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Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) is a promising drug target for antimalarial chemotherapy. In our continuous efforts to develop more potent PfDHODH inhibitors, a unique library of active ingredients from traditional Chinese medicine (TCM) has been collected and was screened in this study. Through the initial screening, we found that coptisine, a natural alkaloid from TCM Coptidis Rhizoma, was a novel and potent inhibitor of PfDHODH with an IC50 value of 1.83 ± 0.08 μ m. At the same time, enzyme kinetic analysis using Lineweaver‐Burk plot indicated that coptisine is an uncompetitive inhibitor for PfDHODH. Thermal shift assay and molecular docking simulation research reveal that coptisine is capable of binding with PfDHODH. Moreover, coptisine exhibits weak inhibition activity against human DHODH, indicating that coptisine is a selective inhibitor of PfDHODH. Taken together, our study highlights the potential of active ingredients in TCM as valuable resource for discovering novel chemical scaffolds for PfDHODH. [ABSTRACT FROM AUTHOR]

A triangle arrayed triple‐screw extruder was used to prepare in situ polypropylene (PP) microfibrillar composites (MFCs) by direct extrusion, in which polyamide 6,6 (PA66) and poly(butylene terephthalate) (PBT) were used as dispersed phases while PP as matrix phase. The morphological evolution of the dispersed phase were investigated by SEM through taking samples along the extruder from different positions. The results showed that the fibrillating mechanism of PA66 was entirely different from that of PBT. Dynamic oscillatory shear rheological properties were used to analyze the effect of different types of in situ microfibrils on the rheological properties of MFCs. The obtained results showed that the storage modulus and complex viscosity of both PP/PA66 and PP/PBT MFCs were improved with increasing fibrillar aspect ratios. The loss tangent tan δ at low frequencies decreased with the increase of fibrillar aspect ratio. Moreover, the gel point concentration of PP/PA66 composite was lower than that of PP/PBT composite. [ABSTRACT FROM AUTHOR]

Abstract: Chronic inflammation is a key driver of cancer development. Nitrite levels, which are regulated by inducible nitric oxide synthase (iNOS), play a critical role in inflammation. While the anti‐oxidant and anti‐inflammatory effects of curcumin, a natural product present in the roots of Curcuma longa have been studied widely, the acute pharmacokinetics (PK) and pharmacodynamics (PD) of curcumin in suppressing pro‐inflammatory markers and epigenetic modulators remain unclear. This study evaluated the PK and PD of curcumin‐induced suppression of lipopolysaccharide (LPS)‐mediated inflammation in rat lymphocytes. LPS was administered intravenously either alone or with curcumin to female Sprague–Dawley rats. Plasma samples were analysed for curcumin concentration and mRNA expression was quantified in lymphocytes. The relative gene expression of several inflammatory and epigenetic modulators was analysed. To investigate the relationship between curcumin concentration and iNOS, TNF‐α, and IL‐6 gene expression, PK/PD modeling using Jusko's indirect response model (IDR) integrating transit compartments (TC) describing the delayed response was conducted. The concentration–time profile of curcumin exhibited a bi‐exponential decline, which was well described by a two‐compartmental pharmacokinetic model. Importantly the results demonstrate that LPS induced gene expression of pro‐inflammatory markers in lymphocytes, with peak expression at approximately 3 h and curcumin suppressed the gene expression in animals administered with LPS. These effects were well captured using the IDR model and an IDR model with the transit compartments. In summary, the PK/PD modeling approach could potentially provide a robust quantitative framework for evaluating the acute anti‐inflammatory and epigenetic effects of curcumin in future clinical trials. [ABSTRACT FROM AUTHOR]

Abstract: The number of elderly patients with cancer is increasing. Medical comorbidities are more common in this population. Little is known regarding the prognostic relevance of comorbidities in elderly patients with nasopharyngeal carcinoma (NPC). Using the National Cancer Data Base (NCDB), we queried patients age >65 years diagnosed with NPC and treated with definitive radiation between 2004 and 2012 to examine the association between comorbidity and survival outcomes. Comorbidity was assessed with the Charlson Comorbidity Index (CCI). The influence of comorbidity on overall survival (OS) was evaluated. Cox proportional hazards model was used to study the impact of comorbidity on OS. A total of 1137 patients met the specified criteria. Median follow‐up was 61.2 months. Five‐year OS was 50.4%. Comorbidities were present in 22.4% of patients, with 17.6% of patients having a CCI score of 1% and 4.8% having a CCI score of ≥2. Patients with a CCI score of 0 had significantly higher 5‐year OS than patients with a CCI score of 1 or ≥2 (53.1% vs. 42.2% vs. 32.9%, P < 0.001). In multivariate analysis, CCI was a statistically significant independent prognostic factor for the risk of death of all causes for patients with a CCI score of 1 (hazard ratio [HR]: 1.242; 95% confidence interval [CI]: 1.002–1.539) or CCI score of ≥2 (HR: 1.625; 95% CI: 1.157–2.283) when compared to patients with a CCI score of 0. Comorbidity as measured by CCI is a strong independent prognostic factor for OS in elderly patients with NPC and lends support to the inclusion of comorbidity assessment due to its prognostic value when treating elderly patients with NPC. [ABSTRACT FROM AUTHOR]

