The mouse is receiving growing interest as a model organism for studying visual perception. However, little is known about how discrimination and learning interact to produce visual conditioned responses. Here, we adapted a two-alternative forced-choice visual discrimination task for mice and examined how training with equiprobable stimuli of varying similarity influenced conditioned response and discrimination performance as a function of learning. Our results indicate that the slope of the gradients in similarity during training determined the learning rate, the maximum performance and the threshold for successful discrimination. Moreover, the learning process obeyed an inverse relationship between discrimination performance and discriminative resolution, implying that sensitivity within a similarity range cannot be improved without sacrificing performance in another. Our study demonstrates how the interplay between discrimination and learning controls visual discrimination capacity and introduces a new training protocol with quantitative measures to study perceptual learning and visually-guided behavior in freely moving mice.
The title compound, C6HCl6N, lies on a mirror plane, the asymmetric unit conataining a half-molecule. Weak intramolecular C—H⋯Cl contacts are observed.
The aim of this study was to improve the drug loading, encapsulation efficiency, and sustained-release properties of supercritical CO2-based drug-loaded polymer carriers via a process of suspension-enhanced dispersion by supercritical CO2 (SpEDS), which is an advanced version of solution-enhanced dispersion by supercritical CO2 (SEDS).
Methotrexate nanoparticles were successfully microencapsulated into poly (L-lactide)-poly(ethylene glycol)-poly(L-lactide) (PLLA-PEG-PLLA) by SpEDS. Methotrexate nanoparticles were first prepared by SEDS, then suspended in PLLA-PEG-PLLA solution, and finally microencapsulated into PLLA-PEG-PLLA via SpEDS, where an “injector” was utilized in the suspension delivery system.
After microencapsulation, the composite methotrexate (MTX)-PLLA-PEG-PLLA microspheres obtained had a mean particle size of 545 nm, drug loading of 13.7%, and an encapsulation efficiency of 39.2%. After an initial burst release, with around 65% of the total methotrexate being released in the first 3 hours, the MTX-PLLA-PEG-PLLA microspheres released methotrexate in a sustained manner, with 85% of the total methotrexate dose released within 23 hours and nearly 100% within 144 hours.
Compared with a parallel study of the coprecipitation process, microencapsulation using SpEDS offered greater potential to manufacture drug-loaded polymer microspheres for a drug delivery system.
drug loading; encapsulation efficiency; methotrexate; nanoparticles; poly(L-lactide); supercritical CO2 sustained release
AIM: To investigate and compare the decompression effect on small bowel obstruction of a long tube inserted using either endoscopic or fluoroscopic placement.
METHODS: Seventy-eight patients with small bowel obstruction requiring decompression were enrolled in the study and divided into two groups. Intubation of a long tube was guided by fluoroscopy in one group and by endoscopy in the other. The duration of the procedure and the success rate for each group were evaluated.
RESULTS: A statistically significant difference in the mean duration of the procedure was found between the fluoroscopic group (32.6 ± 14.6 min) and the endoscopic group (16.5 ± 7.8 min) among the cases classified as successful (P < 0.05). The success rate was significantly different between the groups: 88.6% in the fluoroscopic group and 100% in the endoscopic group (P < 0.05).
CONCLUSION: For patients with adhesive small bowel obstruction, long-tube decompression is recommended and long-tube insertion by endoscopy was superior to fluoroscopic placement.
Long-tube insertion; Small bowel obstruction; Decompression; Gastroscope; Fluoroscopic guidance
AIM: To compare and evaluate the appropriate prognostic indicators of lymph node basic staging in gastric cancer patients who underwent radical resection.
METHODS: A total of 1042 gastric cancer patients who underwent radical resection and D2 lymphadenectomy were staged using the 6th and 7th edition International Union Against Cancer (UICC) N staging methods and the metastatic lymph node ratio (MLNR) staging. Homogeneity, discriminatory ability, and gradient monotonicity of the various staging methods were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations. The area under the curve (AUC) was calculated to compare the predictive ability of the aforementioned three staging methods.
RESULTS: Optimal cut-points of the MLNR were calculated as MLNR0 (0), MLNR1 (0.01-0.30), MLNR2 (0.31-0.50), and MLNR3 (0.51-1.00). In univariate, multivariate, and stratified analyses, MLNR staging was superior to the 6th and 7th edition UICC N staging methods. MLNR staging had a higher AUC, higher linear trend and likelihood ratio χ2 scores and lower AIC values than the other two staging methods.
