The Upregulation of Leucine-Rich Repeat Containing 1 Expression Activates Hepatic Stellate Cells and Promotes Liver Fibrosis by Stabilizing Phosphorylated Smad2/3.

Liver fibrosis poses a significant global health risk due to its association with hepatocellular carcinoma (HCC) and the lack of effective treatments. Thus, the need to discover additional novel therapeutic targets to attenuate liver diseases is urgent. Leucine-rich repeat containing 1 (LRRC1) reportedly promotes HCC development. Previously, we found that LRRC1 was significantly upregulated in rat fibrotic liver according to the transcriptome sequencing data. Herein, in the current work, we aimed to explore the role of LRRC1 in liver fibrosis and the underlying mechanisms involved. LRRC1 expression was positively correlated with liver fibrosis severity and significantly elevated in both human and murine fibrotic liver tissues. LRRC1 knockdown or overexpression inhibited or enhanced the proliferation, migration, and expression of fibrogenic genes in the human hepatic stellate cell line LX-2. More importantly, LRRC1 inhibition in vivo significantly alleviated CCl4-induced liver fibrosis by reducing collagen accumulation and hepatic stellate cells' (HSCs) activation in mice. Mechanistically, LRRC1 promoted HSC activation and liver fibrogenesis by preventing the ubiquitin-mediated degradation of phosphorylated mothers against decapentaplegic homolog (Smad) 2/3 (p-Smad2/3), thereby activating the TGF-ß1/Smad pathway. Collectively, these results clarify a novel role for LRRC1 as a regulator of liver fibrosis and indicate that LRRC1 is a promising target for antifibrotic therapies.

The relationship between mobile phone addiction and time management disposition among Chinese college students：A cross-lagged panel model.

Previous research has identified a negative association between mobile phone addiction and time management disposition among college students; however, the direction of this relationship remains divergent. This study utilized a cross-lagged panel model to elucidate the directionality of the relationship between mobile phone addiction and time management disposition. A total of 466 college students completed two measures at seven-month intervals. The findings revealed a prevalence of mobile phone addiction at 10.94 % and 13.73 % in the two surveys. Notably, both mobile phone addiction and time management disposition demonstrated stability over time. Furthermore, a discernible negative bidirectional relationship was observed between the two. The present findings underscore the importance of timely intervention for college students facing challenges in mobile phone usage and time management.

Language Learning Motivations among Turkish Learners of Chinese as a Foreign Language: A Survey of Five Universities in Turkey.

Research on language learning motivations has been extensive. However, research on learners' motivations for learning Chinese has been underexplored compared to that for learning English. The current study aimed to investigate the motivations among 256 Turkish learners of Chinese as foreign language (CFL) who studied at five universities in Turkey. Participants completed an adapted questionnaire based on Gardner's Attitude/Motivation Test Battery (AMTB). A series of statistical analysis revealed three major findings. First, integrativeness, attitudes towards learning situation and attitudes towards learning Chinese were identified as the three most important motivational variables, followed by instrumentality, and parental encouragement. Language anxiety and passive motivation seemed to play a weaker role in Turkish CFL learners' motivations for learning Chinese at the tertiary level. Second, the results also show that females exhibited higher motivation to learn the target language compared to their male peers. Third, the choice of major among CFL learners appeared to influence their language learning motivations, with a notable distinction between Chinese majors and non-Chinese majors in five motivational variables: integrativeness attitudes towards the learning situation, language anxiety, parental encouragement, and passive motivation.

A Single-Component Molecular Glass Resist Based on Tetraphenylsilane Derivatives for Electron Beam Lithography.

A novel molecular glass (TPSiS) with photoacid generator (sulfonium salt group) binding to tetraphenylsilane derivatives was synthesized and characterized. The physical properties such as solubility, film-forming ability, and thermal stability of TPSiS were examined to assess the suitability for application as a candidate for photoresist materials. The sulfonium salt unit underwent photolysis to effectively generate photoacid on UV irradiation, which catalyzed the deprotection of the t-butyloxycarbonyl groups. It demonstrates that the TPSiS can be used as a 'single-component' molecular resist without any additives. The lithographic performance of the TPSiS resist was evaluated by electron beam lithography. The TPSiS resist can resolve 25 nm dense line/space patterns and 16 nm L/4S semidense line/space patterns at a dose of 45 and 85 µC/cm2 for negative-tone development (NTD). The etching selectivity of the TPSiS resist to Si substrate is 8.6 under SF6/O2 plasma, indicating a potential application. Contrast analysis suggests that the significant solubility switch within a narrow exposure dose range (18-47 µC/cm2) by NTD is favorable for high-resolution patterns. This study supplies useful guidelines for the optimization and development of single-component molecular glass resists with high lithographic performance.

