Idiopathic pulmonary fibrosis (IPF) causes progressive fibrosis and worsening pulmonary function. Prognosis is poor and no effective therapies exist. We show that programmed cell death 5 (PDCD5) ...expression is increased in the lungs of patients with IPF and in mouse models of lung fibrosis. Lung fibrosis is significantly diminished by club cell-specific deletion of Pdcd5 gene. PDCD5 mediates β-catenin/Smad3 complex formation, promoting TGF-β-induced transcriptional activation of matricellular genes. Club cell Pdcd5 knockdown reduces matricellular protein secretion, inhibiting fibroblast proliferation and collagen synthesis. Here, we demonstrate the club cell-specific role of PDCD5 as a mediator of lung fibrosis and potential therapeutic target for IPF.
Breast cancer accounts for 25% of all types of cancer in women, and triple negative breast cancer (TNBC) comprises around 15~20% of breast cancers. Conventional chemotherapy and radiation are the ...primary systemic therapeutic strategies; no other FDA-approved targeted therapies are yet available as for TNBC. TNBC is generally characterized by a poor prognosis and high rates of proliferation and metastases. Due to these aggressive features and lack of targeted therapies, numerous attempts have been made to discover viable molecular targets for TNBC. Massive cohort studies, clinical trials, and in-depth analyses have revealed diverse molecular alterations in TNBC; however, controversy exists as to whether many of these changes are beneficial or detrimental in caner progression. Here we review the complicated tumorigenic processes and discuss critical findings and therapeutic trends in TNBC with a focus on promising therapeutic approaches, the clinical trials currently underway, and potent experimental compounds under preclinical and evaluation.
The main gas‐sensing mechanisms of 2D materials are surface charge transfer by analytes and Schottky barrier (SB) modulation at the interface between the metallic and semiconducting surfaces. In ...particular, dramatic differences in the gas‐sensing performances of 2D materials originate from SB modulation. However, SB sites typically exist only at the interface between the semiconducting channel material and the metal electrode. Herein, in situ formed multiple SBs in a single gas‐sensing channel are demonstrated, which are derived from the heterojunction of metallic Ti3C2 and semiconducting TiO2. In stark contrast with previous techniques, edge‐oxidized Ti3C2 flakes are synthesized by solution oxidation, allowing the uniform formation of TiO2 crystals on all flakes that comprise the gas sensing channel. Oxidized colloidal solutions are subjected to vacuum filtration to automatically form SB sites at the multiple inter‐flake junctions in both the outer surface and inner bulk regions of the film. The TiO2/Ti3C2 composite sensor shows 13.7 times higher NO2 sensitivity as compared with pristine Ti3C2 MXene, while the responses of the reducing gases are almost unchanged. The results suggest a new strategy for improving gas‐sensing performance by maximizing the density of SB sites through a simple method.
Ti3C2 MXene thin films with in situ formed multiple Schottky barriers (SBs) are synthesized by employing a solution‐based oxidation method, selectively forming TiO2 nanocrystals at the edge sites of each individual MXene sheet. Gas sensors based on the TiO2/Ti3C2 heterostructure show a highly enhanced gas response toward nitrogen dioxide gas resulting from SB modulation.
An electronic nose (E‐nose) is an artificial sensing device that mimics the human olfactory system using a multiarray sensor system. However, since the design and fabrication of multiarray sensing ...channels are significantly limited because of the requirement of time‐consuming and nonuniversal processes, the development of commercializable and high‐throughput fabrication approaches are critically required. Herein, high‐resolution top‐down lithography is developed for E‐nose fabrication for the first time. Five different metal oxide semiconductor (MOS) nanopattern channels (NiO, CuO, Cr2O3, SnO2, and WO3) are fabricated into multiarray sensors with high‐throughput using a unique lithographic approach that utilizes the sputtering of grains of the metals via low‐energy ion plasma bombardment. The nanopattern channels show i) high‐resolutions (15 nm scale), ii) high‐aspect‐ratios (11; 14 nm width and 150 nm height), and iii) ultrasmall grains (5.1 nm) with uniformity on a cm2 scale, resulting in high sensitivity toward the target analytes. The E‐nose system, which is composed of five MOS nanopattern channels, can successfully distinguish seven different hazardous analytes, including volatile organic compounds and nitrogen‐containing compounds. It is expected that this unique lithography approach can provide a simple and reliable method for commercializable channel fabrication, and the E‐noses can have further applications in real‐life situations.
