Genotoxicity refers to the ability of harmful substances to damage genetic information in cells. Being exposed to chemical and biological agents can result in genomic instabilities and/or epigenetic ...alterations, which translate into a variety of diseases, cancer included. This concise review discusses, from both a genetic and epigenetic point of view, the current detection methods of different agents' genotoxicity, along with their basic and clinical relation to human cancer, chemotherapy, germ cells and stem cells.
We hypothesized that photodynamic therapy (PDT) with Chlorin e6 (Ce6) enhances antitumor abscopal effects via inhibition of the programmed cell death-1/programmed death-ligand 1 (PD-1/PD-L1) immune ...checkpoint. By using syngeneic melanoma and pancreatic tumor mouse models, we studied the Ce6-PDT-induced immune responses in local and distant tumor microenvironments. In addition, the Ce6-PDT's target in the PD-1/PD-L1 interaction was analyzed in MC38-hPD-L1 colon cancer and PD-1 expressing Jurkat T cell coculture. The tumors in the irradiated and non-irradiated sites in the abscopal effective (Abs
) group of both mouse models were regressed, proving the abscopal effect. The immunogenic effect in the Abs
group was associated with an expansion of T cell and other immune cells infiltration without changes in the CD39
population in either the right or left tumors compared to control group. Furthermore, the abscopal ineffective (Abs
) group demonstrated lesser increase of T cells, decreased immune cell infiltration, and increased CD39-expressing Treg cells without suppression of tumor growth. In the coculture with PD-1-expressing Jurkat T cell, Ce6-PDT efficiently suppressed the PD-1/PD-L1 interactions by increasing the proliferation and cytotoxic activity of CD8
T cells while decreasing CD39-expressing Treg cells in a dose-dependent manner. Likewise, the inhibition of PD-1/PD-L1 interactions was also correlated with the increased production of IL-2 and Granzyme B. Our findings imply that Ce6-PDT is a promising immunotherapy with the potential to improve the abscopal effect.
Unlike graphene, the existence of bandgaps (1-2 eV) in the layered semiconductor molybdenum disulphide, combined with mobility enhancement by dielectric engineering, offers an attractive possibility ...of using single-layer molybdenum disulphide field-effect transistors in low-power switching devices. However, the complicated process of fabricating single-layer molybdenum disulphide with an additional high-k dielectric layer may significantly limit its compatibility with commercial fabrication. Here we show the first comprehensive investigation of process-friendly multilayer molybdenum disulphide field-effect transistors to demonstrate a compelling case for their applications in thin-film transistors. Our multilayer molybdenum disulphide field-effect transistors exhibited high mobilities (>100 cm(2) V(-1) s(-1)), near-ideal subthreshold swings (~70 mV per decade) and robust current saturation over a large voltage window. With simulations based on Shockley's long-channel transistor model and calculations of scattering mechanisms, these results provide potentially important implications in the fabrication of high-resolution large-area displays and further scientific investigation of various physical properties expected in other layered semiconductors.
Although progress has been made in developing tumor microenvironment-responsive delivery systems, the list of cargo-releasing stimuli remains limited. In this study, we report DNA nanothread-cloaked ...nanoparticles for reactive oxygen species (ROS)-rich tumor microenvironment-responsive delivery systems. ROS is well known to strongly induce DNA fragmentation via oxidative stress. As a model anticancer drug, hydrophobic omacetaxine was entrapped in branched cyclam ligand-modified nanoparticles (BNP). DNA nanothreads were prepared by rolling-circle amplification and complexed to BNP, yielding DNA nanothread-cloaked BNP (DBNP). DBNP was unmasked by DNA nanothread-degrading ROS and culture supernatants of LNCaP cells. The size and zeta potential of DBNP were changed by ROS. In ROShigh LNCaP cells, but not in ROSlow fibroblast cells, the uptake of DBNP was higher than that of other nanoparticles. Molecular imaging revealed that DBNP exhibited greater distribution to tumor tissues, compared to other nanoparticles. Ex vivo mass spectrometry-based imaging showed that omacetaxine metabolites were distributed in tumor tissues of mice treated with DBNP. Intravenous administration of DBNP reduced the tumor volume by 80% compared to untreated tumors. Profiling showed that omacetaxine treatment altered the transcriptional profile. These results collectively support the feasibility of using polymerized DNA-masked nanoparticles for selective activation in the ROS-rich tumor microenvironment.
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•LIG sensing platform achieves the dual sensing: K+ and Na+ ion concentration measurement and human motion monitoring.•The hydrophobic LIG electrode prevents corrosion from sweat.•The LIG sensing ...platform monitors muscle contraction/relaxation with high sensitivity.•The LIG sensing platform measures a wide range of ion concentrations with high sensitivity.
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Human sweat monitoring, which unlike blood monitoring can be easily performed on the skin, can provide valuable personal healthcare data, as well as being suitable for use in diagnosis of disease and other conditions. However, despite the tremendous interest in sweat sensing, the development of low-cost, high-efficiency, multi-biometric sensing-capable platforms is still required for the large-scale utilization of wearable biosensors for extensive monitoring with other physiological signals. Here, we propose a wearable multifunctional LIG-based sensor, complete with Arduino-based readout electronics, which simultaneously monitors concentrations of sodium and potassium ions in human sweat as well as strain generated by vital signals (human motion). Our elastomer substrates were fabricated according to the weight of polydimethylsiloxane (PDMS) and lignin. A wearable multifunctional sensor was developed via the formation of laser-induced graphene (LIG) on PDMS/lignin composite substrates using Laser Direct writing (LDW); PDMS/Lignin transforms into the porous structure after laser irradiation. The fabricated sodium and potassium ion-selective electrodes (ISE), and Ag/AgCl electrode on PDMS/lignin composite were used to measure the potential difference at various different concentrations of both Na+(10−1–10−7) and K+ ions (10−1–10−8), and our sensor showed high sensitivity values of 63.6 mV/dec (Na+, n = 6) and 59.2 mV/dec (K+, n = 7), respectively; these results almost completely follow Nernstian behavior (which predicts values of R2 =0.99988 and 0.99855, respectively) and indicate cyclic stability (5000 cycles, Gauge Factor of ~20). This simple fabrication of a multifunctional and cost-effective sensor platform indicates real-time changes of sodium and potassium ions in sweat and strain generated by human body motion.
