Diadenosine tetraphosphate modulated quorum sensing in bacteria treated with kanamycin.

BACKGROUND: The dinucleotide alarmone diadenosine tetraphosphate (Ap4A), which is found in cells, has been shown to affect the survival of bacteria under stress. RESULTS: Here, we labeled Ap4A with biotin and incubated the labeled Ap4A with the total proteins extracted from kanamycin-treated Escherichia coli to identify the Ap4A binding protein in bacteria treated with kanamycin. Liquid chromatography‒mass spectrometry (LCMS) and bioinformatics were used to identify novel proteins that Ap4A interacts with that are involved in biofilm formation, quorum sensing, and lipopolysaccharide biosynthesis pathways. Then, we used the apaH knockout strain of E. coli K12-MG1655, which had increased intracellular Ap4A, to demonstrate that Ap4A affected the expression of genes in these three pathways. We also found that the swarming motility of the apaH mutant strain was reduced compared with that of the wild-type strain, and under kanamycin treatment, the biofilm formation of the mutant strain decreased. CONCLUSIONS: These results showed that Ap4A can reduce the survival rate of bacteria treated with kanamycin by regulating quorum sensing (QS). These effects can expand the application of kanamycin combinations in the treatment of multidrug-resistant bacteria.

Synthesis of fungicidal morpholines and isochromenopyridinones via acid-catalyzed intramolecular reactions of isoindolinones.

Acid-catalyzed intramolecular cyclization or rearrangement of isoindolinone derivatives is described. 3-Hydroxy/ethoxy-3,4-dihydro-6H-[1,4]-oxazino-[3,4-a]-isoindol-6-ones are obtained in moderate to good yields. Further acid-catalyzed intramolecular rearrangement reactions give 6H-isochromeno-[4,3-b]-pyridin-6-ones. The mild reaction conditions with convenient starting materials show broad substrate scope and provide the target compounds as novel pesticide leads with good fungicidal or systemical acquired resistance activities.

A Cadaveric Limb Analysis of the Posterior Tibial Musculotendinous Junction to determine the feasibility of Interosseous Membrane Tendon Transfer.

The transfer of the posterior tibial tendon through the interosseous membrane is potentially an effective treatment to correct the deformity of the foot and ankle. Our study aimed to evaluate the anatomical feasibility of anterior transfer of the posterior tibial tendon through the interosseous membrane route using the musculotendinous junction (MTJ). Eighteen adult cadavers were used. The width and thickness of the tibial posterior MTJ, width of the interosseous membrane at the corresponding level, and the window size of the interosseous membrane were measured. Additionally, the distance between the distal end of the MTJ and the tip of the medial malleolus were recorded. The mean length of the posterior tibial tendon was 83.60 mm, the mean distance of the posterior tibial MTJ to medial malleolus tip was 45.48 mm and the mean length of MTJ was 31.74 mm. The mean width of distal end of MTJ was 7.76 mm, thickness of distal end of MTJ was 4.07 mm and the mean width of the interosseous membrane at the distal end of MTJ was 4.76 mm. We found the mean width of the proximal end of MTJ was 20.68 mm, the mean thickness of proximal end of MTJ was 5.52 mm, and mean width of interosseous membrane at the proximal end of MTJ was 8.76 mm. Our study has demonstrated that a 31 mm length incision made at approximately 45 mm from the proximal end of the medial malleolus can safely reach the MTJ. We recommend an opening length of the interosseous membrane of at least 20 mm.

Menisperdaurines A-W, structurally diverse isoquinoline alkaloids from Menispermum dauricum and their dopamine D1 receptor activities.

