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With the increasing demand for data exchange between nearby devices in proximity-based services, enhancing the security of wireless mutual broadcast (WMB) networks is crucial. However, WMB networks are inherently vulnerable to eavesdropping due to the open broadcast nature of their communication. This paper investigates the improvement of secrecy performance in random-access-based WMB (RA-WMB) networks by integrating physical layer security (PLS) techniques with hybrid duplex (HBD) operations under a stochastic geometry framework. The HBD method balances half-duplex (HD) receiving and full-duplex (FD) transceiving, utilizing self-interference cancellation (SIC) to enhance PLS performance. Key operational parameters, including transmission probability (TxPr), friendly jammer density, and conditions for FD operation, are designed to maximize secrecy performance. The analytical and numerical results demonstrate significant improvements in PLS performance, with SIC playing a critical role, particularly in scenarios with dense legitimate nodes, and with TxPr adjusted to balance HD receiving and FD transceiving based on SIC imperfections. The proposed design principles provide a comprehensive framework for enhancing the security of WMB networks, addressing the complex interplay of interference and SIC in various network configurations.
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A simple spontaneous deposition kit for 210Po determination using alpha spectrometry was newly designed, and polonium deposition characteristics under various physicochemical conditions were evaluated using it. The high-purity silver disc (99.99%) showed high deposition efficiencies of over 85.1% in the HCl concentration range of 0.01-6 M. Optimal physicochemical factors were determined to be a temperature of 90 °C, deposition time of 90 min, and the use of ascorbic acid as a reducing agent in an amount similar to that of the interfering element (Fe).
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BACKGROUND: Delphinidin (DP), an anthocyanidin found in blueberries, has antioxidant and anti-inflammatory effects. This study aimed to investigate the efficacy of DP as a storage medium for avulsed teeth. METHODS: Human periodontal ligament cells were cultured and exposed to DP solution (10, 50, and 100 µM), Dulbecco's modified Eagle's medium, Hank's balanced salt solution and tap water. Cell counting kit-8 assays were performed after 0.5, 1, 6, and 24 h to measure the cell viability. Nitric oxide assays and gelatin zymography were performed to evaluate the anti-inflammatory effects of DP. Reverse transcription-polymerase chain reaction was used to determine the expression levels of inflammatory cytokines. RESULTS: The viability of periodontal ligament cells was greatest at 100 µM DP. At 1 h, 100 µM DP decreased nitric oxide synthesis (p < .0167). Matrix metallopeptidase-9 activity was inhibited by DP in a dose-dependent manner (p < .0167). Moreover, treatment with 100 µM DP decreased the expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 in periodontal ligament cells (p < .0167). CONCLUSIONS: Within the limits of this study, DP preserved the viability and suppressed the inflammatory response of periodontal ligament cells. These findings suggest that DP could be promising for preservation of avulsed teeth.
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Soluções para Preservação de Órgãos , Avulsão Dentária , Humanos , Anti-Inflamatórios/farmacologia , Sobrevivência Celular , Óxido Nítrico , Soluções para Preservação de Órgãos/farmacologia , Ligamento PeriodontalRESUMO
Dental caries is a common disease that not only destroys the rigid structure of the teeth but also causes pulp necrosis in severe cases. Once pulp necrosis has occurred, the most common treatment is to remove the damaged pulp tissue, leading to a loss of tooth vitality and increased tooth fragility. Dental pulp stem cells (DPSCs) isolated from pulp tissue exhibit mesenchymal stem cell-like characteristics and are considered ideal candidates for regenerating damaged dental pulp tissue owing to their multipotency, high proliferation rate, and viability after cryopreservation. Importantly, DPSCs do not elicit an allogeneic immune response because they are non-immunogenic and exhibit potent immunosuppressive properties. Here, we provide an up-to-date review of the clinical applicability and potential of DPSCs, as well as emerging trends in the regeneration of damaged pulp tissue. In addition, we suggest the possibility of using DPSCs as a resource for allogeneic transplantation and provide a perspective for their clinical application in pulp regeneration.
