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Human exposure to aflatoxins (AFs) and zearalenone (ZEA) has not been sufficiently investigated. Here, we analyzed the exposure level and health risks posed by AFs (B1, B2, G1, G2) and ZEA through cooking oil consumption in Shandong, China. The individual daily consumption of cooking oil was calculated through 2745 questionnaires during 2017-2019. The average contamination levels of mycotoxins were estimated by examining 60 cooking oil samples. For the peanut oil, AFs ranged from0.2 to 274 μg/kg, with a positive rate of 66.6% (20/30). Average levels of 36.62 μg/kg AFB

Abnormal climate changes have resulted in over-precipitation in many regions. The occurrence and contamination levels of mycotoxins in crops and cereals have been elevated largely. From 2017 to 2019, we did investigation targeting 15 mycotoxins shown in the wheat samples collected from Shandong, a region suffering over-precipitation in China. We found that deoxynivalenol (DON) was the dominant mycotoxin contaminating wheats, with detection rates 304/340 in 2017 (89.41%), 303/330 in 2018 (91.82%), and 303/340 in 2019 (89.12%). The ranges of DON levels were 4 to 580 μg/kg in 2017, 4 to 3070 μg/kg in 2018, and 4 to 1540 μg/kg in 2019. The exposure levels were highly correlated with local precipitation. Male exposure levels were generally higher than female's, with significant difference found in 2017 (1.89-fold, p = 0.023). Rural exposure levels were higher than that of cities but not statistically significant (1.41-fold, p = 0.13). Estimated daily intake (EDI) and margin of exposure (MoE) approaches revealed that 8 prefecture cities have probabilistically extra adverse health effects (vomiting or diarrhea) cases 100 patients in 100,000 residents attributable to DON exposure. As a prominent wheat-growing area, Dezhou city reached ~ 300/100,000 extra cases while being considered as a major regional contributor to DON contamination. Our study suggests that more effort should be given to the prevention and control of DON contamination in major wheat-growing areas, particularly during heavy precipitation year. The mechanistic association between DON and chronic intestinal disorder/diseases should be further investigated.

A key event featured in the early stage of chronic gut inflammatory diseases is the disordered recruitment and excess accumulation of immune cells in the gut lamina propria. This process is followed by the over-secretion of pro-inflammatory factors and the prolonged overactive inflammatory responses. Growing evidence has suggested that gut inflammatory diseases may be mitigated by butyric acid (BA) or butyrate sodium (NaB). Laboratory studies show that BA and NaB can enhance gut innate immune function through G-protein-mediated signaling pathways while mitigating the overactive inflammatory responses by inhibiting histone deacetylase. The regulatory effects may occur in both epithelial enterocytes and the immune cells in the lamina propria. Prior to further clinical trials, comprehensive literature reviews and rigid examination concerning the underlying mechanism are necessary. To this end, we collected and reviewed 197 published reports regarding the mechanisms, bioactivities, and clinical effects of BA and NaB to modulate gut inflammatory diseases. Our review found insufficient evidence to guarantee the safety of clinical practice of BA and NaB, either by anal enema or oral administration of capsule or tablet. The safety of clinical use of BA and NaB should be further evaluated. Alternatively, dietary patterns rich in "fruits, vegetables and beans" may be an effective and safe approach to prevent gut inflammatory disease, which elevates gut microbiota-dependent production of BA. Our review provides a comprehensive reference to future clinical trials of BA and NaB to treat gut inflammatory diseases.

