mild esophageal motility disorders (27%, 8/30), and the occurrence of ineffective esophageal motivation was 20% (6/30), which were similar with simple GERD patients. The proximal reflux percentages of weak acid reflux and nonacid reflux, abnormal nonacid reflux in GERD patients with extra-esophageal symptoms were significantly higher than those in simple GERD patients [84.6% (73.2%, 100.0%) vs 75.0% (60.0%, 87.65%), P =0.048; 90.0% (45.8%, 100.0%) vs 0(0, 100.0%), P =0.017; 46.7% vs 3.3%, P =0.03]. Conclusions: The pathogenesis of GERD with extra-esophageal symptoms may be different from typical GERD. Increase of proximal esophageal reflux and abnormal nonacid reflux may all participate in the mechanisms of GERD with extra-esophageal symptoms.

A new 3D coordination polymer {[Co2(μ-OH2)(TTPA)(DTDN)2·DMF]·H2O}n (1, TTPA = tris(4-(1H-1,2,4-triazol-1-yl)phenyl)amine, DTDN = 6,6'-dithiodinicotinate) was synthesised and characterised. The redox properties of this framework were elucidated by solid state electrochemical and spectroelectrochemical data. This is the first investigation of the redox behaviour of TTPA in coordination polymers. Furthermore, the incorporation of a paramagnetic Co(ii) metal ion into the framework caused 1 to show spin-flop behaviour as the result of a field-induced magnetic transition. The incorporation of two flexible ligands and Co(ii) metal ions represents a feasible approach for the advancement of multifunctional materials.

The Asia-Pacific region has 60% of the world's population. There is a huge variability in ethnic groups, geography, diseases, and income. The otolaryngology workforce depends on the number of medical graduates, training programs, scope of practice, and available employment. Training has been influenced by the British, Russian, and US training systems, and by local influences and experience. Otolaryngologic diseases are similar to those seen in the United States but with ethnic and regional differences. There are opportunities for humanitarian service but the most sustainable projects will include repetitive visits with transfer of knowledge., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Anterior percutaneous endoscopic transcorporeal cervical discectomy is an alternative operation for cervical disc herniation. However, few reports have evaluated the biomechanical influence of tunnels on vertebrae. We compared biomechanical distinctions between intact and tunneled models of vertebrae to analyze the safety of anterior percutaneous endoscopic transcorporeal cervical discectomy based on a C2-T1 finite element (FE) model., Methods: Groups of C2-T1 FE models were simulated with C4 tunneled by 2 methods (group A: with partial superior endplate excision; group B: without partial superior endplate excision) and various tunnel diameters (6, 8, and 10 mm). All FE models were loaded under a 1-Nm flexion moment., Results: The area and maximum of stress concentrations were correlated with tunnel diameter. The distribution of stress on C4 superior endplates showed no significant difference between B6 and the intact model (P > 0.05), but significant differences with other tunneled models (P < 0.001). Maximum stress on the lateral wall of tunnels was positively correlated with tunnel diameter and induced high risks of cancellous bone fracture for diameters reaching 10 mm in group B and 8 mm in group A., Conclusions: Transcorporeal tunnel in C4 vertebrae without endplate excision should be limited with diameter of 6 mm, and a tunnel diameter >10 mm, excision of the endplate >8 mm, and excision of the center side of the endplate should also be avoided., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A discrete complex [Zn(tpro)₂(H₂O)₂] ( 1 , Htpro = l-thioproline), and two structural isomers of coordination polymers, a 1D chain of [Zn(tpro)₂] n ( 2 ) and a layered structure [Zn(tpro)₂] n ( 3 ), were synthesized and characterized. The discrete complex 1 undergoes a temperature-driven structural transformation, leading to the formation of a 1D helical coordination polymer 2 . Compound 3 is comprised of a 2D homochiral layer network with a (4,4) topology. These layers are mutually linked through hydrogen bonding interactions, resulting in the formation of a 3D network. When 1 is heated, it undergoes nearly complete conversion to the microcrystalline form, i.e., compound 2 , which was confirmed by powder X-ray diffractions (PXRD). The carboxylate motifs could be activated after removing the coordinated water molecules by heating at temperatures of up to 150 °C, their orientations becoming distorted, after which, they attacked the activation sites of the Zn(II) centers, leading to the formation of a 1D helix. Moreover, a portion of the PXRD pattern of 1 was converted into the patterns corresponding to 2 and 3 , and the ratio between 2 and 3 was precisely determined by the simulation study of in-situ synchrotron PXRD expriments. Consequently, such a 0D complex is capable of underdoing structural transformations and can be converted into 1D and/or 2D amino acid-based coordination polymers., Competing Interests: The authors declare no competing financial interests.

