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Cytolethal distending toxin (CDT) belongs to the genotoxin family and is closely related to Campylobacter jejuni-induced gastroenteritis. We recently reported that CDT triggers the danger-associated molecular pattern (DAMP)-associated signaling to exert deleterious effects on host cells. However, how CDT traffics in cells and the mechanism of CDT toxicity remain to be elucidated. In this study, we first reported that CDT interacts with receptor of advanced glycation end product (RAGE) and high mobility group box 1 (HMGB1) to enter the cells. Our results further indicate that CdtB transportation in cells through the dynamin-dependent endocytic pathway and lysosomes is involved in this process. Conversely, knockdown of RAGE using CRISPR-Cas9 resulted in a significant reduction in CDT-arrested cell cycles, indicating that RAGE is essential for CDT action in cells. The results of this study provide valuable insights into the pathogenic potential of CDT-producing bacteria, such as C. jejuni.

Background/Aim: Lung cancer notably contributes to tumor-associated mortality worldwide, and standard chemotherapy is used for lung cancer patients. However, its therapeutic efficacy remains unsatisfactory. This study aimed to evaluate the effects and molecular mechanisms of sorafenib and bufalin combination therapy on lung cancer cells in vitro. Materials and Methods: NCI-H292 cells were treated with sorafenib, bufalin, and sorafenib in combination with bufalin. Cell viability, ROS production, Ca(2+) release, and mitochondrial membrane potential were examined by flow cytometric assay. Annexin V/PI staining and chromatin condensation were examined by the apoptosis assays. Finally the molecular mechanism of apoptosis-associated protein expression was investigated by western blotting. Results: NCI-H292 cells treated with sorafenib in combination with bufalin showed significantly decreased viability, enhanced cellular apoptosis, and DNA condensation when compared to that with sorafenib or bufalin alone. Moreover, the combination treatment exhibited higher reactive oxygen species (ROS) production and lower mitochondrial membrane potential (ΔΨm). The combined treatment resulted in higher expression of SOD but lower catalase compared to sorafenib treatment alone. Compared to sorafenib or bufalin treatment alone, the combination treatment resulted in lower Bcl-2 expression but higher Bax, Bad, APAF-1, caspase-3, and caspase-9. Conclusion: Sorafenib in combination with bufalin shows more potent cytotoxic effects and cell apoptosis than sorafenib or bufalin treatment alone in NCI-H292 cells. The combined treatment significantly enhanced apoptotic cell death in NCI-H292 lung cancer cells by activating ROS-, mitochondria-, and caspase-signaling pathways in vitro.

Pancreatic cancer has higher incidence and mortality rates worldwide. PW06 [(E)-3-(9-ethyl-9H-carbazol-3-yl)-1-(2,5-dimethoxyphenyl) prop-2-en-1-one] is a carbazole derivative containing chalcone moiety which was designed for inhibiting tumorigenesis in human pancreatic cancer. This study is aimed at investigating PW06-induced anticancer effects in human pancreatic cancer MIA PaCa-2 cells in vitro. The results showed PW06 potent antiproliferative/cytotoxic activities and induced cell morphological changes in a human pancreatic cancer cell line (MIA PaCa-2), and these effects are concentration-dependent (IC50 is 0.43 μM). Annexin V and DAPI staining assays indicated that PW06 induced apoptotic cell death and DNA condensation. Western blotting indicated that PW06 increased the proapoptotic proteins such as Bak and Bad but decreased the antiapoptotic protein such as Bcl-2 and Bcl-xL. Moreover, PW06 increased the active form of caspase-8, caspase-9, and caspase-3, PARP, releasing cytochrome c, AIF, and Endo G from mitochondria in MIA PaCa-2 cells. Confocal laser microscopy assay also confirmed that PW06 increased Bak and decreased Bcl-xL. Also, the cells were pretreated with inhibitors of caspase-3, caspase-8, and caspase-9 and then were treated with PW06, resulting in increased viable cell number compared to PW06 treated only. Furthermore, PW06 showed a potent binding ability with hydrophobic interactions in the core site of the Fas-Fas death domains (FADD). In conclusion, PW06 can potent binding ability to the Fas-FADD which led to antiproliferative, cytotoxic activities, and apoptosis induction accompanied by the caspase-dependent and mitochondria-dependent pathways in human pancreatic cancer MIA PaCa-2 cells.