ABSTRACT Highly flexible and electrically conductive graphene nanoparticles/carbon black/silicon rubber (GNPs/CB/SR) based nanocomposite foams were formed by using azodicarbonamide (AC) physical foaming technology. The foaming parameters (foaming agent and foaming time) were analyzed to investigate the influence on the electrical properties and microcellular structure. The electrical percolation threshold of GNPs/CB/SR nanocomposite foams approximately decreases from 25% to 30%, as the volume expansion increases through foaming. Nanocomposite foams with conductive fillers of 3-12 wt %, foaming agent of 12-18 wt %, foaming time of about 150-500 s, relative densities of 1.0-0.4 g/cm3 were achieved, providing a scheme to evaluate the transformation of electrical properties with different foaming degree. It is worth noting that the product of AC agent concentration and foaming time reaches a certain value, and the highest electrical conductivity of foamed nanocomposites could be achieved. The nonmonotonicity changing of the electrical conductivity was demonstrated. Combined with the microtopography characterization, the cell growth effect was introduced to illustrate the transformation mechanism of the electrical conductivity. The relationship between the microcellular structure and the electrical conductivity of the foamed nanocomposites was established, which is essential for further optimizations of the foaming materials for the targeted application. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2018, 135, 45996. [ABSTRACT FROM AUTHOR]

Abstract: Cubic Cu2O/Cu2S particles with a novel truncated edge structure anchoring on reduced graphene oxide (Cu2O/Cu2S‐rGO composites) were synthesized by using a facile growth process. Compared to simple Cu2O cubes and bare Cu2O/Cu2S particles, the Cu2O/Cu2S‐rGO composite shows a competitive capacity and stable cyclic stability as anode materials for sodium‐ion batteries (SIBs). At a low current density of 60 mA g−1, the Cu2O/Cu2S‐rGO composite delivers an initial discharge capacity of 878.6 mAh g−1, stable cycling stability of 417.35 mAh g−1 after 100 cycles, retaining 73.5 % of its initial charge capacity, demonstrating a significantly improved cycling reversibility and structural stability. The enhanced electrochemical performance for Cu2O/CuxS‐rGO composites might be ascribed to the rGO coating and the “breathable” structure formed by Cu2O and Cu2S. The outer coated rGO nanosheets could maintain the structural integrity and electrical conductivity, and the main active component (Cu2O and Cu2S) is present in the form of small clusters, providing “breathable” aggregates capable of effective sequential shrinkage and expansion. [ABSTRACT FROM AUTHOR]

Summary: An up‐regulated gene derived from Bamboo mosaic virus (BaMV)‐infected Nicotiana benthamiana plants was cloned and characterized in this study. BaMV is a single‐stranded, positive‐sense RNA virus. This gene product, designated as NbTRXh2, was matched with sequences of thioredoxin h proteins, a group of small proteins with a conserved active‐site motif WCXPC conferring disulfide reductase activity. To examine how NbTRXh2 is involved in the infection cycle of BaMV, we used the virus‐induced gene silencing technique to knock down NbTRXh2 expression in N. benthamiana and inoculated the plants with BaMV. We observed that, compared with control plants, BaMV coat protein accumulation increased in knockdown plants at 5 days post‐inoculation (dpi). Furthermore, BaMV coat protein accumulation did not differ significantly between NbTRXh2‐knockdown and control protoplasts at 24 hpi. The BaMV infection foci in NbTRXh2‐knockdown plants were larger than those in control plants. In addition, BaMV coat protein accumulation decreased when NbTRXh2 was transiently expressed in plants. These results suggest that NbTRXh2 plays a role in restricting BaMV accumulation. Moreover, confocal microscopy results showed that NbTRXh2‐OFP (NbTRXh2 fused with orange fluorescent protein) localized at the plasma membrane, similar to AtTRXh9, a homologue in Arabidopsis. The expression of the mutant that did not target the substrates failed to reduce BaMV accumulation. Co‐immunoprecipitation experiments revealed that the viral movement protein TGBp2 could be the target of NbTRXh2. Overall, the functional role of NbTRXh2 in reducing the disulfide bonds of targeting factors, encoded either by the host or virus (TGBp2), is crucial in restricting BaMV movement. [ABSTRACT FROM AUTHOR]

