Comparison of effectiveness and safety of Da Vinci robot's "3 + 1" and "4 + 1" modes of treatment for colorectal cancer.

To compare the effectiveness of the Da Vinci Surgical Robot System (DSRS) "3 + 1" and "4 + 1" models for colorectal cancer (CRC). A total of 107 patients with CRC admitted to our hospital from February 2021 to May 2022 were selected for the retrospective analysis. Of these, 57 patients underwent the DSRS "4 + 1" model (control group), while the rest 50 underwent the DSRS "3 + 1" model (research group). The operation time, intraoperative bleeding, number of lymph nodes detected, time of first postoperative urinary catheter removal, time of first feeding, time of first venting and hospitalization were compared between the two groups. The changes of white blood cell (WBC) and C-reactive protein (CRP) levels before and after surgery were detected, and patients' adverse effects and treatment costs between surgery and hospital discharge were counted. The Self-Rating Anxiety Scale (SAS) and the Self-Rating Depression Scale (SDS) were used to assess the psychological state of the patients. There was no difference in operative time, intraoperative bleeding, and number of lymph nodes detected between both groups (P > 0.05), while time to first postoperative urinary catheter removal, time to first feeding, time to first venting, length of stay (LOS), postoperative inflammatory factor levels, incidence of adverse events, and treatment costs were all lower in the research group than in the control group (P < 0.05). SAS and SDS scores decreased after treatment in both groups, but the decrease was more obvious in the research group (P < 0.05). Both DSRS "4 + 1" and "3 + 1" modes have better treatment effects for CRC. However, the "3 + 1" mode has higher safety and lower treatment cost, which can significantly improve the postoperative recovery process of patients and is more worthy to be promoted in clinical practice.

Glycine-ß-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male Cyp2c70 Knockout Mice.

Cyp2c70 knockout mice lack the enzyme that produces muricholic acids and show a "human-like" hydrophobic bile acid pool-induced hepatobiliary injury. In this study, we investigated the potential anti-cholestasis effect of glycine-conjugated ß muricholic acid (G-ß-MCA) in male Cyp2c70 KO mice based on its hydrophilic physiochemical property and signaling property as an farnesoid X receptor (FXR) antagonist. Our results showed that G-ß-MCA treatment for 5 weeks alleviated ductular reaction and liver fibrosis and improved gut barrier function. Analysis of bile acid metabolism suggested that exogenously administered G-ß-MCA was poorly absorbed in the small intestine and mostly deconjugated in the large intestine and converted to taurine-conjugated MCA (T-MCA) in the liver, leading to T-MCA enrichment in the bile and small intestine. These changes decreased the biliary and intestine bile acid hydrophobicity index. Furthermore, G-ß-MCA treatment decreased intestine bile acid absorption via unknown mechanisms, resulting in increased fecal bile acid excretion and a reduction in total bile acid pool size. In conclusion, G-ß-MCA treatment reduces the bile acid pool size and hydrophobicity and improves liver fibrosis and gut barrier function in Cyp2c70 KO mice.

SIRT4 is an independent prognostic factor in bladder cancer and inhibits bladder cancer growth by suppressing autophagy.

