ROR2 Downregulation Activates the MSX2/NSUN2/p21 Regulatory Axis and Promotes Dental Pulp Stem Cell Senescence.

Cellular senescence severely limits the research and the application of dental pulp stem cells (DPSCs). A previous study conducted by our research group revealed a close implication of ROR2 in DPSC senescence, although the mechanism underlying the regulation of ROR2 in DPSCs remains poorly understood so far. In the present study, it was revealed that the expression of the ROR2-interacting transcription factor MSX2 was increased in aging DPSCs. It was demonstrated that the depletion of MSX2 inhibits the senescence of DPSCs and restores their self-renewal capacity, and the simultaneous overexpression of ROR2 enhanced this effect. Moreover, MSX2 knockdown suppressed the transcription of NOP2/Sun domain family member 2 (NSUN2), which regulates the expression of p21 by binding to and causing the 5-methylcytidine methylation of the 3'- untranslated region of p21 mRNA. Interestingly, ROR2 downregulation elevated the levels of MSX2 protein, and not the MSX2 mRNA expression, by reducing the phosphorylation level of MSX2 and inhibiting the RNF34-mediated MSX2 ubiquitination degradation. The results of the present study demonstrated the vital role of the ROR2/MSX2/NSUN2 axis in the regulation of DPSC senescence, thereby revealing a potential target for antagonizing DPSC aging.

Effect of Emodin on Hyperlipidemia and Hepatic Lipid Metabolism in Zebrafish Larvae Fed a High-Cholesterol Diet.

Hyperlipidemia (HLP) is a complex pathological condition results from lipid metabolism disorder, which is closely related to obesity, atherosclerosis and steatohepatitis. Emodin (EM), a natural anthraquinone, exhibits prominent hypolipidemic effects. However, its exact mechanism is still unclear. In this study, we successfully established hyperlipidemic zebrafish model induced by 4 % high-cholesterol diet (HCD) for 10 days and explored the anti-hyperlipidemic roles and underlying mechanisms of EM. The results indicated that EM attenuated the mortality and body mass index (BMI) of zebrafish with HLP, and ameliorated abnormal lipid levels involved in TC, TG, LDL-C and HDL-C levels. Besides, EM effectively reduced lipid accumulation in blood vessels and liver, alleviated hepatic histological damage, and inhibited vascular neutrophil inflammation. Finally, the mRNA expression of molecules related to lipid metabolism were studied by using real-time quantitative polymerase chain reaction (RT-qPCR) to investigated the underlying mechanism. Further results found that treatment with EM up-regulated AMPKα, LDLR, ABCA1 and ABCG1, and down-regulated SREBP-2, PCSK9 and HMGCR expression. In conclusion, EM showed a prominent mitigative effect on lipid metabolism disorder in zebrafish larvae with HCD-stimulated HLP, which was associated with the enhancement of LDL-C uptake and reverse cholesterol transport, and inhibition of cholesterol synthesis.

Controlling the selectivity of an intramolecular Friedel-Crafts alkylation with alkenes using selenium under mild conditions.

An efficiently divergent intramolecular Friedel-Crafts alkylation by unactivated alkenes with seleniranium ion-controlled Markovnikov/anti-Markovnikov specificities under mild conditions has been investigated. 2-Benzoxepin, isochroman, and isochromene can be produced in one-pot procedures from the same substrate in high yields and with high regio- and stereospecificity. The products are challenging to access via 7-endo-trig carbocyclizations and by 7-endo-trig carbocyclization/rearrangement/6-exo-trig oxycyclization and 6-exo-trig carbocyclization/deselenenylation reaction sequences, respectively. Mechanistic experiments indicated that in addition to the stereospecific anti-addition processes of the cyclization reactions, the formation of a stable carbocation after ring opening of the seleniranium ion leads to an NPSP-mediated 7-endo-trig carbocyclization; the steric hindrance of the seleniranium intermediate controls the regioselectivity when using TPSCA at 60 °C, which promotes 6-exo-trig carbocyclization. Two distinct catalytic cycles were proposed, and the structures of transition states and products were identified by ab initio calculations and X-ray analyses.

