Biotoxicity of Halide Perovskites in Mice.

Halide perovskites are crystalline semiconductors with exceptional optoelectronic properties, rapidly developing toward large-scale applications. Lead (II) (Pb2+ ) is the core element used to prepare halide perovskites. Pb2+ can displace key 2+ elements, including calcium, zinc and iron, that regulate vital physiological functions. Sn2+ can replace Pb2+ within the perovskite structure and, if accidentally dispersed in the environment, it readily oxidizes to Sn4+ , which is compatible with physiological functions and thus potentially safe. The 3+ salt bismuth (III) (Bi3+ ) is also potentially safe for the same reason and useful to prepare double perovskites. Here, this work studies the biotoxicity of Pb, Sn, and Bi perovskites in mice for the first time. This work analyses histopathology and growth of mice directly exposed to perovskites and investigate the development of their offspring generation. This study provides the screening of organs and key physiological functions targeted by perovskite exposure to design specific studies in mammalians.

Role of Charlson comorbidity index in predicting the ICU admission in patients with thoracic aortic aneurysm undergoing surgery.

OBJECTIVES: This study aimed to explore the value of the Charlson comorbidity index (CCI) in predicting ICU admission in patients with aortic aneurysm (AA). METHODS: The clinical data of patients were obtained from the Medical Information Mart for Intensive Care-IV database. The association between CCI and ICU admission was explored by restricted cubic spline (RCS), threshold effect analysis, generalized linear model, logistic regression, interaction, and mediation analyses. Its clinical value was evaluated by decision curve analysis (DCA), receiver operating characteristic curve (ROC), DeLong's test, and net reclassification index (NRI) analyses. RESULTS: The ICU admission was significantly associated with the thoracic AA (TAA), unruptured status, and surgery status. Therefore, 288 candidate patients with unruptured TAA who received surgery were enrolled in the further analysis. We found that CCI was independently associated with the ICU admission of candidates (P = 0.005). Further, their nonlinear relationship was observed (adjusted P = 0.008), and a significant turning point of 6 was identified. The CCI had a favorable performance in predicting ICU admission (area under curve = 0.728) and achieved a better clinical net benefit. New models based on CCI significantly improved the accuracy of prediction. Besides the importance of CCI in ICU admission, CCI also exerted important interaction effect (rather than mediating effects) on the association of other variables (such as age and blood variables) with ICU admission requirements (all P < 0.05). CONCLUSIONS: The CCI is an important predictor of ICU admission after surgery in patients with unruptured TAA.

A mass defect filtering combined background subtraction strategy for rapid screening and identification of metabolites in rat plasma after oral administration of Yindan Xinnaotong soft capsule.

The absorbed prototypes and metabolites of traditional Chinese medicines (TCMs) serves an important part in pharmacological action and clinical effects. However, the comprehensive characterization of which is facing actual or possible rigorous challenges due to the lack of data mining methods and the complexity of metabolite samples. Yindan Xinnaotong soft capsule (YDXNT), a typical traditional Chinese medicine prescription consisting of extracts from 8 herbal medicines, is widely used for the treatment of angina pectoris and ischemic stroke in the clinic. This study established a systematic data mining strategy based on ultra-high performance liquid chromatography tandem quadrupole-time-of-fight mass spectrometry (UHPLC-Q-TOF MS) for comprehensive metabolite profiling of YDXNT in rat plasma after oral administration. The multi-level feature ion filtration strategy was primarily conducted through the full scan MS data of plasma samples. All potential metabolites were rapidly fileted out from the endogenous background interference based on the background subtract and the chemical type specifically mass defect filter (MDF) windows including flavonoids, ginkgolides, phenolic acids, saponins, and tanshinones. As the MDF windows of certain types were overlapped, the screened-out potential metabolites were deeply characterized and identified according to their retention times (RT), integrating neutral loss filtering (NLF), diagnostic fragment ions filtering (DFIF), and further confirmed by reference standards. Thus, a total of 122 compounds, consisting of 29 prototype components (16 confirmed with reference standards) and 93 metabolites had been identified. This study provides a rapid and robust metabolite profiling method for researching complicated traditional Chinese medicine prescriptions.

