Reconfigurable Manipulation of Oxygen Content on Metal Oxide Surfaces and Applications to Gas Sensing.

Oxygen vacancies and adsorbed oxygen species on metal oxide surfaces play important roles in various fields. However, existing methods for manipulating surface oxygen require severe settings and are ineffective for repetitive manipulation. We present a method to manipulate the amount of surface oxygen by modifying the oxygen adsorption energy by electrically controlling the electron concentration of the metal oxide. The surface oxygen control ability of the method is verified using first-principles calculations based on density functional theory (DFT), X-ray photoelectron spectroscopy (XPS), and electrical resistance analysis. The presented method is implemented by fabricating oxide thin film transistors with embedded microheaters. The method can reconfigure the oxygen vacancies on the In2O3, SnO2, and IGZO surfaces so that specific chemisorption dominates. The method can selectively increase oxidizing (e.g., NO and NO) and reducing gas (e.g., H2S, NH3, and CO) reactions by electrically controlling the metal oxide surface to be oxygen vacancy-rich or adsorbed oxygen species-rich. The proposed method is applied to gas sensors and overcomes their existing limitations. The method makes the sensor insensitive to one gas (e.g., H2S) in mixed-gas environments (e.g., NO2+H2S) and provides a linear response (R2 = 0.998) to the target gas (e.g., NO2) concentration within 3 s. We believe that the proposed method is applicable to applications utilizing metal oxide surfaces.

In-Memory-Computed Low-Frequency Noise Spectroscopy for Selective Gas Detection Using a Reducible Metal Oxide.

Concerns about indoor and outdoor air quality, industrial gas leaks, and medical diagnostics are driving the demand for high-performance gas sensors. Owing to their structural variety and large surface area, reducible metal oxides hold great promise for constructing a gas-sensing system. While many earlier reports have successfully obtained a sufficient response to various types of target gases, the selective detection of target gases remains challenging. In this work, a novel method, low-frequency noise (LFN) spectroscopy is presented, to achieve selective detection using a single FET-type gas sensor. The LFN of the sensor is accurately modeled by considering the charge fluctuation in both the sensing material and the FET channel. Exposure to different target gases produces distinct corner frequencies of the power spectral density that can be used to achieve selective detection. In addition, a 3D vertical-NAND flash array is used with the fast Fourier transform method via in-memory-computing, significantly improving the area and power efficiency rate. The proposed system provides a novel and efficient method capable of selectively detecting a target gas using in-memory-computed LFN spectroscopy and thus paving the way for the further development in gas sensing systems.

Synergistic improvement of sensing performance in ferroelectric transistor gas sensors using remnant polarization.

Gaseous pollutants, including nitrogen oxides, pose a severe threat to ecosystems and human health; therefore, developing reliable gas-sensing systems to detect them is becoming increasingly important. Among the various options, metal-oxide-based gas sensors have attracted attention due to their capability for real-time monitoring and large response. In particular, in the field of materials science, there has been extensive research into controlling the morphological properties of metal oxides. However, these approaches have limitations in terms of controlling the response, sensitivity, and selectivity after the sensing material is deposited. In this study, we propose a novel method to improve the gas-sensing performance by utilizing the remnant polarization of ferroelectric thin-film transistor (FeTFT) gas sensors. The proposed FeTFT gas sensor has IGZO and HZO as the conducting channel and ferroelectric layer, respectively. It is demonstrated that the response and sensitivity of FeTFT gas sensors can be modulated by engineering the polarization of the ferroelectric layer. The amount of reaction sites in IGZO, including electrons and oxygen vacancy-induced negatively charged oxygen, is changed depending on upward and downward polarization. The results of this study provide an essential foundation for further development of gas sensors with tunable sensing properties.

The Effect of Curcuma phaeocaulis Valeton (Zingiberaceae) Extract on Prion Propagation in Cell-Based and Animal Models.

