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Inflammation, oxidative stress, and apoptosis contribute to myocardial ischemia/reperfusion injury (I/RI). Alpha-lipoic acid (ALA) plays a critical role in I/RI by impeding apoptosis and inflammation. Here, we aimed to explore the underlying mechanisms of ALA after I/RI.The left anterior descending coronary artery (LAD) was ligated, and H9c2 cells were exposed to hypoxia/reoxygenation (H/R) to establish an I/RI model. Prior to this, H9c2 cells and rats were treated using an appropriate amount of ALA. The cardiac function, inflammatory factors, and myocardial pathology were assessed in vitro. We detected cell viability, apoptosis, and oxidative stress-related factors in vivo. Moreover, proteins of the HMGB1/TLR4/NF-κB signaling pathway were detected both in vivo and in vitro.We observed that ALA increased cell viability in vitro and decreased apoptosis in vitro and in vivo. ALA inhibited reactive oxygen species production, decreased malondialdehyde, and increased superoxide dismutase activity to resist oxidative stress in vitro. ALA also reduced the expression of inflammatory cytokines (IL-6, IL-1β, and TNF-α) in vivo. ALA also suppressed the levels of the apoptotic protein, Bax, and increased the expression of the anti-apoptotic protein Bcl-2, in vitro and in vivo. Moreover, we observed that ALA significantly inhibited the cytoplasmic localization of HMGB1, which might attenuate MI/RI or H/R via HMGB1/TLR4/NF-κB pathway.ALA regulates HMGB1 translocation and attenuates I/R via the HMGB1/TLR4/NF-κB signaling pathway, thus impeding apoptosis, oxidation, and inflammation, and might be a potential target for myocardial ischemia/reperfusion injury.

A new phenomenon that a filament discharged only once instead of twice in a cycle of the applied voltage is observed in a square grid pattern in a dielectric barrier discharge (DBD) with a larger gas gap, which is named intermittent discharge. Its spatiotemporal dynamics and the formation mechanism are studied by the multiple photomultiplier tubes and an intensified charge-coupled device. Corresponding to the positions of spots in the picture with an exposure time of 40 ms, there are some bright spots (discharge spots) and black spots (non-discharged spots) in the instantaneous image with an exposure time of 10 μs (a half cycle of the applied voltage). There are at least two bright spots around one black spot and vice versa. The surface discharges (SDS) can be observed between any two adjacent spots. The intensity of the SDS between the bright spot and the black spot is 2.5 times greater than that between two adjacent bright spots, which indicates that the SDS are directional-selective. The intermittent discharge with positive (negative) current polarity changes to that with negative (positive) current polarity, after it sustains up to 14 voltage cycles at the longest. The spatial distribution of the electric field component is calculated through COMSOL software to solve the Poisson equation numerically. It is found that the inhomogeneous distribution of surface electric field is caused by the inhomogeneous distribution of wall charges, which leads to direction-selective SDS. The intermittent discharge is formed by the competition between the direction-selective SDS and volume discharges (VDS) in DBD. This is the reason why the intermittent discharge is generated.

As a wide used protocol in industry, BMS and T&D system, I2C bus with isolation features stands out to provide additional safety protection and noise immunity. This paper introduces an implementation method of the isolated I2C interface device with high reliability and low delay. This device can meet the I2C ultra-high speed working mode with communication frequency of 1.7MHz as well as prevent the occurrence of interlock in bi-directional communication. The device is fabricated in 0.18um CMOS process.

DBC1 has been characterized as a key regulator of physiological and pathophysiological activities, such as DNA damage, senescence and tumorigenesis. However, the mechanism by which the functional stability of DBC1 is regulated has yet to be elucidated. Here, we report that the ubiquitination-mediated degradation of DBC1 is dynamically regulated by the E3 ubiquitin ligase SIAH2 and deubiquitinase OTUD5 under hypoxic stress. Mechanistically, hypoxia promoted the competitive binding of SIAH2 with OTUD5 to DBC1, resulting in the ubiquitination and subsequent degradation of DBC1 through the ubiquitin–proteasome pathway. Siah2 knockout inhibited tumor cell proliferation and migration, which could be rescued by double knockout of Siah2/DBC1. Human tissue microarray analysis further revealed that the SIAH2/DBC1 axis was responsible for tumor progression under hypoxic stress. These findings define a key role of the hypoxia-mediated SIAH2-DBC1 pathway in the progression of human breast cancer and provide novel insights into the metastatic mechanism of breast cancer.

Scholars have researched the current situation and development trend of contemporary watercolor materials in terms of material intervention, material expression language, spiritual connotation in material “materiality,” and practical application of materials, which are of profound significance to the consolidation of the theoretical system of watercolor painting in China. However, how to better analyze and apply watercolor materials on the basis of intelligent computing, as well as the material analysis and application based on intelligent computing in the context of contemporary watercolor painting, still has a lack of research at present. Therefore, this study considers the analysis and application of materials based on intelligent computing in the context of contemporary watercolor painting, in an attempt to seek ways to integrate with Chinese watercolor painting and its own national art.