Isoandrographolide from Andrographis paniculata ameliorates tubulointerstitial fibrosis in ureteral obstruction-induced mice, associated with negatively regulating AKT/GSK-3ß/ß-cat signaling pathway.

Tubulointerstitial fibrosis (TIF) is a prominent pathological manifestation for the progression of almost all chronic kidney diseases (CKDs) to end-stage renal failure. However, there exist few efficient therapies to cure TIF. Our recent results showed that (8R, 12S)-isoandrographolide (ISA), a diterpenoid lactone ingredient of traditional Chinese herbal Andrographis paniculata (Burm.f.) Nees, exhibited anti-pulmonary fibrosis in silica-induced mice. Herein, we investigated the therapeutic effect of ISA on TIF, using mice subjected to unilateral ureteral obstruction (UUO) and human kidney proximal tubular epithelial (HK-2) cells treated with transforming growth factor-ß1 (TGF-ß1) or tumor necrosis factor-α (TNF-α). The pathological changes and collagen deposition results displayed that ISA administration significantly attenuated inflammatory response, ameliorated TIF, and protected the kidney injury. Interestingly, ISA revealed much lower cytotoxicity on HK-2 cells, but exhibited stronger inhibitory effect on tubular epithelial mesenchymal transformation (EMT) and inflammation, as compared to andrographolide (AD), the major ingredient of A. paniculata extract that has been reported to ameliorate TIF in diabetic nephropathy mice. It was further clarified that the amelioration of TIF by ISA was associated with suppressing the aberrant activation of AKT/GSK-3ß/ß-catenin pathway through network pharmacology analysis and experimental validation. Taken together, these findings indicate that ISA is a promising lead compound for development of anti-TIF, and even broad-spectrum anti-fibrotic drugs.

Molecular Glass Resists Based on Tetraphenylsilane Derivatives: Effect of Protecting Ratios on Advanced Lithography.

A series of t-butyloxycarbonyl (t-Boc) protected tetraphenylsilane derivatives (TPSi-Boc x , x = 60, 70, 85, 100%) were synthesized and used as resist materials to investigate the effect of t-Boc protecting ratio on advanced lithography. The physical properties such as solubility, film-forming ability, and thermal stability of TPSi-Boc x were examined to assess the suitability for application as candidates for positive-tone molecular glass resist materials. The effects of t-Boc protecting ratio had been studied in detail by electron beam lithography. The results suggest that the TPSi-Boc x resist with different t-Boc protecting ratios exhibit a significant change in contrast, pattern blur, and the density of bridge defect. The TPSi-Boc70% resist achieves the most excellent patterning capability. The extreme ultraviolet (EUV) lithography performance on TPSi-Boc70% was evaluated by using the soft X-ray interference lithography. The results demonstrate that the TPSi-Boc70% resist can achieve excellent patterning capability down to 20 nm isolated lines at 8.7 mJ/cm2 and 25 nm dense lines at 14.5 mJ/cm2. This study will help us to understand the relationship between the t-Boc protecting ratio and the patterning ability and supply useful guidelines for designing molecular resists.

Effect of aging on color stability and bond strength of dual-cured resin cement with amine or amine-free self-initiators.

This study aimed to evaluate the effect of aging on the color stability and bond strengths of dual-cured resin cements containing amine or amine-free self-initiators. Three dual-cured and one light-cured resin cements were used. The covered (by lithium disilicate ceramic disks) and uncovered groups (n=10) were included. Color measurements were tested after 24 h, 10,000 and 20,000 thermal cycles (TCs). Micro-shear bond strengths (µSBS) were tested after 24 h, 10,000 and 20,000 TCs, and failure modes were analyzed (n=14). Two-way ANOVA and Tukey's test were implemented for color difference (ΔE*ab) and µSBS (α=0.05). The mean ΔE*ab difference was significant among groups (p<0.001). The lowest ΔE*ab values were obtained for dual-cured resin cement with amine-free self-initiators dual-cured cement after aging in all dual-cured resin cements, and the µSBS of the dual-cured resin cements on ceramic was significantly higher than that of the light-cured ones after aging (p<0.001).

