The development of short-wave infrared photodetectors based on various two-dimensional (2D) materials has recently attracted attention because of the ability of these devices to operate at room ...temperature. Although van der Waals heterostructures of 2D materials with type-II band alignment have significant potential for use in short-wave infrared photodetectors, there is a need to develop photodetectors with high photoresponsivity. In this study, we investigated the photogating of graphene using a monolayer-MoS2/monolayer-MoTe2 van der Waals heterostructure. By stacking MoS2/MoTe2 on graphene, we fabricated a broadband photodetector that exhibited a high photoresponsivity (>100 mA/W) and a low dark current (60 nA) over a wide wavelength range (488–1550 nm).
The increasing prevalence of distant metastases from non-small cell lung cancer (NSCLC) indicates an urgent need for novel therapeutic modalities. Brain metastasis is particularly common in NSCLC, ...with severe adverse effects on clinical prognosis. Although the molecular heterogeneity of NSCLC and availability of various targeted agents suggest personalized therapeutic approaches for such brain metastases, further development of appropriate preclinical models is needed to validate the strategies.
We established patient-derived xenografts (PDX) using NSCLC brain metastasis surgical samples and elucidated their possible preclinical and clinical implications for personalized treatment.
NSCLC brain metastases (n = 34) showed a significantly higher successful PDX establishment rate than primary specimens (n = 64; 74% vs. 23%). PDXs derived from NSCLC brain metastases recapitulated the pathologic, genetic, and functional properties of corresponding parental tumors. Furthermore, tumor spheres established in vitro from the xenografts under serum-free conditions maintained their in vivo brain metastatic potential. Differential phenotypic and molecular responses to 20 targeted agents could subsequently be screened in vitro using these NSCLC PDXs derived from brain metastases. Although PDX establishment from primary NSCLCs was significantly influenced by histologic subtype, clinical aggressiveness, and genetic alteration status, the brain metastases exhibited consistently adequate in vivo tumor take rate and in vitro tumor sphere formation capacity, regardless of clinical and molecular conditions.
Therefore, PDXs from NSCLC brain metastases may better represent the heterogeneous advanced NSCLC population and could be utilized as preclinical models to meet unmet clinical needs such as drug screening for personalized treatments.
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•Functionally assembled metal platforms as Lego-like building blocks were prepared by pin and hole systems.•Biomimetic titanium scaffold (BTS) was developed as a mechanical support ...and multi-biomolecule carrier.•The scaffolds can simultaneously deliver growth factor and antibiotic agents in a controlled manner.•This novel fabrication method can be used with various metals, bioactive molecules, architecture, and medical applications.
Natural bone substituting materials derived from living organisms have been utilized to treat bone malfunctioning. However, limited sources and immune issues have led to the use of artificial scaffolds consisting of biocompatible materials. Additionally, a functionally graded porous structure has been acknowledged as an alternative to overcome reduced mechanical properties by pores and alleviate stress shielding effect. In this study, a two-body combination achieved through a densification process, in which recombinant human bone morphogenetic protein-2 (rhBMP-2) and tetracycline hydrochloride (TCH) can be simultaneously released for efficient bone regeneration, is proposed. Biomimetic titanium scaffolds (BTSs), which possess significantly different pore characteristics, are successfully fabricated. The mechanical properties of these parts are proven to be applicable as bone substitutes. The release of rhBMP-2 and TCH from the BTSs is prolonged compared to that of homogenous porous titanium scaffolds (PTSs). The prolonged release of rhBMP-2 from the BTS results in a sustained degree of pre-osteoblast differentiation. The antimicrobial properties of these scaffolds are verified using pathogens. Furthermore, various structures exhibiting different pore characteristics are obtained by mechanical interlocking between components. This study demonstrates that the novel assembled platform as customizable Lego-like building blocks, with its tunable mechanical and multi-biomolecule release properties, is promising for bone tissue engineering.
