C-Axis Aligned Composite InZnO via Thermal Atomic Layer Deposition for 3D Nanostructured Semiconductor.

Amorphous oxide semiconductors have been widely studied for various applications, including thin-film transistors (TFTs) for display backplanes and semiconductor memories. However, the inherent instability, limited mobility, and complexity of multicomponent oxide semiconductors for achieving high aspect ratios and conformality of cation distribution remain challenging. Indium-zinc oxide (IZO), known for its high mobility, also faces obstacles in instability resulting from high carrier doping density and low ionization energy. To address these issues and attain a balance between mobility and stability, adopting a highly aligned structure such as a c-axis aligned crystalline IGZO could be advantageous. However, limited studies have reported enhanced electrical performance using crystalline IZO, likely attributed to the high thermal stability of the individual components (In2O3 and ZnO). Here, we first propose a c-axis aligned composite (CAAC) IZO with superior TFT properties, including a remarkable performance of field-effect mobility (µFE) of 55.8 cm2/(V s) and positive-bias-temperature-stress stability of +0.16 V (2 MV/cm, 60 °C, 1 h), as well as a low subthreshold swing of 0.18 V/decade and hysteresis as 0.01 V, which could be obtained through optimization of growth temperature and composition using thermal atomic layer deposition. These results surpass those of TFTs based on nanocrystalline/polycrystalline/amorphous-IZO. We conducted a thorough investigation of CAAC-IZO and revealed that the growth temperature and cation distribution profoundly influence the crystal structure and device properties. Finally, we observed excellent compositional conformality and 97% step coverage of IZO on a high-aspect-ratio (HAR) structure with an aspect ratio reaching 40:1, which is highly promising for future applications. Our results include a detailed investigation of the influence of the crystal structure of IZO on the film and TFT performance and suggest an approach for future applications.

Feasibility of artificial intelligence-driven interfractional monitoring of organ changes by mega-voltage computed tomography in intensity-modulated radiotherapy of prostate cancer.

PURPOSE: High-dose radiotherapy (RT) for localized prostate cancer requires careful consideration of target position changes and adjacent organs-at-risk (OARs), such as the rectum and bladder. Therefore, daily monitoring of target position and OAR changes is crucial in minimizing interfractional dosimetric uncertainties. For efficient monitoring of the internal condition of patients, we assessed the feasibility of an auto-segmentation of OARs on the daily acquired images, such as megavoltage computed tomography (MVCT), via a commercial artificial intelligence (AI)-based solution in this study. MATERIALS AND METHODS: We collected MVCT images weekly during the entire course of RT for 100 prostate cancer patients treated with the helical TomoTherapy system. Based on the manually contoured body outline, the bladder including prostate area, and rectal balloon regions for the 100 MVCT images, we trained the commercially available fully convolutional (FC)-DenseNet model and tested its auto-contouring performance. RESULTS: Based on the optimally determined hyperparameters, the FC-DenseNet model successfully auto-contoured all regions of interest showing high dice similarity coefficient (DSC) over 0.8 and a small mean surface distance (MSD) within 1.43 mm in reference to the manually contoured data. With this well-trained AI model, we have efficiently monitored the patient's internal condition through six MVCT scans, analyzing DSC, MSD, centroid, and volume differences. CONCLUSION: We have verified the feasibility of utilizing a commercial AI-based model for auto-segmentation with low-quality daily MVCT images. In the future, we will establish a fast and accurate auto-segmentation and internal organ monitoring system for efficiently determining the time for adaptive replanning.

Gold Nanoparticle-Carrying T Cells for the Combined Immuno-Photothermal Therapy.