In this case study, we report the successful treatment of a 35-year-old woman with a hyperdivergent skeletal pattern, open bite and severe transverse deficiency, exhibiting a skeletal Class III malocclusion. The treatment plan included 3D correction of these issues with surgically assisted rapid maxillary expansion (SARME) to solve the transverse deficiency, presurgical orthodontic treatment including aligning and levelling of the teeth in both arches, LeFort I osteotomy and bilateral sagittal split ramus osteotomy, and postsurgical correction of malocclusion. Orthodontic treatment was performed with labial brackets, and the patient achieved satisfactory occlusion and a significantly improved facial profile. Retention at the 1-year follow-up showed stable occlusion and arch forms with a harmonious facial profile.

The importance of teacher leadership has gradually come to be recognized in English Language Teaching (ELT). Research on this topic, however, has focused on program management or learner perception without considering teacher emotions. This study explores the leadership development of one Chinese English teacher who was a subject leader in the 12-Year Basic Education Reform in Taiwan with an aim to show how negative emotions may impede leadership development. Data were gathered from interviews and documents. The results reveal negative emotions—worry, anxiety, powerlessness, exhaustion, and dissatisfaction—in the English subject leader’s journey of developing a school-based curriculum. These emotions not only signify unpreparedness, low self-efficacy, limited support, exhausting work, and a divided vision, but also a disempowerment resulting from a hierarchical leader-follower relationship. This study thus highlights the primacy of learning a new mindset of horizontal teacher leadership and calls attention to the role emotions play in leadership development. 英語教學(ELT)已逐漸注意到教師領導的重要性。但是, 相關研究都著重在組織管理或學習者感知上, 而尚未討論教師的情緒。本研究探討一位在臺灣十二年國教改革中, 身為英語校本課程召集人的領導力發展過程, 重點將展現負面情緒如何阻礙教師領導力的發展。資料主要來自訪談和文件。研究結果顯示, 該英語學科召集人在校本課程的開發過程中, 所面臨的負面情緒, 如憂慮、焦慮、無能為力、疲憊和不滿。這些負面情緒不僅顯示教師領導的準備不足、低自我效能、有限的支援、工作疲憊感和分歧的視野角度, 而且還指出領導者與下屬之間的上下關係剝奪教師的賦權。據此, 本研究凸顯平等教師領導新思維的重要性, 並呼籲情緒在語言教師領導發展中所扮演的重要角色。

Background Falls among older adults are a serious public health problem. Many studies indicate that positive functional fitness performance decreases the risk of falls. A limited amount of previous study has investigated the association between broad functional fitness and the fall risk. This study examines the associations between functional fitness and the risk of falling among community-dwelling older adults. Methods Three waves of cross-sectional data were collected from 2017 to 2019 in Taipei City, Taiwan. Six hundred sixty-five participants aged ≥65 years were randomly recruited from 12 districts of Taipei. Eight functional fitness tests (i.e., back scratch, chair-sit and-reach, 8-ft up-and-go, 30-s sit-to-stand, 30-s arm curl, 30-s single-leg stance, 2-min step, and hand grip strength tests) were performed to record the physical performance of older subjects. A Chinese version of the fall-risk questionnaire (FRQ) was used to calculate the fall risk scores. Linear regression and logistic regression were utilized to estimate the relationships of each functional fitness and fall risk. Result The results showed that 37.45% of older adults had a high risk of falling. It was found for each functional fitness that performance was linearly associated with the risk of falling. Moreover, older adults with low-performance levels in all functional fitness except back-scratching were more likely to have a higher risk of falling. Conclusions Our study indicated that functional fitness performance appears to provide valid predictive guidance for reducing the risk of falling among the older population.

