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Background: An unintentional large dose of dexmedetomidine during sedation can lead to increased side effects such as bradycardia and hypotension. We investigated whether the frequency of bradycardia in patients undergoing surgery under spinal anesthesia and sedation with dexmedetomidine was effected if bispectral index (BIS) was used to monitor the sedation. Methodology: Fifty patients between 20 and 60 y of age, who underwent spinal anesthesia, were included in this study. The patients were divided into two groups (control and BIS groups). Patients in the control group were administered a loading dose of 1 μg/kg dexmedetomidine for the first 10 min without BIS monitoring, followed by a maintenance dose of 0.2 μg/kg/h. Patients in the BIS group received a loading dose of 1 μg/kg dexmedetomidine for the first 10 min. The maintenance dose in this group was administered at the discretion of the anesthesiologist to maintain the BIS score between 50 and 70. The baseline heart rate (HR), lowest HR, and the difference between baseline and the lowest HR were calculated. Results: The baseline HR was 74.4 ± 11.0 beats per minute (bpm) and 80.9 ± 16.0 bpm, in the control and BIS groups respectively (p = 0.098). The difference between the baseline and lowest HR in the control and BIS groups was 19.4 ± 7.6 bpm and 25.5 ± 8.8 bpm, respectively (p = 0.011). Low baseline HR was positively correlated with a reduced lowest HR. Conclusions: The frequency of bradycardia during sedation with dexmedetomidine decreased with BIS monitoring. Patients with a low baseline HR were more likely to develop bradycardia during sedation with dexmedetomidine. Therefore, BIS monitoring may be helpful in patients with low baseline HR. Key words: Bispectral index monitor; Dexmedetomidine; heart rate; spinal anesthesia Citation: Kim J, Kim HY, Yun M, Lee J, Kim JD, Kang D. Bispectral index monitoring during sedation with dexmedetomidine in spinal anesthesia prevents bradycardia: a randomized clinical trial. Anaesth. pain intensive care 2021;26(1):14-19 ; DOI: 10.35975/apic.v26i1.1760

The roles of fibronectin leucine-rich transmembrane protein 2 (FLRT2) in physiological and pathological processes are poorly known. Here, we identify a novel function of FLRT2 in preventing endothelial cell senescence and vascular aging. We found that FLRT2 expression was lower in cultured senescent endothelial cells as well as in aged rat and human vascular tissues. FLRT2 silencing in human endothelial cells induced senescence through mTORC2, but not mTORC1, AKT, and p53. We uncovered that FLRT2 directly associated with ITGB4 and thereby promoted ITGB4 phosphorylation, while inhibition of ITGB4 significantly mitigated the induction of senescence triggered by FLRT2 depletion. Importantly, FLRT2 silencing in mice promoted vascular aging and overexpression of FLRT2 rescued a premature vascular aging phenotype. We propose that FLRT2 could be targeted therapeutically to prevent senescence-associated vascular aging. Subject terms: FLRT2, ITGB4, mTORC2, endothelial cell senescence, vascular aging

Molybdenum disulfide (MoS2) has been regarded as one of the most important n-type two-dimensional (2D) transition metal dichalcogenide semiconductors for nanoscale electron devices. Relatively high contact resistance (RC) remains as an issue in the 2D-devices yet to be resolved. Reliable technique is very compelling to practically produce low RC values in device electronics, although scientific approaches have been made to obtain a record-low RC. To resolve this practical issue, we here use thermal-evaporated ultrathin LiF between channel and source/drain metal to fabricate 2D-like MoS2 field effect transistors (FETs) with minimum RC. Under 4-bar FET method, RC less than ∼600 Ω·μm is achieved from the LiF/Au contact MoS2 FET. Our normal 2-bar FET with LiF thus shows the same mobility as that of 4-bar FET that should have no RC in principle. On the basis of these results, ultrathin LiF is also applied for transparent conducting oxide contact, successfully enabling transparent MoS2 FETs.

