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Summary Background Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma. Methods AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged ≥18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Patients were randomly assigned (2:1) to receive apatinib 750 mg or placebo orally once daily in 28-day treatment cycles. Group allocation was done with a central randomisation system, with a block size of six, and was stratified by Eastern Cooperative Oncology Group performance status, previous sorafenib treatment, and presence of vascular invasion or extrahepatic metastasis. The primary endpoint was overall survival, which was defined as time from randomisation to death from any cause, and was analysed in patients who were randomly assigned and received at least one dose of the study drug. Safety analyses were done in patients who received at least one dose of the study treatment and had post-dose safety assessments. This trial is registered with ClinicalTrials.gov , NCT02329860 . Findings Between April 1, 2014, and May 3, 2017, 400 eligible patients were randomly assigned to receive apatinib (n=267) or placebo (n=133). Seven patients (six in the apatinib group and one in the placebo group) did not receive study treatment and were excluded from efficacy analyses. Overall survival was significantly improved in the apatinib group compared with the placebo group (median 8·7 months [95% CI 7·5‒9·8] vs 6·8 months [5·7‒9·1]; hazard ratio 0·785 [95% CI 0·617‒0·998], p=0·048). 387 patients (257 in the apatinib group and 130 in the placebo group) had a safety assessment after study treatment and were included in safety analyses. The most common treatment-related adverse events of grade 3 or 4 were hypertension (71 [28%] patients in the apatinib group vs three [2%] in the placebo group), hand–foot syndrome (46 [18%] vs none), and decreased platelet count (34 [13%] vs one [1%]). 24 (9%) patients in the apatinib group and 13 (10%) in the placebo group died due to adverse events, but none of these deaths were deemed to be related to treatment by investigators. Interpretation Apatinib significantly improved overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile. Funding Jiangsu Hengrui Medicine.

Purpose Unresectable intrahepatic cholangiocarcinoma (ICC) has a poor prognosis. The aim of this study was to evaluate the efficacy and safety of apatinib for patients with unresectable ICC. Patients and methods A total of 10 patients with unresectable ICC were enrolled for this single-center observational study between March 2, 2016, and August 27, 2019. Subjects received 500 mg apatinib on a daily basis. Tumor response was assessed by 1.1 response evaluation criteria in solid tumors. The progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan-Meier method. The drug-related adverse effects were also monitored. Results Based on the follow-up computed tomography and magnetic resonance imaging after treatment, 4 (40.0%), 4 (40.0%), and 2 (20.0%) patients achieved a partial response, stable disease, and progression of the disease, respectively. The response rate and disease control rate were 40.0% and 80.0%, respectively. The median PFS was 4.5 months (95% confidence interval: 3.157~5.843 months); the median OS was 6.5 months (95% confidence interval: 4.744~8.256 months). Furthermore, 3-, 6-, and 9-month OS rates were 77.5%, 61.7%, and 15.0%, respectively. The most common hematologic grade 3 adverse event was neutropenia (10%); the most common nonhematologic grade 3 adverse events were hypertension (20.0%) and hand-foot syndromes (20.0%). No treatment-related grade 4 or 5 adverse events were recorded. Conclusion Apatinib revealed to have antitumour activity in unresectable ICC patients, with manageable toxicities, and thus might be used as a new treatment option for patients with unresectable ICC.

Chemically reduced graphene (C- rGO) nanosheets were first prepared from graphene oxide (GO), and then the polypropylene (PP) composites synergistically reinforced–toughened by styrene–butadiene rubber (SBR), and C- rGO nanosheets were fabricated via melt blending. The mechanical properties of PP can be considerably improved by synergistically filling with C- rGO nanosheets and SBR, especially for the notched Izod impact strength (IS). The results from the X-ray diffraction, polarizing optical micrographs, scanning electron microscope, differential scanning calorimetric, dynamic mechanical analysis, and thermogravimetric analysis measurements reveal that: (1) the β-phase crystal structure of the PP is formed when the C- rGO and SBR are synergistically filled with PP and its formation plays a role for the enhancement of the impact strength for PP/SBR/C- rGO composites; (2) the dispersion of the C- rGO and SBR in the PP/SBR/C- rGO composites is homogeneous, indicating that synergistic incorporating method decreases the aggregation of nanosheets and thus increases the sites for dissipation of shock for impact energy in the PP/SBR/C- rGO composites; and (3) the thermal analysis shows high thermal stability for the PP/SBR/C- rGO composites.

