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Background: There is an urgent need to identify biomarkers for advanced adenoma, an important precursor of colorectal cancer (CRC). We aimed to determine alterations in ileal juice bile acids associated with colorectal advanced adenoma. Methods: We quantified a comprehensive panel of primary and secondary bile acids and their conjugates using an ultraperformance liquid chromatography triple-quadrupole mass spectrometric assay in ileal juice collected at colonoscopy from 46 study subjects (i.e., 14 biopsy-confirmed advanced adenomas and 32 controls free of adenoma or cancer). Using analysis of covariance (ANCOVA), we examined the differences in bile acid concentrations by disease status, adjusting for age, sex, body mass index, smoking status and type 2 diabetes. Results: The concentrations of hyodeoxycholic acid (HCA) species in ileal juice of the advanced adenoma patients (geometric mean = 4501.9 nM) were significantly higher than those of controls (geometric mean = 1292.3 nM, p = 0.001). The relative abundance of ursodeoxycholic acid (UDCA) in total bile acids was significantly reduced in cases than controls (0.73% in cases vs. 1.33% in controls; p = 0.046). No significant difference between cases and controls was observed for concentrations of total or specific primary bile acids (i.e., cholic acid (CA), chenodeoxycholic acid (CDCA) and their glycine- and taurine-conjugates) and total and specific major secondary bile acids (i.e., deoxycholic acid and lithocholic acid). Conclusions: Colorectal advanced adenoma was associated with altered bile acids in ileal juice. The HCA species may promote the development of colorectal advanced adenoma, whereas gut microbiota responsible for the conversion of CDCA to UDCA may protect against it. Our findings have important implications for the use of bile acids as biomarkers in early detection of colorectal cancer.

Convergent evolution provides powerful opportunities to investigate the genetic basis of complex traits. The Tibetan antelope (Pantholops hodgsonii) and Siberian ibex (Capra sibirica) belong to different subfamilies in Bovidae, but both have evolved similar superfine cashmere characteristics to meet the cold temperature in plateau environments. The cashmere traits of cashmere goats underwent strong artificial selection, and some traces of domestication also remained in the genome. Hence, we investigated the convergent genomic signatures of cashmere traits between natural and artificial selection. We compared the patterns of convergent molecular evolution between Tibetan antelope and Siberian ibex by testing positively selected genes, rapidly evolving genes and convergent amino acid substitutions. In addition, we analyzed the selected genomic features of cashmere goats under artificial selection using whole-genome resequencing data, and skin transcriptome data of cashmere goats were also used to focus on the genes involved in regulating cashmere traits. We found that molecular convergent events were very rare, but natural and artificial selection genes were convergent enriched in similar functional pathways (e.g., ECM-receptor interaction, focal adhesion, PI3K-Akt signaling pathway) in a variety of gene sets. Type IV collagen family genes (COL4A2, COL4A4, COL4A5, COL6A5, COL6A6) and integrin family genes (ITGA2, ITGA4, ITGA9, ITGB8) may be important candidate genes for cashmere formation and development. Our results provide a comprehensive approach and perspective for exploring cashmere traits and offer a valuable reference for subsequent in-depth research on the molecular mechanisms regulating cashmere development and fineness.

To solve the current problem of poor weld formation due to groove width variation in swing arc narrow gap welding, an infrared passive visual sensing detection approach was developed in this work to measure groove width under intense welding interferences. This approach, called global pattern recognition, includes self-adaptive positioning of the ROI window, equal division thresholding and in situ dynamic clustering algorithms. Accordingly, the self-adaptive positioning method filters several of the nearest values of the arc’s highest point of the vertical coordinate and groove’s same-side edge position to determine the origin coordinates of the ROI window; the equal division thresholding algorithm then divides and processes the ROI window image to extract the groove edge and forms a raw data distribution of groove width in the data window. The in situ dynamic clustering algorithm dynamically classifies the preprocessed data in situ and finally detects the value of the groove width from the remaining true data. Experimental results show that the equal division thresholding algorithm can effectively reduce the influences of arc light and welding fume on the extraction of the groove edge. The in situ dynamic clustering algorithm can avoid disturbances from simulated welding spatters with diameters less than 2.19 mm, thus realizing the high-precision detection of the actual groove width and demonstrating stronger environmental adaptability of the proposed global pattern recognition approach.