High‐resolution top‐down lithography is used to develop a multiarray nanopatterned electronic nose. It demonstrates a unique nanolithography, with five distinct metal oxide semiconductor channels with 15 nm resolution and 5.1 nm grain size fabricated using an identical method and achieving successful segregation of seven different gases. This unique top‐down approach can provide a reliable method for channel diversification on a commercial level.
The development of a simple and cost‐effective method for fabricating ≈10 nm scale nanopatterns over large areas is an important issue, owing to the performance enhancement such patterning brings to ...various applications including sensors, semiconductors, and flexible transparent electrodes. Although nanoimprinting, extreme ultraviolet, electron beams, and scanning probe litho‐graphy are candidates for developing such nanopatterns, they are limited to complicated procedures with low throughput and high startup cost, which are difficult to use in various academic and industry fields. Recently, several easy and cost‐effective lithographic approaches have been reported to produce ≈10 nm scale patterns without defects over large areas. This includes a method of reducing the size using the narrow edge of a pattern, which has been attracting attention for the past several decades. More recently, secondary sputtering lithography using an ion‐bombardment technique was reported as a new method to create high‐resolution and high‐aspect‐ratio structures. Recent progress in simple and cost‐effective top‐down lithography for ≈10 nm scale nanopatterns via edge and secondary sputtering techniques is reviewed. The principles, technical advances, and applications are demonstrated. Finally, the future direction of edge and secondary sputtering lithography research toward issues to be resolved to broaden applications is discussed.
The development of a method for fabricating ≈10 nm‐scale nanopatterns over large areas is an important issue. Edge lithography allows for reduction of the size of patterns through a simple and cost‐effective method. More recently, secondary sputtering lithography using an ion bombardment has been reported as a new method. Research on the methodology of the processes and various applications are reviewed.
Although a lot of mitochondria-targeting biothiol probes have been developed and applied to cellular imaging through thiol-induced disulfide cleavage or Michael addition reactions, relatively few ...probes assess mitochondrial GSH with high selectivity over Cys and Hcy and with NIR fluorescence capable of noninvasive imaging in biological samples. In order to monitor mitochondrial GSH with low background autofluorescence, we designed a heptamethine-azo conjugate as an NIR fluorescent probe by introducing a tunable lipophilic cation unit as the biomarker for mitochondria and a nitroazo group as the GSH-selective reaction site as well as the fluorescence quencher. The probe exhibited a dramatic off-on NIR fluorescence response toward GSH with high selectivity over other amino acids including Cys and Hcy. Further application to cellular imaging indicated that the probe was highly responsive to the changes of mitochondrial GSH in cells.
