Designing of anisotropic gradient surfaces for directional liquid transport: Fundamentals, construction, and applications.

Many biological surfaces are capable of transporting liquids in a directional manner without energy consumption. Inspired by nature, constructing asymmetric gradient surfaces to achieve desired droplet transport, such as a liquid diode, brings an incredibly valuable and promising area of research with a wide range of applications. Enabled by advances in nanotechnology and manufacturing techniques, biomimetics has emerged as a promising avenue for engineering various types of anisotropic material system. Over the past few decades, this approach has yielded significant progress in both fundamental understanding and practical applications. Theoretical studies revealed that the heterogeneous composition and topography mainly govern the wetting mechanisms and dynamics behavior of droplets, including the interdisciplinary aspects of materials, chemistry, and physics. In this review, we provide a concise overview of various biological surfaces that exhibit anisotropic droplet transport. We discussed the theoretical foundations and mechanisms of droplet motion on designed surfaces and reviewed recent research advances in droplet directional transport on designed plane surfaces and Janus membranes. Such liquid-diode materials yield diverse promising applications, involving droplet collection, liquid separation and delivery, functional textiles, and biomedical applications. We also discuss the recent challenges and ongoing approaches to enhance the functionality and application performance of anisotropic materials.

An ultrasensitive method for detecting mutations from short and rare cell-free DNA.

Circulating tumor DNA (ctDNA) was short and rare, making the detection performance of the current targeted sequencing methods unsatisfying. We developed the One-PrimER Amplification (OPERA) system and examined its performance in detecting mutations of low variant allelic frequency (VAF) in various samples with short-sized DNA fragments. In cell line-derived samples containing sonication-sheared DNA fragments with 50-150 bp, OPERA was capable of detecting mutations as low as 0.0025% VAF, while CAPP-Seq only detected mutations of >0.03% VAF. Both single nucleotide variant and insertion/deletion can be detected by OPERA. In synthetic fragments as short as 80 bp with low VAF (0.03%-0.1%), the detection sensitivity of OPERA was significantly higher compared to that of droplet digital polymerase chain reaction. The error rate was 5.9×10-5 errors per base after de-duplication in plasma samples collected from healthy volunteers. By suppressing "single-strand errors", the error rate can be further lowered by >5 folds in EGFR T790M hotspot. In plasma samples collected from lung cancer patients, OPERA detected mutations in 57.1% stage I patients with 100% specificity and achieved a sensitivity of 30.0% in patients with tumor volume of less than 1 cm3. OPERA can effectively detect mutations in rare and highly-fragmented DNA.

Bilayer Nanoporous Polyethylene Membrane with Anisotropic Wettability for Rapid Water Transportation/Evaporation and Radiative Cooling.

Both sweat drainage and evaporation play important roles in achieving personal moisture and thermal management during sweat-producing exercises. However, it remains a great challenge to simultaneously realize thermal management through radiative cooling for human body without perspiration. Herein, we report a bilayer nanoporous polyethylene membrane with anisotropic wettability, which possesses superior radiative cooling ability (∼2.6 °C lower than that of cotton) without perspiration. Meanwhile, it realizes efficient sweat drainage and good evaporation cooling property (∼1.0 °C lower than that of cotton) in perspiration to avoid sticky and hot sensation. In addition, it can also block water and fine particulate matter owing to the hydrophobic nanoporous structure. By virtue of the outstanding personal thermal and moisture management performance, it is expected that this study provides inspiration for designing new clothing and medical protective suits with more comfortable microclimates and reducing energy consumption for global sustainability.

Comprehensive Analysis of EGFR-Mutant Abundance and Its Effect on Efficacy of EGFR TKIs in Advanced NSCLC with EGFR Mutations.

