Influence of Barrier Layers on ZrCoCe Getter Film Performance.

Improving the vacuum degree inside the vacuum device is vital to the performance and lifespan of the vacuum device. The influence of the Ti and ZrCoCe barrier layers on the performance of ZrCoCe getter films, including sorption performance, anti-vibration performance, and binding force between the ZrCoCe getter film and the Ge substrate were investigated. In this study, the Ti and ZrCoCe barrier layers were deposited between the ZrCoCe getter films and Ge substrates. The microtopographies of barrier layers and the ZrCoCe getter film were analyzed using scanning electron microscopes. The sorption performance was evaluated using the constant-pressure method. The surface roughness of the barrier layers and the getter films was analyzed via atomic force microscopy. The binding force was measured using a nanoscratch tester. The anti-vibration performance was examined using a vibration test bench. The characterization results revealed that the Ti barrier layer significantly improved the sorption performance of the ZrCoCe getter film. When the barrier material was changed from ZrCoCe to Ti, the initial sorption speed of the ZrCoCe getter film increased from 141 to 176 cm3·s-1·cm-2, and the sorption quantity increased from 223 to 289 Pa·cm3·cm-2 in 2 h. The binding force between the Ge substrate and the ZrCoCe getter film with the Ti barrier layer was 171 mN, whereas that with the ZrCoCe barrier layer was 154 mN. The results showed that the Ti barrier layer significantly enhanced the sorption performance and binding force between the ZrCoCe getter film and the Ge substrate, which improved the internal vacuum level and the stability of the microelectromechanical system vacuum devices.

Integrative Analysis of Transcriptome and Metabolome to Illuminate the Protective Effects of Didymin against Acute Hepatic Injury.

Based on the multiomics analysis, this study is aimed at investigating the underlying mechanism of didymin against acute liver injury (ALI). The mice were administrated with didymin for 2 weeks, followed by injection with lipopolysaccharide (LPS) plus D-galactosamine (D-Gal) to induce ALI. The pathological examination revealed that didymin significantly ameliorated LPS/D-Gal-induced hepatic damage. Also, it markedly reduced proinflammatory cytokines release by inhibiting the TLR4/NF-κB pathway activation, alleviating inflammatory injury. A transcriptome analysis proved 2680 differently expressed genes (DEGs) between the model and didymin groups and suggested that the PI3K/Akt and metabolic pathways might be the most relevant targets. Meanwhile, the metabolome analysis revealed 67 differently expressed metabolites (DEMs) between the didymin and model groups that were mainly clustered into the glycerophospholipid metabolism, which was consistent with the transcriptome study. Importantly, a comprehensive analysis of both the omics indicated a strong correlation between the DEGs and DEMs, and an in-depth study demonstrated that didymin alleviated metabolic disorder and hepatocyte injury likely by inhibiting the glycerophospholipid metabolism pathway through the regulation of PLA2G4B, LPCAT3, and CEPT1 expression. In conclusion, this study demonstrates that didymin can ameliorate LPS/D-Gal-induced ALI by inhibiting the glycerophospholipid metabolism and PI3K/Akt and TLR4/NF-κB pathways.

Small extracellular vesicles derived from hypoxic preconditioned dental pulp stem cells ameliorate inflammatory osteolysis by modulating macrophage polarization and osteoclastogenesis.

Extensive macrophage inflammatory responses and osteoclast formation are predominant during inflammatory or infective osteolysis. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (MSC-sEV) have been shown to exert therapeutic effects on bone defects. However, cultured MSCs are typically exposed to normoxia (21% O2) in vitro, which differs largely from the oxygen concentration in vivo under hypoxic conditions. It is largely unknown whether sEV derived from dental pulp stem cells (DPSCs) cultured under hypoxic conditions (Hypo-sEV) exert better therapeutic effects on lipopolysaccharide (LPS)-induced inflammatory osteolysis than those cultured under normoxic conditions (Nor-sEV) by simultaneously inhibiting the macrophage inflammatory response and osteoclastogenesis. In this study, we show that hypoxia significantly induces the release of sEV from DPSCs. Moreover, Hypo-sEV exhibit significantly improved efficacy in promoting M2 macrophage polarization and suppressing osteoclast formation to alleviate LPS-induced inflammatory calvarial bone loss compared with Nor-sEV. Mechanistically, hypoxia preconditioning markedly alters the miRNA profiles of DPSC-sEV. MiR-210-3p is enriched in Hypo-sEV, and can simultaneously induce M2 macrophage generation and inhibit osteoclastogenesis by targeting NF-κB1 p105, which attenuates osteolysis. Our study suggests a promising potential for hypoxia-induced DPSC-sEV to treat inflammatory or infective osteolysis and identifies a novel role of miR-210-3p in concurrently hindering osteoclastogenesis and macrophage inflammatory response by inhibiting NF-kB1 expression.

