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Enhancing therapeutic efficacy of drugs from reactive oxygen species (ROS) and glutathione (GSH)-responsive matrix and minimizing toxic effects on normal cells remains a challenge in programmable anticancer drug delivery. Herein, ROS- and GSH-responsive paclitaxel (PTX)-loaded polymer dot (PD) with mitochondria-targeting capability was designed by constructing diselenide linkage and triphenylphosphonium (TPP) for tunable PTX release and fluorescence for cancer theranostics. PD-TPP nanocarrier could improve the PTX stability after loading (PD-TPP(PTX)), and the cleavage of diselenide bond in the presence of H2O2 and GSH triggered the controllable PTX release, providing higher fluorescence intensity. As the levels of H2O2 and GSH are higher in cancer cells compared to normal cells, PTX was selectively released from PD-TPP in cancer cells, reducing cell viability (∼25%) and causing enhanced apoptosis of cancer cells compared to normal cells. The PD-TPP(PTX) selectivity was also reflected by distinct fluorescence intensity in HeLa and PC-3 cells (cancer) compared to CHO-K1 cells (normal). Furthermore, conjugated TPP promoted the PD-TPP(PTX) accumulation in mitochondria due to specific targeting of TPP towards mitochondria, allowing PTX release in mitochondria of cancer cells. Hence, this approach could be a potential strategy to enhance therapeutic efficacy of cancer drugs and minimize the side effects on normal cells.

In situ wireless monitoring for cell proliferation and detachment kinetics was conducted using pH-responsive zwitterionic polymer dots (Z-PDs), based on changes in electrochemical signals derived from Z-PD-coated substrates via the interaction of charges transferred between Z-PDs and cells. Z-PD-coated substrates were found to be a potent means to monitor and manipulate cell adhesion and detachment because of their high sensitivity over a wide range of pH conditions, and modification of the coated substrates was confirmed using a wireless system. At neutral pH, Z-PD-coated wireless sensors exhibited π-π stacking involving aromatic rings with hydrophobic interactions, thereby promoting cell proliferation; consequently, an increase in the measured resistance was observed. In contrast, Z-PD-coated substrates triggered by acidic and basic conditions promoted cell detachment, which induced an increase in the resistance compared with Z-PD substrates at pH 6.8, as a result of charges transferred to support Z-PD internalization through cell membranes after detachment. Therefore, as a wireless biosensor with excellent pH responsiveness that facilitates cell proliferation and detachment and whose electrochemical signals could be additionally acquired via a smartphone, Z-PD biosensors demonstrated a more favorable approach for monitoring cell-surface interactions than conventional optically based methods.

The endoplasmic reticulum (ER) apparatus is a part of the secretory pathway that transports proteins to the plasma membrane through vesicle trafficking, enabling post-translational modification of the newly synthesized proteins. Several diseases such as inflammation, neurodegenerative disorder, and bipolar disorder are closely associated with dysfunction of the ER stress response. Herein, we present an ER-targeting, intracellular delivery approach that utilized cell-penetrating peptide (CPP)-conjugated lipid/polymer hybrid nanovehicles (LPNVs). For this, we patched Penetratin, a type of CPP, onto the LPNVs with vesicular membranes formulated with poly(ethylene oxide)-b-poly(ε-caprolactone)-b-poly(ethylene oxide) (PEO-b-PCL-b-PEO) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). We found that the Penetratin-conjugated LPNV (LPNVPnt) was readily taken up by cells and showed specific ER-targeting ability, which was comparable to that of LPNVs conjugated with other types of CPPs. Moreover, we observed that remarkable lysosomal escape of the LPNVs occurred due to effective pH buffering with the aid of PEO-b-PCL-b-PEO. These results highlighted that our LPNVPnt system could pave the way for the development of an elaborate drug delivery technology for ER-targeting at the intracellular level.

The objective of this study was to report the synthesis and characteristics of a dual modality imaging agent, Tc-99m GRFLTGGTGRLLRIS-GHEG-ECG-K(-5-carboxy-X-rhodamine)-NH2 (GRFLT-ECG-ROX), and to verify its feasibility as both molecular imaging and intraoperative guidance agent. GRFLT-ECG-ROX was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of GRFLT-ECG-ROX with Tc-99m was accomplished using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed using LNCaP and PC-3 tumor-bearing murine models. Surgical removal of tumor nodules in murine models with peritoneal carcinomatosis was performed under a fluorescence imaging system. After radiolabeling procedures with Tc-99m, Tc-99m GRFLT-ECG-ROX complexes were prepared in high yield (>96%). The binding affinity value (Kd ) of Tc-99m GRFLT-ECG-ROX for LNCaP cells was estimated to be 9.5 ± 1.3 nM. In gamma camera imaging, the tumor to normal muscle uptake ratios of Tc-99m GRFLT-ECG-ROX increased with time (3.1 ± 0.2, 4.0 ± 0.4, and 6.3 ± 0.9 at 1, 2, and 3 h, respectively). Under real-time optical imaging, the removal of visible nodules was successfully performed. Thus, Tc-99m GRFLT-ECG-ROX could provide both preoperative molecular imaging and fluorescence imaging guidance for tumor removal.

Recently, a great deal of research has focused on the study of self-healing hydrogels possessing electronic conductivity due to their wide applicability for use in biosensors, bioelectronics, and energy storage. The low solubility, poor biocompatibility, and lack of effective stimuli-responsive properties of their sp2 carbon-rich hybrid organic polymers, however, have proven challenging for their use in electroconductive self-healing hydrogel fabrication. In this study, we developed stimuli-responsive electrochemical wireless hydrogel biosensors using ureidopyriminone-conjugated gelatin (Gel-UPy) hydrogels that incorporate diselenide-containing carbon dots (dsCD) for cancer detection. The cleavage of diselenide groups of the dsCD within the hydrogels by glutathione (GSH) or reactive oxygen species (ROS) initiates the formation of hydrogen bonds that affect the self-healing ability, conductivity, and adhesiveness of the Gel-UPy/dsCD hydrogels. The Gel-UPy/dsCD hydrogels demonstrate more rapid healing under tumor conditions (MDA-MB-231) compared to that observed under physiological conditions (MDCK). Additionally, the cleavage of diselenide bonds affects the electrochemical signals due to the degradation of dsCD. The hydrogels also exhibit excellent adhesiveness and in vivo cancer detection ability after exposure to a high concentration of GSH or ROS, and this is comparable to results observed in a low concentration environment. Based on the combined self-healing, conductivity, and adhesiveness properties of the Gel-UPy/dsCD, this hydrogel exhibits promise for use in biomedical applications, particularly those that involve cancer detection, due to its selectivity and sensitivity under tumor conditions.

The conventional precursor mixture based on highly pure and expensive PbI2 (purity >99.99%) is problematic in commercializing perovskite solar cells (PSCs) because of a large deviation in the batch-to-batch photovoltaic performance due to underlying nonstoichiometry and/or the nonperovskite phase. Here, we report on reproducibly efficient (>21%) PSCs based on the ambient-temperature-stable δ-phase FAPbI3 powder, synthesized by reacting PbI2 (either homemade or low-grade commercial product with purity

Several studies have reported that a drug nanocarrier conjugated with ligands having cell binding ability improves drug delivery performance, but multiple cell-targeting and the resultant activation in designated cells has not been investigated yet. This study reports a skin cell multi-targeting vesicular nanocargo system. We selectively conjugated several skin protein-derived cell-targeting peptides (CTPs), including KTTKS, NAP-amide, and Lam332, to amphiphilic polymer-reinforced lipid nanovesicles (PLNVs) to specifically target fibroblasts, melanocytes, and keratinocytes, respectively, through effective association with the corresponding cell membrane receptors. We then showed that CTP-conjugated PLNVs specifically bind to the designated skin cells, even in a mixture of different types of skin cells, eventually leading to skin cell multi-targeting and consequent activation. These results highlight that this CTP-conjugated PLNV system has significant potential for developing an intelligent cellular drug delivery technology for dermatological applications.