Cancer immunotherapy is a promising therapy to treat cancer patients with minimal toxicity, but only a small fraction of patients responded to it as a monotherapy. In this study, a strategy to boost therapeutic efficacy by combining an immunotherapy based on ex vivo expanded tumor-reactive T cells is devised, or adoptive cell therapy (ACT), with photothermal therapy (PTT). Smart gold nanoparticles (sAuNPs), which aggregates to form gold nanoclusters in the cells, are loaded into T cells, and their photothermal effects within T cells are confirmed. When transferred into tumor-bearing mice, large number of sAuNP-carrying T cells successfully infiltrate into tumor tissues and exert anti-tumor activity to suspend tumor growth, but over time tumor cells evade and regrow. Of note, ≈20% of injected doses of sAuNPs are deposited in tumor tissues, suggesting T cells are an efficient nanoparticle tumor delivery vehicle. When T cells no longer control tumor growth, PTT is performed to further eliminate tumors. In this manner, ACT and PTT are temporally coupled, and the combined immuno-photothermal treatment demonstrated significantly greater therapeutic efficacy than the monotherapy.

Feasibility of internal-source tracking with C-arm CT/SPECT imaging with limited-angle projection data for online in vivo dose verification in brachytherapy: A Monte Carlo simulation study.

PURPOSE: The current protocol for use of the image-guided adaptive brachytherapy (IGABT) procedure entails transport of a patient between the treatment room and the 3-D tomographic imaging room after implantation of the applicators in the body, which movement can cause position displacement of the applicator. Moreover, it is not possible to track 3-D radioactive source movement inside the body, even though there can be significant inter- and intra-fractional patient-setup changes. In this paper, therefore, we propose an online single-photon emission computed tomography (SPECT) imaging technique with a combined C-arm fluoroscopy X-ray system and attachable parallel-hole collimator for internal radioactive source tracking of every source position in the applicator. METHODS AND MATERIALS: In the present study, using Geant4 Monte Carlo (MC) simulation, the feasibility of high-energy gamma detection with a flat-panel detector for X-ray imaging was assessed. Further, a parallel-hole collimator geometry was designed based on an evaluation of projection image quality for a 192Ir point source, and 3-D limited-angle SPECT-image-based source-tracking performances were evaluated for various source intensities and positions. RESULTS: The detector module attached to the collimator could discriminate the 192Ir point source with about 3.4% detection efficiency when including the total counts in the entire deposited energy region. As the result of collimator optimization, hole size, thickness, and length were determined to be 0.5, 0.2, and 45 mm, respectively. Accordingly, the source intensities and positions also were successfully tracked with the 3-D SPECT imaging system when the C-arm was rotated within 110° in 2 seconds. CONCLUSIONS: We expect that this system can be effectively implemented for online IGABT and in vivo patient dose verification.

Electrical conductivity, Seebeck coefficient, and crystal growth of p-type tellurium films through temperature dependent RF sputtering.

Te thin films have recently received considerable attention owing to its superior electrical and thermoelectric properties. During the deposition process, if the temperature of the substrate is raised, high crystallinity and improved electrical properties can be expected. In this study, we used radio frequency sputtering for Te deposition to study the relationship between the deposition temperature, crystal size, and electrical performance. As the deposition temperature is increased from room temperature to 100 °C, we observed an increase in crystal size from the x-ray diffraction patterns and full-width half maximum calculations. With this grain size increment, the Hall mobility and Seebeck coefficient of the Te thin film increased significantly from 16 to 33 cm2V-1s-1and 50 to 138µV K-1, respectively. This study reveals the potential of a facile fabrication method for enhanced Te thin films using temperature control and highlights the importance of the Te crystal structure in determining the electrical/thermoelectrical properties. These findings are particularly significant for the development of semiconductor material systems for various applications, including thermoelectric devices, CMOS, FET, and solar devices.

The Preparation and Physiochemical Characterization of Tenebrio molitor Chitin Using Alcalase.

Chitin is mostly produced from crustaceans, but it is difficult to supply raw materials due to marine pollution, and the commonly used chemical chitin extraction method is not environmentally friendly. Therefore, this study aims to establish a chitin extraction process using enzymes and to develop edible insect-derived chitin as an eco-friendly new material. The response surface methodology (RSM) was used to determine the optimal conditions for enzymatic hydrolysis. The optimal conditions for enzymatic hydrolysis by RSM were determined to be the substrate concentration (7.5%), enzyme concentration (80 µL/g), and reaction time (24 h). The solubility and DDA of the mealworm chitosan were 45% and 37%, respectively, and those of the commercial chitosan were 61% and 57%, respectively. In regard to the thermodynamic properties, the exothermic peak of mealworm chitin was similar to that of commercial chitin. In the FT-IR spectrum, a band was observed in mealworm chitin corresponding to the C=O of the NHCOCH3 group at 1645 cm-1, but this band showed low-intensity C=O in the mealworm chitosan due to deacetylation. Collectively, mealworm chitosan shows almost similar physical and chemical properties to commercial chitosan. Therefore, it is shown that an eco-friendly process can be introduced into chitosan production by using enzyme-extracted mealworms for chitin/chitosan production.