A honeycomb-Kagome hexagonal superlattice pattern with dark discharges is observed in a dielectric barrier discharge system for the first time. The spatiotemporal structure of the honeycomb-Kagome hexagonal superlattice pattern with dark discharges is investigated by an intensified charge-coupled device and the photomultipliers show that it is an interleaving of three different sub-lattices, which are bright-spot, invisible honeycomb lattice, and Kagome lattice with invisible frameworks and dim-spots, respectively. The invisible honeycomb lattices and Kagome lattices are actually composed of dark discharges. By using the optical emission spectra method, it is found that the plasma parameters of the three different sub-lattices are different. The influence of the dark discharges on pattern formation is discussed. The results may have significance for the investigation of the dark discharges and will accelerate the development of self-organized pattern dynamics.

Actin-regulating kinase (Ark) plays an important role in controlling endocytosis, which has been shown to be involved in the development and virulence of several fungal pathogens. However, it remains unclear whether Ark1 is required for the development and pathogenicity of an entomopathogenic fungus. Here, MrArk1 (MAA_03415), a homologue of yeast Ark1, was characterized in the insect pathogenic fungus, Metarhizium robertsii. Disruption of MrArk1 led to defects in endocytosis and a marked reduction (58%) in conidiation capacity. The reduced conidiation level was accompanied by repression of several key conidiation-related genes, including brlA, abaA, and wetA. Additionally, the deletion mutant showed a significant decrease in its tolerance to heat shock, but not to UV-B irradiation. Bioassays demonstrated attenuated virulence for the deletion mutant against Galleria mellonella via normal cuticle infection, accompanied by suppressed appressorium formation and reduced transcript levels of several genes involved in cuticle penetration. Taken together, our results indicate that MrArk1 is involved in the heat tolerance, sporulation, and virulence of M. robertsii, and thus is an important factor for sustaining the fungal potential against insect pests.

Aims Honokiol is a hydroxylated biphenyl natural product and displays potent antitumor activity against several cancers including prostate cancer, melanoma, leukemia, and colorectal cancer. The present study was to investigate the in vitro activity of honokiol against A549 and 95-D human lung cancer cells. Main methods A549 and 95-D cells were used with honokiol treatment. Cell viability was determined by CCK-8 assay. The cell migration and apoptosis were evaluated by wound healing assay and TUNEL staining method respectively. The expressions of ER-related proteins were analyzed by western blot and the CHOP siRNA was used to downregulate the CHOP expression. Key findings The results demonstrated that treatment of A549 and 95-D cells with honokiol significantly reduced cell viability in a dose- and time-dependent manner. Furthermore, honokiol treatment decreased cell migration and enhanced cell apoptosis, which is accompanied by the upregulation of the expressions of ER stress-induced apoptotic signaling molecules such as GRP78, phosphorylated PERK, phosphorylated eIF2α, CHOP, Bcl-2, Bax, and cleaved Caspase 9. Honokiol treatment-induced increase of ER stress-related signaling molecules and apoptotic proteins in A549 and 95-D cells were reversed by CHOP siRNA. Significance Collectively, we conclude that ER stress may participate in the action of the anticancer activity of honokiol in A549 and 95-D cells and induction of ER stress-related apoptosis may represent a novel therapeutic intervention for human lung cancer.

Background and purpose Icariin, a major active ingredient in traditional Chinese medicines, is attracting increasing attention because of its unique pharmacological effects against ischaemic heart disease. The histone deacetylase, sirtuin-1, plays a protective role in ischaemia/reperfusion (I/R) injury, and this study was designed to investigate the protective role of icariin in models of cardiac I/R injury and to elucidate the potential involvement of sirtuin-1. Experimental approach I/R injury was simulated in vivo (mouse hearts), ex vivo (isolated rat hearts) and in vitro (neonatal rat cardiomyocytes and H9c2 cells). Prior to I/R injury, animals or cells were exposed to icariin, with or without inhibitors of sirtuin-1 (sirtinol and SIRT1 siRNA). Key results In vivo and in vitro, icariin given before I/R significantly improved post-I/R heart contraction and limited the infarct size and leakage of creatine kinase-MB and LDH from the damaged myocardium. Icariin also attenuated I/R-induced mitochondrial oxidative damage, decreasing malondialdehyde content and increasing superoxide dismutase activity and expression of Mn-superoxide dismutase. Icariin significantly improved mitochondrial membrane homeostasis by increasing mitochondrial membrane potential and cytochrome C stabilization, which further inhibited cell apoptosis. Sirtuin-1 was significantly up-regulated in hearts treated with icariin, whereas Ac-FOXO1 was simultaneously down-regulated. Importantly, sirtinol and SIRT1 siRNA either blocked icariin-induced cardioprotection or disrupted icariin-mediated mitochondrial homeostasis. Conclusions and implications Pretreatment with icariin protected cardiomyocytes from I/R-induced oxidative stress through activation of sirtuin-1 /FOXO1 signalling.

