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Contrast-induced nephropathy (CIN) is one of the most common causes of acute kidney injury (AKI). However, management is still limited, and the cellular response to radiocontrast removal for CIN remains unclear. This study aimed to explore the latent effects of iohexol in cultured renal tubular cells with or without the removal of iohexol by medium replacement. HK2 renal tubular cells were subcultured 24 h before use in CIN experiments. Three treatment groups were established: the control, a radiocontrast (iohexol)-only group at 75 mg I/mL (I-75), and iohexol exposure for 24 h with culture medium replacement (I-75/M). Cell cycle arrest, fibrogenic mediator assays, cell viability, cell function, and cell-cycle-related protein expression were compared between groups. Iohexol induced numerous changes in HK2 renal tubular cells, such as enlarged cell shape, cell cycle arrest, increased apoptosis, and polyploidy. Iohexol inhibited the expression of cyclins, CDKs, ZO-1, and E-cadherin but conversely enhanced the expression of p21 and fibrosis-related genes, including TGF-β1, CTGF, collagen I, collagen III, and HIF-1α within 60 hr after the exposure. Except for the recovery from cell cycle arrest and cell cycle gene expression, notably, the removal of iohexol by medium replacement could not fully recover the renal tubular cells from the formation of polyploid cells, the adhesion or spreading, or the expression of fibrosis-related genes. The present study demonstrates, for the first time, that iohexol exerts latent cytotoxic effects on cultured renal tubular cells after its removal, suggesting that these irreversible cell changes may cause the insufficiency of radiocontrast reduction in CIN, which is worth investigating further.

In this study, a novel on-line two-dimensional (2D) normal phase × normal phase liquid chromatography (NPLC × NPLC) was developed for the separation of weakly polar samples. The 2D NPLC was integrated by a unique designed solvent evaporation (SE) interface, including a 6-port 2-position valve and a 10-port 2-position valve in conjunction with two silica gel-packed enrichment columns. The enrichment columns played a pivotal role in evaporating normal phase (NP) solvent from the first-dimensional NPLC under vacuum and elevated temperature condition. The working parameters of the interface were evaluated comprehensively. To demonstrate the resolving powerful 2D system, we analyzed three natural-sourced weakly polar compounds from the extracts of toad venom, dammar resin, and propolis. To this end, we studied the effects of mobile phase combinations, the second dimensional column length for separation of the extracts from toad venom, and propolis respectively. In general, we have found that excellent separation can be obtained with diversity of NP solvent combinations and longer NPLC column (150 mm long). Moreover, compared with the generally used 2D reversed-phase liquid chromatography (RPLC × RPLC), the NPLC × NPLC method exhibited better separation orthogonality. In conclusion, the new NPLC × NPLC separation method provides potential advantages for analysis of weakly polar samples.

Proteins containing nuclear localization signals (NLSs) are actively transported into the nucleus via the classic importin-α/β-mediated pathway, and NLSs are recognized by members of the importin-α family. Most studies of insect importin-αs have focused on Drosophila to date, little is known about the importin-α proteins in Lepidoptera insects. In this study, we identified four putative importin-α homologs, Spodoptera frugiperda importin-α1 (SfIMA1), SfIMA2, SfIMA4 and SfIMA7, from Sf9 cells. Immunofluorescence analysis showed that SfIMA2, SfIMA4 and SfIMA7 localized to the nucleus, while SfIMA1 distributed in cytoplasm. Additionally, SfIMA4 and SfIMA7 were also detected in the nuclear membrane of Sf9 cells. SfIMA1, SfIMA4 and SfIMA7, but not SfIMA2, were found to associate with the C terminus of AcMNPV DNA polymerase (DNApol) that harbors a typical monopartite NLS and a classic bipartite NLS. Further analysis of protein-protein interactions revealed that SfIMA1 specifically recognizes the bipartite NLS, while SfIMA4 and SfIMA7 bind to both monopartite and bipartite NLSs. Together, our results suggested that SfIMA1, SfIMA4 and SfIMA7 play important roles in the nuclear import of AcMNPV DNApol C terminus in Sf9 cells. This article is protected by copyright. All rights reserved.

Berberine exerts therapeutic effects in inflammation-associated diseases. In a lipopolysaccharide (LPS)-induced endotoxemic acute lung injury (ALI) rat model, berberine alleviated lung injury through different anti-inflammatory mechanisms; however, treatment effects on CX3CL1 expression and shedding remain to be examined. As these processes play important roles in promoting the binding of leukocytes to the endothelium, the CX3CL1/CX3CR1 axis and its related pathways may serve as potential targets for the clinical treatment of ALI. The anti-inflammatory effects of berberine were investigated in LPS-stimulated rats, human umbilical cord vein endothelial cells (HUVECs), and THP-1 monocytic cells. Cx3cl1 expression in rat pulmonary tissues was examined using immunohistochemistry. CX3CL1, CX3CR1, RELA, STAT3, and ADAM10 levels were examined using Western blotting. CX3CL1 and ADAM10 mRNA levels were examined using quantitative real-time polymerase chain reaction. Soluble fractalkine levels in LPS-stimulated rats and HUVECs were examined using the enzyme-linked immunosorbent assay. Berberine significantly mitigated the LPS-induced upregulation of fractalkine and soluble fractalkine in rats and cultured HUVECs. Berberine mitigated the LPS-induced activation of the NF-κB and STAT3 signaling pathways. In THP-1 cells, berberine mitigated the LPS-induced upregulation of CX3CR1. Furthermore, the membrane expression of ADAM10 in LPS-stimulated HUVECs was suppressed by the berberine treatment. Berberine dose-dependently inhibited the LPS-induced activation of the CX3CL1/CX3CR1 axis and fractalkine shedding through ADAM10. These findings reveal a novel molecular mechanism underlying the inhibitory effect of berberine on monocyte adherence to the endothelium during inflammation.

