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951.
    
Melanoma can develop in a congenital melanocytic nevus (CMN). In fact, a large CMN is associated with a high risk of developing melanoma. Although melanomas arising from CMNs are thought to have a pathogenesis distinct from conventional melanomas, no studies have been conducted on the evolution or tumor heterogeneity of CMN melanomas. We applied multi‐region whole‐exome sequencing to investigate the clonal nature of driver events and evolutionary processes in CMNs and melanomas arising from CMNs. In two patients, we observed an independent subclonal evolution in cancerized fields of CMNs and chromosome 8q amplification in both melanomas arising from CMNs. The amplification of MYC, located in chromosome 8q, was correlated with the percentage of tumor cells expressing high levels of MYC protein detected in melanoma cells by immunohistochemistry. Our analysis suggests that each CMN cell may evolve sporadically and that amplification of MYC might be a key event for melanoma development in CMNs.  相似文献   
952.
    
Biomolecules, especially proteins and nucleic acids, have been widely studied to develop biochips for various applications in scientific fields ranging from bioelectronics to stem cell research. However, restrictions exist due to the inherent characteristics of biomolecules, such as instability and the constraint of granting the functionality to the biochip. Introduction of functional nanomaterials, recently being researched and developed, to biomolecules have been widely researched to develop the nanobiohybrid materials because such materials have the potential to enhance and extend the function of biomolecules on a biochip. The potential for applying nanobiohybrid materials is especially high in the field of bioelectronics. Research in bioelectronics is aimed at realizing electronic functions using the inherent properties of biomolecules. To achieve this, various biomolecules possessing unique properties have been combined with novel nanomaterials to develop bioelectronic devices such as highly sensitive electrochemical‐based bioelectronic sensing platforms, logic gates, and biocomputing systems. In this review, recently reported bioelectronic devices based on nanobiohybrid materials are discussed. The authors believe that this review will suggest innovative and creative directions to develop the next generation of multifunctional bioelectronic devices.  相似文献   
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[Purpose] This study aimed to investigate the effects of branched-chain amino acid (BCAA) supplement on delayed onset muscle soreness (DOMS) by analyzing the maximum muscle strength and indicators of muscle damage.[Methods] Twelve men with majors in physical education were assigned to the BCAA group and placebo group in a double-blinded design, and repeated measurements were conducted. DOMS was induced with an isokinetic exercise. Following BCAA administration, the changes in the knee extension peak torque, flexion peak torque, aspartate aminotransferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH) concentrations were analyzed. The maximum knee muscle strength was measured at the baseline (pre-D0) following BCAA administration for 5 days before exercise (-D5, -4D, -3D, -2D, -1D). In contrast, the post-treatment measurements (D3) were recorded after BCAA administration for 3 days (post-D0, D1, D2). Blood samples were obtained before (pre-D0), immediately after (post-D0), 24 h (D1), 48 h (D2), and 72 h (D3) after the exercise to analyze the indicators of muscle strength. BCAA was administered twice daily for 8 days (5 days and 3 days before inducing DOMS and during the experimental period, respectively).[Results] There was no difference in the flexion peak torque between the groups. However, the BCAA group showed a significantly higher extension peak torque at D3 (second isokinetic exercise), compared to the placebo group (p<.05). There was no difference in AST changes between the groups. Nonetheless, the CK and LDH were significantly reduced in the BCAA group, compared to the placebo group. There was no correlation between the extension peak torque and flexion peak torque. However, the CK and LDH increased proportionately in DOMS. Moreover, their concentrations significantly increased with a decreasing peak torque (p<.01).[Conclusion] An exercise-induced DOMS results in a decrease in the peak torque and a proportional increase in the CK and LDH concentrations. Moreover, the administration of BCAA inhibits the reduction of the extension peak torque and elevation of CK and LDH concentrations. Therefore, BCAA might be administered as a supplement to maintain the muscle strength and prevent muscle damage during vigorous exercises that may induce DOMS in sports settings.  相似文献   
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Triple-negative breast cancers (TNBCs) represent 15% to 20% of all breast cancers and are often associated with poor prognosis. The lack of targeted therapies for TNBCs contributes to higher mortality rates. Aberrations in the phosphoinositide-3-kinase (PI3K) and mitogen-activated protein kinase pathways have been linked to increased breast cancer proliferation and survival. It has been proposed that these survival characteristics are enhanced through compensatory signaling and crosstalk mechanisms. While the crosstalk between PI3K and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways has been characterized in several systems, new evidence suggests that MEK5/ERK5 signaling is a key component in the proliferation and survival of several aggressive cancers. In this study, we examined the effects of dual inhibition of PI3K/protein kinase B (Akt) and MEK5/ERK5 in the MDA-MB-231, BT-549, and MDA-MB-468 TNBC cell lines. We used the Akt inhibitor ipatasertib, ERK5 inhibitors XMD8-92 and AX15836, and the novel MEK5 inhibitor SC-1-181 to investigate the effects of dual inhibition. Our results indicated that dual inhibition of PI3K/Akt and MEK5/ERK5 signaling was more effective at reducing the proliferation and survival of TNBCs than single inhibition of either pathway alone. In particular, a loss of Bad phosphorylation at two distinct sites was observed with dual inhibition. Furthermore, the inhibition of both pathways led to p21 restoration, decreased cell proliferation, and induced apoptosis. In addition, the dual inhibition strategy was determined to be synergistic in MDA-MB-231 and BT-549 cells and was relatively nontoxic in the nonneoplastic MCF-10 cell line. In summary, the results from this study provide a unique prospective into the utility of a novel dual inhibition strategy for targeting TNBCs.  相似文献   
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959.
    
