Diagnostic Efficacy and Possible Underlying Mechanisms of Noninvasive Clinical Markers in Hepatocellular Carcinoma.

Background and Aims: In this study, we aimed to evaluate the diagnostic values of alpha-fetoprotein (AFP), soluble AXL (sAXL), des-γ-carboxy prothrombin (DCP), the aspartate aminotransferase-to-platelet ratio index (APRI), and the gamma-glutamyl transpeptidase-to-platelet ratio (GPR) in hepatocellular carcinoma (HCC) and the possible underlying mechanisms of the correlations between them. Methods: We collected serum samples from 190, 128, and 75 patients with HCC, cirrhosis, and chronic viral hepatitis, and from 82 healthy subjects. Serum levels of AFP, sAXL, and DCP were determined, and APRI and GPR values were calculated. Receiver operating characteristic (ROC) curves were used to analyze the diagnostic value of single and combined biomarkers. Results: We detected significant differences between the HCC group and other groups regarding serum AFP, sAXL, DCP, and APRI levels. GPR significantly differed between the HCC group and other groups, except for the liver cirrhosis group. AFP, sAXL, DCP, APRI, and GPR had positive correlations with each other, and AFP showed a higher area under the curve (AUC) and Youden index values, while APRI and DCP showed the highest sensitivity and specificity. Also, when AFP was combined with sAXL, DCP, APRI, and GRP, the highest AUC (0.911) and a higher net reclassification improvement value were obtained compared with those obtained for the individual biomarkers. Conclusions: AFP, sAXL, DCP, APRI, and GPR are independent risk factors for HCC, and the diagnostic performance of AFP combined with sAXL, DCP, APRI, and GPR for HCC diagnosis was superior to that of the individual biomarkers.

Buckling of an elastic fiber with finite length in a soft matrix.

Elastic fibers embedded in a soft matrix are frequently encountered in nature and engineering across different length scales, ranging from microtubules in cytosol and filament networks to dissociative slender fish bones in muscles and fiber-reinforced soft composites. Fibers may buckle when the composite is subjected to compression; this study investigates this issue through a combination of experiments, finite-element simulations and theoretical analysis. Analysis reveals the important role of the interfacial shear forces and leads to an explicit solution to predict the occurrence of buckling for a slender fiber with finite length. The results reported in this paper will help understand the formation of shapes in some natural systems and provide guidelines for the design of soft biocomposites.

Wrinkling pattern evolution of cylindrical biological tissues with differential growth.

Three-dimensional surface wrinkling of soft cylindrical tissues induced by differential growth is explored. Differential volumetric growth can cause their morphological stability, leading to the formation of hexagonal and labyrinth wrinkles. During postbuckling, multiple bifurcations and morphological transitions may occur as a consequence of continuous growth in the surface layer. The physical mechanisms underpinning the morphological evolution are examined from the viewpoint of energy. Surface curvature is found to play a regulatory role in the pattern evolution. This study may not only help understand the morphogenesis of soft biological tissues, but also inspire novel routes for creating desired surface patterns of soft materials.

Inhibitory effects of edaravone in ß-amyloid-induced neurotoxicity in rats.

Amyloid protein can damage nerve cells through a variety of biological mechanisms including oxidative stress, alterations in calcium homeostasis, and proapoptosis. Edaravone, a potent free radical scavenger possessing antioxidant effects, has been proved neuroprotective effect in stroke patients. The current study aimed to investigate the effects of EDA in an Aß-induced rat model of AD, by studying Aß 1-40-induced voltage-gated calcium channel currents in hippocampal CA1 pyramidal neurons, learning and memory behavioral tests, the number of surviving cholinergic neurons in the basal forebrain, and the acetylcholine level in the hippocampus in this rat model of AD. The results showed that the Aß 1-40-induced increase of I Ca can be inhibited by EDA in a dose-dependent manner. Treatment with EDA significantly improved Aß 1-40-induced learning and memory performance. Choline acetyltransferase positive cells in basal forebrain and acetylcholine content in the hippocampus were increased by the administration of EDA as compared with the non-EDA treated Aß 1-40 group. These results demonstrate that EDA can inhibit the neurotoxic effect of Aß toxicity. Collectively, these findings suggest that EDA may serve as a potential complemental treatment strategy for AD.