Combined inhibition of vascular endothelial growth factor receptor (VEGFR) and the programmed cell death protein 1 (PD-1) pathways has shown efficacy in multiple cancers; however, the clinical outcomes show limited benefits and the unmet clinical needs still remain and require improvement in efficacy. Using murine colon carcinoma (CT26) allograft models, we examined the efficacy and elucidated novel tumor microenvironment (TME) remodeling mechanisms underlying the combination of chidamide (a benzamide-based class l histone deacetylase inhibitor; brand name in Taiwan, Kepida®) with VEGF receptor tyrosine kinase inhibitor (TKIs; cabozantinib/regorafenib, etc.) and immune checkpoint inhibitors (ICIs; anti-PD-1/anti-PD-L1/anti-CTLA-4 antibodies). The TME was assessed using flow cytometry and RNA-sequencing to determine the novel mechanisms and their correlation with therapeutic effects in mice with significant treatment response. Compared with ICI alone or cabozantinib/regorafenib + ICI, combination of chidamide + cabozantinib/regorafenib + ICI increased the tumor response and survival benefits. In particular, treatment of CT26-bearing mice with chidamide + regorafenib + anti-PD-1 antibody showed a better objective response rate (ORR) and overall survival (OS). Similar results were observed in anti-PD-1 treatment-resistant mice. After treatment with this optimal combination, in the TME, RNA-sequencing revealed that downregulated mRNAs were correlated with leukocyte migration, cell chemotaxis, and macrophage gene sets, and flow cytometry analysis showed that the cell numbers of myeloid-derived polymorphonuclear suppressor cells and tumor-associated macrophages were decreased. Accordingly, chidamide + regorafenib + anti-PD-1 antibody combination therapy could trigger a novel TME remodeling mechanism by attenuating immunosuppressive cells, and restoring T-cell activation to enhance ORR and OS. Our studies also showed that the addition of Chidamide to the regorafenib + anti-PD-1 Ab combination could induce a durable tumor-specific response by attenuating immune suppression in the TME. In addition, this result suggests that TME remodeling, mediated by epigenetic immunomodulator combined with TKI and ICI, would be more advantageous for achieving a high objective response rate, when compared to TKI plus ICI or ICI alone, and maintaining long-lasting antitumor activity.

Quercetin is a flavonoid polyphenolic compound present in fruits and vegetables that has proven anti-inflammatory activity. The goal of the present investigation was to investigate the effects of quercetin on tumor necrosis factor-α (TNF-α)-induced inflammatory responses via the expression of ICAM-1 and MMP-9 in human retinal pigment epithelial cells (ARPE-19 cells). Real-time PCR, gelatin zymography, and Western blot analysis showed that TNF-α induced the expression of ICAM-1 and MMP-9 protein and mRNA in a time-dependent manner. These effects were attenuated by pretreatment of ARPE-19 cells with quercetin. Quercetin inhibited the TNF-α-induced phosphorylation of PKCδ, JNK1/2, ERK1/2. Quercetin, rottlerin, SP600125 and U0126 attenuated TNF-α-stimulated c-Jun phosphorylation and AP-1-Luc activity. Pretreatment with quercetin, rottlerin, SP600125, or Bay 11-7082 attenuated TNF-α-induced NF-κB (p65) phosphorylation, translocation and RelA/p65-Luc activity. TNF-α significantly increased MMP-9 promoter activity and THP-1 cell adherence, and these effects were attenuated by pretreatment with quercetin, rottlerin, SP600125, U0126, tanshinone IIA or Bay 11-7082. These results suggest that quercetin attenuates TNF-α-induced ICAM-1 and MMP-9 expression in ARPE-19 cells via the MEK1/2-ERK1/2 and PKCδ-JNK1/2-c-Jun or NF-κB pathways.

Proteins containing nuclear localization signals (NLSs) are actively transported into the nucleus via the classic importin-α/β-mediated pathway, and NLSs are recognized by members of the importin-α family. Most studies of insect importin-αs have focused on Drosophila to date, little is known about the importin-α proteins in Lepidoptera insects. In this study, we identified four putative importin-α homologues, Spodoptera frugiperda importin-α1 (SfIMA1), SfIMA2, SfIMA4 and SfIMA7, from Sf9 cells. Immunofluorescence analysis showed that SfIMA2, SfIMA4 and SfIMA7 localized to the nucleus, while SfIMA1 distributed in cytoplasm. Additionally, SfIMA4 and SfIMA7 were also detected in the nuclear membrane of Sf9 cells. SfIMA1, SfIMA4 and SfIMA7, but not SfIMA2, were found to associate with the C terminus of AcMNPV DNA polymerase (DNApol) that harbours a typical monopartite NLS and a classic bipartite NLS. Further analysis of protein-protein interactions revealed that SfIMA1 specifically recognizes the bipartite NLS, while SfIMA4 and SfIMA7 bind to both monopartite and bipartite NLSs. Together, our results suggested that SfIMA1, SfIMA4 and SfIMA7 play important roles in the nuclear import of AcMNPV DNApol C terminus in Sf9 cells.