A sensitive LC-MS/MS method-based pharmacokinetic study of fifteen active ingredients of Yindan Xinnaotong soft capsule in rats and its potential mechanism in the treatment of cardiovascular diseases.

Yindan Xinnaotong soft capsule (YDXNT) is a commonly used Chinese herbal preparation for the clinical treatment of coronary disease. However, there is a lack of pharmacokinetic studies on YDXNT, and its active ingredients and their mechanism in the treatment of cardiovascular diseases (CVD) are still unclear. In this study, 15 absorbed ingredients in rat plasma after oral administration of YDXNT were quickly identified based on liquid chromatography tandem quadrupole time-of-flight mass spectrometry (LC-QTOF MS), and then a sensitive and accurate quantitative method based on ultra-high performance liquid chromatography tandem triple quadrupole mass spectrometry (UHPLC-QQQ MS) was established and validated for simultaneous determination of the 15 ingredients of YDXNT in rat plasma, which was then applied to the pharmacokinetic study. Different types of compounds showed various pharmacokinetic characteristics, for instance, ginkgolides with higher maximum plasma concentration (Cmax), flavonoids presenting concentration-time curve with double peaks, phenolic acids with shorter time to reach maximum plasma concentration (Tmax), saponins with long elimination half-life (t1/2) and tanshinones showing fluctuant plasma concentration. Then the measured analytes were regarded as effective compounds and their potential targets and mechanism of action were predicted by constructing and analyzing the compound-target network of YDXNT and CVD. Those potential active compounds of YDXNT interacted with targets such as MAPK1 and MAPK8, and molecular docking showed that the binding free energies of 12 ingredients with MAPK1 were less than -5.0 kcal/mol, indicating that YDXNT intervened in the MAPK signaling pathway to display its therapeutic effect on CVD.

Swimming exercise prevents hippocampal dendritic spine changes and memory loss caused by aging: An application of a new semi-automated spine analysis software.

Dendritic spines are small, ratchet-like protrusions on neuronal dendrites that form synapses for receiving neuronal messages. Dendritic spine morphology is associated with synapse function. If neurons degrade or are damaged, the spine morphology of neurons changes. Given that most commercially available spine analysis software is expensive and complex, this study investigated a semi-automated spine analysis software, CTSpine, and used previously published data to verify the accuracy of the analysis results of this software. We also applied CTSpine to understand whether aging causes alterations in the hippocampal spine morphology and whether physical exercise can impede dendritic spine changes in 20 male Sprague Dawley rats. The spines of pyramidal cells in the hippocampal Cornu Ammonis 1 (CA1) region in the aging group were more enriched in filopodium type pattern than those in the control group, whereas the spines of the exercised aging group showed a similar pattern to that of the control. No significant changes were observed in neuronal dendritic spines in other hippocampal regions. However, long-term hippocampal memory was considerably decreased in the aging group, which was reversed to some extent in the exercised aging group. CTSpine, a self-developed semi-automatic spine analysis software, showed results similar to those noted in published data and can be effectively applied to the study of dendritic patterns, including neurodevelopment and disease.

The miR-23b/27b/24-1 Cluster Inhibits Hepatic Fibrosis by Inactivating Hepatic Stellate Cells.

