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Parathyroid hormone (PTH) is a hormone that plays a critical role in bone remodeling because it regulates the calcium levels. Either higher or lower than normal range of PTH release can cause serious metabolic disorders such as hyperparathyroidism or hypoparathyroidism. Therefore, the demand of highly sensitive monitoring sensor of PTH is on the rise. However, due to its presence of small size and low concentration in serum, the monitoring of a small change of PTH level is extremely difficult. In this article, we suggested the fabrication of europium complex doped nanoparticles conjugated with PTH antibodies for the sensitive fluorescence monitoring of PTH. For the synthesis of europium complex, 4,4,4-trifluoro-1-(2-naphthyl)-1,3-butanedione (NTA) and trioctylphosphine oxide (TOPO) are used to encapsulate europium. The amphiphilic polymer, polyvinylpyrrolidone (PVP), was applied to hydrophobic europium complex, and then silica shell was synthesized on the complex. Using the europium complex doped silica nanoparticles, we could obtain approximately 4.24-fold enhanced fluorescence in low levels of PTH in PBS, when compared to the conventional enzyme-linked immunosorbent assay (ELISA). In addition, we could obtain the sensitive PTH immunoassay in PTH spiked serum with high selectivity.

A new class of bidentate ligands was prepared by a modular approach involving Rh-catalyzed C-H annulation reactions. The resulting conformationally constrained ligands enabled the Pd-catalyzed C-H alkenylation at electron-rich and sterically less hindered positions of electron-rich arenes while promoting the facile oxidation of Pd(0) intermediates by oxygen. This newly introduced ligand class is complementary to the ligands developed for Pd-catalyzed oxidative reactions and may find broad application in transition-metal-catalyzed reactions.

In this study, organic strip, particle removal efficiency and wettability were investigated at different mixing concentrations of diluted Sulfuric-Peroxide-HF (DSP+) solutions with and without the addition of IPA. Organic strip evaluation was carried out with KrF photoresist (PR), and the strip rate was increased rapidly with the increase in H2SO4 concentration mixed with DI water (DIW). The effects of H2O2 and IPA addition on diluted H2SO4 were observed below 30 vol% of H2SO4. The thickness of PR was increased with the addition of H2O2 to the solutions and the strip rate was increased when IPA was added. Silica particles were used to evaluate particle removal efficiency. The concentration of HF was the predominant factor of increasing PRE, and the addition of H2SO4 and H2O2 assisted in obtaining high PRE, while IPA addition reduced PRE. Decreasing of contact angle was observed with an increase of IPA addition to DSP+ solutions, and improved wettability of DSP+ solutions was expected to effectively clean particles in high-aspect-ratio (HAR) contact holes.

This study aimed to evaluate the efficacy and safety of transplantation with human corneal limbal epithelial (HCLE) cell sheets cultured on carboxymethyl cellulose (CMC)-dopamine (DA)-coated substrates and harvested via enzymatic digestion of CMC with cellulase in a rabbit animal model of limbal stem cell deficiency (LSCD). Synthesized CMC-DA was pretreated onto the surface of culture plates. Then, HCLE cells were cultured on precoated CMC-DA and HCLE cell sheets were harvested using cellulase-containing cell culture medium. HCLE cell sheets were evaluated using a live/dead assay, histological examination, and immunofluorescence staining. For in vivo assessment, HCLE cell sheets were transplanted in a rabbit model of LSCD for 2 weeks to determine the effectiveness of the repair. Primary culture of HCLE cells stained positively for p63, cytokeratin (CK)15, and CK12. HCLE cell sheets were generated with a well-preserved morphology and transparency ranging in size from 15 to 19 mm after cellulase-assisted cell sheet generation. HCLE cell sheets uniformly stained positively for human mitochondria, p63, CK15, CK12, CK3/2p, and zonula occludens (ZO)-1. HCLE cell sheet transplantation in a rabbit model of LSCD improved the corneal opacity and neovascularization scores. Transplanted HCLE cell sheets stained positively for p63 and CK12. Transplantation of HCLE cell sheets harvested on CMC-DA coating combined with cellulase is a safe and efficient procedure for corneal epithelial regeneration in a rabbit model of LSCD. This system could enable a promising strategy to regenerate corneal epithelium by transplantation in ocular surface disorders.

There is great interest in the enhancement of isoflavones as one of the functional ingredients in soybean. This study aimed to investigate the effects of changes in the ecological environment over different planting times on isoflavone content. A total of 28 Korean soybean cultivars were grown at different planting times in late May, mid-June, and early July and their isoflavone content was measured over 2 years (2017 and 2018). Analyses of variance revealed significant effects of genotypes, planting times, years, and their interactions on isoflavone content. The average content of total isoflavone, as well as its component groups of malonylglucoside and aglycon, increased significantly as the seed planting time was delayed from late May to early July. The accumulation of each isoflavone component varied with changes in the planting time. The isoflavone content of the soybean cultivars for soy-sprout and soy-paste and tofu were higher for plantings in early July than for those in late May and/or mid-June, except for the black soybean cultivars. Despite significant correlations of the isoflavone content of the 28 cultivars among the three planting times, the responses of individual cultivars varied in isoflavone content by planting time. When planting was delayed, the time to flowering and maturity was also delayed and the number of days of growth from planting or flowering to maturity decreased; however, this was not related to isoflavone content. When planting was delayed, the temperature during the ripening period from flowering to maturity was lower, which was inversely related to the isoflavone content.