Effect of universal adhesive and silane pretreatment on bond durability of metal brackets to dental glass ceramics.

This study aimed to investigate the effect of universal adhesive and silane pretreatment on the bond durability of metal brackets to dental glass ceramics. Eighty lithium disilicate glass ceramic specimens were randomly assigned to one of four groups (n = 20) defined by the pretreatment and adhesive used: (i) Adper Single Bond 2; (ii) silane + Adper Single Bond 2; (iii) Single Bond Universal; and (iv) silane +Single Bond Universal. Maxillary central incisor metal brackets were bonded on the ceramic surfaces with resin composite. A shear bond strength test was conducted after 24 h of water storage and after 10,000 thermocycles. Adhesive remnant index scoring and field-emission scanning electron microscopy were performed to determine adhesives remaining on the ceramic surfaces and the ceramic ultrastructure following bracket debonding, respectively. After 10,000 thermocycles, specimens treated with Single Bond Universal preserved an appropriate bond strength between brackets and glass ceramics and showed minimum ceramic surface damage following bracket debonding, which was not the case in the other three groups. The application of a silane-containing universal adhesive without silane pretreatment achieves adequate durability of the bond of metal brackets to dental glass ceramics and allows safe debonding, which may aid in optimizing the effectiveness for orthodontic treatment.

Transport of PFOS in aquifer sediment: Transport behavior and a distributed-sorption model.

The objectives of this research were to examine the transport of perfluorooctane sulfonic acid (PFOS) in aquifer sediment comprising different geochemical properties, and to compare the behavior to that observed for PFOS transport in soil and sand. PFOS retardation was relatively low for transport in all aquifer media. The PFOS breakthrough curves were asymmetrical and exhibited extensive concentration tailing, indicating that sorption/desorption was significantly nonideal. The results of model simulations indicated that rate-limited sorption/desorption was the primary cause of the nonideal PFOS transport. Comparison of PFOS transport in aquifer media to data reported for PFOS transport in two soils and a quartz sand showed that PFOS exhibited more extensive elution tailing for the soils, likely reflecting differences in the relative contributions of various media constituents to sorption. A three-component distributed-sorption model was developed that accounted for contributions from soil organic carbon, metal oxides, and silt + clay fraction. The model produced very good predictions of Kd for the five media with lower soil organic­carbon contents (≤0.1%). Soil organic carbon was estimated to contribute 19-42% of the total sorption for all media except the sand, to which it contributed ~100%. The contribution of silt + clay ranged from 51 to 80% for all media except the sand. The only medium for which the contribution of metal-oxides was significant is Hanford, with an estimated contribution of 15%. Overall, the results of the study indicate that sorption of PFOS by these aquifer media comprised contributions from multiple soil constituents.

DeepDSC: A Deep Learning Method to Predict Drug Sensitivity of Cancer Cell Lines.

High-throughput screening technologies have provided a large amount of drug sensitivity data for a panel of cancer cell lines and hundreds of compounds. Computational approaches to analyzing these data can benefit anticancer therapeutics by identifying molecular genomic determinants of drug sensitivity and developing new anticancer drugs. In this study, we have developed a deep learning architecture to improve the performance of drug sensitivity prediction based on these data. We integrated both genomic features of cell lines and chemical information of compounds to predict the half maximal inhibitory concentrations [Formula: see text] on the Cancer Cell Line Encyclopedia (CCLE) and the Genomics of Drug Sensitivity in Cancer (GDSC) datasets using a deep neural network, which we called DeepDSC. Specifically, we first applied a stacked deep autoencoder to extract genomic features of cell lines from gene expression data, and then combined the compounds' chemical features to these genomic features to produce final response data. We conducted 10-fold cross-validation to demonstrate the performance of our deep model in terms of root-mean-square error (RMSE) and coefficient of determination [Formula: see text]. We show that our model outperforms the previous approaches with RMSE of 0.23 and [Formula: see text] of 0.78 on CCLE dataset, and RMSE of 0.52 and [Formula: see text] of 0.78 on GDSC dataset, respectively. Moreover, to demonstrate the prediction ability of our models on novel cell lines or novel compounds, we left cell lines originating from the same tissue and each compound out as the test sets, respectively, and the rest as training sets. The performance was comparable to other methods.

