Highly transparent and flexible Ag nanowire-embedded silk fibroin electrodes for biocompatible flexible and transparent heater

We investigated the electrical, optical and mechanical properties of silver (Ag) nanowire (NW) embedded into a silk fibroin (SF) substrate to create high performance, flexible, transparent, biocompatible, and biodegradable heaters for use in wearable electronics. The Ag NW-embedded SF showed a low sheet resistance of 15 Ω sq⁻¹, high optical transmittance of 85.1%, and a small inner/outer critical bending radius of 1 mm. In addition, the Ag NW-embedded SF showed a constant resistance change during repeated bending, folding, and rolling because the connectivity of the Ag NW embedded into the SF substrate was well maintained. Furthermore, the biocompatible and biodegradable Ag NW-embedded SF substrate served as a flexible interconnector for wearable electronics. The high performance of the transparent and flexible heater demonstrated that an Ag NW-embedded SF-based heater can act as a biocompatible and biodegradable substrate for wearable heaters for the human body.

We demonstrated the characteristics of a transparent, flexible silver nanowire-embedded silk fibroin substrate that can be used as a flexible and biocompatible electrode for wearable electronics.     

Lenalidomide before and after autologous stem cell transplantation for transplant-eligible patients of all ages in the randomized,phase III,Myeloma XI trial

The optimal way to use immunomodulatory drugs as components of induction and maintenance therapy for multiple myeloma is unresolved. We addressed this question in a large phase III randomized trial, Myeloma XI. Patients with newly diagnosed multiple myeloma (n=2,042) were randomized to induction therapy with cyclophosphamide, thalidomide, and dexamethasone (CTD) or cyclophosphamide, lenalidomide, and dexamethasone (CRD). Additional intensification therapy with cyclophosphamide, bortezomib, and dexamethasone (CVD) was administered before autologous stem-cell transplantation to patients with a suboptimal response to induction therapy using a response-adapted approach. After receiving high-dose melphalan with autologous stem cell transplantation, eligible patients were further randomized to receive either lenalidomide alone or observation alone. Co-primary endpoints were progression-free survival (PFS) and overall survival (OS). The CRD regimen was associated with significantly longer PFS (median: 36 vs. 33 months; hazard ratio [HR], 0.85; 95% confidence interval [CI]: 0.75-0.96; P=0.0116) and OS (3-year OS: 82.9% vs. 77.0%; HR, 0.77; 95% CI: 0.63-0.93; P=0.0072) compared with CTD. The PFS and OS results favored CRD over CTD across all subgroups, including patients with International Staging System stage III disease (HR for PFS, 0.73; 95% CI: 0.58-0.93; HR for OS, 0.78; 95% CI: 0.56-1.09), high-risk cytogenetics (HR for PFS, 0.60; 95% CI: 0.43-0.84; HR for OS, 0.70; 95% CI: 0.42-1.15) and ultra-high-risk cytogenetics (HR for PFS, 0.67; 95% CI: 0.41-1.11; HR for OS, 0.65; 95% CI: 0.34-1.25). Among patients randomized to lenalidomide maintenance (n=451) or observation (n=377), maintenance therapy improved PFS (median: 50 vs. 28 months; HR, 0.47; 95% CI: 0.37-0.60; P<0.0001). Optimal results for PFS and OS were achieved in the patients who received CRD induction and lenalidomide maintenance. The trial was registered with the EU Clinical Trials Register (EudraCT 2009-010956-93) and ISRCTN49407852.     

Hesperidin attenuates mitochondrial dysfunction during benzo(a)pyrene‐induced lung carcinogenesis in mice

The present study is designed to assess the mitochondrial status during benzo(a)pyrene (B(a)P)‐induced lung carcinogenesis in Swiss albino mice and to reveal the modulatory effect of hesperidin over it. B(a)P (50 mg/kg body weight)‐induced mitochondrial abnormalities was evident from alterations in mitochondrial lipid peroxides, antioxidant status (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glutathione‐S‐transferase, reduced glutathione, vitamin E, and vitamin C), major tricarboxylic acid (TCA) cycle enzyme activities (isocitrate dehydrogenase, succinate dehydrogenase, malate dehydrogenase, alpha‐ketoglutarate dehydrogenase), electron transport chain (ETC) complexes activities and ATP levels. Ultrastructural changes in lung mitochondria were also in accord with the above aberrations. Hesperidin (25 mg/kg body weight) supplementation effectively counteracted all the above changes and restored cellular normalcy, indicating its protective role during B(a)P‐induced lung cancer.     