This review describes recent advances in transition-metal-catalyzed C-H functionalization reactions of pyrazoles to form new C-C and C-heteroatom bonds on the pyrazole ring. In contrast to traditional cross-coupling reactions that require pre-functionalized pyrazoles, direct C-H functionalization reactions provide access to a wide range of functionalized pyrazoles in a single step. Various strategies are presented and the efficiency and regioselectivity are described with respect to the types of functional groups that are installed.

An efficient protocol for the hydroboration of imines is reported. Lithium halide salts are effective catalysts to convert aldimines and ketimines to their corresponding amines. Here, we report excellent isolated yield of secondary amines (>95%) using 3 mol% lithium bromide in THF at room temperature. In addition, DFT calculations for a plausible reaction pathway are reported.

Graphical abstract, Highlights • Megasonic cleaning performance of Si wafer & polysilicon line pattern is evaluated. • Role of SDS surfactant in the presence of DIW and H2-DIW megasonic cleaning studied. • SDS concentration is found to be a playing key role in obtaining optimized performance. • Bubble dynamics in the megasonic standing wave field are observed using HSC. • Clustering and population density of bubbles is a key factor to enhances the PRE., Acoustic cavitation is used for megasonic cleaning in the semiconductor industry, especially of wafers with fragile pattern structures. Control of transient cavitation is necessary to achieve high particle removal efficiency (PRE) and low pattern damage (PD). In this study, the cleaning performance of solutions with different concentrations of dissolved gas (H2) and anionic surfactant (sodium dodecyl sulfate, SDS) in DIW (DI water) on silicon (Si) wafers was evaluated in terms of PRE and PD. When only DIW was used, PRE was low and PD was high. An increase in dissolved H2 gas concentration in DIW increased PRE; however, PD also increased accordingly. Thus, we investigated the megasonic cleaning performance of DIW and H2-DIW solutions with various concentrations of the anionic surfactant, SDS. At 20 ppm SDS in DIW, PRE reached a maximum value and then decreased with increasing concentration of SDS. PRE decreased slightly with increasing concentrations of SDS surfactant when dissolved in H2-DIW. Furthermore, PD decreased significantly with increasing concentrations of SDS surfactant in both DIW and H2-DIW cases. A high-speed camera setup was introduced to analyze bubble dynamics under a 0.96 MHz ultrasonic field. Coalescence, agglomeration, and the population of multi-bubbles affected the PRE and PD of silicon wafers differently in the presence of SDS surfactant. We developed a hypothesis to explain the change in bubble characteristics under different chemical environmental conditions.

Complementary to Catellani-type reactions and 1:1 coupling of six-membered halo(hetero)arenes and norbornene (NBE) derivatives, Pd-catalyzed 1:2 coupling of five-membered haloheteroarenes with NBEs...

This study presents a quick and reliable approach to the chemoselective partial reduction of tertiary amides to aldehydes in the presence of readily reducible ester groups using commercial DIBALH reagent. Moreover, the developed method was also extended to multi-functional molecules bearing ester moieties, which were successfully chemoselectively reduced to the corresponding aldehydes.

We fabricated the various nano-aperture plasmonic platforms on pyramid and on the flat membranes. The nano-apertures such as circular nanopore and nanoslit pores were fabricated. Optical characteristics were found to be dependent upon the aperture size and the sample thickness. The enhanced optical emission spectra with decreased aperture sizes have been observed due to spp-mediated emission at ~ 500 nm. In addition, the broad emission spectra in the visible and infrared region from the nanoslit array are obtained. The fabricated Au nano-aperture platform with a few nano-meter openings can be utilized as a single-molecule sensor.

In this study, we developed the portable chemiluminescence (CL)-based lateral flow assay (LFA) platform for the detection of cortisol in human serum. Cortisol is well-known as a stress hormone due to its high relevancy for human mental and physical health, such as hypertension or depression. To date, a number of optical devices have provided the sensitive determination of levels of analytes. However, this modality type still requires costly optical modules. The developed CL platform is simply composed of two detection modules along with a loading part for the LFA strip. The LFA membrane contains gold nanoparticle probes conjugated with antibodies against cortisol and horseradish peroxidase (HRP), which can also efficiently increase the luminescent signal by providing many areas for anti-cortisol antibody and HRP. The measured voltage signals coming from the photodiode in a CL reader were compared with a standard microplate reader for the evaluation of accuracy. The linear range observed for cortisol was measured to be 0.78–12.5 μg/dL (R2 = 0.99) with a limit of detection (LOD) of 0.342 μg/dL. In addition, the CL-LFA reader showed a high correlation (R2 = 0.96) with the standard cortisol console (COBAS 8000, Roche), suggesting that our developed CL-based LFA platform can be usable in situ.

A repeated usable electrode sensor for the measurement of glucose in urine has been developed. For improvement of the selectivity in measuring glucose in urine, we fabricated the Pt electrode coated with multilayered composite of glucose oxidase (GOX) and ascorbate oxidase (AOX). This simple layer structure could deliver more electrons from glucose oxidation without interference from ascorbic acids by first oxidizing the ascorbic acids present in urine. Results showed that our newly developed Pt electrode is capable of quantifying the concentrations of glucose in urine in the range between 0 and 1000 mg/dL, as well as maintaining its detection stability during 200 times of repeated measurements. This repeatable use of the sensor is attributable to the solidified structure of AOX and GOX layer.