CONCLUSION: MLNR staging predicts survival after gastric cancer more precisely than the 6th and 7th edition UICC N classifications and should be considered as an alternative to current pathological N staging.
Gastric cancer; Metastatic lymph node ratio; Prognosis
Gastric carcinoma is the second commonest cause of cancer deaths worldwide. Early detection and diagnosis of gastric cancer in the stomach is important for improving the prognosis of gastric cancer. This retrospective study was designed to investigate the value of magnifying narrow-band imaging (NBI) in the diagnosis of precancerous lesions and early gastric cancer.
This study included 122 patients who were diagnosed with early gastric cancer or precancerous gastric lesions by endoscopy. The patients underwent an examination with conventional endoscopy, magnifying NBI, and magnifying chromoendoscopy. Images resolution was evaluated, and the morphology, pit patterns and blood capillary forms of lesions were analyzed. The presence of gastric carcinoma and high grade intraepithelial neoplasia in the biopsy samples was considered as a positive pathological result, which is used to assess accuracy of endoscopic diagnosis.
For image resolution, magnifying NBI and magnifying chromoendoscopy were significantly superior to magnifying conventional endoscopy in morphology, pit pattern and blood capillary form (P < 0.01), and magnifying NBI was significantly superior to magnifying chromoendoscopy in blood capillary form (P < 0.01). IV, V1, and VI type of gastric pit pattern were detected in 14 cases, 43 cases, and 17 cases in patients with high grade intraepithelial neoplasia, respectively. V1 and VI type of gastric pit pattern were detected in 9 cases and 39 cases in patients with early gastric cancer, respectively. The presence of irregular minute vessels and variation in the caliber of vessels was found in 109 cases. The accuracy, sensitivity, specificity, false positive rate and false negative rate for diagnosis of early gastric cancer and precancerous gastric lesions were 68.9%, 95.1%, 63.1%, 24.5%, and 32.4% for conventional endoscopy, 93.6%, 92.7%, 94.5%, 5.7%, and 6.9% for magnifying NBI, and 91.3%, 88.6%, 93.2%, 13.2%, and 21.48% for magnifying chromoendoscopy, respectively.
This study demonstrates that magnifying NBI is superior to conventional endoscopy in the diagnosis of early gastric cancer and precancerous gastric lesions, and can be used for screening early malignancies of the stomach.
In nature, sensory stimuli are organized in heterogeneous combinations. Salient items from these combinations 'stand-out' from their surroundings and determine what and how we learn. Yet, the relationship between varying stimulus salience and discrimination learning remains unclear.
Presentation of the hypothesis
A rigorous formulation of the problem of discrimination learning should account for varying salience effects. We hypothesize that structural variations in the environment where the conditioned stimulus (CS) is embedded will be a significant determinant of learning rate and retention level.
Testing the hypothesis
Using numerical simulations, we show how a modified version of the Rescorla-Wagner model, an influential theory of associative learning, predicts relevant interactions between varying salience and discrimination learning.
Implications of the hypothesis
If supported by empirical data, our model will help to interpret critical experiments addressing the relations between attention, discrimination and learning.
Associative learning; discrimination, salience; associability; behavior
Enhancer of zeste homologue 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PRC2) and catalyses the trimethylation of histone H3 on Lys 27 (H3K27), which represses gene transcription. EZH2 enhances cancer-cell invasiveness and regulates stem cell differentiation. Here, we demonstrate that EZH2 can be phosphorylated at Thr 487 through activation of cyclin-dependent kinase 1 (CDK1). The phosphorylation of EZH2 at Thr 487 disrupted EZH2 binding with the other PRC2 components SUZ12 and EED, and thereby inhibited EZH2 methyltransferase activity, resulting in inhibition of cancer-cell invasion. In human mesenchymal stem cells, activation of CDK1 promoted mesenchymal stem cell differentiation into osteoblasts through phosphorylation of EZH2 at Thr 487. These findings define a signalling link between CDK1 and EZH2 that may have an important role in diverse biological processes, including cancer-cell invasion and osteogenic differentiation of mesenchymal stem cells.
The title compound, C24H40O3·C2H6O, is a substituted tetracyclo[10.2.2.01,10.04,9]hexadecane derivative obtained from the reduction of maleopimaric acid which was isolated from a maleic anhydride modified rosin. In the crystal, the triol molecule and the ethanol solvent molecule are linked by hydroxyl O—H⋯O hydrogen bonds, giving a two-dimensional network structure.