Carboxylated multi-walled carbon nanotubes (MWCNTs-COOH) were selected as the carrier and polypyrrole (PPy) as functional agent to synthesize PPy/MWCNTs dielectric nanofillers via FeCl3 oxidative polymerization of pyrrole (Py) on the surface of MWCNTs-COOHs, and then poly(vinylidene fluoride) based dielectric nanocomposites (PPy/MWCNTs/PVDF) were fabricated by direct melting blending. The effects of the PPy/MWCNTs dielectric nanofillers on the changes of phase behaviors and the mechanical, thermal and dielectric properties of the PPy/MWCNTs/PVDF dielectric nanocomposites were investigated. The results indicated that PPy/MWCNTs/PVDF dielectric nanocomposites showed higher mechanical strength within a certain range of PPy/MWCNTs nanofillers content. When the PPy/MWCNTs content was 10 wt.%, the tensile strength and elastic modulus of the nanocomposites reached 60.2 MPa and 610 MPa respectively, which increased by 24 % and 75 %, in contrast to those of MWCNT-COOH/PVDF dielectric nanocomposites. Dielectric properties tests revealed that the introduction of PPy induced the formation conductive networks and β-type PVDF, and thus enhancing the dielectric constant. the resultant PPy/MWCNTs/PVDF dielectric nanocomposites reached the percolation threshold at the PPy/MWCNTs content of 12 wt.%. The corresponding dielectric constant reached 83, which was 10 times of pure PVDF. Meanwhile, the dielectric constant was also much higher than MWCNTs-COOH/PVDF. Differential scanning calorimeter (DSC) found that the melting and crystallization temperatures of the two nanocomposites were greatly improved compared with pure PVDF, indicating that the addition of dielectric nanofiller improved the thermal property of the nanocomposites.

A wireless magnetoelastic-sensing device for the selective detection of benzo[a]pyrene (BaP) is reported using aminocalix[4]arene (AC4) monolayers as the sensor sensing elements and AC4-modified Au nanoparticles (AC4-Au NPs) as signal-amplifying tags. A sandwich-type detection strategy involves the AC4 self-assembled on the Au-protected sensor surface and AC4-Au NPs, both of which flank the BaP target in sequence. As the AC4-Au NPs combined BaP absorbs on the sensor's surface, there is an increase in the mass load on the sensor, and consequently a decrease in resonance frequency. Under optimal conditions, the sensor shows a linear response to the concentration of BaP in the range of 1.04 × 10−7 M to 1.04 × 10−11 M, with a detection limit of 5.0 × 10−11 M. Other polycyclic aromatic hydrocarbons (PAHs) and environmental pollutants show no interference on the detection.

We report on a wireless magnetoelastic-sensing device for the assay of pathogen with Escherichia coli O157:H7 (E. coli) as a target using chitosan-modified magnetic Fe3O4 nanoparticles (CMNPs) as signal-amplifying tags. At suitable pH the CMNPs, Fe3O4 nanoparticles functionalized with a layer of chitosan, bind to negatively charged E. coli through electrostatic attraction. The E. coli attached CMNPs are magnetically bound to the surface of the magnetoelastic sensor, resulting in enhanced mass loading on the sensor surface that in turn decreases its resonance frequency allowing quantification of E. coli concentrations. The sensor shows a linear response to the logarithmic concentration of E. coli in the range of 10 cells mL−1 to 3.7 × 108 cells mL−1, with a detection limit (LOD) of 10 cells mL−1. Small molecules such as albumin bovine and ovalbumin show no interference on the detection.

A wireless magnetoelastic-sensing device for the detection of polycyclic aromatic hydrocarbons (PAHs) with anthracene as the model target is reported using humic acid-modified magnetic Fe 3 O 4 nanoparticles (HMNPs) as signal-amplifying tags. A sandwich-type detection strategy involves the humic acid (HA)/chitosan composite self-assembled on the polyurethane-protected sensor surface and HMNPs, both of which flank the anthracene target in sequence. As the HMNPs-combined anthracene absorbs to the sensor surface, there is an increase in the mass load on the sensor, and consequently a decrease in resonance frequency. Under optimal conditions, the sensor shows a linear response to polycyclic aromatic hydrocarbons with sensitivity depending on the benzene rings. The sensor shows the largest sensitivity to benzo[ a ]pyrene due to its 5 ring with a detection limit of 3 nM. Tap water, river water and spring water were analyzed with this sensor.