Introduction: Up to a 10-fold difference in clinical outcomes between Australian peritoneal dialysis (PD) units exists. There is an international focus on the harmonization of educational practices in PD to determine whether this may lead to improved patient outcomes., Aims: The aim of this paper is to evaluate the current teaching practices of nurses and patients in Australian PD units., Methods: An online survey with questions on nurse and patient training was made available to PD units in Australia., Results: Thirty-eight (70%) of 54 PD units in Australia completed the survey. A written standardized curricula was utilized in 21 units (55%) for nursing staff and 30 units (79%) for patients, with 23% and 12% including an electronic delivery component for each group, respectively. Universal teaching of adult learning principles was not demonstrated. The hours spent on teaching nursing staff ranged from <15 h in 24% to >100 h in 21% of units. The average number of hours spent by nurses each day to train patients ranged from <2 h in 14% to >6 h in 11% of units, with the average total training days ranging from 2 to 3 days in 14% to over 7 days in 14% of units. Staff and patient competency assessments were performed routinely in 37% and 74% of units, respectively., Conclusions: Considerable differences exist amongst Australian PD units in the education of staff and patients. There is a general lack of delivery and competency assessment to meet educational standards. It remains to be seen if harmonization of educational curricula can translate to improved clinical outcomes., (© 2017 Asian Pacific Society of Nephrology.)

The device characteristics of semiconductor quantum dot lasers have been improved with progress in active layer structures. Self-assembly formed InAs quantum dots grown on GaAs had been intensively promoted in order to achieve quantum dot lasers with superior device performances. In the process of growing high-density InAs/GaAs quantum dots, bimodal size occurs due to large mismatch and other factors. The bimodal size in the InAs/GaAs quantum dot system is eliminated by the method of high-temperature annealing and optimized the in situ annealing temperature. The annealing temperature is taken as the key optimization parameters, and the optimal annealing temperature of 680 °C was obtained. In this process, quantum dot growth temperature, InAs deposition, and arsenic (As) pressure are optimized to improve quantum dot quality and emission wavelength. A 1.3-μm high-performance F-P quantum dot laser with a threshold current density of 110 A/cm 2 was demonstrated.

rDNA loci, composed of hundreds of tandemly duplicated arrays of rRNA genes, are known to be among the most unstable genetic elements due to their repetitive nature. rDNA instability underlies aging (replicative senescence) in yeast cells, however, its contribution to the aging of multicellular organisms is poorly understood. In this study, we investigate the dynamics of rDNA loci during aging in the Drosophila male germline stem cell (GSC) lineage, and show that rDNA copy number decreases during aging. Our study further reveals that this age-dependent decrease in rDNA copy number is heritable from generation to generation, yet GSCs in young animals that inherited reduced rDNA copy number are capable of recovering normal rDNA copy number. Based on these findings, we propose that rDNA loci are dynamic genetic elements, where rDNA copy number changes dynamically yet is maintained through a recovery mechanism in the germline., Competing Interests: KL, JN, GW, NW No competing interests declared, YY Reviewing editor, eLife, (© 2018, Lu et al.)

The detection of chemical explosives is a major area of research interest and is essential for the military as well as homeland security to counter the catastrophic effects of global terrorism. In recent years, tremendous effort has been devoted to the development of luminescent materials for the detection of explosives in the vapor, solution, and solid states with a high degree of selectivity and sensitivity and a rapid response time. Apart from the wide range of organic fluorescent chemosensors, transition metal complexes play a prominent role in the sensing of nitroaromatic explosives owing to their rich photophysical characteristics. This review briefly summarizes the salient features of the design and preparation of transition metal (Zn(ii), Ir(iii), Pd(ii), Pt(ii), Re(i) and Ru(ii)) complexes/metallacycles/metallosupramolecules with emphasis on their photophysical properties, sensing behavior, mechanism of action, and the driving forces for detecting explosives and future prospects and challenges. Most of the probes that have been reported to date act as "turn-off" luminescent sensors because their emission (intensity, lifetime, and quantum yield) is eventually quenched upon sensing with nitroaromatic compounds (NACs) through photo-induced electron or energy transfer. These unique properties of transition metal complexes in response to explosives open up new vistas for the development of real world applications such as on-site detection, in-field security, forensic research, etc.