Acoustic cavitation is used for megasonic cleaning in the semiconductor industry, especially of wafers with fragile pattern structures. Control of transient cavitation is necessary to achieve high particle removal efficiency (PRE) and low pattern damage (PD). In this study, the cleaning performance of solutions with different concentrations of dissolved gas (H2) and anionic surfactant (sodium dodecyl sulfate, SDS) in DIW (DI water) on silicon (Si) wafers was evaluated in terms of PRE and PD. When only DIW was used, PRE was low and PD was high. An increase in dissolved H2 gas concentration in DIW increased PRE; however, PD also increased accordingly. Thus, we investigated the megasonic cleaning performance of DIW and H2-DIW solutions with various concentrations of the anionic surfactant, SDS. At 20 ppm SDS in DIW, PRE reached a maximum value and then decreased with increasing concentration of SDS. PRE decreased slightly with increasing concentrations of SDS surfactant when dissolved in H2-DIW. Furthermore, PD decreased significantly with increasing concentrations of SDS surfactant in both DIW and H2-DIW cases. A high-speed camera setup was introduced to analyze bubble dynamics under a 0.96 MHz ultrasonic field. Coalescence, agglomeration, and the population of multi-bubbles affected the PRE and PD of silicon wafers differently in the presence of SDS surfactant. We developed a hypothesis to explain the change in bubble characteristics under different chemical environmental conditions.

Here we design and optimize a genetically encoded fluorescent indicator, iAChSnFR, for the ubiquitous neurotransmitter acetylcholine, based on a bacterial periplasmic binding protein. iAChSnFR shows large fluorescence changes, rapid rise and decay kinetics, and insensitivity to most cholinergic drugs. iAChSnFR revealed large transients in a variety of slice and in vivo preparations in mouse, fish, fly and worm. iAChSnFR will be useful for the study of acetylcholine in all organisms.

PurposePenile rehabilitation therapy using phosphodiesterase type 5 inhibitors (PDE5i) is used widely as a first-line therapy in patients with erectile dysfunction (ED) after radical prostatectomy (RP). However, many patients undergoing such therapy still complain of inappropriate erectile function (EF). Therefore, we evaluated the efficacy and safety of combined PDE5i therapy as a salvage medical treatment in patients nonresponsive to initial penile rehabilitation using daily PDE5i after nerve-sparing RP. MethodsWe retrospectively reviewed 58 nonresponders (Erection Hardness Score [EHS] of 2 or less) to penile rehabilitation using tadalafil (5 mg) daily for more than 12 weeks and who subsequently received combined PDE5i therapy (tadalafil [5 mg] once daily with sildenafil [50 mg] or udenafil [100 mg] on demand). Success after combined therapy is defined by EHS scores of 3 or 4. Safety was assessed by observing drug tolera-bility and adverse events. ResultsOf the 58 patients, combined therapy was successful in 39.7% of cases. The mean preoperative International Index of Erectile Function (IIEF-5) score was significantly higher in the success group after combined PDE5i therapy compared with the failure group (success group, 15.9 ± 5.1 versus failure group, 12.3 ± 5.6; p = 0.018). According to ED classification based on preoperative IIEF-5 scores, the success rates of no/mild/ mild-to-moderate ED group and moderate/severe ED group were 50.0% (18/36) and 22.7% (5/22), respectively (p = 0.039). The success and failure groups did not differ significantly in any other characteristic. The drugs were tolerated well by all patients and no serious adverse events were observed. ConclusionCombined PDE5i therapy improves EF in patients nonresponsive to standard penile rehabilitation using daily PDE5i after nerve-sparing RP, especially for patients without preoperative moderate or severe ED. In such patients, combined PDE5i therapy could be considered before invasive therapies.

BACKGROUND: Despite major progress in stem cell therapy, our knowledge of the characteristics and tissue regeneration potency of long-term transported cells is insufficient. In a previous in vitro study, we established the optimal cell transport conditions for amniotic fluid stem cells (AFSCs). In the present study, the target tissue regeneration of long-term transported cells was validated in vivo. METHODS: For renal regeneration, transported AFSCs were seeded on a poly(lactide-co-glycolide) scaffold and implanted in a partially resected kidney. The target tissue regeneration of the transported cells was compared with that of freshly harvested cells in terms of morphological reconstruction, histological microstructure reformation, immune cell infiltration, presence of induced cells, migration into remote organs, expression of inflammation/fibrosis/renal differentiation-related factors, and functional recovery. RESULTS: The kidney implanted with transported cells showed recovery of total kidney volume, regeneration of glomerular/renal tubules, low CD4/CD8 infiltration, and no occurrence of cancer during 40 weeks of observation. The AFSCs gradually disappeared and did not migrate into the liver, lung, or spleen. We observed low expression levels of pro-inflammatory cytokines and fibrotic factors; enhanced expression of the genes Wnt4, Pax2, Wt1, and Emx2; and significantly reduced blood urea nitrogen and creatinine values. There were no statistical differences between the performance of freshly harvested cells and that of the transported cells. CONCLUSION: This study demonstrates that long-term transported cells under optimized conditions can be used for cell therapy without adverse effects on stem cell characteristics, in vivo safety, and tissue regeneration potency.

Under extreme ultraviolet (EUV) exposure, the surfaces of EUV mask and optics are exposed to hydrocarbon contaminant, which reduces the imaging performance and lifetime of EUV mask. Thus, an efficient method is required to remove hydrocarbon contaminant from the mask surface. In this work, a mixture of alkaline chemicals and organic solvents has been proposed for the removal of EUV exposed hydrocarbon contaminant from Ru (Ruthenium) capping layer of EUV mask. A hydrocarbon film with similar properties to EUV hydrocarbon contaminant was prepared by PECVD (plasma enhanced chemical vapor deposition). The hydrocarbon removal efficiency was evaluated by using four kinds of quaternary ammonium hydroxides as alkaline chemicals, and DMSO (dimethyl sulfoxide) and THF (tetrahydrofuran) as polar aprotic organic solvents. Among the alkaline chemicals, tetrabutyl ammonium hydroxide, together with an organic solvent, produced effective removal of hydrocarbon from Ru. Removal of hydrocarbon film using a higher polar organic DMSO solvent required a higher concentration and longer time than THF. The combination of megasonic power and cleaning chemistry enhanced the hydrocarbon removal efficiency significantly.