Label-free photothermal optical coherence microscopy to locate desired regions of interest in multiphoton imaging of volumetric specimens.

Biochip-based research is currently evolving into a three-dimensional and large-scale basis similar to the in vivo microenvironment. For the long-term live and high-resolution imaging in these specimens, nonlinear microscopy capable of label-free and multiscale imaging is becoming increasingly important. Combination with non-destructive contrast imaging will be useful for effectively locating regions of interest (ROI) in large specimens and consequently minimizing photodamage. In this study, a label-free photothermal optical coherence microscopy (OCM) serves as a new approach to locate the desired ROI within biological samples which are under investigation by multiphoton microscopy (MPM). The weak photothermal perturbation in sample by the MPM laser with reduced power was detected at the endogenous photothermal particles within the ROI using the highly sensitive phase-differentiated photothermal (PD-PT) OCM. By monitoring the temporal change of the photothermal response signal of the PD-PT OCM, the hotspot generated within the sample focused by the MPM laser was located on the ROI. Combined with automated sample movement in the x-y axis, the focal plane of MPM could be effectively navigated to the desired portion of a volumetric sample for high-resolution targeted MPM imaging. We demonstrated the feasibility of the proposed method in second harmonic generation microscopy using two phantom samples and a biological sample, a fixed insect on microscope slide, with dimensions of 4 mm wide, 4 mm long, and 1 mm thick.

Discovery of a NADPH oxidase inhibitor, (E)-3-cyclohexyl-5-(4-((2-hydroxyethyl)(methyl)amino)benzylidene)-1-methyl-2-thioxoimidazolidin-4-oneone, as a novel therapeutic for Parkinson's disease.

Several lines of evidence indicated that generation of NADPH oxidase (Nox)-mediated reactive oxygen species are associated with neuronal inflammation, leading to Parkinson's disease (PD). Novel benzylidene-1-methyl-2-thioxoimidazolidin-one derivatives as Nox inhibitors were designed and synthesized in order to increase blood-brain barrier (BBB) permeability to target Nox in brain cells. In lucigenin chemiluminescence assay, eight compounds showed excellent inhibition activity against NADPH oxidases and parallel artificial membrane permeability assay (PAMPA) identified compound 11 with high passive permeability. To validate the effect of compound 11 on neuronal inflammation, we tested the regulatory activity of compound 11 in lipopolysaccharide (LPS)-induced production of pro-inflammatory cytokines in BV-2 microglial cells and LPS-mediated microglial migration. Treatment of BV2 cells with compound 11 resulted in suppressed production of pro-inflammatory cytokines and migration activity of BV2 cells in response to LPS. To evaluate the therapeutic efficacy of compound 11 in PD animal model, compound 11 was applied to MPTP-induced PD mouse model. Oral administration of compound 11 (30 mg/kg/daily, 4 weeks) into the mice resulted in suppression of dopaminergic neuronal death in substantia nigra (SN) and in striatum as well as inhibition of microglial migration into SN. These results implicate compound 11 as a novel therapeutic agent for the treatment of PD.

Tropical modulation of East Asia air pollution.

Understanding air pollution in East Asia is of great importance given its high population density and serious air pollution problems during winter. Here, we show that the day-to-day variability of East Asia air pollution, during the recent 21-year winters, is remotely influenced by the Madden-Julian Oscillation (MJO), a dominant mode of subseasonal variability in the tropics. In particular, the concentration of particulate matter with aerodynamic diameter less than 10 micron (PM10) becomes significantly high when the tropical convections are suppressed over the Indian Ocean (MJO phase 5-6), and becomes significantly low when those convections are enhanced (MJO phase 1-2). The station-averaged PM10 difference between these two MJO phases reaches up to 15% of daily PM10 variability, indicating that MJO is partly responsible for wintertime PM10 variability in East Asia. This finding helps to better understanding the wintertime PM10 variability in East Asia and monitoring high PM10 days.