Background Antibiotic resistance is an urgent threat to public health. Prior to the evolution of antibiotic resistance, bacteria frequently undergo response and tend to develop a state of adaption to the antibiotic. Ciprofloxacin is a broad-spectrum antibiotic by damaging DNA. With the widespread clinical application, the resistance of bacteria to ciprofloxacin continues to increase. This study aimed to investigate the transcriptome changes under the action of high concentration of ciprofloxacin in Escherichia coli. Results We identified 773 higher expressed differentially expressed genes (DEGs) and 645 lower expressed DEGs in ciprofloxacin treated cells. Enriched biological pathways reflected the up-regulation of biological process such as DNA damage and repair system, toxin/antitoxin systems, formaldehyde detoxification system, peptide biosynthetic process and cellular protein metabolic process. With KEGG pathway analysis, higher expressed DEGs of kdsA and waa operon were associated with “LPS biosynthesis”. rfbABC operon was related to “streptomycin biosynthesis” and “polyketide sugar unit biosynthesis ”. Lower expressed DEGs of thrABC and fliL operons were associated with “flagellum-dependent cell motility” and “bacterial-type flagellum” in GO terms, and enriched into “biosynthesis of amino acids” and “flagellar assembly” in KEGG pathways. After treatment of ciprofloxacin, bacterial lipopolysacchride (LPS) release was increased by two times, and the mRNA expression level of LPS synthesis genes, waaB, waaP and waaG were elevated (P

Breast cancer has a high incidence and mortality rate worldwide. Several viral vectors including lentiviral, adenoviral and adeno-associated viral vectors have been used in gene therapy for various forms of human cancer, and have shown promising effects in controlling tumor development. Claudin1 (CLDN1) is a member of the tetraspan transmembrane protein family that plays a major role in tight junctions and is associated with tumor metastasis. However, the role of CLDN1 in breast cancer is largely unexplored. In this study, we tested the therapeutic potential of silencing CLDN1 expression in two breast cancer (MDA-MB-231 and MCF7) cell lines using lentiviral vector mediated RNA interference. We found that a CLDN1 short hairpin (shRNA) construct efficiently silenced CLDN1 expression in both breast cancer cell lines, and CLDN1 knockdown resulted in reduced cell proliferation, survival, migration and invasion. Furthermore, silencing CLDN1 inhibited epithelial to mesenchymal transition (EMT) by upregulating the epithelial cell marker, E-cadherin, and downregulating mesenchymal markers, smooth muscle cell alpha-actin (SMA) and Snai2. Our data demonstrated that lentiviral vector mediated CLDN1 RNA interference has great potential in breast cancer gene therapy by inhibiting EMT and controlling tumor cell growth.

Avionics software is safety-critical embedded software, so it has higher security and reliability requirements. How to effectively develop safe and reliable avionics software and control the development time and cost becomes a significant problem. An approach to develop the ARINC653-based software architecture is proposed. It converted the high-level requirements into the software architecture model, and then generated the source code of architecture from the software architecture model. The process helps to keep the consistency and traceability between requirements and architecture.

Airborne airworthiness certification DO-178C software release proposes a higher safety and reliability demands of airborne software. This raises great challenges to airborne software modeling and verification. In order to achieve airborne software high-level requirements objectives, we propose a formal method of modeling high-level requirements based on knowledge graph. The method gives a formal language to describe knowledge graph and constructs knowledge graph collaboratively. Then we represents high-level requirements by causal model and formal modeling of high-level functional requirements and non-functional requirements by knowledge graph. These improve the requirement traceability, namely these are helpful to trace the high-level requirements to system requirements so as to achieve high-level requirements’ traceability objective that DO-178C demands. Additionally, we provide the modeling tool for domain experts to construct knowledge graph collaboratively and realize their high-level requirements modeling. We also give some high-level requirements verification. These are significant to generate safe, reliable, accurate and high-quality airborne software.