Background/aim Demethoxycurcumin (DMC), one of the derivatives of curcumin, has been shown to induce apoptotic cell death in many human cancer cell lines. However, there is no available information on whether DMC inhibits metastatic activity in human glioblastoma cancer cells in vitro. Materials and methods DMC at 1.0-3.0 μM significantly decreased the proliferation of GBM 8401 cells; thus, we used 2.0 μM for further investigation regarding anti-metastatic activity in human glioblastoma GBM 8401 cells. Results The internalized amount of DMC has reached the highest level in GBM 8401 cells after 3 h treatment. Wound healing assay was used to determine cell mobility and results indicated that DMC suppressed cell movement of GBM 8401 cells. The transwell chamber assays were used for measuring cell migration and invasion and results indicated that DMC suppressed cell migration and invasion in GBM 8401 cells. Gelatin zymography assay was used to examine gelatinolytic activity (MMP-2) in conditioned media of GBM 8401 cells treated by DMC and results demonstrated that DMC significantly reduced MMP-2 activity. Western blotting showed that DMC reduced the levels of p-EGFR(Tyr1068), GRB2, Sos1, p-Raf, MEK, p-ERK1/2, PI3K, p-Akt/PKBα(Thr308), p-PDK1, NF-κB, TIMP-1, MMP-9, MMP-2, GSK3α/β, β-catenin, N-cadherin, and vimentin, but it elevated Ras and E-cadherin at 24 h treatment. Conclusion DMC inhibited cancer cell migration and invasion through inhibition of PI3K/Akt and NF-κB signaling pathways in GBM 8401 cells. We suggest that DMC may be used as a novel anti-metastasis agent for the treatment of human glioblastoma cancer in the future.

The macro domain is an ADP-ribose (ADPR) binding module, which is considered to act as a sensor to recognize nicotinamide adenine dinucleotide (NAD) metabolites, including poly ADPR (PAR) and other small molecules. The recognition of macro domains with various ligands is important for a variety of biological functions involved in NAD metabolism, including DNA repair, chromatin remodeling, maintenance of genomic stability, and response to viral infection. Nevertheless, how the macro domain binds to moieties with such structural obstacles using a simple cleft remains a puzzle. We systematically investigated the Middle East respiratory syndrome-coronavirus (MERS-CoV) macro domain for its ligand selectivity and binding properties by structural and biophysical approaches. Of interest, NAD, which is considered not to interact with macro domains, was co-crystallized with the MERS-CoV macro domain. Further studies at physiological temperature revealed that NAD has similar binding ability with ADPR because of the accommodation of the thermal-tunable binding pocket. This study provides the biochemical and structural bases of the detailed ligand-binding mode of the MERS-CoV macro domain. In addition, our observation of enhanced binding affinity of the MERS-CoV macro domain to NAD at physiological temperature highlights the need for further study to reveal the biological functions., Meng-Hsuan Lin et al. investigate MERS-CoV macro domain binding selectivity with NAD and NAD metabolites under various conditions. At physiological temperature, NAD is observed to have enhanced binding affinity to the MERS-CoV macro domain, shedding light on a new possible role of the MERS-CoV macro domain in viral replication.

Background/Aim: Ouabain, isolated from natural plants, exhibits anticancer activities; however, no report has presented its mechanism of DNA damage induction in human osteosarcoma cancer cells in vitro. The aim of this study was to investigate whether ouabain induces DNA damage and repair, accompanied with molecular pathways in human osteosarcoma cancer U-2 OS cells in vitro. Materials and Methods: The percentage of viable cell number was measured by flow cytometric assay; DNA damage was assayed by DAPI staining, comet assay, and agarose gel electrophoresis. DNA damage and repair associated protein expressions were assayed by western blotting assays. Results: Ouabain reduced total cell viability, induced chromatin condensation, DNA fragmentation, and DNA damage in U-2 OS cells. Ouabain increased p-ATM(Ser1981), p-ATR(Ser428), and p53 at 2.5-10 μM, increased p-p53(Ser15) at 10 μM; however, it decreased p-MDM2(Ser166) at 2.5-10 μM. Ouabain increased p-H2A.X(Ser139), MDC-1, and PARP at 2.5-10 μM and BRCA1 at 5-10 μM; however, it decreased DNA-PK and MGMT at 2.5-10 μM in U-2 OS cells at 48 h treatment. Ouabain promoted expression and nuclear translocation of p-H2A.X(Ser139) in U-2 OS cells and this was confirmed by confocal laser microscopy. Conclusion: Ouabain reduced total viable cell number through triggering DNA damage and altering the protein expression of DNA damage and repair system in U-2 OS cells in vitro.