Quantum‐dot (QD) photovoltaics (PVs) offer promise as energy‐conversion devices; however, their open‐circuit‐voltage (VOC) deficit is excessively large. Previous work has identified factors related to the QD active layer that contribute to VOC loss, including sub‐bandgap trap states and polydispersity in QD films. This work focuses instead on layer interfaces, and reveals a critical source of VOC loss: electron leakage at the QD/hole‐transport layer (HTL) interface. Although large‐bandgap organic materials in HTL are potentially suited to minimizing leakage current, dipoles that form at an organic/metal interface impede control over optimal band alignments. To overcome the challenge, a bilayer HTL configuration, which consists of semiconducting alpha‐sexithiophene (α‐6T) and metallic poly(3,4‐ethylenedioxythiphene) polystyrene sulfonate (PEDOT:PSS), is introduced. The introduction of the PEDOT:PSS layer between α‐6T and Au electrode suppresses the formation of undesired interfacial dipoles and a Schottky barrier for holes, and the bilayer HTL provides a high electron barrier of 1.35 eV. Using bilayer HTLs enhances the VOC by 74 mV without compromising the JSC compared to conventional MoO3 control devices, leading to a best power conversion efficiency of 9.2% (>40% improvement relative to relevant controls). Wider applicability of the bilayer strategy is demonstrated by a similar structure based on shallow lowest‐unoccupied‐molecular‐orbital (LUMO) levels.  相似文献   
960.
    
The lateral resolution of continuous wave (CW) stimulated emission depletion (STED) microscopy is enhanced about 12% by applying annular‐shaped amplitude modulation to the radially polarized excitation beam. A focused annularly filtered radially polarized excitation beam provides a more condensed point spread function (PSF), which contributes to enhance effective STED resolution of CW STED microscopy. Theoretical analysis shows that the FWHM of the effective PSF on the detection plane is smaller than for conventional CW STED. Simulation shows the donut‐shaped PSF of the depletion beam and confocal optics suppress undesired PSF sidelobes. Imaging experiments agree with the simulated resolution improvement.   相似文献   
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