Epigenetic modifications such as histone modifications and cytosine hydroxymethylation are linked to tumorigenesis. Loss of 5-hydroxymethylcytosine (5 hmC) by teneleven translocation 1 (TET1) down-regulation facilitates tumor initiation and development. However, the mechanisms by which loss of TET1 knockdown promotes malignancy development remains unclear. Here, we report that TET1 knockdown induced epithelial-mesenchymal transition (EMT) and increased cancer cell growth, migration, and invasion in DLD1 cells. Loss of TET1 increased EZH2 expression and reduced UTX-1 expression, thus increasing histone H3K27 tri-methylation causing repression of the target gene E-cadherin. Ectopic expression of the H3K27 demethylase UTX-1 or EZH2 depletion both impeded EZH2 binding caused a loss of H3K27 methylation at epithelial gene E-cadherin promoter, thereby suppressing EMT and tumor invasion in shTET1 cells. Conversely, UTX-1 depletion and ectopic expression of EZH2 enhancedEMTand tumor metastasis in DLD1 cells. These findings provide insight into the regulation of TET1 and E-cadherin and identify EZH2 as a critical mediator of E-cadherin repression and tumor progression. [ABSTRACT FROM AUTHOR]

Summary: Richter Syndrome, an aggressive lymphoma occurring in patients with chronic lymphocytic leukaemia (CLL), has a generally poor prognosis and anthracycline‐based chemoimmunotherapy regimens designed to treat de novo diffuse large B‐cell lymphoma achieve modest clinical benefit. R‐EPOCH (rituximab, etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) has demonstrated greater activity against aggressive B‐cell histologies but has not been studied in Richter Syndrome. We conducted a retrospective cohort study of 46 Richter Syndrome patients treated with first‐line R‐EPOCH at our institution between 1 January 2006 and 31 May 2014. The median progression‐free survival (PFS) was 3·5 months [95% confidence interval (CI): 2·0–7·6] and median overall survival (OS) was 5·9 months (95% CI: 3·2–10·3). Toxicity was high and 30% of patients died without progression or response. Patients with a complex CLL karyotype had significantly shorter PFS and OS (P = 0·005 and P = 0·002, respectively). Multivariable analysis identified complex CLL karyotype as the most significant predictor of decreased survival [Hazard ratio (HR) 2·72, 95% CI: 1·14–6·52, P = 0·025], adjusting for number of prior CLL treatments (P = 0·036). Richter Syndrome patients with complex CLL karyotype experience poor survival with R‐EPOCH treatment and novel approaches are needed for these patients. In contrast, survival of patients without a complex CLL karyotype was similar to patients with de novo diffuse large B‐cell lymphoma. [ABSTRACT FROM AUTHOR]

Background Environmental enrichment ( EE) has been shown to enhance cognitive function in mouse models of Alzheimer's disease ( AD). Magnesium-L-threonate (MgT) is a compound with a newly discovered effect to rescue learning and memory function in aging and AD mice. Aim To study the additive therapeutic effect of EE combined with MgT ( EM) and the potential mechanism underlying the effects. Materials and Methods APP/ PS1 mice were treated with EE, MgT, or combination of EE and MgT ( EM) and compared for restored memory function. Results EM was more effective in improving cognition and spatial memory than either treatment alone in either long-term (12 months, started at 3 months old, which was before disease manifestation) or short-term (3 months, started at 6 months old, which was after disease manifestation) treatment. The behavioral improvement has coincided with rescue of synaptic contacts in the hippocampal region of the AD mouse brain. Immunoblots also showed that EM but neither single treatment rescued the activity reduction in Ca MKII and CREB, two important downstream molecules in the N-methyl-D-aspartate receptor ( NMDAR) pathway. Conclusion Environmental enrichment and MgT may synergistically improve recognition and spatial memory by reducing synaptic loss and restoring the NMDAR signaling pathway in AD mice, which suggests that combination of EE and MgT may be a novel therapeutic strategy for AD. [ABSTRACT FROM AUTHOR]

Abstract: Background: Treatment non‐adherence is a challenge to achieve asthma control. However, few prospective studies were done for exploring asthma patient adherence in real world. Objectives: To evaluate treatment adherence and causes of non‐adherence in a large asthma Chinese population. To analyze newly‐diagnosed patients' adherence first time. Methods: About 1582 asthma patients' data were collected from 12 study centers in China from February, 2012 to October, 2012. Disease and treatment information of subjects were collected were at first clinic visit, at 4, 12, and 24 weeks after that, follow‐up phone calls were carried out for recording subjects' treatment adherence based on their self‐reports. Subjects who reported non‐adherence were additionally asked to choose the primary non‐adherence cause from a list of nine potential causes. Results: Treatment adherence rate of all subjects markedly decreased from 83.3% at week 4 to 42.0% at week 24 after the first clinic visit. Significantly, at week 24, good treatment adherence rate in newly‐diagnosed patients was lower than those patients with asthma history (22.9% vs. 63.9%, P < .001). Newly‐diagnosed patients were three times more likely to become non‐adherence than those patients with asthma history. Female patients had lower treatment adherence rate than male patients (38.3% vs. 45.6%, P = .006). Subjects in 30‐39 year age group had the worst treatment adherence (27.3%). The most commonly chosen cause for non‐adherence was “relief of symptoms after short‐term controller medication use” (43.8%). Conclusions: Asthma patients' treatment adherence could be improved by improving patient education, doctor/patient partnership, and level of medical service in Chinese population. [ABSTRACT FROM AUTHOR]