This study aimed to produce fabrics by the digital light processing (DLP) three-dimensional (3D) printing technology and using a polyurethane acrylate photopolymer as the printing material. The effect of the acrylate oligomer concentration on printing was evaluated. The DLP 3D printing conditions, such as the curing time and layer thickness, were controlled considering the physical properties, such as the tensile strength, elongation, and crease recovery of the 3D printed material. The optimal printing conditions were as follows: concentration of acrylate oligomer in the photopolymer: 10% (v/v); curing time per layer: 14 s; and layer thickness: 100 µm. These results are expected to guide further studies on the development of fabrics using DLP 3D printing technology.

Background Fast growing cancer cells require greater amounts of ATP than normal cells. Although glycolysis was suggested as a source of anabolic metabolism based on lactate production, the main source of ATP to support cancer cell metabolism remains unidentified. Methods We have proposed that the oxoglutarate carrier SLC25A11 is important for ATP production in cancer by NADH transportation from the cytosol to mitochondria as a malate. We have examined not only changes of ATP and NADH but also changes of metabolites after SLC25A11 knock down in cancer cells. Findings The mitochondrial electron transport chain was functionally active in cancer cells. The cytosolic to mitochondrial NADH ratio was higher in non-small cell lung cancer (NSCLC) and melanoma cells than in normal cells. This was consistent with higher levels of the oxoglutarate carrier SLC25A11. Blocking malate transport by knockdown of SLC25A11 significantly impaired ATP production and inhibited the growth of cancer cells, which was not observed in normal cells. In in vivo experiments, heterozygote of SLC25A11 knock out mice suppressed KRASLA2 lung tumor formation by cross breeding. Interpretation Cancer cells critically depended on the oxoglutarate carrier SLC25A11 for transporting NADH from cytosol to mitochondria as a malate form for the purpose of ATP production. Therefore blocking SLC25A11 may have an advantage in stopping cancer growth by reducing ATP production. Fund The Basic Science Research Program through the National Research Foundation of Korea funded by the Ministry of Science and ICT to SYK (NRF-2017R1A2B2003428).

Fabrication of high-quality perovskite films with a large grain size and fewer defects is always crucial to achieve efficient and stable perovskite solar cells (PSCs). Here, we report a simple and effective method for crystal growth and defect passivation via additive engineering. It is found that bidentate ligand 2,2′-bipyridine (Bpy) and tridentate ligand 2,2′:6′,2′′-terpyridine (Tpy) show a positive effect on the power conversion efficiency (PCE) while a negative effect is observed for monodentate pyridine (Py). Bpy or Tpy additives increase the grain size and carrier lifetimes, which indicates that the degree of interaction between Lewis acid species in the precursor solution and pyridine derivatives plays a critical role in modulating grain growth and passivating defects. Moreover, device stability is improved upon introduction of Bpy or Tpy additives, which is mainly ascribed to suppressed trap-assisted non-radiative recombination as a consequence of reduced defect density. This work highlights the importance of rational engineering of additives for the purpose of simultaneous realization of morphological improvement and defect passivation in efficient and stable PSCs.

A thermally stable perovskite solar cell (PSC) based on a new molecular hole transporter (MHT) of 1,3-bis(5-(4-(bis(4-methoxyphenyl) amino)phenyl)thieno[3,2-b]thiophen-2-yl)-5-octyl-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione (coded HL38) is reported. Hole mobility of 1.36 × 10-3 cm2 V-1 s-1 and glass transition temperature of 92.2 °C are determined for the HL38 doped with lithium bis(trifluoromethanesulfonyl)imide and 4-tert-butylpyridine as additives. Interface engineering with 2-(2-aminoethyl)thiophene hydroiodide (2-TEAI) between the perovskite and the HL38 improves the power conversion efficiency (PCE) from 19.60% (untreated) to 21.98%, and this champion PCE is even higher than that of the additive-containing 2,2',7,7'-tetrakis(N,N-di-p-methoxyphenylamine)-9,9'-spirobifluorene (spiro-MeOTAD)-based device (21.15%). Thermal stability testing at 85 °C for over 1000 h shows that the HL38-based PSC retains 85.9% of the initial PCE, while the spiro-MeOTAD-based PSC degrades unrecoverably from 21.1% to 5.8%. Time-of-flight secondary-ion mass spectrometry studies combined with Fourier transform infrared spectroscopy reveal that HL38 shows lower lithium ion diffusivity than spiro-MeOTAD due to a strong complexation of the Li+ with HL38, which is responsible for the higher degree of thermal stability. This work delivers an important message that capturing mobile Li+ in a hole-transporting layer is critical in designing novel MHTs for improving the thermal stability of PSCs. In addition, it also highlights the impact of interface design on non-conventional MHTs.

Bacterial cellulose nanofibrils (BCNFs), possessing excellent biocompatibility as well as hygroscopicity, are receiving high interest as a biomaterial for biomedical and healthcare treatments, since they exert various interactions with tissues after surface modification with biochemicals such as peptides, proteins, and catechols. Herein, we report a BCNF-based skin adhesion system, wherein cell penetrating peptide (CPP)-conjugated BCNFs were employed to enhance the attraction to the skin under wet conditions. For this, we conjugated Bac7, a type of CPP, with the carboxylate of 2,2,6,6-tetramethylpiperidine-1-oxyl radical (TEMPO)-oxidized BCNFs. We showed that Bac7-conjugated BCNFs exhibited both hydrophobic and electrostatic interactions with the cell membrane, which eventually led to the remarkable adhesion against the skin surface. Furthermore, we demonstrated that such tailored skin attraction played a key role in improving skin water retention.

The self-renewal properties of human pluripotent stem cells (hPSCs) contribute to their efficacy in tissue regeneration applications yet increase the likelihood of teratoma formation, thereby limiting their clinical utility. To address this issue, we developed a tool to specifically target and neutralize undifferentiated hPSCs, thereby minimizing tumorigenicity risk without negatively affecting regenerated and somatic tissues. Specifically, we conjugated a monoclonal antibody (K6-1) previously generated in our laboratory against desmoglein 2 (Dsg2), which is highly differentially expressed in undifferentiated hPSCs versus somatic tissues, to the chemotherapeutic agent doxorubicin (DOX). The K6-1-DOX conjugates were selectively targeted and incorporated into Dsg2-positive hPSCs, leading to pH-dependent endosomal release and nuclear localization of DOX with subsequent cytotoxicity via an apoptotic caspase cascade. Conversely, Dsg2-negative fibroblasts showed minimal conjugate uptake or cytotoxicity, suggesting that K6-1-DOX treatment would yield few side effects owing to off-target effects. Selective removal of undifferentiated stem cells was also supported by in vivo studies using a mouse xenograft model, wherein hIgG-DOX- but not K6-1-DOX-pretreated-hPSC injection led to teratoma development. Together, these results validated the ability of the Dsg2-targeted antibody-anticancer drug conjugate to facilitate the safety of stem cell therapies.