Peroxisomes, being indispensable organelles, play an important role in different biological processes in eukaryotes. PEX33, a filamentous fungus-specific peroxin of the docking machinery of peroxisomes, is involved in the virulence and development of other fungal pathogens. However, it is not clear whether PEX33 is necessary for the pathogenicity and development of an insect pathogenic fungus. In the present study, we report the presence of homologs of PEX33, namely MrPEX33 (MAA_05331), in the entomopathogenic fungus, Metarhizium robertsii. An M. robertsii transgenic strain expressing the fusion protein with MrPEX33-GFP and mCherry-PTS1 showed that MrPEX33 localizes to peroxisomes. The results also demonstrated that MrPEX33 is involved in the peroxisomal import pathway by peroxisomal targeting signals. Targeted gene deletion of MrPEX33 led to a significant decline in the asexual sporulation capacity, which was accompanied by downregulation of several conidiation-associated genes, such as wetA, abaA, and brlA. More importantly, our bioassay results showed that the virulence of ∆MrPEX33 mutants, against Galleria mellonella through cuticle infection, was greatly reduced. This was further accompanied by a significant drop in appressorium formation and cuticle penetration. Additionally, ∆MrPEX33 mutants showed a significant decrease in tolerance to cell wall integrity and oxidative stress. Taken together, our results suggest that MrPEX33 is involved in the cuticle infection-related morphogenesis and pathogenicity. KEY POINTS: • MrPEX33 is a specific peroxin of the docking machinery of peroxisomes. • MrPEX33 localizes to peroxisomes and is involved in the import of matrix proteins. • MrPEX33 is involved in the pathogenicity associated with cuticle infections.

Background Bone marrow mesenchymal stem cells (BMSCs) have been used as important cell-based tools for clinical applications. Oxidative stress-induced apoptosis causes a low survival rate after transplantation, and the underlying mechanisms remain unknown. The endoplasmic reticulum (ER) and mitochondria are vital organelles regulated by adenosine monophosphate (AMP)-activated protein kinase (AMPK), especially during oxidative stress injury. Melatonin exerts an antioxidant effect by scavenging free radicals. Here, we aimed to explore whether cytoprotective melatonin relieves ER stress-mediated mitochondrial dysfunction through AMPK in BMSCs after oxidative stress injury. Methods Mouse BMSCs were isolated and exposed to H2O2 in the absence or presence of melatonin. Thereafter, cell damage, oxidative stress levels, mitochondrial function, AMPK activity, ER stress-related proteins, and apoptotic markers were measured. Additionally, the involvement of AMPK and ER stress in the melatonin-mediated protection of BMSCs against H2O2-induced injury was investigated using pharmacologic agonists and inhibitors. Results Melatonin improved cell survival and restored mitochondrial function. Moreover, melatonin intimately regulated the phosphorylation of AMPK and molecules associated with ER stress pathways. AMPK activation and ER stress inhibition following melatonin administration improved the mitochondrial membrane potential (MMP), reduced mitochondria-initiated oxidative damage, and ultimately suppressed apoptotic signaling pathways in BMSCs. Cotreatment with N-acetyl-l-cysteine (NAC) significantly enhanced the antioxidant effect of melatonin. Importantly, pharmacological AMPK activation/ER stress inhibition promoted melatonin-induced cytoprotection, while pharmacological AMPK inactivation/ER stress induction conferred resistance to the effect of melatonin against H2O2 insult. Conclusions Our data also reveal a new, potentially therapeutic mechanism by which melatonin protects BMSCs from oxidative stress-mediated mitochondrial apoptosis, possibly by regulating the AMPK-ER stress pathway.

5-Fluorouracil (5-FU) resistance or multidrug resistance (MDR) has become a major obstacle in clinical treatment of cancers including colorectal cancer (CRC). Aberrant activation of phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT) pathway may lead to unlimited growth and chemoresistance in CRC cells, which thus could be a promising therapeutic target. As a long-term used traditional Chinese folk-medicine, Scutellaria barbata D. Don (SB) processes specific anticancer activity, but its activity against cancer chemoresistance is less known. Therefore, using a 5-FU-resistant CRC cell line HCT-8/5-FU, in this study we evaluated the therapeutic efficacy of the ethanol extracts of SB (EESB) against 5-FU resistance and explored the possible molecular mechanisms. We found that EESB significantly suppressed proliferation and promoted apoptosis in HCT-8/5-FU cells. Additionally, EESB displayed remarkable effect enhancing the retention of the ATP-binding cassette (ABC) transporter substrate, rhodamine‑123 (Rh‑123) in HCT-8/5-FU cells. Furthermore, EESB obviously downregulated the expression of cyclin D1, Bcl-2 and ABCG2, while upregulated p21 and Bax expression. Moreover, EESB showed a prominent suppressive effect on the activation of PI3K/AKT pathway. The findings suggested that Scutellaria barbata D. Don was able to inhibit chemoresistance in colorectal cancer by suppression of the PI3K/AKT pathway.