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From mechanical syringes to electric field-assisted injection devices, precise control of liquid droplet generation has been sought after, and the present state-of-the-art technologies have provided droplets ranging from nanoliter to subpicoliter volume sizes. In this study, we present a new laser-driven method to generate liquid droplets with a zeptoliter volume, breaking the fundamental limits of previous studies. We guided an infrared laser beam through a hollow optical fiber (HOF) with a ring core whose end facet was coated with single-walled carbon nanotubes. The laser light was absorbed by this nanotube film and efficiently generated a highly localized microring heat source. This evaporated the liquid inside the HOF, which rapidly recondensed into zeptoliter droplets in the surrounding air at room temperature. We spectroscopically confirmed the chemical structures of the liquid precursor maintained in the droplets by atomizing dye-dissolved glycerol. Moreover, we explain the fundamental physical principles as well as functionalities of the optical atomizer and perform a detailed characterization of the droplets. Our approach has strong prospects for nanoscale delivery of biochemical substances in minuscule zeptoliter volumes.
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Since daily drinking water is one of the major source for the ingestion of radiotoxic 222Rn and 226Ra, the demand for a simple method to determine these two radionuclides has significantly increased. In the present study, a rapid, simple sequential analysis method for determining 222Rn and 226Ra in drinking water using a liquid scintillation counter was developed. The method employs solvent extraction and correction equations for the effect of native 222Rn for 226Ra analysis. Validation and examination of applicability for drinking water analysis were conducted using 222Rn-injected water and 226Ra standard source. Minimum required counting times for examining drinking water on Quantulus 1220 and Hidex 300SL were estimated via minimum detectable activity depending on the counting time. In addition, the correction method, including an equation for reducing analysis time by more than 10 days, was suggested based on the analytical results for different elapsed times between sampling and measurement.
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Água Potável , Monitoramento de Radiação , Rádio (Elemento) , Poluentes Radioativos da Água , Rádio (Elemento)/análise , Contagem de Cintilação , Poluentes Radioativos da Água/análise , Abastecimento de ÁguaRESUMO
We report copper(II) arsenite (CuAS)-integrated polymer micelles (CuAS-PMs) as a new class of Fenton-like catalytic nanosystem that can display reactive oxygen species (ROS)-manipulating anticancer therapeutic activity. CuAS-PMs were fabricated through metal-catechol chelation-based formation of the CuAS complex on the core domain of poly (ethylene glycol)-b-poly(3,4-dihydroxy-L-phenylalanine) (PEG-PDOPA) copolymer micelles. CuAS-PMs maintained structural robustness under serum conditions. The insoluble state of the CuAS complex was effectively retained at physiological pH, whereas, at endosomal pH, the CuAS complex was ionized to release arsenite and cuprous Fenton catalysts (Cu+ ions). Upon endocytosis, CuAS-PMs simultaneously released hydrogen peroxide (H2O2)-generating arsenite and Fenton-like reaction-catalyzing Cu+ ions in cancer cells, which synergistically elevated the level of highly cytotoxic hydroxyl radicals (â¢OH), thereby preferentially killing cancer cells. Animal experiments demonstrated that CuAS-PMs could effectively suppress the growth of solid tumors without systemic in vivo toxicity. The design rationale of CuAS-PMs may provide a promising strategy to develop diverse oxidative stress-amplifying agents with great potential in cancer-specific therapy.
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Antineoplásicos , Arsenitos , Nanopartículas , Animais , Antineoplásicos/química , Arsenitos/farmacologia , Cobre , Peróxido de Hidrogênio/química , Nanopartículas/química , Estresse OxidativoRESUMO
We report a new method to optically manipulate a single dielectric particle along closed-loop polygonal trajectories by crossing a suite of all-fiber Bessel-like beams within a single water droplet. Exploiting optical radiation pressure, this method demonstrates the circulation of a single polystyrene bead in both a triangular and a rectangle geometry enabling the trapped particle to undergo multiple circulations successfully. The crossing of the Bessel-like beams creates polygonal corners where the trapped particles successfully make abrupt turns with acute angles, which is a novel capability in microfluidics. This offers an optofluidic paradigm for particle transport overcoming turbulences in conventional microfluidic chips.
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Although some cell types may be defined anatomically or by physiological function, a rigorous definition of cell state remains elusive. Here, we develop a quantitative, imaging-based platform for the systematic and automated classification of subcellular organization in single cells. We use this platform to quantify subcellular organization and gene expression in >30,000 individual human induced pluripotent stem cell-derived cardiomyocytes, producing a publicly available dataset that describes the population distributions of local and global sarcomere organization, mRNA abundance, and correlations between these traits. While the mRNA abundance of some phenotypically important genes correlates with subcellular organization (e.g., the beta-myosin heavy chain, MYH7), these two cellular metrics are heterogeneous and often uncorrelated, which suggests that gene expression alone is not sufficient to classify cell states. Instead, we posit that cell state should be defined by observing full distributions of quantitative, multidimensional traits in single cells that also account for space, time, and function.