BACKGROUND: Nucleosome-localized sirtuin 4 (SIRT4) was found to function as an oncogene and tumor suppressor gene in different tumors. However, the clinical significance of SIRT4 in bladder urothelial carcinoma (BLCA) has not been assessed, nor has the function of SIRT4 in BLCA been analyzed. METHODS: In this study, we assessed the levels of SIRT4 protein in BLCA tissues and its association with clinicopathological parameters and overall survival time of BLCA patients by immunohistochemical staining of tissue microarrays containing 59 BLCA patients. Then, we constructed BLCA cell lines (T24) with overexpression or interference of SIRT4 by lentiviral infection. The effects of SIRT4 on the proliferation, migration and invasive ability of T24 cells were investigated using cell counting kit-8 (CCK-8) assays, wound healing assays, and migration and invasion assays. Moreover, we also investigated the effect of SIRT4 on the cell cycle and apoptosis of T24 cells. Mechanistically, we explored the relationship between SIRT4 and autophagy and its role in the inhibition of BLCA. RESULTS: We found by immunohistochemistry that SIRT4 protein levels were reduced in BLCA and that lower SIRT4 levels were associated with larger tumor volumes, later T-staging and later AJCC staging in BLCA patients and were an independent prognostic factor in BLCA patients. Overexpression of SIRT4 significantly inhibited the proliferative viability, scratch healing capacity, migratory capacity, and invasive capacity of T24 cells, while interference with SIRT4 had the opposite effect. Moreover, overexpression of SIRT4 significantly inhibited the cell cycle and increased the apoptosis rate of T24 cells. Mechanistically, SIRT4 inhibits BLCA growth by suppressing autophagic flow. CONCLUSIONS: Our study suggests that SIRT4 is an independent prognostic factor for BLCA and that SIRT4 plays a tumor suppressor role in BLCA. This suggests a potential target for SIRT4 in the diagnosis and treatment of BLCA.

Combining ASBT inhibitor and FGF15 treatments enhances therapeutic efficacy against cholangiopathy in female but not male Cyp2c70 KO mice.

Therapeutic reduction of hydrophobic bile acids exposure is considered beneficial in cholestasis. The Cyp2c70 KO mice lack hydrophilic muricholic acids and have a human-like hydrophobic bile acid pool resulting in hepatobiliary injury. This study investigates if combining an apical sodium-dependent bile acid transporter inhibitor GSK2330672 (GSK) and fibroblast growth factor-15 (FGF15) overexpression, via simultaneous inhibition of bile acid synthesis and gut bile acid uptake, achieves enhanced therapeutic efficacy in alleviating hepatobiliary injury in Cyp2c70 KO mice. The effects of GSK, adeno-associated virus (AAV)-FGF15, and the combined treatment on bile acid metabolism and cholangiopathy were compared in Cyp2c70 KO mice. In female Cyp2c70 KO mice with more severe cholangiopathy than male Cyp2c70 KO mice, the combined treatment was more effective in reversing portal inflammation, ductular reaction, and fibrosis than AAV-FGF15, while GSK was largely ineffective. The combined treatment reduced bile acid pool by ∼80% compared to ∼50% reduction by GSK or AAV-FGF15, and enriched tauro-conjugated ursodeoxycholic acid in the bile. Interestingly, the male Cyp2c70 KO mice treated with AAV-FGF15 or GSK showed attenuated cholangiopathy and portal fibrosis but the combined treatment was ineffective despite reducing bile acid pool. Both male and female Cyp2c70 KO mice showed impaired gut barrier integrity. AAV-FGF15 and the combined treatment, but not GSK, reduced gut exposure to lithocholic acid and improved gut barrier function. In conclusion, the combined treatment improved therapeutic efficacy against cholangiopathy than either single treatment in the female but not male Cyp2c70 KO mice by reducing bile acid pool size and hydrophobicity.

Effects of three glutenins extracted in acidic, neutral and alkaline urea solutions on the retrogradation of wheat amylose and amylopectin.

Three glutenins (glutenin 1, glutenin 2, and glutenin 2) were extracted in acidic, neutral and alkaline urea solutions respectively. All of the three glutenins are rich in glutamic acid (Glu, >30 %) and proline (Pro, >20 %). Glutenin 1, extracted at pH 5, shows higher contents of hydrophilic amino acids as serine (Ser, 5.25 %), aspartic acid (Asp, 2.99 %), tyrosine (Tyr, 3.11 %), arginine (Arg, 2.09 %) and threonine (Thr, 2.11 %) than the other two glutenins. The retrogradation of three glutenins with amylose/amylopectin indicated that glutenin 1 showed significant inhibition effect on the retrogradation of wheat amylose. The characterizations of amylose retrograded with glutenin 1 by FT-IR, XRD, DSC and solid 13C NMR showed that new hydrogen bonds between Glu, Tyr and wheat amylose were formed, which prevented the formation of hydrogen bonds between amylose themselves. Glycosidic bonds between some hydroxyl groups of C6 in wheat amylose and certain hydroxyl groups of Ser and Thr in glutenin with specific chain length were present. The macromolecules with steric hindrance prevented the rearrangement of amylose into regular crystals. The retrogradation of wheat amylose was inhibited in this way. This study provides a key targeting step to control the retrogradation of amylose.

