A systematic review on diagnosis and treatment of gastrointestinal diseases by magnetically controlled capsule endoscopy and artificial intelligence.

Background: Magnetically controlled capsule endoscopy (MCCE) is a non-invasive, painless, comfortable, and safe equipment to diagnose gastrointestinal diseases (GID), partially overcoming the shortcomings of conventional endoscopy and wireless capsule endoscopy (WCE). With advancements in technology, the main technical parameters of MCCE have continuously been improved, and MCCE has become more intelligent. Objectives: The aim of this systematic review was to summarize the research progress of MCCE and artificial intelligence (AI) in the diagnosis and treatment of GID. Data Sources and Methods: We conducted a systematic search of PubMed and EMBASE for published studies on GID detection of MCCE, physical factors related to MCCE imaging quality, the application of AI in aiding MCCE, and its additional functions. We synergistically reviewed the included studies, extracted relevant data, and made comparisons. Results: MCCE was confirmed to have the same performance as conventional gastroscopy and WCE in detecting common GID, while it lacks research in detecting early gastric cancer (EGC). The body position and cleanliness of the gastrointestinal tract are the main factors affecting imaging quality. The applications of AI in screening intestinal diseases have been comprehensive, while in the detection of common gastric diseases such as ulcers, it has been developed. MCCE can perform some additional functions, such as observations of drug behavior in the stomach and drug damage to the gastric mucosa. Furthermore, it can be improved to perform a biopsy. Conclusion: This comprehensive review showed that the MCCE technology has made great progress, but studies on GID detection and treatment by MCCE are in the primary stage. Further studies are required to confirm the performance of MCCE.

Early gastric cancer segmentation in gastroscopic images using a co-spatial attention and channel attention based triple-branch ResUnet.

BACKGROUND AND OBJECTIVE: The artificial segmentation of early gastric cancer (EGC) lesions in gastroscopic images remains a challenging task due to reasons including the diversity of mucosal features, irregular edges of EGC lesions and nuances between EGC lesions and healthy background mucosa. Hence, this study proposed an automatic segmentation framework: co-spatial attention and channel attention based triple-branch ResUnet (CSA-CA-TB-ResUnet) to achieve accurate segmentation of EGC lesions for aiding clinical diagnosis and treatment. METHODS: The input gastroscopic image sequences of the triple-branch segmentation network CSA-CA-TB-ResUnet is firstly generated by the designed multi-branch input preprocessing (MBIP) module in order to fully utilize massive correlation information among multiple gastroscopic images of the same a lesion. Then, the proposed CSA-CA-TB-ResUnet performs the segmentation of EGC lesion, in which the co-spatial attention (CSA) mechanism is designed to activate the spatial location of EGC lesions by leveraging on the correlations among multiple gastroscopic images of the same EGC lesion, and the channel attention (CA) mechanism is introduced to extract subtle discriminative features of EGC lesions by capturing the interdependencies between channel features. Finally, two gastroscopic images datasets from different digestive endoscopic centers in the southwest and northeast regions of China respectively were collected to validate the performances of proposed segmentation method. RESULTS: The correlation information among gastroscopic images was confirmed to be able to improve the accuracy of EGC segmentation. On another unseen dataset, our EGC segmentation method achieves Jaccard similarity index (JSI) of 84.54% (95% confidence interval (CI), 83.49%-85.56%), threshold Jaccard index (TJI) of 81.73% (95% CI, 79.70%-83.61%), Dice similarity coefficient (DSC) of 91.08% (95% CI, 90.40%-91.76%) and pixel-wise accuracy (PA) of 91.18% (95% CI, 90.43%-91.87%), which is superior to other state-of-the-art methods. Even on the challenging small lesions, the segmentation results of our CSA-CA-TB-ResUnet-based method are consistently and significantly better than other state-of-the-art methods. We also compared the segmentation result of our model with the diagnostic accuracy with junior/senior expert. The comparison results indicated that our model performed better than the junior expert. CONCLUSIONS: This study proposed a novel CSA-CA-TB-ResUnet-based EGC segmentation method and it has a potential for real-time application in improving EGC clinical diagnosis and minimally invasive surgery.