Background/aim Hydrogen peroxide (H2O2) is one of the reactive oxygen species (ROS), which can induce apoptotic cell death in numerous cancer cells. Pterostilbene (PTE), a natural polyphenolic compound, induces cell apoptosis in many human cancer cells. Materials and methods We investigated whether PTE could enhance H2O2-induced cell apoptosis in human keratinocyte HaCaT cells in vitro. The morphological change of HaCaT cells was observed and photographed under a contrast-phase microscope. The percentage of cell viability was measured by propidium iodide exclusion assay. Cell apoptosis was performed by Annexin V/PI double staining and assayed by flow cytometer. DNA condensation was measured by DAPI staining. The protein expression was determined by western blotting. ROS production-associated proteins were also assayed by confocal laser scanning microscopy. Results PTE pre-treatment enhanced H2O2 (600 μM)-induced cell morphological changes and reduced the total cell number (cell viability). The decreased cell viability in HaCaT cells was through induction of apoptotic cell death, which was confirmed by Annexin V/PI double staining and DAPI staining. Western blotting studies indicated that HaCaT cells which were pre-treated with PTE (100 μM) and then co-treated with H2O2 (600 μM) for 12 h showed significantly increased levels of SOD (Cu/Zn), SOD (Mn), Bax, caspase-3, caspase-8, caspase-9, PARP, p53, p-p53, and p-H2A.X but decreased levels Bcl-2 and catalase. Results also showed that HaCaT cells pre-treated with PTE and then co-treated with H2O2 had increased expression of SOD (Cu/Zn) and glutathione but decreased catalase. Conclusion These observations suggest that PTE pre-treatment can enhance the H2O2-induced apoptotic cell death in keratinocyte cells and may be an effective candidate for the treatment of proliferative keratinocytes.

SARS-CoV-2 is a novel pathogen causing pneumonia named COVID-19 and leading to a severe pandemic since the end of 2019. The genome of SARS-CoV-2 contains a macro domain that may play an important role in regulating ADP-ribosylation in host cells and initiating viral replication. Here, we report the 1H, 13C, and 15N resonance assignments of the SARS-CoV-2 macro domain. This work provides the ground for further structural deciphering and biophysical investigation in protein function and antiviral agent design. Supplementary Information The online version of this article (10.1007/s12104-020-09996-x) contains supplementary material, which is available to authorized users.

We demonstrate a high-performance normally-OFF AlGaN/GaN fin metal–insulator–semiconductor high electron mobility transistor (fin-MISHEMT) on silicon with a low work function metal-source contact ledge (LWFM-SCL). In order to realize the normally-OFF operation, an optimized gate-recessed fin structure is used. The fin structure inherently containing a gate-connected field plate (FP) design improves the breakdown voltage ( ${V}_{\text {BD}}$ ). Moreover, the LWFM-SCL can improve the device overall ON-resistance ( ${R}_{ \mathrm{ON}}$ ) by lowering the gate–source access resistance ( ${R}_{\text {a}}$ ). The proposed device with a gate–drain length ( ${L}_{\text {GD}}$ ) of 7 $\mu \text{m}$ exhibits superior characteristics such as a threshold voltage ( $V_{\text {TH}}$ ) of +1.2 V, maximum drain current ( ${I}_{\text {D, max}}$ ) of 825 mA/mm, ON-state/OFF-state current ( ${I}_{ \mathrm{ON}}/{I}_{ \mathrm{OFF}}$ ) ratio of 109–1010, subthreshold swing (SS) of 76 mV/decade, ${V}_{\text {BD}}$ of 810 V, and specific ${R}_{ \mathrm{ON}}$ ( ${R}_{\text {on, sp}}$ ) of 0.63 $\text{m}\Omega \cdot $ cm2. It also possesses excellent ${V}_{\text {TH}}$ hysteresis, temperature stability, and dynamic ${R}_{ \mathrm{ON}}$ characteristics. These results suggest that the proposed device is very suitable for high power switching applications.