BACKGROUND & AIMS: Hepatic fibrosis is characterized by hepatic stellate cell (HSC) activation and transdifferentiation-mediated extracellular matrix (ECM) deposition, which both contribute to cirrhosis. However, no antifibrotic regimen is available in the clinic. microRNA-23b/27b/24-1 cluster inhibition of transforming growth factor-ß (TGF-ß) signaling during hepatic development prompted us to explore whether this cluster inhibits HSC activation and hepatic fibrosis. METHODS: Experimental fibrosis was studied in carbon tetrachloride (CCl4)-treated C57BL/6 mice. After administration of miR-23b/27b/24-1 lentivirus or vehicle, animals were euthanized for liver histology. In primary rat HSC and HSC-T6, the anti-fibrotic effect of miR-23b/27b/24-1 cluster was furtherly investigated by RNA-sequencing, luciferase reporter assay, western blotting and bioinformatic means. RESULTS: In this study, we showed that increasing the miR-23b/27b/24-1 level through intravenous delivery of miR-23b/27b/24-1 lentivirus ameliorated mouse hepatic fibrosis. Mechanistically, the miR-23b/27b/24-1 cluster directly targeted messenger RNAs, which reduced the protein expression of 5 secretory profibrotic genes (TGF-ß2, Gremlin1, LOX, Itgα2, and Itgα5) in HSCs. Suppression of the TGF-ß signaling pathway by down-regulation of TGF-ß2, Itgα2, and Itgα5, and activation of the bone morphogenetic protein signaling pathway by inhibition of Gremlin1, decreased extracellular matrix secretion of HSCs. Furthermore, down-regulation of LOX expression softened the ECM. Moreover, a reduction in tissue inhibitors of metalloproteinase 1 expression owing to weakened TGF-ß signaling increased ECM degradation. CONCLUSIONS: Hepatic overexpression of the miR-23b/27b/24-1 cluster blocked hepatic fibrosis and may be a novel therapeutic regimen for patients with hepatic fibrosis.

Sodium bicarbonate transporter NBCe1 regulates proliferation and viability of human prostate cancer cells LNCaP and PC3.

Studies on cultured cancer cells or cell lines have revealed multiple acid extrusion mechanisms and their involvement in cancer cell growth and progression. In the present study, the role of the sodium bicarbonate transporters (NBCs) in prostate cancer cell proliferation and viability was examined. qPCR revealed heterogeneous expression of five NBC isoforms in human prostate cancer cell lines LNCaP, PC3, 22RV1, C4-2, DU145, and the prostate cell line RWPE-1. In fluorescence pH measurement of LNCaP cells, which predominantly express NBCe1, Na+ and HCO3--mediated acid extrusion was identified by bath ion replacement and sensitivity to the NBC inhibitor S0859. NBCe1 knockdown using siRNA oligonucleotides decreased the number of viable cells, and pharmacological inhibition with S0859 (50 µM) resulted in a similar decrease. NBCe1 knockdown and inhibition also increased cell death, but this effect was small and slow. In PC3 cells, which express all NBC isoforms, NBCe1 knockdown decreased viable cell number and increased cell death. The effects of NBCe1 knockdown were comparable to those by S0859, indicating that NBCe1 among NBCs primarily contributes to PC3 cell proliferation and viability. S0859 inhibition also decreased the formation of cell spheres in 3D cultures. Immunohistochemistry of human prostate cancer tissue microarrays revealed NBCe1 localization to the glandular epithelial cells in prostate tissue and robust expression in acinar and duct adenocarcinoma. In conclusion, our study demonstrates that NBCe1 regulates acid extrusion in prostate cancer cells and inhibiting or abolishing this transporter decreases cancer cell proliferation.

Increased Alcohol Consumption in Mice Lacking Sodium Bicarbonate Transporter NBCn1.

The previous reports on an addiction vulnerability marker in the human SLC4A7 gene encoding the Na/HCO3 transporter NBCn1 suggest that this pH-regulating protein may affect alcohol-related behavior and response. Here, we examined alcohol consumption and sensitivity to the sedative effects of alcohol in male NBCn1 knockout mice. These mice displayed lower pH in neurons than wildtype controls, determined by intracellular pH in hippocampal neuronal cultures. Neurons from knockout mice had a higher action potential threshold and a more depolarized membrane potential, thus reducing membrane excitability. In a two-bottle free choice procedure, knockout mice consumed more alcohol than controls and consistently increased alcohol consumption after repeated alcohol deprivation periods. Quinine and sucrose preference was similar between genotypes. Knockout mice showed increased propensity for alcohol-induced conditioned place preference. In loss of righting reflex assessment, knockout mice revealed increased sensitivity to alcohol-induced sedation and developed tolerance to the sedation after repeated alcohol administrations. Furthermore, chronic alcohol consumption caused NBCn1 downregulation in the hippocampus and striatum of mice and humans. These results demonstrate an important role of NBCn1 in regulation of alcohol consumption and sensitivity to alcohol-induced sedation.