Our objective was to investigate the effect of various reimmunization schemes for hepatitis B in adults with low or undetectable anti-HBs titers. Over 2 years, 10 μg of Saccharomyces cerevisiae-recombinant hepatitis B virus (HBV) vaccine (synthesized in China) was used in at least one standardized scheme to immunize 2,310 healthy male and nonpregnant female adults. Of these, 240 subjects tested negative for hepatitis B markers. These 240 subjects were equally divided into 4 groups. The first group, designated Engerix-40, was revaccinated with 40 μg Engerix-B; the second, Engerix-20, was revaccinated with 20 μg Engerix-B; the third, Chinese-20, was revaccinated with 20 μg Chinese-made yeast-recombinant vaccine; and the last group, Chinese-10, was revaccinated with 10 μg Chinese-made yeast-recombinant vaccine. Blood samples were collected before and 1, 2, 8, and 12 months after the first injection. The anti-HBs-positive conversion rates of the Engerix-40, Engerix-20, and Chinese-20 groups were higher than that of the Chinese-10 group (P < 0.01). Over time, the anti-HBs conversion rate increased in all groups, but values were significantly different from those for the other groups only in the Chinese-10 group (P < 0.001). The anti-HBs geometric mean titers (GMTs) of the Engerix-40, Engerix-20, and Chinese-20 groups were higher than in the Chinese-10 group (P < 0.05). Increased doses raise and maintain anti-HBs titers in subjects with low or undetectable titers after HBV vaccination.
Herpes simplex type 1 (HSV1) replicates in epithelial cells and secondarily enters local sensory neuronal processes, traveling retrograde to the neuronal nucleus to enter latency. Upon reawakening newly synthesized viral particles travel anterograde back to the epithelial cells of the lip, causing the recurrent cold sore. HSV1 co-purifies with amyloid precursor protein (APP), a cellular transmembrane glycoprotein and receptor for anterograde transport machinery that when proteolyzed produces A-beta, the major component of senile plaques. Here we focus on transport inside epithelial cells of newly synthesized virus during its transit to the cell surface. We hypothesize that HSV1 recruits cellular APP during transport. We explore this with quantitative immuno-fluorescence, immuno-gold electron-microscopy and live cell confocal imaging. After synchronous infection most nascent VP26-GFP-labeled viral particles in the cytoplasm co-localize with APP (72.8+/−6.7%) and travel together with APP inside living cells (81.1+/−28.9%). This interaction has functional consequences: HSV1 infection decreases the average velocity of APP particles (from 1.1+/−0.2 to 0.3+/−0.1 µm/s) and results in APP mal-distribution in infected cells, while interplay with APP-particles increases the frequency (from 10% to 81% motile) and velocity (from 0.3+/−0.1 to 0.4+/−0.1 µm/s) of VP26-GFP transport. In cells infected with HSV1 lacking the viral Fc receptor, gE, an envelope glycoprotein also involved in viral axonal transport, APP-capsid interactions are preserved while the distribution and dynamics of dual-label particles differ from wild-type by both immuno-fluorescence and live imaging. Knock-down of APP with siRNA eliminates APP staining, confirming specificity. Our results indicate that most intracellular HSV1 particles undergo frequent dynamic interplay with APP in a manner that facilitates viral transport and interferes with normal APP transport and distribution. Such dynamic interactions between APP and HSV1 suggest a mechanistic basis for the observed clinical relationship between HSV1 seropositivity and risk of Alzheimer's disease.
Epidermal growth factor receptor (EGFR) can undergo post-translational modifications, including phosphorylation, glycosylation and ubiquitylation, leading to diverse physiological consequences and modulation of its biological activity. There is increasing evidence that methylation may parallel other post-translational modifications in the regulation of various biological processes. It is still not known, however, whether EGFR is regulated by this post-translational event. Here, we show that EGFR Arg 1175 is methylated by an arginine methyltransferase, PRMT5. Arg 1175 methylation positively modulates EGF-induced EGFR trans-autophosphorylation at Tyr 1173, which governs ERK activation. Abolishment of Arg 1175 methylation enhances EGF-stimulated ERK activation by reducing SHP1 recruitment to EGFR, resulting in augmented cell proliferation, migration and invasion of EGFR-expressing cells. Therefore, we propose a model in which the regulatory crosstalk between PRMT5-mediated Arg 1175 methylation and EGF-induced Tyr 1173 phosphorylation attenuates EGFR-mediated ERK activation.