Fish farming seriously influences the aquatic environment because most dietary phosphorus (P) is excreted in the effluent. To increase the P utilization in fish, molecular techniques should be explored given the remarkable development of these techniques. Thus, to identify the candidate genes related to P utilization and molecular alterations following administration of a P-deficient diet in seabass Lateolabrax japonicus, we assessed the de novo pituitary, gill, intestine, liver, kidney, scales and vertebra transcriptomes, and we compared the expression of hepatic genes with three diets varying in P and Ca levels: diet I (0.4% P, 0.3% Ca), diet II (0.8% P, 0.3% Ca), and diet III (0.8% P, 3% Ca). In total, we identified 99,392 unigenes, and 37,086 (37.31%) unigenes were annotated. The results showed that 48 unigenes were significantly (P<0.05) up-regulated, while 55 genes were significantly down-regulated in the liver of group I compared with group II. Offering the P-sufficient and high Ca diet, diet III significantly up-regulated 24 unigenes and down-regulated 46 genes in the liver. There were significant differences in the regulation of 8 unigenes (3 up-regulated and 5 down-regulated) between groups II and III. Gene ontology (GO) functional enrichment and KEGG pathway analysis of differently expressed genes were performed for each pair of groups. The GO analysis showed that a large number of biological processes were significantly altered between P-deficient and P-sufficient treatments (I vs II and I vs III). Comparing group I and group II, seven KEGG terms were enriched significantly: glycine, serine and threonine metabolism, one carbon pool by folate, arginine and proline metabolism, the biosynthesis of unsaturated fatty acids, fatty acid elongation, drug metabolism-cytochrome P450, and fatty acid metabolism. There was no significantly enriched KEGG pathway between groups II and III. In conclusion, our study revealed that a P-deficient diet could increase catabolism and decrease anabolism of protein, as highlighted by low protein efficiency in fish fed the P-deficient diet. Furthermore, P-deficiency could motivate the biosynthesis of fatty acids. However, the dietary Ca level had no significant effect on the growth and expression of hepatic genes in L. japonicus., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: To identify whether chitinase 3-like 1 (CHI3L1) serves as a suitable biomarker for the prognosis of esophageal squamous cell carcinoma (ESCC) and to analyze this protein's cellular source., Methods: An ELISA was conducted to detect the concentration of CHI3L1 in the serum of 150 ESCC patients diagnosed between January 2001 and February 2005. The prognostic relevance of CHI3L1 was evaluated by a Kaplan-Meier and Cox regression analysis. The immunohistochemistry was reanalyzed, and fluorescent staining was utilized to explore the cellular origins of CHI3L1. We stimulated monocyte-derived macrophages (MDMs) with either IL-6 or the supernatant of the ESCC cell line Eca-109 and later investigated the level of CHI3L1 by qPCR and ELISA., Results: The level of serum CHI3L1 was higher in older patients (≥ 60) than in patients under the age of 60 ( P = 0.001). The patients with higher levels of CHI3L1 had a significantly shorter overall survival, whereas the traditional markers, carcinoembryonic antigen and squamous cell carcinoma antigen, were less effective ( P > 0.05). A multivariate Cox analysis ( P = 0.001) indicated that CHI3L1 was an independent prognostic factor for ESCC patients. Peritumoral macrophages in ESCC exhibited high levels of CHI3L1. Interleukin-6 (IL-6) and the supernatant of Eca-109 containing IL-6 stimulated MDMs to secrete CHI3L1. The serum concentration of CHI3L1 in the ESCC patients showed a weak correlation with the laboratory inflammatory parameters neutrophil (NEU, P = 0.045), neutrophil/lymphocyte rate (NLR, P = 0.016), and C-reactive protein (CRP, P < 0.001)., Conclusion: Our study first established a connection between the pretreated CHI3L1 and patients with ESCC, and the serum CHI3L1 was primarily secreted by ESCC-surrounded macrophages., Competing Interests: Conflict-of-interest statement: The authors declare no potential conflicts of interest.

