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Objective: Lung adenocarcinoma (LUAD) is the most common type of lung cancer. However, predictive biomarkers for early efficacy and prognosis evaluation in patients with surgically resected LUAD are not completely explained. Methods: Differentially expressed genes (DEGs), gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were identified between thirteen LUAD tissues and five normal lung tissues were analyzed by RNA sequencing (RNA-Seq). The expression of DEGs was confirmed by qRT-PCR and a validated cohort from GEPIA. Protein-protein interaction (PPI) network of the top 5% DEGs was constructed by STRING and visualized in Cytoscape. Immunofluorescence results were acquired from clinical specimens from LUAD patients. The expression of FHL1 was analyzed by ImageJ. Survival analysis was performed using the GEPIA dataset. Results: Consistent with the RNA-Seq data, validation of DEGs expression by qRT-PCR and GEPIA cohort showed that FHL1 and SLIT3 were down-regulated in LUAD patient tissues compared with non-tumor tissues. Moreover, FHL1 was significantly reduced in LUAD cell lines compared to the bronchial epithelium cell line (P Conclusion: Our findings provide two novel candidates, FHL1 and SLIT3, for prognostic evaluation and treatments after surgery.

Loofah seeds ribosome inactivating protein luffin-α was fused with a tumor-targeting peptide NGR to create a recombinant protein, and its inhibitory activity on tumor cells and angiogenesis were assessed.

A novel ecological-microbial fuel cell (E-MFC) was constructed based on the mutualistic symbiosis relationship among wetland plants Ipomoea aquatic, benthic fauna Tubifex tubifex (T. tubifex) and microorganisms. The maximum power densities of sediment MFC (S-MFC), wetland plant MFC (WP-MFC) and E-MFC were 6.80 mW/m2, 10.60 mW/m2 and 15.59 mW/m2, respectively. Ipomoea aquatic roots secreted organic matter as electricigens’ fuel for electricity generation, while T. tubifex decomposed decaying leaves and roots into soluble organic matter and plant nutrients, forming a co-dependent and mutually beneficial system, which was conducive to bioelectricity production. The E-MFC obtained the highest nitrogen removal, and the removal efficiencies of NH4+-N and NO3−-N were 90.4% and 96.5%, respectively. Hydraulic retention time (HRT), cathodic aeration and T. tubifex abundance had significant effects on E-MFC power generation. The performeance boost of E-MFC was closely related to anodic microbial community change caused by the introduction of T. tubifex.

Adipogenesis is a multi-step process orchestrated by activation of numerous TFs, whose cooperation and regulatory network remain elusive. Activating transcription factor 4 (ATF4) is critical for adipogenesis, yet its regulatory network is unclarified. Here, we mapped genome-wide ATF4 binding landscape and its regulatory network by Chip-seq and RNA-seq and found ATF4 directly modulated transcription of genes enriching in fat cell differentiation. Motifs of TFs especially CTCF were found from ATF4 binding sites, suggesting a direct role of ATF4 in regulating adipogenesis associated with CTCF and other TFs. Deletion of CTCF attenuated adipogenesis while overexpression enhanced adipocyte differentiation, indicating CTCF is indispensable for adipogenesis. Intriguingly, combined analysis of Chip-seq data of these two TFs showed that ATF4 co-localized with CTCF in the promoters of key adipogenic genes including Cebpd and PPARg and co-regulated their transactivation. Moreover, ATF4 directly regulated CTCF expression and interacted with CTCF in differentiated 3T3-L1 cells. In vivo, downregulation of ATF4 suppressed the expression of CTCF, Cebpd, and PPARg, leading to reduced adipose tissue expansion in refeeding mice. Consistently, mRNA expression of ATF4 and CTCF was positively correlated with each other in human subcutaneous adipose tissue and inversely associated with BMI, indicating a possible involvement of these two TFs in adipose development. Taken together, our data propose for the first time that ATF4 and CTCF work cooperatively to control adipogenesis and adipose development via orchestrating transcription of adipogenic genes. Our findings reveal novel therapeutic targets in obesity treatment.