Deletion of the Na/HCO3 Transporter NBCn1 Protects Hippocampal Neurons from NMDA-induced Seizures and Neurotoxicity in Mice.

The Na/HCO3 cotransporter NBCn1/SLC4A7 can affect glutamate neurotoxicity in primary cultures of rat hippocampal neurons. Here, we examined NMDA-induced neurotoxicity in NBCn1 knockout mice to determine whether a similar effect also occurs in the mouse brain. In primary cultures of hippocampal neurons from knockouts, NMDA had no neurotoxic effects, determined by lactate dehydrogenase release and nitric oxide synthase (NOS)-dependent cGMP production. Male knockouts and wildtypes (6-8 weeks old) were then injected with NMDA (75 mg/kg; ip) and hippocampal neuronal damages were assessed. Wildtypes developed severe tonic-clonic seizures, whereas knockouts had mild seizure activity (motionless). In knockouts, the NOS activity, caspase-3 expression/activity and the number of TUNEL-positive cells were significantly low. Immunochemical analysis revealed decreased expression levels of the NMDA receptor subunit GluN1 and the postsynaptic density protein PSD-95 in knockouts. Extracellular recording from hippocampal slices showed no Mg2+/NMDA-mediated epileptiform events in knockouts. In conclusion, these results show a decrease in NMDA neurotoxicity by NBCn1 deletion. Given that acid extrusion has been known to prevent pH decrease and protect neurons from acid-induced damage, our study presents novel evidence that acid extrusion by NBCn1 stimulates neurotoxicity.

Mycobacterium tuberculosis Infection Induces Low-Density Granulocyte Generation by Promoting Neutrophil Extracellular Trap Formation via ROS Pathway.

The roles and characteristics of low-density granulocytes (LDGs) have recently attracted attention; however, the mechanism of the formation of LDGs is yet unclear. In one of our previous studies, the frequency of LDGs was significantly elevated in the peripheral blood of tuberculosis patients, and in situ activation contributed to the generation of LDGs upon Mycobacterium tuberculosis infection. However, the underlying molecular mechanisms are yet to be elucidated. In the present study, the release of neutrophil extracellular traps (NETs) and the levels of ROS were regulated before the normal-density granulocytes (NDGs) to be infected with M. tuberculosis, and the conversion of NDGs to LDGs was monitored subsequently as well. The results showed that tuberculosis-related LDGs spontaneously released high levels of NETs. Promoting the release of NETs led to increase in the conversion of NDGs to LDGs in M. tuberculosis infection, while inhibiting the release of NETs suppressed this conversion after the infection. The M. tuberculosis infection significantly increased the ROS levels in neutrophils and the conversion of NDGs to LDGs. Scavenging ROS or blocking the ROS generation of M. tuberculosis-infected NDGs significantly suppressed the release of NETs and blocked the generation of LDGs. Moreover, inhibiting the formation of NETs without affecting the levels of ROS significantly decreased the conversion of NDGs to LDGs after M. tuberculosis infection. Overall, this study demonstrated that M. tuberculosis could induce the generation of LDGs by promoting the release of NET via ROS pathway.

A Scan of Obesogenic Environments and a Spatial Inference of Obesity Prevalence in Chinese Children and Adolescents: Based on the Chinese Health and Nutrition Survey 2011 Data.