INTRODUCTION: A qualitative detection method for EGFR mutations is not sufficient to guide precise targeted therapy in clinical practice. The aim of this study was to explore the relationship between the abundance of EGFR mutations and efficacy of EGFR tyrosine kinase inhibitors (TKIs). METHODS: We used the amplification refractory mutation system (ARMS) method optimized with competitive blockers and specific mutation quantitation (ARMS+) to quantitatively evaluate the abundance of EGFR mutations in 201 patients with advanced NSCLC. A cutoff value of the abundance of EGFR mutations was determined by receiver operating characteristic analysis in a training group and validated in a validation group. RESULTS: The abundance of EGFR activating mutation by ARMS+ was significantly associated with objective response to EGFR TKIs. The abundance of 19DEL was significantly higher than that of L858R, with cutoff values for 19DEL and L858R of 4.9% and 9.5%, respectively. The median progression-free survival in the high group was significantly longer than that in the low group (19DEL, 15.0 versus 2.0 months [p < 0.001] and L858R, 12.3 versus 2.0 months [p < 0.001]) in the training set. Similar results were also observed in the validation set. Nine of 13 patients harboring T790M mutation achieved a partial response to EGFR TKIs. Most (seven of nine) were identified to have a low abundance of T790M mutation. The abundance of EGFR mutations appeared to be more significantly associated with the copy number of EGFR mutations from circulating tumor DNA in 19DEL group. CONCLUSION: The abundance of EGFR activating mutation by ARMS+ was significantly associated with objective response to EGFR TKIs. The abundance of EGFRT790M mutation may have an adverse impact on progression-free survival rather than on objective response rate in patients with advanced EGFR-mutant NSCLC treated with EGFR TKIs.

A preliminary study on the relationship between circulating tumor cells count and clinical features in patients with non-small cell lung cancer.

BACKGROUND: To evaluate the clinical value of circulating tumor cells (CTC) count in peripheral venous blood of patients with non-small cell lung carcinoma (NSCLC). METHODS: A total of 50 NSCLC patients who were diagnosed in Wuxi No. 2 People's Hospital from January 2013 to December 2013 were selected as the NSCLC group, 35 patients with lung benign tumor as the benign group, and 28 healthy subjects as the normal control group. Venous blood samples (3 mL) were collected in all subjects for counting the CTC, and a result of ≥8.7 was judged to be positive. The relationships between the positive rate of CTC and the age, sex, pathological type, and clinical stage of NSCLC were analyzed. RESULTS: CTC count was significantly higher in NSCLC group than in benign group and normal control group. In NSCLC patients, CTC count was not significantly correlated with sex, age, or the pathological type (P>0.05) but was closely related to clinical stage (P<0.01). Among NSCLC patients, CTC count significantly increased along with tumor progression. CONCLUSIONS: CTC count shows certain correlation with the clinical features of NSCLC and thus can, to certain extent, reflect the status of the disease.

Folate receptor-positive circulating tumor cells as a novel diagnostic biomarker in non-small cell lung cancer.

The study aims to determine the efficacy and feasibility of a novel folate receptor (FR)-based circulating tumor cell (CTC) detection method in the diagnosis of non-small cell lung cancer (NSCLC). CTCs were collected from 3 ml of blood based on negative enrichment by immunomagnetic beads and then labeled by a conjugate of a tumor-specific ligand folate and an oligonucleotide. After washing off redundant conjugates, the bound conjugates were removed and analyzed by quantitative polymerase chain reaction. The captured cells were validated as tumor cells by immunofluorescence staining. In the evaluation of clinical utility, the results showed that the CTC levels of 153 patients with NSCLC were significantly higher than the controls (49 healthy donors and 64 patients with benign lung diseases; P < .001). With a threshold of 8.64 CTC units, the method showed a sensitivity of 73.2% and a specificity of 84.1% in the diagnosis of NSCLC, especially a sensitivity of 67.2% in stage I disease. Compared with the existing clinical biomarkers such as neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), cyfra21-1, and squamous cell carcinoma antigen (SCC Ag), the method showed the highest diagnostic efficiency (area under the curve, 0.823; 95% confidence interval, 0.773-0.874). Together, our results demonstrated that FR-positive CTCs were feasible diagnostic biomarkers in patients with NSCLC, as well as in early-stage tumors.