Prion diseases are neurodegenerative disorders in humans and animals for which no therapies are currently available. Here, we report that Curcuma phaeocaulis Valeton (Zingiberaceae) (CpV) extract was partly effective in decreasing prion aggregation and propagation in both in vitro and in vivo models. CpV extract inhibited self-aggregation of recombinant prion protein (PrP) in a test tube assay and decreased the accumulation of scrapie PrP (PrPSc) in ScN2a cells, a cultured neuroblastoma cell line with chronic prion infection, in a concentration-dependent manner. CpV extract also modified the course of the disease in mice inoculated with mouse-adapted scrapie prions, completely preventing the onset of prion disease in three of eight mice. Biochemical and neuropathological analyses revealed a statistically significant reduction in PrPSc accumulation, spongiosis, astrogliosis, and microglia activation in the brains of mice that avoided disease onset. Furthermore, PrPSc accumulation in the spleen of mice was also reduced. CpV extract precluded prion infection in cultured cells as demonstrated by the modified standard scrapie cell assay. This study suggests that CpV extract could contribute to investigating the modulation of prion propagation.

Improved Clinical and Radiologic Outcomes Seen after Superior Capsule Reconstruction using Long Head Biceps Tendon Autograft.

PURPOSE: The objective of this study was to investigate the clinical and radiologic outcomes after superior capsule reconstruction (SCR) with biceps tendon (BT) for irreparable rotator cuff tears. METHODS: The retrospective study period was May 2015 through February 2018. The average follow-up was 32 months (24-48 months) after surgery. Study inclusion criteria included an arthroscopic SCR performed using only our technique and minimum 2-year clinical follow-up by office visit and survey. Exclusion criteria included irreparable subscapularis tear and those patients lost to follow-up. This method enabled SCR by using the extraarticular portion and the intraarticular portion and making it 2 to 3 bundles by moving back and forth in the intraarticular area. Physical examination and functional scoring procedures were performed before surgery and at 3, 6, 12, and 24 months after surgery. Radiography and magnetic resonance imaging (MRI) were performed before surgery, after surgery (only radiography), and at 6 and 24 months after surgery. RESULTS: Fifty-three shoulders involving 45 consecutive patients underwent BT technique for irreparable massive rotator cuff tears. The visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES), and constant score (CS) showed statistically significant improvement (VAS, 4.1-1.0; ASES, 60.9-82.7; and CS, 64.9-80.0; P < .0001). The shoulder active range of motion improved significantly by 23 for forward elevation (125.3-148.4; P < .0001) and by 12 for external rotation (38.0-50.9, P < .0001). The acromiohumeral distance (AHD) was significantly increased by 2.7 mm (4.4 ± 1.4 mm -> 7.1 ± 1.3 mm). No graft tear was detected in 39 patients (86.7%) during follow-up (24-48 months). CONCLUSIONS: SCR via our technique improved clinical and radiologic outcomes. Thirty-five (77.7%) patients achieved 17-point improvement (the minimally clinically important difference) in the last follow-up of ASES score. Clinical scores and AHD had significantly increased, and good healed rate (86.7%) was observed in MRI. LEVEL OF EVIDENCE: Level IV, retrospective case series.

Self-Assembling Peptides and Their Application in the Treatment of Diseases.

Self-assembling peptides are biomedical materials with unique structures that are formed in response to various environmental conditions. Governed by their physicochemical characteristics, the peptides can form a variety of structures with greater reactivity than conventional non-biological materials. The structural divergence of self-assembling peptides allows for various functional possibilities; when assembled, they can be used as scaffolds for cell and tissue regeneration, and vehicles for drug delivery, conferring controlled release, stability, and targeting, and avoiding side effects of drugs. These peptides can also be used as drugs themselves. In this review, we describe the basic structure and characteristics of self-assembling peptides and the various factors that affect the formation of peptide-based structures. We also summarize the applications of self-assembling peptides in the treatment of various diseases, including cancer. Furthermore, the in-cell self-assembly of peptides, termed reverse self-assembly, is discussed as a novel paradigm for self-assembling peptide-based nanovehicles and nanomedicines.