Cellular senescence is associated with inflammation and the senescence-associated secretory phenotype (SASP) of secreted proteins. Vascular smooth muscle cell (VSMC) expressing the SASP contributes to chronic vascular inflammation, loss of vascular function, and the developments of age-related diseases. Although VSMC senescence is well recognized, the mechanism of VSMC senescence and inflammation has not been established. In this study, we aimed to determine whether prednisolone (PD) attenuates adriamycin (ADR)-induced VSMC senescence and inflammation through the SIRT1-AMPK signaling pathway. We found that PD inhibited ADR-induced VSMC senescence and inflammation response by decreasing p-NF-κB expression through the SIRT1-AMPK signaling pathway. In addition, Western blotting revealed PD not only increased SIRT1 expression but also increased the phosphorylation of AMPK at Ser485 in ADR-treated VSMC. Furthermore, siRNA-mediated downregulation or pharmacological inhibitions of SIRT1 or AMPK significantly augmented ADR-induced inflammatory response and senescence in VSMC despite PD treatment. In contrast, the overexpression of SIRT1 or constitutively active AMPKα (CA-AMPKα) attenuated cellular senescence and p-NF-κB expression. Taken together, the inhibition of p-NF-κB by PD through the SIRT1 and p-AMPK (Ser485) pathway suppressed VSMC senescence and inflammation. Collectively, our results suggest that anti-aging effects of PD are caused by reduced VSMC senescence and inflammation due to reciprocal regulation of the SIRT1/p-AMPK (Ser485) signaling pathway.

The kinase Aurora B forms the chromosomal passenger complex (CPC) together with Borealin, INCENP, and Survivin to mediate chromosome condensation, the correction of erroneous spindle-kinetochore attachments, and cytokinesis. Phosphorylation of histone H3 Thr3 by Haspin kinase and of histone H2A Thr120 by Bub1 concentrates the CPC at the centromere. However, how the CPC is recruited to chromosome arms upon mitotic entry is unknown. Here, we show that asymmetric dimethylation at Arg2 on histone H3 (H3R2me2a) by protein arginine methyltransferase 6 (PRMT6) recruits the CPC to chromosome arms and facilitates histone H3S10 phosphorylation by Aurora B for chromosome condensation. Furthermore, in vitro assays show that Aurora B preferentially binds to the H3 peptide containing H3R2me2a and phosphorylates H3S10. Our findings indicate that the long-awaited key histone mark for CPC recruitment onto mitotic chromosomes is H3R2me2a, which is indispensable for maintaining appropriate CPC levels in dynamic translocation throughout mitosis., The proteins of the chromosomal passenger complex help chromosomes condense before cell division, but how this complex arrives at chromosomes was not known. Here the authors show that PRMT6 methylates histone H3 to recruit the chromosomal passenger complex.

As silicon-based metal oxide semiconductor field effect transistors get closer to their scaling limit, the importance of resistive random-access memory devices increases due to their low power consumption, high endurance and retention performance, scalability, and fast switching speed. In the last couple of years, organic–inorganic lead halide perovskites have been used for resistive switching applications, where they outperformed conventional metal oxides in terms of large on/off ratio and low power consumption. However, there were scarce reports on lead-free perovskites for such applications. In this report, we prepared lead-free Au/A3Bi2I9/Pt/Ti/SiO2/Si (A is either Cs+ or Rb+) devices and tested their resistive switching characteristics. They showed a forming step prior to repeating switching, low operating voltage (0.09 V for Rb3Bi2I9 and 0.1 V for Cs3Bi2I9), large on/off ratio (>107), relatively high endurance (200 cycles for Rb3Bi2I9 and 400 cycles for Cs3Bi2I9 cycles), and high retention (1000 s)....

High-efficiency perovskite solar cells are generally fabricated by using highly pure (>99.99 %) PbI2 mixed with an organic iodide in polar aprotic solvents. However, the use of such an expensive chemical may impede progress toward large-scale industrial applications. Here, we report on the synthesis of perovskite powders by using inexpensive low-grade (99 %) PbI2 and on the photovoltaic performance of perovskite solar cells prepared from a powder-based single precursor. Pure APbI3 [A=methylammonium (MA) or formamidinium (FA)] perovskite powders were synthesized by treating low-grade PbI2 with MAI or FAI in acetonitrile at ambient temperature. The structural phase purity was confirmed by X-ray diffraction. The solar cell with a MAPbI3 film prepared from the synthesized perovskite powder demonstrated a power conversion efficiency (PCE) of 17.14 %, which is higher than the PCE of MAPbI3 films prepared by using both MAI and PbI2 as precursors (PCE=13.09 % for 99 % pure PbI2 and PCE=16.39 % for 99.9985 % pure PbI2 ). The synthesized powder showed better absorption and photoluminescence, which were responsible for the better photovoltaic performance. For the FAPbI3 powder, a solution with a yellow non-perovskite δ-FAPbI3 powder synthesized at room temperature was found to lead to a black perovskite film, whereas a solution with the black perovskite α-FAPbI3 powder synthesized at 150 °C was not transformed into a black perovskite film. The α↔δ transition between the powder and film was assumed to correlate with the difference in the iodoplumbates in the powder-dissolved solution. An average PCE of 17.21 % along with a smaller hysteresis [ΔPCE=PCEreverse -PCEforward )=1.53 %] was demonstrated from the perovskite solar cell prepared by using δ-FAPbI3 powder; this PCE is higher than the average PCE of 17.05 % with a larger hysteresis (ΔPCE=2.71 %) for a device based on a conventional precursor solution dissolving MAI with high-purity PbI2 . The smaller hysteresis was indicative of fewer defects in the resulting FAPbI3 film prepared by using the δ-FAPbI3 powder.

We developed a Tc-99m and TAMRA-labeled peptide, Tc-99m arginine-arginine-leucine (RRL) peptide (TAMRA-GHEG-ECG-RRL), to target tumor cells and evaluated the diagnostic performance of Tc-99m TAMRA-GHEG-ECG-RRL as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-RRL was synthesized using Fmoc solid-phase peptide synthesis. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with PC-3 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-RRL complexes were prepared in high yield (>96%). The Kd of Tc-99m TAMRA-GHEG-ECG-RRL determined by saturation binding was 41.7 ± 7.8 nM. Confocal microscopy images of PC-3 cells incubated with TAMRA-GHEG-ECG-RRL showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of RRL. Specific uptake of Tc-99m TAMRA-GHEG-ECG-RRL was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In conclusion, in vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-RRL in tumors. Tc-99m TAMRA-GHEG-ECG-RRL has potential as a dual-modality tumor imaging agent.

Currently, the most efficient perovskite solar cells (PSCs) mainly use planar and mesoporous titanium dioxide (TiO2) as an electron-transport layer (ETL). However, because of its intrinsic photocatalytic properties, TiO2 can decompose perovskite absorber and lead to poor stability under solar illumination (ultraviolet light). Herein, a simplified architectural ETL-free PSC with enhanced efficiency and outstanding photostability is produced by the facile deposition of a bathocuproine (BCP) interlayer. Power conversion efficiency of the ETL-free PSC improves from 15.56 to 19.07% after inserting the BCP layer, which is the highest efficiency reported for PSCs involving an ETL-free architecture, versus 19.03% for the n–i–p full device using TiO2 as an ETL. The BCP interlayer has been demonstrated to have several positive effects on the photovoltaic performances of devices, such as “modulation doping” of the perovskite layer, modification of FTO surface work function, and enhancing the charge-transfer efficien...