Preschool-aged children typically perform worse than 20/20 on visual acuity testing in the absence of ocular or visual pathway abnormalities due to non-ocular issues, including concentration, cooperation, and/or confidence. As a result, vision screening for this age group can be a challenge. The "Rule of 8" is an easy-to-remember, highly effective mnemonic that clinicians can use to help differentiate children who are performing visual acuity testing at age-appropriate levels from those who may need further evaluation. [J Pediatric Ophthalmol Strabismus. 2017;54:e75-e76.]., (Copyright 2017, SLACK Incorporated.)

A dynamic metal-organic framework that consists of d-champhorate-based homochiral protuberant-grid-type networks can successively participate in gate-opening and closing processes for many cycles, which were triggered by the stimuli of the adsorption and desorption of CO 2 to highly and specifically recognize CO 2 over N 2 and H 2 with a high CO 2 uptake of 90 mg g -1 under 35 bar at 298 K. It is highly thermally stable and the structure remains intact at least for ten reversible gate-opening and -closing processes. Thus, it is a potential candidate for industrial CO 2 capture and facile release.

Two broadly known characteristics of germ cells in many organisms are their development as a 'cyst' of interconnected cells and their high sensitivity to DNA damage. Here we provide evidence that in the Drosophila testis, connectivity serves as a mechanism that confers to spermatogonia a high sensitivity to DNA damage. We show that all spermatogonia within a cyst die synchronously even when only a subset of them exhibit detectable DNA damage. Mutants of the fusome, an organelle that is known to facilitate intracyst communication, compromise synchronous spermatogonial death and reduces overall germ cell death. Our data indicate that a death-promoting signal is shared within the cyst, leading to death of the entire cyst. Taken together, we propose that intercellular connectivity supported by the fusome uniquely increases the sensitivity of the germline to DNA damage, thereby protecting the integrity of gamete genomes that are passed on to the next generation.

The self-assembly of a samarium-based metal-organic framework [Sm 2 (bhc)(H 2 O) 6 ] n (1) in good yield was achieved by reacting Sm(NO 3 ) 3 ·6H 2 O with benzenehexacarboxylic acid (bhc) in a mixture of H 2 O-EtOH under hydrothermal conditions. A structural analysis showed that compound 1 crystallized in a space group of Pnmn and adopted a 3D structure with (4,8) connected nets. Temperature dependent dielectric measurements showed that compound 1 behaves as a high dielectric material with a high dielectric constant (κ = 45.1) at 5 kHz and 310 K, which is comparable to the values for some of the most commonly available dielectric inorganic metal oxides such as Sm 2 O 3 , Ta 2 O 5 , HfO 2 , and ZrO 2 . In addition, electrical measurements of 1 revealed an electrical conductivity of about 2.15 × 10 -7 S/cm at a frequency of 5 kHz with a low leakage current (I leakage = 8.13 × 10 -12 Amm -2 ). Dielectric investigations of the Sm-based MOF provide an effective path for the development of high dielectric materials in the future.

Three dendrimers, (t-Bu-G 2 N) 2 , CC(t-Bu-G 1 N) 3 and (t-Bu-G 1 N) 2 , with 3,5-di-tert-butyl amidobenzene as a common peripheral moiety were prepared in 64-83% yields and characterized. The bulk solids had high BET surface areas of 136-138 m 2 /g, which were similar for the three dendrimers in spite of their different molecular weight (ranging from 1791 to 2890). It was concluded that the peripheral amide groups do not imbed in the interstitial space of neighbouring dendrimer molecules but rather build a supramolecular architecture through strong intermolecular H-bonds. This mode of assembly generates voids in the bulk dendrimers responsible for sorption properties. The X-ray crystal structure analysis of a compound representing the peripheral moiety of the dendrimers and the FT-IR and powder-XRD data for (t-Bu-G 1 N) 2 suggest the proposed supramolecular structure. The isosteric heats of CO 2 sorption (Q st ) for (t-Bu-G 2 N) 2 were significantly higher than those for the other two dendrimers, which is consistent with the formation of a different type of voids within the interstitial space of the molecule. It is suggested that the interstitial void space can be designed and tuned to adjust its properties to a particular task, such as the separation of gases or a catalytic reaction facilitated by the dendrimer.