Metal-organic compounds are a family of electrode materials with structural diversity and excellent thermal stability for rechargeable batteries. Here, we fabricated a hierarchical nanocomposite with metal-organic cuprous tetracyanoquinodimethane (CuTCNQ) in a 3 D conductive carbon nanofibers (CNFs) network by in situ growth, and evaluated it as flexible cathode for sodium-ion batteries (SIBs). CuTCNQ in such flexible composite electrode is able to exhibit a high capacity of 252 mAh g−1 at 0.1 C and highly reversible stability for 1200 cycles within the voltage range of 2.5-4.1 V (vs. Na+/Na). A high specific energy of 762 Wh kg−1 was obtained with high average potential of 3.2 V (vs. Na+/Na). The in situ-formed electroactive metal-organic composites with tailored nanoarchitecture provide a promising alternative choice for high-performance cathode materials in SIBs with high energy. [ABSTRACT FROM AUTHOR]

Rendering large volumes of vector data is computationally intensive and therefore time consuming, leading to lower efficiency and poorer interactive experience. Graphics processing units (GPUs) are powerful tools in data parallel processing but lie idle most of the time. In this study, we propose an approach to improve the performance of vector data rendering by using the parallel computing capability of many-core GPUs. Vertex transformation, largely a mathematical calculation that does not require communication with the host storage device, is a time-consuming procedure because all coordinates of each vector feature need to be transformed to screen vertices. Use of a GPU enables optimization of a general-purpose mathematical calculation, enabling the procedure to be executed in parallel on a many-core GPU and optimized effectively. This study mainly focuses on: (1) an organization and storage strategy for vector data based on equal pitch alignment, which can adapt to the GPU's calculating characteristics; (2) a paging-coalescing transfer and memory access strategy for vector data between the CPU and the GPU; and (3) a balancing allocation strategy to take full advantage of all processing cores of the GPU. Experimental results demonstrate that the approach proposed can significantly improve the efficiency of vector data rendering. [ABSTRACT FROM AUTHOR]

Abstract: The triethylamine promoted reaction of ethyl glycinate hydrochloride with but‐2‐ynedioate in ethanol at room temperature afforded a new kind of 1,3‐dipolar azomethine ylide. The sequential [3+2] cycloaddition of the new azomethine ylide with 2‐arylidene‐1,3‐indanediones or 2‐arylideneoxindoline‐2‐ones successfully resulted in functionalized spiro[indene‐2, 3′‐pyrrolidines] or spiro[indoline‐3, 3′‐pyrrolidine] derivatives in moderate to good yields and with high diastereoselectivity. The relative configuration of the spiro compounds were clearly elucidated by analysis of NMR spectra and determination of single crystal structures. [ABSTRACT FROM AUTHOR]

Repeated low-dose challenge designs in nonhuman primate studies have recently received attention in the literature as a means of evaluating vaccines for HIV prevention and identifying immune surrogates for their protective effects. Existing methods for surrogate identification in this type of study design rely on the assumption of homogeneity across subjects (namely, independent infection risks after each challenge within each subject and conditional on covariates). In practice, random variation across subjects is likely to occur because of unmeasured biologic factors. Failure to account for this heterogeneity or within-subject correlation can result in biased inference regarding the surrogate value of immune biomarkers and underpowered study designs for detecting surrogate endpoints. In this paper, we adopt a discrete-time survival model with random effects to account for between-subject heterogeneity, and we develop estimators and testing procedures for evaluating principal surrogacy of immune biomarkers. Simulation studies reveal that the heterogeneous model achieves substantial bias reduction compared to the homogeneous model, with little cost of efficiency. We recommend the use of this heterogeneous model as a complementary tool to existing methods when designing and analyzing repeated low-dose challenge studies for evaluating surrogate endpoints. [ABSTRACT FROM AUTHOR]

Herein we describe the design and synthesis of a novel family of bifunctional, chiral bicyclo[2.2.1]heptadiene ligands bearing aryl and secondary amido groups, and demonstrate their usefulness in the RhI-catalyzed enantioselective addition reaction of arylboronic acids to N-diphenylphosphinyl ( N-DPP)-protected aldimines. Unlike the analogous RhI-catalysts comprising diene ligands substituted with aryl and carboxylic ester groups, or only with aryl groups, the addition reaction proceeded with high stereoselectivity. The protocol tolerated a range of N-DPP-aldimines and arylboronic acids, producing the desired optically active N-DPP-protected amines with yields between 31-99 % and with ee values up to 91-99 %. The synthetic utility of the method was demonstrated by the conversion of N-DPP-protected amine 3 ae into the antifungal agent, bifonazole ( 13). [ABSTRACT FROM AUTHOR]