Selenium is a nonmetal trace element that is critical for several redox reactions and utilized to produce the amino acid selenocysteine (Sec), which can be incorporated into selenoproteins. Selenocysteine lyase (SCL) is an enzyme which decomposes Sec into selenide and alanine, releasing the selenide to be further utilized to synthesize new selenoproteins. Disruption of the selenocysteine lyase gene (Scly) in mice (Scly−/− or Scly KO) led to obesity with dyslipidemia, hyperinsulinemia, glucose intolerance and lipid accumulation in the hepatocytes. As the liver is a central regulator of glucose and lipid homeostasis, as well as selenium metabolism, we aimed to pinpoint hepatic molecular pathways affected by the Scly gene disruption. Using RNA sequencing and metabolomics, we identified differentially expressed genes and metabolites in the livers of Scly KO mice. Integrated omics revealed that biological pathways related to amino acid metabolism, particularly alanine and glycine metabolism, were affected in the liver by disruption of Scly in mice with selenium adequacy. We further confirmed that hepatic glycine levels are elevated in male, but not in female, Scly KO mice. In conclusion, our results reveal that Scly participates in the modulation of hepatic amino acid metabolic pathways.

Background: Hepatocellular carcinoma (HCC) pathogenesis involves the alteration of multiple liver-specific metabolic pathways. We systematically profiled cancer- and liver-related classes of metabolites in HCC and adjacent liver tissues and applied supervised machine learning to compare their potential yield for HCC biomarkers. Methods: Tumor and corresponding liver tissue samples were profiled as follows: Bile acids by ultra-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS), phospholipids by LC-MS/MS, and other small molecules including free fatty acids by gas chromatography—time of flight MS. The overall classification performance of metabolomic signatures derived by support vector machine (SVM) and random forests machine learning algorithms was then compared across classes of metabolite. Results: For each metabolite class, there was a plateau in classification performance with signatures of 10 metabolites. Phospholipid signatures consistently showed the highest discrimination for HCC followed by signatures derived from small molecules, free fatty acids, and bile acids with area under the receiver operating characteristic curve (AUC) values of 0.963, 0.934, 0.895, 0.695, respectively, for SVM-generated signatures comprised of 10 metabolites. Similar classification performance patterns were observed with signatures derived by random forests. Conclusion: Membrane phospholipids are a promising source of tissue biomarkers for discriminating between HCC tumor and liver tissue.

A three-dimensional numerical model is used to simulate heat transfer and fluid flow phenomena in fiber laser + gas metal arc welding (GMAW) hybrid welding of an aluminum alloy, which incorporates three-phase coupling and is able to depict the keyhole dynamic behavior and formation process of the keyhole-induced porosity. The temperature profiles and fluid flow fields for different arc powers are calculated and the percent porosities of weld beads were also examined under different conditions by X-ray non-destructive testing (NDT). The results showed that the computed results were in agreement with the experimental data. For hybrid welding, with raising arc power, the keyhole-induced porosity was reduced. Besides the solidification rate of the molten pool, the melt flow was also closely related to weld porosity. A relatively steady anti-clockwise vortex caused by arc forces tended to force the bubble to float upwards at the high temperature region close to the welding heat source, which benefits the escape of the gas bubble from the melt pool. When increasing the arc power, the anti-clockwise region was strengthened and the risk of the gas bubble for capture by the liquid/solid interface underneath the keyhole tip was diminished, which resulted in the lower weld percent porosity.

A positive surge is an unsteady open channel flow motion characterized by an increase of flow depth. In previous experimental studies, a positive surge was typically induced by either a sudden increase of discharge in a channel or by the rapid closure of a downstream sluice gate, thus leading to a steep initial profile. However, in many instances, the evolution of a positive surge is of a progressive manner (e.g., in the downstream navigation canal during the emptying operation of lock chambers). In the present work, the inception and development of a positive surge induced by a progressive increase of discharge was investigated in a rectangular channel with a smooth bed. Both undular and breaking surges were studied. The results demonstrate that the maximum wave height at the first wave crest of an undular surge is in very close agreement with the McCowan theory. Additionally, the wave amplitude essentially shows a linearly increasing trend with an increasing surge Froude number up to Fr0 = 1.26 to 1.28, whereas it tends to suggest a power law reduction for larger surge Froude numbers. Moreover, the dispersion of undular surges is consistent with the linear wave theory only for surge Froude numbers close to unity. Overall, the present study demonstrates the unique features of positive surges induced by a progressive increase of discharge.