Milk phospholipids have been used as functional ingredients in foods. However, there have been no reports on how the polarity of lipids affects their digestibility. This study aims to isolate milk phospholipids from dairy products, to characterize them chromatographically, and assess their digestibility and antioxidant activities in vitro. The results revealed that their lipolysis reaction rate constants were significantly different ( p 0.05 ) between milk phospholipids and triacylglycerols, and thus the degradation of both lipids complied with first-order reaction kinetics. Furthermore, the cellular uptake of milk phospholipids was determined with HT-29 cell model, and they were not found to be absorbed intact during intestinal digestion. Milk phospholipids exhibited significant antioxidant activity in vitro, while their cellular antioxidant activity was very limited. The results of this study provide useful information for the design of milk phospholipid-based carrier systems.

Milk phospholipids (MPLs) have been used as ingredients for food fortification, such as bakery products, yogurt, and infant formula, because of their technical and nutritional functionalities. Starting from either buttermilk or beta serum as the original source, this review assessed four typical extraction processes and estimated that the life-cycle carbon footprints (CFs) of MPLs were 87.40, 170.59, 159.07, and 101.05 kg CO2/kg MPLs for membrane separation process, supercritical fluid extraction (SFE) by CO2 and dimethyl ether (DME), SFE by DME, and organic solvent extraction, respectively. Regardless of the MPL content of the final products, membrane separation remains the most efficient way to concentrate MPLs, yielding an 11.1−20.0% dry matter purity. Both SFE and solvent extraction processes are effective at purifying MPLs to relatively higher purity (76.8−88.0% w/w).

Neuroinflammation and oxidative stress are involved in cerebral ischemia-reperfusion, in which Interleukin 1 (IL-1), as an effective intervention target, is implicated. Interleukin-1 receptor antagonist (IL-1RA) is the natural inhibitor of IL-1, but blood-brain barrier (BBB) limits the brain penetration of intravenously administered IL-1RA, thereby restricting its therapeutic effect against neuroinflammation. In this study, we evaluated the potential effects of anti-inflammation and anti-oxidative stress of a novel protein IL-1RA-PEP, which fused IL-1RA with a cell penetrating peptide (CPP). Studies were carried out in transient middle cerebral artery occlusion (MCAO) in rats and oxygen glucose deprivation/reoxygenation (OGD/R) in primary cortical neurons. In MCAO rat model, IL-1RA-PEP (50 mg/kg) injected i.v., penetrated BBB effectively, and alleviated brain infarction, cerebral edema, neurological deficit score and motor performance as well as inhibited the inflammatory cytokines expression. Furthermore, our results firstly showed that IL-1RA-PEP also regulated the oxidases expression, decreased the levels of NO, MDA and ROS. In addition, the inhibitory effects of IL-1RA-PEP on oxidative stress and inflammation were confirmed in rat cortical neurons induced by OGD/R, it reduced ROS, IL-6 and TNF-α. Further study showed that the effects of IL-1RA-PEP were closely associated with the NF-κB and p38 pathways which were proved respectively by their inhibitors JSH-23 and SB203580. Our results indicated that IL-1RA-PEP could effectively penetrate the brain of MCAO rats, alleviated the cerebral ischemia reperfusion injury by inhibiting neuroinflammation and oxidative stress, showing a great clinical potential for stroke.