Immune checkpoint inhibitors (ICIs) have shown clinical benefit in solid tumors, with modest rates of clinical response. Hence, improved therapeutic approaches need to be investigated. Herein, we assessed a combination of chidamide plus celecoxib (called CC-01) combined with programmed cell death protein 1 (PD-1) blockade in a CT26 model as potent tumor microenvironment (TME) regulator. The antitumor activity was assessed by measuring tumor size, overall response rate, and survival rate. Immune profiling of tumor-infiltrating lymphocytes was performed by flow cytometry. Tumor tissues were assessed by chip assay to predict the possible pathway. Tumor size was significantly reduced in mice treated with CC-01 combined with or without anti-PD-1 antibody, however the triple combination therapy consistently demonstrated that it significantly increased both the ORR and survival rate in term of clinical applications. In the combination group, immune landscape profiling revealed decreased populations of immunosuppressive regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Analysis of the mouse tumor chip data using Gene Ontology enrichment analysis of biological processes revealed that the triple combination upregulated genes associated with responses to interferon-gamma. Our results demonstrated that CC-01 possessed potent TME regulatory properties, augmenting the antitumor effect when combined with ICIs. This antitumor effect was achieved by altering the immune landscape in TILs (tumor-infiltrating lymphocytes) and was associated with immune cell activation in the TME. Furthermore, CC-01 demonstrated potent anticancer immune response activity, mainly reducing the number and function of several immunosuppressive cells. The combination of CC-01 with an ICI will further enhance the anticancer effect and boost the immune response rate. Collectively, our results support the clinical evaluation of CC-01 in combination with ICIs in several advanced cancers.

An integrated microfluidic Au nanoparticle (AuNP) aptasensor device is proposed for monitoring the concentration of potassium (K

Background.Chemotherapy-induced thrombocytopenia (CIT) is a serious complication among patients with gynecological malignancies, yet management options are limited. This study aimed at reporting the potential of the Chang Gung platelet elevating formula (CGPEF), a prescription with a fixed proportion of Chinese herbs, for improving CIT among gynecologic cancer patients.Materials.From 1/1/2007 to 31/12/2009, a total of 23 patients with two consecutive CIT episodes (≤ 100×103/μL) (last cycle: C0; index cycle: C1) received the CGPEF from the nadir of platelet count of C1 and through the subsequent chemotherapy cycles (C2 and beyond). The CGPEF was taken orally four times a day. The evolution of platelet counts of 18 patients after administration of CGPEF was analyzed (2 patients had different chemotherapy regimens after CGPEF, two patients discontinued CGPEF due to the flavor and the amount of CGPEF, and one patient had no further chemotherapy).Results.Most of the patients had recurrent ovarian cancer (11/18, 61%) with a median of 2.5 previous chemotherapy regimens, and carboplatin-based regimens were the most commonly used for these patients (13/18, 72%). The trend of successive CIT could be reversed after taking CGPEF. Also, the platelet nadir was higher after CGPEF treatment (16.5×103/μL versus 32×103/μL, before and after CGPEF treatment, resp.,p= 0.002). Moreover, the chemotherapy interval decreased from 30.5 days to 24 days. No thrombocytosis, clinical bleeding, thromboembolism, or other adverse events were found among these patients.Conclusions.The CGPEF is worthy of further large-scale, well-designed clinical trials for CIT among gynecological cancer patients.

No.8 Bridge is the site where Yang River flows into Guanting Reservoir. It’s an important guarantee for the water safety of Guanting Reservoir that the water quality meets the standards steadily at No.8 Bridge. Based on the monitoring data from 2006 to 2013, the interannual and annual trends and correlations among DO, NH3-N and COD of Yang River were analyzed. The factors affecting DO were also discussed. The results showed that DO and COD met the fourth-class standard for surface water. NH3-N decreased year by year and its standard-reaching rate ran up to 70% since 2009. DO and COD, NH3-N was negatively correlated, but not significant, indicating that COD and NH3-N were not important factors affecting DO. DO varied along with seasons, autumn (mean 7.47mg /L) > spring (mean 7.35mg /L) > winter (mean 6.95mg /L) > summer (mean 6.35mg /L). Temperature is an important factor affecting DO. The possible impact on water environment of Guanting Reservoir caused by DO decrease should be paid special attention.