Effects of internal pressure and surface tension on the growth-induced wrinkling of mucosae.

Surface wrinkling of mucosae is crucial for the biological functions of many living tissues. In this paper, we investigate the instability of a cylindrical tube consisting of a mucosal layer and a submucosal layer. Our attention is focused on the effects of internal pressure and surface tension on the critical condition and mode number of surface wrinkling induced by tissue growth. It is found that the internal pressure plays a stabilizing role but basically has no effect on the critical mode number. Surface tension also stabilizes the system and reduces the critical mode number of surface patterns. Besides, the thinner the mucosal layer, the more significant the effect of surface tension. This work may help gain insights into the surface wrinkling and morphological evolution of such tubular organs as airways and esophagi.

Spherical indentation method for determining the constitutive parameters of hyperelastic soft materials.

A comprehensive study on the spherical indentation of hyperelastic soft materials is carried out through combined theoretical, computational, and experimental efforts. Four widely used hyperelastic constitutive models are studied, including neo-Hookean, Mooney-Rivlin, Fung, and Arruda-Boyce models. Through dimensional analysis and finite element simulations, we establish the explicit relations between the indentation loads at given indentation depths and the constitutive parameters of materials. Based on the obtained results, the applicability of Hertzian solution to the measurement of the initial shear modulus of hyperelastic materials is examined. Furthermore, from the viewpoint of inverse problems, the possibility to measure some other properties of a hyperelastic material using spherical indentation tests, e.g., locking stretch, is addressed by considering the existence, uniqueness, and stability of the solution. Experiments have been performed on polydimethylsiloxane to validate the conclusions drawn from our theoretical analysis. The results reported in this study should help identify the extent to which the mechanical properties of hyperelastic materials could be measured from spherical indentation tests.

[Study on the spectrophotometric determination of hydroxyl free radical from low power trench-type ultrasound].

Under the condition of different pH (7-11) and different ethanol volume fraction (45% to 85%), the ultraviolet-visible absorption spectra of malachite green were studied in neutral and alkaline ethanol solution, the maximum absorption wavelength at 620 nm was found, and the matching degree of standard curve was better established. In low power trench-type ultrasound apparatus, the absorption of the malachite green solution was measured under ultrasound and non-ultrasound, respectively. the difference values of the ultraviolet absorption of the malachite green solution under low power trench-type ultrasound were measured results of the hydroxyl free radical oxidation degrading malachite green, therefore hydroxyl free radical from low power trench-type ultrasound was determined indirectly. Then the contents of hydroxyl free radical in four conditions were measured. The detection limit of the method of 8.4 x 10(-6) mmol x L(-1) and the relative standard deviation of the method of 9.4 x 10(-5) - 3.7 x 10(-4) mmol x L(-1) were determined, a higher testing precision and good reproducibility were confirmed. It can be applied for fast detection of neutral and alkaline ethanol solution system in the case of very low concentration of hydroxyl free radicals. Since malachite green is heat sensitive, so compared to measuring temperature, the method possessed better functions for thermal effects of ultrasound.

Characterization of oligomeric procyanidins and identification of quercetin glucuronide from lotus ( Nelumbo nucifera Gaertn.) seedpod.

Procyanidins are a class of polyphenols in the plant kingdom. Lotus ( Nelumbo nucifera Gaertn.) seedpods, the inedible part of lotus and a byproduct during the production of lotus seeds, were found to be a new source rich in procyanidins. Detailed information about oligomeric procyanidins in lotus seedpods remains unknown. In this study, lotus seedpods were extracted using 60% aqueous methanol and characterized with phloroglucinolysis and liquid chromatography (mass spectrometry with an electrospray ionization source). The results indicate that the oligomeric and polymeric fraction had a mean degree of polymerization of 3.2 and 15.4, respectively, and consisted of (+)-catechin (m/z 289), gallocatechin or epigallocatechin (m/z 305), quercetin glycoside (m/z 463), quercetin glucuronide (m/z 477), procyanidin dimers (m/z 577.1), proanthocyanidin dimer gallate (m/z 593.3), prodelphinidin dimers (m/z 609.1), procyanidin trimers (m/z 865.1), etc. Quercetin glucuronide was further purified using flash chromatography and identified as quercetin-3-O-ß-glucuronide by determining its exact mass using ion-trap time-of-flight mass spectrometry and ¹H and ¹³C nuclear magnetic resonance, ¹H-detected heteronuclear single-quantum coherence, and ¹H-detected heteronuclear multiple-bond correlation analyses.