With continued advances in semiconductor devices below 10 nm, the required specification for ultraclean wafer surfaces (i.e., achieving metal contamination 95% in all conditions because it reacted with both the chelating agents and HF.

Plasmonic nanostructures have been recently used in elevated temperature applications such as sensing of high-energy systems and localized heat generation for heat-assisted magnetic recording, thermophotovaltaics, and photothermal therapy. However, plasmonic nanostructures exposed to elevated temperature often experience permanent deformations, which could significantly degrade performance of the plasmonic devices. Therefore, understanding of thermal deformation of plasmonic nanostructures and its influence on the device performance is essential to the development of robust high-performance plasmonic devices. Here, we report thermal deformation of lithographic planar gold nanopatch and nanohole arrays and its influence on surface plasmon resonance sensing. The gold nanostructures are fabricated on a silicon substrate and on the end-face of an optical fiber using electron-beam lithography and focused-ion-beam lithography, respectively. The fabricated gold nanostructures are exposed to cyclic thermal loading in the range of 25 °C to 500 °C. Through experimental and numerical studies, we investigate (i) thermal deformation modes of the gold nanostructures, (ii) influence of the gold nanostructure geometry on the degree and mechanism of the thermal deformation, and (iii) influence of the thermal deformation on performance of surface plasmon resonance sensing. The obtained understanding from these studies is expected to help guide the development of robust high-performance plasmonic sensors for monitoring in elevated temperature environments. Although the current work is focused on gold nanostructures, it can be extended to provide useful insights on thermal deformation of refractory plasmonic nanostructures at extreme temperature.

Thin films of several microns in thickness are ubiquitously used in packaging, electronics, and acoustic sensors. Here we demonstrate that natural wood can be directly converted into an ultrathin film with a record-small thickness of less than 10 μm through partial delignification followed by densification. Benefiting from this aligned and laminated structure, the ultrathin wood film exhibits excellent mechanical properties with a high tensile strength of 342 MPa and a Young’s modulus of 43.6 GPa, respectively. The material’s ultrathin thickness and exceptional mechanical strength enable excellent acoustic properties with a 1.83-times higher resonance frequency and a 1.25-times greater displacement amplitude than a commercial polypropylene diaphragm found in an audio speaker. As a proof-of-concept, we directly use the ultrathin wood film as a diaphragm in a real speaker that can output music. The ultrathin wood film with excellent mechanical property and acoustic performance is a promising candidate for next-generation acoustic speakers., Thin films of several microns in thickness are ubiquitously used in packaging, electronics, and acoustic sensors. Here the authors demonstrate an ultrathin wood film with an aligned and laminal structure and acoustic properties which allows application of the film as diaphragm for an audio speaker.

BACKGROUND: The preservation of stem cell viability and characteristics during cell transport from the bench to patients can significantly affect the success of cell therapy. Factors such as suspending medium, time, temperature, cell density, and container type could be considered for transport conditions. METHODS: To establish optimal conditions, human amniotic fluid stem cells’ (AFSCs) viabilities were analyzed under different media {DMEM(H), DMEM/F-12, K-SFM, RPMI 1640, α-MEM, DMEM(L), PBS or saline}, temperature (4, 22 or 37 °C), cell density (1 × 10(7) cells were suspended in 0.1, 0.5, 1.0 or 2.0 mL of medium) and container type (plastic syringe or glass bottle). After establishing the transport conditions, stem cell characteristics of AFSCs were compared to freshly prepared cells. RESULTS: Cells transported in DMEM(H) showed relatively higher viability than other media. The optimized transport temperature was 4 °C, and available transport time was within 12 h. A lower cell density was associated with a better survival rate, and a syringe was selected as a transport container because of its clinical convenience. In compare of stem cell characteristics, the transported cells with established conditions showed similar potency as the freshly prepared cells. CONCLUSION: Our findings can provide a foundation to optimization of conditions for stem cell transport.

Generation of smoke is inevitable during surgical procedures. Some volatile organic compounds (VOCs) in surgical smoke are known to be strong carcinogens. We used a prototype of a multi-layered complex filter in an attempt to eliminate VOCs. From June 2015 to July 2015, 20 patients underwent transperitoneal laparoscopic nephrectomy for renal cell carcinoma. Smoke (pre-filter) was collected 20 min after the electrocautery device was first used during the surgery, by the direct collection method, with a 5-L Tedlar® gas-sampling bag. Twenty and 120 min after the filter was applied, smoke (post-filter) was again collected using the same method. The sample was analyzed by gas chromatography and mass spectrography. The cancer risk and hazard quotient were analyzed based on US Environmental Protection Agency guidelines. Twenty patients with a median age of 54.5 (30–80) years were enrolled in the study. Eighteen VOCs were detected using the Japanese indoor air standards mix analysis. The total elimination rate of the VOCs was 86.49 ± 2.83%. The post-filter (120 min) cancer risk (mean ± standard deviation) reduced to a negligible level for benzene, ethylbenzene, and styrene except 1,2-dichloroethane. The post-filter (120 min) hazard quotient for each compound decreased to levels posing a negligible risk for acetone, hexane, benzene, toluene, p-xylene, o-xylene, and styrene. Strong carcinogens, such as 1,2-dichloroethane, benzene, and ethylbenzene, were eliminated by more than 85% by using this activated carbon fiber filter and the risks from these compounds decreased to an almost negligible level. We suggest using every measure, including these filters, to protect the health of operating room personnel.