Background and Aims Radiofrequency ablation (RFA) has been used as a valuable treatment modality for various unresectable malignancies. EUS-guided radiofrequency ablation (EUS-RFA) of the porcine ...pancreas was reported to be feasible and safe in our previous study, suggesting that EUS-RFA may be applicable as an adjunct and effective alternative treatment method for unresectable pancreatic cancer. This study aimed to assess the technical feasibility and safety of EUS-RFA for unresectable pancreatic cancer. Methods An 18-gauge endoscopic RFA electrode and a radiofrequency generator were used for the procedure. The length of the exposed tip of the RFA electrode was 10 mm. After insertion of the RFA electrode into the mass, the radiofrequency generator was activated to deliver 20 to 50 W ablation power for 10 seconds. Depending on tumor size, the procedure was repeated to sufficiently cover the tumor. Results EUS-RFA was performed successfully in all 6 patients (median age 62 years, range 43-73 years). Pancreatic cancer was located in the head (n = 4) or body (n = 2) of the pancreas. The median diameter of masses was 3.8 cm (range 3cm-9cm). Four patients had stage 3 disease, and 2 patients had stage 4 disease. After the procedure, 2 patients experienced mild abdominal pain, but there were no other adverse events such as pancreatitis or bleeding. Conclusions EUS-RFA could be a technically feasible and safe option for patients with unresectable pancreatic cancer.
The transcription factor NFκB is activated by phosphorylation and acetylation and plays important roles in inflammatory and immune responses in the cell. Additionally, posttranslational modification ...of the NFκB p65 subunit by O-linked N-acetylglucosamine (O-GlcNAc) has been reported, but the modification site of O-GlcNAc on NFκB p65 and its exact function have not been elucidated. In this work, we show that O-GlcNAcylation of NFκB p65 decreases binding to IκBα and increases transcriptional activity under hyperglycemic conditions. Also, we demonstrate that both Thr-322 and Thr-352 of NFκB p65 can be modified with O-GlcNAc, but modification on Thr-352, not Thr-322, is important for transcriptional activation. Our findings suggest that site-specific O-GlcNAcylation may be a reason why NFκB activity increases continuously under hyperglycemic conditions.
Background and Aims Although fully covered self-expandable metal stents (FCSEMSs) have been commonly used for EUS-guided biliary drainage (EUS-BD), FCSEMS migration is a main limitation of this ...procedure. In the present study we evaluated the technical and clinical success rates, adverse events, and long-term outcomes of a newly developed hybrid stent that has been customized for EUS-BD. Methods From September 2011 to May 2015, 54 consecutive patients with biliary obstruction were enrolled in this prospective, observational study. These patients were candidates for alternative BD techniques because of failed ERCP. The hybrid metal stent used for EUS-BD in this study was partially covered, had anchoring flaps, and is commercially available in Korea. Results EUS-guided hepaticogastrostomy (EUS-HGS) was performed in 21 patients and EUS-guided choledochoduodenostomy (EUS-CDS) in 33 patients. The technical and clinical success rates of EUS-BD were 100% (54/54) and 94.4% (51/54), respectively. Immediate adverse events developed after EUS-BD in 9 patients (16.6%; cholangitis in 3, bleeding in 2, self-limited pneumoperitoneum in 3, and abdominal pain in 1). Proximal or distal stent migration was not observed during the follow-up period (median, 148.5 days; IQR, 79.7-244), and the mean stent patency duration was 166.3 days and 329.1 days in the EUS-HGS and EUS-CDS groups, respectively. Conclusions EUS-BD with the hybrid metal stent is technically feasible and can effectively treat biliary obstruction after failed ERCP. EUS-BD with the hybrid metal stent can reduce stent-related adverse events, especially stent migration.
