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BACKGROUND Before tyrosine kinase inhibitor (TKI) therapy can be administered in patients with advanced non-small cell lung cancer (NSCLC), EGFR mutation testing is required. However, few studies have evaluated the extent of EGFR testing in real-world practice in China. METHODS A multicenter, observational study of EGFR testing in NSCLC patients in North China was conducted. Treatment-naive patients or those with postoperative recurrent stage IIIB/IV NSCLC were enrolled. The primary objective was EGFR testing rate. Secondary objectives included EGFR mutation status, EGFR testing methods and specimens, factors associated with EGFR testing, and overall survival with or without EGFR testing. RESULTS Overall, 2809 patients with stage IIIB/IV NSCLC were enrolled; 90.78% had adenocarcinoma. The EGFR screening rate was 42.54%. EGFR testing rates were higher in tumor samples obtained by lymph node puncture, and in patients with urban medical insurance, adenocarcinoma, non-smokers, or those located in developed cities (all P < 0.001). The EGFR mutation rate was 46.44%. The most commonly used specimens for EGFR testing were biopsy tumor samples (67.53%). PCR-based methods (72.05%), Sanger sequencing (5.36%), and Luminex liquid chip (5.10%) were the most frequently used testing platforms. Similar positive EGFR mutation rates were achieved with different platforms. TKI therapy was the first-line treatment administered to most EGFR-positive patients (56.22%), and chemotherapy in EGFR-negative patients (84.88%). Overall survival was higher in EGFR-tested than in untested patients (27.50 vs. 19.73 months; P = 0.007). CONCLUSION Real-world EGFR testing rates for NSCLC in North China were relatively low because of clinical and social factors, including medical insurance coverage.

Summary The commonly utilized phosphodiesterase type 5 inhibitors do not lead to satisfactory penile erection after radical prostatectomy mainly because of insufficient nitric oxide drive from the damaged cavernous nerves. The aim of this study was to assess the efficacy and mechanisms of icariin in combination with daily sildenafil on neurogenic erectile dysfunction and penile atrophy in a rat model of bilateral cavernous nerves injury. Sixty male Sprague–Dawley rats injected with 5-ethynyl-2-deoxyuridine (50 mg/kg) at postnatal day 1 for the purpose of tracking endogenous stem cells in penis. Forty-eight rats of bilateral cavernous nerves injury were randomized equally into gavage feeding of vehicle, sildenafil (10 mg/kg), icariin (1.5 mg/kg) and sildenafil + icariin, respectively. Twelve sham-operated rats served as control. The intracavernous pressure and mean arterial pressure was measured and mid-penile cross sections were histologically examined 5 weeks after surgery. Western blotting of cavernous tissue protein was also performed. Animals treated with sildenafil + icariin had significantly higher mean intracavernous pressure/mean arterial pressure ratio relative to other rats with bilateral cavernous nerves injury (p

This study was designed to compare the protein-binding characteristics of aspirin-zinc complex (AZN) with those of aspirin itself. AZN was synthesized and interacted with a model transport protein, human serum albumin (HSA). Three-dimensional fluorescence, ultraviolet-visible and circular dichroism (CD) spectra were used to characterize the interaction of AZN with HSA under physiological conditions. The interaction mechanism was explored using a fluorescence quenching method and thermodynamic calculation. The binding site and binding locality of AZN on HSA were demonstrated using a fluorescence probe technique and Förster non-radiation energy transfer theory. Synchronous fluorescence and CD spectra were employed to reveal the effect of AZN on the native conformation of the protein. The HSA-binding results for AZN were compared with those for aspirin under consistent experimental conditions, and indicated that aspirin acts as a guide in AZN when binding to Sudlow's site I, in subdomain IIA of the HSA molecule. Moreover, compared with aspirin, AZN showed greater observed binding constants with, but smaller changes in the α-helicity of, HSA, which proved that AZN might be easier to transport and have less toxicity in vivo.