A total of 33 structurally diverse isoquinoline alkaloids were isolated from the rhizomes of Menispermum dauricum, including seventeen benzylisoquinoline analogues (menisperdaurines A-Q, 1-17), five protoberberine analogues (menisperdaurines R-V, 18-22), a quaternary phenanthrene alkaloid (menisperdaurine W, 23) and ten known compounds (24-33). Compound structures, including absolute configurations, were determined by extensive spectroscopic methods, quantum chemical calculations of chemical shifts, and calculated and experimental electronic circular dichroism (ECD) data. Compounds 1-5 were glycosidic benzylisoquinolines with glucose moieties attached at the C-12 position. Compound 8 was the first example that was isolated from the rhizomes of Menispermum dauricum, benzylisoquinoline and an aromatic unit connected by a sugar bridge. Compounds were evaluated for their inhibitory effects on the dopamine D1 receptor. Compounds 1, 8, 21, 24 and 29 showed potent D1 antagonistic activities, with IC50 values ranging from 1.0 to 4.5 µM. Compound 1 exhibited the highest antagonistic activity with an IC50 value of 1.0 ± 0.2 µM.

Synthesis, Characterization, and the Antioxidant Activity of Phenolic Acid Chitooligosaccharide Derivatives.

A series of phenolic acid chitooligosaccharide (COS) derivatives synthesized by two mild and green methods were illuminated in this paper. Seven phenolic acids were selected to combine two kinds of COS derivatives: the phenolic acid chitooligosaccharide salt derivatives and the phenolic-acid-acylated chitooligosaccharide derivatives. The structures of the derivatives were characterized by FT-IR and 1H NMR spectra. The antioxidant experiment results in vitro (including DPPH-radical scavenging activity, superoxide-radical scavenging activity, hydroxyl-radical scavenging ability, and reducing power) demonstrated that the derivatives exhibited significantly enhanced antioxidant activity compared to COS. Moreover, the study showed that the phenolic acid chitooligosaccharide salts had stronger antioxidant activity than phenolic-acid-acylated chitooligosaccharide. The cytotoxicity assay of L929 cells in vitro indicated that the derivatives had low cytotoxicity and good biocompatibility. In conclusion, this study provides a possible synthetic method for developing novel and nontoxic antioxidant agents which can be used in the food and cosmetics industry.

Antimicrobial and Antioxidant Activities of N-2-Hydroxypropyltrimethyl Ammonium Chitosan Derivatives Bearing Amino Acid Schiff Bases.

N-2-hydroxypropyltrimethyl ammonium chloride chitosan (HACC), a cationic quaternary ammonium salt polymer exhibiting good solubility in water, is widely used because of its low toxicity and good biocompatibility. Herein, through ion exchange reaction, we prepared N-2-hydroxypropyltrimethyl ammonium chitosan derivatives bearing amino acid Schiff bases with good biological activities. The accuracy of the structures was verified by FT-IR and 1H NMR. The antibacterial activity, antifungal activity, and scavenging ability of DPPH radical and superoxide radical of HACC derivatives were significantly improved compared with that of HACC. In particular, HACGM (HACC-potassium 2-((2-hydroxy-3-methoxybenzylidene)amino)acetate) and HACGB (HACC-potassium 2-((5-bromo-2-hydroxybenzylidene)amino)acetate) showed good inhibitory effect on bacteria and fungi, including Staphylococcus aureus, Escherichia coli, Botrytis cinerea, and Fusarium oxysporum f. sp. cubense. The inhibition rate of HACGB on Staphylococcus aureus and Escherichia coli could reach 100% at the concentration of 0.1 mg/mL, and the inhibition rate of HACGM and HACGB on Botrytis cinerea and Fusarium oxysporum f. sp. cubense could also reach 100% at the concentration of 0.5 mg/mL. Improving antimicrobial and antioxidant activities of HACC could provide ideas and experiences for the development and utilization of chitosan derivatives.

Alarmone Ap4A is elevated by aminoglycoside antibiotics and enhances their bactericidal activity.