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Células-Tronco Pluripotentes Induzidas , Diferenciação Celular/genética , Humanos , Miócitos Cardíacos/metabolismo , Transcriptoma/genéticaRESUMO
The antitumor capabilities of agonistic anti-4-1BB mAbs have made them an attractive target for tumor immunotherapy. However, the adverse side effects associated with agonist antibodies have hindered their clinical development. Here, we aimed to study the immune-related adverse events of repeated doses and long-term use of agonistic anti-4-1BB mAbs. We show that chronic activation of 4-1BB signals induced the accumulation of IFN-γ-producing PD-1+CD8+ T cells in the secondary lymphoid organs of tumor-bearing mice by increasing the number of dividing CD8+ T cells, which was beneficial for suppressing tumor growth in the early phase of anti-4-1BB induction. However, repeated exposure to anti-4-1BB mAbs led to granuloma development in tumor-draining lymph nodes (TDLNs) of mice due to recruitment and accumulation of macrophages via the CD8+ T cell-IFN-γ axis. This was accompanied by excessive lymph node swelling, which impaired the sequential activation of CD8+ T cells. Our data provide insights into the immune-related adverse events of long-term agonist 4-1BB antibody dosing, which should be considered during the clinical development of immunomodulating therapy.
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Linfócitos T CD8-Positivos , Neoplasias , Animais , Granuloma/patologia , Linfonodos , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias/patologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose TumoralRESUMO
CD137, a member of the TNFR family, is a costimulatory receptor, and CD137L, a member of the TNF family, is its ligand. Studies using CD137- and CD137L-deficient mice and antibodies against CD137 and CD137L have revealed the diverse and paradoxical effects of these two proteins in various cancers, autoimmunity, infections, and inflammation. Both their cellular diversity and their spatiotemporal expression patterns indicate that they mediate complex immune responses. This intricacy is further enhanced by the bidirectional signal transduction events that occur when these two proteins interact in various types of immune cells. Here, we review the biology of murine CD137/CD137L, particularly, the complexity of their proximal signaling pathways, and speculate on their roles in immune responses.
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Ligante 4-1BB/imunologia , Transdução de Sinais/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Animais , CamundongosRESUMO
In contrast to current efforts to quantify the radiation pressure of light using nano-micromechanical resonators in cryogenic conditions, we proposed and experimentally demonstrated the radiation pressure measurement in ambient conditions by utilizing a macroscopic mechanical longitudinal oscillator with an effective mass of the order of 20 g. The light pressure on a mirror attached to the oscillator was recorded in a Michelson interferometer and results showed, within the experimental accuracy of 3.9%, a good agreement with the harmonic oscillator model without free parameters.
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Organic light-emitting diodes (OLEDs) are established as a mainstream light source for display applications and can now be found in a plethora of consumer electronic devices used daily. This success can be attributed to the rich luminescent properties of organic materials, but efficiency enhancement made over the last few decades has also played a significant role in making OLEDs a practically viable technology. This report summarizes the efforts made so far to improve the external quantum efficiency (EQE) of OLEDs and discusses what should further be done to push toward the ultimate efficiency that can be offered by OLEDs. The study indicates that EQE close to 58% and 80% can be within reach without and with additional light extraction structures, respectively, with an optimal combination of cavity engineering, low-index transport layers, and horizontal dipole orientation. In addition, recent endeavors to identify possible applications of OLEDs beyond displays are presented with emphasis on their potential in wearable healthcare, such as OLED-based pulse oximetry as well as phototherapeutic applications based on body-attachable flexible OLED patches. OLEDs with fabric-like form factors and washable encapsulation strategies are also introduced as technologies essential to the success of OLED-based wearable electronics.
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Pulse oximetry sensors have been playing a key role as devices to monitor elemental yet critical human health states. Conventional pulse oximetry sensors, however, have relatively large power consumption, impeding their use as stand-alone, continuous monitoring systems that can easily be integrated with everyday life. Here, we exploit the design freedom offered by organic technologies to realize a reflective patch-type pulse oximetry sensor with ultralow power consumption. On the basis of flexible organic light-emitting diodes and organic photodiodes designed via an optical simulation of color-sensitive light propagation within human skin, the proposed monolithically integrated organic pulse oximetry sensor heads exhibit successful operation at electrical power as low as 24 µW on average. We thereby demonstrate that organic devices not only have form factor advantages for such applications but also hold great promise as enablers for all-day wearable health monitoring systems.