Summary Induction of HIV-1 broadly neutralizing antibodies (bnAbs) to date has only been observed in the setting of HIV-1 infection, and then only years after HIV transmission. Thus, the concept has emerged that one path to induction of bnAbs is to define the viral and immunologic events that occur during HIV-1 infection, and then to mimic those events with a vaccine formulation. This concept has led to efforts to map both virus and antibody events that occur from the time of HIV-1 transmission to development of bnAbs. This work has revealed that a virus-antibody “arms race” occurs in which a HIV-1 transmitted/founder (TF) Env induces autologous neutralizing antibodies that can not only neutralize the TF virus but also can select virus escape mutants that in turn select affinity-matured neutralizing antibodies. From these studies has come a picture of bnAb development that has led to new insights in host–pathogen interactions and, as well, led to insight into immunologic mechanisms of control of bnAb development. Here, we review the progress to date in elucidating bnAb B cell lineages in HIV-1 infection, discuss new research leading to understanding the immunologic mechanisms of bnAb induction, and address issues relevant to the use of this information for the design of new HIV-1 sequential envelope vaccine candidates.

Glucosamine hydrochloride 1 was treated with 1,3-dicarbonyl compounds to obtain 2-methyl-5-(1,2,3,4-tetrahydroxy-butyl) pyrrole 2a and 2b, respectively. Under the role of NaIO4, 2a and 2b were successfully transformed into the related 5-formal pyrrole derivative 3a and 3b, respectively. Compounds 4a–4d and 5a–5e were obtained by reacting 3a and 3b with chlorinated hydrocarbons by alkylation reactions, respectively. The structures of all new products were confirmed by IR, NMR, and HRMS spectra.

Background Increasing evidence indicates that nonalcoholic fatty liver disease (NAFLD) is linked to an increased risk of extra-hepatic conditions. However, it is currently uncertain whether NAFLD is associated with the risk of gastroesophageal reflux disease (GERD). We performed a systematic review and meta-analysis of relevant studies to examine the association between NAFLD and the risk of GERD. Methods We searched PubMed, Scopus, Embase and Web of Science from 1 January 1975 to 15 December 2018, using predefined terms to identify cross-sectional, case-control and cohort studies investigating the association between NAFLD and GERD. Results Nine observational studies involving 185 118 subjects were eligible for inclusion in the meta-analysis. Overall, NAFLD was significantly associated with an increased risk of GERD (random effect OR 1.28; 95% CI: 1.12-1.44, I2 = 82%). Moreover, the significant association between NAFLD and GERD was consistent both for studies with adjusted OR/HR (n = 6, random effect OR = 1.16, 95% CI: 1.03-1.30) and those with unadjusted OR/HR (n = 3, random effect OR = 2.09, 95% CI: 1.62-2.56) as measures of effect. Both funnel plot and Egger's test suggested the existence of publication bias. However, a sensitivity analysis by sequentially omitting each study did not alter the pooled outcome,suggesting the robustness of the association. Conclusion NAFLD is associated with an increased risk of GERD. However, future large and cohort studies are still needed to determine the causal relationship between NAFLD and the risk of GERD.

The article describes the design, manufacturing, modelling and testing of a hybrid composite support made from auxetic open cell foam liners and curved thermoplastic plates with rhomboidal perforations for human body support. Both the foam and the curved perforated plate have in-plane negative Poisson's ratio behaviour. The static bending stiffness of the hybrid auxetic composite support is modelled using an analytical and Finite Element approach benchmarked against experimental results from three-point bending tests. The benchmarked Finite Element models are used to develop a map of optimised static stiffness versus the geometry of the rhomboidal perforations. A Design of Experiment testing campaign is also carried out on 16 hybrid auxetic composite plates to understand the interaction and correlation of the static bending versus the geometry of the perforations and the contribution given by the auxetic foam liner.