To obtain efficient organic light-emitting diodes (OLEDs), the degradation in the surface properties of the indium tin oxide (ITO) electrode during the device fabrication should be prevented. In this study, we investigated the effect of the waiting time of ITO in the entry chamber before the transfer to the deposition chamber on the device performances of OLEDs. The current density and luminance of the OLED significantly decreased owing to the reduced hole injection with the increase in the waiting time. The origin of the reduced hole injection was estimated to be (1) the formation of trap sites at the interface between ITO and hole-transport layer and (2) decreased work function of ITO by an interface dipole. These phenomena could be attributed to the contamination of the ITO surface by the waiting under a relatively low vacuum and room light illumination.

Embedded extrusion printing facilitates the fabrication of complex biological structures using soft hydrogels that are challenging to construct using conventional manufacturing methods. While this targeting strategy is appealing, the residues of support materials on the printed objects have been overlooked. Here, we quantitatively compare the bath residues on fibrin gel fibers printed in granular gel baths that are conjugated with fluorescent probes for visualization, including physically crosslinked gellan gum (GG) and gelatin (GEL) baths and chemically crosslinked polyvinyl alcohol baths. Notably, all support materials can be detected on a microscopic scale, even on structures without any visible residues. Quantitative results indicate that baths with smaller size or lower shear viscosity show more and deeper diffusion into the extruded inks, and the removal efficiency of support materials depends mainly on the dissolving property of the granular gel baths. The residual amount of chemically cross-linked support materials on fibrin gel fibers is 28–70 μg mm−2, which is tens of times higher than physically cross-linked GG (7.5 μg mm−2) and GEL (0.3 μg mm−2) baths. Meanwhile, cross-sectional images suggest that most gel particles are distributed around the fiber surface, but a small amount is in the fiber center. Such bath residues or the blank pores created by the removal of gel particles induce changes in product surface morphology, physicochemical and mechanical properties, impeding cell adhesion. This study will draw attention to the effects of residual support materials on printed structures and encourage the development of new strategies to diminish these residues or to take advantage of the residual support baths to improve product performances.

Two-dimensional (2D) transition metal dichalcogenide (TMD) hetero PN junctions with a van der Waals (vdW) interface have received much attention, because PN diodes are basically important to control the vertical current across the junction. Interestingly, the same vdW PN junction structure can be utilized for junction field-effect transistors (JFETs) where in-plane current is controlled along the junction. However, 2D vdW JFETs seem rarely reported, despite their own advantages to achieve when good vdW junction is secured. Here, we present high-performance p-MoTe2 JFETs using almost perfect vdW organic Alq3/p-MoTe2 junctions and demonstrate organic NPB/n-MoS2 JFETs. The p- and n-channel JFETs stably show high mobilities of 60-80 and ∼800 cm2/V s, respectively, along with a high ON/OFF current ratio (>1 × 105) and minimal gate leakage at 5 V even after a few months. Such performances are attributed to a quality vdW junction at organic layer/TMD interfaces.

Background: There are several advantages of low flow anesthesia including safety, economics, and eco-friendliness. However, oxygen concentration of fresh gas flow and inspired gas are large different in low flow anesthesia. This is a hurdle to access to low flow anesthesia. In this study, we aimed to investigate the change in inhaled oxygen concentration in low flow anesthesia using oxygen and medical air.Methods: A total of 60 patients scheduled for elective surgery with an American Society of Anesthesiologist physical status I or II were enrolled and randomly allocated into two groups. Group H: Fresh gas flow rate (FGF) 4 L/min (FiO₂ 0.5). Group L: FGF 1 L/min (FiO₂ 0.5). FGF was applied 4 L/min in initial phase (10 min) after intubation. After initial phase FGF was adjusted according to groups. FGF continued at the end of surgery. Oxygen and inhalation anesthetic gas concentration were recorded for 180 min at 15 min interval.Results: The inspired oxygen concentration decreased by 5.5% during the first 15 min in the group L. Inspired oxygen decreased by 1.5% during next 15 min. Inspired oxygen decreased by 1.4% for 30 to 60 min. The inspired oxygen of group L is 35.4 ± 4.0% in 180 min. The group H had little difference in inspired oxygen concentration over time and decreased by 1.8% for 180 min.Conclusions: The inspired oxygen concentration is maintained at 30% or more for 180 min in patients under 90 kg. Despite some technical difficulties, low flow anesthesia may be considered.