This study deals with the effect of fly ash and recycled sand on the flexural behavior of SFRCCs (steel fiber-reinforced cementitious composites)-filled steel tubes. As a result of the compressive ...test, the elastic modulus was reduced by the addition of micro steel fiber, and the fly ash and recycled sand replacement decreased the elastic modulus and increased the Poisson's ratio. As a result of the bending and direct tensile tests, strength enhancement by the incorporation of micro steel fibers was observed, and a smooth descending curve was confirmed after initial cracking. As a result of the flexural test on the FRCC-filled steel tube, the peak load of all specimens was similar, and the applicability of the equation presented by AISC was high. The deformation capacity of the steel tube filled with SFRCCs was slightly improved. As the elastic modulus of the FRCC material lowered and the Poisson's ratio increased, the denting depth of the test specimen deepened. This is believed to be due to the large deformation of the cementitious composite material under local pressure due to the low elastic modulus. From the results of the deformation capacities of the FRCC-filled steel tubes, it was confirmed that the contribution of indentation to the energy dissipation capacity of steel tubes filled with SFRCCs was high. From the comparison of the strain values of the steel tubes, in the steel tube filled with SFRCC incorporating recycled materials, the damage was properly distributed between the loading point and both ends through crack dispersion, and consequently, rapid curvature changes did not occur at both ends.
Metastatic relapse of primary lung cancer leads to therapeutic resistance and unfavorable clinical prognosis; therefore, identification of key molecules associated with metastatic conversion has ...significant clinical implications. We previously identified a link between early brain metastasis of lung adenocarcinoma and amplification of the α-smooth muscle actin (ACTA2) gene. The aim of present study was to investigate the prognostic and functional significance of ACTA2 expression in cancer cells for the metastatic potential of lung adenocarcinomas.
ACTA2 expression was analyzed in tumor cells from 263 patients with primary lung adenocarcinomas by immunohistochemistry, and was correlated with clinicopathologic parameters. The expression of ACTA2 in human lung adenocarcinoma cells was modulated with short hairpin RNAs (shRNA) and siRNAs specifically targeting ACTA2.
The patients with lung adenocarcinomas with high ACTA2 expression in tumor cells showed significantly enhanced distant metastasis and unfavorable prognosis. ACTA2 downregulation remarkably impaired in vitro migration, invasion, clonogenicity, and transendothelial penetration of lung adenocarcinoma cells without affecting proliferation. Consistent with the in vitro results, depletion of ACTA2 in human lung adenocarcinoma PC14PE6 cells significantly reduced their metastatic potential without altering their tumorigenic potential. Expression of c-MET and FAK in lung adenocarcinoma cells was also reduced by ACTA2-targeting siRNAs and shRNAs, and was accompanied by a loss of mesenchymal characteristics.
These findings indicate that ACTA2 regulates c-MET and FAK expression in lung adenocarcinoma cells, which positively and selectively influence metastatic potential. Therefore, ACTA2 could be a promising prognostic biomarker and/or therapeutic target for metastatic lung adenocarcinoma.
Necrosis is a hallmark of glioblastoma (GBM) and is responsible for poor prognosis and resistance to conventional therapies. However, the molecular mechanisms underlying necrotic ...microenvironment-induced malignancy of GBM have not been elucidated. Here, we report that transglutaminase 2 (TGM2) is upregulated in the perinecrotic region of GBM and triggered mesenchymal (MES) transdifferentiation of glioma stem cells (GSC) by regulating master transcription factors (TF), such as C/EBPβ, TAZ, and STAT3. TGM2 expression was induced by macrophages/microglia-derived cytokines via NF-κB activation and further degraded DNA damage-inducible transcript 3 (GADD153) to induce C/EBPβ expression, resulting in expression of the MES transcriptome. Downregulation of TGM2 decreased sphere-forming ability, tumor size, and radioresistance and survival in a xenograft mouse model through a loss of the MES signature. A TGM2-specific inhibitor GK921 blocked MES transdifferentiation and showed significant therapeutic efficacy in mouse models of GSC. Moreover, TGM2 expression was significantly increased in recurrent MES patients and inversely correlated with patient prognosis. Collectively, our results indicate that TGM2 is a key molecular switch of necrosis-induced MES transdifferentiation and an important therapeutic target for MES GBM.
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