Oviposition-deterrent,ovicidal, and repellent activities of indigenous plant extracts against <Emphasis Type="Italic">Anopheles subpictus</Emphasis> Grassi (Diptera: Culicidae)

Insecticides of botanical origin may serve as suitable alternative biocontrol techniques in the future. The leaf acetone, ethyl acetate, and methanol extracts of Aegle marmelos (Linn.) Correa ex Roxb, Andrographis lineata Wallich ex Nees, and Cocculus hirsutus (L.) Diels were tested for oviposition-deterrent, ovicidal, and repellent activities against Anopheles subpictus Grassi (Diptera: Culicidae). The percentage of effective oviposition repellency of 92.60 , 93.04, 95.20, 88.26, 92.80, 94.01, 95.77, 96.93, and 92.54 at 500 ppm and the lowest repellency of 47.14, 58.00, 56.52, 64.93, 71.09, 66.42, 50.62, 57.62, and 65.73 at 31.25 ppm in acetone, ethyl acetate, and methanol extracts of Aegle marmelos, Andrographis lineata, and Cocculus hirsutus, respectively. The oviposition activity index (OAI) value of acetone, ethyl acetate, and methanol extracts of Aegle marmelos, Andrographis lineata, and Cocculus hirsutus at 500 ppm were −0.86, −0.87, −0.90, −0.78, −0.87, −0.86, −0.91, −0.94, and −0.86 respectively. The OAI values revealed that the solvent plant extracts have deterrent effect, and they caused a remarkable negative response resulting in oviposition of very few eggs. Mean percent hatchability of the ovicidal activity was observed 24 h after treatment. The percent hatchability was inversely proportional to the concentration of extract and directly proportional to the eggs. Mortality of 100% with ethyl acetate extract of Aegle marmelos, methanol extracts Aegle marmelos, Andrographis lineata, and Cocculus hirsutus were exerted at 1,000 ppm. The maximum repellent activity was observed at 500 ppm in methanol extracts of Aegle marmelos, Andrographis lineata, and ethyl acetate extract of Cocculus hirsutus, and the mean complete protection time ranged from 90 to 120 min with the different extracts tested. These results suggest that the leaf extracts of Aegle marmelos, Andrographis lineata, and Cocculus hirsutus have the potential to be used as an ideal ecofriendly approach for the control of the Anopheles subpictus. Therefore, this study provides first report on the oviposition, ovicidal, and repellent activities against malaria vector, Anopheles subpictus of plant extracts from Southern India.     

Predictive value of p53 and pRb expression in superficial bladder cancer patients treated with BCG and interferon-alpha

BACKGROUND: Nuclear p53 and retinoblastoma protein (pRb) were reported to be poor prognostic indicators for transitional cell carcinoma of the bladder. The authors sought to determine the prognostic value of nuclear p53 and pRb in superficial bladder transitional cell carcinoma patients who were treated with intravesical bacille Calmette-Guerin (BCG) or BCG with interferon-alpha (IFN-alpha). METHODS: A prospective histological review was performed for 80 superficial bladder transitional cell carcinoma patients who underwent postresection intravesical regimes of BCG (81 mg, n = 33 or 27 mg, n = 20) or BCG (27 mg) with IFN-alpha (n = 27), and followed for a mean of 4.5 years. Hematoxylin and eosin (H & E) and immunoperoxidase staining were performed on tissue sections. Nuclear p53 and pRb immunoreactivity were assessed semiquantitatively, by using a combination of staining extent and intensity, to categorize overexpression or underexpression. Data were analyzed by using chi-square analysis, multiple logistic regression, and Kaplan-Meier curves. RESULTS: pRb expression was not associated with patient outcome after BCG-alone therapy, but pRb underexpression was significantly associated with BCG nonresponse and tumor recurrence (P = .047) after BCG and IFN-alpha (BCG + IFN-alpha) therapy. Low-grade tumors were associated with pRb overexpression, with or without nuclear p53 underexpression (P = .019; P = .043, respectively). p53 expression alone or in combination with pRb expression had no significant relation with tumor response to BCG alone or BCG + IFN-alpha with respect to recurrence, progression, or cancer-specific death. CONCLUSIONS: Nuclear pRb underexpression may be predictive of nonresponse and cancer recurrence after intravesical BCG + IFN-alpha therapy. Nuclear p53 expression or its combination with pRb expression is not associated with post-BCG clinical outcome, so p53 expression or p53 with pRb expression should not be used to influence decisions concerning BCG-alone or BCG + IFN-alpha therapy.     