Association of breastfeeding duration, birth weight, and current weight status with the risk of elevated blood pressure in preschoolers.

BACKGROUND/OBJECTIVES: Few studies have examined the effects of the weight status at birth and preschool age on the risk of elevated blood pressure (EBP) in early childhood, and whether the effects can be modified by breastfeeding duration remains unclear. We aimed to evaluate the effects of high birth weight (HBW) with overweight/obese or abdominal obesity on the risk of EBP in preschoolers, and further evaluate the effects classified by breastfeeding duration (<6 and ≥6 months). SUBJECTS/METHODS: This cross-sectional study was conducted in 2018 in Zhuhai, China. Out of 2390 3-4-year-old preschoolers originally recruited, a total of 1899 were included in the analysis. Logistic regression analysis was performed to examine the effects of the weight status at the two age points and breastfeeding duration on the risk of EBP. RESULTS: Preschoolers with current overweight/obese had a 1.13-fold increased risk of EBP than those with persistent normal weight, irrespective of their birth weight. However, the preschoolers with HBW had no increased risk of EBP, when they became normal weight (OR 1.70, 0.78-3.72). Similar results were found for the current abdominal obesity and the risk of EBP. In addition, the EBP risk of obese status was minimized if preschoolers were breastfed for ≥6 months. CONCLUSIONS: Obesity status at preschool age can increase the risk of EBP, irrespective of birth weight. However, this EBP risk can be mitigated if HBW changes to current normal weight. Longer breastfeeding duration can partially offset the risk of EBP in preschoolers with obesity status.

Nonideal Transport and Extended Elution Tailing of PFOS in Soil.

The objective of this research was to examine the influence of nonideal sorption/desorption on the transport of polyfluorinated alkyl substances (PFASs) in soil, with a specific focus on characterizing and quantifying potential extended, mass-transfer-limited elution behavior. Perfluorooctane sulfonic acid (PFOS) was used as a representative PFAS, and miscible-displacement experiments were conducted with two soils comprising contrasting geochemical properties. The influence of nonlinear, rate-limited, hysteretic, and irreversible sorption/desorption on transport was investigated through experiments and model simulations. The breakthrough curves measured for PFOS transport in the two soils were asymmetrical and exhibited extensive elution tailing, indicating that sorption/desorption was significantly nonideal. The widely used two-domain sorption kinetics model could not fully simulate the observed transport behavior, whereas a multirate model employing a continuous distribution of sorption domains was successful. The overall results indicated that sorption/desorption was significantly rate-limited and that nonlinear, hysteretic, and irreversible sorption/desorption had minimal impact on PFOS transport. Comparison of PFOS transport data to data reported for two hydrophobic organic contaminants (HOCs) showed that the HOCs exhibited much more extensive elution tailing, likely reflecting differences in sorption/desorption mechanisms. The projected influence of rate-limited sorption/desorption on PFOS transport at the field scale was investigated through simulation. The results of the study suggest that rate-limited sorption/desorption may affect the field-scale transport of PFOS and other PFAS for systems influenced by transient or short-residence-time conditions and in some cases could possibly increase the amount of flushing required to reduce PFOS concentrations to levels below those associated with human-health concerns.

The effect of monowave and polywave light-polymerization units on the adhesion of resin cements to zirconia.