Colorectal cancer (CRC) is one of the most common malignancies worldwide. The majority of patients are not suitable for surgery due to the presence of metastatic disease at the time of diagnosis, which has led to a high mortality rate for patients with CRC. Lymphangiogenesis, formation of new lymphatic vessels, plays an critical role in cancer progression particularly in cancer metastasis. Vascular endothelial growth factor-C (VEGF-C) has been previously demonstrated to play a pivotal role in cancer metastasis and therefore has become an attractive target for anticancer treatments. Pien Tze Huang (PZH) is a well-known traditional Chinese formula, which has exhibited significant therapeutic effects against CRC. However, the molecular mechanisms underlying its anticancer effects, particularly in regards to antimetastasis activity, still require further elucidation. In the present study, we evaluated the effects of PZH on cell migration and VEGF-C expression using various human CRC cell lines. Moreover, using a VEGF‑C-stimulated human lymphatic endothelial cell (HLEC) model, we demonstrated that PZH suppresses lymphangiogenesis by attenuating cell migration and tube formation. This indicates that PZH possesses significant antimetastatic activity. Moreover, suppression of lymphangiogenesis by PZH via the downregulation of VEGF-C may be a potential molecular mechanism by which PZH inhibits metastasis in CRC.

Cardiac fibrosis is a pathophysiological process characterized by excessive deposition of extracellular matrix. We developed a cardiac hypertrophy model using transverse aortic constriction (TAC) to uncover mechanisms relevant to excessive deposition of extracellular matrix in mouse myocardial cells. TAC caused upregulation of Tripartite motif protein 72 (TRIM72), a tripartite motif-containing protein that is critical for proliferation and migration. Importantly, in vivo silencing of TRIM72 reversed TAC-induced cardiac fibrosis, as indicated by markedly increased left ventricular systolic pressure and decreased left ventricular end-diastolic pressure. TRIM72 knockdown also attenuated deposition of fibrosis marker collagen type I and α-smooth muscle actin (α-SMA). In an in vitro study, TRIM72 was similarly upregulated in cardiac fibroblasts. Knockdown of TRIM72 markedly suppressed collagen type I and α-SMA expression and significantly decreased the proliferation and migration of cardiac fibroblasts. However, TRIM72 overexpression markedly increased collagen type I and α-SMA expression and increased the proliferation and migration of cardiac fibroblasts. Further study demonstrated that TRIM72 increased phosphorylated STAT3 in cardiac fibroblasts. TRIM72 knockdown in cardiac fibroblasts resulted in increased expression of Notch ligand Jagged-1 and its downstream gene and Notch-1 intracellular domain. Inhibition of Notch-1 abrogated sh-TRIM72-induced cardiac fibrosis. Together, our results support a novel role for TRIM72 in maintaining fibroblast-to-myofibroblast transition and suppressing fibroblast growth by regulating the STAT3/Notch-1 pathway.

A UV-initiated thiol-ene click reaction was utilized to synthesize the multifunctional POSS-based silane coupling agent (OTS) from Octavinyl silsesquioxane (OVS) and 3-mercaptopropyltrimethoxysilane (MPTMS). Through supercritical drying, a series of hybrid aerogels with different OTS contents were successfully prepared by two-step sol-gel method using OTS and tetraethyl orthosilicate (TEOS) as the main precursors. In the formation of hybrid aerogels, the nucleation of OTS with flexible side chains had a significant effect on the size of the secondary particles and pore structure of aerogels. Compared with silica aerogels prepared from single TEOS, the hybrid aerogels had more uniform mesoporous and higher specific surface area. The result revealed all hybrid aerogels owned mesoporous structure (3–4 nm), low thermal conductivity (0.038–0.044 W m−1 K−1) and remarkable high specific surface area (945–1283 m2 g−1). The outstanding properties made hybrid aerogels promising as adsorbents or thermal insulation materials.

Cancer stem cells (CSCs) are proposed to be closely correlated with the development and progression of tumors, as well as with chemo- and radioresistance. Targeting CSCs may therefore be a promising potential strategy for the treatment of cancer. Currently, natural products have received great interest due to their therapeutic efficacy and reduced adverse effects compared with modern chemotherapeutics. As a significant component of a number of traditional Chinese medicine formulas, the medicinal herb Hedyotis diffusa Willd. (HDW) has long been utilized in China to clinically treat a variety of malignancies, including colorectal cancer (CRC). Previously, the authors of the present study reported that HDW suppressed CRC growth through multiple mechanisms, including promoting apoptosis, and inhibiting cell proliferation and tumor angiogenesis. To additionally investigate its mode of action, the present study isolated a stem-like side population (SP) from colorectal cancer HT-29 cells to investigate the effect of ethanol extract of HDW on CSCs. It was observed that HDW was able to markedly downregulate the expression of CSC marker leucine-rich repeat-containing G-protein coupled receptor 5 and also significantly decrease the proportion of SP in HT-29 cells, in a dose-dependent manner. Furthermore, HDW treatment significantly and dose-dependently inhibited the viability and sphere formation, and induced cell morphological changes of isolated HT-29 SP cells. In addition, HDW greatly suppressed the messenger RNA expression of several critical genes that mediate CSC features, including ATP-binding cassette, sub-family B, member 1, β-catenin, c-Myc, proliferating cell nuclear antigen and survivin. In conclusion, the present study indicates that HDW may exert inhibitory effects on cancer stem cells.