Smoking and high-sensitivity C-reactive protein (hs-CRP) are risk factors for coronary artery spasm (CAS), which is characterized by the increased interleukin-6 (IL-6) level and monocyte counts; however, limited data are available regarding the role of cigarette-embedded nicotine in the modulation of monocytic inflammatory activity in CAS.We investigated and elucidated the putative roles and associations of nicotine, monocytic IL-6, α7 nicotinic acetylcholine receptor (α7-nAChR), and CRP in CAS development.We demonstrated that a significantly increased α7-nAChR (p = 0.001) and IL-6 (p = 0.0036) messenger RNA (mRNA) expression in the serum of patients with CAS. Serum hs-CRP levels exhibited a strong positive correlation with the monocytic mRNA expression of α7-nAChR (r = 0.71, p 0.001) and IL-6 (r = 0.49, p = 0.006). The α7-nAChR and IL-6 expression levels of the CAS group were also positively correlated (r = 0.63, p 0.001). Compared with the untreated controls, THP-1 cells and patient-derived monocytes treated with different concentrations of CRP displayed significantly increased expression levels of α7-nAChR mRNA and protein (p = 0.0054), in a dose-dependent manner. We also demonstrated that compared with the IL-6 expression elicited by CRP alone (p = 0.0489), the CRP-induced rise in monocytic IL-6 mRNA and protein expression in the presence of nicotine (p = 0.0002), is mediated by α7-nAChR activation and the deregulation of the human p38 mitogen-activated protein kinases (MAPK) signaling pathway.Our data demonstrate that the elevated monocytic IL-6 and α7-nAChR mRNA and protein expression levels are associated with the interaction between nicotine and CRP positively modulates CAS development. Our study suggests the potential role of α7-nAChR mRNA and/or protein expression as a diagnostic biomarker for CAS.

Tissue factor (TF) is the primary cause of atherothrombosis, the rupture of atherosclerotic plaques with subsequent thrombosis, leading to acute cardiovascular events, such as myocardial infarction and stroke. Wogonin (Wog) is an active component of Scutellaria baicalensis, used for inflammatory diseases, atherosclerosis, and hyperlipidemia. The anticoagulant effect of Wog on TF expression remains unexplored. In this study, we have investigated the effects of Wog on TF gene expression and its underlying molecular mechanism in human vascular endothelial cells (ECs). We found that Wog dose-dependently inhibited PMA-enhanced TF mRNA, protein, and activity in ECs. This inhibition was attributed to its decreasing nuclear accumulations of transcription factors, phospho-c-Jun and early growth response-1(Egr-1), not nuclear factor-κB (NF-κB), through blocking extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) signaling pathways. Reduction by Wog of Egr-1 nuclear level and Egr-1/DNA binding activity was associated with its inhibition of Egr-1 de novo synthesis. Wog as well as inhibitors to ERK and JNK suppressed TF promoter activity and protein expression in reporter gene and Western blot analyses. Furthermore, it also exhibited anticoagulant function by inhibiting TF expression and activity in tumor necrosis factor-alpha (TNF-α)- and lipopolysaccharide (LPS)-treated ECs and THP-1 cells. These results suggest that Wog inhibits ERK/Egr-1- and JNK/AP-1-mediated transactivation of TF promoter activity, leading to downregulation of TF expression and activity induced by inflammatory mediators. Wog targeting pathological TF expression without affecting its basal level may be a safer templet in the development of anticoagulant agent for cardiovascular thrombotic diseases related to atherothrombosis.

BackgroundIn Asian countries, many patients with type 2 diabetes fail to achieve controlled glycated hemoglobin (HbA1c) levels while taking several classes of oral hypoglycemic agents (OHAs). Traditional Chinese medicine could be an alternative therapeutic option for poorly controlled type 2 diabetes. YH1 is a concentrated Chinese herbal extract formula that combines Rhizoma Coptidis and Shen-Ling-Bai-Zhu-San. This randomized, double-blind, placebo-controlled pilot study evaluated YH1 as an add-on medication for poorly controlled type 2 diabetes.MethodsForty-six patients with poorly controlled type 2 diabetes were randomly assigned 1:1 to the YH1 or placebo group. Before the trial, all subjects had received three or more classes of OHAs with HbA1c > 7.0% (53 mmol/mol) and a body mass index ≥ 23 kg/m2. During the 12-week trial, participants continued to take OHAs without any dose or medication changes. The primary endpoint was the percentage change in HbA1c level. Per-protocol analysis was applied to the final evaluation.ResultsAt week 12, there was an 11.1% reduction in HbA1c from baseline and a 68.9% increase in homeostatic model assessment (HOMA) of β cell function in the YH1 group, which also exhibited significant reductions in two-hour postprandial glucose (-26.2%), triglycerides (-29.5%), total cholesterol (-21.6%), low-density lipoprotein cholesterol (-17.4%), body weight (-0.5%), and waist circumference (-1.1%). The changes in fasting plasma glucose, HOMA insulin resistance and symptom scores were not significantly different between the YH1 and placebo groups. No serious adverse events occurred during this clinical trial.ConclusionsThis pilot study indicates that YH1 together with OHAs can improve hypoglycemic action and β-cell function in overweight/obese patients with poorly controlled type 2 diabetes. YH1 is a safe add-on medication for OHAs and has beneficial effects on weight control and lipid metabolism. A larger study population with longer treatment and follow-up periods is required for further verification.