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Técnicas Biossensoriais/métodos , Monitorização Fisiológica/instrumentação , Oximetria/instrumentação , Oxigênio/metabolismo , Pele/metabolismo , Dispositivos Eletrônicos Vestíveis/normas , Técnicas Biossensoriais/instrumentação , Desenho de Equipamento , Humanos , Processamento de Sinais Assistido por ComputadorRESUMO
The CRISPR-Cas system is a well-established RNA-guided DNA editing technique widely used to modify genomic DNA sequences. I used the CRISPR-Cas9 system to change the second and third nucleotides of the triplet TCT of human TNSFSF9 in HepG2 cells to TAG to create an amber stop codon. The TCT triplet is the codon for Ser at the 172nd position of TNSFSF9. The two substituted nucleotides, AG, were confirmed by DNA sequencing of the PCR product followed by PCR amplification of the genomic TNFSF9 gene. Interestingly, sequencing of the cDNA of transcripts of the edited TNFSF9 gene revealed that the TAG had been re-edited to the wild type triplet TCT, and 1 or 2 bases just before the triplet had been deleted. These observations indicate that CRISPR-Cas9-mediated editing of bases in target genomic DNA can be followed by spontaneous re-editing (correcting) of the bases during transcription.
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Ligante 4-1BB/genética , Sistemas CRISPR-Cas , Edição de Genes/métodos , Genômica/métodos , HumanosRESUMO
In this work, we investigate whether S-nitrosoglutathione (GSNO)-conjugated hyaluronic acid-based self-assembled nanoparticles (GSNO-HANPs) can be useful as a chemosensitizing agent to improve the anticancer activity of doxorubicin (DOX). The GSNO-HANPs were prepared by aqueous assembly of GSNO-conjugated HA with grafted poly(lactide- co-glycolide). Aqueous GSNO stability shielded within the assembled environments of the GSNO-HANPs was greatly enhanced, compared to that of free GSNO. The NO release from the GSNO-HANPs was facilitated in the presence of hyaluronidase-1 (Hyal-1) and ascorbic acid at intracellular concentrations. Microscopic analysis showed GSNO-HANPs effectively generated NO within the cells. We observed that NO made the human MCF-7 breast cancer cells vulnerable to DOX. This chemosensitizing activity was supported by the observation of an increased level of ONOO- (peroxynitrite), a highly reactive oxygen species, upon co-treatment with the GSNO-HANPs and DOX. Apoptosis assays showed that GSNO-HANP alone exhibited negligible cytotoxic effects and reinforced apoptotic activity of DOX. Animal experiments demonstrated the effective accumulation of GSNO-HANPs in solid MCF-7 tumors and effectively suppressed tumor growth in combination with DOX. This hyaluronic acid-based intracellularly NO-releasing nanoparticles may serve as a significant chemosensitizing agent in treatments of various cancers.
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Ácido Hialurônico/química , Animais , Citoplasma , Doxorrubicina , Sistemas de Liberação de Medicamentos , Humanos , Células MCF-7 , Nanopartículas , Óxido NítricoRESUMO
CD137 (4-1BB) is a T-cell costimulatory molecule, and agonstic CD137 antibodies are currently being evaluated in the clinic as cancer immunotherapy. Recently, it was found that CD137-/- mice or mice injected with agonistic anti-CD137 antibodies exhibit heightened antitumor responses, contrary to expectations based on other knowledge of CD137 function. Here, we report findings related to reverse signaling by CD137 ligand (CD137L) in antigen-presenting dendritic cells (DC) in tumors that address these paradoxical results. Specifically, CD137L suppressed intratumoral differentiation of IL12-producing CD103+ DC and type 1 tumor-associated macrophages (TAM). Differentiation of these cell types is important because they are required to generate IFNγ-producing CD8+ cytotoxic T lymphocytes (Tc1). Notably, CD137L blockade increased levels of IL12 and IFNγ, which promoted intratumoral differentiation of IFNγ-producing Tc1, IL12-producing CD103+ DC, and type 1 TAM within tumors. Our results offer an explanation for the paradoxical effects of CD137 blockade, based on differential immunomodulatory effects of CD137 signaling and reverse signaling in T cells and DC, respectively. Further, they show how CD137L blockade can seed a forward-feedback loop for activation of CD103+ DC/type 1 TAM and Tc1 that can create a self-perpetuating cycle of highly effective immunosurveillance. Cancer Res; 77(21); 5989-6000. ©2017 AACR.