Organic–inorganic halide perovskite is believed to be a potential candidate for high efficiency solar cells because power conversion efficiency (PCE) was certified to be more than 22%. Nevertheless, mismatch of PCE due to current density (J)–voltage (V) hysteresis in perovskite solar cells is an obstacle to overcome. There has been much lively debate on the origin of J–V hysteresis; however, effective methodology to solve the hysteric problem has not been developed. Here we report a universal approach for hysteresis-free perovskite solar cells via defect engineering. A severe hysteresis observed from the normal mesoscopic structure employing TiO2 and spiro-MeOTAD is almost removed or does not exist upon doping the pure perovskites, CH3NH3PbI3 and HC(NH2)2PbI3, and the mixed cation/anion perovskites, FA0.85MA0.15PbI2.55Br0.45 and FA0.85MA0.1Cs0.05PbI2.7Br0.3, with potassium iodide. Substantial reductions in low-frequency capacitance and bulk trap density are measured from the KI-doped perovskite, which is ...

Reactive oxygen species (ROS)-responsive materials for the selective and sensitive electrochemical detection of cancer cells have been studied comprehensively, especially owing to the variable concentration of H2O2 in normal and tumor cells. In this report, we develop a real-time electrochemical sensor based on diselenide-functionalized dopamine-conjugated hyaluronic acid polymer dots (PD(HA/DP)-DiSe) nanoparticles coated on a substrate that could be used for selective tumor diagnosis by tuning the coated surface morphology. The hyaluronic acid-based cancer cell-targeted PD(HA/DP)-DiSe-coated surface demonstrates selectivity and sensitivity toward ROS because of the change in the optical fluorescence after treatment. Owing to cleavage of the Se-Se bond and the formation -Se-OH/-Se-OOH, the PD(HA/DP)-DiSe coated-surface is tuned from a sphere-like to a sheet-like form with smaller size changing the electronic impedance of the sensor. A real-time in vitro selective diagnosis conducts by connecting the sensor to the wireless system and produces an accurate result to distinguish different ratios of MDCK:MDA-MB-231 and MDCK:HeLa cells. Finally, the developed ROS-responsive sensor could specifically differentiate the cancer microenvironment, which is helpful for advanced and selective biomedical purposes.

A tumor microenvironment-responsive wireless strain-pressure hydrogel sensor based on pH-induced controllable nanoparticles was designed for cancer detection in vitro–in vivo model, with excellent ability to distinguish between cancer and normal cells. The pH-responsive nanoparticles (CD-PNB), comprising diol–diol crosslinked semiconducting carbon dots (CDs) and non-conductive polymer (PNB), are sensitive to acidic tumor microenvironments and play crucial role in demonstrating tumor-selective strain-pressure responses. Upon application of strain and pressure, CD-PNB@PVA hydrogel produced distinct electronic signals in the presence of cancer cells (HeLa, PC-3), exhibiting higher strain–pressure sensitivity compared to the normal cells (MDCK, CHO-K1). The strain and pressure gage factors for cancer-cell-treated CD-PNB@PVA hydrogel were found to be 0.7439 and 5.3052 kPa−1, which were higher than normal-cell-treated CD-PNB@PVA hydrogel (0.5009 and 4.2720 kPa−1). CD-PNB@PVA hydrogel demonstrated excellent response in tumor-bearing mice based on in situ and ex situ measurements, with no inflammation during hydrogel implantation. Moreover, wireless sensing system was used along with CD-PNB@PVA hydrogel to simplify monitoring process and obtain real-time conductivity and strain–pressure profiles on smartphone. Thus, this approach constructs a tumor microenvironment-responsive strain–pressure hydrogel sensor and presents potential for sensitive and selective tumor detection in point-of-care diagnostic applications.

A self-repairable and reusable self-powered electronic skin sensor is developed from NIR/pH-responsive polymer dot (PD) embedded hydrogel with amplified mechanical and electrochemical properties after self-healing. The pH/NIR-controlled mechanical, electrochemical and self-healing performance of the designed hydrogel is achieved by manipulating the hydrogen bond formation with tunable mobility from the PD components. The hydrogel formed at pH 7.4, after treatment with pH 10 and NIR-driven healing, the mechanical stretchability (585%), conductivity (6.8 mS cm−1), capacitance (184.2 mF cm−2), and gauge factor (1.09) was increased by 125%, 4.9 times, 37%, and 72%, respectively. Further, the hydrogel system was explored as a reusable physiological strain sensor which showed excellent strain sensitivity of 0.36 kPa−1 with remarkable repeatability of 12,000 stretching-bending operations over two cutting-healing cycles. The real-time pH/NIR-dependent amplified sensing performance is effectively monitored remotely by using a wireless connection via a smartphone. Additionally, the hydrogel-based supercapacitor was attached with a solar cell for a self-powered body sensor that works seamlessly under sunlight. The integrated system obtains enhanced energy storage upon healing, reaching an overall power conversion efficiency of 2.32%. The NIR/pH-driven durability, the reproducible amplified mechanical and electrical performance of the self-powered electronic skin can be efficiently used for detecting movements ranging from a subtle human wrist pulse to rough finger motions presenting their potential application in wearable human-health monitoring systems.

Cellular senescence is caused by a wide range of intracellular and extracellular stimuli and influences physiological functions, leading to the progression of age-related diseases. Many studies have shown that cellular senescence is related to phosphatase and tension homolog deleted on chromosome ten (PTEN) loss and mammalian target of rapamycin (mTOR) activation. Although it has been reported that mTOR complex 1 (mTORC1) is major anti-aging target in several cell types, the functions and mechanisms of mTOR complex 2 (mTORC2) during aging have not been elucidated in vascular smooth muscle cells (VSMCs). Therefore, the aim of this study was to reveal the relationship between PTEN and mTORC2 during VSMC senescence. We found adriamycin-induced VSMC senescence was accompanied by reduced PTEN protein expression and upregulation of the mTORC2-Akt (Ser 473) pathway and that fisetin treatment reduced VSMC senescence by increasing PTEN and decreasing mTORC2 protein levels. Furthermore, PTEN played a primary role in the anti-aging effect of fisetin, and fisetin-activated PTEN directly regulated the mTORC2-Akt (Ser 473) signaling pathway, and attenuated senescence phenotypes such as senescence-associated β-galactosidase (SA-β-gal) and the p53-p21 signaling pathway in VSMCs. In mouse aortas, fisetin delayed aging by regulating the PTEN-mTORC2-Akt (Ser473) signaling pathway. These results suggest PTEN and mTORC2 are associated with cellular senescence in VSMCs and that the mTORC2-Akt (Ser 473) signaling pathway be considered a new target for preventing senescence-related diseases.