Second messenger molecules play important roles in the responses to various stimuli that can determine a cell's fate under stress conditions. Here, we report that lethal concentrations of aminoglycoside antibiotics result in the production of a dinucleotide alarmone metabolite-diadenosine tetraphosphate (Ap4A), which promotes bacterial cell killing by this class of antibiotics. We show that the treatment of Escherichia coli with lethal concentrations of kanamycin (Kan) dramatically increases the production of Ap4A. This elevation of Ap4A is dependent on the production of a hydroxyl radical and involves the induction of the Ap4A synthetase lysyl-tRNA synthetase (LysU). Ectopic alteration of intracellular Ap4A concentration via the elimination of the Ap4A phosphatase diadenosine tetraphosphatase (ApaH) and the overexpression of LysU causes over a 5,000-fold increase in bacterial killing by aminoglycosides. This increased susceptibility to aminoglycosides correlates with bacterial membrane disruption. Our findings provide a role for the alarmone Ap4A and suggest that blocking Ap4A degradation or increasing its synthesis might constitute an approach to enhance aminoglycoside killing potency by broadening their therapeutic index and thereby allowing lower nontoxic dosages of these antibiotics to be used in the treatment of multidrug-resistant infections.

First report of Neofusicoccum parvum causing leaf spot disease on Macadamia integrifolia in China.

The macadamia industry is developing rapidly in China. A brown leaf spot disease was noted in six Macadamia integrifolia plantations in Lincang, Yunnan, in October 2021. Over 60% of trees sampled had brown leaf spot symptoms, among approx.15,000 trees planted in these areas. Lesions (3 to 5 mm dia.) were small round brown spots with yellow edges. Lesions on severely infected leaves were darker and larger, with irregular shape (8 to 10 mm long, 3 to 6 mm wide). About 10% of diseased leaves had lesions characterized by a shot hole surrounded by a yellow halo. Potential pathogens were isolated from four randomly-selected symptomatic leaves from each of the six plantations by cutting lesion edges into small pieces. The pieces were surface sterilized, placed onto water agar containing 100 ppm aureomycin and incubated for 5 days at 24°C in the dark. Subculturing microbial growth on potato dextrose agar produced single-hyphal isolates with white fluffy aerial mycelia that turned pale olivaceous gray after 4 to 5 days. In four randomly-selected cultures, conidia were single celled, hyaline, spindle shaped to oval, and measured 10.9 to 16.3 µm long and 4.0 to 6.2 µm wide (n = 50). These characteristics matched those of Neofusicoccum parvum (Pavlic et al. 2009). Isolate LC013 was randomly selected as a representative individual for molecular identification. Internal transcribed spacer (ITS; ITS1/ITS4 primers; White et al. 1990), beta-tubulin gene (tub2; BT2A/BT2B primers; Glass and Donaldson 1995) and translation elongation factor 1-alpha gene (tef1-α; EF1-728F/EF2 primers; Carbone and Kohn 1999; O'Donnell et al. 1998) regions were PCR amplified from genomic DNA. Sequences of the products were used to BLAST probe the type specimen nucleotide sequences in GenBank. The LC013 sequences (GenBank accessions OM392021 (ITS); OM453641 (tub2); OM567656 (tef1-α)) had >99% sequence identity with analogous sequences from the type specimen of N. parvum CBS 138823 (accessions AY236943 (ITS); AY236917 (tub2); AY236888 (tef1-α)). Isolate LC013 was sister to N. parvum type strain in a maximum-likelihood (ML) tree constructed from analogous concatenated ITS, tef1-α, and tub2 sequences of 27 species that are phylogenetically closely-related to LC013 based on the ITS single locus ML tree. Koch's postulates were tested twice with two isolates by wounding leaves of four 14-month-old M. integrifolia seedlings with a sterile needle and placing a 5-mm-diameter agar plug containing N. parvum on the wound site. PDA plugs alone were used as uninoculated controls. Leaves were covered with sealed bags to maintain >90% humidity for 24 hours. All plants were kept in the same glasshouse under natural conditions. Leaves of inoculated plants began to discolor at 5 days post-inoculation (dpi). Brown spot symptoms were observed at 9 dpi. Control plants were symptomless. N. parvum was re-isolated from leaf lesions of the infected plants, but not from control plants, thus fulfilling Koch's postulates. N. parvum is an aggressive pathogen that causes severe disease on important tree and woody species, including M. integrifolia (Liddle et al. 2019). In China, it has been reported to cause leaf spot disease on 26 plant species (Farr and Rossman 2022), but this is the first report of N. parvum causing leaf spot disease on M. integrifolia. Further investigation is required to estimate the importance of this pathogen to the macadamia industry in China.

