Highly accurate disease diagnosis and highly reproducible biomarker identification with PathFormer.

Biomarker identification is critical for precise disease diagnosis and understanding disease pathogenesis in omics data analysis, like using fold change and regression analysis. Graph neural networks (GNNs) have been the dominant deep learning model for analyzing graph-structured data. However, we found two major limitations of existing GNNs in omics data analysis, i.e., limited-prediction/diagnosis accuracy and limited-reproducible biomarker identification capacity across multiple datasets. The root of the challenges is the unique graph structure of biological signaling pathways, which consists of a large number of targets and intensive and complex signaling interactions among these targets. To resolve these two challenges, in this study, we presented a novel GNN model architecture, named PathFormer, which systematically integrate signaling network, priori knowledge and omics data to rank biomarkers and predict disease diagnosis. In the comparison results, PathFormer outperformed existing GNN models significantly in terms of highly accurate prediction capability (~30% accuracy improvement in disease diagnosis compared with existing GNN models) and high reproducibility of biomarker ranking across different datasets. The improvement was confirmed using two independent Alzheimer's Disease (AD) and cancer transcriptomic datasets. The PathFormer model can be directly applied to other omics data analysis studies.

Comparison of biochemical characteristics and gel properties of chicken myofibrillar protein affected by heme-iron and nonheme-iron oxidizing systems.

In this study, the effect of hemin and non-heme iron on the biochemical and gelling properties of chicken myofibrillar protein (MP) was compared. Results revealed that free radicals from hemin incubated MP were significantly higher than that in FeCl3 incubated samples (P < 0.05), and had higher ability to initiate protein oxidation. The carbonyl content, surface hydrophobicity, random coil increased with oxidant concentration, whereas the total sulfhydryl and α-helix content decreased in both oxidizing systems. The turbidity and particle size were increased after oxidant treatment, indicating oxidation promoted the cross-linking and aggregation of protein, and the degree of aggregation was higher in hemin treated MP compared with that incubated with FeCl3. The biochemical changes of MP resulted in an uneven and loose gel network structure, which significantly reduced the gel strength and water holding capacity (WHC) of the gel.

Proteomic Analysis of Potential Targets for Non-Response to Infliximab in Patients With Ulcerative Colitis.

Background: Infliximab (IFX) is a potent therapeutic agent used for the treatment of conventional refractory ulcerative colitis (UC). However, the high non-response rate of IFX brings difficulties to clinical applications. In the context of proteomics research, our study of differentially expressed proteins (DEPs) is essential for non-response to IFX in UC patients and provides powerful insights into underlying drug resistance mechanisms. Methods: A total of 12 UC patients were divided into responders to IFX (UCinfG), non-responders to IFX (UCinfL), severe UC (UCsevere) without an IFX treatment history, and mild UC (UCmild) without an IFX treatment history. Subsequently, DEPs were identified from intestinal biopsy tissue between responders and non-responders to IFX by a label-free proteomic quantitative approach, and the general principle of functional protein screening was followed to deduce the potential drug targets and predictors for non-response to IFX in UC patients. Meanwhile, these targets excluded DEPs caused by the severity of inflammation for the first time. The differential expressions of candidate protein targets were validated at the gene sequence level using GEO2R analysis of the GEO database and qRT-PCR in some independent cohorts. Results: A total of 257 DEPs were screened out by mass spectrometry between UCinfG and UCinfL groups, excluding 22 DEPs caused by the severity of inflammation, and compared and verified at the gene sequence level in the Gene Expression Omnibus (GEO) database. Finally, five DEPs, including ACTBL2 (Q562R1), MBL2 (P11226), BPI (P17213), EIF3D (O15371), and CR1 (P17927), were identified as novel drug targets and predictive biomarkers for non-response to IFX. The drug targets were confirmed in the GEO database of the microarray results from three independent cohorts of 70 human intestinal biopsies and validated in qPCR data from 17 colonic mucosal biopsies. Among them, CR1 might affect the activation of the lectin pathway via complement-coated bacteria to play an opsonizing role in inflammation-related pathways closely associated with non-responders to IFX. Conclusion: This is the first report of proteomics analysis for the identification of novel drug targets based on intestinal biopsy tissue, which is significant for hypotheses for mechanistic investigation that are responsible for non-response to IFX and the development of clinical new pharmaceutical drugs.