Effects of Amylopectins from Five Different Sources on Disulfide Bond Formation in Alkali-Soluble Glutenin.

Wheat, maize, cassava, mung bean and sweet potato starches have often been added to dough systems to improve their hardness. However, inconsistent effects of these starches on the dough quality have been reported, especially in refrigerated dough. The disulfide bond contents of alkali-soluble glutenin (ASG) have direct effects on the hardness of dough. In this paper, the disulfide bond contents of ASG were determined. ASG was mixed and retrograded with five kinds of amylopectins from the above-mentioned botanical sources, and a possible pathway of disulfide bond formation in ASGs by amylopectin addition was proposed through molecular weight, chain length distribution, FT-IR, 13C solid-state NMR and XRD analyses. The results showed that when wheat, maize, cassava, mung bean and sweet potato amylopectins were mixed with ASG, the disulfide bond contents of alkali-soluble glutenin increased from 0.04 to 0.31, 0.24, 0.08, 0.18 and 0.29 µmol/g, respectively. However, after cold storage, they changed to 0.55, 0.16, 0.26, 0.07 and 0.19 µmol/g, respectively. The addition of wheat amylopectin promoted the most significant disulfide bond formation of ASG. Hydroxyproline only existed in the wheat amylopectin, indicating that it had an important effect on the disulfide bond formation of ASG. Glutathione disulfides were present, as mung bean and sweet potato amylopectin were mixed with ASG, and they were reduced during cold storage. Positive/negative correlations between the peak intensity of the angles at 2θ = 20°/23° and the disulfide bond contents of ASG existed. The high content of hydroxyproline could be used as a marker for breeding high-quality wheat.

Two-dimensional natural hyperbolic materials: from polaritons modulation to applications.

Natural hyperbolic materials (HMs) in two dimensions (2D) have an extraordinarily high anisotropy and a hyperbolic dispersion relation. Some of them can even sustain hyperbolic polaritons with great directional propagation and light compression to deeply sub-wavelength scales due to their inherent anisotropy. Herein, the anisotropic optical features of 2D natural HMs are reviewed. Four hyperbolic polaritons (i.e., phonon polaritons, plasmon polaritons, exciton polaritons, and shear polaritons) as well as their generation mechanism are discussed in detail. The natural merits of 2D HMs hold promise for practical quantum photonic applications such as valley quantum interference, mid-infrared polarizers, spontaneous emission enhancement, near-field thermal radiation, and a new generation of optoelectronic components, among others. The conclusion of these analyses outlines existing issues and potential interesting directions for 2D natural HMs. These findings could spur more interest in anisotropic 2D atomic crystals in the future, as well as the quick generation of natural HMs for new applications.

Three-dimensional reconstruction from a fringe projection system through a planar transparent medium.

A vision measurement system is placed in a protective cover made of a transparent medium to avoid environmental influences. Due to the deflection of light rays on the front and rear surfaces of the transparent medium, the imaging position of an object on the camera target plane is deviated, which makes the traditional vision detection methods based on the triangulation principle produce large measurement errors. This work introduces a three-dimensional (3D) reconstruction method by fringe projection system through a planar transparent medium. We derive the coordinate transformation relationship between a real-object point and a pseudo-object point caused by light refraction based on Snell's law of flat refraction. Based on the relationship, a modified fringe projection method is proposed for unbiased 3D reconstruction. Two experiments, including 3D shape measurement of a white plate with ring markers and 3D shape measurement of a regular spherical object are conducted. The results demonstrate the effectiveness of the proposed method in such measurement environment.