Factors affecting the outcome of full pulpotomy in permanent posterior teeth diagnosed with reversible or irreversible pulpitis.

This study aimed to investigate the factors affecting the success rate of full pulpotomy in permanent posterior teeth with pulpitis. The study included 105 permanent posterior teeth clinically diagnosed as reversible or irreversible pulpitis in 92 patients aged 18-82 years. All teeth underwent a full pulpotomy using mineral trioxide aggregate as a capping material and were recalled for clinical and radiographic evaluation at 3, 6, 12, and 24 months postoperatively. The overall success rate after the 12-month review was above 90%, and failed cases mainly occurred during the first 12 months after treatment. In this study, the treatment outcome of pulpotomy was not related to sex, or tooth position and the cause of pulpitis. To analyze the influence of age on the treatment outcome, all the teeth were allocated to three groups: group 1 (18-39 years); group 2 (40-59 years); and group 3 (≥ 60 years). A significant difference in success rate was found between groups 1 and 3 (P = 0.014). These results suggest that pulpotomy can be used as an alternative treatment for permanent mature teeth diagnosed with pulpitis and that aging is one factor affecting the treatment outcome.

Didymin Ameliorates Liver Fibrosis by Alleviating Endoplasmic Reticulum Stress and Glycerophospholipid Metabolism: Based on Transcriptomics and Metabolomics.

Introduction: Origanum vulgare L. is a traditional Chinese herb, having a strong hepatoprotective effect. In our previous experiments, we have isolated an ingredient from this herb and identified it as didymin. This study aimed to investigate the effects and underlying mechanisms of didymin on liver injury and fibrosis, elucidating whether it was the pharmacodynamic material basis of Origanum vulgare L. Methods: Mice were injected with CCl4 for 10 weeks to induce liver fibrosis, followed by didymin treatment for 6 weeks. Then, biochemical analysis and histopathological examinations were conducted to evaluate the therapeutic effects of didymin in alleviating fibrosis. Next, the possible mechanisms of didymin were predicted by transcriptomics and then verified by the multiple relevant examinations. Results: The pharmacodynamic experiments indicated that didymin significantly attenuated CCl4-induced hepatic injury and fibrogenesis, as evidenced by the ameliorative pathological tissue, low transaminase activity, and decreased collagen accumulation. Interestingly, the transcriptome analysis predicted that the potential targets were likely to be endoplasmic reticulum stress (ERS), inflammation, apoptosis, and metabolic pathways. And the predictions were then verified by the following examinations: (1) didymin significantly inhibited ERS by regulating the ATF6, IRE1α, and PERK pathways; (2) didymin markedly alleviated hepatocyte apoptosis by restoring the expression of Bcl-2 and caspase families, as well as the mitochondrial dysfunction; (3) didymin significantly decreased the production of the pro-inflammatory cytokines (IL-1ß and IL-6); (4) didymin inhibited the glycerophospholipid metabolism pathway by decreasing the synthesis of phosphatidylethanolamines and phosphatidylcholines. Conclusion: Our findings demonstrate that didymin can ameliorate liver fibrosis, which is mainly attributed to the inhibition of ERS, inflammation, and glycerophospholipid metabolism.

Tormentic Acid Ameliorates Hepatic Fibrosis in vivo by Inhibiting Glycerophospholipids Metabolism and PI3K/Akt/mTOR and NF-κB Pathways: Based on Transcriptomics and Metabolomics.

This study aimed to investigate the effects and underlying mechanisms of tormentic acid (TA) on carbon tetrachloride (CCl4)-induced liver fibrosis in rats. The rats were intragastrically administered with 50% CCl4 for 9 weeks to induce hepatic fibrosis, followed by various agents for 6 weeks. Transcriptomic analysis was carried out to predict the potential targets, and then multiple examinations were performed to verify the prediction. The results showed that TA significantly alleviated liver injury and fibrosis, as evidenced by the ameliorative pathological tissue, low transaminase activity, and decreased collagen accumulation. Besides, TA markedly reduced hepatocyte apoptosis by regulating the expression of caspase-3 and Bcl-2 families. The transcriptomic analysis revealed 2,173 differentially expressed genes (DEGs) between the TA and model groups, which could be enriched in the metabolic pathways and the PI3K/Akt and NF-κB signaling pathways. The metabolomics analysis showed that TA could regulate the glycerophospholipid metabolism pathway by regulating the synthesis of phosphatidylserines, phosphatidylethanolamines and phosphatidylcholines. Moreover, the integrative analysis of the transcriptomics and metabolomics data indicated that TA inhibited the glycerophospholipid metabolism pathway by inhibiting the expression of LPCAT4, PTDSS2, PLA2G2A and CEPT1. In addition, the relevant signaling pathways analysis confirmed that TA inhibited HSCs activation by blocking the PI3K/Akt/mTOR pathway and ameliorated inflammatory injury by inhibiting the NF-κB pathway. In conclusion, TA significantly alleviates liver fibrosis in vivo by inhibiting the glycerophospholipid metabolism pathway and the PI3K/Akt/mTOR and NF-κB signaling pathways.