This paper presents a theoretical analysis of a pulsed bicomponent contaminant emission into a free-surface wetland flow. The basic equations are for the bicomponent contaminant transport in the wetland flow under the combined action of advection, mass dispersion, and ecological reaction at the phase averaged scale. The effect of the ecological reaction is separated from the hydrodynamic effect via a set of widely used transforms. The analytical solution for the evolution of the depth-averaged concentration is rigorously derived, with a limiting case covering the known solution for the single component contaminant transport. It is found that the depth-averaged species concentration of the bicomponent contaminant can approach an equilibrium state determined by the distribution coefficient.

In this paper, a reliability analysis of symmetric Vertical-channel Ni-SAlicided poly-Si thin-film transistors (VSA-TFTs) is performed for the first time. First, we compare the drain-induced barrier-lowering effect (DIBL) of VSA-TFTs. The VSA-TFTs with thinner gate oxide thickness, an offset structure, and a longer floating n+ region have better immunity to DIBL. Second, VSA-TFTs with a longer floating n+ region also have better immunity under hot-carrier (HC) stress and self-heating (SH) stress. However, VSA-TFTs with a shorter floating n+ region also have better immunity to positive gate bias (PGB) stress. Consequently, in order to optimize reliability characteristics, including SH stress, HC stress, and PGB stress, it is necessary to modulate the length of the floating n+ region. Third, the PGB stress, rather than SH stress or HC stress, becomes a major issue for VSA-TFTs under the stress bias below 4 V. In other words, PGB stress will dominate the degradation behaviors when the stress bias is not high enough to achieve SH stress and HC stress. Finally, the worst degradation condition of VSA-TFTs under HC stress, similar to that of most TFT devices, occurs when the stress of VG is less than half of VD.

Leukocyte adhesion to endothelium plays a critical initiating role in inflammation. Berberine, an anti-inflammatory natural compound, is known to attenuate lipopolysaccharide (LPS)-induced lung injury and improve survival of endotoxemic animals with mechanism not fully clarified. This study investigated the effects of berberine on the LPS-induced leukocyte-endothelial cell adhesion both in vivo and in vitro. We first established an animal model to observe the in vivo LPS-induced adhesion of leukocytes to the endothelium of venules in the lung tissue dose-dependently. Pretreatment of LPS-stimulated rats with berberine for 1 h reduced the leukocyte-endothelium adhesion and vascular cell adhesion molecule-1 (VCAM-1) expression in lung. Pretreatment of LPS-stimulated vascular endothelial cells with berberine also dose-dependently decreased the number of adhered THP-1 cells and VCAM-1 expression at both RNA and protein levels. Berberine was further confirmed to inhibit the nuclear translocation and DNA binding activity of LPS-activated nuclear factor-kappa B (NF-kappa B). These data demonstrated an additional molecular mechanism for the profound anti-inflammatory effect of berberine.

Baiyangdian lake is typical macrophytic lake, located in North China. With the economic and social development, as well as the impact of global climate change, the water pollution problem has been being a serious impact on the salubrious development of regional ecosystems. The local government has adopted a change of water storage basin to approach to fundamentally solve the problems of water pollution with the ecological water transfer in lake basins. In this paper, collecting the typical water pollutants data before and after ecological water transfer, using of ArcGIS software we have researched the diffusion mode and the enrichment regulation of the water pollutants from the perspective of spatial distribution caused by the ecological water transfer. The results show that there has a strong detention of the pollutants spread in Baiyangdian lake. With the ecological water transfer, there is a positive significance onto the local water deterioration, but not a fundamental solution onto the whole lake environmental issues. It still needs to develop the integrated control-rehabilitation managements and technologies for water pollutants combined with special land-water broken terrain and the local climate in Baiyangdian lake.

Aim of the study A traditional Chinese formulation Huang-Lian-Jie-Du-Tang (HLJDT) exerts anti-inflammatory effects. The present study aimed to investigate the effect of HLJDT on the LPS-stimulated leukocyte–endothelial cell adhesion and VCAM-1 gene expression both in vivo and in vitro. Materials and methods HLJDT was extracted from rhizoma coptidis, radix scutellariae, cortex phellodendri and fructus gardeniae in a weight rario of 1:1:1:1. In vivo leukocyte–endothelial cell adhesion was observed in rat lung after LPS stimulation (5 mg/kg, i.p.) with or without HLJDT (350 or 700 mg/kg, i.g.) pretreatment. The protein expression of vascular cell adhesion molecule 1 (VCAM-1) was analyzed by immunohistochemical method. In vitro leukocyte–endothelial cell adhesion was performed by examining the adhesion of THP-1 cells to LPS-stimulated human vascular endothelial cells with or without HLJDT pretreatment. The VCAM-1 expression at the RNA and protein levels was investigated by RT-PCR and western blot analysis, respectively. The activation of NF-κB was examined by the nuclear translocation of NF-κB by immunocytochemical method. Results In vivo, HLJDT dose-dependently reduced the number of leukocytes adhered to endothelium and VCAM-1 protein expression in lung venules of LPS-challenged rats. In vitro, HLJDT dose-dependently decreased the number of THP-1 cells adhered to LPS-stimulated endothelial cells and the expression of VCAM-1 both at the RNA and protein levels. The LPS-induced nuclear translocation of NF-kappa B in endothelial cells was also dose-dependently inhibited by HLJDT. Conclusions The present study demonstrated an additional mechanism underlying the anti-inflmmatory effect of HLJDT by inhibiting the leukocyte–endothelial cell adhesion and VCAM-1 gene expression. The inhibition of NF-kappa B activation by HLJDT might suggest a profound anti-inflammatory consequences.