Recently, organic photovoltaics (OPVs) have attracted attention as a next-generation energy source as their power conversion efficiency (PCE) has significantly improved. To increase the PCE of OPVs further, a fundamental understanding of material properties of a new organic semiconductor is highly important. Copper naphthalocyanine (CuNc) is composed of macrocyclic ligands with extended benzene rings of copper phthalocyanine (CuPc). Thus, it can be considered as a potential candidate for an efficient p-type organic semiconductor, similar to a well-known conventional p-type organic semiconductor CuPc. In this study, we investigated the electronic structure of thermally evaporated CuNc on indium tin oxide (ITO) wit in situ ultraviolet and X-ray photoelectron spectroscopy (UPS and XPS) and density functional theory (DFT) calculations. DFT calculations predict that CuNc has a lower ionization energy (IE) and band gap than CuPc. However, the IE measured by UPS and the band gap measured by UV-vis absorption of the deposited film were much higher than CuPc. Derived from the measured UPS, XPS spectra and DFT calculation results, we concluded that CuNc could be decomposed with thermal evaporation in a vacuum and the pyrrole-based material might be deposited on ITO. The increased IE and band gap were attributed to the disappearance of the highest occupied molecular orbital originating from the macrocyclic ligands with D4h symmetry. Therefore, the thermal evaporation method would not be a suitable method to obtain the CuNc film for device application, and the alternative solution process at low temperature would be more adequate.

Poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PEDOT:PSS) films were fabricated using an electrospray deposition (ESD) method. The ESD PEDOT:PSS films exhibited higher PSS content on the surface than spin-coated PEDOT:PSS films, which results in a higher work function. Based on this result, metal-electrode-free inverted organic photovoltaics (OPVs) were fabricated. The ESD PEDOT:PSS was used as the top electrode on the poly(3-hexythiophene-2,5-diyl) (P3HT):[6,6]-phenyl C61 butyric acid methyl ester (PCBM) light-absorbing layer. The power conversion efficiency (PCE) of OPVs was significantly increased with the 1,4,5,8,9,11-hexaazatriphenylene hexacarbonitrile layer. The improved PCE would be attributed to the suppression of exciton quenching at the P3HT:PCBM and PEDOT:PSS interface.

To dope 2D semiconductor channels, charge-transfer doping has generally been done by thermal deposition of inorganic or organic thin-film layers on top of the 2D channel in bottom-gate field-effect transistors (FETs). The doping effects are reproducible in most cases. However, such thermal deposition will damage the surface of 2D channels due to the kinetic energy of depositing atoms, causing hysteresis or certain degradation. Here, a more desirable charge-transfer doping process is suggested. A damage-free charge-transfer doping is conducted for 2D MoTe

2D crystals can serve as templates for the realization of new van der Waals (vdW) heterostructures via controlled assembly of low-dimensional functional components. Among available 2D crystals, black phosphorus (BP) is unique due to its puckered atomic surface topography, which may lead to strong epitaxial phenomena through guided vdW assembly. Here, it is demonstrated that a BP template can induce highly oriented assembly of C

Bis(trifluoromethane)sulfonimide lithium salt (Li-TFSI) has been popularly employed as an efficient p-dopant that increases the conductivity of a hole transport layer (HTL) in perovskite solar cells and dye-sensitized solar cells. However, the working mechanism of the Li-TFSI dopant is a long-standing question. The hygroscopicity of Li-TFSI makes it difficult to isolate the exact doping mechanism. In this study, we unveil the role of Li-TFSI in the p-doping to the N,N′-di(1-naphthyl)-N,N′-diphenyl-(1,1′-biphenyl)-4,4′-diamine (NPB) HTL. A series of systematic in situ measurements using ultraviolet and inverse photoelectron spectroscopy reveal that electron transfer from NPB to Li-TFSI occurs due to the lower-lying negative polaronic level of Li-TFSI rather than the positive polaronic level of NPB. The hole injection barrier between NPB and indium tin oxide is significantly reduced with Li-TFSI doping, enhancing the device performance of hole-only devices and organic light-emitting diodes dramatically. With excessive dopants, however, the agglomerative property of Li-TFSI became dominant, decreasing the doping efficiency. These results provide robust guidelines for developing an efficient doping method for a molecular system with high conductivity.