The accumulations of excess lipids within liver and serum are defined as non-alcoholic fatty liver disease (NAFLD) and hyperlipemia respectively. Both of them are components of metabolic syndrome that greatly threaten human health. Here, a recombinant fusion protein (SAK-HV) effectively treated NAFLD and hyperlipemia in high-fat-fed ApoE-/- mice, quails and rats within just 14 days. Its triglyceride and cholesterol-lowering effects were significantly better than that of atorvastatin during the observation period. We explored the lipid-lowering mechanism of SAK-HV by the hepatic transcriptome analysis and serials of experiments both in vivo and in vitro. Unexpectedly, SAK-HV triggered a moderate energy and material-consuming liver proliferation to dramatically decrease the lipids from both serum and liver. We provided the first evidence that PGC-1α mediated the hepatic synthesis of female hormones during liver proliferation, and proposed the complement system-induced PGC-1α-estrogen axis via the novel STAT3-C/EBPβ-PGC-1α pathway in liver as a new energy model for liver proliferation. In this model, PGC-1α ignited and fueled hepatocyte activation as an "igniter"; PGC-1α-induced estrogen augmented the energy supply of PGC-1α as an "ignition amplifier", then triggered the hepatocyte state transition from activation to proliferation as a "starter", causing triglyceride and cholesterol-lowering effects via PPARα-mediated fatty acid oxidation and LDLr-mediated cholesterol uptake, respectively. Collectively, the SAK-HV-triggered distinctive lipid-lowering strategy based on the new energy model of liver proliferation has potential as a novel short-period biotherapy against NAFLD and hyperlipemia.

Milk fats and related dairy products are multi-functional ingredients in bakeries. Bakeries are critical local industries in Western countries, and milk fats represent the most important dietary lipids in countries such as New Zealand. Milk fats perform many roles in bakery products, including dough strengthening, textural softeners, filling fats, coating lipids, laminating fats, and flavor improvers. This review reports how milk fats interact with the ingredients of main bakery products. It also elaborates on recent studies on how to modulate the quality and digestibility of baked goods by designing a new type of fat mimetic, in order to make calorie- and saturated fat-reduced bakery products. It provides a quick reference for both retailers and industrial manufacturers of milk fat-based bakery products.

Phospholipids are important ingredients in milk. They serve as bioactive components with processing functionalities, despite representing only a small proportion of total milk lipids. There has been increasing interest in vesicle properties and health effects of milk phospholipids. However, there are limited reports on industry-scale manufacturing of related commercial products. This contribution aims to elucidate the industrial processes of manufacturing milk phospholipid products including phospholipid extraction and fraction as well as summarizing determination assays of milk phospholipids. In addition to industrial production, this review elaborates on application aspects, such as the biological properties of milk phospholipids and their technical importance as delivery vesicles of liposomes and phytosomes. In addition, new insights on large-scale production of milk phospholipids and new applications such as phytosomes and antioxidant properties are discussed.

Evidences have shown that phytosome assemblies are novel drug delivery system. However, studies of phytosomes in food applications are scarce. The characteristics of milk phospholipid assemblies and their functionality in terms of in vitro digestibility and bioavailability of encapsulated nutrients (ascorbic acid and α-tocopherol) were studied. The phytosomes were fabricated using ethanolic evaporation technique. Spectral analysis revealed that polar parts of phospholipids formed hydrogen bonds with ascorbic acid hydroxyl groups, further, incorporating ascorbic acid or α-tocopherol into the phospholipid assembly changed the chemical conformation of the complexes. Phospholipid-ascorbic acid phytosomes yielded an optimal complexing index of 98.52 ± 0.03% at a molar ratio of 1:1. Phytosomes exhibited good biocompatibility on intestinal epithelial cells. The cellular uptake of ascorbic acid was 29.06 ± 1.18% for phytosomes. It was higher than that for liposomes (24.14 ± 0.60%) and for ascorbic acid aqueous solution (1.17 ± 0.70%).

Milk fat has been used as functional ingredient in bread making. However, incorporation of enzymatically-treated milk fat into bread recipes and their effects on bread properties have not been explored. This study aims to ascertain the impact of lipase-treated milk fat on bread quality in comparison with untreated bread controls. As a result of lipase treatment, dough structure was strengthened, and loaf volume improved. In vitro digestion revealed that the glycaemic load of breads with lipase-treated milk fat was significantly lower than that of control samples ( p 0.05 ). In addition, lipase treatment reduced the crumb water activity. The study provides a novel and practical method to improve bread functionalities and lower product glycaemic response, without detrimental effects on the quality of the final products.