The present study aimed to investigate the effects of steamed notoginseng single-flavored medicine, herb pairs, compound medicine on anemia rats induced by N-acetyl phenyl hydrazine (APH) to explore the underlying hematinic regulation mechanisms. Rats were randomly divided into seven groups: control group (CG); model group (MG); positive control group (PCG); steamed notoginseng group (SNG); ginseng group (GG); herbal pair group (HPG) and compound prescription group (CPG). Day 12 of the experiment, the blood routine examination of the rats was measured. At the same time, the rats' plasma and urine samples were collected. An Ultra-performance Liquid Chromatography-Quadrupole-Time-of-Flight / Mass Spectrometry (UPLC-Q-TOF/MS) with unsupervised principal component analysis (PCA) and supervised partial least squares discriminant analysis (PLS-DA) combined analytical method was established for metabolomics study of steamed notoginseng. Compared with the CG, red blood cell (RBC) and hemoglobin (Hb) levels in the MG were significantly lower (P l -valine and arachidonic acid, and 14 biomarkers up-regulated such as protoporphyrin IX and nicotinamide; 28 metabolites such as proline, histidine, phenylalanine, l -arginine and l -tyrosine were up-regulated in urine of the MG. The metabolic level of biomarkers could be changed to a normal state after the rats were given steamed notoginseng, herb pairs, and compound prescriptions. It is presumed that steamed notoginseng plays a role in blood enriching through 12 metabolic pathways, including valine, leucine and isoleucine biosynthesis, phenylalanine, tyrosine and tryptophan biosynthesis, retinol metabolism and so on.

This study demonstrates an enhancement-mode (E-mode) InAlN/GaN MOSHEMT on a silicon substrate with a Schottky tri-drain extension (STDE) to yield a large breakdown voltage ( $\text{V}_{\text {BD}}$ ) while maintaining a low on-resistance ( $\text{R}_{\text {on}}$ ). The E-mode operation is realized by a recessed tri-gate nanowire structure. The STDE functions as a drain-connected field plate (FP) to effectively distribute the electric field (E-field) around the drain contact edge, improving the $\text{V}_{\text {BD}}$ . Moreover, through the metal of the STDE directly contacting the 2-D electron gas (2-DEG) from the sidewalls, a low specific $\text{R}_{\text {on}}$ ( $\text{R}_{\text {on, sp}}$ ) is achieved. The proposed device with a gate-to-drain length ( $\text{L}_{\text {GD}}$ ) of $5~\mu \text{m}$ exhibits a threshold voltage ( $\text{V}_{\text {TH}}$ ) of +0.9 V, large maximum drain current ( $\text{I}_{\text {D, max}}$ ) of 815 ± 27 mA/mm, high $\text{I}_{\text {on}}/\text{I}_{\text {off}}$ ratio of 1010, steep subthreshold swing (SS) of 67 mV/decade, superior $\text{V}_{\text {BD}}$ of 830 V, and low $\text{R}_{\text {on, sp}}$ of 0.74 ± 0.04~\text{m}\Omega \cdot cm2. With $\text{L}_{\text {GD}}$ of $10~\mu \text{m}$ , a $\text{V}_{\text {BD}}$ of 1190 V is achieved, corresponding to a $\text{R}_{\text {on, sp}}$ of 1.39 ± $0.07~\text{m}\Omega \cdot$ cm2. These results reveal great potential for future E-mode power device applications.

Novel Al 0.75 Ga 0.25 N/Al x Ga 1-x N/Al 0.75 Ga 0.25 N/AlN metal-oxide-semiconductor heterostructure field-effect transistors (MOS-HFETs) with symmetrically-graded widegap Al x Ga 1-x N channel (x = 0.75 → 0.25 → 0.75) grown on a SiC substrate are investigated. Al 2 O 3 was devised as the gate dielectric by using a non-vacuum ultrasonic spray pyrolysis deposition (USPD) technique. Device characteristics with respect to different etch depths of the source/drain recesses were studied. For a 2-μm gate length (L G ), the present widegap V-shape-channel MOS-HFET has shown improved maximum drain-source current density (I DS,max ) of 299.3 A/mm at V DS = 20 V, I DS density at V GS = 0 V (I DSS0 ) of 153.9 mA/mm, on/off-current ratio (I on /I off ) of 1.4 × 10 7 , extrinsic transconductance (g m , max ) of 16.7 mS/mm, two-terminal off-state gate-drain breakdown voltage (BV GD ) of -379 V, and three-terminal on-state drain-source breakdown voltage (BV DS ) of 339 V. Besides, superior deep-UV sensing performance with high spectral responsivity (SR) of 1780 (810.2) A/W at wavelength λ = 250 (300) nm are also achieved.