A fast, simple and sensitive high performance liquid chromatographic (HPLC) method has been developed for determination of 10α-methoxy-6-methyl ergoline-8β-methanol (MDL, a main metabolite of nicergoline) in human plasma. One-step liquidâliquid extraction (LLE) with diethyl ether was employed as the sample preparation method. Tizanidine hydrochloride was selected as the internal standard (IS). Analysis was carried out on a Diamonsil ODS column (150 mmÃ4.6 mm, 5 μm) using acetonitrileâammonium acetate (0.1 mol/L) (15/85, v/v) as mobile phase at detection wavelength of 224 nm. The calibration curves were linear over the range of 2.288â73.2 ng/mL with a lower limit of quantitation (LLOQ) of 2.288 ng/mL. The intra- and inter-day precision values were below 13% and the recoveries were from 74.47% to 83.20% at three quality control levels. The method herein described was successfully applied in a randomized crossover bioequivalence study of two different nicergoline preparations after administration of 30 mg in 20 healthy volunteers. Keywords: Nicergoline, 10α-methoxy-6-methylergoline-8β-methanol (MDL), HPLC, Plasma-drug concentration, Bioequivalence study

Sleep-Disordered Breathing (SDB) is a prevalent affliction, which can range from simple snoring to severely obstructive sleep apnea. Compared to current treatment options of SDB, traditional Chinese medicine (TCM) provides a noninvasive way to relieve SDB-related symptoms and deaths. The purpose of this retrospective study was to observe the progression of adult SDB patients who had taken compound formula SZ + NUH (concentrated herbal granules) for four weeks. Depending on subjects’ individual needs, minor additions of formulas or single herbs were allowed. We found a significant amount of relief from snoring among the 118 enrolled subjects, according to before-after scores observed through the Snore Outcome Survey (SOS). Furthermore, as projected from the moderate linear correlation in before-after scores, we inferred that those cases with more severe snoring at baseline had greater improvement after treatment. Excessive daytime sleepiness was also significantly improved according to the results of the Epworth Sleepiness Scale (ESS). Assessment, using the SF-36 (Taiwanese version) revealed possible benefits of SZ + NUH in improving multiple facets of subjects’ quality of life. During treatment, no significant side effects occurred. In conclusion, the TCM compound formula based on SZ + NUH could be a safe and effective option for SDB treatment.

This paper reports the impacts of NH3 plasma treatment time, oxide overetching depth, and gate oxide thickness on symmetric vertical-channel Ni-salicided poly-Si thin-film transistors (VSA-TFTs) for the first time. off-state currents may be improved by increasing the oxide overetching depth. The on/ off current ratio may be also improved by increasing the oxide overetching depth. The NH3 plasma optimum treatment time of VSA-TFTs is significantly shorter than that of conventional top-gate horizontal-channel TFTs. The performance of VSA-TFTs is degraded by NH3 plasma treatment for too long a time. VSA-TFTs with 15-nm gate oxide thickness display better subthreshold swing (

A ±10.5 V programmable pulse generator (PPG) fabricated by high-voltage (HV) BCD CMOS technology is demonstrated, where a charge pump composed of five cascaded voltage doublers is included to boost the voltage from 2.5 V to be higher than 10 V. A cross-voltage-domain operational amplifier is proposed to carry out voltage level conversion and amplification. HV analogue switches are also proposed to change the direction of output currents. The proposed 16-channel PPG is realised on silicon, where the die area is 5.43 mm2. Physical measurements justify that the maximum output current is 525 μA, and the largest voltage of the pulses is ±10.5 V.

In this paper, silicon-oxide-nitride-oxide-semiconductor (SONOS) devices with embedded silicon nanocrystals (Si-NCs) in silicon nitride using in situ method with multilevel and 2-b/cell operation have been successfully demonstrated. The proposed in situ Si-NC deposition method exhibits the advantages of low cost, simplicity, and compatibility with modern IC processes. SONOS memories with embedded Si-NCs exhibit a significantly improved performance with a large memory window (> 5.5 V), low operating voltage (P/E voltage: Vg = 6 V, Vd = 7 V and Vg = -7 V, Vd = 10 V, respectively), greater tolerable gate and drain disturbance (Vt shift 108 s for 13% charge loss), and excellent endurance performance (after 104 P/E cycles with a memory window of 3 V).

In this letter, for the first time, we have successfully fabricated silicon-oxide-nitride-oxide-silicon (SONOS) devices with embedded silicon nanocrystals (Si-NCs) in silicon nitride using in situ method. This process is simple and compatible to modern IC processes. Different Si-NCs deposition times by in situ method were investigated at first. SONOS devices with embedded Si-NCs in silicon nitride exhibit excellent characteristics in terms of larger memory windows (> 5.5 V), lower operation voltage, high P/E speed, and longer retention time (> 108 s for 13% charge loss).