Capsule endoscopy with retention of 4 years: A case report.

INTRODUCTION AND IMPORTANCE: Capsule endoscopy has been widely used in the diagnosis of small bowel diseases. Most CE can be smoothly excreted through the digestive tract. However, very few retention of CE may happen. CASE PRESENTATION: A 64-year-old man had been suffering from intermittent abdominal pain for 10 years. Capsule endoscopy was performed in local hospital 4 years ago. He was initially diagnosed with Crohn's disease and started on treatment. CTE and X-ray film of abdomen showed a suspected capsule endoscopy on the right side of pelvic cavity. Surgery was performed to remove the capsule. After the surgical treatment, no gastrointestinal symptoms relapsed for 9 months. CLINICAL DISCUSSION: It isn't uncommon for capsule endoscopy to be detained in Crohn's disease, because Strictures are the commonest complication of Crohn's disease. In order to prevent intestinal retention of capsule endoscopy, risk assessment should be carried out before capsule endoscopy. If detained CE isn't removed successfully by drug therapy and endoscopic therapy, surgery treatment has to be considered. CONCLUSION: In the present case, capsule endoscopy was found in the small intestine after 4 years, and the reason is worth pondering. We strongly recommend performing routine CTE, MRE and patency capsule examination before capsule endoscopy for patients suspected of stenosis. Routine abdominal X-ray film after examination is also useful for timely detection of capsule retention.

Exploring the regulating mechanism of heat induced gelation of myosin by binding with Mb hemin prosthetic group.

The properties, structure and water holding capacity of myosin were analyzed after incubated with myoglobin (Mb) hemin prosthetic group. The results revealed moderate oxidation of hemin prosthetic group could improve the solubility of myosin. Besides, it could stretch the protein structure and cross-link the molecules to form the soluble polymer. Hence, moderate oxidation could improve the gel properties and the gel network structure. However, excessive oxidation would greatly reduce the physical and chemical properties of myosin, which was not conducive to the gel formation and would lead to a decrease in water retention. Moreover, fluorescence spectroscopy and cyclic voltammetry (CV) proved hemin prosthetic group had a high affinity for myosin. The interaction mechanism was further studied by molecular docking and molecular dynamics (MD) simulations. This study provides some fundamental prospects to be applied in the functional regulation of meat protein.

Effect of myoglobin, hemin, and ferric iron on quality of chicken breast meat.

OBJECTIVE: The objective was to evaluate the impact of different forms of iron including myoglobin, hemin, and ferric chloride on the quality of chicken breast meat. METHODS: Chicken breast muscles were subjected to 1, 2, 3 mg/mL of FeCl3, myoglobin and hemin treatment respectively, and the production of reactive oxygen species (ROS) and malondialdehyde, meat color, tenderness, water holding capacity and morphology of meat was evaluated. RESULTS: Hemin was found to produce more ROS and induce greater extent of lipid oxidation than myoglobin and ferric chloride. However, it showed that hemin could significantly increase the redness and decrease the lightness of the muscle. Hemin was also shown to be prominent in improving water holding capacity of meat, maintaining a relatively higher level of the immobilized water from low-field nuclear magnetic resonance measurements. Morphology observation by hematoxylin-eosin staining further confirmed the results that hemin preserved the integrity of the muscle. CONCLUSION: The results indicated that hemin may have economic benefit for the industry based on its advantage in improving water holding capacity and quality of meat.

Chemo-enzymatic synthesis, characterization, in vitro antioxidant capacity and oxidative stability studies of novel phosphatidylcholines with ω-3/ω-6 PUFAs and phenolic acids.

