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Using custom made experimental apparatus, the art of electrochemical etching was systematically studied for fabricating micro/nano tungsten probes with controllable tip profiles of exponential, conical, multidiameter, and calabashlike shapes. The characteristic parameters of probe including length, aspect ratio, and tip apex radius could also be well defined. By combining of static and dynamic etching, the conical-shape probe with length up to several millimeters, controllable tip apex radius, and cone angle could be fabricated. In addition, by continuously lifting the tungsten wire up during the electrochemical etching with different speeds and distances, the multidiameter shape probe could be fabricated. Finally by controlling the anodic flow, the multiple "neck-in" could be realized creating a calabashlike probe. The aspect ratio of probes depends on (i) the effective contact time between the surrounding electrolyte and the wire, (ii) the neck-in position of immersed tungsten wire. Under the optimized etching parameters, tungsten probes with a controllable aspect ratio from 20:1 to 450:1, apex radius less than 20 nm, and cone angle smaller than 3° could be achieved. The technique is well suited for the tungsten probe fabrication with a stabilized stylus contour, ultra-sharp apex radius, and high production reproducibility. The art for preparing microprobes will facilitate the application of such microprobes in diverse fields such as dip-pen nanolithography, scanning probe microscopy, micromachining, and biological cellular studies.

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This paper reports a new method to characterize the mechanical properties, such as the elasticity, of a thin elastomeric film. A sensitive microscope visualization instrument is developed for measuring the deformation of a circular membrane of thickness less than 200 µm, under a constant load. The elastic deformation of the thin membrane was measured laterally. A theoretical model is constructed to quantitatively correlate the elasticity to the deformation profile of the membrane. The good agreement between the experimental and theoretical results facilitates the determination of the elastic modulus of a thin elastomeric membrane.

Background Identification of potential novel targets for reversing resistance to Epidermal Growth Factor Receptor (EGFR)-tyrosine kinase inhibitors (EGFR-TKIs) holds great promise for the treatment of relapsed lung adenocarcinoma (LUAD). In the present study, we aim to investigate the role of methyltransferase-like 7B (METTL7B) in inducing EGFR-TKIs resistance in LUAD and whether it could be a therapeutic target for reversing the resistance. Methods METTL7B-overexpressed LUAD cell lines, gefitinib and osimertinib-resistant Cell-Derived tumor Xenograft (CDX) and Patient-Derived tumor Xenograft (PDX) mouse models were employed to evaluate the role of METTL7B in TKIs resistance. Ultraperformance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) was used to identify the metabolites regulated by METTL7B. Methylated RNA immunoprecipitation (MeRIP)-qPCR analysis was performed to measure the N6-methyladenosine (m6A) status of mRNA of METTL7B targeted genes. Gold nanocluster-assisted delivery of siRNA targeting METTL7B (GNC-siMETTL7B) was applied to evaluate the effect of METTL7B in TKIs resistance. Results Increased expression of METTL7B was found in TKIs-resistant LUAD cells and overexpression of METTL7B in LUAD cells induced TKIs resistance both in vitro and in vivo. Activated ROS-metabolism was identified in METTL7B-overexpressed LUAD cells, accompanied with upregulated protein level of GPX4, HMOX1 and SOD1 and their enzymatic activities. Globally elevated m6A levels were found in METTL7B-overexpressed LUAD cells, which was reduced by knock-down of METTL7B. METTL7B induced m6A modification of GPX4, HMOX1 and SOD1 mRNA. Knock-down of METTL7B by siRNA re-sensitized LUAD cells to gefitinib and osimertinib both in vitro and in vivo. Conclusions This study uncovered a new critical link in METTL7B, glutathione metabolism and drug resistance. Our findings demonstrated that METTL7B inhibitors could be used for reversing TKIs resistance in LUAD patients.