A novel one-pot reaction has been developed for the efficient synthesis of pyrrolo[2,1-a]isoquinolines and 1-dearyllamellarin core from (E)-(2-nitrovinyl)benzenes and azomethine ylides generated in situ. This strategy provides a concise total synthesis of the lamellarin core and lamellarin G trimethyl ether using electrophilic substitution and palladium-catalyzed Suzuki-Miyaura cross-coupling reactions.

Metal-organic frameworks (MOFs) with low density, high porosity, and easy tunability of functionality and structural properties, represent potential candidates for use as semiconductor materials. The rapid development of the semiconductor industry and the continuous miniaturization of feature sizes of integrated circuits toward the nanometer (nm) scale require novel semiconductor materials instead of traditional materials like silicon, germanium, and gallium arsenide etc. MOFs with advantageous properties of both the inorganic and the organic components promise to serve as the next generation of semiconductor materials for the microelectronics industry with the potential to be extremely stable, cheap, and mechanically flexible. Here, a perspective of recent research is provided, regarding the semiconducting properties of MOFs, bandgap studies, and their potential in microelectronic devices., (© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

High-fat diets may have favorable effects on growth and cost, but high-fat diets often induce excessive fat deposition, resulting in liver damage. This study aimed to identify the hepatoprotective of a Chinese herb (berberine) for blunt snout bream (Megalobrama amblycephala). Fish were fed with a normal diet (LFD, 5 % fat), high-fat diet (HFD, 15 % fat) or berberine-supplemented diets (BSD, 15 % fat with berberine 50 or 100 mg/kg level) for 8 weeks. After the feeding, histology, oxidative status and mitochondrial function of liver were assessed. The results showed that HFD caused fat accumulation, oxidative stress and apoptosis in hepatocytes of fish. Hepatocytes in HFD group appeared to be hypertrophied, with larger liver cells diameter than these of LFD group. Berberine-supplemented diets could attenuate oxidative stress and hepatocytes apoptosis. HFD induced the decreasing mitochondrial complexes activities and bulk density and surface area density. Berberine improved function of mitochondrial respiratory chain via increasing the complex activities. Moreover, the histological results showed that berberine has the potential to repair mitochondrial ultrastructural damage and elevate the density in cells. In conclusion, our study demonstrated that berberine has attenuated liver damage induced by the high fat mainly via the protection for mitochondria.

The skull base attachment of the second lamella and suprabullar pneumatization are likely to be consistent landmarks if they are systematically classified. This study aimed to classify the pneumatization pattern according to the second lamella skull base attachment. A total of 202 computed tomography sides of 101 patients who underwent endoscopic sinus surgery were studied. Suprabullar pneumatization was defined as air cells present above the ethmoid bulla between the second and third lamellae. Its pattern was classified according to the air cell number and location as in the frontal cell classification. Type 0 suprabullar pneumatization was defined as no air cells between the ethmoid bulla and skull base; type 1, as a single suprabullar cell; and type 2, as multiple suprabullar cells above the ethmoid bulla. In type 3 pneumatization, the second lamella extended into the frontal sinus forming a frontal bullar cell. Type 2 was the most prevalent (40.1 %), followed by types 1, 3, and 0 (24.3, 23.3, and 12.4 %, respectively). The distance between the second lamella and anterior ethmoid artery was 8.93, 8.30, 8.50, and 11.25 mm in types 0, 1, 2, and 3 pneumatization, respectively. No patients had intraoperative injuries in the anterior ethmoid artery or lateral lamella. The second lamella skull base attachment and suprabullar pneumatization pattern could be systematically classified and be a consistent landmark to identify the frontal sinus opening.