Amorphous InGaZnO semiconductors have been rapidly developed as active charge-transport materials in thin film transistors (TFTs) because of their cost effectiveness, flexibility, and homogeneous characteristics for large-area applications. Recently, InZnSnO (IZTO) with superior mobility (higher than 20 cm

Simple Summary RNA-binding proteins (RBPs) play central roles in regulating posttranscriptional expression of genes. Many of them are known to be deregulated in a wide variety of cancers. Dysregulated RBPs influence the expression levels of target RNAs related to cancer phenotypes, such as proliferation, apoptosis, angiogenesis, senescence, and EMT/invasion/metastasis. Thus, understanding the molecular functions of RBPs and their roles in cancer-related phenotypes can lead to improved therapeutic strategies. Abstract RNA-binding proteins (RBPs) crucially regulate gene expression through post-transcriptional regulation, such as by modulating microRNA (miRNA) processing and the alternative splicing, alternative polyadenylation, subcellular localization, stability, and translation of RNAs. More than 1500 RBPs have been identified to date, and many of them are known to be deregulated in cancer. Alterations in the expression and localization of RBPs can influence the expression levels of oncogenes, tumor-suppressor genes, and genome stability-related genes. RBP-mediated gene regulation can lead to diverse cancer-related cellular phenotypes, such as proliferation, apoptosis, angiogenesis, senescence, and epithelial-mesenchymal transition (EMT)/invasion/metastasis. This regulation can also be associated with cancer prognosis. Thus, RBPs can be potential targets for the development of therapeutics for the cancer treatment. In this review, we describe the molecular functions of RBPs, their roles in cancer-related cellular phenotypes, and various approaches that may be used to target RBPs for cancer treatment.

Loss of PTEN, the major negative regulator of the PI3K/AKT pathway induces a cellular senescence as a failsafe mechanism to defend against tumorigenesis, which is called PTEN-loss-induced cellular senescence (PICS). Although many studies have indicated that the mTOR pathway plays a critical role in cellular senescence, the exact functions of mTORC1 and mTORC2 in PICS are not well understood. In this study, we show that mTOR acts as a critical relay molecule downstream of PI3K/AKT and upstream of p53 in PICS. We found that PTEN depletion induces cellular senescence via p53-p21 signaling without triggering DNA damage response. mTOR kinase, a major component of mTORC1 and mTORC2, directly binds p53 and phosphorylates it at serine 15. mTORC1 and mTORC2 compete with MDM2 and increase the stability of p53 to induce cellular senescence via accumulation of the cell cycle inhibitor, p21. In embryonic fibroblasts of PTEN-knockout mice, PTEN deficiency also induces mTORC1 and mTORC2 to bind to p53 instead of MDM2, leading to cellular senescence. These results collectively demonstrate for the first time that mTOR plays a critical role in switching cells from proliferation signaling to senescence signaling via a direct link between the growth-promoting activity of AKT and the growth-suppressing activity of p53.

SnOx thin films were successfully deposited by the thermal atomic layer deposition (ALD) method using N,N′-tert-butyl-1,1-dimethylethylenediamine stannylene(II) as a precursor and ozone and water as reactants. The growth of SnO and SnO2 films could be easily controlled by employing different reactants and utilizing different ozone and water concentrations, respectively. The formation of both SnO and SnO2 films exhibited typical surface-limiting reaction characteristics, although their growth behaviors differ from one another. The combined studies of density functional theory calculations and experimental analyses showed that the difference in growth behavior of the SnO and SnO2 films can be attributed to the stability of ozone and water on the SnO2 and SnO films. SnO and SnO2 films have different crystal structures and both films were crystallized from the amorphous to polycrystalline states following an increase in the deposition temperature. The absorbance and refractive index of the thin films were inv...

In organolead halide perovskite solar cells (PSCs), interfacial properties between the perovskite and charge transport layers are the critical factors governing charge extraction efficiency. In this study, the effect of interfacial energetics between two-step spin-coated methylammonium lead iodide (MAPbI3) with different methylammonium iodide (MAI) concentrations and C60 on the charge extraction efficiency is investigated. The electronic structures of perovskite films are significantly varied by the MAI concentrations due to the changes in the residual precursor and MA+ defect content. As compared to the optimum PSCs with 25 mg mL–1 MAI, PSCs with other MAI concentrations show significantly lower power conversion efficiencies and severe hysteresis. The energy level alignment at the C60/MAPbI3 interface determined by ultraviolet and inverse photoelectron spectroscopy measurements reveals the origin of distinct differences in device performances. The conduction band offset at the C60/MAPbI3 interface plays ...