A High-Accuracy Calibration Method for a Telecentric Structured Light System.

We propose a method for accurately calibrating a telecentric structured light system consisting of a camera attached to a bilateral telecentric lens and a pin-hole projector. The proposed method can be split into two parts: axial calibration and transverse calibration. The first part is used for building the relationship between phase and depth by means of a planar plate with ring markers on its surface at several different positions in the measuring volume. The second part is used for establishing the relationship between transverse coordinates and pixel positions with the depth offered by a translation stage and the extracted ring centers. Compared with existing methods that require projector calibration, the proposed method can avoid a propagation of the correspondence error between the camera imaging plane and projector imaging plane, thus increasing calibration accuracy. The calibrated telecentric structured light system is further used for three-dimensional (3D) reconstructions of a planar, a ruled surface, and complex surfaces. Experimental results demonstrate that the proposed system calibration method can be used for accurate 3D measurement.

TFEB regulates sulfur amino acid and coenzyme A metabolism to support hepatic metabolic adaptation and redox homeostasis.

Fatty liver is a highly heterogenous condition driven by various pathogenic factors in addition to the severity of steatosis. Protein insufficiency has been causally linked to fatty liver with incompletely defined mechanisms. Here we report that fatty liver is a sulfur amino acid insufficient state that promotes metabolic inflexibility via limiting coenzyme A availability. We demonstrate that the nutrient-sensing transcriptional factor EB synergistically stimulates lysosome proteolysis and methionine adenosyltransferase to increase cysteine pool that drives the production of coenzyme A and glutathione, which support metabolic adaptation and antioxidant defense during increased lipid influx. Intriguingly, mice consuming an isocaloric protein-deficient Western diet exhibit selective hepatic cysteine, coenzyme A and glutathione deficiency and acylcarnitine accumulation, which are reversed by cystine supplementation without normalizing dietary protein intake. These findings support a pathogenic link of dysregulated sulfur amino acid metabolism to metabolic inflexibility that underlies both overnutrition and protein malnutrition-associated fatty liver development.

Temperature-dependent circular conversion dichroism from chiral metasurfaces patterned in Dirac semimetal Cd3As2.

Chiral metasurfaces patterned with L-shaped holes in a thin film of Dirac semimetal Cd3As2 are designed. The impact of temperature T on circular conversion dichroism, mainly characterized by circular polarization differential transmittance (CPDT), is studied by rigorous coupled-wave analysis. The results show that decreasing T will give rise to the appearance of much more narrow CPDT peaks and dips, and the maximum differential transmittance between two opposite circularly polarized light can reach above 0.60 by optimizing the structural parameters at 80 K. As the T increases, the differential transmittance gradually decreases, and the CPDT peak and dip values exhibit variation tendencies of 'Z' and 'S' types, respectively. Two simple formulae of CPDT extreme values with respect to T are derived, predicting that the decreasing tendency will reach saturation when T ≥ 500 K. Differing from the wavelength-independent variation trend of differential transmittance, CPDT extremum positions mainly show a blueshift (redshift) tendency at the wavelength λ > 10 µm (λ < 5 µm) as the T increases. Moreover, evolutions of CPDT with various factors including the thickness of Cd3As2, incident and azimuth angles are also clearly unveiled.