STATEMENT OF PROBLEM: Although newly developed photoinitiators can make up for the limitations of camphorquinone, their absorption spectra are different. However, little attention has been paid to the compatibility of available wavelength spectra of light-polymerization units (LPUs) and photoinitiators within resin cements. PURPOSE: The purpose of this in vitro study was to evaluate the effect of monowave and polywave light-emitting diode (LED) units on the adhesion of dual-polymerizing self-adhesive resin cements to monolithic zirconia. MATERIAL AND METHODS: Monowave LPUs and polywave LPUs were chosen to polymerize 2 dual-polymerizing self-adhesive resin cements. Ninety-six zirconia disks were randomly divided into 4 groups as different combinations of LPUs and resin cements, namely ES-U200, BS-U200, ES-SC, and BS-SC. Resin cements were adhered to zirconia disks, and the microshear bond strength (µSBS) test was conducted after 24 hours of H2O storage (24 h) and 10 000 thermocycles (10k/TC). Failure modes were examined by stereomicroscopy and scanning electron microscopy (SEM). The degree of conversion (DC) was tested both immediately and 24 hours later. In statistical analyses, 2-way ANOVA and the Tukey honestly significant difference post hoc test were performed for µSBS and DC results, and chi-square test was performed for failure mode analysis (α=.05 for all tests). RESULTS: The 2-way ANOVA demonstrated that different combinations of LPUs and resin cements, as well as different artificial aging levels, significantly influenced microshear bond strength values (P<.001). The interactions between 2 factors were also significant (P<.001). The BS-SC group possessed relatively high bond strength in both 24-hour and 10k/TC aging levels. For the same resin cement, no significant difference was found in the immediate DC (P=.405 for U200 and P=.708 for SC). At 24 hours, DC and BS-U200 values were significantly higher than ES-U200 values (P=.002), whereas BS-SC values were not significantly different from ES-SC values (P=.284). CONCLUSIONS: Within the limitation of this in vitro study, the emission spectra of LED units significantly influenced the bond strengths, DC, and failure mode of dual-polymerizing self-adhesive resin cements to zirconia at both immediate and artificial aging levels. The LPU should provide light energy to match the absorption wavelengths of photoinitiators in the resin cements.

Comprehensive retention model for PFAS transport in subsurface systems.

A comprehensive compartment model is presented for PFAS retention that incorporates all potential processes relevant for transport in source zones. Miscible-displacement experiments were conducted to investigate separately the impact of adsorption at the air-water and decane-water interfaces on PFAS retention and transport. Two porous media were used, a quartz sand and a soil, and perfluorooctanesulfonic acid (PFOS) was used as the model PFAS. The breakthrough curves for transport under water-unsaturated conditions were shifted noticeably rightward (delayed arrival) compared to the breakthrough curves for saturated conditions, indicating greater retardation due to adsorption at the air-water or decane-water interface. The retardation factor was 7 for PFOS transport in the sand for the air-water system, compared to 1.8 for saturated conditions. PFOS retardation factors for transport in the soil were 7.3 and 3.6 for unsaturated (air-water) vs saturated conditions. Air-water interfacial adsorption is a significant source of retention for PFOS in these two systems, contributing more than 80% of total retention for the sand and 32% for the soil. For the experiments conducted with decane residual emplaced within the sand, adsorption at the decane-water interface contributed more than 70% to total retention for PFOS transport. Methods to determine or estimate key distribution variables are presented for parameterization of the model. Predicted retardation factors were similar to the measured values, indicating that the conceptual model provided adequate representation of the relevant retention processes and that the parameter estimation methods produced reasonable values. The results of this work indicate that adsorption by fluid-fluid interfaces in variably saturated porous media can be a significant retention process for PFAS that should be considered when characterizing their transport and fate behavior in source zones.

Acidic pH weakens the bonding effectiveness of silane contained in universal adhesives.