ABSTRACT Flexible and wearable smart fabrics are becoming increasingly popular in healthcare and motion monitoring because of their potential applications in flexible and stretchable electronics. The integration of ordinary fabric with conductive fillers provides the fabric with new and intriguing functions, such as sensation. In this study, a low-cost and efficient manner was used to fabricate a highly reliable conductive composite on fabric as an effective sensing material for gesture recognition. A strain sensor was fabricated by the incorporation of the highly conductive polyaniline (PANI) polymer, graphene nanoplatelets (GNPs), and a handful of silicon rubber (SR) onto elastic Lycra fabric via a spin-coating method. We demonstrated that the fabric strain sensor was able to detect and monitor the bending angle of a human finger. By means of the covered structure of the PANI and GNPs, the composite fabric could bear a 40% maximum strain and possess the pleasant characteristic of stretching and bending. The gauge factor of the fabric strain sensor reached 67.3; this was an improvement of approximately four times compared to sensors without PANI microparticles. Finally, the superior performance of our strain sensor through the integration of five strain sensors on a glove for the motion detection of fingers was demonstrated. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45340. [ABSTRACT FROM AUTHOR]

In this study, polyamide-66/poly(2,6-dimethyl-1,4-phenylene oxide) (PA66/PPO) blends with high viscosity ratio were processed by a self-designed triangle-arrayed triple-screw extruder (TTSE, which simulates extensional flow) and a commercial twin-screw extruder (TSE), respectively. Furthermore, in order to improve the mechanical properties of the immiscible PA66/PPO blends, PPO-grafted maleic anhydride (PPO- g-MA) and styrene-ethylene-butylene-styrene (SEBS) block copolymer were used. The mechanical properties, phase morphology, and rheological properties of both binary PA66/PPO blends and toughened PA66/PPO/PPO- g-MA blends were comprehensively investigated to compare the above mentioned two processing method. Samples processed with TTSE exhibited better mechanical properties than the TSE-processed blends. The morphologies of the blends were examined by scanning electron microscopy, exhibiting smaller particles sizes and narrower particle size distributions, which were attributed to the significant effects of extensional flow in TTSE. The toughening mechanism of compatibilized blends was investigated through morphology analysis, dynamic mechanical, and rhelogical analysis. Thus, TTSE with an extensional effect was proved to be efficient in the blending of high viscosity ratio polymers. POLYM. ENG. SCI., 57:1090-1098, 2017. © 2016 Society of Plastics Engineers [ABSTRACT FROM AUTHOR]

Aim To investigate the relationships between demographic characteristics of the elderly, type of long-term care (LTC) facilities, and the reasons for moving into LTC facilities. Methods Research participants included people aged over 65 years, living in LTC facilities. A total of 1280 questionnaires were distributed to 111 LTC facilities in Taiwan; 480 questionnaires were retrieved, and 232 were included in the valid sample. The study used a non-linear canonical correlation analysis, which assesses the relationships among similar sets of categorical variables. Results The results showed that the older adults in quadrant I were characterized by being involved in the decision-making regarding the choice of LTC facilities and received economic support from their children. The older adults in quadrant II mainly lived in LTC facilities to receive medical care, whereas those in quadrant III typically included individuals with low income, who did not choose to live in LTC facilities. Furthermore, those in quadrant IV had positive cognitions associated with LTC facilities. Conclusions We believe that the results of the present study will facilitate policy-making in the field of LTC, provide reference to the practitioners and the older adults, and identify the types of decisions older adults make when moving into LTC facilities, thus assisting older adults to improve their strategies regarding staying in LTC facilities. Geriatr Gerontol Int 2017; 17: 1319-1327. [ABSTRACT FROM AUTHOR]

Alloying-type Sn material has been considered as an excellent anode material for sodium-ion batteries (SIBs). However, the limitation of capacity is still a challenge that remains to be solved. In this approach, we introduce a facile two-step hydrothermal route to prepare hollow SnO2/SnS2 hybrids and investigate their electrochemical performances as anodes in SIBs for the first time. Benefiting from their structural features, the hollow SnO2/SnS2 hybrids exhibit a high reversible sodium storage capacity of about 485.64 mA h g−1 at 300 mA g−1 after 100 cycles with a capacity retention of 78.7 %, which is much higher than 25.9 % for bare SnO2 hollow spheres and 28.5 % for bare SnS2 nanosheets. Taking into consideration the outstanding performance and the special structural design, this work could provide a potential strategy to improve the electrochemical performances of tin-based electrodes, as well as that of other anodes in SIBs. [ABSTRACT FROM AUTHOR]