Highly effective removal of antibiotics from aqueous solution by magnetic ZnFe2O4/activated carbon composite.

Water pollution from antibiotics has attracted a lot of attention for its serious threat to human health. In this study, a magnetic adsorbent (zinc ferrite/activated carbon (ZnFe2O4/AC) was synthesized via microwave method to effectively remove gemifioxacin mesylate (GEM) and moxifloxacin hydrochloride (MOX). Based on the porosity of AC and the magnetism of ZnFe2O4, the resulting ZnFe2O4/AC has high adsorption capacities and can be easily separated from the solid-liquid system via a magnetic field. The largest adsorption capacities for GEM and MOX can reach up to 433.4 mg g-1 and 388.8 mg g-1, respectively, higher than those of reported adsorbents such as MIL-101 and MOF-808. Fastest adsorptions of GEM and MOX were found at 5 min, and solution pH and coexisting salts do not have a significant influence on the adsorption process. The adsorption mechanism analysis indicates that electrostatic interaction and H-bond interaction contribute to the effective adsorption.

[Identification of a Novel Mutation of EPB41 Gene in a Family Affected with Hereditary Elliptocytosis].

OBJECTIVE: To analyse potential genetic cause of a family affected with hereditary elliptocytosis （HE）. METHODS: Peripheral blood samples from this HE family were collected. Targeted capture and high-throughput sequencing of 4 813 genetic disease-associated genes was performed in four members of the family. Possible causative genetic variation was obtained and further confirmed by Sanger sequencing. Fifty healthy control subjects were recruited for detection of the candidate variation. RESULTS: High-throughput sequencing detected a nonsense mutation c.1215G>A（p.Trp405Ter）in exon 13 of the EPB41 gene in the proband and his mother presenting with moderate anemia. The pathogenicity of this loss-of-function mutation is very strong, because the G→A transition leads to introduce the premature stop codon instead of tryptophan codon at position 405, which producing a truncating protein with loss of important functional domains. This causative mutation is extremely rare in the population, and it has not yet been reported. The grandmother of the proband was heterozygous for the same mutation. Genotype-phenotype cosegregation was observed in this family. This mutation was not found in the 50 unrelated healthy controls. CONCLUSION: The c.1215G>A mutation of the EPB41 gene probably accounts for the disease in this HE family. This study reports a pathogenic EPB41 mutation in a Chinese HE family for the first time.

Evolution of plastid genomes of Holcoglossum (Orchidaceae) with recent radiation.

BACKGROUND: The plastid is a semiautonomous organelle with its own genome. Plastid genomes have been widely used as models for studying phylogeny, speciation and adaptive evolution. However, most studies focus on comparisons of plastid genome evolution at high taxonomic levels, and comparative studies of the process of plastome evolution at the infrageneric or intraspecific level remain elusive. Holcoglossum is a small genus of Orchidaceae, consisting of approximately 20 species of recent radiation. This made it an ideal group to explore the plastome mutation mode at the infrageneric or intraspecific level. RESULTS: In this paper, we reported 15 complete plastid genomes from 12 species of Holcoglossum and 1 species of Vanda. The plastid genomes of Holcoglossum have a total length range between 145 kb and 148 kb, encoding a set of 102 genes. The whole set of ndh-gene families in Holcoglossum have been truncated or pseudogenized. Hairpin inversion in the coding region of the plastid gene ycf2 has been found. CONCLUSIONS: Using a comprehensive comparative plastome analysis, we found that all the indels between different individuals of the same species resulted from the copy number variation of the short repeat sequence, which may be caused by replication slippage. Annotation of tandem repeats shows that the variation introduced by tandem repeats is widespread in plastid genomes. The hairpin inversion found in the plastid gene ycf2 occurred randomly in the Orchidaceae.

Phylogenomics of Orchidaceae based on plastid and mitochondrial genomes.