Novel phosphatidylcholines containing PUFAs and phenolic acids were synthesized from egg phosphatidylcholine (PC), PUFAs (docosahexaenoic, arachidonic and linoleic acids) and phenolic acids (caffeic, ferulic and p-coumaric acids) as substrates. The structures of modified PCs were confirmed by spectral analysis and were evaluated for antioxidant activities. The modified PCs containing caffeic and ferulic acids exhibited excellent antioxidant activities compared with butylated hydroxytoluene (BHT) and α-tocopherol. The synthesized compounds were also evaluated for the oxidative stabilities in liposome and organic solvent. The modified PCs showed more oxidative stable compared with standard PUFA-PCs and PUFA-PCs + BHT. Results showed that the oxidative stability decreased with increasing degree of unsaturation in organic solvent whereas in liposomes, increased with increasing degree of unsaturation due to tight packed configuration. In this study, phenolic acids were found to render protections for PUFAs in modified PCs from oxidation. Modified PCs may have great potential for applications in food, cosmetic and pharmaceutical industries.

Lipid oxidation induced by heating in chicken meat and the relationship with oxidants and antioxidant enzymes activities.

The aim of the current research was to examine lipid oxidation in chicken meat heated to different temperatures followed by refrigerator storage and the factors contributing to lipid oxidation. It showed that lipid oxidation was significantly promoted when meat was heated up to 70°C and stored for 2 and 4 D as measured by thiobarbituric acid reactive substance. The monounsaturated fatty acids and polyunsaturated fatty acids also decreased significantly (P < 0.05) with the increase of heating temperature. The liberation of nonheme iron and increase of hydroxyl radical were observed in heated chicken meat, and the activities of antioxidant enzymes was decreased considerably at higher temperatures. The changes of these prooxidants and antioxidants might constitute a possible mechanism for the stronger lipid oxidation in heated meat.

The Effect of Temperature and Strain Rate on the Interfacial Behavior of Glass Fiber Reinforced Polypropylene Composites: A Molecular Dynamics Study.

To make better use of fiber reinforced polymer composites in automotive applications, a clearer knowledge of its interfacial properties under dynamic and thermal loadings is necessary. In the present study, the interfacial behavior of glass fiber reinforced polypropylene (PP) composites under different loading temperatures and strain rates were investigated via molecular dynamics simulation. The simulation results reveal that PP molecules move easily to fit tensile deformation at higher temperatures, resulting in a lower interfacial strength of glass fiber-PP interface. The interfacial strength is enhanced with increasing strain rate because the atoms do not have enough time to relax at higher strain rates. In addition, the non-bonded interaction energy plays a crucial role during the tensile deformation of composites. The damage evolution of glass fiber-PP interface follows Weibull's distribution. At elevated temperatures, tensile loading is more likely to cause cohesive failure because the mechanical property of PP is lower than that of the glass fiber-PP interface. However, at higher strain rates, the primary failure mode is interfacial failure because the strain rate dependency of PP is more pronounced than that of the glass fiber-PP interface. The relationship between the failure modes and loading conditions obtained by molecular dynamics simulation is consistent with the author's previous experimental studies.

Deep-learning model for predicting 30-day postoperative mortality.

BACKGROUND: Postoperative mortality occurs in 1-2% of patients undergoing major inpatient surgery. The currently available prediction tools using summaries of intraoperative data are limited by their inability to reflect shifting risk associated with intraoperative physiological perturbations. We sought to compare similar benchmarks to a deep-learning algorithm predicting postoperative 30-day mortality. METHODS: We constructed a multipath convolutional neural network model using patient characteristics, co-morbid conditions, preoperative laboratory values, and intraoperative numerical data from patients undergoing surgery with tracheal intubation at a single medical centre. Data for 60 min prior to a randomly selected time point were utilised. Model performance was compared with a deep neural network, a random forest, a support vector machine, and a logistic regression using predetermined summary statistics of intraoperative data. RESULTS: Of 95 907 patients, 941 (1%) died within 30 days. The multipath convolutional neural network predicted postoperative 30-day mortality with an area under the receiver operating characteristic curve of 0.867 (95% confidence interval [CI]: 0.835-0.899). This was higher than that for the deep neural network (0.825; 95% CI: 0.790-0.860), random forest (0.848; 95% CI: 0.815-0.882), support vector machine (0.836; 95% CI: 0.802-870), and logistic regression (0.837; 95% CI: 0.803-0.871). CONCLUSIONS: A deep-learning time-series model improves prediction compared with models with simple summaries of intraoperative data. We have created a model that can be used in real time to detect dynamic changes in a patient's risk for postoperative mortality.