The effects of senescence associated secretory phenotype (SASP) from therapy-induced senescent endothelial cells on tumor microenvironment (TME) remains to be clarified. Here, we investigated effects of ionizing radiation (IR)- and doxorubicin-induced senescent HUVEC on TME. MDA-MB-231 cancer cells treated with conditioned medium (CM) from senescent HUVEC or co-cultured with senescent HUVEC significantly increased cancer cell proliferation, migration, and invasion. We found that CXCL11 plays a principal role in the senescent CM-induced aggressive activities of MDA-MB-231 cells. When we treated HUVEC with a neutralizing anti-CXCL11 antibody or CXCL11 SiRNA, or treated MDA-MB-231 cells with CXCR3 SiRNA, we observed synergistic diminution of the ability of the HUVEC SASP to alter the migration and spheroid invasion of cancer cells. ERK activation was involved in the HUVEC SASP-induced aggressive activity of MDA-MB-231 cells. Finally, we observed the in vivo effect of CXCL11 from the senescent HUVEC in tumor-bearing mice. Together, our results demonstrate that SASP from endothelial cells experiencing therapy-induced senescence promotes the aggressive behavior of cancer cells, and that CXCL11 can potentially be targeted to prevent the adverse effects of therapy-induced senescent endothelial cells on the tumor microenvironment.

Cellular senescence can be triggered by various intrinsic and extrinsic stimuli. We previously reported that silencing of 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (PAPSS2) induces cellular senescence through augmented fibroblast growth factor receptor 1 (FGFR1) signaling. However, the exact molecular mechanism connecting heparan sulfation and cellular senescence remains unclear. Here, we investigated the potential involvement of heparan sulfate proteoglycans (HSPGs) in augmented FGFR1 signaling and cellular senescence. Depletion of several types of HSPGs revealed that cells depleted of syndecan 1 (SDC1) exhibited typical senescence phenotypes, and those depleted of PAPSS2-, SDC1-, or heparan sulfate 2-O sulfotransferase 1 (HS2ST1) showed decreased FGFR1 internalization along with hyperresponsiveness to and prolonged activation of fibroblast growth factor 2 (FGF2)-stimulated FGFR1- v-akt murine thymoma viral oncogene homolog (AKT) signaling. Clathrin- and caveolin-mediated FGFR1 endocytosis contributed to cellular senescence through the FGFR1-AKT-p53-p21 signaling pathway. Dynasore treatment triggered senescence phenotypes, augmented FGFR1-AKT-p53-p21 signaling, and decreased SDC1 expression. Finally, the replicatively and prematurely senescent cells were characterized by decreases of SDC1 expression and FGFR1 internalization, and an increase in FGFR1-AKT-p53-p21 signaling. Together, our results demonstrate that properly sulfated SDC1 plays a critical role in preventing cellular senescence through the regulation of FGFR1 endocytosis.

Long noncoding RNAs (lncRNAs) regulating diverse cellular processes implicate in many diseases. However, the function of lncRNAs in cellular senescence remains largely unknown. Here we identify a novel long intergenic noncoding RNA Linc-ASEN expresses in prematurely senescent cells. We find that Linc-ASEN associates with UPF1 by RNA pulldown mass spectrometry analysis, and represses cellular senescence by reducing p21 production transcriptionally and posttranscriptionally. Mechanistically, the Linc-ASEN-UPF1 complex suppressed p21 transcription by recruiting Polycomb Repressive Complex 1 (PRC1) and PRC2 to the p21 locus, and thereby preventing binding of the transcriptional activator p53 on the p21 promoter through histone modification. In addition, the Linc-ASEN-UPF1 complex repressed p21 expression posttranscriptionally by enhancing p21 mRNA decay in association with DCP1A. Accordingly, Linc-ASEN levels were found to correlate inversely with p21 mRNA levels in tumors from patient-derived mouse xenograft, in various human cancer tissues, and in aged mice tissues. Our results reveal that Linc-ASEN prevents cellular senescence by reducing the transcription and stability of p21 mRNA in concert with UPF1, and suggest that Linc-ASEN might be a potential therapeutic target in processes influenced by senescence, including cancer.