Ozone is thought to advance wound healing by inhibiting inflammation, but the mechanism of this phenomenon has not been determined. Although the zebrafish is often used in regeneration experiments, there has been no report of zebrafish treated with ozonated water. We successfully established a zebrafish model of ozonated water treatment and demonstrate that ozonated water stimulates the regeneration of the zebrafish caudal fin, its mechanism, and time dependence. The growth rate of the caudal fin and the number of neutrophils migrating to the caudal fin wound after resection were higher in the experimental (ozonated) group than in the control group, preliminarily confirming that ozone-promoted regeneration is related to the stimulation of an early inflammatory response by ozone. Ozone modulated the expression of tumor necrosis factor-α (TNF-α) in two ways by regulating interleukin 10 (IL-10) expression. Therefore, ozone promotes tissue regeneration by regulating the inflammatory pathways. This effect of ozone in an experimental zebrafish model is demonstrated for the first time, confirming its promotion of wound healing and the mechanism of its effect in tissue regeneration. These results will open up new directions for ozone and regeneration research.

We report on the striped superlattice pattern in dielectric barrier discharge for the first time. The spatiotemporal structure of the striped superlattice pattern is investigated by a high-speed framing camera. The result shows that the striped superlattice pattern consists of three different transient sub-lattices which are striped-dots, stripes, and small-dots surrounding a striped-dot, respectively. Images of a single frame indicate that the stripes which look like they are diffused are actually made up of individual filaments. The optical emission spectra of different sub-lattices are collected and investigated; it is found that plasma parameters of the three different transient sub-lattices are different. The formation mechanism of the striped superlattice pattern is discussed. And a tunable plasma photonic crystal with one and two-dimensions structures which has the dynamic controllability based on the striped superlattice pattern is present.

We report on a novel dielectric barrier discharge (DBD) instrument with asymmetrical electrodes. It consists of three water electrodes, one big electrode faces to two small electrodes placed side by side, any one of two small electrodes connects with a high-voltage diode which can control on or off of applied power. Using this DBD experimental setup, the phenomenon of forming two kinds of different patterns at the different parts of discharge gap simultaneously is investigated for the first time. The spatio-temporal characteristic of these different patterns limited by the boundary which contains two connected same circles is studied. It is shown that although the power source is applied on one part of the discharge gap at a half period because of existence of high voltage photodiode, the discharge occurs at both areas in each half period of the applied voltage. Results have prospective applications for studying the discharge mechanism and different characteristic of positive and negative charges in forming of pattern.

A novel type of white-eye pattern in a dielectric barrier discharge system has been investigated in this paper. It is a superposition of a hexagonal lattice and a white-eye stripe in appearance and evolves from a white-eye square grid state with the applied voltage increasing. Its spatio-temporal dynamics obtained by an intensified charge-coupled device shows that it consists of three transient rectangular sublattices. The spatiotemporally resolved evolutions of the molecular vibrational temperature and electron density of the pattern are measured by optical emission spectra. The evolution of surface charge distribution is given and its effect on the self-organized pattern formation is discussed.

Hedyotis diffusa Willd (HDW) is a widely used traditional Chinese medicine in clinical therapy to treat various types of cancer, including colorectal cancer (CRC), but its effective polar fractions and functional mechanisms remain unclear. The aim of the present study was to determine the most effective extract of HDW and to investigate its effects on the regulation of CRC cell proliferation and apoptosis, as well as to investigate the underlying molecular mechanisms. The results demonstrated that the chloroform extract of HDW (CEHDW) exhibited the most anticancer ability. Furthermore, results of the MTT assay, colony formation, carboxyfluorescein diacetate succinimidyl ester assay and annexin V/propidium iodide staining suggested that CEHDW significantly inhibits proliferation and promotes apoptosis in the SW620 CRC cell line. Additionally, reverse transcription-polymerase chain reaction and western blot analysis demonstrated that CEHDW treatment downregulated the expression of Survivin, proliferating cell nuclear antigen, Cyclin D1, cyclin-dependent kinase 4 and B-cell lymphoma 2 (Bcl-2), and upregulated the expression of Bcl-2-associated X protein at the mRNA and protein levels. CEHDW also decreased the phosphorylation of protein kinase B (AKT) and extracellular-signal-regulated kinase (ERK), which indicated that the suppression of the AKT and ERK signaling pathways may be one of the underlying molecular mechanisms by which CEHDW exhibited its anticancer effect. Thus, CEHDW may be a promising agent for anticancer therapy.