The influence of ultrasound and adenosine 5'-monophosphate marination on tenderness and structure of myofibrillar proteins of beef

Objective: The aim was to investigate the influence of ultrasound and adenosine 5'-monophosphate (AMP) marination (UAMP) on tenderness and structure of myofibrillar proteins of beef. Methods: Five groups, the untreated meat (Control), deionized water marination (DW), ultrasound followed by DW (UDW), AMP marination (AMP), and ultrasound followed by AMP (UAMP) were studied. Myofibrillar fragmentation, cooking loss, shear force, thermograms, histological observation of meats and myofibrillar proteins properties were investigated in these different treatments. Results: The results showed that UAMP significantly increased MFI from 152 (control), 231 (AMP) and 307 (UDW) to 355 (P < 0.05), respectively. The lowest cooking loss, shear force and peak denaturation temperature were observed in UAMP. In histological observation, UDW and UAMP had more fragmented muscular bundles than the others. Furthermore, a drastic increase in α-helix and decrease in ß-sheet of myofibrillar proteins was observed in UAMP, implying the disaggregation of protein samples. The synchronous fluorescence spectra of myofibrillar proteins in UAMP suggested the combination of ultrasound and AMP could accelerate the unfolding molecular structure and destroying hydrophobic interactions. The results of circular dichroism and synchronous fluorescence spectra for myofibrillar proteins coincided with the microstructures of beef. Conclusion: The results indicate that ultrasound combined with AMP improved meat tenderness not only by disruption in muscle integrity, increasing water retention, but also altering their spatial structure of myofibrillar proteins.

Interaction of heat shock protein 90 B1 (Hsp90B1) with liposome reveals its potential role in protection the integrity of lipid membranes.

Heat shock proteins of 90kDa (Hsp90) are molecular chaperones essential for protein homeostasis. Besides chaperone activity, Hsp90 exhibits other cellular functions at membranes, yet how it interacts with membranes remains elusive. We report here that Hsp90B1 interacts with phospholipid membranes. We first cloned the full-length open reading frame of Hsp90B1 from Anas platyrhnchos (ApHsp90B1), and the gene was then heterologously expressed and purified. SPR analysis show the purified ApHsp90B1 interacts with phospholipid membranes with high affinity (KD 176±25nM), and the interaction occurs over a wide range of pH, which is especially distinct under acidic conditions. Tryptophan fluorescence and far-UV CD spectra studies find that the interaction of ApHsp90B1 with phospholipid membrane induces microenvironment changes of tryptophan residues and conformational change of some regions in ApHsp90B1, which might be the reason of its increased ATPase activity upon addition phospholipid vesicles. Importantly, the interaction of ApHsp90B1 with phospholipid vesicles significantly reduces lipolysis of the membrane phospholipid, suggesting that the interaction of Hsp90B1 with membrane could preserve membrane integrity. The present study therefore demonstrates for the first time that Hsp90B1 exhibits high affinity for phospholipid membrane and suggest Hsp90B1 play an important role in membrane-stabilizing via its interaction with membrane phospholipids.

The effect of adenosine 5'-monophosphate (AMP) on tenderness, microstructure and chemical-physical index of duck breast meat.