A major limitation of screening breast ultrasound (US) is a substantial number of false-positive biopsy. This study aimed to develop a deep learning-based computer-aided diagnosis (DL-CAD)-based ...diagnostic model to improve the differential diagnosis of screening US-detected breast masses and reduce false-positive diagnoses. In this multicenter retrospective study, a diagnostic model was developed based on US images combined with information obtained from the DL-CAD software for patients with breast masses detected using screening US; the data were obtained from two hospitals (development set: 299 imaging studies in 2015). Quantitative morphologic features were obtained from the DL-CAD software, and the clinical findings were collected. Multivariable logistic regression analysis was performed to establish a DL-CAD-based nomogram, and the model was externally validated using data collected from 164 imaging studies conducted between 2018 and 2019 at another hospital. Among the quantitative morphologic features extracted from DL-CAD, a higher irregular shape score (P = .018) and lower parallel orientation score (P = .007) were associated with malignancy. The nomogram incorporating the DL-CAD-based quantitative features, radiologists' Breast Imaging Reporting and Data Systems (BI-RADS) final assessment (P = .014), and patient age (P < .001) exhibited good discrimination in both the development and validation cohorts (area under the receiver operating characteristic curve, 0.89 and 0.87). Compared with the radiologists' BI-RADS final assessment, the DL-CAD-based nomogram lowered the false-positive rate (68% vs. 31%, P < .001 in the development cohort; 97% vs. 45% P < .001 in the validation cohort) without affecting the sensitivity (98% vs. 93%, P = .317 in the development cohort; each 100% in the validation cohort). In conclusion, the proposed model showed good performance for differentiating screening US-detected breast masses, thus demonstrating a potential to reduce unnecessary biopsies.
Studies investigating the precision of 3-dimensional (3D) printed casts for fixed prosthodontics are scarce.
The purpose of this in vitro study was to compare the accuracy and reproducibility of ...dental casts made by the conventional method and by 3D printing.
A master model was designed and fabricated with polyetherketoneketone. Ten specimens were fabricated with Type IV dental stone with polyvinyl siloxane. A light scanner was used to scan the master model, and the data were converted to standard tessellation language (STL) files. Three different types of 3D printers (Objet EDEN260V, ProMaker D35, and LC-3Dprint) were used to make 10 specimens each. All specimens were scanned by the light scanner, and the scanned files were superimposed on the files of the master model with specialized software to analyze the volumetric changes. The Kruskal-Wallis test, Mann-Whitney U tests, and Bonferroni method were performed with statistical analysis software (α=.05).
The volumetric changes in casts made by the conventional method and by the 3D printers were significantly different. The conventional casts showed smaller volumetric change than the 3D-printed casts. Significant differences (P<.05) were found among the different types of 3D printers. The ultraviolet-polymerizing polymer with digital light processing exhibited the smallest volumetric change. In 3D color maps, the deformations were in similar patterns with all the 3D printers.
The conventional method of die fabrication was more reliable than that of 3D printers.
Self‐assemblies (i.e., nanoclusters) of the RAS GTPase on the membrane act as scaffolds that activate downstream RAF kinases and drive MAPK signaling for cell proliferation and tumorigenesis. ...However, the mechanistic details of nanoclustering remain largely unknown. Here, size‐tunable nanodisc platforms and paramagnetic relaxation enhancement (PRE) analyses revealed the structural basis of the cooperative assembly processes of fully processed KRAS, mutated in a quarter of human cancers. The cooperativity is modulated by the mutation and nucleotide states of KRAS and the lipid composition of the membrane. Notably, the oncogenic mutants assemble in nonsequential pathways with two mutually cooperative ‘α/α’ and ‘α/β’ interfaces, while α/α dimerization of wild‐type KRAS promotes the secondary α/β interaction sequentially. Mutation‐based interface engineering was used to selectively trap the oligomeric intermediates of KRAS and probe their favorable interface interactions. Transiently exposed interfaces were available for the assembly. Real‐time NMR demonstrated that higher‐order oligomers retain higher numbers of active GTP‐bound protomers in KRAS GTPase cycling. These data provide a deeper understanding of the nanocluster‐enhanced signaling in response to the environment. Furthermore, our methodology is applicable to assemblies of many other membrane GTPases and lipid nanoparticle‐based formulations of stable protein oligomers with enhanced cooperativity.
Size‐tunable nanodisc platforms and NMR revealed the structural mechanism for the cooperative self‐assembly of both wild‐type and oncogenic mutants of native, fully processed KRAS on the membrane. The cooperativity is modulated by the mutation and nucleotide states of KRAS and the lipid composition of the membrane. Higher‐order oligomers retain higher numbers of active GTP‐bound protomers by reducing GTP hydrolysis and increasing GDP/GTP exchange.
PDF