Comprehensive analysis of transcriptomics and metabolomics to illustrate the underlying mechanism of helenalin against hepatic fibrosis.

This study aimed to investigate the protective mechanisms of helenalin on hepatic fibrosis. In brief, rats were intragastrically administrated with 50% CCl4 for 9 weeks to induce liver fibrosis, followed by treatment with various agents for 6 weeks. The effects of helenalin on hepatic injury were assessed by pathological examinations. The potential targets were predicted by the "Drug-Disease" bioinformatic analysis and then verified by multiple experiments. Moreover, the underlying mechanism was investigated by transcriptomics and metabolomics as a whole. The results showed that helenalin significantly alleviated hepatocyte necrosis and hepatic injury, as proved by the pathological examinations. Also, helenalin markedly attenuated hepatocyte apoptosis by regulating the expression of caspase-3 and Bcl-2 families. Besides, helenalin could significantly reduce collagen accumulation, as evidenced by the decreased contents of collagen, hyaluronic acid and laminin. Moreover, helenalin significantly down-regulated the phosphorylation of PI3K, Akt, FAK, mTOR and P70S6K, and PTEN protein expression, suggesting that helenalin inhibited the PI3K/Akt signaling cascade. Meanwhile, helenalin inhibited the NF-κB signaling pathway by reducing the phosphorylation of IκBα, NF-κB p65 and IKKα/ß, alleviating inflammation response. Interestingly, the analysis of transcriptomics and metabolomics indicated that helenalin inhibited the glycerophospholipid metabolism pathway by down-regulating the target genes (CHKA, ETNPPL, LYPLA1, PCYT2, PLD4 and PNPLA6), ultimately ameliorating hepatocyte damage. In conclusion, helenalin ameliorates hepatic fibrosis by regulating the PI3K/Akt and NF-κB signaling pathways and the glycerophospholipid metabolism pathway.

Design of an AIE-Active Flexible Self-Assembled Monolayer Probe for Trace Nitroaromatic Compound Explosive Detection.

In this work, a series of molecules TPE-PA-n (n = 3-11) were designed with classic aggregation-induced emission (AIE) 1,1,2,2-tetraphenylethene (TPE) for self-assembled monolayers (SAMs), which are applied for the detection of trace nitroaromatic compound (NAC) explosives. Phosphoric acid that acts as an anchor is used to connect with TPE through alkyl chains of various lengths. It is found that the alkyl chains play a role in pulling TPE luminogens to aggregate for light emission, which can affect the fluorescence and sensing performance of the SAMs. Ulteriorly, a model is built to explore the influence of the alkyl chain length on the device performance, which is determined by the three effects of the alkyl chain: flexibility, the coupling effect, and the odd-even effect. By comparison, the functional molecules with the chain length of 8 were finally selected and further applied for NAC sensors. By means of fluorescence spectra, the SAM sensor was proved to have good stability, reversibility, selectivity, and sensitivity, and its detection limits for trinitrotoluene, dinitrotoluene, and nitrobenzene were 1.2, 6.0, and 35.7 ppm, respectively. This work provides new ideas for the design and preparation of flexible sensors for trace NAC detection with high performance, low cost, and easy operation.

Prediction and verification of target of helenalin against hepatic stellate cell activation based on miR-200a-mediated PI3K/Akt and NF-κB pathways.