The development of colorectal cancer (CRC) is strongly associated with the imbalance of various intracellular signal transduction cascades, including protein kinase B (AKT), mitogen-activated protein kinase 1 (MAPK), signal transducer and activator of transcription 3 (STAT3), as well as crosstalk between these signaling networks. At present, anti-tumor agents are often single-targeted and therefore are not always therapeutically effective. Moreover, long-term use of these anti-tumor agents often generates drug resistance and potential side effects. These problems highlight the urgent need for the development of novel and more effective anti-cancer drugs. Hedyotis diffusa Willd (HDW) has been used as a major component in traditional Chinese medicine for the clinical treatment of colorectal cancer, with a limited number of adverse effects. However, the molecular mechanisms, which underlie its anti-cancer activity, still require further elucidation. In the present study, using xenograft models and various different human CRC cell lines, the efficacy of the ethanol extract of HDW (EEHDW) against tumor growth was evaluated, and its underlying molecular mechanisms of action were investigated. It was demonstrated that EEHDW was able to inhibit cancer growth in vivo and in vitro. Furthermore, EEHDW was able to suppress the activation of several CRC-associated signaling pathways and was able to regulate the expression of various inflammatory and angiogenic factors. This resulted in the induction of apoptosis and inhibition of cellular proliferation, as well as tumor angiogenesis. The present study demonstrated that EEHDW is able to exhibit anti-cancer activity due to its ability to affect multiple intracellular targets, which suggests that it may be a novel multi-potent therapeutic agent for the treatment of colorectal cancer.

Metastasis is one of the most aberrant behaviors of cancer cells. Patients with cancers, including colorectal cancer (CRC), have a higher risk of tumor recurrence and cancer-related mortality once metastasis is diagnosed. Existing treatment strategies fail to cure cancer mostly due to the onset of metastasis. Therefore, metastasis remains a challenge in cancer treatment. Some complementary and alternative medical therapies using traditional Chinese medicine have been demonstrated to be clinically effective in cancer treatment. Scutellaria barbata D. Don (SB) is a promising medicinal herb. It was previously reported that the ethanol extract of SB (EESB) is able to promote apoptosis, and inhibit cell proliferation and angiogenesis in human colon cancer cells. However, the anticancer effect of SB and the underlying mechanism require further investigation, particularly its role against metastasis. To further elucidate the antimetastatic effect of SB, MTT and Transwell assays were used in the present study to evaluate the effect of EESB on the proliferation, migration and invasion of the CRC cell line HCT-8. In addition, western blot analysis was performed to detect the expression of matrix metalloproteinases (MMPs), cadherins and other metastasis-associated proteins. EESB significantly reduced HCT-8 cell viability and attenuated the migration and invasion ability of HCT-8 cells in a dose-dependent manner. In addition, EESB decreased the expression of MMP-1, MMP-2, MMP-3/10, MMP-9 and MMP-13, and proteins in the phosphoinositide 3-kinase (PI3K)/AKT and transforming growth factor (TGF)-β/Smad pathways, but not the epithelial-mesenchymal transition (EMT)-related factors E-cadherin and N-cadherin. In conclusion, the results suggested that SB inhibits CRC cell metastasis via the suppression of PI3K/AKT and TGF-β/Smad signaling pathways, which may represent a mechanism by which SB exerts an anticancer effect.

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract, and threatens the survival and health of patients with CRC. Chemotherapy remains one of the main therapeutic approaches for patients with CRC; however, drug resistance limits the long‑term use. CRC cells with multi‑drug resistance (MDR) exhibit increased survival times and metastatic potential, which may lead to the recurrence and metastasis of CRC. In addition, MDR is one of the major causes of chemotherapy failure in clinical treatment. Hedyotis diffusa Willd (HDW) has been used in the treatment of inflammation‑associated diseases and malignant tumors, including CRC. The authors previously demonstrated that HDW could reverse MDR in CRC cells; however, its underlying mechanism, particularly in MDR‑associated metastasis, remains to be elucidated. In the present study, the drug‑resistant CRC cell line HCT‑8/5‑fluorouracil (5‑FU) was used to investigate the effect of HDW on the growth and metastasis of cancer cells. Cell viability was assessed using the MTT assay. Cell adhesion potential was evaluated using adhesion experiments. Cell migration was assessed using wound healing and Transwell assays. The mRNA and protein expression levels of crucial factors in the transforming growth factor‑β (TGF‑β) signaling pathway, including TGF‑β, Mothers against decapentaplegic homolog 4 (SMAD4), neural (N)‑cadherin, and epithelial (E)‑cadherin, were analyzed using the reverse transcription‑semi‑quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that the HCT‑8/5‑FU cell line was more resistant to 5‑FU and thus can be used as the resistant cell model. HDW was able to inhibit the viability, and adhesive, migratory and invasion potential of the HCT‑8/5‑FU cells. In addition, HDW was able to downregulate the expression of TGF‑β, SMAD4 and N‑cadherin, and upregulate E‑cadherin, at the gene and protein level. In conclusion, the results demonstrated that HDW may suppress the metastasis of 5‑FU‑resistant CRC cells via regulation of the TGF‑β signaling pathway, which was also considered to be one of the underlying mechanisms of its anti‑CRC effect.