[Discovery of exogenous ligands for orphan receptor BRS-3 from Chinese herbs].

Bombesin receptor subtype-3(BRS-3) is an orphan receptor in the bombesin receptor family. Its signal transduction mechanism and biological function have attracted much attention. Seeking the ligand for BRS-3 is of great significance for exploring its function. Considering the fact that the activation of BRS-3 receptor can induce the change in intracellular Ca~(2+) concentration, the fluo-rometric imaging plate reader(FLIPR) was utilized for ligand screening at the cellular level. Among more than 400 monomeric compounds isolated from Chinese herbs, yuanhunine from Corydalis Rhizoma and sophoraisoflavanone A and licoriphenone from Glycyrrhizae Radix et Rhizoma antagonized BRS-3 to varying degrees. It was confirmed in HEK293 cells expressing BRS-3 that yuanhunine, sophoraisoflavanone A, and licoriphenone inhibited the calcium current response after the activation of BRS-3 by [D-Phe~6,ß-Ala~(11),Phe~(13),Nle~(14)]bombesin-(6-14) in a dose-dependent manner with the IC_(50) values being 8.58, 4.10, and 2.04 µmol·L~(-1), respectively. Further study indicated that yuanhunine and sophoraisoflavanone A exhibited good selectivity for BRS-3. In this study, it was found for the first time that monomers derived from Chinese herbs had antagonistic activity against orphan receptor BRS-3, which has provided a tool for further study of BRS-3 and also the potential lead compounds for new drug discovery. At the same time, it provides reference for the research and development of innovative drugs based on the active ingredients of Chinese herbs.

[Application of Methylprednisolone Sodium Succinate Combined with Tropisetron in Prevention of Nausea and Vomiting under Microvascular Decompression of Hemifacial Spasm].

Objective To evaluate the effect of methylprednisolone sodium succinate combined with tropisetron on postoperative nausea and vomiting(PONV)under microvascular decompression of hemifacial spasm.Methods From January to June 2019,485 patients undergoing microvascular decompression for facial spasm at Department of Neurosurgery,Peking University People's Hospital were randomly assigned into two groups with random number table method.For group A(n=242),2 ml saline was administrated by intravenous drip before induction and 5 mg tropisetron after operation.For group B(n=243),40 mg methylprednisolone sodium succinate was administrated by intravenous drip before induction and 5 mg tropisetron after operation.The anesthesia time,operation time,and incidence of PONV in 0-24 h and 24-48 h were recorded for the comparison of the remedial treatment rate of nausea and vomiting between the two groups.Results There was no significant difference in age,gender,smoking history,body mass index value,American Society of Anesthesiologists score,medical history,surgical side,PONV history,operation time or anesthesia time between the two groups(all P > 0.05).The incidence of PONV in group A was 35.5% and 18.2% during 0-24 h and 24-48 h,respectively,which was significantly higher than that(18.5%,χ 2=7.331,P=0.007;8.2%,χ 2=4.364,P=0.037)in group B.The application rate of antiemetic drugs in group A was 15.2% and 8.7% during 0-24 h and 24-48 h,respectively,which was significantly higher than that(5.3%,χ 2=5.327,P=0.021;2.0%,χ 2=4.432,P=0.035)in group B.Conclusion The combination of methylprednisolone sodium succinate and tropisetron can effectively prevent PONV under microvascular decompression of hemifacial spasm,with the performance superior to single drug treatment.

Exosome-transferred hsa_circ_0014235 promotes DDP chemoresistance and deteriorates the development of non-small cell lung cancer by mediating the miR-520a-5p/CDK4 pathway.