Avionic software architecture has transit from a federated avionics architecture to an integrated modular avionics (IMA) .ARINC 653 (Avionics Application Standard Software Interface) is a software specification for space and time partitioning in Safety-critical avionics Real-time operating systems. Methods to transform the abstract avionics application logic function to the executable model have been brought up, however with less consideration about the code generating input and output model specific for ARINC 653 platform and inner-task synchronous dynamic interaction order sequence. In this paper, we proposed an AADL-based model-driven design methodology to fulfill the purpose to automatically generating Cµ executable model on ARINC 653 platform from the ARINC653 architecture which defined as AADL653 in order to facilitate the development of the avionics software constructed on ARINC653 OS. This paper presents the mapping rules between the AADL653 elements and the elements in Cµ language, and define the code generating rules , designs an automatic C µ code generator .Then, we use a case to illustrate our approach. Finally, we give the related work and future research directions., {"references":["C.B.Watkins and R.Walter, \"Transitioning from federated avionics architectures to Integrated Modular Avionics,\" In Proceedings of the\nIEEE/AIAA 26th Digital Avionics Systems Conference (DASC -07), October 2007.","Airlines electronic engineering committee (AEEC), avionics application\nsoftware standard interface - ARINC specification 653- part 1 (REQUIRED SERVICES), December 2005, ARINC, Inc.","ARINC 653 - An Avionics Standard for Safe, Partitioned Systems\". Wind River Systems / IEEE Seminar. August 2008.\nhttp://www.computersociety.it/wp-content/uploads/ 2008/08/ieee-cc-arin\nc653_final.pdf. Retrieved 2009-05-30.","\"ARINC 653 - An Avionics Standard for Safe, Partitioned Systems\" .\nWind River Systems / IEEE Seminar. August 2008. Retrieved\n2009-05-30.","Heath, Steve (2003). Embedded systems design. EDN series for design\nengineers (2 ed.). Newnes. p. 2. ISBN 978-0-7506-5546-0.","Sandeep K. Shukla, \"Model-Driven Engineering and Safety-Critical\nEmbedded Software,\" Computer, vol. 42, no. 9, pp. 93-95,Sept. 2009,\ndoi:10.1109/MC.2009.294","P. Feiler, B. Lewis, and S. Vestal. The SAE AADL standard: A basis for\nmodel-based architecture-driven embedded systems engineering. In\nProceedings of the RTAS 2003, Workshop on Model-Driven Embedded\nSystems, IEEE CS, 2003.","SAE Aerospace. SAE AS5506: Architecture Analysis and Design\nLanguage (AADL), Version 2.0, 2009.","SAE AS5506/2: Behavior Annex, January 17, 2011.\n[10] Telecom ParisTech AADL corner, Code generation , Ocarina AADL\ntoolsuite, http://penelope.enst.fr/aadl\n[11] Pierre Dissaux, Ellidiss Technologies,STOOD5.2 AADL tutorial,May\n2007.\n[12] Shenglin Gui, Liang Ma, Lei Luo, Limeng Yin ,Yun Li, UCaG: An\nAutomatic C Code Generator for AADL Based Upon DeltaOS,\n978-0-7695-3489-3/08, 2008 IEEE.\n[13] Wang, Ying Ma, Dianfu Zhao, Yongwang Zou, Lu Zhao, Xianqi, \"An\nAADL-based modeling method for ARINC653-based avionics software\"\n, 2011 IEEE 35th Annual Computer Software and Applications\nConference - COMPSAC 2011 ,pp. 224 - 229, July 2011.\n[14] A. Gamatié, T. Gautier, \"Synchronous modeling of avionics applications\nusing the Signal language,\" In Proceedings of the IEEE 9th Real-Time and Embedded Technology and Applications Symposium (RTAS-03),\nMay 2003."]}