A 39-year-old man with chronic bleeding from Rendu-Osler-Weber disease in the small intestine was treated with argon plasma coagulation using a custom-made probe under double-balloon enteroscopy. A 10 month follow-up showed no evidence of bleeding.
AIM: To investigate the role of heme oxygenase-1 (HO-1) in pathogenesis of experimental hepatorenal syndrome (HRS).
METHODS: Rats were divided into liver cirrhotic group, zinc protoporphyrin IX (ZnPP) treatment group, cobalt protoporphyrin (CoPP) treatment group and sham group. Biliary cirrhosis was established by bile duct ligation in the first three groups. Rats in the ZnPP and CoPP treatment groups received intraperitoneal injection of ZnPP and CoPP, respectively, 24 h before sample collection. Expression of HO-1 mRNA in kidney was detected by reverse-transcription polymerase chain reaction, while protein expression was determined by immunohistochemical analysis. Hematoxylin and eosin staining was performed to observe liver cirrhosis and renal structure. Renal artery blood flow, mean arterial pressure and portal vein pressure, 24 h total urinary volume, serum and urine sodium concentrations, and creatinine clearance rate (Ccr) were also measured.
RESULTS: The HO-1 mRNA and protein expression levels in kidney, 24 h total urinary volume, renal artery blood flow, serum and urine sodium concentration and Ccr were lower in cirrhotic group than in sham group (P < 0.05). However, they were significantly lower in ZnPP treatment group than in cirrhotic group and significantly higher in CoPP treatment group than in cirrhotic group (P < 0.05).
CONCLUSION: Low HO-1 expression level in kidney is an important factor for experimental HRS.
Heme oxygenase-1; Carbon monoxide; Hepatorenal syndrome; Zinc protoporphyrin IX; Cobalt protoporphyrin; Bile duct ligation; Biliary cirrhosis
The title compound, C23H38O2, a tetracyclo[10.2.2.01,10.04,9] hexadecane structure, crystallized with four independent molecules in the asymmetric unit. In the crystal, these independent molecules are linked by O—H⋯O hydrogen bonds, forming a polymeric chain propagating in 
Objective: Angiogenic therapy is emerging as a potential strategy for the treatment of ischemic heart disease but is limited by a relatively short half-life of growth factors. Fibrin glue (FG) provides a reservoir for controlled-release of growth factors. The aim of this study was to evaluate the effects of basic fibroblast growth factor (bFGF) incorporating FG on angiogenesis and cardiac performance in a canine infarct model. Methods: Acute myocardial infarction was induced by ligation of the left anterior descending coronary artery (LAD). Group I (n=6) underwent ligation of LAD alone. In Group II, transmural channels were created in the infarct area (n=6). In Group III, non-transmural channels were created to locate FG cylinders containing bFGF (n=6). Eight weeks after operation, myocardial perfusion was assessed by single photon emission computed tomography, cardiac function by echocardiography, and vascular development by immunohistochemical staining. Results: Total vascular density and the number of large vessels (internal diameter ≥50 μm) were dramatically higher in Group III than in Groups I and II at eight weeks. Only the controlled-release group exhibited an improvement in regional myocardial perfusion associated with lower defect score. Animals in Group III presented improved cardiac regional systolic and diastolic functions as well as global systolic function in comparison with the other two groups. Conclusions: Enhanced and sustained angiogenic response can be achieved by controlled-release bFGF incorporating FG within transmyocardial laser channels, thus enabling improvement in myocardial perfusion and cardiac function.
Angiogenesis; Basic fibroblast growth factor; Controlled release; Ischemic heart disease
In the title compound, C25H36N2O2S, the cyclohexane and morpholine rings adopt chair conformations. The cyclohexene and cyclohexane rings form a trans ring junction with the two methyl groups in axial positions. The N—H and C=O bonds in the urea group are anti to each other. The crystal structure is stabilized by intermolecular N—H⋯O hydrogen bonds.