BACKGROUND: Circular RNAs (circRNAs) play crucial roles in the development and progression of human cancers, including non-small cell lung cancer (NSCLC). However, most of these circRNAs, such as hsa_circ_0014235, are not fully identified in functions and mechanisms. METHODS: The isolated exosomes from serum specimens were identified using transmission electron microscopy (TEM). The expression of hsa_circ_0014235, miR-520a-5p and cyclin-dependent kinase 4 (CDK4) was detected by real-time quantitative polymerase chain reaction (qPCR). For functional assays, cell proliferation, colony formation ability, migration, invasion, cell apoptosis and cell cycle progression were determined using cell counting kit-8 (CCK-8) assay, colony formation assay, wound healing assay, transwell assay and flow cytometry assay, respectively. The expression of CDK4 and other indicated marker proteins was detected by western blot. The predicted target relationship between miR-520a-5p and hsa_circ_0014235 or cyclin-dependent kinase 4 (CDK4) was verified by dual-luciferase reporter assay or RNA immunoprecipitation (RIP) assay. RESULTS: The expression of hsa_circ_0014235 was notably elevated in NSCLC serum-derived exosomes, tumor tissues and cells. NSCLC serum-derived exosomes promoted NSCLC cell resistance to cisplatin (DDP), cell proliferation, migration and invasion in vitro, as well as tumor growth and DDP resistance in vivo. Hsa_circ_0014235 overexpression enhanced DDP resistance and facilitated cell malignant behaviors. MiR-520a-5p was a target of hsa_circ_0014235, and rescue experiments showed that miR-520a-5p restoration reversed the effects of hsa_circ_0014235 overexpression. Moreover, CDK4 was a target of miR-520a-5p, and rescue experiments showed that CDK4 knockdown reversed the aggressive effects of miR-520a-5p inhibition on NSCLC progression. CONCLUSIONS: Exosome-transmitted hsa_circ_0014235 promoted NSCLC malignant development by mediating the miR-520a-5p/CDK4 regulatory axis.

Identifying Novel ATX Inhibitors via Combinatory Virtual Screening Using Crystallography-Derived Pharmacophore Modelling, Docking Study, and QSAR Analysis.

Autotaxin (ATX) is considered as an interesting drug target for the therapy of several diseases. The goal of the research was to detect new ATX inhibitors which have novel scaffolds by using virtual screening. First, based on two diverse receptor-ligand complexes, 14 pharmacophore models were developed, and the 14 models were verified through a big test database. Those pharmacophore models were utilized to accomplish virtual screening. Next, for the purpose of predicting the probable binding poses of compounds and then carrying out further virtual screening, docking-based virtual screening was performed. Moreover, an excellent 3D QSAR model was established, and 3D QSAR-based virtual screening was applied for predicting the activity values of compounds which got through the above two-round screenings. A correlation coefficient r2, which equals 0.988, was supplied by the 3D QSAR model for the training set, and the correlation coefficient r2 equaling 0.808 for the test set means that the developed 3D QSAR model is an excellent model. After the filtering was done by the combinatory virtual screening, which is based on the pharmacophore modelling, docking study, and 3D QSAR modelling, we chose nine potent inhibitors with novel scaffolds finally. Furthermore, two potent compounds have been particularly discussed.

Meta-analysis of single-stage versus two-staged management for concomitant gallstones and common bile duct stones.