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Ligante 4-1BB/imunologia , Anticorpos Monoclonais/farmacologia , Neoplasias/imunologia , Transdução de Sinais/efeitos dos fármacos , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/imunologia , Ligante 4-1BB/metabolismo , Animais , Anticorpos Monoclonais/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Diferenciação Celular/imunologia , Linhagem Celular Tumoral , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/imunologia , Interferon gama/imunologia , Interferon gama/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos Endogâmicos BALB C , Camundongos Knockout , Neoplasias/genética , Neoplasias/metabolismo , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/imunologia , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/genética , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/metabolismoRESUMO
Mineral trioxide aggregate (MTA) is a calcium silicate-based bioactive material that has been extensively used in dentistry. MTA has been highlighted in its diverse biological functions and excellent clinical outcomes. However, limited insight into the intracellular signaling pathways has been provided to explain the biological activities of MTA. Here, we firstly elucidate that the extracellular calcium-sensing receptor (CaSR) is a major signaling mediator of MTA-induced biological reactions through versatile live imaging techniques of human dental pulp cells (hDPCs). We found that MTA activates diverse CaSR downstream pathways; notably, CaSR activation essentially requires dual modulation of extracellular Ca2+ and pH via MTA. Among the CaSR downstream pathways, Ca2+ mobilization from intracellular stores by the phospholipase C pathway plays an important role in osteogenic differentiation of hDPCs by regulating transcriptional activity. Our findings shed light on the signal transduction mechanism of MTA, thus providing a crucial molecular basis for the use of MTA in regenerative dental therapy.
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Compostos de Alumínio/farmacologia , Compostos de Cálcio/farmacologia , Óxidos/farmacologia , Receptores de Detecção de Cálcio/metabolismo , Silicatos/farmacologia , Adolescente , Cálcio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Combinação de Medicamentos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Humanos , Concentração de Íons de Hidrogênio , Espaço Intracelular/metabolismo , Osteogênese/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Adulto JovemRESUMO
We have examined the effect of progranulin (PGRN) on human T cell proliferation and its underlying mechanism. We show that PGRN inhibits the PHA-induced multiplication of T lymphocytes. It increases the number of iTregs when T lymphocytes are activated by PHA but does not do so in the absence of PHA. PGRN-mediated inhibition of T lymphocyte proliferation, as well as the induction of iTregs, was completely reversed by a TGF-ß inhibitor or a Treg inhibitor. PGRN induced TGF-ß secretion in the presence of PHA whereas it did not in the absence of PHA. Our findings indicate that PGRN suppresses T lymphocyte proliferation by enhancing the formation of iTregs from activated T lymphocytes in response to TGF-ß.
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Peptídeos e Proteínas de Sinalização Intercelular/farmacologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Humanos , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/metabolismo , Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Fator de Crescimento Transformador beta/metabolismoRESUMO
OBJECTIVES: In this study, we characterized human dental pulp cells (HDPCs) obtained by different culture methods to establish the most suitable methodology for dental tissue engineering and regenerative endodontic applications. MATERIALS AND METHODS: HDPCs were isolated by the outgrowth method (HDPCs-OG), the enzymatic digestion method (collagenase/dispase/trypsin, HDPCs-ED), or the combination of both methods (HDPCs-Combined). The expression of mesenchymal stem cell markers (CD105, CD90, and CD73) was investigated. In vitro differentiation capacities of HDPCs into adipogenic, osteogenic, and chondrogenic lineages were compared. Differentiation markers were analyzed by quantitative reverse-transcription polymerase chain reaction (RT-PCR) and western blotting. RESULTS: Our data indicated that whole HDPCs-ED, HPDCs-OG, and HDPCs-Combined could be differentiated into adipogenic, chrondrogenic, and osteogenic cell types. However, we found that the methods for isolating and culturing HDPCs influence the differentiation capacities of cells. HDPCs-OG and HDPCs-ED were preferably differentiated into adipogenic and osteogenic cells, respectively. Differentiation markers shown by RT-PCR and western blotting analysis were mostly upregulated in the treated groups compared with the control groups. CONCLUSIONS: Our findings confirmed that cell populations formed by two different culture methods and the combined culture method exhibited different properties. The results of this study could provide an insight into regenerative endodontic treatment using HDPCs.