To identify the vascular alteration by photodynamic therapy (PDT), the utilization of high-resolution, high-speed, and wide-field photoacoustic microscopy (PAM) has gained enormous interest. The ...rapid changes in vasculature during PDT treatment and monitoring of tumor tissue activation in the orthotopic pancreatic cancer model have received limited attention in previous studies. Here, a fully two-axes waterproof galvanometer scanner-based photoacoustic microscopy (WGS-PAM) system was developed for in vivo monitoring of dynamic variations in micro blood vessels due to PDT in an orthotopic pancreatic cancer mouse model. The photosensitizer (PS), Chlorin e6 (Ce6), was utilized to activate antitumor reactions in response to the irradiation of a 660 nm light source. Microvasculatures of angiogenesis tissue were visualized on a 40 mm
area using the WGS-PAM system at 30 min intervals for 3 h after the PDT treatment. The decline in vascular intensity was observed at 24.5% along with a 32.4% reduction of the vascular density at 3 h post-PDT by the analysis of PAM images. The anti-vascularization effect was also identified with fluorescent imaging. Moreover, Ce6-PDT increased apoptotic and necrotic markers while decreasing vascular endothelial growth factor (VEGF) expression in MIA PaCa-2 and BxPC-3 pancreatic cancer cell lines. The approach of the WGS-PAM system shows the potential to investigate PDT effects on the mechanism of angiographic dynamics with high-resolution wide-field imaging modalities.
Along with the development of industry and the improvement of people’s living standards, peoples’ demand on resources has greatly increased, causing energy crises and environmental pollution. In ...recent years, photocatalytic technology has shown great potential as a low-cost, environmentally-friendly, and sustainable technology, and it has become a hot research topic. However, current photocatalytic technology cannot meet industrial requirements. The biggest challenge in the industrialization of photocatalyst technology is the development of an ideal photocatalyst, which should possess four features, including a high photocatalytic efficiency, a large specific surface area, a full utilization of sunlight, and recyclability. In this review, starting from the photocatalytic reaction mechanism and the preparation of the photocatalyst, we review the classification of current photocatalysts and the methods for improving photocatalytic performance; we also further discuss the potential industrial usage of photocatalytic technology. This review also aims to provide basic and comprehensive information on the industrialization of photocatalysis technology.
When the board provides quality monitoring and advising to corporate managers, firms can achieve their goal, and so firm value increases. Board diversity is one of the issues that can affect the ...board effectiveness through influencing the quality of monitoring and advising. Hence, many prior studies have analyzed the effect of board diversity in various dimensions such as gender, age, race, ethnicity, education background on firm value or performance. However, prior studies do not reach out to the religious diversity of the board. So, this study investigates the relationship between religious diversity of the board and firm value. Using unique data of religion of directors for companies listed in Korea from 2008 to 2011, this study provides the following empirical results. In general, a high level of religious diversity has a positive impact on the firm value. However, when the degree of religious diversity of the board exceeds a certain point, religious diversity shows a negative relationship with the firm value. In addition, if the religion of directors is concentrated in one religion (when the level of diversity is low), firm value is lower than other control firms. The empirical finding of this study shows that religious diversity of the board matters in a similar way of other dimension of the board diversity.
In this paper, we have extended the previous study of the thermodynamics and phase transition of the Schwarzschild black hole in the rainbow gravity to the Schwarzschild–AdS black hole where metric ...depends on the energy of a probe. Making use of the Heisenberg uncertainty principle and the modified dispersion relation, we have obtained the modified local Hawking temperature and thermodynamic quantities in an isothermal cavity. Moreover, we carry out the analysis of constant temperature slices of a black hole. As a result, we have shown that there also exists another Hawking–Page-like phase transition in which case a locally stable small black hole tunnels into a globally stable large black hole as well as the standard Hawking–Page phase transition from a hot flat space to a black hole.
Malfunction of ubiquitin-proteasome system is tightly linked to tumor formation and tumor metastasis. Targeting the ubiquitin-pathway provides a new strategy for anti-cancer therapy. Despite the ...parts played by ubiquitin modifiers, removal of ubiquitin from the functional proteins by the deubiquitinating enzymes (DUBs) plays an important role in governing the multiple steps of the metastatic cascade, including local invasion, dissemination, and eventual colonization of the tumor to distant organs. Both deregulated ubiquitination and deubiquitination could lead to dysregulation of various critical events and pathways such as apoptosis and epithelial-mesenchymal transition (EMT). Recent TCGA study has further revealed the connection between mutations of DUBs and various types of tumors. In addition, emerging drug design targeting DUBs provides a new strategy for anti-cancer therapy. In this review, we will summarize the role of deubiquitination and highlight the recent discoveries of DUBs with regards to multiple metastatic events including anti-apoptosis pathway and EMT. We will further discuss the regulation of deubiquitination as a novel strategy for anti-cancer therapy.
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