Preparation of two-dimensional (2D) heterostructures is important not only fundamentally, but also technologically for applications in electronics and optoelectronics. Herein, we report a facile colloidal method for the synthesis of WO n-WX2 ( n=2.7, 2.9; X=S, Se) heterostructures by sulfurization or selenization of WO n nanomaterials. The WO n-WX2 heterostructures are composed of WO2.9 nanoparticles (NPs) or WO2.7 nanowires (NWs) grown together with single- or few-layer WX2 nanosheets (NSs). As a proof-of-concept application, the WO n-WX2 heterostructures are used as the anode interfacial buffer layer for green quantum dot light-emitting diodes (QLEDs). The QLED prepared with WO2.9 NP-WSe2 NS heterostructures achieves external quantum efficiency (EQE) of 8.53 %. To our knowledge, this is the highest efficiency in the reported green QLEDs using inorganic materials as the hole injection layer. [ABSTRACT FROM AUTHOR]

The autophagy-lysosome pathway (ALP) is a primary means by which damaged organelles and long-lived proteins are removed from cells and their components recycled. Impairment of the ALP has been found to be linked to the pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized by the accumulation of protein aggregates and loss of dopaminergic neurons in the midbrain. In recent years, some active compounds derived from plants have been found to regulate the ALP and to exert neuroprotective effects in experimental models of PD, raising the possibility that autophagy enhancement may be an effective therapeutic strategy in PD treatment. In this review, we summarize recent findings of natural products that enhance ALP and thereby protect against PD. Research articles were retrieved from PubMed using relevant keywords in combination. Papers related to the topic were identified, and then the reliability of the experiments was assessed in terms of methodology. The results suggest that targeting the ALP with natural products is a promising strategy for PD treatment. However, risk of bias exists in some studies due to the defective methodology. Rigorous experimental design following the guidelines of autophagy assays, molecular target identification and in vivo efficacy evaluation is critical for the development of ALP enhancers for PD treatment in future studies. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

A water-soluble fluorescent sensor based on the interaction of twisted cucurbit[14]uril ( tQ[14]) and thiazole orange (TO) in aqueous solution was developed. Formation of the tQ[14]/TO complex gives rise to stronger fluorescence in both neutral and acidic aqueous solutions compared with that of free TO. Further experiments on the interaction of the tQ[14]/TO complex with metal ions revealed that, from a series of nineteen selected common metal ions, 1) only Hg2+ can lead to fluorescence enhancement and then quenching of the tQ[14]/TO (2:1) complex in neutral aqueous solution; 2) only Ba2+ can induce fluorescence quenching of the tQ[14]/TO (2:1) complex in aqueous HCl solution (pH 2); furthermore, the tQ[14]/TO/Ba2+ systems exhibit reversible changes in fluorescent intensity on successively adding SO42− and Ba2+; and 3) only Ba2+ or Pb2+ can induce fluorescence quenching of the tQ[14]/TO (15:1) complex in aqueous HCl solution (pH 2). Thus, the tQ[14]/TO complex can act as a supramolecular fluorescence-based sensor for the determination of Hg2+, Ba2+, and Pb2+ ions. [ABSTRACT FROM AUTHOR]

Combining multiple markers can improve classification accuracy compared with using a single marker. In practice, covariates associated with markers or disease outcome can affect the performance of a biomarker or biomarker combination in the population. The covariate-adjusted receiver operating characteristic (ROC) curve has been proposed as a tool to tease out the covariate effect in the evaluation of a single marker; this curve characterizes the classification accuracy solely because of the marker of interest. However, research on the effect of covariates on the performance of marker combinations and on how to adjust for the covariate effect when combining markers is still lacking. In this article, we examine the effect of covariates on classification performance of linear marker combinations and propose to adjust for covariates in combining markers by maximizing the nonparametric estimate of the area under the covariate-adjusted ROC curve. The proposed method provides a way to estimate the best linear biomarker combination that is robust to risk model assumptions underlying alternative regression-model-based methods. The proposed estimator is shown to be consistent and asymptotically normally distributed. We conduct simulations to evaluate the performance of our estimator in cohort and case/control designs and compare several different weighting strategies during estimation with respect to efficiency. Our estimator is also compared with alternative regression-model-based estimators or estimators that maximize the empirical area under the ROC curve, with respect to bias and efficiency. We apply the proposed method to a biomarker study from an human immunodeficiency virus vaccine trial. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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Isoflavones are natural substances that exhibit hormone-like pharmacological activities. The separation of isoflavones remains an analytical challenge because of their similar structures. We show that ultra-high performance supercritical fluid chromatography can be an appropriate tool to achieve the fast separation of 12 common dietary isoflavones. Among the five tested columns the Torus DEA column was found to be the most effective column for the separation of these isoflavones. The impact of individual parameters on the retention time and separation factor was evaluated. These parameters were optimized to develop a simple, rapid, and green method for the separation of the 12 target analytes. It only took 12.91 min using gradient elution with methanol as an organic modifier and formic acid as an additive. These isoflavones were determined with limit of quantitation ranging from 0.10 to 0.50 μg/mL, which was sufficient for reliable determination of various matrixes. [ABSTRACT FROM AUTHOR]