Highly ordered TiO(2) nanotube arrays are with unique photoelectrical properties due to their highly ordered nanostructure and the resulted short charge transportation path. We report, for the first time, on the application of Ag nanoparticle-modified TiO(2) nanotubes (Ag/TiO(2) NTs) in the electrochemiluminescence detection of polycyclic aromatic hydrocarbons (PAHs) using the Ag/TiO(2) NT film as working electrode and S(2)O(8)(2-) as coreactant, with benzo(a)pyrene (BaP) as the model compound. The hydrophobic BaP absorbs onto the TiO(2) NTs surface, and oxidized with consumption of the excited TiO(2) (TiO(2)(*+)) resulting in a decrease in ECL. Under the optimal conditions, a detection limit of 1.0 x 10(-12) M is achieved with a linear range of 3.0 x 10(-12) approximately 1.0 x 10(-9) M. Compounds which can not be oxidized by the excited TiO(2) (TiO(2)(*+)), such as benzene, naphthalene (NAP), anthracene (ANT), and tris-2,3-dibrominepropyl isocyanurate (TBC) show little interference on the detection, whereas PAHs with more than four rings can be detected by the proposed method.

Trinitrotoluene, usually known as TNT, is a kind of chemical explosive with hazardous and toxic effects on the environment and human health. National and societal security concerns have dictated an increasing need for the analytical detection of TNT with rapidity, high sensitivity and low cost. This work demonstrates a novel method using L-cysteine-capped CdTe quantum dots (QDs) to assay TNT, based on the formation of a Meisenheimer complex between TNT and cysteine. The fluorescence (FL) of quantum dots quench because electrons of the QDs transfer to the TNT molecules via the formation of a Meisenheimer complex. TNT can be detected with a low detection limit of 1.1 nM. Studies on the selectivity of this method show that only TNT can generate an intense signal response. The synthesized QDs are excellent nanomaterials for TNT detection. In addition, TNT in soil samples is also analyzed by the proposed method.

Escherichia coli O157: H7 is detected using a remote-query (wireless, passive) magnetoelastic sensor platform to which a 1 µm-thick layer of Bayhydrol 110 and then a layer of functionalized mannose is applied. The multivalent binding of lectin concanavalin A (Con A) to the E. coli surface O-antigen and mannose favors the strong adhesion of E. coli to the mannose modified magnetoelastic sensor; E. coli is rigidly and strongly attached on the mannose-modified sensor through Con A, which works as a bridge to bind to the E. coli surface O-antigen and mannose modified sensor surface. As E. coli is bound to the sensor its resonance frequency shifts, enabling quantification of E. coli concentration with a limit of detection of 60 cells/mL and a linear logarithmic response range of 6.0×101 to 6.1×109 cells/mL. The analysis can be directly conducted without incubation, and completed in 3 h or less.

We report a novel method for biological thiols detection using ssDNA/silver nanoparticles system. The adsorbing ssDNA supplies silver nanoparticles high density charge to rescue nanoparticles from aggregation induced by salt. However, homocysteine (cysteine or glutathione) is conjugated more powerfully than ssDNA to AgNPs via Ag-S bond, which holds back ssDNA binding to AgNPs surface. When salt is added, AgNPs aggregation occurs and the corresponding color changes from yellow to brown after these biological thiols is introduced. A high sensitivity can be achieved using salt as an amplifier to assay thiols. In our study, a favorable linear correlation between the A(0)/A(x) ratio and homocysteine concentration was obtained in the range of 10 to 500 nM with a low detection limit of 10 nM, indicating that homocysteine could be analyzed at low concentration. A concentration as low as 300 nM homocysteine caused a visible color change. As well as, cysteine and glutathione can be detected at a detection limit of 50 nM and 100 nM, respectively. In addition, study on the selectivity of this method shows that only homocysteine, cysteine and glutathione can generate signal response.