Background: This study investigated on bacterial contamination of the rhinoplasty field. The effect of preoperative chlorhexidine treatment on decreasing bacterial contamination in the rhinoplasty field is examined., Methods: Thirty patients who underwent rhinoplasty were block randomized into a chlorhexidine, regular-soap, or control group comprising ten participants each. The chlorhexidine group was subjected to chlorhexidine showering, shampooing, and facial-cleansing 12 h prior to the operation. The regular-soap group was subjected to cleansing with regular soap, and the control group did not have any skin pretreatment. Bacterial cultures were done 12 h preoperatively from nasal cavity and perinasal skin, immediately preoperatively from perinasal skin and at 1 and 2 h intraoperatively from operation field. Culture results were compared between the three groups, according to operation time, or whether infection-prone procedure was performed., Results: The bacterial species and colony-forming unit numbers at preoperative nasal cavity and perinasal skin were similar. In all three groups, Coagulase - negative staphylococcus was the most common bacteria found in the rhinoplasty field. The numbers of Staphylococcus aureus and Corynebacterium decreased rapidly after preoperative chlorhexidine treatment. The infection-prone procedure was associated with increased bacterial numbers over time during the operation. In all three groups, there was no postoperative infection in a follow-up period of 6 months., Conclusion: Rhinoplasty is confirmed as a clean contaminated operation with skin flora consistently found in the operation field. Chlorhexidine pretreatment in rhinoplasty patients has a tendency to decrease the numbers of Staphylococcus aureus and Corynebacterium on the perinasal skin., Level of Evidence: Randomized controlled trial, Level I.

An evanescent wave infrared chemical sensor was developed to selectively detect volatile amines with heterocyclic or phenyl ring. To achieve this goal, a rhenium-based metallacycle with a "molecular-trap" structure was designed and synthesized as host molecules to selectively trap amines with heterocyclic or phenyl ring through Re-amine and π-π interactions. To explore the trapping properties of the material, a synthesized Re-based molecular trap was treated on an IR sensing element, and wide varieties of volatile organic compounds (VOCs) were examined to establish the selectivity for detection of amines. Based on the observed IR intensities, the Re-based molecular trap favors interaction with amines as evidenced by the variation of absorption bands of the Re molecular trap. With extra π-π interaction force, molecules, such as pyridine and benzylamine, could be detected. After optimization of the parameters for IR sensing, a rapid response in the detection of pyridine was observed, and the linear ranges were generally up to 10 mg/L with a detection limit around 5.7 μg/L. In the presence of other VOCs, the recoveries in detection of pyridine were all close to 100%.

A new 3D tubular zinc phosphite, Zn 2 (C 22 H 22 N 8 ) 0.5 (HPO 3 ) 2 ⋅H 2 O (1), incorporating a tetradentate organic ligand was synthesized under hydro(solvo)thermal conditions and structurally characterized by single-crystal X-ray diffraction. Compound 1 is the first example of inorganic zincophosphite chains being interlinked through 1,2,4,5-tetrakis(imidazol-1-ylmethyl)benzene to form a tubular porous framework with unusual organic-inorganic hybrid channels. The thermal and chemical stabilities, high capacity for CO 2 adsorption compared to that for N 2 adsorption, and interesting optical properties of LED devices fabricated using this compound were also studied., (© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Light-emitting diodes (LEDs) have drawn tremendous potential as a replacement of traditional lighting due to its low-power consumption and longer lifetime. Nowadays, the practical white LEDs (WLED) are contingent on the photon down-conversion of phosphors containing rare-earth elements, which limits its utility, energy, and cost efficiency. In order to resolve the energy crisis and to address the environmental concerns, designing a direct WLED is highly desirable and remains a challenging issue. To circumvent the existing difficulties, in this report, we have designed and demonstrated a direct WLED consisting of a strontium-based metal-organic framework (MOF), {[Sr(ntca)(H2O)2]·H2O}n (1), graphene, and inorganic semiconductors, which can generate a bright white light emission. In addition to the suitable design of a MOF structure, the demonstration of electrically driven white light emission based on a MOF is made possible by the combination of several factors including the unique properties of graphene and the appropriate band alignment between the MOF and semiconductor layer. Because electroluminescence using a MOF as an active material is very rare and intriguing and a direct WLED is also not commonly seen, our work here therefore represents a major discovery which should be very useful and timely for the development of solid-state lighting.

A transition-metal-free coupling annulation reaction of arynes, ketones, and alkynoates has been demonstrated. Using this formal [2 + 2 + 2] cycloaddition reaction, a wide variety of naphthalene derivatives were conveniently constructed in one pot with high efficiency. In addition, this novel and valid annulation has been successfully applied to the synthesis of 1-phenanthrenol derivatives.