Background: Clinical prediction rules (CPRs) provide an objective method of assessment in the diagnosis of acute appendicitis. There are a number of available CPRs for the diagnosis of appendicitis, but it is unknown which performs best. Aim: The aim of this study was to identify what CPRs are available and how they perform when diagnosing appendicitis in adults. Method: A systematic review was performed in accordance with the PRISMA guidelines. Studies that derived or validated a CPR were included. Their performance was assessed on sensitivity, specificity and area under curve (AUC) values. Results: Thirty-four articles were included in this review. Of these 12 derived a CPR and 22 validated these CPRs. A narrative analysis was performed as meta-analysis was precluded due to study heterogeneity and quality of included studies. The results from validation studies showed that the overall best performer in terms of sensitivity (92%), specificity (63%) and AUC values (0.84-0.97) was the AIR score but only a limited number of studies investigated at this score. Although the Alvarado and Modified Alvarado scores were the most commonly validated, results from these studies were variable. The Alvarado score outperformed the modified Alvarado score in terms of sensitivity, specificity and AUC values. Conclusion: There are 12 CPRs available for diagnosis of appendicitis in adults. The AIR score appeared to be the best performer and most pragmatic CPR. [ABSTRACT FROM AUTHOR]

In patients without associated myocardial diseases, characterized by left bundle branch block and inferior axis morphologies, repetitive idiopathic right ventricular tachycardias and ventricular premature contractions typically arise from right ventricular outflow tract (RVOT). Accumulated evidences have shown that radiofrequency catheter ablation is a useful treatment for patients with RVOT ventricular arrhythmias (VAs). Interestingly, several medical centers have shown that pulmonary artery (PA) is a potential novel site for catheter ablation in RVOT-like VAs, particularly in patients where termination of RVOT VAs at the usual site fails. In this review, we comprehensively demonstrated that RVOT VAs were successfully terminated at the site of PA, analyzed the characteristics of surface electrocardiogram and endocardial potentials, and explored the underlying mechanisms for these cases. [ABSTRACT FROM AUTHOR]

Although two-dimensional (2D) metal oxide/sulfide hybrid nanostructures have been synthesized, the facile preparation of ultrathin 2D nanosheets in high yield still remains a challenge. Herein, we report the first high-yield preparation of solution-processed ultrathin 2D metal oxide/sulfide hybrid nanosheets, that is, Ti xTa1− xS yO z ( x=0.71, 0.49, and 0.30), from Ti xTa1− xS2 precursors. The nanosheet exhibits strong absorbance in the near-infrared region, giving a large extinction coefficient of 54.1 L g−1 cm−1 at 808 nm, and a high photothermal conversion efficiency of 39.2 %. After modification with lipoic acid-conjugated polyethylene glycol, the nanosheet is a suitable photothermal agent for treatment of cancer cells under 808 nm laser irradiation. This work provides a facile and general method for the preparation of 2D metal oxide/sulfide hybrid nanosheets. [ABSTRACT FROM AUTHOR]

Although sodium-ion batteries (SIBs) are considered as alternatives to lithium-ion batteries (LIBs), the electrochemical performances, in particular the energy density, are much lower than LIBs. A metal-organic compound, cuprous 7,7,8,8-tetracyanoquinodimethane (CuTCNQ), is presented as a new kind of cathode material for SIBs. It consists of both cationic (CuII↔CuI) and anionic (TCNQ0↔TCNQ−↔ TCNQ2−) reversible redox reactions, delivering a discharge capacity as high as 255 mAh g−1 at a current density of 20 mA g−1. The synergistic effect of both redox-active metal cations and organic anions brings an electrochemical transfer of multiple electrons. The transformation of cupric ions to cuprous ions occurs at near 3.80 V vs. Na+/Na, while the full reduction of TCNQ0 to TCNQ− happens at 3.00-3.30 V. The remarkably high voltage is attributed to the strong inductive effect of the four cyano groups. [ABSTRACT FROM AUTHOR]

ABSTRACT Novel optically active and racemic poly( N-propargylamides) bearing tyrosine pendants (LPT, DPT, and RPT) were synthesized and characterized. The polymers possessed moderate molecular weights and were thoroughly soluble in common organic solvents. The secondary structure of these three polymers in chloroform was studied and the results indicated that LPT and DPT could adopt helical structures with predominantly one-handed screw sense according to their intense Cotton effect and large specific rotation values, while RPT adopted random coiled polymer chain. The amide groups could form amide-amide hydrogen bonds to engender the twist of dihedral angle and the strong steric repulsion of phenol groups might have the opposite effect on the helix. The helical structure of the optically active polymers were conclusively constructed and stabilized by the optimization of intra- and intermolecular hydrogen bonding and steric repulsion of the side chains. Moreover, the infrared emissivity values of LPT and DPT at 30 °C were 0.682 and 0.671, which were much lower than RPT. LPT and DPT also showed superior heat resistance due to their unique helical conformation. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 44824. [ABSTRACT FROM AUTHOR]