Anticancer Effect of the Ethyl Acetate Fraction from Orostachys japonicus on MDA-MB-231 Human Breast Cancer Cells through Extensive Induction of Apoptosis, Cell Cycle Arrest, and Antimetastasis.

The antibreast cancer activities of the ethyl acetate fraction from Orostachys japonicus (OJEF) were investigated in MDA-MB-231 human breast cancer cells through WST assay, DAPI staining, flow cytometry analysis, and western blotting. OJEF effectively inhibited MDA-MB-231 cells by inducing apoptosis via intrinsic, extrinsic, and endoplasmic reticulum (ER) stress response pathways, cell cycle arrest at the G1/S phase, and antimetastasis including inhibition of tight junction, adherens junction, invasion, and migration. The MAPK family-mediated upstream signal transduction through p-p38 and p-ERK was considered to affect the downstream signal transduction including induction of apoptosis, cell cycle arrest, and antimetastasis. In conclusion, we executed an integrated study on the anticancer activities of OJEF, which extensively induced apoptosis, cell cycle arrest, and antimetastasis in estrogen-independent MDA-MB-231 human breast cancer cells known to be liable to metastasize.

Upregulation of MicroRNA-1246 Is Associated with BRAF Inhibitor Resistance in Melanoma Cells with Mutant BRAF.

PURPOSE: Intrinsic and acquired resistance limit the therapeutic benefits of inhibitors of oncogenic BRAF in melanoma. To identify microRNAs (miRNAs) associated with resistance to a BRAF inhibitor, we compared miRNA expression levels in three cell lines with different BRAF inhibitor sensitivity. MATERIALS AND METHODS: miRNA microarray analysis was conducted to compare miRNA expression levels. Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) was performed to confirm the expression of differentially expressed miRNAs. The cellular effects of miR-1246 were further examined by MTT assay, immunoblotting analysis, cell cycle analysis, flow cytometric assay of apoptosis, and autophagy assay. RESULTS: The miRNA microarray analysis and qRT-PCR identified five miRNAs (miR-3617, miR-92a-1, miR-1246, miR-193b-3p, and miR-17-3p) with expression that was consistently altered in two BRAF inhibitor-resistant cell lines. Among the five miRNAs, a miR-1246 mimic significantly reduced the antiproliferative effects of the BRAF inhibitor PLX4720 in BRAF inhibitor-resistant A375P (A375P/Mdr) cells, suggesting that miR-1246 upregulation confers acquired resistance to BRAF inhibition. In particular, apoptosis was identified as a major type of cell death in miR-1246-transfected cells; however, necrosis predominated in mimic-control-transfected cells, indicating that the resistance to PLX4720 in miR-1246 mimic-transfected cells is predominantly due to a reduction in necrosis. Furthermore, we found that miR-1246 promoted G2/M arrest through autophagy as a way to escape cell death by necrosis and apoptosis in response to PLX4720. The promotion of BRAF inhibitor resistance by miR-1246 was associated with lowered levels of p-ERK. CONCLUSION: These results suggest that miR-1246 may be a potential therapeutic target in melanoma with acquired resistance to BRAF inhibitors.

Suppression of lytic replication of Kaposi's sarcoma-associated herpesvirus by autophagy during initial infection in NIH 3T3 fibroblasts.

Kaposi's sarcoma-associated herpesvirus (KSHV) is the infectious cause of the angioproliferative neoplasm Kaposi's sarcoma (KS). We first confirmed the susceptibility of NIH 3T3 fibroblasts to KSHV by infecting them with BCP-1-derived KSHV. Lytic replication of KSHV was confirmed by PCR amplification of viral DNA isolated from culture supernatants of KSHV-infected cells. The template from KSHV-infected NIH 3T3 cells resulted in an intense viral DNA PCR product. A time course experiment revealed the disappearance of KSHV-specific DNA in culture supernatant of NIH 3T3 cells during a period between 48 h and 72 h postinfection. Furthermore, 3 days postinfection, infected NIH 3T3 cells showed no evidence of latent or lytic transcripts, including LANA, vFLIP, vCyclin, and vIL-6. These results imply that KSHV infection in NIH 3T3 cells is unstable and is rapidly lost on subsequent culturing. Additionally, we detected an enhancement of autophagy early in infection with KSHV. More interestingly, inhibition of autophagy by Beclin 1 siRNA or 3-methyladenine significantly increased the amount of KSHV-specific DNA in the culture supernatant of NIH 3T3 cells when compared to the group treated with KSHV infection alone, implying that autophagy prevents lytic replication of KSHV. Taken together, our data suggest that autophagy could be one of the cellular mechanisms utilized by host cells to promote viral clearance.