The interfacial properties of organolead halide perovskite solar cells (PSCs) affect the exciton and charge-transport dynamics significantly. Thus, proper modification of the interfaces between perovskite and charge-transport layers is an efficient method to increase the power conversion efficiency (PCE) of PSCs. In this work, we explore the effect of a nonionic surfactant, that is, Triton X-100 (TX) additive, in the poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) (PEDOT:PSS) hole-transport layer. The electronic structure of TX-modified PEDOT:PSS is investigated with ultraviolet/X-ray photoelectron spectroscopy and X-ray absorption spectroscopy with various TX concentrations. The surface of the TX-modified PEDOT:PSS layer showed high TX content, and thus the semimetallic properties of PEDOT:PSS were suppressed conspicuously by its insulating nature. With the TX-modified PEDOT:PSS, the PCE of methylammonium lead iodide (MAPbI3) PSCs increased significantly. To elucidate the origin of the improved device performance, the electrical properties and photoluminescence were investigated comprehensively. Consequently, it was found that the TX additive inhibits interface recombination between PEDOT:PSS and MAPbI3, which is caused by the suppression of semimetallic properties of the PEDOT:PSS surface. Hence, we fabricated flexible PSCs successfully using a graphene electrode and TX-modified PEDOT:PSS.

Two dimensional (2D) p-MoTe2 channel-based nonvolatile memory transistors with ferroelectric P(VDF-TrFE) polymer has been studied using a bottom-gate device architecture, which is introduced to dramatically reduce both of the switching and drain voltages to minimum 8 V and 10 mV, respectively. In fact, most of 2D-channel ferroelectric FETs with the same P(VDF-TrFE) polymer have used top-gate architectures, utilizing high switching pulse voltages over 20–25 V due to the existence of dead layer, which is unavoidably formed at the interface between P(VDF-TrFE) and thermal-deposited Al top gate. Key effects to realize such a low 8–13 V switching thus originate from the bottom-gate architecture. On the one hand, keys to obtain the low operation/drain voltage come from anneal-free Ohmic contact which is obtained using H2O2 solution. Thanks to the low operation voltages of 10 mV, consuming power in the nonvolatile FETs can be minimized to ~a few pW for OFF/Erase state and ~a few hundred pW for ON/Program although it eventually becomes ~nW and ~30 nW for OFF and ON states in a practical circuit operation to switch organic light emitting diodes. Our approaches of bottom-gate architecture and H2O2 contact nicely work even for transparent nonvolatile memory FET.

Recently, a hole-transport-layer (HTL)-free structure was proposed to decrease the cost of organic lead halide perovskite solar cell (PSC) fabrication. In HTL-free PSCs, instead of using an HTL insertion, the HTL material can be added directly into a perovskite precursor solution to improve hole transport. For example, copper thiocyanate (CuSCN) is used for p-type doping of methylammonium lead triiodide (MAPI) via spin coating from a mixed solution. However, the optimum annealing temperature for CuSCN-doped MAPI (CuSCN:MAPI) PSCs is lower than the 100 °C that is typical for undoped MAPI PSCs. In this study, the origin of such lower annealing temperatures of CuSCN:MAPI PSCs is investigated. The highest power conversion efficiency (PCE) and enhanced electron transport in CuSCN:MAPI are obtained with annealing at 60 °C. Using transmission electron microscopy-energy-dispersive X-ray spectroscopy, it is revealed that annealing at 60 °C results in the uniform distribution of CuSCN, while the annealing at 100 °C induces the aggregation of CuSCN with a diameter of ~20 nm. A large energy barrier formed by the shallow-lying conduction band minimum of these CuSCN clusters hinders electron transport. The lower PCE of CuSCN:MAPI PSCs with annealing at 100 °C is attributed to this deterioration in the electron transport.