Functional validation of the simplified in vitro 3D Co-culture based BBB model.

Various methods of generating 2D and 3D in vitro blood-brain barrier (BBB) models have previously been published with the objective of developing therapeutics for brain diseases. In general, published methods including our published method demonstrate that in vivo-like semi-permeable barrier can be generated. To further verify that an in vitro BBB model closely represents BBB, functional validation is required. Here, we functionally validate our in vitro 3D BBB model using rituximab as a representative therapeutic antibody and previously published anti-TfR (transferrin receptor) antibodies as representative BBB-penetrating antibodies. We demonstrate that our BBB model can efficiently block rituximab while allowing receptor-mediated transcytosis (RMT) of anti-TfR antibodies. In addition, we showed that RMT efficacy of anti-TfR antibodies with different binding affinity can be displayed using our BBB model. In conclusion, this demonstrates that our BBB model functionally mimics the BBB as well as having BBB-like physical properties, further establishing our BBB model as a screening tool for discovery and development of therapeutics for brain diseases.

Simplified in vitro 3D co-culture-based blood-brain barrier model using transwell.

The blood-brain barrier (BBB) is a major hurdle for treatment of brain diseases. To overcome this, precise and reproducible BBB model is one of the key factors for successful evaluation of BBB-penetrating efficacy of developmental drugs. Thus, in vitro BBB model recapitulating the physiological structure of the BBB is a valuable tool for drug discovery and development for brain diseases. Here, we develop a simplified 3D co-culture-based BBB model using immortalized human brain endothelial cells and immortalized human astrocytes mixed with Matrigel allowing model preparation within 30 min. We directly compare our 3D BBB model to a 2D BBB model comprised solely of immortalized brain endothelial cells, to demonstrate that our 3D BBB model blocks penetration of Dextran molecules with various molecular weights, remain durable and impermeable even in a BBB-degrading condition, and rapidly form tight junctions while the 2D BBB model do not. In conclusion, this establishes our simplified 3D BBB model as a valuable tool for high throughput screening of drug candidates for brain diseases.

Handgrip Strength and Cognitive Function among Elderly Koreans: Insights from the Korean Longitudinal Study of Ageing.

This study aims to assess handgrip strength as a predictor of cognitive decline within men and women in Korea. A random-intercept logistic regression is fit to estimate the status changes in cognitive function throughout all rounds of the KLoSA, a nationally-representative survey of adults aged 45 years and older. Males in the highest quartile were 71.9% less likely to experience cognitive impairment than those in the lowest quartile. The odds of cognitive impairment for men in the third and second quartiles reduced by 62.6% and 60.4% respectively. Similarly, the odds of cognitive impairment for women declined as 72.7%, 63.0%, and 41.8% for fourth, third, and second quartile, respectively, compared with the lowest quartile. These results imply that assessing and monitoring handgrip strength may enable us to identify subgroups of the elderly with higher likelihood of cognitive impairment in Korea.

Facile synthesis of an organic/inorganic hybrid 2D structure tincone film by molecular layer deposition.

Organic/inorganic hybrid tincone films were deposited by molecular layer deposition (MLD) using N,N'-tert-butyl-1,1-dimethylethylenediamine stannylene(II) as a precursor and hydroquinone (HQ) as an organic reactant. From previous studies it is known that SnO can be fabricated through a reaction with H2O, which has low oxidizing power. Similarly, when combined with HQ having a bi-functional hydroxyl group, SnO-based 2D hybrid tincones can be produced. In most aromatic ring-based metalcones described in previous studies, graphitization by pyrolysis occurred during post-annealing. In this study of tincones fabricated with a divalent precursor after a vacuum post-annealing process, the structural rearrangement of the SnO and the benzene ring bonds proceeded to form a SnO-based hybrid 2D structure. The rearrangement of the resulting structure occurred through π-π stacking (without pyrolysis) of the benzene ring. To understand the mechanism of fabrication of 2D hybrid tincones by π-π stacking of the benzene ring and the increase of the crystallinity of SnO after the annealing process, the structural rearrangement was observed using X-ray photoelectron spectroscopy (XPS), grazing incidence X-ray diffraction (GIXRD), grazing-incidence wide-angle X-ray scattering (GIWAXS), and Raman spectroscopy. Thereafter, the design of the crystal structure was investigated.