Biosensor development for bacterial detection is critical to preventing infectious disease outbreaks caused by bacterial contamination. Recent studies have focused on colorimetric sensors, but high limit of detection (LOD) has restricted their application for sensitive bacterial detection. Here, we designed a reusable, sensitive smartphone-based electrochemical biosensor which uses electroconductive boronic acid-modified polymer dot (B-PD)-coated electrode to detect bacterial contamination. The pH-selective boronic acid in B-PD promotes binding between sensor and bacteria via increased diol-diol kinetics of boronic acid at pH 7.4. B-PD-coated electrodes can detect both gram-negative (E. coli) and gram-positive (S. aureus) bacteria by observing the conductivity change after attachment (101-107 CFU/mL), with high sensitivity, as indicated by low LOD (E. coli=100.8 CFU/mL, S. aureus=101 CFU/mL). The electronic signal from bacterial detection is transmitted to smartphone by connecting B-PD-coated electrode with wireless microcontroller, which allows for simple in-line monitoring. This biosensor demonstrated excellent performance in detecting bacteria in real environmental samples, along with good selectivity towards bacteria, even in the presence of interfering compounds. Moreover, by maintaining boronic acid-diol interaction, B-PD-coated electrode can be reused after applying pH shock (pH

Skin aging is a complex process and involves extrinsic and intrinsic processes with distinct characteristics. Understanding skin aging requires knowledge of the senescence of human dermal fibroblasts (HDFs) and the biological mechanisms involved in this process. However, the molecular mechanism responsible for the aging of HDFs is still not clear. Therefore, we investigated mechanisms of autophagy, inflammation, and cellular senescence by Western blotting, immunofluorescence, real-time PCR, and senescence-associated β-galactosidase (SA-β-gal) staining in senescent HDFs. We found SRT1720 inhibited the inductions of inflammatory cytokines and cellular senescence by deacetylating acetyl-NF-κB levels and enhancing levels of autophagy-associated proteins and SIRT1 in senescent HDFs. However, the NF-κB activator prostratin attenuated signals associated with autophagy, such as those of LC3-II and Beclin-1, but increased inflammatory cytokine levels and cellular senescence. Notably, the expression levels of SIRT1 and autophagy-associated proteins were higher in aged mice administered SRT1720 than in old mice, and SRT1720 also decreased levels of acetyl-NF-κB, inflammatory cytokines, and senescence markers, which was in accord with in vitro results. These findings support that SRT1720 acts as an anti-aging agent and inhibits the inductions of inflammatory cytokines and senescence by regulating the SIRT1/acetyl-NF-κB signaling pathway and activating autophagy in senescent HDFs.

We developed a Tc-99m and fluorescence-labeled peptide, Tc-99m TAMRA-GHEG-ECG-VAPG to target tumor cells and evaluated the diagnostic performance as a dual-modality imaging agent for tumor in a murine model. TAMRA-GHEG-ECG-VAPG was synthesized by using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-VAPG with Tc-99m was done by using ligand exchange via tartrate. Binding affinity and in vitro cellular uptake studies were performed. Gamma camera imaging, biodistribution, and ex vivo imaging studies were performed in murine models with SW620 tumors. Tumor tissue slides were prepared and analyzed with immunohistochemistry by using confocal microscopy. After radiolabeling procedures with Tc-99m, Tc-99m TAMRA-GHEG-ECG-VAPG complexes were prepared in high yield (>96%). The Kd of Tc-99m TAMRA-GHEG-ECG-VAPG determined by saturation binding was 16.8 ± 3.6 nM. Confocal microscopy images of SW620 cells incubated with TAMRA-GHEG-ECG-VAPG showed strong fluorescence in the cytoplasm. Gamma camera imaging revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumors. Tumor uptake was effectively blocked by the coinjection of an excess concentration of VAPG. Specific uptake of Tc-99m TAMRA-GHEG-ECG-VAPG was confirmed by biodistribution, ex vivo imaging, and immunohistochemistry stain studies. In vivo and in vitro studies revealed substantial uptake of Tc-99m TAMRA-GHEG-ECG-VAPG in tumor cells. Tc-99m TAMRA-GHEG-ECG-VAPG has potential as a dual-modality tumor imaging agent.

Cobalt is an essential metal that is required for the generation of vitamin B12. However, exposure to excess cobalt for a prolonged period may adversely affect the human body, causing hepatotoxicity, pulmonary fibrosis, and neurotoxicity. 3-Aminotriazole (3-AT) is a catalase inhibitor that is often used to examine the cellular role of catalase. In the present study, we showed that 3-AT treatment significantly reduced cobalt (II) chloride (CoCl2)-induced cytotoxicity in HepG2 cells by suppressing the expression and activation of apoptotic markers, caspase-3 and poly adenosine diphosphate ribose polymerase (PARP). Mechanistically, 3-AT treatment attenuated CoCl2-induced accumulation of reactive oxygen species (ROS) and expression of RO S-responsive genes. Furthermore, the CoCl2-induced mitochondrial membrane potential (Δψm) shift and mitochondrial damage were attenuated by 3-AT. Taken together, these findings suggest that 3-AT alleviates CoCl2-induced cytotoxicity by reducing ROS generation and protecting against mitochondrial damage.

Chemical interaction at a heterojunction interface induced by an appropriate chemical linker is of crucial importance for high efficiency, hysteresis-less, and stable perovskite solar cells (PSCs). Effective interface engineering in PSCs is reported via a multifunctional chemical linker of 4-imidazoleacetic acid hydrochloride (ImAcHCl) that can provide a chemical bridge between SnO2 and perovskite through an ester bond with SnO2 via esterification reaction and an electrostatic interaction with perovskite via imidazolium cation in ImAcHCl and iodide anion in perovskite. In addition, the chloride anion in ImAcHCl plays a role in the improvement of crystallinity of perovskite film crystallinity. The introduction of ImAcHCl onto SnO2 realigns the positions of the conduction and valence bands upwards, reduces nonradiative recombination, and improves carrier life time. As a consequence, average power conversion efficiency (PCE) is increased from 18.60% ± 0.50% to 20.22% ± 0.34% before and after surface modification, respectively, which mainly results from an enhanced voltage from 1.084 ± 0.012 V to 1.143 ± 0.009 V. The best PCE of 21% is achieved by 0.1 mg mL-1 ImAcHCl treatment, along with negligible hysteresis. Moreover, an unencapsulated device with ImAcHCl-modified SnO2 shows much better thermal and moisture stability than unmodified SnO2 .

Bisphenol A [BPA, 2,2-bis-(4-hydroxyphenyl)propane] is one of the most prevalent synthetic environmental estrogens; as an endocrine disruptor, it is associated with endocrine-related cancers including breast, ovarian, and prostate. However, the mechanisms by which BPA contributes to carcinogenesis are unclear. This study aims to clarify its toxic effects on mitotic cells and investigate the molecular mechanism. In vitro effects of BPA on mitotic progression were examined by performing experiments on HeLa cells. Proteins involved in mitotic processes were detected by Western blot, live cell imaging, and immunofluorescence staining. The results showed that BPA increased chromosomal instability by perturbing mitotic processes such as bipolar spindle formation and spindle microtubule attachment to the kinetochore. BPA prolonged mitotic progression by disturbing spindle attachment and concomitant activating spindle assembly checkpoint (SAC). Mechanistically, BPA interfered proper localization of HURP to the proximal ends of spindle microtubules, Kif2a to the minus ends of spindle microtubules, and TPX2 on the mitotic spindle. This mislocalization of microtubule associated proteins (MAPs) is postulated to lead to spindle attachment failure. Furthermore, BPA caused multipolar spindle by inducing centriole overduplication and premature disengagement. Although BPA acts as an estrogen receptor (ER) agonist, mitotic defects caused by BPA occurred in an ER-independent manner. Our findings indicate that BPA may stimulate carcinogenesis not only by acting as an endocrine disruptor but also by increasing chromosomal instability during mitosis.