To advance our knowledge of orchid relationships and timing of their relative divergence, we used 76 protein-coding genes from plastomes (ptCDS) and 38 protein-coding genes from mitochondrial genomes (mtCDS) of 74 orchids representing the five subfamilies and 18 tribes of Orchidaceae, to reconstruct the phylogeny and temporal evolution of the Orchidaceae. In our results, the backbone of orchid tree well supported with both datasets, but there are conflicts between these trees. The phylogenetic positions of two subfamilies (Vanilloideae and Cypripedioideae) are reversed in these two analyses. The phylogenetic positions of several tribes and subtribes, such as Epipogiinae, Gastrodieae, Nerviliinae, and Tropidieae, are well resolved in mtCDS tree. Thaieae have a different position among higher Epidendroideae, instead of sister to the higher Epidendroideae. Interrelationships of several recently radiated tribes within Epidendroideae, including Vandeae, Collabieae, Cymbidieae, Epidendreae, Podochileae, and Vandeae, have good support in the ptCDS tree, but most are not resolved in the mtCDS tree. Conflicts between the two datasets may be attributed to the different substitution rates in these two genomes and heterogeneity of substitution rate of plastome. Molecular dating indicated that the first three subfamilies, Apostasioideae, Cypripedioideae and Vanilloideae, diverged relatively quickly, and then there was a longer period before the last two subfamilies, Orchidoideae and Epidendroideae, began to radiate. Most mycoheterotrophic clades of Orchidaceae evolved in the last 30 million years with the exception of Gastrodieae.

Novel plasmid-mediated colistin resistance gene mcr-7.1 in Klebsiella pneumoniae.

Objectives: To identify a novel plasmid-mediated colistin resistance gene in Klebsiella pneumoniae isolated from chickens in China. Methods: WGS was used to identify a novel colistin resistance gene. The transferability of plasmids carrying mcr-7.1 was investigated by conjugation experiments. The expression of the mcr-7.1 gene was examined using an expression vector. Results: A novel plasmid-mediated colistin resistance gene mcr-7.1, sharing 70% amino acid identity with the mcr-3 gene, was identified in three K. pneumoniae strains isolated from chickens in China. The mcr-7.1 gene was found in an IncI2-type plasmid (pSC20141012) that co-harboured the blaCTX-M-55 gene in one isolate. pSC20141012 can be transferred from K. pneumoniae SC20141012 to Escherichia coli J53Azr, exhibiting a ≥8-fold increase in colistin MIC compared with the recipient E. coli J53Azr. Conclusions: We identified a novel plasmid-mediated colistin resistance gene named mcr-7.1 in K. pneumoniae in China. The prevalence of mcr-7.1 in various species of human and animal origin needs to be investigated immediately.

Correlation of Brain Perfusion with White Matter Hyperintensity, Brain Atrophy, and Cognition in Patients with Posterior Cerebral Artery Stenosis and Subjective Cognitive Decline.

BACKGROUND This study aimed to investigate the correlation of brain perfusion with white matter hyperintensity (WMH), brain atrophy, and cognition in patients with moderate to severe posterior cerebral artery stenosis (PCAS). MATERIAL AND METHODS 65 patients with memory decline as the main complaint and no history of brain infarction were recruited from the Department of Neurology of Tongji Hospital. Patients with moderate to severe PCAS were included in case group, and subjects with normal intracranial blood vessels served as controls. The demographics and vascular risk factors were recorded. Montreal Cognitive Assessment (MoCA) was used to evaluate the cognition. CT perfusion imaging was performed, and WASID was employed for the assessment of intracranial artery stenosis. The region of interest (ROI) was analyzed based on the whole brain perfusion. Cranial MRI was performed, and Scheltens scoring system was used for the assessment of WMH on FLAIR. T1 weighed images were obtained, and global cortical atrophy (GCA) scale was employed for the assessment of brain atrophy. The detections of brain perfusion, WMH and brain atrophy were done at centrum ovale, parietal lateral ventricle and basal ganglia layers. RESULTS In PCAS patients we found low perfusion in the antecornu and postcornu blood supply areas at the lateral ventricle, the blood supply area of the anterior cerebral artery, the blood supply area of the posterior cerebral artery, and the blood supply area at the hippocampus as compared with control subjects (p<0.05). As compared with control subjects, the incidence of WMH in the blood supply areas at the deep brain and lateral ventricle was significantly higher in PCAS patients (p<0.05). When compared with controls, the incidence of brain atrophy increased significantly in PCAS patients (p<0.01). Correlation analysis showed the brain perfusion at the blood supply area of the posterior cerebral artery was positively correlated to the total MoCA score and negatively correlated to the severity of WMH at the blood supply area of the posterior cerebral artery (p<0.05). Further analysis showed the brain perfusion at the blood supply area of the posterior cerebral artery was negatively associated with cortex supplied by the posterior cerebral artery, posterior cingulate, and hippocampus (p<0.01). CONCLUSIONS PCAS patients have a higher incidence of brain atrophy, and the perfusion at the area supplied by the posterior cerebral artery is correlated to the severity of brain atrophy and of WMH, as well as to cognition decline.