OBJECTIVE: The purpose of this article was to compare the effectiveness and safety of single-stage (laparoscopic cholecystectomy [LC] plus laparoscopic common bile duct exploration [LCBDE]) with two-stage (LC plus endoscopic retrograde cholangiopancreatography (ERCP)/endoscopic sphincterotomy [EST]) in management for concomitant gallstones and common bile duct (CBD) stones. MATERIALS AND METHODS: Systematic review and meta-analysis of randomised controlled trials (RCTs) comparing outcomes following single-stage with two-stage management for concomitant gallstones and CBD stones published from 1990 to 2017 in PubMed, Embase and the Science Citation Index. The primary outcomes were stone clearance from the CBD, post-operative morbidity and mortality. The secondary outcomes were retained stone, conversion to other procedures, length of hospital stay and total operating time. Pooled risk ratio (RR) or weighted mean differences (WMD) with 95% confidence intervals (95% CIs) were calculated using either the fixed effects model or random effects model. RESULTS: Eleven RCTs studies were included in this analysis. These studies included a total of 1338 patients: 666 underwent LC + LCBDE and 672 underwent LC + ERCP/EST. The meta-analysis showed that no significant difference was noted between the two groups regarding CBD stone clearance (RR: 1.06; 95% CI: 0.99-1.14; P= 0.12), post-operative morbidity (RR: 1.03; 95% CI: 0.79-1.34; P= 0.81), mortality (RR: 0.30; 95% CI: 0.06-1.41; P= 0.13), retained stone (RR: 0.91; 95% CI: 0.57-1.47; P= 0.71), conversion to other procedures (RR: 0.80; 95% CI: 0.55-0.16; P= 0.23), length of hospital stay (WMD: 1.24, 95% CI: 3.57-1.09, P= 0.30), total operating time (WMD: 25.42, 95% CI: 22.38-73.22, P= 0.30). CONCLUSION: Single-stage is efficient and safe in the treatment of patients with concomitant gallstones and CBD stones while avoiding the second procedure. In selected patients, single-stage management for concomitant gallstones and CBD stones might be considered as the preferred approach. However, the findings have to be carefully interpreted due to the existence of heterogeneity, in addition, patient's condition, operator's experience also should be taken into account in making treatment decisions.

Development of an in silico prediction model for chemical-induced urinary tract toxicity by using naïve Bayes classifier.

The urinary tract toxicity is one of the major reasons for investigational drugs not coming into the market and even marketed drugs being restricted or withdrawn. The objective of this investigation is to develop an easily interpretable and practically applicable in silico prediction model of chemical-induced urinary tract toxicity by using naïve Bayes classifier. The genetic algorithm was used to select important molecular descriptors related to urinary tract toxicity, and the ECFP-6 fingerprint descriptors were applied to the urinary tract toxic/non-toxic fragments production. The established naïve Bayes classifier (NB-2) produced 87.3% overall accuracy of fivefold cross-validation for the training set and 84.2% for the external test set, which can be employed for the chemical-induced urinary tract toxicity assessment. Furthermore, six important molecular descriptors (e.g., number of N atoms, AlogP, molecular weight, number of H acceptors, number of H donors and molecular fractional polar surface area) and toxic and non-toxic fragments were obtained, which would help medicinal chemists interpret the mechanisms of urinary tract toxicity, and even provide theoretical guidance for hit and lead optimization.

Splice Variants of the Castor WRI1 Gene Upregulate Fatty Acid and Oil Biosynthesis When Expressed in Tobacco Leaves.

The plant-specific WRINKLED1 (WRI1) is a member of the AP2/EREBP class of transcription factors that positively regulate oil biosynthesis in plant tissues. Limited information is available for the role of WRI1 in oil biosynthesis in castor bean (Ricinus connunis L.), an important industrial oil crop. Here, we report the identification of two alternatively spliced transcripts of RcWRI1, designated as RcWRI1-A and RcWRI1-B. The open reading frames of RcWRI1-A (1341 bp) and RcWRI1-B (1332 bp) differ by a stretch of 9 bp, such that the predicted RcWRI1-B lacks the three amino acid residues "VYL" that are present in RcWRI1-A. The RcWRI1-A transcript is present in flowers, leaves, pericarps and developing seeds, while the RcWRI1-B mRNA is only detectable in developing seeds. When the two isoforms were individually introduced into an Arabidopsiswri1-1 loss-of-function mutant, total fatty acid content was almost restored to the wild-type level, and the percentage of the wrinkled seeds was largely reduced in the transgenic lines relative to the wri1-1 mutant line. Transient expression of each RcWRI1 splice isoform in N. benthamiana leaves upregulated the expression of the WRI1 target genes, and consequently increased the oil content by 4.3-4.9 fold when compared with the controls, and RcWRI1-B appeared to be more active than RcWRI1-A. Both RcWRI1-A and RcWRI1-B can be used as a key transcriptional regulator to enhance fatty acid and oil biosynthesis in leafy biomass.