Central catadioptric cameras are widely used in virtual reality and robot navigation, and the camera calibration is a prerequisite for these applications. In this paper, we propose an easy calibration method for central catadioptric cameras with a 2D calibration pattern. Firstly, the bounding ellipse of the catadioptric image and fleld of view (FOV) are used to obtain the initial estimation of the intrinsic parameters. Then, the explicit relationship between the central catadioptric and the pinhole model is used to initialize the extrinsic parameters. Finally, the intrinsic and extrinsic parameters are reflned by nonlinear optimization. The proposed method does not need any fltting of partial visible conic, and the projected images of 2D calibration pattern can easily cover the whole image, so our method is easy and robust. Experiments with simulated data as well as real images show the satisfactory performance of our proposed calibration method.

This letter is the first to successfully demonstrate the 2-bit/cell wrapped-selected-gate (WSG) SONOS thin-film transistor (TFT) memory using source-side injection (SSI). Because of the higher programming efficiency of SSI, a memory window of approximately 3 V can be easily achieved in 10 μs and 30 ms for the program and erase modes, respectively. In addition, we performed an excellent 2-bit/cell distinguish margin for 3-V memory window in WSG-SONOS TFT memory. The optimal reliability of the endurance and data retention tests can be executed by adjusting the applied voltage appropriately.

For the first time, we construct poly-Si thin-film transistors (TFTs) with novel L-shaped poly-Si fin channels (poly-Si TFTs with L-fin channels, called LFin-TFTs). The L-fin channels of LFin-TFTs are similar to the multiple-gated fin channels of FinFETs. The LFin-TFTs exhibit a low supply gate voltage (3 V), a good subthreshold swing (SS) ~ 190 mV/dec, and a high on/off current ratio (ION/IOFF)>; 106 (VD=1 V) without hydrogen-related plasma treatments. After Ni salicidation, the devices exhibit steep SS ~ 148 mV/dec and ION/IOFF ~ 107. After NH3 plasma treatment, the characteristics of the devices are further improved. The LFin-TFTs have steeper SS ~ 132 mV/dec, higher (ION/IOFF)>; 107, and threshold voltage (VTH) ~ 0.036 V.

We have successfully fabricated novel sub-10-nm gate-all-around Si nanowire (NW) poly-Si TFTs with raised source/drain structure (GAA RSDNW-TFTs). The Si NW dimension is about 7×12 nm. A superior smooth elliptical shape is obtained, for the first time, in the category of poly-Si NW TFTs through the use of a novel fabrication process requiring no advanced lithographic tools. The GAA RSDNW-TFTs exhibit low supply gate voltage (3 V), steep subthreshold swing ~99 mV/dec, and high ION/IOFF >; 107 (VD = 1 V) without hydrogen-related plasma treatments. Furthermore, the DIBL of GAA RSDNW-TFTs is well controlled. These improvements can be attributed to the 3-D gate controllability, raised S/D structure, and sub-10-nm Si NW channel. These novel GAA RSDNW-TFTs are, thus, quite suitable for system-on-panel and 3-D IC applications.

In this letter, for the first time, one-time-programmable (OTP) memory fabricated on the low-temperature poly-Si p-channel thin-film transistor (TFT) with metal-induced lateral-crystallization channel layer and high-kappa dielectrics is demonstrated. The state of this OTP memory can be identified by the scheme of gate-induced drain leakage current measurement. The OTP-TFT memory has good electrical characteristics in terms of low threshold voltage Vth ~ -0.78 V, excellent subthreshold swing ~ 105 mV/dec, low operation voltage, faster programming speeds, and excellent reliability characteristics.

A high programming speed with a low-power-consumption wrapped-select-gate poly-Si-oxide-nitride-oxide-silicon memory is successfully demonstrated using the novel dynamic threshold source-side-injection programming technique. The select gate embedded in such particular memory structure acts like a dynamic MOSFET resulting in programming current (I PGM) that can be enhanced in this DT mode, easily attaining a high programming speed of about 100 ns. It still doubles the memory density by achieving the 2-bit/cell operation with MLC under DT mode.

In this letter, fluorine ion implantation with low- temperature solid-phase crystallized activation scheme is used to obtain a high-performance HfO2 low-temperature poly-Si thin- film transistor (LTPS-TFT) for the first time. The secondary ion mass spectrometer (SIMS) analysis shows a different fluorine profile compared to that annealed at high temperature. About one order current reduction of Imin is achieved because 25% grain- boundary traps are passivated by fluorine implantation. In addition, the threshold voltage instability of hot carrier stress is also improved with the introduction of fluorine. The LTPS-TFT with HfO2 gate dielectric and fluorine preimplantation can simultaneously achieve low VTH ~ 1.32 V, excellent subthreshold swing ~0.141 V/dec, and high ION/Imin current ratio ~1.98 times 107.

In this letter, the characteristics of positive bias temperature instability (PBTI) and hot carrier stress (HCS) for the low-temperature poly-Si thin-film transistors (LTPS-TFTs) with gate dielectric are well investigated for the first time. Under room temperature stress condition, the. PBTI shows a more serious degradation than does HCS, indicating that the gate bias stress would dominate the hot carrier degradation behavior for LTPS-TFT. In addition, an abnormal behavior of the degradation with different drain bias stress under high-temperature stress condition is also observed and identified in this letter. The degradation of device's performance under high-temperature stress condition can be attributed to the damages of both the gate dielectric and the poly-Si grain boundaries.