[The relationship between endoplasmic reticulum stress and its particular apoptosis way caspase-12 and apoptosis in renal cortex of diabetic rats].

OBJECTIVE: To investigate the expressions of 78-kDa glucose-regulated protein (GRP78) and Caspase-12 and their relationship with apoptosis in renal cortex of diabetic rats. METHODS: Uninephrectomized Wistar rats were used to induce diabetes by intraperitoneal injection of Streptozotocin (STZ 65 mg/kg). After 8 weeks, the expression and distribution of GRP78, Caspase-12, proliferating cell nuclear antigen (PCNA) were examined by immunohistochemistry. Flow cytometry was used to detect the levels of protein of GRP78 and Caspase-12. Apoptosis was evaluated by means of terminal deoxynucleotidyl transferase-mediated d-UDP nick-end labeling (TUNEL) and Flow cytometry. Serum creatinine, blood urea nitrogen and 24-hour urine protein excretion were checked. RESULTS: Compared with those in normal control group, the numbers of apoptosis and the expression of GRP78, Caspase-12 in glomerular and tubular cells were much higher in the diabetic kidneys at 8 weeks. There was no significant difference between group A and group B. CONCLUSION: Activation of endoplasmic reticulum stress may play an important role in the development of diabetic nephropathy.

Surface wrinkling patterns on a core-shell soft sphere.

The three-dimensional patterns of surface wrinkling on a core-shell soft sphere are investigated through buckling and postbuckling analyses under differential tissue growth or shrinkage. With increasing deformation, the sphere first exhibits a buckyball-like wrinkling pattern and then undergoes a wrinkle-to-fold transition into labyrinth folded patterns, in agreement with experimental observations. This transition involves dynamic movement, rotation, and coalescence of polygons formed during the initial buckling.

The effects of Leu or Val residues on cell selectivity of α-helical peptides.

In this study, the peptides were designed to compare the effect of multiple Leu or Val residues as the hydrophobic side of an α-helical model on their structure, function, and interaction with model membranes. The Leu-rich peptides displayed 4- to 16-fold stronger antimicrobial activity than Val-rich peptides, while Val-containing peptides showed no haemolysis and weak cytotoxicity. The peptides LR and VR showed an α-helical-rich structure under a membranemimicking environment. Different cell selectivity for Leu- or Val-containing peptides correlated with the targeted cell membranes. The Leu-rich peptide LR(W) and Val-rich peptide VR(W) interacted preferentially with negatively charged phospholipids over zwitterionic phospholipids. VR(W) displayed no interaction with zwitterionic phospholipids, which was consistent with its lack of haemolytic activity. The ability of LR to depolarize bacterial cells was much greater than that of VR. Val- and Leu-rich peptides appeared to kill bacteria in a membrane-targeted fashion, with different modes of action. Leu-rich peptides appeared to be active via a membrane-disrupting mode, while Val-rich peptides were active via the formation of small channels.

Growth and surface folding of esophageal mucosa: a biomechanical model.

Mucosal folding in such biological vessels as esophagus and airway is essential to their physiological functions and can be affected by some diseases, e.g., inflammation, edema, lymphoma, and asthma. A biomechanical model within the framework of finite deformation theory is proposed to address the mucosal folding induced by the growth and residual stresses in the tissue. A hyperelastic constitutive law is adopted for the mucosal layer, which grows in a cylindrical lumen. The fields of the engendered displacements and residual stresses are solved analytically. Furthermore, the instability analysis predicts the folding number, which agrees well with our experimental observations. This study not only sheds light on the biomechanical mechanisms underlying mucosal folding but also provides a promising approach for determining the residual stress level in living tissues under different physiological or pathological conditions according to their folding features.

[The effect of Janus kinase 2 inhibitor AG490 on renal tubular epithelial-myofibroblast transdifferentiation induced by interleukin-1ß].