Combined ASBT Inhibitor and FGF15 Treatment Improves Therapeutic Efficacy in Experimental Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: Pharmacologic agents targeting bile acid signaling show promise for treating nonalcoholic steatohepatitis (NASH). However, clinical findings suggest that new treatment strategies with enhanced therapeutic efficacy and minimized undesired effects are needed. This preclinical study investigates whether combining an apical sodium-bile acid transporter (ASBT) inhibitor GSK233072 (GSK672) and fibroblast growth factor-15 (FGF15) signaling activation improves anti-NASH efficacy. METHODS: Mice with high fat, cholesterol, and fructose (HFCFr) diet-induced NASH and stage 2 fibrosis are used as a NASH model. GSK672 or AAV8-TBG-FGF15 interventions are administered alone or in combination to HFCFr diet-fed mice. RESULTS: The combined treatment significantly enhances therapeutic efficacy against steatosis, inflammation, ballooning, and fibrosis than either single treatment. Mechanistically, the synergistic actions of GSK672 and FGF15 on inhibiting gut bile acid reuptake and hepatic bile acid synthesis achieve greater magnitude of bile acid pool reduction that not only decreases bile acid burden in NASH livers but also limits intestinal lipid absorption, which, together with FGF15 signaling activation, produces weight loss, reduction of adipose inflammation, and attenuated hepatocellular organelle stress. Furthermore, the combined treatment attenuates increased fecal bile acid excretion and repressed bile acid synthesis, which underlie diarrhea and hypercholesterolemia associated with ASBT inhibition and FGF19 analogue, respectively, in clinical settings. CONCLUSIONS: Concomitant ASBT inhibition and FGF15 signaling activation produce metabolic changes that partially mimic the bariatric surgery condition whereby lipid malabsorption and increased FGF15/19 signaling synergistically mediate weight loss and metabolic improvement. Further clinical studies may be warranted to investigate whether combining ASBT inhibitor and FGF19 analogue enhances anti-NASH efficacy and reduced treatment-associated adverse events in humans.

Gut-restricted apical sodium-dependent bile acid transporter inhibitor attenuates alcohol-induced liver steatosis and injury in mice.

BACKGROUND: Recent studies have shown that human and experimental alcohol-related liver disease (ALD) is robustly associated with dysregulation of bile acid homeostasis, which may in turn modulate disease severity. Pharmacological agents targeting bile acid metabolism and signaling may be potential therapeutics for ALD. METHODS: The potential beneficial effects of a gut-restricted apical sodium-dependent bile acid transporter (ASBT) inhibitor were studied in a chronic-plus-binge ALD mouse model. RESULTS: Blocking intestinal bile acid reabsorption by the gut-restricted ASBT inhibitor GSK2330672 attenuated hepatic steatosis and liver injury in a chronic-plus-binge ALD mouse model. Alcohol feeding is associated with intestinal bile acid accumulation but paradoxically impaired ileal farnesoid × receptor (FXR) function, and repressed hepatic cholesterol 7α-hydrolase (CYP7A1) expression despite decreased hepatic small heterodimer partner (SHP) and ileal fibroblast growth factor 15 (FGF15) expression. ASBT inhibitor treatment decreased intestinal bile acid accumulation and increased hepatic CYP7A1 expression, but further decreased ileal FXR activity. Alcohol feeding induces serum bile acid concentration that strongly correlates with a liver injury marker. However, alcohol-induced serum bile acid elevation is not due to intrahepatic bile acid accumulation but is strongly and positively associated with hepatic multidrug resistance-associated protein 3 (MRP4) and MRP4 induction but poorly associated with sodium-taurocholate cotransporting peptide (NTCP) expression. ASBT inhibitor treatment decreases serum bile acid concentration without affecting hepatocyte basolateral bile acid uptake and efflux transporters. CONCLUSION: ASBT inhibitor treatment corrects alcohol-induced bile acid dysregulation and attenuates liver injury in experimental ALD.

Hyperspectral Imaging for the Nondestructive Quality Assessment of the Firmness of Nanguo Pears Under Different Freezing/Thawing Conditions.