Background/aim Demethoxycurcumin (DMC), a derivate of curcumin from natural plants, exerts antitumor effects on various human cancer cells in vitro and in vivo. Nevertheless, no reports have disclosed whether DMC can affect the growth of human cervical cancer cells in vivo. Therefore we investigated the antitumor effects of DMC on a HeLa cell xenograft model in nude mice in this study. Materials and methods Twenty-four nude mice were subcutaneously injected with HeLa cells. All mice were randomly divided into control, low-dose DMC (30 mg/kg), and high-dose DMC (50 mg/kg) groups and individual mice were treated intraperitoneally accordingly every 2 days. Results DMC significantly reduced tumor weights and volumes of HeLa cell xenografts in mice, indicating the suppression of growth of xenograft tumors. Conclusion These effects and findings might provide evidence for investigating the potential use of DMC as an anti-cervical cancer drug in the future.

The explorations of non-Hermiticity have been devoted to investigate the disorder-induced many-body localization (MBL). However, the sensitivity of the spatial boundary conditions and the interplay of the non-Hermitian skin effect with many-body phenomena are not yet clear. For a MBL system in the presence of non-reciprocal tunnelings and random disorder potential, we identify two different complex-real spectral transitions, one is present for both open and periodic boundaries while the other is present only for open boundaries of a coupled non-Hermitian chains. The later is driven due to the inter-chain coupling at weak disorder where the level statistics of the real eigenenergy phase follows Gaussian orthogonal ensemble. We further characterize wavefunctions through the (biorthogonal) inverse participation ratio and fractal dimension, which reveal the suppression of skin effect in the non-Hermitian MBL phase. Finally, we demonstrate that the quench dynamics of the local particle density, spin imbalance, and entanglement entropy also signify the hallmark of the boundary effects and non-ergodic character of many-body localization., 11 pages, 10 figures; version accepted for publication in Phys. Rev. B

Chronic inflammation induces autoimmune disorders and chronic diseases. Several natural products activate nuclear factor erythroid 2-related factor 2 (Nrf2) signaling, attenuating inflammatory responses. Ergosta-7,9(11),22-trien-3β-ol (EK100) isolated from Cordyceps militaris showed anti-inflammatory and antioxidative activity, but those mechanisms are still unclear. This study is the first to investigate EK100 on antioxidant Nrf2 relative genes expression in LPS-stimulated macrophage-like cell lines. The results showed that EK100 reduced IL-6 (interleukin-6) and tumor necrosis factor-α production. EK100 also attenuated a mitogen-activated protein kinase/activator protein-1 (MAPK/AP-1) pathway and interleukin-6/Janus kinase/signal transducer and activator of transcription (IL-6/JAK/STAT) pathway in LPS-stimulated cells. Toll-like receptor 4 (TLR4) inhibitor CLI-095 and MAPK inhibitors can synergize the anti-inflammatory response of EK100 in LPS-stimulated cells. Moreover, EK100 activated Nrf2/HO-1 (heme oxygenase-1) signaling in LPS-stimulated murine macrophage-like RAW 264.7 cells, murine microglial BV2 cells, and human monocytic leukemia THP-1 cells. However, Nrf2 small interfering RNA (Nrf2 siRNA) reversed EK100-induced antioxidative proteins expressions. In conclusion, EK100 showed anti-inflammatory responses via activating the antioxidative Nrf2/HO-1 signaling and inhibiting TLR4 related MAPK/AP-1 induced IL-6/JAK/STAT pathways in the LPS-stimulated cells in vitro. The results suggest EK100 acts as a novel antioxidant with multiple therapeutic targets that can potentially be developed to treat chronic inflammation-related diseases.

Gastric cancer has a poor prognosis; once cancer has metastasized, it can easily lead to patient death. Melittin is one of the major components extracted from the bee venom. It has been shown that melittin emerges antitumor activities against many human cancer cell lines. Our results indicated that melittin at 0.2-0.5 µm significantly reduced total cell viability in human gastric cancer AGS cells. At low concentrations (0.05-0.15 µm), melittin displayed antimetastasis effects and inhibited cell adhesion and colony formation. Besides, it inhibited cell motility and suppressed cell migration and invasion. Melittin inhibited the activities of MMP-2 and MMP-9 and the integrity of cell membrane in AGS cells. Furthermore, Western blotting results showed that melittin decreased the protein expressions of Wnt/BMP and MMP-2 signaling pathways. Based on these observations, melittin inhibited cell migration and invasion of AGS cells through multiple signaling pathways. It may be used to treat metastasized gastric cancers in the future.