Described in this paper are the results of an investigation on the extension of the C-H alkyliminylation and acylation of alkenes with secondary amides. The nucleophilic partner has been extended to cover a series of functionalized alkenes bearing functional groups including ester, α, β-unsaturated ester, uncongested ketone groups, as well as enol derivatives of acetaldehyde such as enol ether and enamides. The electrophilic partner has been extended from N-(2,6-dimethylphenyl) and N-methyl amides to N-n-butyl, and N-cyclohexyl amides. The results demonstrated that the method can be used to synthesize a number of functionalized α, β-unsaturated ketimines and α, β-enones in an efficient, high yielding, and one-pot manner. The method was applied to a concise synthesis of ( E)-6-styryltetrahydro-2 H-pyran-2-one ( 5), an immediate intermediate in the syntheses of a series of styryllactone natural products including (±)-goniothalamine ( 6), (±)-goniothalamine oxide ( 7), (±)-goniodiol ( 8), (±)-leiocarpin A ( 9), (±)-9-deoxygoniopypyrone ( 10), and (±)-7- epi-goniodiol ( 11). [ABSTRACT FROM AUTHOR]

Epstein-Barr virus (EBV)-encoded RNAs (EBER) in tumor tissue and cell-free plasma EBV-DNA (pEBVd) are detected in EBV-associated lymphomas. Studies have suggested that EBER+ peripheral T-cell lymphomas (PTCL) have worse prognosis but the role of EBV in these neoplasms remains unclear. pEBVd is quantitative and more easily amenable to standardization than EBER, but frequency of pEBVd detection, clinical impact and agreement with EBER status in PTCL are unknown. We retrospectively assessed frequency of detectable pre-treatment pEBVd, presence of EBER in tumor tissue, and outcomes in 61 of 135 EBV-assessable PTCL patients. Fifteen of 61 patients (24.5%, 95% CI: 14-37%) were pre-treatment pEBVd+, with no significant differences in baseline characteristics or treatment between pEBVd+ and pEBVd− patients. EBER-ISH was performed on 10 pEBVd+ and 35 pEBVd− tumors. All 10 pEBVd+ patients were EBER+, but 9 pEBVd− patients were also EBER+. With median follow up of 24 months (range 1-96), overall survival (OS) was shorter in pEBVd+ compared to pEBVd− patients (13 vs. 72 months; p = 0.04). In our retrospective study, pre-treatment pEBVd was elevated in 25% of PTCL patients, was highly specific for EBER+ tumors, and was associated with shorter survival. pEBVd should be further explored as a prognostic variable and tumor biomarker in PTCL. [ABSTRACT FROM AUTHOR]

A novel and sensitive voltammetric method was proposed for separation and determination of glutathione (GSH) and L-tyrosine (Tyr) at acetylene black and chitosan modified glassy carbon electrode (AB-CS/GCE). By introducing chlorogenic acid (CGA) as a new electrocatalytic mediator, GSH could be detected at much lower potential with symmetric peak shape. Acetylene black and chitosan composite served as current signal amplifier for sensitive detection. The electrochemical behavior of GSH and Tyr in the presence of CGA was studied at AB-CS/GCE and complete separation of anodic peaks was achieved. Under the optimum conditions, the electrocatalytic oxidation peak current of GSH showed a linear dependence on its concentration in the ranges of 2.0×10−7-4.0×10−5 M with the detection limit of 5.8×10−8 M (S/N=3), while the oxidation peak current of Tyr was linear to its concentration from 2.5×10−6 to 4.3×10−4 M with the detection limit of 9.2×10−7 M (S/N=3) by differential pulse voltammetry (DPV). The established method has been applied to the simultaneous determination of GSH and Tyr in human urine with satisfactory results. [ABSTRACT FROM AUTHOR]

The performance of simple permafrost distribution models widely used on the Qinghai-Tibet Plateau (QTP) has not been fully evaluated. In this study, two empirical models (the elevation model and mean annual ground temperature model) and three semi-physical models (the surface frost number model, the temperature at the top of permafrost model and the Kudryavtsev model) were investigated. The simulation results from the models were compared to each other and validated against existing permafrost maps of the entire QTP and in three representative areas investigated in the field. The models generally overestimated permafrost distribution in the investigated areas, but they captured the broad characteristics of permafrost distribution on the entire QTP, and performed best in areas with colder, continuous permafrost. Large variations in performance occurred at elevations of 3800-4500 m asl and in areas with thermally unstable permafrost. The two empirical models performed best in areas where permafrost is strongly controlled by elevation, such as eastern QTP. In contrast, the three semi-physical models were better in southern island permafrost areas with relatively flat terrain, where local factors considerably impact the distribution of permafrost. Model performance could be enhanced by explicitly considering the effects of elevation zones and regional conditions. Copyright © 2017 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]