e16578 Background: Cabozantinib is a multitarget tyrosine kinase inhibitor and getting attention in these days through its combination with immune checkpoint inhibitors. In this article, we analyze the efficacy of cabozantinib in patients with metastatic ccRCC in Korean who had progression after 1 or more VEGFR TKI therapies. Methods: Seventy-five patients from Jan.2019 to Dec. 2021 at Yonsei Cancer Center who had received cabozantinib treatment in second to fourth line of therapy were retrospectively reviewed. The primary endpoint was PFS. The secondary outcomes were the response rate, disease control rate (DCR), and OS. The evaluable subjects for efficacy were those who had at least one response evaluation. Results: Among 75 patients, 57 (76.0%) were male and median age was 59 years (range 33-81). Median follow up time was 12.1 months. There were 22 (29.3%) patients of second line, 38 (50.7%) of third line and 15 (20.0%) of fourth line of treatment. Median PFS was 5.6 months (95% CI, 4.6-6.6). Median OS was 13.6 months (95% CI, 5.0-22.2). The PFS based on the line of treatment was 4.7 months for second line, 5.6 months for third line and 12.0 months for 4th line. Proportion of patients who were previously treated with ICI was different between treatment line groups and showed increasing trend toward later line; 13.6% of second line, 31.6% of third line, and 66.7% of fourth line, respectively. The objective response rate was 8.0% with 6 patients of partial response. The DCR was 69.3%. The major toxicities were similar with the western population and most of them were less than CTCAE grade 3. Most common grade 3 or 4 AEs were anemia, hand-foot syndrome, fatigue, and stomatitis. There were no grade 5 AEs. Conclusions: Our results demonstrate that cabozantinib is an effective treatment option after first line TKI in Korean ccRCC patients with manageable toxicities. Notably, its tolerability in the advanced line of treatment and synergy with ICIs are suggested in this study despite heterogeneous patients of real world setting. This is the first real world data with cabozantinib in Asian patients.

Simple and rapid simultaneous detection and killing of bacteria is crucial for addressing health issues related to pathogenic bacteria. Here, we describe the design of a wireless electrochemical and luminescent sensor for bacteria detection using surface-coatable electrochemically generated fluorescent carbon dots (FCDs), which were synthesized from a cationic polymer. The FCDs were further integrated with near-infrared (NIR)-responsive cesium tungsten oxide (CsWO3) by utilizing catechol moieties on the FCD surface for photothermal-based antibacterial activity. The CsWO3–FCD nanohybrids showed strong fluorescence emission, which was quenched due to interaction between the cationic FCD surface and the anionic bacterial cell wall. This interaction could also be observed electrochemically according to the change in resistance values before and after binding with bacteria. In this study, the limit of detection (LOD) was determined at 70 CFU/mL for Escherichia coli and 131 CFU/mL for Staphylococcus aureus using the luminescent method and

Adenovirus infections are associated with respiratory (especially upper respiratory) infection and gastrointestinal disease and occur primarily in infants and children. Although rare in adults, severe lower respiratory adenovirus infections including pneumonia are reported in specific populations, such as military recruits and immunocompromised patients. Antiviral treatment is challenging due to limited clinical experience and lack of well-controlled randomized trials. Several previously reported cases of adenoviral pneumonia showed promising efficacy of cidofovir. However, few reports discussed the efficacy of cidofovir in acute respiratory distress syndrome (ARDS). We experienced 3 cases of adenoviral pneumonia associated with ARDS and treated with cidofovir and respiratory support, including extracorporeal membrane oxygenation (ECMO). All 3 patients showed a positive clinical response to cidofovir and survival at 28 days. Cidofovir with early ECMO therapy may be a therapeutic option in adenoviral ARDS. A literature review identified 15 cases of adenovirus pneumonia associated with ARDS.

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αV β3 . In the present study, we successfully developed a TAMRA-GHEG-ECG-SDV peptide labeled with both Tc-99 m and TAMRA to target the integrin αV β3 of tumor cells; furthermore, we evaluated the diagnostic performance of Tc-99 m TAMRA-GHEG-ECG-SDV as a dual-modality imaging agent for tumor of the murine model. TAMRA-GHEG-ECG-SDV was synthesized using Fmoc solid-phase peptide synthesis. Radiolabeling of TAMRA-GHEG-ECG-SDV with Tc-99 m was done using ligand exchange methods. Labeling stability and cytotoxicity studies were performed. Gamma camera imaging, biodistribution and ex vivo imaging studies were performed in murine models with HT-1080 and HT-29 tumors. A tumor tissue slide was prepared and analyzed using confocal microscopy. After radiolabeling procedures with Tc-99 m, the Tc-99 m TAMRA-GHEG-ECG-SDV complexes were prepared in high yield (>99%). In the gamma camera imaging study, a substantial uptake of Tc-99 m TAMRA-GHEG-ECG-SDV into HT-1080 tumor (integrin αV β3 positive) and low uptake of Tc-99 m TAMRA-GHEG-ECG-SDV into HT-29 tumor (integrin αV β3 negative) were demonstrated. A competition study revealed that HT-1080 tumor uptake was effectively blocked by the co-injection of an excess concentration of SDV. Specific uptake of Tc-99 m TAMRA-GHEG-ECG-SDV was confirmed by biodistribution, ex vivo imaging and confocal microscopy studies. Our in vivo and in vitro studies revealed substantial uptake of Tc-99 m TAMRA-GHEG-ECG-SDV in the integrin αV β3 -positive tumor. Tc-99 m TAMRA-GHEG-ECG-SDV could be a good candidate for a dual-modality imaging agent targeting tumor angiogenesis. Copyright © 2016 John Wiley & Sons, Ltd.

Aging is one of the risk factors for the development of cardiovascular diseases. During the progression of cellular senescence, cells enter a state of irreversible growth arrest and display resistance to apoptosis. As a flavonoid, quercetin induces apoptosis in various cells. Accordingly, we investigated the relationship between quercetin-induced apoptosis and the inhibition of cellular senescence, and determined the mechanism of oxidative stress-induced vascular smooth muscle cell (VSMC) senescence. In cultured VSMCs, hydrogen peroxide (H2O2) dose-dependently induced senescence, which was associated with increased numbers of senescence-associated β-galactosidase-positive cells, decreased expression of SMP30, and activation of p53-p21 and p16 pathways. Along with senescence, expression of the anti-apoptotic protein Bcl-2 was observed to increase and the levels of proteins related to the apoptosis pathway were observed to decrease. Quercetin induced apoptosis through the activation of AMP-activated protein kinase. This action led to the alleviation of oxidative stress-induced VSMC senescence. Furthermore, the inhibition of AMPK activation with compound C and siRNA inhibited apoptosis and aggravated VSMC senescence by reversing p53-p21 and p16 pathways. These results suggest that senescent VSMCs are resistant to apoptosis and quercetin-induced apoptosis attenuated the oxidative stress-induced senescence through activation of AMPK. Therefore, induction of apoptosis by polyphenols such as quercetin may be worthy of attention for its anti-aging effects.

