Sculpting nanostructures into different geometries in either one or two dimensions produces a wide range of colorful elements in microscopic prints. However, achieving different shades of gray and ...control of color saturation remain challenging. Here, we report a complete approach to color and grayscale generation based on the tuning of a single nanostructure geometry. Through two-photon polymerization lithography, we systematically investigated color generation from the basic single nanopillar geometry in low-refractive-index (n < 1.6) material. Grayscale and full color palettes were achieved that allow decomposition onto hue, saturation, and brightness values. This approach enabled the “painting” of arbitrary colorful and grayscale images by mapping desired prints to precisely controllable parameters during 3D printing. We further extend our understanding of the scattering properties of the low-refractive-index nanopillar to demonstrate grayscale inversion and color desaturation and steganography at the level of single nanopillars.
Interactive materials capable of changing appearance upon exposure to external stimuli, such as photonic inks, are generally difficult to achieve on a large scale as they often require self‐assembly ...processes that are difficult to control macroscopically. Here this problem is overcome by preparing arrays of cellulose nanocrystal (CNC) microfilms from discrete nanoliter sessile droplets. The obtained microfilms show extremely uniform and intense color, enabling exceptional consistency in optical appearance across the entire array. The color can be controlled through the initial ink formulation, enabling the printing of polychromatic dot‐matrix images. Moreover, the high surface‐to‐volume ratio of the microfilms and the intrinsic hydrophilicity of the natural building block allow for a dramatic real‐time colorimetric response to changes in relative humidity. The printed CNC microfilm arrays overcome the existing issues of scalability, optical uniformity, and material efficiency, which have held back the adoption of CNC‐based photonic materials in cosmetics, interactive‐pigments, or anticounterfeit applications.
Large‐scale patterned arrays of photonic cellulose nanocrystal microfilms are prepared from sessile droplets. Strong planar anchoring within each nanoliter droplet, combined with a controlled drying process, suppresses the “coffee ring effect” and results in well‐aligned photonic films. Such iridescent microfilm arrays display highly uniform and intense structural color and are highly responsive, displaying a dramatic real‐time colorimetric response to humidity.
We aimed to investigate the effects of adiponectin on liver cancer growth and metastasis and explore the underlying mechanisms.
An orthotopic liver tumor nude mice model with distant metastatic ...potential was applied. Either Ad-adiponectin (1 x 10(8); treatment group) or Ad-luciferase (control group) was injected via portal vein after tumor implantation. Tumor growth and metastasis were monitored by Xenogen In vivo Imaging System. Hepatic stellate cell activation by alpha-smooth muscle actin staining, microvessel density by CD34 staining, macrophage infiltration in tumor tissue, and cell signaling leading to invasion, migration Rho kinase (ROCK), IFN-inducible protein 10 (IP10), and matrix metalloproteinase 9, and angiogenesis vascular endothelial growth factor (VEGF) and angiopoietin 1 were also compared. Tumor-nontumor margin was examined under electron microscopy. Direct effects of adiponectin on liver cancer cells and endothelial cells were further investigated by a series of functional studies.
Tumor growth was significantly inhibited by adiponectin treatment, accompanied by a lower incidence of lung metastasis. Hepatic stellate cell activation and macrophage infiltration in the liver tumors were suppressed by adiponectin treatment, along with decreased microvessel density. The treatment group had less Ki-67-positive tumor cells and downregulated protein expression of ROCK1, proline-rich tyrosine kinase 2, and VEGF. Tumor vascular endothelial cell damage was found in the treatment group under electron microscopy. In vitro functional study showed that adiponectin not only downregulated the ROCK/IP10/VEGF signaling pathway but also inhibited the formation of lamellipodia, which contribute to cell migration.
Adiponectin treatment significantly inhibited liver tumor growth and metastasis by suppression of tumor angiogenesis and downregulation of the ROCK/IP10/matrix metalloproteinase 9 pathway.
Aside from the multikinase inhibitor sorafenib, there are no effective systemic therapies for the treatment of advanced hepatocellular carcinoma.
To assess the efficacy of everolimus in patients with ...advanced hepatocellular carcinoma for whom sorafenib treatment failed.
EVOLVE-1 was a randomized, double-blind, phase 3 study conducted among 546 adults with Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma and Child-Pugh A liver function whose disease progressed during or after sorafenib or who were intolerant of sorafenib. Patients were enrolled from 17 countries between May 2010 and March 2012. Randomization was stratified by region (Asia vs rest of world) and macrovascular invasion (present vs absent).
Everolimus, 7.5 mg/d, or matching placebo, both given in combination with best supportive care and continued until disease progression or intolerable toxicity. Per the 2:1 randomization scheme, 362 patients were randomized to the everolimus group and 184 patients to the placebo group.
The primary end point was overall survival. Secondary end points included time to progression and the disease control rate (the percentage of patients with a best overall response of complete or partial response or stable disease).
No significant difference in overall survival was seen between treatment groups, with 303 deaths (83.7%) in the everolimus group and 151 deaths (82.1%) in the placebo group (hazard ratio HR, 1.05; 95% CI, 0.86-1.27; P = .68; median overall survival, 7.6 months with everolimus, 7.3 months with placebo). Median time to progression with everolimus and placebo was 3.0 months and 2.6 months, respectively (HR, 0.93; 95% CI, 0.75-1.15), and disease control rate was 56.1% and 45.1%, respectively (P = .01). The most common grade 3/4 adverse events for everolimus vs placebo were anemia (7.8% vs 3.3%, respectively), asthenia (7.8% vs 5.5%, respectively), and decreased appetite (6.1% vs 0.5%, respectively). No patients experienced hepatitis C viral flare. Based on central laboratory results, hepatitis B viral reactivation was experienced by 39 patients (29 everolimus, 10 placebo); all cases were asymptomatic, but 3 everolimus recipients discontinued therapy.