Hepatic stellate cell (HSC) activation is a crucial event in the progress of liver fibrosis. In this study, the target of helenalin was firstly predicted by bioinformatics analysis, and then the prediction was verified by various experiments. HSC-T6 cells were activated by interleukin-1 beta (IL-1ß) and then treated with helenalin. Moreover, HSC-T6 cells were transfected with miR-200a mimic or inhibitor, and the effect of helenalin on the miR-200a-mediated PI3K/Akt and NF-κB signaling pathways was investigated. The bioinformatics analysis indicated that miR-200a might regulate the PI3K/Akt pathway, NF-κB activation, Bcl-2 family and Caspases, ultimately affecting cell survival and apoptosis. Interestingly, the molecular docking demonstrated that the target of helenalin might be miR-200a-mediated the PI3K/Akt and NF-κB pathways. Moreover, the experiments showed that helenalin administration led to the inactivation of HSC-T6 cells, as evidenced by the inhibition of cell proliferation, α-SMA expression and collagen production. The mechanism studies showed that helenalin reduced collagen accumulation by restoring the balance of MMPs/TIMPs. Moreover, helenalin markedly suppressed HSC activation by inhibiting the PI3K/Akt pathway and alleviated inflammatory response by blocking the NF-κB signal transduction. Further study indicated that helenalin up-regulated miR-200a expression, thus leading to the inhibition of the PI3K/Akt and NF-κB signaling pathways. In conclusion, helenalin inhibits HSC activation via inhibiting the miR-200a-mediated PI3K/Akt and NF-κB pathways, and it may be developed as a potential medicine for the treatment of liver fibrosis.

Preparation of the lingual canal in mandibular first premolar with canal bifurcation.

The aim of this study was to establish an effective method of locating and negotiating the lingual canal in mandibular first premolars with two canals during root canal preparation. A total of 125 mandibular first premolars with radicular grooves were collected, and after micro-computed tomography scanning, 50 mandibular first premolars with a Vertucci V/III canal form were selected based on the inclusion criteria. Access cavities were prepared, and the lingual canals (LCs) were searched in four following steps: step 1 direct vision and a straight K-file; step 2 stereomicroscopy and a straight K-file; step 3 stereomicroscopy and a pre-curved K-file; and step 4 a long-neck bur. After localization, the LCs were instrumented. In most cases, access to the LC was achieved by step 2 (19/50, 38%) or step 3 (22/50, 44%). In three cases (6%), step 1 alone was enough to achieve access to the orifice, and in six cases (12%), access to the lingual canal was not achieved until step 4. Overall, 43 of the 50 mandibular first premolars (86%) were successfully instrumented, and the remaining seven failed. Two cases failed in the process of negotiating the canal to full length and five cases failed due to procedural errors (ledge formation, canal perforation, vertical fracture, or instrument separation). The LC in mandibular first premolars is a major endodontic challenge. A stereomicroscope and a pre-curved K file are suggested to be valuable tools for detecting and accessing the extra LC.

Genotype, biofilm formation ability and specific gene transcripts characteristics of endodontic Enterococcus faecalis under glucose deprivation condition.

OBJECTIVE: To study the relationship between the specific gene and biofilm formation ability of seven wild type Enterococcus faecalis (E. faecalis) under glucose deprivation conditions. DESIGN: Wild type E. faecalis (3RC, 5RC, 25RC, 31RC, 33RC, 37RC, 58RC) extracted from the teeth with persistent apical periodontitis were cultured under glucose deprivation conditions and then resequenced. The biofilm formation ability was compared using primary adherence assay, confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). The transcriptional level of biofilm formation-related genes (ace, gelE, efa, esp and fsrB) were detected. RESULTS: Genomic resequencing showed that 3RC and 58RC (Class B) were similar, while 5RC, 25RC, 31RC, 33RC and 37RC (Class A) were similar. Based on primary adherence assay, CLSM and SEM results, biofilm formation ability of Class B strains was lower, while Class A strains were higher when compared with control group (0.25 % glucose). Furthermore, compared with control group (0.25 % glucose), the transcriptional levels of ace, efa and fsrB genes were upregulated in all strains; the transcriptional levels of gelE were downregulated in Class B strains, upregulated in Class A strains; the transcriptional levels of esp of Class B strains were downregulated, while upregulated in 25RC, 31RC and 37RC (Class A), and not observed in 5RC and 33RC. CONCLUSION: The genotypes of wild type E. faecalis of different persistent periapical periodontitis teeth are different. The genotype differences and the transcription levels of related virulence genes (ace, gelE, efa, esp and fsrB) are related to the biological phenotype.

Bilayer Polyaniline-WO3 Thin-Film Sensors Sensitive to NO2.

In this work, a novel bilayer polyaniline-WO3 (PANI-WO3) thin film on the fluorine-doped tin oxide (FTO) glass substrate was prepared by hydrothermal synthesis and in situ chemical oxidative polymerization methods. Until now, no one has ever made attempts to use the PANI-WO3 composite on the FTO glass substrate to detect NO2 gas. The composite showed excellent sensing performance for NO2 detection at an operation temperature of 50 °C and a detection limit of 2 ppm. With regard to the PANI-WO3 hybrid, the response value for NO2 at 30 ppm is 60.19 and is three times higher than that for pure WO3 at 50 °C. Besides, the PANI-WO3 hybrid had excellent stability. The improvement of gas sensing was assigned to the creation of p-n heterojunctions between p-type PANI and n-type WO3, larger specific surface, increase of oxygen vacancies, and a wide conduction channel provided by PANI.