Scutellaria barbata D. Don (SB) is a well known formula in traditional Chinese medicine, which exhibits potent anticancer effects on various cancers. Many miRNAs play crucial roles in the regulation of cancer, for instance, miR‑34a functions as a tumor suppressor, and is often downregulated during cancer. In this study, we investigated the role of ECSB in suppressing the growth of human colon cancer HCT‑8 cells, and whether this is mediated by regulation of miR‑34a and its downstream target genes, using real-time PCR and western blot analysis. ECSB treatment significantly inhibited the proliferation of HCT‑8 cells and promoted apoptosis in a dose-dependent manner. In addition, ECSB treatment significantly increased the level of miR‑34a expression and decreased the levels of Bcl-2, Notch1/2 and Jagged1 expression. Furthermore, knockdown of miR‑34a expression through transfection of anti-miR‑34a oligonucleotide was significantly reversed by ECSB treatment. Likewise, knockdown of miR‑34a resulted in significant upregulation of Bcl-2, Notch1/2 and Jagged1 expression, which was reversed following ECSB treatment. Therefore, this study reveals that ECSB inhibited cancer cell growth via promoting apoptosis and inhibiting proliferation, through regulation of miR‑34a. These findings further support the use of ECSB as an effective therapeutic agent against colon cancer.

Hedyotis diffusa Willd (HDW) is a widely used traditional Chinese medicine in clinical therapy to treat various types of cancer, including colorectal cancer (CRC), but its effective polar fractions and functional mechanisms remain unclear. The aim of the present study was to determine the most effective extract of HDW and to investigate its effects on the regulation of CRC cell proliferation and apoptosis, as well as to investigate the underlying molecular mechanisms. The results demonstrated that the chloroform extract of HDW (CEHDW) exhibited the most anticancer ability. Furthermore, results of the MTT assay, colony formation, carboxyfluorescein diacetate succinimidyl ester assay and annexin V/propidium iodide staining suggested that CEHDW significantly inhibits proliferation and promotes apoptosis in the SW620 CRC cell line. Additionally, reverse transcription-polymerase chain reaction and western blot analysis demonstrated that CEHDW treatment downregulated the expression of Survivin, proliferating cell nuclear antigen, Cyclin D1, cyclin-dependent kinase 4 and B-cell lymphoma 2 (Bcl-2), and upregulated the expression of Bcl-2-associated X protein at the mRNA and protein levels. CEHDW also decreased the phosphorylation of protein kinase B (AKT) and extracellular-signal-regulated kinase (ERK), which indicated that the suppression of the AKT and ERK signaling pathways may be one of the underlying molecular mechanisms by which CEHDW exhibited its anticancer effect. Thus, CEHDW may be a promising agent for anticancer therapy.

We report on the investigation of the bright-dim hollow hexagonal superlattice pattern (BDHHSP) in dielectric barrier discharge (DBD) for the first time. It bifurcates from a hexagon pattern as the applied voltage increases. The spatiotemporal structure investigated by using an intensified charge device and a lens-aperture photomultiplier tube system shows that the BDHHSP is an interleaving of three different sub-lattices, which are bright spots, dim spots, and halos, respectively, and dim spots are located at the center of the triangle formed by three bright spots. But not all the centers of each triangle have a dim spot. The formation mechanism of the phenomenon called selectively insert discharge is discussed. The results have significance for the selective mechanism of discharge position in the DBD system.

Ischemia reperfusion (IR) injury (IRI) is associated with poor prognoses in the settings of both cardiac surgery and ischemic heart disease and causes mitochondrial oxidative stress and cell death. Silent information regulator 1 (SIRT1), a member of the histone deacetylase family, exerts anti-IRI effects. Bakuchiol (BAK), an analog of resveratrol and a monoterpene phenol isolated from the seeds of Psoralea corylifolia (Leguminosae), protects tissues from injury. This study was designed to investigate the protective effects of BAK treatment in the setting of myocardial IRI and to elucidate the potential mechanism of those effects. Prior to induction of IR, isolated rat hearts or cardiomyocytes were exposed to BAK in either the absence or presence of the SIRT1 inhibitors Sirtinol and SIRT1 siRNA. BAK exerted cardioprotective effects, as evidenced by the improvements noted in cardiac function following ischemia, attenuated myocardial apoptosis, and changes in several biochemical parameters (including increases in the level of the anti-apoptotic protein Bcl2, decreases in the level of the pro-apoptotic protein Bax, and decreases in the cleaved Caspase 3 level). However, Sirtinol and SIRT1 siRNA each blocked BAK-induced cardioprotection by inhibiting SIRT1 signaling. Additionally, BAK significantly increased the activities of mitochondrial succinate dehydrogenase, cytochrome c oxidase, and mitochondrial superoxide dismutase and decreased the production of malondialdehyde. These findings suggested that BAK significantly attenuated IR-induced mitochondrial oxidative damage. However, Sirtinol and SIRT1 siRNA abolished BAK-dependent mitochondrial function. In summary, our results demonstrate that BAK treatment attenuates IRI by attenuating IR-induced mitochondrial oxidative damage via the activation of SIRT1/PGC-1α signaling.