Cantharidin (CTD), a sesquiterpenoid bioactive substance, has been reported to exhibit anticancer activity against various types of cancer cells. The aim of the present study was to investigate the apoptosis effects and the underlying mechanisms of CTD on osteosarcoma U-2 OS cells. Results showed that CTD induced cell morphologic changes, reduced total viable cells, induced DNA damage, and G2/M phase arrest. CTD increased the production of reactive oxygen species and Ca2+, and elevated the activities of caspase-3 and −9, but decreased the level of mitochondrial membrane potential. Furthermore, CTD increased the ROS- and ER stress-associated protein expressions and increased the levels of pro-apoptosis-associated proteins, but decreased that of anti-apoptosis-associated proteins. Based on these observations, we suggested that CTD decreased cell number through G2/M phase arrest and the induction of cell apoptosis in U-2 OS cells and CTD could be a potential candidate for osteosarcoma treatments.

This letter demonstrates a novel enhancement-mode (E-mode) tri-gate nanowire InAlN/GaN MOSHEMT with ultrasonic spray pyrolysis deposition (USPD) deposited Al2O3 as the gate dielectric layer. The proposed device reveals a threshold voltage ( ${V}_{\text {TH}}$ ) of +2.3 V and a maximum drain current ( ${I}_{D, \text {max}}$ ) of 705 mA/mm. It also exhibits superior electrical performances, including a high ON-state/ OFF-state current ( ${I}_{ {{ \scriptscriptstyle {\text {ON}}}}}/{I}_{ {{ \scriptscriptstyle {\text {OFF}}}}}$ ) ratio of 109–1010, a steep subthreshold swing (SS) of 65 mV/decade, and a large breakdown voltage (BV) of 800 V with a leakage current of 0.7 $\mu \text{A}$ /mm while keeping a low-specific ON-resistance ( ${R}_{ {{ \scriptscriptstyle {\text {ON}}}}, \text {sp}}$ ) of 1.04 $\text{m}\Omega \cdot \text {cm}^{\text {2}}$ . This novel E-mode device presents a great potential for power device applications.

Recent research on English-medium instruction (EMI) has examined university instructors’ professional identities in science and social science rather than in the humanities. To fill the gap...

Background/aim Evidence has indicated that fisetin induces cytotoxic effects in human cancer cell lines, including the inhibition of cell migration and invasion, however, the exact molecular mechanism of action of fisetin in human osteosarcoma cells remains unclear. Materials and methods The anti-metastatic mechanisms of fisetin in human osteosarcoma U-2 OS cells were investigated in vitro. Results Fisetin reduced the viability of cells at different concentrations (2.5, 5 and 10 μM) as measured by flow cytometric assay. Fisetin suppressed cell mobility, migration and invasion of U-2 OS cells, as shown by wound healing assay and transwell filter chambers, respectively. The gelatin zymography assay showed that fisetin inhibited MMP-2 activity in U-2 OS cells. Results from western blotting indicated that fisetin reduced the levels of pEGFR, SOS-1, GRB2, Ras, PKC, p-ERK1/2, p-JNK, p-p-38, VEGF, FAK, RhoA, PI3K, p-AKT, NF-ĸB, uPA, MMP-7, MMP-9, and MMP-13, but increased GSK3β and E-cadherin in U-2 OS cells after 48 h of treatment. Conclusion Fisetin can be used in the future, as a target for the treatment of metastasis of human osteosarcoma cells.