Identification of novel uracil derivatives incorporating benzoic acid moieties as highly potent Dipeptidyl Peptidase-IV inhibitors.

Dipeptidyl Peptidase-IV (DPP-4) is a validated therapeutic target for type 2 diabetes. Aiming to interact with both residues Try629 and Lys554 in S2' site, a series of novel uracil derivatives 1a-l and 2a-i incorporating benzoic acid moieties at the N3 position were designed and evaluated for their DPP-4 inhibitory activity. Structure-activity relationships (SAR) study led to the identification of the optimal compound 2b as a potent and selective DPP-4 inhibitor (IC50 = 1.7 nM). Docking study revealed the additional salt bridge formed between the carboxylic acid and primary amine of Lys554 has a key role in the enhancement of the activity. Furthermore, compound 2b exhibited no cytotoxicity in human hepatocyte LO2 cells up to 50 µM. Subsequent in vivo evaluations revealed that the ester of 2b robustly improves the glucose tolerance in normal mice. The overall results have shown that compound 2b has the potential to a safe and efficacious treatment for T2DM.

Electrical Properties of Ultrathin Hf-Ti-O Higher k Gate Dielectric Films and Their Application in ETSOI MOSFET.

Ultrathin Hf-Ti-O higher k gate dielectric films (~2.55 nm) have been prepared by atomic layer deposition. Their electrical properties and application in ETSOI (fully depleted extremely thin SOI) PMOSFETs were studied. It is found that at the Ti concentration of Ti/(Ti + Hf) ~9.4%, low equivalent gate oxide thickness (EOT) of ~0.69 nm and acceptable gate leakage current density of 0.61 A/cm2 @ (V fb - 1)V could be obtained. The conduction mechanism through the gate dielectric is dominated by the F-N tunneling in the gate voltage range of -0.5 to -2 V. Under the same physical thickness and process flow, lower EOT and higher I on/I off ratio could be obtained while using Hf-Ti-O as gate dielectric compared with HfO2. With Hf-Ti-O as gate dielectric, two ETSOI PMOSFETs with gate width/gate length (W/L) of 0.5 µm/25 nm and 3 µm/40 nm show good performances such as high I on, I on/I off ratio in the magnitude of 105, and peak transconductance, as well as suitable threshold voltage (-0.3~-0.2 V). Particularly, ETSOI PMOSFETs show superior short-channel control capacity with DIBL <82 mV/V and subthreshold swing <70 mV/decade.

[Cross-sectional study on rates and influential factors of standard medication for antiretroviral therapy in preventing mother-to-child transmission of HIV].

OBJECTIVE: To understand the status of standard medication of antiretroviral therapy and identify its correlationship with preventing mother-to-child transmission of HIV (PMTCT). METHODS: Qualitative and quantitative methods for measuring of standard medication towards antiretroviral therapy of PMTCT were used in a cross-sectional study of 167 pregnant women who had accessed to PMTCT services and 57 physicians providing service from January 2005 to June 2007 in 5 HIV epidemic counties in Yunnan province. RESULTS: A total of 167 mothers were recruited, of which 65.87% (110/167) demonstrated for standard medication. The percentage of rational selection of antivirus-therapy regimen was 88.02% (147/167). HIV positive mothers with rational using medicine during labor covered 81.37% (131/161). 87.42% (146/167) of women demonstrated good compliance. The main correlations with the standard medication level of HIV positive pregnant women and their infants were as follows: diagnose time (OR = 2.617; 95% CI: 1.184 - 5.783), place of delivery (OR = 0.064; 95% CI: 0.007 - 0.607), minorities (OR = 0.344; 95% CI: 0.162 - 0.730), understanding of HIV women for antiretroviral therapy (OR = 6.843; 95% CI: 1.449 - 32.312), and doctors' cognition about the regimen for antiretroviral therapy was not enough; 5 key knowledge points (purpose of PMTCT, the consequence of not requiring standard medication, the effect of knowing regimens, the relationship of CD4 levels and selected regimens, the side effect of the relevant medicine) score rate was 47.72% (136/285). CONCLUSION: The proportions of standard medication in PMTCT antiretroviral therapy were not high. Standard medication might be associated with multiple factors from doctors, patients and society. It is necessary to make some steps to improve standard medication of antiretroviral therapy in PMTCT.