A novel kind of chip which is used in high precision and low cost arc detection circuit (leakage detection included) was designed. Based on CSMC's 0.5pm process, the pad is specially designed to produce a specific capacitor. Cascode current mirror and trimming capacitors are used to generate a precise timing signal. High speed, large bandwidth and low offset op-amps with rail to rail output stage are used to realize the function of precise amplification of the current information. The chip is designed and simulated on the platform of Cadence. The experimental result shows that the chip can detect arc which is wider than 150ns and generate the corresponding interrupt signal.

Hypoxia-induced angiogenesis plays an important role in the development and metastasis of solid tumors and is highly regulated by HIF-1α/VEGF-A pathway. Therefore, inhibiting tumor angiogenesis via suppression of HIF-1α/VEGF-A signaling represents a promising strategy for anticancer treatment. As a traditional Chinese medicine formula, Pien Tze Huang (PZH) has long been used as a folk remedy for cancer in China and Southeast Asia. Previously, we reported that PZH inhibits colorectal cancer (CRC) growth both in vivo and in vitro. To elucidate the antitumor mechanisms of PZH, in the present study we used human umbilical vein endothelial cells (HUVEC) and colorectal carcinoma HCT-8 cells to evaluate the effects of PZH on hypoxia-induced angiogenesis and investigated the underlying molecular mechanisms. We found that PZH could inhibit hypoxia-induced migration and tube formation of HUVEC cells in a dose-dependent manner, although the low concentrations of PZH had no effect on HUVEC viability. Moreover, PZH inhibited hypoxia-induced activation of HIF-1αsignaling and the expression of VEGF-A and/or VEGFR2 in both HCT-8 and HUVEC cells. Collectively, our findings suggest that PZH can inhibit hypoxia-induced tumor angiogenesis via suppression of HIF-1α/VEGF-A pathway.

Metastasis is the leading cause of cancer-related mortality in almost all types of cancers, including colorectal cancer (CRC). Epithelial-mesenchymal transition (EMT) is a critical process during the metastatic cascade. This process may be a potential target for the diagnosis and treatment of CRC. Pien Tze Huang (PZH), a well-known traditional Chinese formula, has been demonstrated to be clinically effective in treating various types of human malignancies, including CRC. Our published data suggest that PZH can induce apoptosis, as well as inhibit cell proliferation and tumor angiogenesis, thus suppressing CRC growth in vitro and in vivo. We evaluated the therapeutic efficacy of PZH against CRC metastasis using a CRC liver metastasis mouse model to further explore the mechanisms underlying the antitumor action of PZH. MTT, migration, and Matrigel invasion assays were used to assess the effect of PZH on cell viability, migration and invasion. We then established an orthotopic liver metastasis model of colon cancer using microsurgical techniques. Mice were intragastrically administered 234 mg/kg/day dose of either PZH or saline for 14 days. The body and tumor weights of the mice were measured after they were sacrificed. Moreover, we examined the effect of PZH inhibition on liver metastasis. Finally, EMT-related proteins and the TGF-β signaling pathway were assessed using immunohistochemical staining (IHS). The present data revealed that PZH significantly inhibited the migration and invasion of CT-26 cells in a dose-dependent manner, which affirmed the inhibitory effect of PZH on CRC cell metastasis. No significant change was observed between the in vivo primary tumor growth and body weight. However, the control group had five cases of liver metastasis (5/6), whereas one case was found in the PZH group (1/6). Thus, PZH exhibited therapeutic efficacy against CRC metastasis without apparent toxicity. The inhibitory effect of PZH on EMT resulted in an increase in E-cadherin expression, as well as a decrease in N-cadherin expression. In addition, PZH significantly inhibited TGF-β, as well as the phosphorylation of Smad2/3 and Smad4 in the tumor tissues, indicating its suppressive action on TGF-β signaling. These molecular effects ultimately resulted in the inhibition of cancer cell EMT and tumor metastasis.

We report on the study of moving filaments in a honeycomb pattern in a dielectric barrier discharge system using photomultipliers, a high-speed video camera, and a spectrometer. The honeycomb pattern bifurcates from the hexagonal super-lattice pattern with increasing voltage. It is found that the honeycomb framework is composed of filaments with irregular reciprocating motion, which indicates that the honeycomb framework results from statistical self-organization. The spatiotemporal dynamics show that the pattern consists of three different sub-lattices. The plasma parameters (molecular vibrational temperature and electron density) of the pattern, determined from the optical emission spectra, show that different sub-lattices are in different plasma states. Based on these measurements, the mechanism of the movement of filaments is analyzed briefly.

The dark-ring white-eye square super-lattice pattern was studied in dielectric barrier discharge system for the first time. Each unit cell of the pattern consisted of a central bright spot surrounded by a dark ring. The structure of dark ring around the center bright spot was similar to the white-eye, which was called the dark-ring white-eyes. The spatial-temporal dynamics of the dark-ring white-eye square super-lattice pattern was investigated by high speed frame camera (HSFC). The results showed that the dark-ring white-eye square super-lattice pattern was an interleaving of four different sub-structures. The discharge sequence was center bright dot-bright dot halo-vertex square-vertex connection in each half voltage cycle. The formation mechanism of dark-ring white-eye square super-lattice pattern and dark ring was explained by surface charges theory.