Chemically modulating monoamine neurotransmitter serotonin undergoes a physiological reaction of enzyme intermediated peroxidation to reconstruct dimeric self-assembled complex. A standard bivalent ligand approach dimeric serotonin increases structural and functional scaffolding with recognition-binding sites that are fundamentally more friendly than monovalent binding sites. Dimerization reaction accelerates the catalytic activity of one-electron oxidation at the C(4) position of serotonin to generate dual phenolic radicals in the presence of horseradish (HRP) and hydrogen peroxide (H2O2). Herein, we suggest the dimeric serotonin-based colorimetric assay, which presents a new rapid, sensitive, selective, and quantitative visualization. The dimeric serotonin possesses the capability to recognize intermolecular interaction units that cause aggregation scaffold of gold nanoparticles (GNPs), providing inexpensive and straightforward analytical needs. As a proof of visual and spectral analysis, peroxidative dimeric serotonin demonstrated sensitive and robust results. The calorimetric method enables highly sensitive detection of serotonin in phosphate buffer, and in human serum samples at nanomolar levels with a LOD of 2.6 nM and 2.81 nM, respectively, and the sensor possesses a dynamic range of 100–300 nM in buffer condition. Also, as proof of concept, visible color imaging of immunosensors which is appropriate for fast visible testing at detection limits as low as 2.90 nM concentration.

This study investigates the effect of the adhesion and removal of particles such as silica (SiO2), tantalum (Ta) and polystyrene latex (PSL) from three different kinds of EUV (extreme ultra violet) mask surfaces, specifically silicon (Si), tantalum nitride (TaN), and ruthenium (Ru). The results show that inorganic particles such as silica and Ta deposited on Si surface are harder to remove from its surface than from TaN and Ru surfaces. This is due not only to the presence of van der Waals forces but also the hydrogen bonding force between them. On the other hand, an organic contaminant such as PSL particles deposited on Si is easily removed from the surface. This is due to the presence of van der Waals forces between the surface and particles. Inorganic particles deposited on a Ru surface are easily removed from its surface compared with a Si surface. However, PSL particles deposited on a Ru surface are hard to remove due to the presence of pi bonding between the Ru surface and the PSL particles. To weaken the chemical bonding (pi bond), a tetramethylammonium hydroxide (TMAH) cleaning solution is used to improve the removal efficiency of PSL particles on the Ru surface.

Enoyl-ACP reductase (ENR, also known as FabI) has received considerable interest as an anti-bacterial target due to its essentiality in fatty acid synthesis. All the FabI structures reported to date, regardless of the organism, are composed of homo-tetramers, except for two structures: Bacillus cereus and Staphylococcus aureus FabI (bcFabI and saFabI, respectively), which have been reported as dimers. However, the reason for the existence of the dimeric form in these organisms and the biological meaning of dimeric and tetrameric forms of FabI are ambiguous. Herein, we report the high-resolution crystal structure of a dimeric form of Bacillus anthracis FabI (baFabI) and the crystal structures of tetrameric forms of baFabI in the apo state and in complex with NAD+ and with NAD+-triclosan, at 1.7 A, 1.85 A, 1.96 A, and 1.95 A, respectively. Interestingly, we found that baFabI with a His6-tag at its C-terminus exists as a dimer, whereas untagged-baFabI exists as a tetramer. The His6-tag may block the dimer-tetramer transition, since baFabI has relatively short-length amino acids (255LG256) after the 310-helix η7 compared to those of FabI of other organisms. The dimeric form of baFabI is catalytically inactive, because the α-helix α5 occupies the NADH-binding site. During the process of dimer-tetramer transition, this α5 helix rotates about 55° toward the tetramer interface and the active site is established. Therefore, tetramerization of baFabI is required for cofactor binding and catalytic activity.

Sustained operation of high-performance, ITER-baseline scenario plasmas at the high levels of input power ( ≲ 40 MW ) required to achieve ∼15 MW of D-T fusion power in JET-ILW requires careful optimisation of the fuelling to avoid an unacceptable disruption rate due to excessive radiation, primarily from W impurities, which are sputtered by edge-localised modes (ELMs) from the divertor targets. By using a train of ELM-pacing pellets from a high-frequency pellet injector to promote regular ELMs, which flush W and other impurities from the confined plasma, such high-performance plasmas can be sustained (for ∼5 s) while maintaining a high normalised confinement factor H 98,y2 ∼ 1, which would otherwise be degraded by reducing the pedestal confinement if a higher rate of D2 gas fuelling were used instead of the pellets to mitigate the W contamination. The causes underlying the improved performance and energy confinement obtained using this combined, gas and pellet fuelling scheme is investigated here in some detail.