An advanced wetting method is used to prepare a composite with a high content of ceramic particles in a matrix of photocured polymethylmethacrylate. The method allows for the preparation at minimum stirring of high quality samples with up to 59% solid in volume. The samples present reasonable flow characteristics prior to curing, with high hardness and fracture toughness in the fully cured state. Practical implications of the preparation method for dental restorative applications are studied. The method is also useful in the preparation of similar composites for other practical applications.

A 16-channel stimulation waveform generator ASIC using high voltage CMOS technology to generate high voltage stimulation signals for Spinal Cord Stimulation (SCS) systems is presented in this study. To enlarge the voltage swing on high-impedance electrodes, the output stage of the proposed for the SCS systems is implemented on silicon using a 0.25 µm high-voltage (60 V) devices. Particularly, a charge pump composed of 5 cascaded voltage doublers is used to boost the core voltage (2.5 V) to higher than 10 V required by the SCS systems to execute electrical stimulation therapy [1]. A total of 16 stimulation waveform generators are included to drive 16 sets of electrodes, where each generator is composed of an HV operational amplifier and an HV analog switch. Compared with existing commercial products, the proposed SCS system attains better flexibility to meet the spinal cord stimulation high voltage demand in addition to the reduction of cost and PCB size.

A 60 V battery charger implemented using TSMC 0.25 µm Bipolar-CMOS-DMOS (BCD) 60 V process is presented in this work. A novel transition method is proposed to ensure smooth transitions between constant current (CC) and constant voltage (CV) modes. Since the proposed approach would require only additional diodes, power consumption and chip area are conserved in comparison with other sophisticated methods proposed in prior works. The charger sources a current of 50 mA in CC mode and has an efficiency of 75% ∼ 80% throughout the charging sequence. The supply voltage is kept at 3 volts higher than the battery voltage throughout the charging sequence to maintain charging efficiency. A thermal protection circuit is included in this design to prevent the charger from operating at a temperature over the maximum allowed temperature.

In this letter, for the first time, a novel p-n-diode (PND) structure of SONOS-type thin-film transistor (TFT) nonvolatile memory (NVM) with embedded silicon nanocrystals (Si-NCs) in the silicon nitride layer using an in situ method is successfully demonstrated. This novel structure has many advantages, including high density and suitability for 3-D circuit integration. Hot-electron injection and hot-hole injection are used as the program and erase methods, respectively. The sensing current of the three-terminal PND-TFT NVM is 10-7 A by the band-to-band tunneling current. A much larger memory window (> 12 V) and good data retention time (> 108 s for 12% charge loss) are exhibited. The device appears to have great potential for system-on-panel applications.

We have successfully fabricated the symmetric vertical-channel Ni-salicided polycrystalline silicon thin-film transistors (VSA-TFTs) for the first time. The transfer characteristics of VSA-TFTs show a sharp turning between subthreshold and on state. The off -state currents can be improved by a modified overetching of oxide, equivalent dual-gate structure, and n+ floating-region length. The on-state currents can be enhanced by Ni-salicidation. The VSA-TFTs display a good subthreshold swing of 220 mV/dec, steep mobility increase (field-effect mobility of 76 cm2/V·s), and large on/off-current ratio of more than 109 (IOFF = 4 × 10-14, ION = 7 × 10-5, and Wmask/Lmask = 10 μm/3 μm).

We report the growth study of ZnSe onto (NH 4 ) 2 S x -pretreated GaAs substrates. In situ reflection high-energy electron diffraction (RHEED) showed that the (NH 4 ) 2 S x -treated GaAs (001) surface took a streaky (1×1) RHEED pattern at room temperature and a new surface reconstruction after heating up to 200°C. The new reconstruction pattern is characterized by curved lines between the integral reflection diffraction rods. We attributed this pattern to the composite of a (2×1) reconstruction pattern of the (001) surface and the reflection diffraction at {11 n } ( n is estimated to be 5) surfaces of terraces formed at the (001) surface in the (NH 4 ) 2 S x Solution. We speculate that these terraces are enlarged at the surface of the overgrown ZnSe and contribute to enhance the growth rate of ZnSe throughout the entire stage of the heteroepitaxy.

II-VI wide-gap semiconductors, such as ZnSe, CdS and ZnS are very promising materials for the potential application to optoelectronic devices which cover from blue to ultra violet spectral region. To this end, it is important to develop the fabrication technique. Although epilayers of good quality have been grown on GaAs substrates by molecular beam epitaxy (MBE), metalorganic molecular beam epitaxy (MOMBE) and organometallic vapour phase epitaxy (OMVPE), it is still difficult to obtain epilayers of device quality. Recently, we have found that the surface pretreatment technique plays an important role in fabricating high-quality epilayers through in-situ RHEED monitoring in the MOMBE system. In this paper, we report that layer-by-layer or two-dimensional growth of ZnSe is successfully achieved from an initial stage of growth, if the GaAs is pretreated by (NH4)2Sx, solution. Furthermore, we also report that not only the ZnSe/GaAs interface properties but also the optical qualities of ZnSe and ZnS epilayers are greatly improved by this pretreatment.