ErbB2, a metastasis-promoting oncoprotein, is overexpressed in ~25% of invasive/metastatic breast cancers, but in 50–60% of non-invasive ductal carcinomas in situ (DCIS). It has been puzzling how a subset of ErbB2-overexpressing DCIS develops into invasive breast cancer (IBC). We found that co-overexpression of 14-3-3ζ in ErbB2-overexpressing DCIS conferred a higher risk of progression to IBC. ErbB2 and 14-3-3ζ overexpression, respectively, increased cell migration and decreased cell adhesion, two prerequisites of tumor cell invasion. 14-3-3ζ overexpression reduced cell adhesion by activating the TGFβ/Smads pathway that led to ZFHX1B/SIP-1 upregulation, E-cadherin loss, and epithelial-mesenchymal transition (EMT). Importantly, patients whose breast tumors overexpressed both ErbB2 and 14-3-3ζ had higher rates of metastatic recurrence and death than those whose tumors overexpressed only one.
In the crystal structure of the title compound, C16H19NO, molecules are linked through a pair of N—H⋯O hydrogen bonds, forming chains along the a axis.
The title compound, C24H34O6·2C3H7NO, which was isolated from fumaric-modified rosin, has four asymmetrically fused six-membered rings and three carboxylic acid substituents. It contains two fused and unbridged cyclohexane rings, which form a trans ring junction with a chair conformation. The asymmetric unit includes one fumaropimaric acid and two dimethylformamide molecules. The crystal structure is stabilized through intermolecular O—H⋯O hydrogen bonds between dimethylformamide and fumaropimaric acid.
The title compound [systematic name: (1R)-methyl 6-bromo-7-isopropyl-1,4a-dimethyl-1,2,3,4,4a,9,10,10a-octahydrophenanthrene-1-carboxylate], C21H29BrO2, was synthesized from N-bromosuccinimide and methyl dehydroabietate, which was prepared through an esterification reaction using dehydroabietic acid and methanol as raw materials. The three six-membered rings adopt planar (mean deviation = 0.002 Å) half-chair and chair conformations. The two cyclohexane rings form a trans ring junction with the two methyl groups in axial positions. The crystal structure is stabilized by weak intermolecular C—H⋯O contacts along the b axis.
The title compound, C20H32O2, has been isolated from hydrogenated rosin. There are two independent molecules in the asymmetric unit. In each molecule, the cyclohexane ring assumes a chair conformation, while the two cyclohexene rings adopt half-chair and envelope conformations. Intermolecular O—H⋯O hydrogen bonding between carboxyl groups links pairs of independent molecules into dimers.
The title compound, C10H16O3, with a bicyclo[3.1.1]heptane unit, was obtained by oxidation of β-pinene. The asymmetric unit contains two independent molecules with similar geometry: the six-membered rings in both molecules adopt envelope conformations. In the crystal, the independent molecules exist as O—H⋯O hydrogen-bonded dimers. The dimers are linked into helical chains along the b axis by O—H⋯O hydrogen bonds.
AIM: To investigate acute nonvariceal bleeding in the upper gastrointestinal (GI) tract and evaluate the effects of endoscopic hemoclipping.
METHODS: Sixty-eight cases of acute nonvariceal bleeding in the upper GI tract were given endoscopic treatment with hemoclip application. Clinical data, endoscopic findings, and the effects of the therapy were evaluated.
RESULTS: The 68 cases (male:female = 42:26, age from 9 to 70 years, average 54.4) presented with hematemesis in 26 cases (38.2%), melena in nine cases (13.3%), and both in 33 cases (48.5%). The causes of the bleeding included gastric ulcer (29 cases), duodenal ulcer (11 cases), Dieulafoy’s lesion (11 cases), Mallory-Weiss syndrome (six cases), post-operative (three cases), post-polypectomy bleeding (five cases), and post-sphincterotomy bleeding (three cases); 42 cases had active bleeding. The mean number of hemoclips applied was four. Permanent hemostasis was obtained by hemoclip application in 59 cases; 6 cases required emergent surgery (three cases had peptic ulcers, one had Dieulafoy’s lesion, and two were caused by sphincterotomy); three patients died (two had Dieulafoy’s lesion and one was caused by sphincterotomy); and one had recurrent bleeding with Dieulafoy’s lesion 10 mo later, but in a different location.
CONCLUSION: Endoscopic hemoclip application was an effective and safe method for acute nonvariceal bleeding in the upper GI tract with satisfactory outcomes.
Gastrointestinal hemorrhage; Endoscopy; Hemoclip; Hemostasis
The title compound, C26H37NO5, which was synthesized from monoethanolamine and maleopimaric acid, consists of two fused and unbridged cyclohexane rings. They form a trans ring junction with a chair conformation. The two methyl groups are in axial positions. In the crystal, intermolecular O—H⋯O hydrogen bonds link adjacent molecules into a layer structure. Two C—H⋯O interactions are also present.