Metastasis accounts for 90% of cancer death worldwide, and effective therapeutic strategies are lacking. The aim of this work is to identify the key drivers in tumor metastasis and screen therapeutics for treatment of esophageal squamous cell carcinoma (ESCC). Gene Ontology analysis of The Cancer Genome Atlas (TCGA) gene expression datasets of ESCC patients with or without lympy metastasis identifies that TGFβ2 is highly enriched in the pathways essential for tumor metastasis and upregulates in the metastatic ESCC tumors. High TGFβ2 expression in ESCC correlates with metastasis and patient survival, and functionally contributes to tumor metastasis via activating extracellular signal‐regulated kinases (ERK) signaling. By screening of a library consisting of 429 bioactive compounds, imperatorin is verified as a novel TGFβ2 inhibitor, with robustly suppressive effect on tumor metastasis in multiple mice models. Mechanistically, direct binding of imperatorin and CREB1 inhibits phosphorylation, nuclear translocation of CREB1, and its interaction with TGFβ2 promoter, represses TGFβ2 expression and fibroblasts‐secreted CCL2, and then inactivates ERK signaling to block cancer invasion and abrogates the paracrine effects of fibroblasts on tumor angiogenesis and metastasis. Overall, the findings suggest the use of TGFβ2 as a diagnostic and prognostic biomarker and therapeutic target in ESCC, and supports the potential of imperatorin as a novel therapeutic strategy for cancer metastasis.

The paper describes the manufacturing, testing and modelling of a class of open cell polyurethane foams doped with multi-walled carbon nanotubes and nano polyurethane dispersions and subjected to quasi-static cycling compressive loading at large deformations. The doped nano-ink foams areproduced using a multiple steps dip coating technique that makes possible the development of nanobased porous materials by post-processing existing off-the-shelf open cell foams. Tests are carried out up to 18.5% of compressive strain to identify loading/unloading moduli and energy absorbedafter 5 cycles of stabilization. Hyperelastic Ogden models also considering the Mullins effect for cyclic loading are used to identify the constitutive parameters for these foams. The results show that the use of the multi-walled carbon nanotube layers provide an effective increase of the stiffness andenergy absorbed compared to pristine and nano polyurethane dispersions-treated foams. The volume average energy absorbed after the stabilization cycles is increased by 200% compared to thepristine foam when the multi-walled carbon nanotube layers are used. The parameters of the constitutive models extracted from the tests show that these nano-ink foams can be modelled following state-of-the-art hyperelastic representations

To evaluate the effect of CuO nanoparticles (NPs) on root growth, root reactive oxygen species (ROS) production, and the expression of 2 genes (OsCDC2 and OsCYCD) associated with root growth of Oryza sativa (rice), rice roots were treated with 5 mg/L CuO NP suspension, 5 mg/L CuO bulk particle suspension, and 0.27 mg/L CuSO4 · 5H2O solution, with distilled water as control. The results indicated that CuO NPs and Cu2+ severely inhibited the elongation and biomass of rice roots after 72-h exposure. Dyeing with 7′-dichlorodihydrofluorescein–diacetate (DCFH–DA) showed that in all 3 treatment groups, the fluorescence was primarily located in the meristem zone, demonstrating that the meristem zone was where ROS were primarily generated. In addition, a significant increase in ROS was detected in the meristem zone of roots treated with the CuO NP suspension and the CuSO4 · 5H2O solution, both of which greatly influenced the expression level of OsCDC2 and OsCYCD. The impact of Cu2+ on these 2 genes was smaller than that of CuO NPs. The Cu content in roots of rice after treatment with CuO NPs was much higher than that found after the other treatments, which indicated that CuO NPs may have been absorbed into root tissue. Collectively, these data suggest that growth inhibition, higher ROS production, and gene expression inhibition may be caused not only by the ions themselves, but also the NPs. Environ Toxicol Chem 2015;34:554–561. © 2014 SETAC

BACKGROUND 1,2,4-Triazolo[4,3-a]pyridine derivatives represent a new series of compounds that possess good herbicidal activity against Echinochloa crusgalli (L.) Beauv., Setaria faberii, Digitaria sanguinalis (L.) Scop., Brassica juncea Coss., Amaranthus retroflexus L. and Eclipta prostrata L. RESULTS A total of 23 novel 1,2,4-triazolo[4,3-a]pyridine derivatives were synthesised and identified by 1H NMR, IR, single-crystal X-ray diffraction, mass-spectroscopic and elemental analysis, and their herbicidal activities were tested against E. crusgalli (L.) Beauv., S. faberii, D. sanguinalis (L.) Scop., B. juncea Coss., A. retroflexus L. and E. prostrata L. at 150 g a.i. ha−1. It was found that the title compound 8-chloro-3-(4-propylphenyl)-[1,2,4]-triazolo[4,3-a]pyridine possesses high herbicidal activity and a broad spectrum against the 22 test weeds, with an inhibition effect of about 50% at a dosage of 37.5 g a.i. ha−1, and is safe for corn, cotton and rice at a dosage of 150 g a.i. ha−1. Furthermore, comparative molecular field analysis contour models were established to study the structure–activity relationship of the title compounds. CONCLUSION It is possible that, with further structure modification, 1,2,4-triazolo[4,3-a]pyridine derivatives, which possess good herbicidal activities, may become novel lead compounds for the development of herbicides against dicotyledonous weeds. © 2014 Society of Chemical Industry