OBJECTIVE: To identify the characteristics of Chinese obesogenic environments at a provincial level, infer a spatial distribution map of obesity prevalence in 31 provinces, and provide a foundation for development of policy to reduce obesity in children and adolescents. METHODS: After scanning obesity data on subjects aged 7-17 years from 12 provinces in the China Health and Nutrition Survey 2011 and environmental data on 31 provinces from the China Statistical Yearbook 2011 and other sources, we selected 12 predictors. We used the 12 surveyed provinces as a training sample to fit an analytical model with partial least squares regression and prioritized the 12 predictors using variable importance in projection. We also fitted a predictive model with Bayesian analysis. RESULTS: We identified characteristics of obesogenic environments. We fitted the predictive model with a deviance information criterion of 61.96 and with statistically significant (P < 0.05) parameter estimates of intercept [95% confidence interval (CI): 329.10, 963.11], log(oil) (CI: 13.11, 20.30), log(GDP) (CI: 3.05, 6.93), log(media) (CI: -234.95, -89.61), and log(washing-machine) (CI: 0.92, 5.07). The total inferred average obesity prevalence among those aged 7-17 was 9.69% in 31 Chinese provinces in 2011. We also found obvious clustering in occurrences of obesity in northern and eastern provinces in the predicted map. CONCLUSION: Given complexity of obesity in children and adolescents, concerted efforts are needed to reduce consumption of edible oils, increase consumption of vegetables, and strengthen nutrition, health, and physical activity education in Chinese schools. The northern and eastern regions are the key areas requiring intervention.

Nickel-catalyzed direct C-H bond sulfenylation of acylhydrazines.

A Ni-catalyzed direct C-H bond sulfenylation of acylhydrazines was developed. The reaction used N-(pyridinyl)hydrazine as the bidentate-directing group, which can be smoothly removed through reductive N-N cleavage. This system can bear various important functional groups, providing an efficient route for the preparation of diverse diaryl sulfides.

Study on influencing factors of Pickering emulsions stabilized by hydroxyapatite nanoparticles with nonionic surfactants.

Emulsions were prepared using hydroxyapatite nanoparticles and nonionic surfactant sorbitan monooleate (Span 80) as emulsifier. Effects of Span 80 concentration, emulsification time, emulsification rate, poly(l-lactic acid) (PLLA) concentration and the surface chemical properties of hydroxyapatite nanoparticles on emulsion properties were systematically studied. The results showed that emulsion would undergo a phase inversion from oil-in-water (O/W) type to water-in-oil (W/O) type with an increase in Span 80 concentration. All of the above factors are closely related to emulsion type and stability. SEM results indicated that cured materials with different structures were obtained using these emulsions as templates via in situ evaporation; especially, open-cell porous structures were obtained by a mixture of hydroxyapatite and a moderate concentration of Span 80. The mechanism of this emulsion system is proposed in relation to the emulsion properties and cured material structure, which should be attributed to the formation of hydrogen bonds between hydroxyapatite and Span 80 by hydroxyl groups as well as their location changes in the emulsion.

Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Active Tuberculosis Patients.

BACKGROUND/AIMS: Dysregulated expression of circular RNAs (circRNAs) was demonstrated to be implicated in many diseases. Here, we aimed to determine circRNA profile in peripheral blood mononuclear cells (PBMCs) from active tuberculosis (TB) patients to identify novel biomarkers for TB. METHODS: Expression profile of circRNAs in PBMCs from 3 active pulmonary TB patients and 3 healthy controls were analyzed by microarray assay. Six circRNAs were selected for validation using real time-quantitative PCR (qRT-PCR) in 40 TB patients and 40 control subjects. Receiver operating characteristic (ROC) curve was constructed to evaluate their values in TB diagnosis. Hsa_circRNA_001937 was chosen for further evaluation in an independent cohort consisting of 115 TB, 40 pneumonia, 40 COPD, 40 lung cancer patients and 90 control subjects. An eight-month follow up was performed in 20 newly diagnosed TB patients to investigate the expression change of hsa_circRNA_001937 after chemotherapy. RESULTS: We revealed and confirmed that a number of circRNAs were dysregulated in TB patients. Of the six studied physio circRNAs, the levels of hsa_circRNA_001937, hsa_circRNA_009024 and hsa_ circRNA_005086 were significantly elevated and hsa_circRNA_102101, hsa_circRNA_104964 and hsa_circRNA_104296 were significantly reduced in PBMCs from TB patients as compared to healthy controls. ROC curve analysis suggested that hsa_circRNA_001937 has the largest area under the curve (AUC = 0.873, P<0.001). Hsa_circRNA_001937 was significantly increased in patients with TB compared with patients with pneumonia, COPD and lung cancer. Hsa_ circRNA_001937 was correlated with TB severity (r = 0.4053, P = 0.010) and its expression significantly decreased after treatment. CONCLUSION: This study identified a set of deregulated circRNAs in active TB PBMCs, our data also suggest that hsa_circRNA_001937 can be used as a potential diagnostic biomarker of TB.