Rs739837 Polymorphism in MiR-885-3p Binding Site Within 3'-Untranslated Region of Vitamin D Receptor is Associated with a Decreased Risk of Pressure Ulcers.

BACKGROUND/AIMS: Accumulative evidence has shown that miR-885-3p plays a crucial role in human carcinogenesis. From miRNA database, we also found that rs739837 polymorphism in miR-885-3p binding site within 3'-untranslated region of Vitamin D receptor (VDR), compromising the suppressive effect of miR-885-3p on VDR. Moreover, Vitamin D is involved in controlling the cell immune response and may play a role in pressure ulcers development. However, whether this polymorphism is actually linked with pressure ulcers remains unclear. The aim of the present study was to investigate the potential association between the rs739837 polymorphism and pressure ulcers, and to explore molecular mechanism of VDR in pressure ulcers. METHODS: Luciferase assays were performed to validate the relationship between miR-885 and VDR, which was confirmed by western-blotting analysis. The relationship between rs739837 and the risk of pressure ulcers was explored using logistic regression analysis. RESULTS: We first conducted statistical analysis to explore the association between the rs739837 genotype and risk of pressure ulcers, and found that the polymorphism genotype was significantly associated with the risk of pressure ulcers (OR 0.68, 95% CI 0.43-0.95, P value = 0.02). We then searched the miRNA database online and identified VDR as a direct target. We established the negative regulatory relationship between miR-885-3p and VDR using luciferase assays. Meanwhile, we transfected cells with scramble control, miR-885-3p mimics, VDR siRNA and miR-885-3p inhibitors. The results further confirmed the negative regulatory relationship between miR-885-3p and VDR. CONCLUSION: VDR is a virtual target of miR-885-3p, and rs739837 might be a predictive biomarker for the risk of pressure ulcers.

Towards Identifying and Reducing the Bias of Disease Information Extracted from Search Engine Data.

The estimation of disease prevalence in online search engine data (e.g., Google Flu Trends (GFT)) has received a considerable amount of scholarly and public attention in recent years. While the utility of search engine data for disease surveillance has been demonstrated, the scientific community still seeks ways to identify and reduce biases that are embedded in search engine data. The primary goal of this study is to explore new ways of improving the accuracy of disease prevalence estimations by combining traditional disease data with search engine data. A novel method, Biased Sentinel Hospital-based Area Disease Estimation (B-SHADE), is introduced to reduce search engine data bias from a geographical perspective. To monitor search trends on Hand, Foot and Mouth Disease (HFMD) in Guangdong Province, China, we tested our approach by selecting 11 keywords from the Baidu index platform, a Chinese big data analyst similar to GFT. The correlation between the number of real cases and the composite index was 0.8. After decomposing the composite index at the city level, we found that only 10 cities presented a correlation of close to 0.8 or higher. These cities were found to be more stable with respect to search volume, and they were selected as sample cities in order to estimate the search volume of the entire province. After the estimation, the correlation improved from 0.8 to 0.864. After fitting the revised search volume with historical cases, the mean absolute error was 11.19% lower than it was when the original search volume and historical cases were combined. To our knowledge, this is the first study to reduce search engine data bias levels through the use of rigorous spatial sampling strategies.

Study on Tandem Polymer Light Emitting Devices.