Fisetin, a naturally occurring flavonoid, is found in common fruits and vegetables and has been shown to induce cytotoxic effects in many human cancer cell lines. No information has shown that fisetin induced cell cycle arrest and apoptosis in mouse leukemia WEHI-3 cells. We found that fisetin decreased total viable cells through G0/G1 phase arrest and induced sub-G1 phase (apoptosis). We have confirmed fisetin induced cell apoptosis by the formation of DNA fragmentation and induction of apoptotic cell death. Results indicated that fisetin induced intracellular Ca[Formula: see text] increase but decreased the ROS production and the levels of [Formula: see text]m in WEHI-3 cells. Fisetin increased the activities of caspase-3, -8 and -9. Cells were pre-treated with inhibitors of caspase-3, -8 and -9 and then treated with fisetin and results showed increased viable cell number when compared to fisetin treated only. Fisetin reduced expressions of cdc25a but increased p-p53, Chk1, p21 and p27 that may lead to G0/G1 phase arrest. Fisetin inhibited anti-apoptotic protein Bcl-2 and Bcl-xL and increased pro-apoptotic protein Bax and Bak. Furthermore, fisetin increased the protein expression of cytochrome c and AIF. Fisetin decreased cell number through G0/G1 phase arrest via the inhibition of cdc25c and induction of apoptosis through caspase-dependent and mitochondria-dependent pathways. Therefore, fisetin may be useful as a potential therapeutic agent for leukemia.

Demethoxycurcumin (DMC), a derivate of curcumin, has been shown to induce apoptotic cell death in human glioblastoma multiforme GBM 8401 cells via cell cycle arrest and induction of cell apoptosis. However, there is no report showing DMC suppresses glioblastoma multiforme cells in vivo. In the present study, we investigated the effects of DMC on GBM8401 cells in vivo. At first, we established a luciferase-expressing stable clone named GBM 8401/luc2. Second, mice were inoculated subcutaneously with GBM 8401/luc2 cells to generate a xenograft tumor mice model. After inoculation, tumor volume reached 100–120 mm3, and all mice were randomly divided into three groups: Group I was treated with 110 µL phosphate-buffered solution (PBS) containing 0.1% dimethyl sulfoxide, Group II with 30 mg/kg of DMC, and Group III with 60 mg/kg of DMC. Mice from each group were given the oral treatment of DMC by gavage for 21 days. The body weight and tumor volume were recorded every 3 days. DMC significantly decreased the tumor volumes, and 60 mg/kg treatment showed a higher decrease in tumor volumes than that of 30 mg/kg, However, DMC did not affect the body weights. The photons emitted from mice tumors were detected with Xenogen IVIS imaging system, DMC at both doses decreased the total photon flux and 60 mg/kg treatment of DMC has low total photon flux than that of 30 mg/kg. The tumor volumes and weights in 60 mg/kg treatment of DMC were lower than that of 30 mg/kg. Immunohistochemical analysis was used to measure protein expression of tumors and results showed that DMC treatment led to lightly staining with anti-Bcl-2 and -XIAP and 60 mg/kg treatment of DMC has lighter staining with anti-Bcl-2 and -XIAP than that of 30 mg/kg. The higher dose (60 mg/kg) of DMC has higher signals of cleaved-caspase-3 than that of the lower dose (30 mg/kg). Furthermore, the hematoxylin and eosin (H&amp, E) staining of liver tissues showed no significant difference between DMC-treated and control-groups. Overall, these observations showed that DMC suppressed tumor properties in vivo and DMC may be used against human glioblastoma multiforme in the future.

Dynamics in correlated quantum matter is a hard problem, as its exact solution generally involves a computational effort that grows exponentially with the number of constituents. While a remarkable progress has been witnessed in recent years for one-dimensional systems, much less has been achieved for interacting quantum models in higher dimensions, since they incorporate an additional layer of complexity. In this work, we employ a variational method that allows for an efficient and controlled computation of the dynamics of quantum many-body systems in one and higher dimensions. The approach presented here introduces a variational class of wavefunctions based on complex networks of classical spins akin to artificial neural networks, which can be constructed in a controlled fashion. We provide a detailed prescription for such constructions and illustrate their performance by studying quantum quenches in one- and two-dimensional models. In particular, we investigate the nonequilibrium dynamics of a genuinely interacting two-dimensional lattice gauge theory, the quantum link model, for which we have recently shown -- employing the technique discussed thoroughly in this paper -- that it features disorder-free localization dynamics [P. Karpov et al., Phys. Rev. Lett. 126, 130401 (2021)]. The present work not only supplies a framework to address purely theoretical questions but also could be used to provide a theoretical description of experiments in quantum simulators, which have recently seen an increased effort targeting two-dimensional geometries. Importantly, our method can be applied to any quantum many-body system with a well-defined classical limit., 19 pages, 12 figures; version published in Physical Review B