The hippo pathway is a critical transcriptional regulator of cell growth, proliferation, and migration in cancer, furthermore,YAP-TEAD complexes act as a major role in the pathway. S-palmitoylation of cysteine residues in TEAD proteins is required for their stability and function in hippo pathway signaling. Recently, it has become manifested that the dysregulation of hippo pathway effectors (MST1/2 and LATS1/2) is involved in oncogenesis. These effectors inactivate translocation of YAP and TAZ into the nucleus. The translocation of YAP/TAZ is responsible for acting as transcriptional coactivators by binding to the transcription factor, TEADs resulting in the transcription of cancer-related genes that drive tumor growth. Since YAP/TAZ are considered to be natively unfolded and can be difficult to handle as a drug target, TEAD is regarded as an excellent therapeutic target for intervention of the hippo pathway. SJP1901 is a small molecule of TEAD inhibitor with potential as drug candidates in malignant mesothelioma and other types of cancer. Based on the results of structure-based drug design, hit compounds were synthesized and their efficacy was evaluated.The compounds effectively inhibited palmitoylation of TEAD proteins and showed remarkable efficacy in reporter gene assay using TEAD responsive element (TRE)-integrated MCF7 with nano molar IC50 concentrations. The excellent anti-tumor effect of SJP1901 was revealed via cell proliferation inhibition assay (nano molar IC50 concentrations) andanalysis of inhibited transcription activity for target genes (CTGF and CYR61) usingmalignant mesothelia cell lines (NCI-H226, NCI-H2052 and MSTO-211H) known to display hippo pathway-dependent cell growth. In addition, these compounds showed lower toxicities in normal cells such as Fa2N4, CCD-18co and WI38 (IC50>10 μM). In conclusion, we obtained potent small molecules which inactivate TEAD proteins by directly inhibiting their palmitoylation. SJP1901 showed outstanding anti-cancer effects through regulating hippo pathway-mediated target genes and lower toxicitiy in normal cells. In vivo efficacy study and research to expand the indications are currently ongoing. Citation Format: Jihyun Um, Janghyun Lee, Kwangwoo Hwang, Sujin Park, Jooyoung Hyun, Dohyeong Lee, Jeongmin Lee, Li-Kyung Kim, Moon Jung Back, Seong Jun Park, Hwan Jung Lim, You-Keun Shin, Hei-Cheul Jeung, Jaewoong Lee, Hyun Tae Kim, Yongbin Park, Hoseok Kwon, Min-Hyo Ki. SJP1901, a small molecule inhibitor targeting hippo pathway by directly inhibiting TEAD palmitoylation in hippo pathway-dependent cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1295.

Laccases are multicopper containing oxidase enzymes that are highly important in environmental remediation and biotechnology. To date, complex Copper containing materials have been reported as laccase mimic, and the possibility of a non-Cu laccase mimic remained unknown. In this work, we report an exceptionally simple functional laccase mimic based on coral-like silver citrate (AgCit) microstructures. The AgCit was synthesized by a simple precipitation method and was found to possess excellent laccase-like activity capable of oxidizing phenolic substrates and the endocrine hormone adrenaline. Compared to the natural laccase enzyme, our reported laccase-mimic has a higher υmax and lower Km value using adrenaline as a substrate. In addition, the AgCit laccase mimic was observed to be stable at extreme pH, higher temperature, and suitable for long-term storage at room temperature. The laccase-like properties of the AgCit nanozyme were successfully applied for the quantification and degradation of various phenolic pollutants and the adrenaline hormone.

For 28nm NAND flash memory, the aspect ratio of shallow trench isolation (STI) becomes large, and it makes difficult to fill STI structure by conventional oxide film without void formation. Several gap-fill methods such as high density plasma (HDP) and thermal chemical vapor deposition (CVD) are widely accepted, but they are difficult to make gap fill without void because of gap-fill margin. Recently, STI fill has been tried with polysilazane (PSZ) based inorganic spin-on dielectric (SOD) film. PSZ oxide has its good gap-fill ability, low moisture content and high etching resistance. However, PSZ oxide would produce amine etch residue during the NF3 dry etching process because of NH3component in PSZ oxide. For preventing this resudue, it is very important to control process parameters affecting the chemical reaction because the etch rate, and the surface quality depend upon the process reaction. During the STI etching back process, other layer also exposed. So, selectivity between other oxide must be considered. In this study, we have employed plasma dry etching of nitrogen trifluoride (NF3) and H2O mixtures. We studied the effect of the gas chemistry on the etching of oxides. The materials used for these experiments were thermally grown SiO2 (1000Å, 10000Å), PSZ oxide (500Å), TEOS (315Å) and ALD oxide (300Å). Samples of size 25 x 25 mm were cleaned first in diluted SC-1 [NH4OH(25%): H2O2(38%): DIW =1:2:50] at 60°C for 10 min. The etching mechanism of PSZ oxide was investigated in plasma activated NF3/H2O gas. This process generates ammonium hexafluorosilicate ((NH4)2SiF6) as a by-product. By-products were formed on the PSZ surface which was confirmed by observing N–H, NH4+ and SiF6 2-peak in ATR-FTIR spectrum. These peaks are representative of (NH4)2SiF6 powder composition. Etch rates of several SiO2 were reported as a function of H2O ratio, substrate temperature, and pressure. NF3/H2O mixtures were excited using pulsed RF plasma. The NF3 flow rate for all experiments was kept at 150 sccm. The temperatures were varied from 8 to18ºC, the chamber pressures from 7 to 9 Torr., the H2O flow rates from 1500 to 2500 sccm and process times from 20 to 100 sec. Helium was used as a carrier gas. After dry etching, an annealing process was performed. The reaction mechanism was proposed by analyzing the oxide layer surface. We used an ellipsometer to measure the oxide thickness for evaluation of the etch rate. Also, various analyzing tools such as SEM, contact angle analyzer, and FT-IR were used to characterize the surface contaminants. The optimized drying process provides the high selectivity without any residue formation.

The synthesis of indazoles from pyrazoles and internal alkynes is described. Instead of complex benzenoid compounds, readily available pyrazoles were used for the preparation of indazoles by reaction of the C-H bonds of the heterocyclic ring. Oxidative benzannulation was also applied to imidazoles, providing benzimidazoles. This convergent strategy enabled alteration of the photochemical properties of benzo-fused diazoles by varying the substituents at the benzene ring, thus leading to the development of tetraarylindazoles as new fluorophores.