Colistin Resistance Gene mcr-1 and Its Variant in Escherichia coli Isolates from Chickens in China.

The mcr-1 gene was detected in 5.11% (58/1136) of Escherichia coli isolates of chicken origin from 13 provinces in China. A novel mcr-1 variant, named mcr-1.3, encoding an Ile-to-Val functional variant of MCR-1 was identified in a sequence type 155 (ST155) strain. An mcr-1.3-containing IncI2 plasmid, pHeN867 (60,757 bp), was identified. The transfer of pHeN867 led to a 32-fold increase in the MIC of colistin in the recipient, exhibiting an effect on colistin resistance that was similar to that of mcr-1.

[Effect of processing time of Polygoni Multiflori Radix on content changes of 16 componens].

To study 48 h processing time of Polygoni Multiflori Radix on its contents and changes of chemical components. HPLC was used to determine the contents of various components in 22 Polygoni Multiflori Radix samples with different processing time, and then the fingerprint similarity analysis and clustering analysis were used for characteristics analysis. Results showed that the similarity was between 0.9-1.0, with good correlation between the samples. In the clustering analysis, the 22 Polygoni Multiflori Radix and processed Polygoni Multiflori Radix samples were classified into 4 types according to the composition changes. The results demonstrated that 4-5 h was the best processing time, providing references for quality control and further study of Polygoni Multiflori Radix.

The application of HPLC-MS/MS to studies of pharmacokinetics and interconversion of isoliquiritigenin and neoisoliquiritigenin in rats.

A specific and sensitive HPLC-MS/MS method was developed and validated for the simultaneously quantification of isoliquiritigenin (ISL) and neoisoliquiritin (NIS) in rat plasma by oral administration. Analytes were analyzed on an Agilent 6460 LC-MS/MS system (Agilent, USA) using an Agilent Zorbax SB-C18 column (4.6 × 150 mm, 5 µm). Gradient elution was applied for the analyte separation using a mobile phase composed of 0.1% formic acid aqueous solution and methanol at a flow rate of 1.0 mL/min with a total running time of 12 min. The calibration curves for ISL and NIS showed good linearity in the concentrations ranging from 0.001 to 4.000 µg/mL with correlation coefficients >0.998. The precision, accuracy, recovery and stability were deemed acceptable. The method was applied to the pharmacokinetics study of ISL and NIS in rats by single and combination administration. The result showed that Cmax and AUC0→t of ISL were markedly increased from 0.53 to 1.20 µg/mL, and from 69.63 to 200.74 min µg/mL by combination administration. The mean t1/2 value was also prolonged from 64.55 to 203.74 min in the combination group. These results indicated that NIS may have been metabolized to ISL which increased the absorption and extended the elimination of ISL. However, little difference was found for NIS pharmacokinetics parameters between single NIS and the combination group, which suggested that there was no significant biotransformation of ISL to NIS. Copyright © 2015 John Wiley & Sons, Ltd.

Clinical and MRI outcomes of HA injection following arthroscopic microfracture for osteochondral lesions of the talus.