The main cables are key complements of the suspension bridge. The temperature properties of main cables have significant effects on the structural responses of entire bridge. This paper presents a numerical method for temperature analysis of main cable for suspension bridge. The finite element (FE) model of main cable section is developed as homogeneous material using Plan elements. The material parameters for thermal analysis are determined based on equivalent principle. The third type thermal boundary conditions of a sunny day are calculated and then applied on the FE model for transient thermal analysis. The numerical results are compared with the experimental measurements of a full scale main cable for validation of the thermal analysis method. The results present good agreement with respect to the measurements. The temperature variations exactly explicate the changes of environmental conditions such as solar radiation and ambient temperature of daily. This FE model-based thermal analysis can provide a high effective and precision method for analysis of temperature and induced structural responses of main cables and suspension bridge.

Transient stability constrained optimal power flow (TSCOPF) is an important and difficult problem. When multiple contingencies are considered, a reliable contingency filtering technique should be used to reduce the scale of TSCOPF problem. This study brings in the concepts of active contingency and critical contingency, and develops a novel contingency filtering strategy. Based on time-domain numerical simulations, the proposed contingency filtering strategy first screens all the considered contingencies and identifies active contingencies whose severe indices violate the pre-defined threshold of transient stability, then further finds out the critical contingencies in which some generators are most severely disturbed according to the severe indices trajectories. The severe indices can be such as maximal relative rotor angles, maximal transient generator voltage dips and so on. Taking only the critical contingencies into account, the scale of TSCOPF problem is reduced significantly. Interior point method is used to solve the reduced TSCOPF problem. Numerical results on several cases indicate that the proposed contingency filtering technique is reliable and efficient. Compared with the conventional TSCOPF approach, which involves all the contingencies, the proposed contingency filtering strategy possesses overwhelming advantages in CPU time and memory consumption, and is hopeful to solve TSCOPF problems with many contingencies.

Transmission capability for multi-infeed HVDC power transmission system is an important issue which is concerned by many power companies greatly. From the view of the problems caused by large scale multi-infeed HVDC, the main limiting factors of DC access capability are analyzed. Based on these a method to solve DC access capability considering many limits, such as peaking capability, multi-infeed short circuit ratio, voltage stability, frequency stability and transient stability is proposed, by which the DC access capability assessment in East China Power Grid is worked out. For the main limiting factors the suggestions to improve DC access capability and optimize the layout of multi-infeed HVDC are proposed.

This paper analyses the principle and effect of active laser high repetition frequency jamming in the semi-active laser guidance. According to existing decoding methods for active laser high repetition frequency jamming, a cascade way of multiple FPGAs is proposed and its principle and rule are introduced, especially, the cascade and codec synchronization methods are involved, providing a new thought for confronting the laser high repetition frequency jamming. At last, future trend of laser high repetition frequency jamming countermeasure is summarized.

Organisms must be able to rapidly alter gene expression in response to changes in their nutrient environment. This review summarizes evidence that epigenetic modifications of chromatin depend on particular metabolites of intermediary metabolism, enabling the facile regulation of gene expression in tune with metabolic state. Nutritional or dietary control of chromatin is an often-overlooked, yet fundamental regulatory mechanism directly linked to human physiology. Nutrient-sensitive epigenetic marks are dynamic, suggesting rapid turnover, and may have functions beyond the regulation of gene transcription, including pH regulation and as carbon sources in cancer cells.

Alpha B-crystallin (CRYAB) maps within the nasopharyngeal carcinoma (NPC) tumor-suppressive critical region 11q22-23 and its downregulation is significantly associated with the progression of NPC. However, little is known about the functional impact of CRYAB on NPC progression. In this study we evaluated the NPC tumor-suppressive and progression-associated functions of CRYAB. Activation of CRYAB suppressed NPC tumor formation in nude mice. Overexpression of CRYAB affected NPC progression-associated phenotypes such as loss of cell adhesion, invasion, interaction with the tumor microenvironment, invasive protrusion formation in three dimensional Matrigel culture, as well as expression of epithelial-mesenchymal transition-associated markers. CRYAB mediates this ability to suppress cancer progression by inhibition of E-cadherin cytoplasmic internalization and maintenance of β-catenin in the membrane that subsequently reduces the levels of expression of critical downstream targets such as cyclin-D1 and c-myc. Both ectopically expressed and recombinant CRYAB proteins were associated with endogenous E-cadherin and β-catenin, and, thus, the cadherin/catenin adherens junction. The CRYAB α-crystallin core domain is responsible for the interaction of CRYAB with both E-cadherin and β-catenin. Taken together, these results indicate that CRYAB functions to suppress NPC progression by associating with the cadherin/catenin adherens junction and modulating the β-catenin function.