SRC-family kinases (SFKs) have been implicated in Alzheimer's disease (AD), but their mode of action was scarcely understood. Here, we show that LYN plays an essential role in amyloid β (Aβ)-triggered neurotoxicity and tau hyperphosphorylation by phosphorylating Fcγ receptor IIb2 (FcγRIIb2). We found that enzyme activity of LYN was increased in the brain of AD patients and was promoted in neuronal cells exposed to Aβ 1-42 (Aβ1-42). Knockdown of LYN expression inhibited Aβ1-42-induced neuronal cell death. Of note, LYN interacted with FcγRIIb2 upon exposure to Aβ1-42 and phosphorylated FcγRIIb2 at Tyr273 within immunoreceptor tyrosine-based inhibitory motif in neuronal cells. With the use of the structure-based drug design, we isolated KICG2576, an ATP-competitive inhibitor of LYN. Determination of cocrystal structure illustrated that KICG2576 bound to the cleft in the LYN kinase domain and inhibited LYN with a half-maximal inhibitory concentration value of 0.15 μM. KICG2576 inhibited Aβ- or FcγRIIb2-induced cell death, and this effect was better than pyrazolopyrimidine 1, a widely used inhibitor of SFK. Upon exposure to Aβ, KICG2576 blocked the phosphorylation of FcγRIIb2 and translocation of phosphatidylinositol 3,4,5-trisphosphate 5-phosphatase 2, a binding protein to the phosphorylated FcγRIIb2, to the plasma membrane, resulting in the inhibition of tau hyperphosphorylation, the downstream event of Aβ1-42-FcγRIIb2 binding. Furthermore, intracerebroventricular injection of KICG2576 into mice ameliorated Aβ-induced memory impairment. These results suggest that LYN plays a crucial role in Aβ1-42-mediated neurotoxicity and tau pathology, providing a therapeutic potential of LYN in AD.-Gwon, Y., Kim, S.-H., Kim, H. T., Kam, T.-I., Park, J., Lim, B., Cha, H., Chang, H.-J., Hong, Y. R., Jung, Y.-K. Amelioration of amyloid β-FcγRIIb neurotoxicity and tau pathologies by targeting LYN.

Fluorescent copper microspheres (CMS) with high quantum yield (72.9 %) were synthesized by an efficient, one-pot, and rapid aggression-induced mechanism. The CMS was bright brick-red luminescent under UV light and have shown an excitation independent emission at 670 nm. The emission intensity of CMS was significantly quenched by the addition of nicotinamide adenine dinucleotide (NADH) when excited at 275 nm, providing a linear range with the logarithmic concentration of NADH, suitable for the detection of low concentrations of NADH. Similarly, the emission intensity at 670 nm was enhanced when excited at 340 nm, providing a linear range for NADH determination in the higher concentration. Thus, a dual-mode sensing platform for the determination of NADH was established by utilizing the fluorescent quenching and enhancement properties of NADH over CMS. Addition of other common interfering molecules and ions induced only a meager change in the fluorescent intensity of CMS, suggesting the high selectivity of the sensor. The linear range observed for NADH by exploring the fluorescent quenching properties was from 24.8−575.2 μM (R2 = 0.99) with a L.O.D of 2.4 μM. Meanwhile, the linear range observed for NADH by utilizing the fluorescent enhancing properties was from 625 μM-2.30 mM (R2 = 0.98) with a L.O.D of 322.5 μM.

The effect of biochar application on soil physics and nitrous oxide (N₂O) emission from upland soil for broccoli cultivation was investigated. Sesame straw biochar (SB) was applied at amounts 0 (IF), 50 (SB50), 100 (SB100), 200 (SB200) kg 10a -1 , respectively. SB addition to the upland soil decreased bulk density, and increased porosity and soil respiration. The N₂O emission rates in all treatments were higher in the order of IF ≧ SB50 ＞ SB100 ≧ SB200 treatments. Global warming potential in SB200 treatment decreased by 15.1% compared to IF treatment. Therefore, SB application in upland soil can improve soil physics and reduce N₂O emission.

This study evaluated the changes of phytoestrogen contents and antioxidant activities of soybean-powder milk (SPM) prepared from yellow soybean during fermentation with Lactobacillus plantarum P1201. In consequence, the levels of total phenolic and isoflavone-aglycone contents, ABTS and DPPH radical-scavenging activities, and FRAP assay values increased, while isoflavone-glycoside contents decreased during fermentation. The highest levels of daidzein, glycitein, and genistein were present in the Daepung SPM at concentrations of 177.92, 20.64, and 106.14 μg/g, respectively after 60 h of fermentation. Moreover, Daepung SPM showed the highest DPPH radical-scavenging activity of 48.54%, an ABTS radical-scavenging activity of 99.25%, and a FRAP assay value of 0.84 at the end of fermentation. The fermented Daepung SPM possessed highest isoflavone aglycone contents and antioxidant activities, which can be utilized for the development of functional foods.

Recent studies have revealed that autophagy is induced under various disease conditions; however, the role of autophagy in pathological states is controversial.quinone oxidoreductase 1 (NQO1) is a highly inducible cytoprotective gene that regulates reactive oxygen species (ROS) generation. In this study, we examined whether NQO1 deficiency affects the autophagy process in response to cisplatin-induced nephrotoxicity.In vitro, NQO1 and autophagy-associated proteins were induced after cisplatin treatment and the autophagosomes markedly increased in the cisplatin-treated NQO1-knockdown ACHN cells together with increased ROS production. In vivo, NQO1-KO mice displayed a significant increase in cisplatin-induced acute kidney injury (AKI), as indicated by elevated tubular damage and apoptosis as well as by suppressed cytoprotective signals. In agreement with the in vitro findings, NQO1-KO cisplatin-treated mice displayed a notable increase in autophagy-associated protein expression compared with their wild-type counterparts. Meanwhile, the expression of Ras-related protein 7, which participates in autophagosome maturation and lysosome fusion, markedly decreased in NQO1-KO mice, indicating hampered progress in late autophagy, and was accompanied by increased p62 protein expression. Moreover, NQO1 deletion enhanced the effect of the mammalian target of the rapamycin inhibitor, rapamycin, and led to enhanced tuberous sclerosis complex 2 phosphorylation through AMP-activated protein kinase activation.These results indicate that autophagy may be enhanced to counter the increased stress due to NQO1 deficiency, an oxidative stress barrier. The present results demonstrate the significant influence of NQO1 on the autophagy process and support the hypothesis that autophagy plays a protective role under oxidative stress conditions. Antioxid. Redox Signal. 24, 867-883.