PURPOSE: The purpose of this study was to compare the clinical and magnetic resonance imaging (MRI) outcomes of arthroscopic microfracture surgery alone or in combination with hyaluronic acid (HA) injection in the treatment of osteochondral lesions of the talus. METHODS: Thirty-five patients with osteochondral lesions of the talus who underwent arthroscopic microfracture were included and followed up for at least 9 months post-operatively. The patients were randomly divided into non-injection group (n = 17) who received treatment with microfracture surgery alone and injection group (n = 18) who also accepted intra-articular injection of HA post-operatively. Quantitative MRI was used to evaluate the cartilage repair after surgery. American Orthopaedic Foot and Ankle Society (AOFAS) Ankle-Hind foot Scale scores and Visual Analogue Scale (VAS) scores were used to evaluate clinical outcomes. RESULTS: After operation, the MRI outcomes showed that the thickness index was higher (0.8 ± 0.1 vs. 0.7 ± 0.1) and the T2 index was lower (1.2 ± 0.1 vs. 1.4 ± 0.1) in the injection group than in the non-injection group (P < 0.01). As for the volumes of subchondral bone marrow oedema, there are no significant differences between groups (n.s.). Compared with the non-injection group, the AOFAS score and the VAS score yielded a higher level of improvement in injection group at final follow-up post-operatively (P < 0.05). CONCLUSIONS: Arthroscopic microfracture is a safe and effective procedure for osteochondral lesions of the talus. Intra-articular HA injection as an adjunct to arthroscopic microfracture might offer better functional recovery than microfracture alone. LEVEL OF EVIDENCE: II.

The Influence of Aconitum carmichaelii Debx. on the Pharmacokinetic Characteristics of Main Components in Rheum palmatum L.

Rhei Radix et Rhizoma was one of the commonly used traditional Chinese medicines, and the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata was the basic herb pair applied in many Chinese traditional prescription. Rhubarb anthraquinones were the main bioactive materials of Rhei Radix et Rhizoma. To elucidate the compatibility of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata, the pharmacokinetics of rhubarb anthraquinones as the main marker constituents were investigated. In the present study, pharmacokinetic differences of rhubarb anthraquinones were detected after oral administration of extract of Rheum palmatum L. and compatibility with Aconitum carmichaelii Debx. After oral administration, no difference of peak time can be found for anthraquinones between rhubarb group and compatibility group. But Cmax and area under the curve of aloe-emodin, emodin and chrysophanol in compatibility group were significantly higher than that in rhubarb group. Although the Cmax of rhein in compatibility group was much lower than that in rhubarb group, the area under the curve value was similar in two groups. The clearance and t1/2 of rhubarb anthraquinone were also changed after compatibility. The change of pharmacokinetics characteristics of rhubarb anthraquinone after compatibility may be caused by the drug-drug interaction medicated by chemical reaction and cytochromes P450.

Pharmacokinetics and bioavailability study of neoline in Beagle dogs.

This paper is aim to investigate the pharmacokinetics and absolute bioavailability of neoline in Beagle dogs, and provide a theoretical basis for further study. Ethyl acetate was used for liquid-liquid extracting after 10% ammonia alkalizing. The method of UPLC-Q-TOF-MS was established for the determination of neoline plasma concentrations. Beagle dogs were orally or intravenously administered with neoline for pharmacokinetic and absolute bioavailability study. Good linear relationship of neoline was found over the range of 0.1-4 mg x L(-1) (R2 = 0.9982) and 2-100 microg x L(-1) (R2 = 0.9945). Intra-and inter-day precision, expressed as the relativestandard (RSD) were less than 5.0%. Accuracy, expressed as the relative error (RE) was within 90.0%-115%. The recovery of neoline in dog plasma was more than 80%. After 6 mg x kg(-1) for ig and 1 mg x kg(-1) for iv administration of neoline, the main pharmacokinetic parameters were analyzed with Winnonlin software. t(1/2) were (313.88 +/- 63.18), (236.33 +/- 229.84) min, and AUC(0-infinity) were (58,027.40 +/- 14,132.69), (473,578.02 +/- 82,333.08) min x microg x L(-1) for ig and iv administration respectively. The absolute bioavail ability was (73.15 +/- 10.29) %. The method of UPLC-Q-TOF-MS described in the report was sensitive, reliable and specific, and suitable for pharmacokinetic study of neoline in Beagle dog. The high absolute bioavailability of neoline in dog suggested good absorption of neline which was worth of further investigation.