OBJECTIVES: Some silane-containing universal adhesives were introduced that a separate ceramic primer was unnecessary to glass-ceramic bonding because of incorporated silane. We aimed to investigate the effectiveness of silane in universal adhesives with acidic media. METHODS: A functional γ-methacryloxypropyltrimethoxysilane (γ-MPTS) was used, and its pH value was adjusted to 2.7 by adding hydrochloric acid (HCl) or 10-methacryloxydecyl phosphate (MDP). The prepared acidic silane solutions after 2h or 10d storage were characterized by Fourier transform infrared spectroscopy (FTIR), 1H and 13C nuclear magnetic resonance (NMR) spectroscopy. Micro-shear bond strength (µSBS) was used to evaluate the bonding performance of glass ceramics. Two silane-containing and two silane-free universal adhesives were included. Field-emission scanning electron microscopy fractography analysis was also performed. RESULTS: FTIR, 1H and 13C NMR revealed that the hydrolysis of γ-MPTS and the self-condensation reaction of silanol groups occurred over time under acidic conditions (HCl or MDP solution). This reaction formed the siloxane oligomers. For glass-ceramic bonding, the µSBS of acidic silane after 10 d storage was lower than that of silane stored for 2h storage (p<0.05), although the difference among the µSBS of the four universal adhesives were nonsignificant (p>0.05). Additionally, cohesive failure was the main fracture pattern of universal adhesive bonding. SIGNIFICANCE: The effectiveness of silane contained in low pH universal adhesives can be weakened by dehydration self-condensation and consequently became unstable. For the enhancement of glass-ceramic bonding efficiency with universal adhesives, a separate ceramic primer was recommended.

[Bile-resistant Gram-negative bacteria effect of different kinds of root decoction pieces].

To investigate the microbial contamination in Chinese herbal decoction pieces with different functional types by studying the total aerobic microbial count (TAMC), and total yeast and mould count (TYMC) in 40 samples of 8 types of root decoction pieces; further evaluate the contamination load of bile-resistant Gram-negative bacteria, and identify the Gram-negative bacteria by using biochemical identification system for Gram-negative bacteria. Our results showed that the TAMC value was more than 1 000 CFU•g⁻¹ in 85% (34/40) samples, and was more than 100 CFU•g⁻¹ in 30% (12/40) samples; the contamination of bile-resistant Gram-negative bacteria was detected in 45% (18/40) of the samples. The bile-resistant Gram-negative bacteria load of seven batches of samples was N>1 000 MPN•g⁻¹. Sixteen bacterium strains including Serratia plymouthensis, Cedecea neteri, Escherichia vulneris, Klebsiella oxytoca, Enterobacter amnigenus, E. cloacae, E. sakazakii, Proteus penneri and E. gergoviae were obtained and identified. E. cloacae was the predominant bacterium that was isolated from Salviae Miltiorrhizae Radix et Rhizoma, while E. amnigenus, Yersinia pseudotuberculosis was the typical bacterium of Ophiopogonis Radix and Codonopsis Radix, respectively. All these suggested that the contamination of bile-resistant Gram-negative bacteria was severe for the root decoction pieces in Wuhan city. Microbial species have certain selection specificity for medicinal ingredients, so the type and limit of control bacteria for detection should be formulated according to the pollution type and quantity of bile-resistant Gram-negative bacteria.

High-performance therapeutic quercetin-doped adhesive for adhesive-dentin interfaces.

Almost half of dental restorations have failed in less than 10 years, and approximately 60% of practice time has been consumed to replace these dental restorations. As such, contemporary dentin adhesives should be modified to treat secondary caries and prevent the degradation of adhesive-dentin interfaces. To achieve this goal, we developed a versatile therapeutic adhesive in the present study by incorporating quercetin, which is a naturally derived plant extract, into a commercial adhesive at three concentrations (100, 500 and 1000 µg/mL). An unmodified adhesive served as a control. The antibacterial ability on Streptococcus mutans biofilm, conversion degree, microtensile bond strength, failure modes, in situ zymography, nanoleakage expression and cytotoxicity of quercetin-doped adhesive were comprehensively evaluated. Results showed that the quercetin-doped adhesive (500 µg/mL) preserved its bonding properties against collagenase ageing and inhibited the growth of S. mutans biofilm. Efficient bonding interface sealing ability, matrix metalloproteinase inhibition and acceptable biocompatibility were also achieved. Thus, a simple, safe and workable strategy was successfully developed to produce therapeutic adhesives for the extension of the service life of adhesive restorations.

In vivo inhibitory activity of andrographolide derivative ADN-9 against liver cancer and its mechanisms involved in inhibition of tumor angiogenesis.