Dry-Etchable Molecular Layer-Deposited Inhibitor Using Annealed Indicone Film for Nanoscale Area-Selective Deposition.

In semiconductor production, the technology node of a device is becoming extremely small below 5 nm. Area selective deposition (ASD) is a promising technique for creating improved overlay or self-alignment, remedying a conventional top-down method. However, the conventional materials and process (self-assembled monolayer, polymer and carbon film fabricated by chemical vapor deposition, and spin coating) for ASD are not suitable for highly conformal deposition. Thus, we investigated a new strategy to deposit conformal films in ASD by molecular layer deposition (MLD). The MLD processes were conducted for an indicone film deposited by INCA-1 (bis(trimethysily)amidodiethyl indium) and hydroquinone (HQ), as well as an alucone film deposited by TMA (trimethylaluminum) and HQ. After thermal heat treatment of the MLD films, variations in thickness, refractive index, and constituent elements of the annealed MLD films were investigated. The indicone film was used as an inhibiting layer for ASD and was etchable with a dry-etching process. The reactive ion etching process on annealed indicone film was optimized according to plasma power, gas concentration, and working pressure. Ruthenium (Ru) ALD was then performed on the annealed MLD films to investigate nucleation delaying cycles and inhibiting properties. A patterned substrate with an MLD/Si line was created via the RIE process, which was allowed to observe the selectivity of the annealed MLD films. In addition, a patterned substrate of SiO2/annealed indicone/Mo was used to investigate the Ru-selective ALD at the nanoscale. The Ru thin film was selectively deposited on the Mo side-wall surface of a 3D trench structure. The growth of the Ru film was inhibited selectively on an annealed indicone surface of approximately 5 nm.

Dickkopf-1 promotes angiogenesis by upregulating VEGF receptor 2-mediated mTOR/p70S6K signaling in hepatocellular carcinoma.

The expression of Dickkopf-1 (DKK1), a negative regulator of the Wnt/ß-catenin signaling pathway, is upregulated in hepatocellular carcinoma (HCC). Here, we investigated the tumorigenic and angiogenic potential of DKK1 in HCC. Stable cell lines were established using the clustered regularly interspaced short palindromic repeats (CRISPR)-associated nuclease 9 (CRISPR/Cas9)-based DKK1 knock-out system in Hep3B cells and the tetracycline-based DKK1 inducible system in Huh7 cells. Multicellular tumor spheroids (MCTSs) were cultured using Hep3B stable cells. We also employed xenografts generated using Hep3B stable cells and transgenic mouse models established using hydrodynamic tail vein injection. The angiogenic potential increased in HUVECs treated with CM from Huh7 stable cells with high DKK1 expression and Hep3B wild-type cells. DKK1 accelerated the downstream molecules of vascular endothelial growth factor receptor 2 (VEGFR2)-mediated mTOR/p70 S6 kinase (p70S6K) signaling. MCTSs generated using Hep3B wild-type cells promoted compact spheroid formation and increased the expression of CD31 and epithelial-mesenchymal transition (EMT) markers, and increased the VEGFR2-mediated mTOR/p70S6K signaling, compared to the controls (all P<0.01). Xenograft tumors generated using Hep3B cells with DKK1 knock-out (n=10) exhibited slower growth than, the controls (n=10) and the expression of Ki-67, VEGFR2, CD31 and EMT markers decreased (all P<0.05). In addition, forced DKK1 expression with HRAS in transgenic mouse livers (n=5) resulted in the formation of more tumors and increased expression of downstream molecules of VEGFR2-mediated mTOR/p70S6K signaling pathway as well as Ki67, CD31 and EMT markers (P<0.05), compared to that of the controls (n=5). Our findings indicate that DKK1 facilitates angiogenesis and tumorigenesis by upregulating VEGFR2-mediated mTOR/p70S6K signaling in HCC.