We report tandem polymer light emitting devices by using the PEDOT∶PSS/ZnO/PEIE charge generation layer (CGL) and investigate the influences of the conductance and thickness of PEDOT∶PSS layer on the properties of the devices. The results indicate that the conductance and thickness of PEDOT∶PSS layer have marginal impact on the J-V characteristics of the devices, while significant influences of device efficiency upon utilization of different PEDOT∶PSS specimens mainly come from their different strengths on exciton quenching. Luminance efficiency of TOLEDs with the PEDOT∶PSS thickness of 60 nm in CGL is better than TOLEDs with the PEDOT∶PSS thickness of 30 nm in CGL, the reason is that PEDOT∶PSS thickness of 60 nm the surface topography is more even . Luminance efficiency and driving voltage of the tandem devices match the sum of the luminance efficiency and driving voltage of the component light-emitting units, respectively, indicating that charges generated in the CGL can be injected efficiently into the adjacent light-emitting units. Incorporation of a V2O5 layer into the CGL structure only slightly affects the J-V and LE-I characteristics of the tandem devices, suggesting that the utilization of the PEDOT∶PSS/ZnO/PEIE CGL enables the simplification of the CGL structure without compromising device performance. The luminescence spectra of TOLEDs obviously involves two light emitting unit of spectrum, which shows that two light emitting unit in TOLEDs is normal work. Measurements on the capacitance-voltage characteristics of the CGL-based devices confirm that under negative bias (ITO anode) charges are accumulated and displaced in the CGL, which is totally in line with the full operation of light emitting units in the tandem devices. PEDOT∶PSS/ZnO/PEIE layer is evidenced the effective CGL. On this basis, for the first time we report tandem polymer light emitting devices containing three SY-PPV light-emitting units，which show the mixture of luminance efficiency and external quantum efficiency of 21.7 cd·A-1 and 6.95%, similar to the total luminance efficiency and external quantum efficiency of constituent LEUs. At 5 000 cd·m-2, the luminance efficiency and external quantum efficiency of the tandem devices are 20.5 cd·A-1 and 6.6%. Thus, the increase in the number of light emitting units leads to almost no performance losses, implying the robustness of the PEDOT∶PSS/ZnO/PEIE CGL. Tandem polymer light emitting devices containing three SY-PPV light-emitting units of the luminescent spectra is close to the light emitting unit. Further efforts on the optimization of hole injection layer in the CGL to minimize exciton quenching are underlying to promote the luminance efficiency of tandem polymer light emitting devices.

Antidepressant activity of astilbin: involvement of monoaminergic neurotransmitters and BDNF signal pathway.

Depression and related mood disorders are among the world's greatest public health problems. Previous studies have demonstrated that astilbin (AST) has broad pharmacological functions which may modulate numerous pathways, such as antioxidant, scavenging free radicals, anti-inflammatory and so on, similarly to some of other flavonoids. In this study, the antidepressant-like effect of AST was investigated using chronic unpredictable mild stress (CUMS) model of depression in mice. The results showed that chronic administration of AST at doses of 10, 20 and 40 mg/kg (intraperitoneally (i.p.), 21 d) reduced depressive-like behaviors of mice in the forced swim test (FST), tail suspension test (TST) and sucrose preference test (SPT) without affecting locomotor activity. AST increased the contents of serotonin (5-HT) and dopamine (DA) in the frontal cortex of CUMS mice. Additionally, it was shown that AST treatment restored the CUMS-induced inhibition of extracellular signal-regulated kinase (ERK) 1/2 and AKT phosphorylation in the frontal cortex, conformed to the brain-derived neurotrophic factor (BDNF) expression. Our findings suggest that AST has antidepressant activities and the mechanisms, at least in part, relate to up-regulation of monoaminergic neurotransmitters (5-HT and DA) and activation of the BDNF signaling pathway.

Intraureteral Metastasis From Colon Cancer Mimicking Primary Ureteral Carcinoma on FDG PET/CT.

ABSTRACT: Hematogenous or lymphatic intraureteral metastasis from distant primary cancer is very rare. We present contrast-enhanced CT and FDG PET/CT findings in a case of intraureteral metastasis from colonic adenocarcinoma 3 years after colectomy. The intraureteral showed moderate enhancement on contrast-enhanced CT and increased FDG uptake on PET/CT mimicking a primary ureteral carcinoma. This case suggests that metastatic tumor of the ureter should be considered in the differential diagnosis in patients with hypermetabolic ureteral lesion and known malignancy.