It is well known that liver cancer is a highly aggressive malignancy with poor prognosis. Andrographolide (AD), a major bioactive component of Andrographis paniculata (Burm. F.), is a potential anti-cancer pharmacophore and the synthesis of AD derivatives with better cytotoxicity to cancer cells has attracted considerable attentions. In the present study, we evaluated the in vivo inhibitory effects of ADN-9, a 15-benzylidene substituted derivative of AD, on the growth and metastasis of murine hepatoma H22 using an orthotopic xenograft model and a subcutaneous xenograft model, and we further studied the anti-angiogenic action and the related mechanisms of ADN-9 in vivo and in vitro. Importantly, ADN-9 remarkably suppressed the growth and metastasis of both orthotopic and subcutaneous xenograft tumors, and the serum AFP level in orthotopic hepatoma-bearing mice treated with 100mg/kg ADN-9 (ig.) was decreased to the normal level. We also found that ADN-9 showed stronger abilities than AD in shrinking tumors, suppressing the invasion and metastasis of H22 cells, decreasing the MVD and promoting tumor cell apoptosis in subcutaneous xenograft of mice. Additionally, ADN-9 exhibited stronger inhibitory activity than AD against the migration and VEGF-induced capillary-like tube formation in HUVECs, which was further proved to be associated with attenuating VEGF/VEGFR2/AKT signaling pathway. The present research provides the first evidence that a 15-substituted AD derivative is more promising than the parent compound in therapeutic treatment of liver cancer.

Effect of silane pretreatment on the immediate bonding of universal adhesives to computer-aided design/computer-aided manufacturing lithium disilicate glass ceramics.

The aim of this study was to investigate the effect of silane pretreatment on the universal adhesive bonding between lithium disilicate glass ceramic and composite resin. IPS e.max ceramic blocks etched with hydrofluoric acid were randomly assigned to one of eight groups treated with one of four universal adhesives (two silane-free adhesives and two silane-containing adhesives), each with or without silane pretreatment. Bonded specimens were stored in water for 24 h. The shear bond strength (SBS) of the ceramic-resin interface was measured to evaluate bond strength, and the debonded interface after the SBS test was analysed using field-emission scanning electron microscopy to determine failure mode. Light microscopy was performed to analyse microleakage and marginal sealing ability. Silane pretreatment significantly and positively influenced SBS and marginal sealing ability. For all the universal adhesive groups, SBS increased and the percentage of microleakage decreased after the pretreatment. Without the pretreatment, SBS and the percentage of microleakage were not significantly different between the silane-containing universal adhesive groups and the silane-free groups. Cohesive failure was the main fracture pattern. The results suggest that additional silane pretreatment can effectively improve the bonding strength and marginal sealing of adhesives to lithium disilicate glass ceramics. The bonding performance of silane-containing universal adhesives without pretreatment is similar to that of silane-free adhesives.

Pannexin3 inhibits TNF-α-induced inflammatory response by suppressing NF-κB signalling pathway in human dental pulp cells.

Human dental pulp cells (HDPCs) play a crucial role in dental pulp inflammation. Pannexin 3 (Panx3), a member of Panxs (Pannexins), has been recently found to be involved in inflammation. However, the mechanism of Panx3 in human dental pulp inflammation remains unclear. In this study, the role of Panx3 in inflammatory response was firstly explored, and its potential mechanism was proposed. Immunohistochemical staining showed that Panx3 levels were diminished in inflamed human and rat dental pulp tissues. In vitro, Panx3 expression was significantly down-regulated in HDPCs following a TNF-α challenge in a concentration-dependent way, which reached the lowest level at 10 ng/ml of TNF-α. Such decrease could be reversed by MG132, a proteasome inhibitor. Unlike MG132, BAY 11-7082, a NF-κB inhibitor, even reinforced the inhibitory effect of TNF-α. Quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA) were used to investigate the role of Panx3 in inflammatory response of HDPCs. TNF-α-induced pro-inflammatory cytokines, interleukin (IL)-1ß and IL-6, were significantly lessened when Panx3 was overexpressed in HDPCs. Conversely, Panx3 knockdown exacerbated the expression of pro-inflammatory cytokines. Moreover, Western blot, dual-luciferase reporter assay, immunofluorescence staining, qRT-PCR and ELISA results showed that Panx3 participated in dental pulp inflammation in a NF-κB-dependent manner. These findings suggested that Panx3 has a defensive role in dental pulp inflammation, serving as a potential target to be exploited for the intervention of human dental pulp inflammation.