Everolimus did not improve overall survival in patients with advanced hepatocellular carcinoma whose disease progressed during or after receiving sorafenib or who were intolerant of sorafenib.
clinicaltrials.gov Identifier: NCT01035229.
We report on the directed self-assembly of sub-10 nm gold nanoparticles confined within a template comprising channels of gradually varying widths. When the colloidal lattice parameter is mismatched ...with the channel width, the nanoparticles rearrange and break their natural close-packed ordering, transiting through a range of structural configurations according to the constraints imposed by the channel. While much work has been done in assembling ordered configurations, studies of the transition regime between ordered states have been limited to microparticles under applied compression. Here, with coordinated experiments and Monte Carlo simulations we show that particles transit through a more diverse set of self-assembled configurations than observed for compressed systems. The new insight from this work could lead to the control and design of complex self-assembled patterns other than periodic arrays of ordered particles.
Directing the self-assembly of sub-10-nm nanoparticles has been challenging because of the simultaneous requirements to achieve a densely packed monolayer and rearrange nanoparticles to assemble ...within a template. We met both requirements by separating the processes into two steps by first forming a monolayer of gold nanoparticles on a suitable liquid subphase of anisole and then transferring it edgewise onto a silicon substrate with a prepatterned template comprising nanoposts and nanogratings. Doing so resulted in nanoparticles that assembled in commensuration with the template design while exhibiting appreciable template-induced strain. These dense arrays of nanostructures could either be directly applied or used as lithographic masks in applications for light collection, chemical sensing, and data storage.
Background
In early‐stage non–small cell lung cancer (NSCLC), recurrence is frequently observed. Circulating tumor DNA (ctDNA) has emerged as a noninvasive tool to risk stratify patients for ...recurrence after curative intent therapy. This study aimed to risk stratify patients with early‐stage NSCLC via a personalized, tumor‐informed multiplex polymerase chain reaction (mPCR) next‐generation sequencing assay.
Methods
This retrospective cohort study included patients with stage I–III NSCLC. Recruited patients received standard‐of‐care management (surgical resection with or without adjuvant chemotherapy, followed by surveillance). Whole‐exome sequencing of NSCLC resected tissue and matched germline DNA was used to design patient‐specific mPCR assays (Signatera, Natera, Inc) to track up to 16 single‐nucleotide variants in plasma samples.
Results
The overall cohort with analyzed plasma samples consisted of 57 patients. Stage distribution was 68% for stage I and 16% each for stages II and III. Presurgery (i.e., at baseline), ctDNA was detected in 15 of 57 patients (26%). ctDNA detection presurgery was significantly associated with shorter recurrence‐free survival (RFS; hazard ratio HR, 3.54; 95% confidence interval CI, 1.00–12.62; p = .009). In the postsurgery setting, ctDNA was detected in seven patients, of whom 100% experienced radiological recurrence. ctDNA positivity preceded radiological findings by a median lead time of 2.8 months (range, 0–12.9 months). Longitudinally, ctDNA detection at any time point was associated with shorter RFS (HR, 16.1; 95% CI, 1.63–158.9; p < .0001).
Conclusions
ctDNA detection before surgical resection was strongly associated with a high risk of relapse in early‐stage NSCLC in a large unique Asian cohort. Prospective studies are needed to assess the clinical utility of ctDNA status in this setting.
Circulating tumor DNA (ctDNA) detection before surgical resection was strongly associated with a high risk of relapse in early‐stage non–small cell lung cancer in a large unique Asian cohort. In addition, ctDNA detection longitudinally after surgery identified patients who recurred, with ctDNA positivity preceding radiological findings.
We aimed to explore the precise molecular mechanism of early and invasive tumor growth in a small-for-size graft after liver transplantation and to identify the distinct molecular signature linked to ...acute-phase injury and late-phase tumor invasiveness.
Acute phase small-for-size liver graft injury plays an important role in tumor recurrence after liver transplantation. For prevention of such recurrence, understanding of its underlying mechanism will be important in developing novel therapeutic strategies.
An orthotopic rat liver transplantation model was applied using whole grafts and small-for-size (50%) grafts. The recipients were injected with hepatoma cell lines via the portal vein to mimic tumor recurrence after liver transplantation. Tumor invasive properties were compared between the tumor developed from small and whole graft. Gene signatures of acute phase graft injury (days 1 and 3) and late phase tumor recurrence (days 14 and 21) were screened using cDNA microarray analysis and further confirmed by quantitative RT-PCR. The potential gene candidate CXCL10 was singled out for further functional studies to investigate its role in tumor progression.
A number of genes linked to inflammatory responses and tumor invasiveness were found over-expressed in small-for-size liver grafts and/or tumors developed in small liver grafts by cDNA microarray screening. Real-time RT-PCR also confirmed that the gene CXCL10 was over-expressed not only in small-for-size graft at the early phase, but also in tumor from small-for-size graft at the late phase after liver transplantation. In vitro functional studies further confirmed that CXCL10 promoted tumor-invasion-related properties and tumor-associated macrophage activation.
CXCL10 over-expression, the distinct gene signature of acute-phase graft injury and tumor invasiveness in small-for-size liver grafts, may contribute to early tumor recurrence after liver transplantation. CXCL10 and its downstream signals may be potential therapeutic targets in the prevention of tumor recurrence after liver transplantation using small-for-size graft.
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