Firmness changes in Nanguo pears under different freezing/thawing conditions have been characterized by hyperspectral imaging (HSI). Four different freezing/thawing conditions (the critical temperatures, numbers of cycles, holding time and cooling rates) were set in this experiment. Four different pretreatment methods were used: multivariate scattering correction (MSC), standard normal variate (SNV), Savitzky-Golay standard normal variate (S-G-SNV) and Savitzky-Golay multiplicative scattering correction (S-G-MSC). Combined with competitive adaptive reweighted sampling (CARS) to identify characteristic wavelengths, firmness prediction models of Nanguo pears under different freezing/thawing conditions were established by partial least squares (PLS) regression. The performance of the firmness model was analyzed quantitatively by the correlation coefficient (R), the root mean square error of calibration (RMSEC), the root mean square error of prediction (RMSEP) and the root mean square error of cross validation (RMSECV). The results showed that the MSC-PLS model has the highest accuracy at different cooling rates and holding times; the correlation coefficients of the calibration set (Rc) were 0.899 and 0.927, respectively, and the correlation coefficients of the validation set (Rp) were 0.911 and 0.948, respectively. The accuracy of the SNV-PLS model was the highest at different numbers of cycles, and the Rc and the Rp were 0.861 and 0.848, respectively. The RMSEC was 65.189, and the RMSEP was 65.404. The accuracy of the S-G-SNV-PLS model was the highest at different critical temperatures, with Rc and Rp values of 0.854 and 0.819, respectively, and RMSEC and RMSEP values of 74.567 and 79.158, respectively.

Study on Optimization Technology to Strengthen Ni-Based Composite Coating Electroplate Containing Nanodiamond.

Ni-based composite coating containing nanodiamonds was deposited on the substrate of Q235A low-carbon steel in a traditional Watts solution, without any additive. The nanodiamond grains prepared by detonation synthesis were measured by Transmission electron microscope (TEM) and X-ray diffraction (XRD). The electrochemical behavior of Ni2+ ion in the composite bath including nanodiamonds was studied by linear sweep voltammetry experiments, and the morphology, elastic modulus, and hardness of Ni-based composite coating were characterized using Scanning Electron microscope (SEM) and the nano-indenter XP tester. Effects of the nanodiamond concentration in the bath, stirring speed, and the electroplate mode on the properties of Ni-based composite coating were investigated. The results show that the reduction of Ni2+ ion in the electroplating process increased initially, and then decreased as the nanodiamond concentration in the bath increased from 4 g/L to 16 g/L, irrespective of whether direct current (DC), single-pulse, or double-pulse electroplating mode was used. The highest over-potential could be obtained when the nanodiamond concentration in the bath was 8 g/L. Moreover, the hardness and elastic modulus of the composite coating prepared by the DC electroplating mode were 4.68 and 194.30 GPa, respectively. By using the same plating parameters, the coating prepared by the double-pulse electroplating mode showed better properties, with hardness and elastic modulus values of 5.22 and 197.38 GPa, respectively.

Hyperspectral Imaging for Evaluating Impact Damage to Mango According to Changes in Quality Attributes.

Evaluation of impact damage to mango (Mangifera indica Linn) as a result of dropping from three different heights, namely, 0.5, 1.0 and 1.5 m, was conducted by hyperspectral imaging (HSI). Reflectance spectra in the 900⁻1700 nm region were used to develop prediction models for pulp firmness (PF), total soluble solids (TSS), titratable acidity (TA) and chroma (∆b*) by a partial least squares (PLS) regression algorithm. The results showed that the changes in the mangoes' quality attributes, which were also reflected in the spectra, had a strong relationship with dropping height. The best predictive performance measured by coefficient of determination (R²) and root mean square errors of prediction (RMSEP) values were: 0.84 and 31.6 g for PF, 0.9 and 0.49 oBrix for TSS, 0.65 and 0.1% for TA, 0.94 and 0.96 for chroma, respectively. Classification of the degree of impact damage to mango achieved an accuracy of more than 77.8% according to ripening index (RPI). The results show the potential of HSI to evaluate impact damage to mango by combining with changes in quality attributes.

TLR2 expression doesn't change in ox-LDL mediated inflammation in Human umbilical vein endothelial cells under high glucose culture.