The electrodeposition of Zn–Ni alloy coatings containing less than 11% Ni was performed in a sulfuric acid bath. We investigated the influence of the Ni content in the electrodeposit on the corrosion behavior of the alloy in detail, focusing mainly on the evolution of internal stress. The initial corrosion rates of specimens before salt spray testing were closely related to the internal stress and the Zn–6 wt% Ni coating showed better corrosion resistance than those of the other investigated coating due to the smallest internal stress. However, it was shown that the amount of residual Ni and a concentration reversal between Zn and Ni at the Zn–Ni/steel interface became more significant as the corrosion proceeded. In addition, closely packed nodular grains with hairline cracks and the formation of electrochemically noble γ-Ni 5 Zn 21 phase were observed at the highest Ni concentration of 10 wt%. And the cross-sectional distributions of alloying elements were more homogeneous with increasing Ni content in the deposit. Electrochemical test results with the resulting specimens with different salt spray testing times were also presented. At the highest Ni concentration, the sacrificial property to steel substrate was maintained with extended testing time, showing minimal corrosion current density. Regarding Zn–Ni alloy coatings for automotive applications, a decrease in corrosion depth with increasing Ni content after long-term exposure to salt spray was observed, indicating improved perforation resistance.

Thirty-eight Pea (Pisum sativum L.) genotypes were screened to identify varieties to be suitable for sprout. Based on seed yield and sprout qualities such as whole length and sprout yield, five genotypes (PI269803, PI343278, PI343283, PI343300 and PI 343307) were primarily selected as candidates for pea sprouts. In order to determine optimal cultivation condition for pea sprouting, growth characteristics were investigated according to the change of germination temperature and days for sprouting. Whole length and hypocotyl length were observed to increase as a time dependent manner at each tested temperature (20, 23, and ). However, whole length, hypocotyl length, and sprout yield were highly increased at compared to 20 and . Especially, PI269803 and PI343300 showed higher sprout yield than the others. In addition, the effect of the change of germination temperature on antioxidant properties was estimated by measuring total phenolic content (TPC) and free radical scavenging activity (DPPH and ABST activity). TPC and DPPH/ABST activities of PI269803 and PI343300 were higher at than at 20 and , while antioxidant properties of PI343278 and PI343283 were decreased in a temperature-dependent manner. The results show a high degree of correlation between TPC and antioxidant activities and suggest that the temperature change for pea sprouting could be responsible for antioxidant properties. Taken together, these results provide optimal cultivation conditions for pea sprouting and suggest that PI269803 and PI343300 with high sprout yield and antioxidant properties could be used for pea sprouts.

BACKGROUND: We fabricated anti-inflammatory scaffold using Mg(OH)(2)-incorporated polylactic acid-polyglycolic acid copolymer (MH-PLGA). To demonstrate the anti-inflammatory effects of the MH-PLGA scaffold, an animal model should be sensitive to inflammatory responses. The interleukin-10 knockout (IL-10 KO) mouse is a widely used bowel disease model for evaluating inflammatory responses, however, few studies have evaluated this mouse for the anti-inflammatory scaffold. METHODS: To compare the sensitivity of the inflammatory reaction, the PLGA scaffold was implanted into IL-10 KO and C57BL/6 mouse kidneys. Morphology, histology, immunohistochemistry, and gene expression analyses were carried out at weeks 1, 4, 8, and 12. The anti-inflammatory effect and renal regeneration potency of the MH-PLGA scaffold was also compared to those of PLGA in IL-10 KO mice. RESULTS: The PLGA scaffold-implanted IL-10 KO mice showed kidneys relatively shrunken by fibrosis, significantly increased inflammatory cell infiltration, high levels of acidic debris residue, more frequent CD8-, C-reactive protein-, and ectodysplasin A-positive cells, and higher expression of pro-inflammatory and fibrotic factors compared to the control group. The MH-PLGA scaffold group showed lower expression of pro-inflammatory and fibrotic factors, low immune cell infiltration, and significantly higher expression of anti-inflammatory factors and renal differentiation related genes compared to the PLGA scaffold group. CONCLUSION: These results indicate that the MH-PLGA scaffold had anti-inflammatory effects and high renal regeneration potency. Therefore, IL-10 KO mice are a suitable animal model for in vivo validation of novel anti-inflammatory scaffolds.

A strategy in which complementary species are paired for the preparation of α-heteroaryl esters and amides from heteroarenes was developed. Readily available α-haloacetates and α-acetamides provided the requisite acetate and acetamide groups via three distinctive reactive species, namely nucleophilic carbanions, alkylpalladium complexes, and photoredox-generated electrophilic radicals. Based on their electronic properties, these intermediates were matched with various five-membered heteroarenes, such as pyrazoles, imidazoles, thiophenes, furans, pyrroles, and indoles. These flexible protocols offer easy access to α-heteroaryl acetic acid derivatives and expand the scope of heteroarenes that can be utilized for C−H alkylation.