Evidence for ammonium conductance in a mouse thick ascending limb cell line.

In this study, we examined an ammonium conductance in the mouse thick ascending limb cell line ST-1. Whole cell patch clamp was performed to measure currents evoked by NH4Cl in the presence of BaCl2, tetraethylammonium, and BAPTA Application of 20 mmol/L NH4Cl induced an inward current (-272 ± 79 pA, n = 9). In current-voltage (I-V) relationships, NH4Cl application caused the I-V curve to shift down in an inward direction. The difference in current before and after NH4Cl application, which corresponds to the current evoked by NH4Cl, was progressively larger at more negative potentials. The reversal potential for NH4Cl was +15 mV, higher than the equilibrium potential for chloride, indicating that the current should be due to NH4+ We then injected ST-1 poly(A) RNA into Xenopus oocytes and performed two-electrode voltage clamp. NH4Cl application in the presence of BaCl2 caused the I-V curve to be steeper. The NH4+ current was retained at pH 6.4, where endogenous oocyte current was abolished. The NH4+ current was unaffected by 10 µmol/L amiloride but abolished after incubation in Na+-free media. These results demonstrate that the renal cell line ST-1 produces an NH4+ conductance.

Utilization of a Wheat660K SNP array-derived high-density genetic map for high-resolution mapping of a major QTL for kernel number.

In crop plants, a high-density genetic linkage map is essential for both genetic and genomic researches. The complexity and the large size of wheat genome have hampered the acquisition of a high-resolution genetic map. In this study, we report a high-density genetic map based on an individual mapping population using the Affymetrix Wheat660K single-nucleotide polymorphism (SNP) array as a probe in hexaploid wheat. The resultant genetic map consisted of 119 566 loci spanning 4424.4 cM, and 119 001 of those loci were SNP markers. This genetic map showed good collinearity with the 90 K and 820 K consensus genetic maps and was also in accordance with the recently released wheat whole genome assembly. The high-density wheat genetic map will provide a major resource for future genetic and genomic research in wheat. Moreover, a comparative genomics analysis among gramineous plant genomes was conducted based on the high-density wheat genetic map, providing an overview of the structural relationships among theses gramineous plant genomes. A major stable quantitative trait locus (QTL) for kernel number per spike was characterized, providing a solid foundation for the future high-resolution mapping and map-based cloning of the targeted QTL.

Effect of stearic acid modified HAp nanoparticles in different solvents on the properties of Pickering emulsions and HAp/PLLA composites.

Stearic acid (Sa) was used to modify the surface properties of hydroxyapatite (HAp) in different solvents (water, ethanol or dichloromethane(CH2Cl2)). Effect of different solvents on the properties of HAp particles (activation ratio, grafting ratio, chemical properties), emulsion properties (emulsion stability, emulsion type, droplet morphology) as well as the cured materials (morphology, average pore size) were studied. FT-IR and XPS results confirmed the interaction occurred between stearic acid and HAp particles. Stable O/W and W/O type Pickering emulsions were prepared using unmodified and Sa modified HAp nanoparticles respectively, which indicated a catastrophic inversion of the Pickering emulsion happened possibly because of the enhanced hydrophobicity of HAp particles after surface modification. Porous materials with different structures and pore sizes were obtained using Pickering emulsion as the template via in situ evaporation solvent method. The results indicated the microstructures of cured samples are different form each other when HAp was surface modified in different solvents. HAp particles fabricated using ethanol as solvent has higher activation ratio and grafting ratio. Pickering emulsion with higher stability and cured porous materials with uniform morphology were obtained compared with samples prepared using water and CH2Cl2 as solvents. In conclusion, surface modification of HAp in different solvents played a very important role for its stabilized Pickering emulsion as well as the microstructure of cured samples. It is better to use ethanol as the solvent for Sa modified HAp particles, which could increase the stability of Pickering emulsion and obtain cured samples with uniform pore size.