Development and validation of a UHPLC-qTOF-MS method for quantification of fuziline in rat plasma and its application in a pharmacokinetic study.

A specific and sensitive UHPLC-qTOF-MS method was developed and validated for quantification of fuziline in rat plasma after oral administration of three dosages. The analyte was separated on an Acquity UPLC BEH C18 column with a total running time of 3 min using a mobile phase of 0.1% formic acid aqueous solution and methanol (80:20, v/v) at a flow-rate of 0.25 mL/min. The calibration curves for fuziline showed good linearity in the concentrations ranging from 1 to 200 ng/mL with correlation coefficients >0.997. The precision, accuracy, recovery and stability were deemed acceptable. The method was applied to a pharmacokinetics study of fuziline in rats. The mean half-life was 5.93, 6.13 and 5.12 h for 1, 2 and 4 mg/kg oral administration of fuziline, respectively. The peak concentration and area under the concentration-time curve increased linearly with the doses. The sum of these results indicated that, in the range of the doses examined, the pharmacokinetics of fuziline in rat was based on first-order kinetics.

[Comparison of self-controlled retruded approach and bimanual manipulation method on the relationship of incisal point displacement in the mandibular retruded contact position].

OBJECTIVE: To evaluate the relationship of incisal point displacements in the mandibular retruded contact position (RCP) between the self-controlled retruded approach and bimanual manipulation method. METHODS: Twelve healthy young volunteers were selected. The RCP was guided through the self-controlled retruded approach and bimanual manipulation method. The track of the incisal point was recorded, using the mandibular movement trace recording system. The movement direction of the incisal point in horizontal plane was observed. The distance between the incisal point of the RCP and intercuspal contact position (ICP) was measured. RESULTS: Except one volunteer's incisal point movement direction of the RCP was oblique, others were straight toward posterior. The displacements of the incisal point from the ICP to RCP guided through self-controlled approach and bimanual manipulation method were (1.15 ± 0.64) mm, (0.98 ± 0.29) mm respectively. There was no statistical significance between the two methods (P > 0.05). CONCLUSION: The displacements of the incisal point from the ICP to RCP guided through self-controlled approach and bimanual manipulation method are approximately the same.

Hinesol attenuates DSS-induced ulcerative colitis through the suppression of Src-mediated NF-κB and chemokine signaling pathway.

As a common inflammatory bowel disease, ulcerative colitis (UC) is featured with inflammation, oxidative damage, and the impairment of intestinal mucosal barrier, which bring threat to patients' quality of live. Hinesol, derived from Atractylodes lancea, is a unique sesquiterpenoid. Our study proposed to survey the effects and mechanism of hinesol in UC. UC mouse model was constructed using dextran sulfate sodium (DSS). Lipopolysaccharide (LPS) was applied for RAW264.7 cells stimulation to construct cell inflammatory model. The changes of disease activity index (DAI), body weight, colon length, and intestinal pathology in mice were analyzed to estimate the severity of colitis. Enzyme-linked immunosorbent assay was applied to check the changes of interleukin (IL)-1ß, IL-18, IL-6, and tumor necrosis factor (TNF)-α. The levels of myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-px), catalase (CAT), and malondialdehyde (MDA) were estimated by corresponding reagent kit. The changes of phosphorylated (p)-NF-κB P65, and p-IκBα, ZO-1, Occludin, Claudin-1, Src, XCL1, CCL2, and CXCL16 protein were examined using western blot. Flow cytometry and cell counting kit-8 assay were utilized for assessment of cell apoptosis and viability. We found that DSS reduced mice body weight, increased DAI, shorten colon length, and led to severe enteric mucosal injury, while hinesol improved the above symptoms induced by DSS. In DSS mice, hinesol raised the levels of ZO-1, Occludin, Claudin-1, SOD, GSH-px, and CAT and decreased the levels of TNF-α, IL-18, IL-1ß, IL-6, MPO, and MDA. Additionally, in DSS mice and LPS-stimulated RAW264.7 cells, hinesol inhibited the high expression of Src, XCL1, CCL2, CXCL16, p-NF-κB P65, and p-IκBα. The molecular docking showed that there was a good interaction between hinesol and Src. Moreover, in LPS-stimulated RAW 264.7 cells, Src overexpression partially reversed the inhibition of hinesol on cell apoptosis, pro-inflammatory factors, and oxidative stress. In conclusion, hinesol alleviated DSS-induced colitis, which might have a bearing on the inhibition of Src-mediated NF-κB and chemokine signaling pathway.