Optimal power flow (OPF) is a large scale nonlinear non-convex optimization problem. In the last decades many algorithms are developed to solve these problems and the interior point method (IPM) is a popular one. The primal-dual IPMs and their later developments have attracted much research interest. Impressed by the improvements in convergent performance of the further developed multiple centrality corrections IPM in linear programming (LP), this paper extended it to nonlinear programming and made certain modifications to make it adaptable to the nonlinear OPF. Test results on several cases ranging from 9-bus to 2746-bus system indicate the efficiency and high convergence of the proposed algorithm, which outperforms the original multiple centrality corrections IPM. Comparisons between the proposed method and other forms of interior point methods are also given to show its advantage in convergent performance.

When phase shifters are used as control devices in optimal power flow (OPF), the symmetry of the admittance matrix is destroyed; this introduces some difficulties in the implementation of interior point OPF. This paper presents an efficient approach to handle phase shifters in an interior point OPF algorithm. First, a new power/current injection model of phase shifters is proposed. Then, a detailed explanation of how to integrate this model into the existing interior point OPF code is presented. This integration of phase shifters only requires minor modifications to the existing interior point OPF code by updating Jacobian/Hessian matrices of objective and constraints in each iterate. The distinguished features of the proposed approach are: (i) box constraints are used instead of implicit constraints; (ii) no additional buses are introduced, so the dimensions of Jacobian and Hessian matrices remain the same; and (iii) the admittance matrix is constant, and remains symmetric. Numerical studies on several power systems up to 2383 buses indicate that the proposed approach is simple and efficient. Copyright © 2009 John Wiley & Sons, Ltd.

Glioblastomas and brain metastases are highly proliferative brain tumors with short survival times. Previously, using (13)C-NMR analysis of brain tumors resected from patients during infusion of (13)C-glucose, we demonstrated that there is robust oxidation of glucose in the citric acid cycle, yet glucose contributes less than 50% of the carbons to the acetyl-CoA pool. Here, we show that primary and metastatic mouse orthotopic brain tumors have the capacity to oxidize [1,2-(13)C]acetate and can do so while simultaneously oxidizing [1,6-(13)C]glucose. The tumors do not oxidize [U-(13)C]glutamine. In vivo oxidation of [1,2-(13)C]acetate was validated in brain tumor patients and was correlated with expression of acetyl-CoA synthetase enzyme 2, ACSS2. Together, the data demonstrate a strikingly common metabolic phenotype in diverse brain tumors that includes the ability to oxidize acetate in the citric acid cycle. This adaptation may be important for meeting the high biosynthetic and bioenergetic demands of malignant growth.

Acetyl-CoA represents a central node of carbon metabolism that plays a key role in bioenergetics, cell proliferation and the regulation of gene expression. How highly glycolytic or hypoxic tumors are able to produce sufficient quantities of this metabolite to support cell growth and survival under nutrient-limiting conditions remains poorly understood. Here we show that the nucleocytosolic acetyl-CoA synthetase enzyme, ACSS2, supplies a key source of acetyl-CoA for tumors by capturing acetate as a carbon source. Despite exhibiting no gross deficits in growth or development, adult mice lacking ACSS2 exhibit a significant reduction in tumor burden in two different models of hepatocellular carcinoma. ACSS2 is expressed in a large proportion of human tumors and its activity is responsible for the majority of cellular acetate uptake into both lipids and histones. These observations may qualify ACSS2 as a targetable metabolic vulnerability of a wide spectrum of tumors.