A refined pharmacophore identifies potent 4-amino-7-chloroquinoline-based inhibitors of the botulinum neurotoxin serotype A metalloprotease

We previously identified structurally diverse small molecule (non-peptidic) inhibitors (SMNPIs) of the botulinum neurotoxin serotype A (BoNT/A) light chain (LC). Of these, several (including antimalarial drugs) contained a 4-amino-7-chloroquinoline (ACQ) substructure and a separate positive ionizable amine component. The same antimalarials have also been found to interfere with BoNT/A translocation into neurons, via pH elevation of the toxin-mediated endosome. Thus, this structural class of small molecules may serve as dual-function BoNT/A inhibitors. In this study, we used a refined pharmacophore for BoNT/A LC inhibition to identify four new, potent inhibitors of this structural class (IC50's ranged from 3.2 to 17 muM). Molecular docking indicated that the binding modes for the new SMNPIs are consistent with those of other inhibitors that we have identified, further supporting our structure-based pharmacophore. Finally, structural motifs of the new SMNPIs, as well as two structure-based derivatives, were examined for activity, providing valuable information about pharmacophore component contributions to inhibition.     

Larvicidal activity of green synthesized silver nanoparticles using bark aqueous extract of Ficus racemosa against Culex quinquefasciatus and Culex gelidus

ObjectiveTo investigate the larvicidal activity of synthesized silver nanoparticles (Ag NPs) utilizing aqueous bark extract of Ficus racemosa (F. racemosa) was tested against fourth instar larvae of filariasis vector, Culex quinquefasciatus (Cx. quinquefasciatus) and japanese encephalitis vectors, Culex gelidus (Cx. gelidus).MethodsThe synthesized Ag NPs was characterized by UV-vis spectrum, X-ray diffraction (XRD), Scanning electron microscopy (SEM) and Fourier transform infrared (FTIR). The larvicidal activities were assessed for 24 h against the larvae of Cx. quinquefasciatus and Cx. gelidus with varying concentrations of aqueous bark extract of F. racemosa and synthesized Ag NPs. LC₅₀ and r² values were calculated.ResultsThe maximum efficacy was observed in crude aqueous extract of F. racemosa against the larvae of Cx. quinquefasciatus and Cx. gelidus (LC₅₀=67.72 and 63.70 mg/L; r²=0.995 and 0.985) and the synthesized Ag NPs (LC₅₀=12.00 and 11.21 mg/L; r²=0.997 and 0.990), respectively. Synthesized Ag NPs showed the XRD peaks at 2 θ values of 27.61, 29.60, 35.48, 43.48 and 79.68 were identified as (210), (121), (220), (200) and (311) reflections, respectively. The FTIR spectra of Ag NPs exhibited prominent peaks at 3 425, 2 878, 1 627 and 1 382 in the region 500-3 000 cm^?1. The peaks correspond to the presence of a stretching vibration of (NH) C=O group. SEM analysis showed shape in cylindrical, uniform and rod with the average size of 250.60 nm.ConclusionsThe biosynthesis of silver nanoparticles using bark aqueous extract of F. racemosa and its larvicidal activity against the larvae of disease spreading vectors. The maximum larvicidal efficacy was observed in the synthesized Ag NPs.     

NRAMP1 and hGPX1 gene polymorphism and response to bacillus Calmette-Guérin therapy for bladder cancer

Background

The natural resistance-associated macrophage protein 1 (NRAMP1) gene is associated with susceptibility to Mycobacterium tuberculosis in humans and to bacillus Calmette-Guérin (BCG) in mice. The detoxification enzyme, human glutathione peroxidase 1 (hGPX1), is associated with recurrence of bladder cancer (BCa).

Objective

To determine whether NRAMP1 and hGPX1 gene polymorphisms correlate with response to BCG immunotherapy for non–muscle-invasive BCa (NMIBC).

Design, setting, and participants

DNA was obtained from the peripheral blood of 99 NMIBC patients who were prospectively randomized to receive postresection intravesical BCG (81 mg [n = 50] or 27 mg [n = 19]) or BCG (27 mg) with interferon alpha (IFN-α; n = 30). The median follow-up time was 60 mo.

Intervention

Intravesical BCG or BCG–IFN-α.

Measurements

Restriction fragment length polymorphism (RFLP) analysis was performed to identify polymorphisms in the NRAMP1 promoter region (GT repeat number) and at position 543 (aspartate [D] and/or asparagine [N] expression) within the NRAMP1 protein (D543N) and position 198 (proline and/or leucine expression) within the hGPX1 protein (Pro198Leu). Data were analyzed using χ² analysis, multivariate analysis, and Kaplan-Meier curves.

Results and limitations

On univariate analysis, the NRAMP1 D543N G:G genotype had decreased cancer-specific survival (CSS; p = 0.036). The hGPX1 CT genotype (Pro-Leu) had decreased recurrence time (p = 0.03) after BCG therapy. On multivariate analysis, patients with the NRAMP1 D543N G:G genotype and allele 3 (GT)n polymorphism had decreased recurrence time (p = 0.014 and p = 0.03) after BCG therapy. The limitation of this study was its small sample size.

Conclusions

Polymorphisms of the NRAMP1 and hGPX1 genes may be associated with recurrence of BCa after BCG immunotherapy.