SnO

Cellular senescence refers to an irreversible growth arrest that is triggered by various intrinsic and extrinsic stresses. Many recent studies have demonstrated that cellular senescence plays a crucial role in the regression of tumors exposed to ionizing radiation (IR), but the underlying mechanism remains unknown. Here we show that the activation of integrin β4 is essential for IR-induced cellular senescence. IR treatment results in the phosphorylation of integrin β4 at tyrosine residue 1510, leading to activation of the integrin α6β4-Src-AKT signaling pathway. We further reveal that the IR-induced phosphorylation of integrin β4 is regulated by the cholesterol content and membrane fluidity. We also find that IR-induced p53-caspase signaling is independent of integrin α6β4-Src-AKT signaling. Finally, we show that siRNA- or inhibitor-mediated blockade of integrin α6β4-Src-AKT signaling switches the post-irradiation fate from senescence to apoptosis, under p53 activated condition, in both cancer cells and tumor tissues of xenograft mice. On the basis of our finding that, integrin α6β4 is specifically activated and acts primarily to induce premature senescence in irradiated cancer cells, we propose that this integrin may be a valuable target and biomarker for radiotherapy.

RNA-binding proteins (RBPs) are involved in mRNA splicing, maturation, transport, translation, storage and turnover. Here, we identified ACOT7 mRNA as a novel target of human WIG1. ACOT7 mRNA decay was triggered by the microRNA miR-9 in a WIG1-dependent manner via classic recruitment of Argonaute 2 (AGO2). Interestingly, AGO2 was also recruited to ACOT7 mRNA in a WIG1-dependent manner in the absence of miR-9, which indicates an alternative model whereby WIG1 controls AGO2-mediated gene silencing. The WIG1–AGO2 complex attenuated translation initiation via an interaction with translation initiation factor 5B (eIF5B). These results were confirmed using a WIG1 tethering system based on the MS2 bacteriophage coat protein and a reporter construct containing an MS2-binding site, and by immunoprecipitation of WIG1 and detection of WIG1-associated proteins using liquid chromatography-tandem mass spectrometry. We also identified WIG1-binding motifs using photoactivatable ribonucleoside-enhanced crosslinking and immunoprecipitation analyses. Altogether, our data indicate that WIG1 governs the miRNA-dependent and the miRNA-independent recruitment of AGO2 to lower the stability of and suppress the translation of ACOT7 mRNA.

Cellular senescence is a complex biological process that leads to irreversible cell-cycle arrest. Various extrinsic and intrinsic insults are associated with the onset of cellular senescence and frequently accompany genomic or epigenomic alterations. Cellular senescence is believed to contribute to tumor suppression, immune response, and tissue repair as well as aging and age-related diseases. Long noncoding RNAs (lncRNAs) are >200 nucleotides long, poorly conserved, and transcribed in a manner similar to that of mRNAs. They are tightly regulated during various cellular and physiological processes. Although many lncRNAs and their functional roles are still undescribed, the importance of lncRNAs in a variety of biological processes is widely recognized. RNA-binding proteins (RBPs) have a pivotal role in posttranscriptional regulation as well as in mRNA transport, storage, turnover, and translation. RBPs interact with mRNAs, other RBPs, and noncoding RNAs (ncRNAs) including lncRNAs, and they are involved in the regulation of a broad spectrum of cellular processes. Like other cell fate regulators, lncRNAs and RBPs, separately or cooperatively, are implicated in initiation and maintenance of cellular senescence, aging, and age-related diseases. Here, we review the current understanding of both lncRNAs and RBPs and their association with oxidative stress, senescence, and age-related diseases.

High-throughput sequencing analyses have revealed that transposable elements (TEs) comprise approximately half of the human genome and frequently involved in genomic rearrangements and instability by various mechanisms. Interestingly, many noncoding RNAs (ncRNAs) contain TEs and the TE-containing ncRNAs that have been implicated in cellular processes and various diseases in mammals. In this study, we retrieved 94 human long noncoding RNAs (lncRNAs; >200 nucleotides in length) from lncRNAdb and analyzed TEs which are embedded within the lncRNAs, focusing on their chromosomal distribution. The result showed that TEs occupy ~27 % of the lncRNA transcripts in mass and lncRNA containing TEs are enriched in human chromosome 11. We further analyzed subfamily of the TEs and found that most of the TEs belong to AluSx and L1 which are the most successful TE subfamilies in the human genome. Numerous lncRNAs have been reported to be expressed in a cell-type specific manner. Thus, using reverse transcription PCR with specific primers for the lncRNAs, we examined their expression pattern in human normal tissues and cancer cells. Most of the lncRNAs were universally amplified from 20 different types of normal human tissues but some of them displayed tissue-specific expression. Especially, 11 lncRNAs were expressed only in human cancer cells, implying the possibility of their involvement in carcinogenesis.