It is well known that converging channel can generate elongational deformation field. In this study, novel dynamical converging channels were successfully incorporated into plant fiber-reinforced thermoplastics composites processing. A dynamical elongational deformation field (DEDF) generated by these channels was studied. The fiber organization and damage in the DEDF has been investigated in terms of its relationship to changes in rotating speed of the channels. A vane extruder based on these channels was used to prepare sisal fiber-reinforced polypropylene composites. By investigating rapidly cooled samples in the vane extruder, sisal fiber in the center part of these channels has an orientation with an angle to the discharging direction. Rotating speed increases from 30 to 90 r/min result in 30.99–42.7% decreases in average fiber length. The issues of fiber distribution and voids formation have been related to the mechanical properties of the composites, particularly tensile strength and modulus. Increased rotating speeds from 30 to 90 r/min results in tensile strength and modulus increases of about 21.3% and 11.6%, respectively. The majority of this change is caused by decreased voids formation with the increases of speed, which is in agreement with scanning electron microscopy of the composites. POLYM. COMPOS., 2012. © 2011 Society of Plastics Engineers

To investigate the coordination chemistry of 1-subsitituted tetrazole derivatives compared with the 5-subsitituted tetrazole derivatives and to get a better knowledge of the influence of the metal ions and co-ligand for the structures of the complexes, three complexes based upon tetrazolate groups were synthesized and structurally characterized by X-ray single-crystal diffraction: [CoLCl2] (1), [ZnLCl2] (2), and [Cu4L2(N3)8]n (3) [L = 2-(1-phenyl-1H-tetrazol-5-ylsulfanylmenthyl)pyridine]. In complexes 1 and 2, the C–H···N and C–H···Cl intermolecular hydrogen bonds results in 2D supramolecular structures, which can be rationalized to be a (63) topology when the centroid of each molecule was treated as a 3-connected node with three other molecules around it. In 3, the μ-1,1 coordination modes of N3– and the bridging coordination mode of L build a 2D layer structure. In complexes 1 and 2, hydrogen bonding interactions play important roles in increasing the dimensionality of supramolecular assemblies. Meanwhile, the electronic spectrum of complex 1 and the fluorescent properties of complex 2 were also studied.

In the present paper, we deal with the electromagnetic properties of Fe-rich microwire polymer meta-composites prepared by embedding glass-coated Fe-based microwires into the E-glass prepreg matrices in a parallel fashion. The free-space measurement shows that a transmission window was created by adjusting the wire spacing below 7mm, which indicates that double negative index had been obtained. The correlation between the left-handed feature with the local dielectric response has been established. The ‘natural' double negative behaviour is attributed to the intrinsic domain structure of Fe-based ferromagnetic wires. (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim)

Targeting specific aerospace coating applications, highly conductive carbon nanotubes were rigorously dispersed into a commercial topcoat PU matrix to produce nanocomposites for electrostatic dissipation and/or de-icing coatings. Systematic evaluation on a range of properties that are pertaining to the targeted applications showed that, comparing with pure PU film, an addition of 1 wt.-% functionalized MWNTs resulted in a significant improvement in the tensile strength and modulus; a 6.5 °C shift in glass transition temperature; a six orders of magnitude decrease in electrical resistivity and 24% improvement in thermal diffusivity. The durable, light color, and flexible nanocomposite with sufficiently low surface resistivity meet the requirements for aerospace coating applications.