A one-pot acid-mediated reaction has been developed for the N-H/α,β-C(sp(3))-H trifunctionalization of pyrrolidine without any metallic reagents or external oxidants. This reaction involves the intermolecular [3 + 2] cycloaddition of in situ-generated azomethine ylides with acrylic esters to provide facile access to 2,3-dihydro-1H-pyrrolizine derivatives in high yields under mild conditions.

Unlabelled: We compared the degree of postoperative iris distortion with the diamond-shaped Malyugin ring and the circular Visitec I-Ring iris dilators using postoperative iris photographs in a patient with bilateral small nondilating pupils. Routine phacoemulsification was performed in the right eye with the assistance of a Malyugin ring for iris dilation. One month later, the same procedure was performed in the left eye using the circular ring for iris dilation. Anterior chamber slitlamp photographs were taken of both eyes. The amount of distortion in the postoperative pupils was calculated using the ratio of the postoperative pupil area to the area of the circle of best fit. The circular ring, constructed from a softer material, resulted in 11% distortion and the Malyugin ring, 49%, suggesting that the circular ring caused less trauma to the iris., Financial Disclosure: None of the authors has a financial or proprietary interest in any material or method mentioned., (Copyright © 2016 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Mesenchymal stem cells (MSCs) are suitable seed cells for bone tissue engineering because they can self-renew and undergo differentiation into osteogenic, adipogenic, chondrogenic, or myogenic lineages. Vascular endothelial growth factor-a (VEGF-a), an angiogenic factor, is also involved in osteogenesis and bone repair. However, the effects of VEGF-a on osteogenic MSCs differentiation remain unknown. It was previously reported that bone morphogenetic protein9 (BMP9) is one of the most important osteogenic BMPs. Here, we investigated the effects of VEGF-a on BMP9-induced osteogenesis with mouse embryo fibroblasts (MEFs). We found that endogenous VEGF-a expression was undetectable in MSCs. Adenovirus-mediated expression of VEGF-a in MEFs potentiated BMP9-induced early and late osteogenic markers, including alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). In stem cell implantation assays, VEGF-a augmented BMP9-induced ectopic bone formation. VEGF-a in combination with BMP9 effectively increased the bone volume and osteogenic activity. However, the synergistic effect was efficiently abolished by the phosphoinositide 3-kinase (PI3K)/AKT inhibitor LY294002. These results demonstrated that BMP9 may crosstalk with VEGF-a through the PI3K/AKT signaling pathway to induce osteogenic differentiation in MEFs. Thus, our findings demonstrate the effects of VEGF-a on BMP9-induced bone formation and provide a new potential strategy for treating nonunion fractures, large segmental bony defects, and/or osteoporotic fractures.

In this study, it was the first time that we simultaneously quantified nimesulide and its possible metabolites M1, M2, M3 and M4 by employing liquid chromatography-tandem mass spectrometry (LC-MS/MS). Nimesulide-d5 was used as internal standard (IS) for validation. Analytes and IS were recovered from human plasma by protein precipitation with acetonitrile. Prepared plasma samples were analyzed under the same LC-MS/MS conditions, and chromatographic separation was realized by using an Ultimate C18 column, with run time being 5min for each sample. Our results showed that various analytes within their concentration ranges could be quantified accurately by using the method. Mean intra- and inter-day accuracies ranged from -4.8% to 4.8% (RE), and intra- and inter-assay precision ≤6.2% (RSD). The following parameters were validated: specificity, recovery, matrix effects, dilution integrity, carry-over, sample stability under a variety of storage and handling conditions (room temperature, freezer, freeze-thaw and post-preparative) and stock solution stability. Pharmacokinetics of nimesulide and its metabolites were calculated based on the analysis of samples collected from twelve Chinese healthy volunteers after single oral dose of 100mg nimesulide tablets. By applying the pharmacokinetic determination into human samples, we preliminarily detected a new metabolite of nimesulide (M4*), and the concentration of M4* was relatively higher in plasma. Furthermore, we predicted part of conceivable metabolism pathway in plasma of after oral administration of 100mg nimesulide tablets. This research provided an experimental basis for further studies on metabolic activation and biotransformation of nimesulide, and for more comprehensive conjecture of its metabolic pathways., (Copyright © 2016. Published by Elsevier B.V.)