Factors influencing the stability and type of hydroxyapatite stabilized Pickering emulsion.

Hydroxyapatite (HAp) nanoparticle stabilized Pickering emulsion was fabricated with poly(l-lactic acid) dissolved in dichloromethane (CH2Cl2) solution as oil phase and HAp aqueous dispersion as aqueous phase. Pickering emulsion was cured via in situ solvent evaporation method. Effect of PLLA concentrations, pH value, HAp concentrations, oil-water ratio, emulsification rates and times were studied on emulsion stability and emulsion type, etc. The results indicated emulsion stability increased with the increase of HAp concentration, emulsification rate and time; it is very stable when pH value of aqueous phase was adjusted to 10. Stable W/O and O/W emulsions were fabricated successfully using as-received HAp particles as stabilizer by adjusting the fabricating parameters. The interaction between HAp and PLLA played an important role to stabilize Pickering emulsions. SEM results indicated that both microsphere and porous materials were fabricated using emulsion stabilized by unmodified HAp nanoparticles, implying that both W/O and O/W emulsion type were obtained.

Photocurable high internal phase emulsions (HIPEs) containing hydroxyapatite for additive manufacture of tissue engineering scaffolds with multi-scale porosity.

Porous composites containing hydroxyapatite (HA) were templated from high internal phase emulsions (HIPEs) and were further structured using direct-write UV stereolithography to produce composite scaffolds with multi-scale porosity. FTIR, TGA and SEM analyses confirmed that HA was retained after photocuring and subsequent treatments and was incorporated within the polymerised HIPE (polyHIPE). The addition of HA particles to the polyHIPE caused changes in the mechanical properties of the material. An increase in both the Young's modulus and maximum stress at yield was observed compared with the pure polyHIPE from 1.544±0.231 to 4.614±0.775 and 0.177±0.009 to 0.267±0.034MPa, respectively. Except at very high concentrations, adding HA did not adversely cause the phase separation of the HIPE or the porous microstructure of the resulting polyHIPE. In combination with a photoinitiator, the HIPE emulsion containing HA was investigated as a photocurable resin for stereolithography-based additive manufacturing. The material was readily processable into "woodpile" structures via direct-write UV stereolithography, producing scaffolds with multi-scale porosity which may be useful for medical applications such as tissue engineering. In conclusion, HA was successfully added into polyHIPEs, producing a similar porous structure to that of the pure polyHIPE whilst improving the mechanical performance.

Liganded Vitamin D Receptor Through Its Interacting Repressor Inhibits the Expression of Type I Collagen α1.

Hepatic fibrosis is a reversible process involving plenty of transcription factors and pathways. Vitamin D receptor (VDR) as a member of ligand-induced transcription factors can interact with 9-cis retinoid X receptor (RXR) and VDR-interacting repressor (VDIR) to mediate transactivation or transrepression in the absence or in the presence of VDR ligand to regulate the expression of VDR target genes. The active form of vitamin D [1α,25(OH)2D3] can downregulate the expression of type I collagen both α1 and α2 (COLIα1 and COLIα2) in hepatic stellate cells (HSC-T6) in a time-dependent fashion, which provides a new direction for hepatic fibrosis therapy. As one of VDR target genes, rat COLIα1 gene contains 1αnVDRE (E-box1 and E-box2) in its promoter, and unliganded VDR/RXR may bind to 1αnVDRE through VDIR to mediate transactivation, whereas liganded VDR/RXR may bind to 1αnVDRE through VDIR for transrepression. The results suggested a sort of relying on each other relationship between VDR/RXR and VDIR in regulating the expression of COLIα1 gene in HSC-T6 cells, which established VDR as a potential target for blocking and even reversing hepatic fibrosis.