Gentianine alleviates dextran sulfate sodium-induced ulcerative colitis via inhibition of TLR4/NLRP3-mediated pyroptosis.

OBJECTIVES: Ulcerative colitis (UC) is a common inflammatory bowel disorder. Gentiana scabra Bunge is a traditional medicinal plant that is used to treat a variety of diseases. Studies have shown that gentianine (GTN) from Gentiana scabra inhibits the development of inflammatory diseases. The purpose of this study was to investigate the effect and possible mechanism of action of GTN on UC in mice. METHODS: An animal model of UC was established using dextran sulfate sodium (DSS). Mice were administered intraperitoneally with GTN (12.5, 25, or 50 mg/kg/day) for seven days. Body weight and disease activity index (DAI) were monitored daily during GTN administration. Colon length, pathological changes, and myeloperoxidase (MPO) activity were measured following GTN administration. The signalling pathways regulated by GTN were analysed using machine learning. HT-29 cells were used to verify the effect and mechanism of action of GTN on UC in vitro. RESULTS: GTN suppressed weight loss, shortened colon length, alleviated colon injury, and reduced the DAI score and MPO activity of mice with UC in a dose-dependent manner. Further analysis showed that GTN inhibited the NOD-like receptor (NLR) signalling pathway. GTN markedly decreased the levels of NLR signalling pathway-related proteins. Moreover, GTN decreased the levels of pyroptosis-related proteins, IL-1ß and IL-18. The in vitro data were consistent with those of animal experiments. Furthermore, TLR4 and NLRP3 overexpression eliminated the protective effects of GTN in HT-29 cells. CONCLUSION: Gentianine alleviated DSS-induced UC by inhibiting TLR4/NLRP3-mediated pyroptosis.

Structural stabilities and natural half-metallic properties of OsXCoSi (X=Ti, Zr, Hf) quaternary Heusler alloys series first-principles calculations.

Based on first-principles calculation of density functional theory, this study investigates the structural stability, magnetic properties, and electronic properties of the three different phases (i.e. type 1, type 2, and type 3) of OsXCoSi (X=Ti, Zr, Hf) in a new quaternary Heusler alloy series. The corresponding equilibrium lattice constants of each type are optimized, and the change of formation enthalpy and elastic constant phonon spectrum show that the OsXCoSi (X=Ti, Zr, Hf) alloy is thermodynamically, dynamically and mechanically stable. Furthermore, the bonding features of each phase are discussed. It is found that all type 1 structures of OsXCoSi (X=Ti, Zr, Hf) exhibit natural half-metallicity (HM) in equilibrium lattice constant, and their equilibrium lattice constants in the ground state were determined to be 5.909 Å for OsTiCoSi, 6.155 Å for OsZrCoSi, and 6.100 Å for OsHfCoSi. Meanwhile, by testing the alloy under different pressures, the range of the integer magnetic moment non-equilibrium lattice constants for the three alloys OsTiCoSi, OsZrCoSi, and OsHfCoSi are 5.710 Š∼ 6.329 Å, 5.696 Š∼ 6.1557 Å and 5.716 Š∼6.1009 Å, respectively, which is wide and is more close to the practical application for spin-polarized materials. In addition, its magnetic moment is consistent with the values given by the Slater-Pauling rule. Furthermore, the forming of the HM gap is examined by analysing the total and partial density of states, energy bands of alloy's electronic property, with respect to the calculated results. What's more, special attention is paid to the differences of the properties for series Heusler alloys. It is found that the electronics properties distinction is mainly based on valence electron changes. However, the lattice constants are susceptible to size of a nucleus.