In general, expression of transglutaminase 2 (TGase 2) is upregulated in renal cell carcinoma (RCC), resulting in p53 instability. Previous studies show that TGase 2 binds to p53 and transports it to the autophagosome. Knockdown or inhibition of TGase 2 in RCC induces p53-mediated apoptosis. Here, we screened a chemical library for TGase 2 inhibitors and identified streptonigrin as a potential therapeutic compound for RCC. Surface plasmon resonance and mass spectroscopy were used to measure streptonigrin binding to TGase 2. Mass spectrometry analysis revealed that streptonigrin binds to the N-terminus of TGase 2 (amino acids 95&ndash, 116), which is associated with inhibition of TGase 2 activity in vitro and with p53 stabilization in RCC. The anti-cancer effects of streptonigrin on RCC cell lines were demonstrated in cell proliferation and cell death assays. In addition, a single dose of streptonigrin (0.2 mg/kg) showed marked anti-tumor effects in a preclinical RCC model by stabilizing p53. Inhibition of TGase 2 using streptonigrin increased p53 stability, which resulted in p53-mediated apoptosis of RCC. Thus, targeting TGase 2 may be a new therapeutic approach to RCC.

Surface passivation of perovskite grains is one of the promising methods to reduce recombination and improve stability of perovskite solar cells (PSCs). We herein report the effect of a melaminium iodide additive on the photovoltaic performance of PSCs based on (FAPbI3)0.875(CsPbBr3)0.125 perovskite. Cyclic −C═N– and primary amine in melamine are a good hydrogen bond acceptor and Lewis base, which can interact with both the organic cation and Lewis acidic lead iodide in the perovskite film. Melaminium iodide is synthesized and added to the precursor solution, which is directly spin-coated to form the perovskite film. The presence of melaminium iodide additive reduces the trap density from 1.02 × 1016 to 0.645 × 1016 cm–3, which leads to the reduction of nonradiative recombination and thereby improving the mean open-circuit voltage and the fill factor from 1.054 to 1.095 V and from 0.693 to 0.725 V, receptively. In addition, photocurrent–voltage hysteresis is reduced by the melaminium iodide additive, whic...

Previously we have demonstrated transglutaminase 2 (TGase 2) inhibition abrogated renal cell carcinoma (RCC) using GK921 (3-(phenylethynyl)-2-(2-(pyridin-2-yl)ethoxy)pyrido[3,2-b]pyrazine), although the mechanism of TGase 2 inhibition remains unsolved. Recently, we found that the increase of TGase 2 expression is required for p53 depletion in RCC by transporting the TGase 2 (1-139 a.a)-p53 complex to the autophagosome, through TGase 2 (472-687 a.a) binding p62. In this study, mass analysis revealed that GK921 bound to the N terminus of TGase 2 (81-116 a.a), which stabilized p53 by blocking TGase 2 binding. This suggests that RCC survival can be stopped by p53-induced cell death through blocking the p53-TGase 2 complex formation using GK921. Although GK921 does not bind to the active site of TGase 2, GK921 binding to the N terminus of TGase 2 also inactivated TGase 2 activity through acceleration of non-covalent self-polymerization of TGase 2 via conformational change. This suggests that TGase 2 has an allosteric binding site (81-116 a.a) which changes the conformation of TGase 2 enough to accelerate inactivation through self-polymer formation.

경북대학교 식품공학부 및 식품생물산업연구소Imported Valencia oranges were evaluated to determine the relationship between the fruit size and its quality. The orange size was classified into three groups on a commercial basis: small (140~160 g/113±5 fruit/box), medium (190~220 g/88±5 fruit/box), and large (250~280 g/72±5 fruit/box). The physicochemical and sensory properties were analyzed to evaluate the orange quality. No significant difference in the peel thickness and flesh ratio was detected across the fruit sizes. The juice yield of the medium-sized orange and the TSS/TA ratios of the medium-sized and large oranges showed the highest value, respectively (p

Herein, we describe the fabrication and characterization of carbonized disulfide core-crosslinked polymer dots with pH-cleavable colorimetric nanosensors, based on diol dye-conjugated fluorescent polymer dots (L-PD), for reduction-triggered paclitaxel (PTX) release during fluorescence imaging-guided chemotherapy of tumors. L-PD were loaded with PTX (PTX loaded L-PD), via &pi, &ndash, &pi, stackings or hydrophobic interactions, for selective theragnosis by enhanced release of PTX after the cleavage of disulfide bonds by high concentration of glutathione (GSH) in a tumor. The nano-hybrid system showed fluorescence quenching behavior with less than 2% of PTX released under physiological conditions. However, in a tumor microenvironment, the fluorescence recovered at an acidic-pH, and PTX (approximately 100% of the drug release) was released efficiently out of the matrix by reduction caused by the GSH level in the tumor cells, which improved the effectiveness of the cancer treatment. Therefore, the colorimetric nanosensor showed promising potential in distinguishing between normal and cancerous tissues depending on the surrounding pH and GSH concentrations so that PTX can be selectively delivered into cancer cells for improved cancer diagnosis and chemotherapy.

A novel aporphine alkaloid was isolated from the leaves of Epimedium koreanum Nakai during activity-guided fractionation in search of compounds with an anticholinesterase activity. The structure of the new compound was assigned as 1,10-methoxy-7-hydroxy-aporphine (1), which we have named epimediphine. Unambiguous (1)H-NMR and (13)C-NMR data for epimediphine are described. Epimediphine inhibited an acetylcholinesterase (AchE) activity in a dose-dependent manner with an IC50 value of 3.1 µM. Meanwhile, tacrine, dehydroevodiamine and physostigmine, which are therapeutic drugs or candidates for AD, exhibited an anti-AchE activity with IC50 values of 0.4, 37.9 and 0.12 µM, respectively.

The serine-aspartic acid-valine (SDV) peptide binds specifically to integrin αvβ3. We developed a Tc-99m and TAMRA labeled peptide, Tc-99m SDV-ECG-K-TAMRA for multimodal imaging of angiogenesis. Tc-99m SDV-ECG-K-TAMRA was prepared in high yield (>96%) and showed low cytotoxicity. Tc-99m tetrofosmin images 1 week after operation, revealed significantly decreased perfusion of the ischemic hindlimb, and the perfusion recovered gradually for 4 weeks. In contrast, Tc-99m SDV-ECG-K-TAMRA uptake was maximal 1 week after the operation (ischemic-to-non-ischemic uptake ratio =5.03±1.01) and decreased gradually. The ischemic-to-non-ischemic ratio of Tc-99m SDV-ECG-K-TAMRA and Tc-99m tetrofosmin was strongly negatively correlated (r =-0.94). A postmortem analysis revealed increased angiogenesis markers and uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Our in vivo and in vitro studies revealed substantial uptake of Tc-99m SDV-ECG-K-TAMRA by ischemic tissue. Tc-99m SDV-ECG-K-TAMRA could be a good candidate dual-modality imaging agent to assess angiogenesis.

Wild grape extract (WGE) was added into hwajeon at different concentrations (0, 5, 15, 30, 50% of water). The resulting hwajeon were analyzed for their physicochemical and sensory properties. With increasing concentrations of WGE, the pH of dough and hwajeon decreased, and their degrees brix and color intensity increased, presumably due to the presence of tartaric acid, sugar, and anthocyanin in the WGE. The WGE-enriched hwajeon showed higher hardness, gumminess, and chewiness than control hwajeon, which might have been because the sugar and tartaric acid in the WGE partially inhibited starch gelatinization during heat processing. Nevertheless, all the sensory properties and preference were higher in WGE-enriched hwajeon than controls, which could be partially attributed to the fact of that the WGE-enriched hwajeon retained relatively higher moisture. It is suggested that WGE-enriched hwajeon with high preference could be prepared without loss of hwajeon quality.