Ultra-Low-Dose Spectral CT Based on a Multi-level Wavelet Convolutional Neural Network.

Spectral computed tomography (CT) based on a photon-counting detector (PCD) is a promising technique with the potential to improve lesion detection, tissue characterization, and material decomposition. PCD-based scanners have several technical issues including operation in the step-and-scan mode and long data acquisition time. One straightforward solution to these issues is to reduce the number of projection views. However, if the projection data are under-sampled or noisy, it would be challenging to produce a correct solution without precise prior information. Recently, deep-learning approaches have demonstrated impressive performance for under-sampled CT reconstruction. In this work, the authors present a multilevel wavelet convolutional neural network (MWCNN) to address the limitations of PCD-based scanners. Data properties of the proposed method in under-sampled spectral CT are analyzed with respect to the proposed deep-running-network-based image reconstruction using two measures: sampling density and data incoherence. This work presents the proposed method and four different methods to restore sparse sampling. We investigate and compare these methods through a simulation and real experiments. In addition, data properties are quantitatively analyzed and compared for the effect of sparse sampling on the image quality. Our results indicate that both sampling density and data incoherence affect the image quality in the studied methods. Among the different methods, the proposed MWCNN shows promising results. Our method shows the highest performance in terms of various evaluation parameters such as the structural similarity, root mean square error, and resolution. Based on the results of imaging and quantitative evaluation, this study confirms that the proposed deep-running network structure shows excellent image reconstruction in sparse-view PCD-based CT. These results demonstrate the feasibility of sparse-view PCD-based CT using the MWCNN. The advantage of sparse view CT is that it can significantly reduce the radiation dose and obtain images with several energy bands by fusing PCDs. These results indicate that the MWCNN possesses great potential for sparse-view PCD-based CT.

Quantitative Photothermal Characterization with Bioprinted 3D Complex Tissue Constructs for Early-Stage Breast Cancer Therapy Using Gold Nanorods.

Plasmonic photothermal therapy (PPTT) using gold nanoparticles (AuNPs) has shown great potential for use in selective tumor treatment, because the AuNPs can generate destructive heat preferentially upon irradiation. However, PPTT using AuNPs has not been added to practice, owing to insufficient heating methods and tissue temperature measurement techniques, leading to unreliable and inaccurate treatments. Because the photothermal properties of AuNPs vary with laser power, particle optical density, and tissue depth, the accurate prediction of heat generation is indispensable for clinical treatment. In this report, bioprinted 3D complex tissue constructs comprising processed gel obtained from porcine skin and human decellularized adipose tissue are presented for characterization of the photothermal properties of gold nanorods (AuNRs) having an aspect ratio of 3.7 irradiated by a near-infrared laser. Moreover, an analytical function is suggested for achieving PPTT that can cause thermal damage selectively on early-stage human breast cancer by regulating the heat generation of the AuNRs in the tissue.

Facile rearrangement of molecular layer deposited metalcone thin films by electron beam irradiation for area selective atomic layer deposition.

Area selective atomic layer deposition (AS-ALD) is a promising future technology for the realization of a 5 nm scale Si complementary field effect transistor (FET) and its application in industry. AS-ALD is one of the "bottom-up" technologies, which is a key process that can reduce the cost of fabrication and decrease positional error as an alternative to the conventional "top down" technology. We researched an inhibitor for AS-ALD using molecular layer deposited (MLD) films annealed by electron beam irradiation (EBI). We studied the effect of EBI on an indicone film that was fabricated by using bis(trimethylsilyl)amidodiethyl indium (INCA-1), hydroquinone (HQ), an alucone film fabricated by using trimethylaluminum (TMA) and 4-mercaptophenol (4MP). The EBI effect on MLD films was evaluated by investigating the changes in thickness, composition and structure. In order to observe the selectivity of the annealed indicone film, atomic layer deposition of ZnO was performed on the annealed indicone/silicon line pattern, and it was found that the surface of annealed indicone can inhibit ALD of ZnO for 20 cycles as compared to a Si surface.