Direct evidence of chemical interaction and origin of electron accumulation at a “buried” methylammonium lead triiodide (CH3NH3PbI3, hereafter “MAPI”)/TiO2 interface is presented in this study for the first time. Despite the high power conversion efficiency of perovskite solar cells (PSCs) using a TiO2 electron transport layer, the MAPI/TiO2 interface is believed as an electron accumulation position during device operation. To elucidate the cause of the electron accumulation, the energy level alignment at the MAPI/TiO2 interface should be understood. However, a buried MAPI/TiO2 interface forms after a thick MAPI layer deposition; thus, the electronic structure of the MAPI/TiO2 interface cannot be measured using surface-sensitive photoelectron spectroscopy in a conventional stack-up manner. In this study, we investigated the electronic structure of a buried MAPI/TiO2 interface by removing the MAPI and organic layers using solvent immersion. As a result, we reveal that a conduction band minimum (CBM) mismatch occurs owing to the Ti O Pb bonding on the TiO2 surface. The Ti O Pb bonds form by the Pb ions penetrating during the spin coating of the MAPI solution. When a [6,6]-phenyl C61 butyric acid methyl ester (PCBM) layer was inserted, the CBM mismatch was removed owing to the high work function of PCBM.

Elastomers show improved properties when reinforced with nanoclay at low filler loadings, but dispersion of the clay is difficult in non-polar polymers, such as ethylene propylene diene monomer (EPDM). In this work several compatibilization approaches were studied, including the addition of EPDM modified with maleic anhydride (EPDM-g-MA) and the use of organoclay modified with maleic anhydride-grafted liquid vinyl polybutadiene (LVPB-g-MA). The use of LVPB-g-MA-modified organoclay increased the degree of dispersion as measured by X-ray diffraction, giving increased thermal stability and modulus, and decreased swelling. Flame resistance was poorer for the EPDM/LVPB-g-MA- modified organoclay system compared to the unmodified EPDM/organoclay compound. The resistivity of the nanoclay-filled composites was lower than the reference EPDM compound, but dielectric properties for the LVPB-g-MA modified organoclay were similar to the reference.

Radiotherapy represents the most effective non-surgical modality in cancer treatment. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression, and are involved in many biological processes and diseases. To identify miRNAs that influence the radiation response, we performed miRNA array analysis using MCF7 cells at 2, 8, and 24 h post irradiation. We demonstrated that miR-770-5p is a novel radiation-inducible miRNA. When miR-770-5p was overexpressed, relative cell number was reduced due to increased apoptosis in MCF7 and A549 cells. Transcriptomic and bioinformatic analyses revealed that PDZ-binding kinase (PBK) might be a possible target of miR-770-5p for regulation of radiosensitivity. PBK regulation mediated by direct targeting of miR-770-5p was demonstrated using luciferase reporter assays along with wild-type and mutant PBK-3′untranslated region constructs. Radiation sensitivity increased and decreased in miR-770-5p- and anti-miR-770-5p-transfected cells, respectively. Consistent with this result, transfection of short interfering RNA against PBK inhibited cell proliferation, while ectopic expression of PBK restored cell survival from miR-770-5p-induced cell death. In addition, miR-770-5p suppressed tumor growth, and miR-770-5p and PBK levels were inversely correlated in xenograft model mice. Altogether, these data demonstrated that miR-770-5p might be a useful therapeutic target miRNA that sensitizes tumors to radiation via negative regulation of PBK.

SiP (System-in-Package) solution realizes an extremely small sized system which is suitable for mixed-signal mobile applications. However, integration of digital and RF dies with a number of interconnections between them within limited area can cause noise coupling from digital circuits to RF circuits. In this paper, a fully operating T-DMB (Terrestrial Digital Multimedia Broadcasting) system is implemented in a form of a 3-D (three-dimensional) SiP by stacking dies, on which a series of design methodologies to improve the noise isolation level between digital and RF signals, is applied. As a result, the size of system is reduced to 10mm x 10mm, which is the smallest size for full T-DMB system with multimedia, and RF sensitivity is enhanced by 17dB and 45dB for band-3(173-240MHz) and L-band (1.452~1.492GHz), respectively.