Avionics software is safe-critical embedded software and its architecture is evolving from traditional federated architectures to Integrated Modular Avionics (IMA) to improve resource usability. ARINC 653 (Avionics Application Standard Software Interface) is a software specification for space and time partitioning in Safety-critical avionics Real-time operating systems. Arinc653 uses two-level scheduling strategies, but current modeling tools only apply to simple problems of Arinc653 two-level scheduling, which only contain time property. In avionics industry, we are always manually allocating tasks and calculating the timing table of a real-time system to ensure it-s running as we design. In this paper we represent an automatically generating strategy which applies to the two scheduling problems with dependent constraints in Arinc653 partition run-time environment. It provides the functionality of automatic generation from the task and partition models to scheduling policy through allocating the tasks to the partitions while following the constraints, and then we design a simulating mechanism to check whether our policy is schedulable or not, {"references":["Jean-Louis Camus, \"The Airbome Software Development Challenge,\"\nWhite Paper, ESTEREL TECHNOLOGIES, March 2010.","Sandeep K. Shukla, \"Model-Driven Engineering and Safety-Critical\nEmbedded Software,\" Computer, vol. 42, no. 9, pp. 93-95, Sept. 2009,\ndoi:10.1109/MC.2009.294","SAE Aerospace. SAE AS5506: Architecture Analysis and Design\nLanguage (AADL), Version 2.0, 2009.","C.B.Watkins and R.Walter, \"Transitioning from federated avionics\narchitectures to Integrated Modular Avionics,\" In Proceedings of the\nIEEE/AIAA 26th Digital Avionics Systems Conference (DASC -07),\nOctober 2007.","John Rushby,Partitioning in Avionics Architectures:Requirements,\nMechanisms, and Assurance, Langley Research Center Prepared for\nLangley Research Center Hampton, Virginia 23681-2199","Airlines electronic engineering committee (AEEC), avionics application\nsoftware standard interface - ARINC specification 653 - part 1\n(REQUIRED SERVICES), December 2005, ARINC, Inc.","ARINC CHARACTERISTIC 702A-3, December 15, 2006, ARINC, Inc.","F Singhoff, J Legrand, L Nana, L Marce Cheddar : a Flexible Real Time\nScheduling Framework in ACM SIGADA 2004 International conference\nProceedings (2004)"]}

Modern avionics architecture is evolving from traditional federated architecture to Integrated Modular Avionics (IMA) architecture. ARINC653 standard, which is employed in the avionics industry, supports partitioning core concept in IMA. Furthermore, avionic software has very high safety and reliability requirements in safety- critical domains. Therefore, how to develop high-integrity avionics software constructed on ARINC653 architecture becomes a very significant problem nowadays. In this paper we propose an automatic RT-Java code generation approach based on the AADL model for ARINC653 (AADL653) to enable the development of RT-Java ARINC653-based avionics software more productive and trustworthy. Our main contribution in this paper includes: (1) a mapping from the AADL653 model to a high-integrity RT-Java programming model for ARINC653 (RT-Java653); (2) an ARINC653-compliant RT-Java code generation algorithm suitable for complex multi-task collaboration interaction situation. Accordingly, we implement this RT-Java class library and corresponding code generator. Moreover, a simplified multi-task flight application as a case study is given to illustrate our approach and the preliminary experiment results show the validity of our approach.

To study the expression of cyclooxygenase-2 (COX-2) gene in breast cancer and its clinicopathologic characteristics.With beta-actin gene as reference, the COX-2 mRNA was monitored in 30 specimens of breast cancer tissue and adjacent normal breast tissue by reverse transcription-polymerase chain reaction (RT-PCR).The COX-2 mRNA expression was significantly upregulated in most breast cancer tissues with range of 0.05 - 0.91 (median 0.56), which was rare in normal breast tissue with range of 0 - 0.09 (median 0). The difference of COX-2 mRNA expression between cancer and normal breast tissue was significant (rank sum test, P0.05). COX-2 overexpression in breast cancer was related to its lymph node metastasis (P0.05) but not to age, tumor size, pathologic grade or pathologic type (P0.05).The level of COX-2 mRNA expression is obviously higher in the breast cancer tissue than that in normal breast tissue. COX-2 overexpression may play a crucial role in the carcinogenesis, development of cancer and lymph node metastasis in breast cancer patients.