OBJECTIVE: To investigate the effect of AG490, a Janus kinase 2 inhibitor, on epithelial-myofibroblast transdifferentiation induced by interleukin-1ß (IL-1ß). METHODS: Cultured human renal tubular epithelial cell line (HKCs) were divided into three groups: blank control group, IL-1ß (5 ng/ml) group and AG490 group (IL-1ß 5 ng/ml+AG490 10 µmol/L). The cells in all groups were collected at 24, 48, 72 hours after intervention. Immunocytochemistry and Western blotting analysis were used to determine the expressions of cytokeratin-18 (CK-18) and α-smooth muscle actin (α-SMA). RESULTS: The higher expression of CK-18 (1.25±0.08) and mild expression of α-SMA (0.17±0.01) were found in blank control group. In IL-1ß group, the protein level of CK-18 was gradually decreased with prolongation of stimulus (24 hours : 0.69±0.04, 48 hours: 0.52±0.03, 72 hours: 0.30±0.01), while the expression level of α-SMA was gradually increased (24 hours: 0.56±0.04, 48 hours: 1.05±0.07, 72 hours: 1.43±0.07), and the difference between blank control group and IL-1ß group was statistically significant (all P<0.05). The administration of AG490 could restore the expression of CK-18 (24 hours: 1.07±0.07, 48 hours: 0.93±0.06, 72 hours: 0.83±0.06), and inhibit the expression of α-SMA induced by IL-1ß (24 hours: 0.33± 0.01, 48 hours: 0.52±0.01, 72 hours: 0.61±0.04). There was significant difference between AG490 group and IL-1ß group (all P<0.05). The results of immunocytochemistry and that of Western blotting were identical. CONCLUSION: IL-1ß can induce the transdifferentiation of renal tubular epithelial cells, up-regulate the expression of α-SMA, induce the renal tubular epithelial cells to transform to myofibroblast, while AG490 can inhibit the effect of IL-1ß.

Surface effects in various bending-based test methods for measuring the elastic property of nanowires.

The size-dependent elastic property of nanowires induced by the surface effect is investigated by using the core-shell model. The overall effective elastic moduli of nanowires with regular polygonal cross-sections are unified into a simple and explicit relation. It is found that the effect of surface elasticity on the elastic moduli can be well characterized by two dimensionless material and geometric parameters with clear physical meaning. Finite element simulations demonstrate that the derived theoretical relation is applicable for all the vibration, bending, and buckling test methods for measuring the mechanical properties of nanowires. The analytical result is also validated by comparing it with relevant experimental measurements. This study is helpful not only for interpreting various phenomena associated with size-dependent mechanical properties of nanowires but also for developing and evaluating test techniques for material characterization at the nanoscale.

Diethyl 4-[4-(dimethyl-amino)phen-yl]-2,6-dimethyl-1,4-dihydro-pyridine-3,5-dicarboxyl-ate.

In the title compound, C(21)H(28)N(2)O(4), the dihydro-pyridine ring adopts a flattened boat conformation. The mean plane of the dihydro-pyridine ring and the attached benzene ring form a dihedral angle of 85.1 (1) Å. One of two ethyl fragments is disordered between two conformations in a 0.67 (4):0.33 (4) ratio. In the crystal structure, mol-ecules related by translation along the a axis are linked into chains via inter-molecular N-H⋯O hydrogen bonds.

[Expression and implication of osteopontin in renal cortex of diabetic rats].

OBJECTIVE: To investigate the expression and implication of osteopontin (OPN) in renal cortex of diabetic rats. METHODS: Experimental diabetes was reproduced in uninephrectomized rats by giving streptozotocin (STZ). The animals were divided into two groups: control group and diabetic group (each n=24). Immunohistochemistry and Western blotting were used to detect the protein expression of OPN, CD68, and proliferating cell nuclear antigen (PCNA). At the same time the mRNA expression of OPN was detected by in situ hybridization. RESULTS: Compared with control group, blood glucose, blood urea nitrogen (BUN), 24-hour urine protein quantum and quantification of OPN protein significantly increased while creatinine clearance rate (CCr) was significantly decreased in diabetic rat group 1, 2, 4 and 8 weeks after STZ injection. The protein of PCNA were also higher than that of control group 1 and 2 weeks after STZ injection (all P<0.05), and the increase in CD68 was observed at week 4 and week 8. CONCLUSION: Overexpression of OPN may be responsible for the proliferation of tubular cells at early stage of diabetic nephropathy and for the accumulation of macrophage at later stage.