Microbial Biosynthesis of L-Malic Acid and Related Metabolic Engineering Strategies: Advances and Prospects.

Malic acid, a four-carbon dicarboxylic acid, is widely used in the food, chemical and medical industries. As an intermediate of the TCA cycle, malic acid is one of the most promising building block chemicals that can be produced from renewable sources. To date, chemical synthesis or enzymatic conversion of petrochemical feedstocks are still the dominant mode for malic acid production. However, with increasing concerns surrounding environmental issues in recent years, microbial fermentation for the production of L-malic acid was extensively explored as an eco-friendly production process. The rapid development of genetic engineering has resulted in some promising strains suitable for large-scale bio-based production of malic acid. This review offers a comprehensive overview of the most recent developments, including a spectrum of wild-type, mutant, laboratory-evolved and metabolically engineered microorganisms for malic acid production. The technological progress in the fermentative production of malic acid is presented. Metabolic engineering strategies for malic acid production in various microorganisms are particularly reviewed. Biosynthetic pathways, transport of malic acid, elimination of byproducts and enhancement of metabolic fluxes are discussed and compared as strategies for improving malic acid production, thus providing insights into the current state of malic acid production, as well as further research directions for more efficient and economical microbial malic acid production.

Identification and engineering a C4-dicarboxylate transporter for improvement of malic acid production in Aspergillus niger.

Modification of C4-dicarboxylate transport processes is an important strategy for the development of efficient malic acid producing cell factory in Aspergillus niger. However, there is a lack of identification and functional research of malic acid transport proteins, which seriously hinders the construction of high-yield malic acid metabolic engineering strains. A C4-dicarboxylate transport protein (DCT) DCT1 is identified as major malic acid transport protein and exhibits significant elevation in malic acid production when overexpressed. DCT1 is found by homology searches and domain analyses with SpMAE1 from Schizosaccharomyces pombe as the template. Phylogenetic and domain analyses show that DCTs belong to voltage-dependent slow-anion channel transporter (SLAC1) family and are members of Tellurite-resistance/Dicarboxylate Transporter (TDT) Family. DCT1 disruption dramatically decreases malic acid titer by about 85.6% and 96.2% at 3 days and 5 days compared with the parent strain, respectively. Meanwhile, the citric acid titers increase by 36.4% and 13.7% at 3 days and 5 days upon DCT1 deficiency. These results suggest that DCT1 is the major malic acid transporter in A. niger. Overexpression of dct1 with its native promoter significantly improves malic acid production yielding up to 13.86 g/L and 30.79 g/L at 3 days and 5 days, respectively, which is 36.8% and 22.8% higher than those in the parent strain. However, the citric acid has no significant change during the 5-day fermentation. These results demonstrate the importance of C4-dicarboxylate transporters for the efficient production of malic acid. Furthermore, enhancement of malic acid transport process is a feasible approach of efficient malic acid production in this citric acid producing A. niger strain. KEY POINTS: • A dicarboxylate transporter DCT1 is identified as a major malic acid transporter. • DCT1 deficiency results in significant decrease of malic acid. • DCT1 overexpression leads to increased titers of malic acid. • Enhancement of malic acid transport is vital for malic acid production in A. niger.

Improved Production of Malic Acid in Aspergillus niger by Abolishing Citric Acid Accumulation and Enhancing Glycolytic Flux.

Microbial fermentation was widely explored to produce malic acid. Previously, Aspergillus niger has been successfully engineered, and a high titer of malic acid was achieved with strain S575, but it also produced a high level of byproduct citric acid. Here, the capability of A. niger in malic acid biosynthesis was further improved by eliminating the accumulation of citric acid and enhancing glycolytic flux. Characterization of variant mutants suggested that disruption of cexA, a gene encoding citric acid transporter located on cell membrane, abolished citric acid accumulation. However, cexA-deficient strain S895 showed significantly decreased malic acid production. Further analysis of S895 indicated that the transcription level of genes involved in glucose transportation and glycolytic pathway was significantly reduced, and the corresponding enzyme activity was also lower than those of S575. Individual overexpression of genes encoding glucose transporter MstC and key enzymes (hexokinase HxkA, 6-phosphofructo-2-kinase PfkA, and pyruvate kinase PkiA) involved in irreversible reactions of glycolic pathway increased malic acid production. Accordingly, genes of mstC, hxkA, pfkA, and pkiA were overexpressed altogether in S895, and the resultant strain S1149 was constructed. The titer of malic acid in fed-batch fermentation with S1149 reached 201.13 g/L. Compared with S575, the byproduct of citric acid was completely abolished in S1149, and the ratio of malic acid/glucose was increased from 1.27 to 1.64 mol/mol, the highest yield reported so far, and the fermentation period was shortened from 9 to 8 days. Thus, a strain with great industrial application potential was developed by engineering nine genes in A. niger, and a pilot fermentation technology was exploited.