BACKGROUND: Adenosine 5'-monophosphate (AMP) is often used in meat and poultry soups as a flavor enhancer (flavor modifier), or as food additives for specific nutritional purposes. Our previous research as well as evidence from others showed that actomyosin could be dissociated into myosin and actin by AMP in extracted muscle solution. However, there is no report available on the application of AMP to dissociate actomyosin and to improve meat tenderness. The objectives of this study were to evaluate the effect of AMP on duck meat tenderness and other quality traits and to explore the mechanism of the action of AMP on meat tenderness. RESULTS: Duck breast muscle was treated with 0, 10, 20, 30, 40 mmol L(-1) AMP at 5 °C for 10 h and examined for shear force, microstructure, actomyosin dissociation, myofibril fragmentation index (MFI), pH, water content, cooking loss, CIE* color (L*, a*, b*), inosine monophosphate (IMP) and free amino acid (FAA) contents. Results showed that shear force, cooking loss, L* and b* of the muscles significantly decreased after AMP treatment (P < 0.05); actomyosin dissociation, MFI, pH, water content, fiber diameter, sarcomere length, IMP and ammonia significantly increased (P < 0.05); no significant change in a* or other FAA content was observed (P > 0.05), and muscle shrinkage in transverse and longitudinal directions were restrained after AMP treatment. CONCLUSION: The results suggest that AMP could notably improve meat tenderness, and this effect was probably mainly through increasing muscle pH, promoting actomyosin dissociation and disrupting the Z-line; meanwhile, the conversion of AMP to IMP may contribute to the flavor of meat.

Application and optimization of the tenderization of pig Longissimus dorsi muscle by adenosine 5'-monophosphate (AMP) using the response surface methodology.

Based on single factor experiments, NaCl concentration, adenosine 5'-monophosphate (AMP) concentration and temperature were selected as independent variables for a three-level Box-Behnken experimental design, and the shear force and cooking loss were response values for regression analysis. According to the statistical models, it showed that all independent variables had significant effects on shear force and cooking loss, and optimal values were at the NaCl concentration of 4.15%, AMP concentration of 22.27 mmol/L and temperature of 16.70°C, which was determined with three-dimensional response surface diagrams and contour plots. Under this condition, the observed shear force and cooking loss were 0.625 kg and 8.07%, respectively, exhibiting a good agreement with their predicted values, showing the good applicability and feasibility of response surface methodology (RSM) for improving pork tenderness. Compared with control pig muscles, AMP combined with NaCl treatment demonstrated significant effects on improvement of meat tenderness and reduction of cooking loss. Therefore, AMP could be regarded as an effective tenderization agent for pork.

Optimization of the Tenderization of Duck Breast Meat by Adenosine 5'-Monophosphate (AMP) using Response Surface Methodology.

This study aimed to characterize and optimize the tenderization condition of duck breast meat by adenosine 5'-monophosphate (AMP), with the aid of response surface methodology (RSM). The results showed that the optimal conditions for the tenderization of duck breast meat were at the NaCl concentration of 3.99 g/100 g, AMP concentration of 13.83 mmol/L, temperature of 15.32°C, and marinating time of 8 h. Compared with control duck breast meat, AMP combined with NaCl treatment demonstrated significant effects on improvement of meat tenderness and decrease of cooking loss. Such effects might be ascribed to the combination of a series of biochemical reactions, e.g. increase of muscle pH, dissociation of actomyosin and inhibition of meat shrinkage. Therefore, the mixture of AMP and NaCl could be regarded as an effective tenderization agent for duck breast meat.

Novel L-lactic acid biosensors based on conducting polypyrrole-block copolymer nanoparticles.

The development of advanced nanomaterials for the highly efficient electrical detection of biological species has attracted great attention. Here, novel polypyrrole-Pluronic F127 nanoparticles (PPy-F127 NPs) with conducting and biocompatibility properties were synthesized and used to construct a L-lactic acid biosensor that could be applied in biochemical assays. The PPy-F127 NPs were characterized by transmission electron microscopy (TEM), elemental analysis and UV-vis spectroscopy. Lactate oxidase (LOx) structure variation on the PPy-F127 NPs was investigated by circular dichroism (CD). The cyclic voltammetric results indicated that LOx immobilized on the PPy-F127 NPs exhibited direct electron transfer reaction with a formal potential value (E(0)') of 0.154 V vs. SCE. Moreover, the biosensor had good electrocatalytic activity toward L-lactic acid with a wide linear range (0.015-37.5 mM) and a low detection limit of 0.0088 mM. The regression equation was I (µA) = 0.02353c (mM) + 1.4135 (R(2) = 0.9939). The L-lactic acid biosensor had a good anti-interference property towards uric acid (UA), ascorbic acid (AA), glucose and cysteine. The idea and method provide a promising platform for the rapid development of biosensors that can be used in the detection of biological species.