IRX5 suppresses osteogenic differentiation of hBMSCs by inhibiting protein synthesis.

In our previous study, IRX5 has been revealed a significant role in adipogenesis of hBMSCs. Considering the expansion of adipose tissue in bone marrow in aged and ovariectomy-related osteoporosis, the effect of IRX5 on the osteogenesis of BMSCs still needs to be elucidated. In vivo, models of aging-induced and ovariectomy-induced osteoporotic mice, and in vitro studies of IRX5 gene gain- and loss-of-function in hBMSCs were employed. Histology, immunofluorescence, qRT-PCR, and Western blot analysis were performed to detect the functions of IRX5 in hBMSCs osteogenic differentiation. RNA-seq, transmission electron microscopy, Seahorse mito-stress assay, and Surface Sensing of Translation assay were conducted to explore the effect of mammalian/mechanistic target of rapamycin (mTOR)-mediated ribosomal translation and mitochondrial functions in the regulation of hBMSCs differentiation by IRX5. As a result, elevated IRX5 protein expression levels were observed in the bone marrow of osteoporotic mice compared to normal mice. IRX5 overexpression attenuated osteogenic processes, whereas IRX5 knockdown resulted in enhanced osteogenesis in hBMSCs. RNA-seq and enrichment analysis unveiled that IRX5 overexpression exerted inhibitory effects on ribosomal translation and mitochondrial functions. Furthermore, the application of the mTOR activator, MHY1485, effectively reversed the inhibitory impact of IRX5 on osteogenesis and mitochondrial functions in hBMSCs. In summary, our findings suggest that IRX5 restricts mTOR-mediated ribosomal translation, consequently impairing mitochondrial OxPhos, which in turn results in osteogenic dysfunction of hBMSCs.

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.

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.

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.

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.

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.

[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.

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.

Effect of pretreatment with calcium-containing desensitizer on the dentine bonding of mild self-etch adhesives.

Desensitizing agents are frequently applied to sensitive teeth and may affect subsequent resin bonding. The current study aimed to evaluate the bonding performance of two self-etch adhesives containing functional monomers to dentine pretreated with three new calcium-containing desensitizers. No desensitizer was applied in the control group. Groups 1, 2, and 3 were treated with an arginine-calcium carbonate-containing polishing paste, a casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)-containing paste, and an experimental hydroxyapatite paste, respectively. G-Bond and Clearfil S(3) Bond were used for bonding after desensitizer treatments. The microtensile bond strength (µTBS) was tested (n = 20 beams per group) and failure mode distribution was analyzed. Scanning electron microscopy was used to observe the occlusion of dentinal tubules. The mean (±SD) µTBS values, expressed in MPa, of groups 1, 2, and 3 and the control group were, respectively, 30.81 (7.79), 44.41 (8.02), 31.49 (6.13), and 41.40 (8.67) for G-Bond and 39.63 (9.59), 32.55 (7.86), 37.50 (8.60), 27.90 (6.52) for S3 Bond. Most failures were recorded as adhesive failure (69.375%), instead of cohesive failure or mixed failure. The dentinal tubules were seldom plugged in group 2, but were mostly occluded in groups 1 and 3. Two-way anova indicated that desensitizer application in association with a compatible adhesive system should be used when endeavoring to control hypersensitivity without adverse interference in bonding.

Effect of a functional desensitizing paste containing 8% arginine and calcium carbonate on the microtensile bond strength of etch-and-rinse adhesives to human dentin.

PURPOSES: To evaluate (1) the effect of a desensitizing paste containing 8% arginine and calcium carbonate on the microtensile bond strength between dentin and etch-and-rinse adhesive systems; and (2) to examine the dentin tubules occlusion quantitatively. METHODS: 48 freshly extracted intact human mandibular third molars were divided randomly into three groups. The mid-coronal dentin of each tooth was exposed and treated. Group A: no treatment; Group B: specimens were polished with a desensitizing paste containing 8% arginine and calcium carbonate using a rotary cup operating at a low speed for 3 seconds, followed by an additional duration of 3 seconds (total operation time of 6 seconds), according to the manufacturer's instructions; Group C: specimens were handled in the same way with the exception of an increased operation time of 9 seconds, twice (total operation time of 18 seconds). Each group was randomly divided into two subgroups in order to evaluate the effectiveness of two different adhesive agents. A two-step etch-and-rinse adhesive agent (Adper SingleBond 2) and a three-step etch-and-rinse adhesive agent (Adper ScotchBond Multi-purpose) were applied to dentin surfaces. Then, microtensile bond strengths of the six subgroups were tested. Dentin surfaces were analyzed using field-emission scanning electron microscopy (FESEM) and laser scanning confocal microscopy (LSCM). RESULTS: There was no significant difference in microtensile bond strength between the control group and the experimental groups treated with the 8% arginine and calcium carbonate desensitizing paste during the application of etch-and-rinse adhesives. Both FESEM and LSCM showed that the desensitizing paste occluded dentin tubules effectively.

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.

Effect of an 8.0% arginine and calcium carbonate in-office desensitizing paste on the microtensile bond strength of self-etching dental adhesives to human dentin.

PURPOSE: To evaluate in the laboratory the effect of an 8.0% arginine and calcium carbonate desensitizing paste in occluding open dentin tubules and examine the effect of bonding between the adhesive agents and dentin after being treated with the desensitizing paste. METHODS: Two self-etching adhesives were used. Intact human premolars extracted for orthodontic reasons were used within 3 months of extraction. The occlusal enamel was removed and dentin slices were polished. The dentin tubules were opened by etching with a 1% citric acid solution for 20 seconds to simulate a postoperative sensitivity model. Then the specimens were randomly assigned into five groups. Group A: specimens without any treatment (control). Group B: specimens were polished with a slurry (SiO2) for 30 seconds. Groups C, D and E: 8.0% arginine and calcium carbonate desensitizing paste was applied. Specimens in Group C were polished for 3 seconds, and then repeated for another 3 seconds for a total of 6 seconds, according to the manufacturer's instructions: specimens in Group D were polished twice for 9 seconds for a total of 18 seconds; and specimens in Group E were treated for an extended time of 30 seconds. Each group was randomly divided into two sub-groups in order to evaluate the effect on two different adhesive agents. A one-step self-etching adhesive agent (G-Bond) and a two-step self-etching adhesive agent (F1-Bond II) were applied following the manufacturers' instructions. Then microtensile bond strengths of the 10 groups were tested. SEM was used to evaluate the laboratory effect of the desensitizing paste in occluding open dentin tubules. Statistical analysis was carried out using SPSS version 16.0. RESULTS: The SEM observations showed that the 8.0% arginine and calcium carbonate desensitizing paste could occlude the dentin tubules effectively, and thus may have potential benefits in preventing postoperative sensitivity based on the hydrodynamic theory. An extended application time of 18 or 30 seconds showed no adverse effect of the desensitizing paste on the bonding performance to dentin when using self-etching adhesives containing functional monomers such as 4-MET like G-Bond.

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).

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.

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.

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.