Development of a Cre-loxP-based genetic system in Aspergillus niger ATCC1015 and its application to construction of efficient organic acid-producing cell factories.

The filamentous fungus Aspergillus niger is widely used in the biotechnology industry for the production of chemicals and enzymes. Engineering of this valuable organism to improve its productivity is currently hampered by the lack of efficient genetic tools. Here, a Cre-loxP-based system for gene editing in A. niger was developed and its application in construction of A. niger cell factories to produce various organic acids was explored. Two established inducible systems, the xylanase A gene promoter Pxln and Tet-on system, were examined for driving cre expression and thus selection marker hyh deletion. Under inducing conditions, the efficiency of loxP site-specific recombination in the strain with cre driven by Pxln is about 2%, while cre driven by Tet-on system is about 34% which was used as the platform strain for further genetic engineering. As a proof of application of this system, strains containing different copies of oxaloacetate acetylhydrolase-encoding gene (oahA) were constructed, and the resultant strain S428 showed as high as 3.1-fold increase in oxalic acid production. Furthermore, an efficient malate-producing strain was generated through four-step genetic manipulation (oahA deletion, pyc, mdh3 and C4-dicarboxylate transporter gene c4t318 insertion). The resultant strain S575 achieved a titer 120.38 g/L malic acid with the flask culture, and a titer 201.24 g/L malic acid in fed-batch fermentation. These results demonstrated that this modified Cre-loxP system is a powerful tool for genetic engineering in A. niger, which has the potential to be genetically modified as a viable aciduric platform strain to produce high levels of various organic acids.

Analysis of differentially expressed proteins in zebrafish (Danio rerio) embryos exposed to chlorpyrifos.

In this study, the protein expression profiles of zebrafish embryos under chlorpyrifos (CPF) stress were investigated. Zebrafish embryos were exposed to 0.25 mg/L CPF, and embryo samples were collected until 24 h post-fertilization (hpf). To gain a better understanding of the response of zebrafish embryos to CPF exposure, two-dimensional polyacrylamide gel electrophoresis (2D PAGE) coupled with mass spectrometry was employed to carry out a comparative proteomic analysis. Total proteins were extracted from the control and treated samples, separated by 2D PAGE, and visualized by silver staining. A total of 59 protein spots showed reproducible changes compared with the control. Of these 59 spots, 19 were selected and subjected to matrix-assisted laser desorption/ionization (MALDI) tandem time-of-flight mass spectrometry (TOF/TOF) analysis; 9 differentially expressed proteins were successfully identified, including 3 up-regulated proteins and 6 down-regulated proteins. The increased expression of 3 proteins associated with detoxification and stress response suggested that the activation of protective proteins was required in zebrafish embryos exposed to CPF. On the other hand, the decreased expression of 6 proteins is mainly involved in cytoskeleton structure, protein translation, signal transduction and lipoprotein metabolism. These data may help us understand the functions and the molecular mechanisms of these proteins in zebrafish embryos' response to CPF exposure.

Genome sequence of Paracoccus sp. Strain TRP, a Chlorpyrifos Biodegrader.

Paracoccus sp. strain TRP, isolated from activated sludge, could completely biodegrade chlorpyrifos and 3,5,6-trichloro-2-pyridinol. Here we report the draft genome sequence of Paracoccus sp. strain TRP, which could be used to predict genes for xenobiotic biodegradation and metabolism.