Crystalline cuprous oxide (Cu2O) particles were successfully deposited on poly(3,4-ethylenedioxythiophene) [PEDOT] coated indium tin oxide (ITO) glass. PEDOT film was first prepared on ITO glass by electrochemical polymerization. Crystalline Cu2O particles were then deposited on the PEDOT film by applying various electrochemical synthesis methods using a copper sulfate precursor. The effects of applied electrochemical methods on the compositions, grain sizes and shapes, and surface morphologies of the electrodeposited films were investigated. The micro structures of Cu2O particles were confirmed by scanning electron microscopy (SEM) and X-ray diffraction (XRD). When the cyclic voltammetry (CV) and chronoamperometry (CA) were applied, fine Cu2O particles of cubic and pyramidal phase were formed, respectively. However, bare ITO electrode was used, metallic copper particle was obtained. It shall be assumed that PEDOT might act as a buffer layer in electrochemical reduction of cuprous ion. The details of PEDOT behavior will be the topic of future studies.

A simulated moving bed (SMB) technology was applied to the separation of homoharringtonine (HHT) and harringtonine (HT), which were known to have the potentiality of being used as anti-cancer agents. First, a series of pulse injection experiments were performed for estimation of the adsorption isotherm and mass-transfer parameters of HHT and HT. The estimated parameters were utilised in the SMB optimisation tool based on the standing wave design method. From the optimisation tool prepared, the SMB operating parameters (zone flow rates and step time) that led to the highest throughput were obtained under the constraints of product purities (=99.0%) and pressure drop (≤1000 psi). Such an optimisation work was then extended to determine an optimal size of the adsorbent particle for the SMB of interest. The results showed that a particle size of 29 µm was the optimal one for maximising the SMB throughput under the conditions that the column configuration was 2–2–2–2 and the length of each column was 25 cm. If the SMB had the particle size other than 29 µm, its throughput was limited by either the maximum operating pressure or the mass-transfer efficiency. Finally, an efficient procedure of removing a mobile-phase additive (ammonium formate) from the product stream of the aforementioned SMB system was developed using a liquid–liquid extraction (LLE) technique. From the results of this study, it was confirmed that the SMB process coupled with a LLE procedure could be highly effective in separating HHT and HT with high throughout and high purity. Une technologie de lit mobile simule (LMS) a ete appliquee a la separation de l'homoharringtonine (HHT) et l'harringtonine (HT), dont on sait qu'ils ont le potentiel d'etre utilises comme agents anticancereux. D'abord, une serie d'experiences d'injection intermittente a ete realisee pour estimer l'isotherme d'adsorption et les parametres de transfert de masse de l'HHT et de l'HT. Les parametres estimes ont ete utilises dans l'outil d'optimisation du LMS fonde sur la methode de conception de l'onde stationnaire. Pour l'outil d'optimisation prepare, les parametres de fonctionnement du LMS (debits de zone et temps de l'etape) qui ont mene au plus grand debit ont ete obtenus dans les contraintes des puretes du produit (= 99,0%) et de la perte de charge (≤1000 lb/po2). Un tel travail d'optimisation a ensuite ete prolonge pour determiner une taille optimale de la particule adsorbante pour le LMS d'interet. Les resultats ont indique qu'une taille de particule de 29 µm etait la taille optimale pour maximiser le debit du LMS sous les conditions que la configuration de la colonne etait 2–2–2–2 et la longueur de chaque colonne etait de 25 cm. Si le LMS presentait une taille de particule autre que 29 µm, son debit etait limite par soit la pression de fonctionnement maximale ou l'efficacite du transfert de masse. Enfin, une procedure efficace de retrait d'un additif de phase mobile (formiate d'ammonium) du produit du systeme de LMS susmentionne a ete creee a l'aide d'une technique d'extraction liquide-liquide. A partir des resultats de cette etude, on a confirme que le processus du LMS associe a une procedure d'extraction liquide-liquide pourrait etre tres efficace pour separer l'HHT et l'HT avec un debit eleve et une purete elevee.

Composites of poly(3,4-ethylenedioxythiophene) (PEDOT) and Ag particles were prepared by electrochemical polymerization of 3,4-ethylenedioxythiophene (EDOT) and the simultaneous electrochemical reduction of AgNO3 in the presence of poly(vinyl pyrrolidone) (PVP) as a stabilizer. The formation of Ag particles with PVP of various molecular weights and an electrochemical method was investigated. When the high PVP molecular weight was added to the Ag/PEDOT film, the average size of the Ag particles was high. Homogenous spherical Ag particles were observed when cyclic voltammetry was used in the reaction system, whereas chronoamperometry revealed aggregated Ag particles. UV-visible spectroscopy revealed the synchronized formation of Ag particles and PEDOT. The morphology and dispersion of the Ag particles in PEDOT were characterized by scanning electron microscopy. These results suggest that well dispersed homogenous Ag particles can be obtained by applying the proper electrochemical methods or by selecting the optimum PVP molecular weight.

Interface engineering to form an interlayer via ion exchange reaction is reported. A FA0.88 Cs0.12 PbI3 formamidinium (FA) perovskite layer is first prepared, then FAPF6 solution with different concentrations is spin-coated on top of the perovskite film, which leads to a partial substitution of iodide by PF6- ion. The second phase with nominal composition of FA0.88 Cs0.12 PbI3-x (PF6 )x is grown at the grain boundary, which has island morphology and its size depends on the FAPF6 solution concentration. The lattice is expanded and bandgap is reduced due to inclusion of larger PF6- ions. The power conversion efficiency (PCE) is significantly enhanced from 17.8% to 19.3% as a consequence of improved fill factor and open-circuit voltage (Voc ). In addition, current-voltage hysteresis is reduced. Post-treatment with FAPF6 reduces defect density and enhances carrier lifetime, which is responsible for the improved photovoltaic performance and reduced hysteresis. The unencapsulated device with post-treated perovskite film demonstrates better stability than the pristine perovskite, where the initial PCE retains over 80% after 528 h exposure under relative humidity of around 50-70% in the dark and 92% after 360 h under one sun illumination.

Fractional precipitation based on the difference in solubility of crude paclitaxel dissolved in methanol, to which distilled water must be added, is the most effective method for the pre-purification of paclitaxel. In this study, the effect of the distilled water feeding and mixing method on the efficiency of fractional precipitation and the formation of paclitaxel precipitate were evaluated. When the distilled water was added all at once, the highest purity (∼57.0%) and yield (∼81.0%) were obtained, and a spherical precipitate was formed by the clustering of crystal branches. On the other hand, when the distilled water was added intermittently in several aliquots, the purity and yield tended to decrease with increasing number of additions, and the precipitate took the form of a cross or pentagon with less clustering of branches. Not mixing after the addition of distilled water resulted in high purity (∼57.0%) and the formation of a spherical precipitate that showed increased branching around the nucleus over time. In contrast, when the sample was mixed intermittently after adding distilled water, paclitaxel was obtained in high yield (∼99.7%). Continuously mixing the sample after adding distilled water, however, caused the precipitate crystals to be broken into smaller pieces.