BACKGROUND: Inflammatory responses induced by ox-LDL play important roles in atherogenesis, and could be promoted in diabetic patients. Toll-like receptor (TLR)2 is an innate inflammatory receptor, and is enhanced in human umbilical vein endothelial cells (HUVECs) under high glucose conditions. Ox-LDL-TLR2 pathway activation and further inflammation in monocytes are involved in the atherosclerosis formation. OBJECTIVE: What role of TLR2 plays on ox-LDL-induced inflammation in HUVECs remains unclear, especially in high glucose conditions. The purpose of this study is to explore the effect and role of ox-LDL-TLR2 pathway on the inflammatory responses in HUVECs. METHODS: 1 hour prior to the treatment, HUVECs were treated with or without neutralizing anti-TLR2 antibody. After that, HUVECs were treated with ox-LDL (20, or 40 µg/ml) or LPS (200 ng/ml) under normal and high glucose conditions. The expressions of ICAM-1 and TLR2 protein were analyzed by immunoblotting, and IL-6 and IL-8 were measured by ELISA. RESULTS: Compared with those in normal glucose condition, IL-6 and IL-8 expression were increased in high glucose condition. The stimulation of ox-LDL and LPS both increased the expression of ICAM-1, IL-6 and IL-8, but did not change TLR2 protein expression in both normal and high glucose conditions. Additionally, the expression of ICAM-1, IL-6 and IL-8 was not changed when TLR2 was knocked out under these two conditions. CONCLUSION: The inflammatory responses induced by Ox-LDL were not changed with or without TLR2 under both normal and high glucose conditions in HUVECs. Our study indicates TLR2 is not involved in the ox-LDL mediated endothelial injury under high glucose conditions, which is an important step of atherosclerosis formation in diabetes.

Damage properties simulations of self-healing composites.

Self-healing materials are inspired by biological systems in which damage triggers an autonomic healing response. The damage properties of a self-healing polymer composite were investigated by numerical simulation in this paper. Unit cell models with single-edge centered crack and single-edge off-centered crack were employed to investigate the damage initiation and crack evolution by the extended finite element method (XFEM) modeling. The effect of microcapsule's Young's modulus on composites was investigated. Result indicates the microcapsule's Young's modulus has little effect on the unit cell's carrying capacity. It was found that during the crack propagation process, its direction is attracted toward the microcapsules, which makes it helpful for the microcapsules to be ruptured by the propagating crack fronts resulting in release of the healing agent into the cracks by capillary action.

Carcinine has 4-hydroxynonenal scavenging property and neuroprotective effect in mouse retina.

PURPOSE: Oxidative stress induces retinal damage and contributes to vision loss in progressive retinopathies. Carcinine (ß-alanyl-histamine) is a natural imidazole-containing peptide derivative with antioxidant activity. It is predicted to scavenge 4-hydroxynonenal (4-HNE), a toxic product of lipid oxidation. The aim of this study was to confirm the 4-HNE scavenging effect and evaluate the neuroprotective effect of carcinine in mouse retina subjected to oxidative stress. METHODS: HPLC coupled with mass spectrometry was used to analyze carcinine and 4-HNE-carcinine adduct. Protection of retinal proteins from modification by 4-HNE was tested by incubating carcinine with retinal protein extract and 4-HNE. Modified retinal proteins were quantified by dot-blot analysis. Mice were treated with carcinine (intravitreal injection and gavage) and exposed to bright light to induce oxidative damage in the retina. Photoreceptor degeneration was measured by histology and electroretinography. Retinal levels of retinol dehydrogenase 12 (RDH12) were measured by immunoblot analysis, after exposure to bright light and in retinal explants after exposure to 4-HNE. RESULTS: The ability of carcinine to form an adduct with 4-HNE, as well as to prevent and even reverse the adduction of retinal proteins by the toxic aldehyde was demonstrated in vitro. Carcinine, administered by intravitreal injection or gavage, strongly protected mouse retina against light-induced photoreceptor degeneration and had a protective effect on RHD12, a protein found specifically in photoreceptor cells. CONCLUSIONS: This study suggests that carcinine can be administered noninvasively to efficiently protect photoreceptor cells from oxidative damage. Carcinine could be administered daily to prevent vision loss in progressive retinopathies.