Activin A, exendin-4, and glucose stimulate differentiation of human pancreatic ductal cells.

Islet transplantation is one treatment option for diabetes mellitus. However, novel sources of pancreatic islets or insulin-producing cells are required because the amount of donor tissue available is severely limited. Pancreatic ductal cells are an alternative source of ß-cells because they have the potential to differentiate into insulin-producing cells. We investigated whether treatment of human pancreatic ductal cells with activin A (ActA) and exendin-4 (EX-4) stimulated transdifferentiation of the cells, both in vitro and in vivo. We treated human pancreatic ductal cells with ActA and EX-4 in high-glucose media to induce differentiation into insulin-producing cells and transplanted the cells into streptozotocin-induced diabetic nude mice. Co-treatment of mice with ActA and EX-4 promoted cell proliferation, induced expression of pancreatic ß-cell-specific markers, and caused glucose-induced insulin secretion compared with the ActA or EX-4 mono-treatment groups respectively. When pancreatic ductal cells treated with ActA and EX-4 in high-glucose media were transplanted into diabetic nude mice, their blood glucose levels normalized and insulin was detected in the graft. These findings suggest that pancreatic ductal cells have a potential to replace pancreatic islets for the treatment of diabetes mellitus when the ductal cells are co-treated with ActA, EX-4, and glucose to promote their differentiation into functional insulin-producing cells.

Trophic molecules derived from human mesenchymal stem cells enhance survival, function, and angiogenesis of isolated islets after transplantation.

BACKGROUND: Mesenchymal stem cells (MSCs), also known as multipotent progenitor cells, release several factors that support cell survival and enhance wound healing. We hypothesized that MSC-secreted molecules would induce a trophic effect in pancreatic islet culture conditions. METHODS: Pancreatic islets were co-cultured with MSCs, and ADP/ATP ratios, glucose stimulated insulin secretion (GSIS), and DNA fragmentation were evaluated to measure islet quality and viability in vitro. The induction of signal molecules related to the control of survival, function, and angiogenesis was also analyzed. Cell quality assays, DNA fragmentation assays, and islet transplantation into streptozotocin-induced diabetic mice were performed using MSC-conditioned medium (CM)-cultured islets. Furthermore, we identified soluble molecules within MSC-CM. RESULTS: Islets co-cultured with MSCs demonstrated lower ADP/ATP ratios, and higher GSIS indexes and viability. Furthermore, co-cultured islets revealed higher levels of anti-apoptotic signal molecules (X-linked inhibitor of apoptosis protein, Bcl-xL, Bcl-2, and heat shock protein-32) and demonstrated increased vascular endothelial growth factor receptor 2 and Tie-2 mRNA expression and increased levels of phosphorylated Tie-2 and focal adhesion kinase protein. Islets cultured in MSC-CM demonstrated lower ADP/ATP ratios, less apoptosis, and a higher GSIS indexes. Diabetic mice that received islet transplants (200 islet equivalent) cultured in MSC-CM for 48 hr demonstrated significantly lower blood glucose levels and enhanced blood vessel formation. In addition, interleukin-6, interleukin-8, vascular endothelial growth factor-A, hepatocyte growth factor, and transforming growth factor-beta were detected at significant levels in MSC-CM. CONCLUSIONS: These results suggest that the trophic factors secreted by human MSCs enhance islet survival and function after transplantation.