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Aiming at the problem of traffic data distribution shift caused by new unknown attacks in the industrial Internet, a malicious traffic identification method based on neighborhood filtering and stable learning was proposed to enhance the effectiveness and robustness of the existing graph neural network model in identifying known malicious traffic. Firstly, the graph structure of the traffic data was modeled to capture the topological relationship and interaction mode in communication behavior. Secondly, the traffic subgraph was divided based on the neighborhood filtering mechanism of biased sampling to eliminate the pseudo-homogeneity between communication behaviors. Finally, the statistical independence of high-dimensional traffic features was realized by applying graph representation learning and stable learning strategies, combined with adaptive sample weighting and collaborative loss optimization methods. The experimental results on two benchmark datasets show that compared with the baseline method, the recognition performance of the proposed method is increased by more than 2.7% in the new unknown attack scenario, which shows its high efficiency and practicability in the industrial Internet environment. [ABSTRACT FROM AUTHOR]

Current treatment for hemophilia A is based on replacement therapy that is the most effective method by using recombinant clotting factor FⅧ (rFⅧ). Although the safety and effectiveness of replacement therapy has been proved by clinical practice for the last decades, FⅧ products are temporally limited because of a short half-life and requiring prophylactic injections frequently for most patients, usually three times per week or every other day. Frequent intravenous injection not only brings physical pain to the patient, but also produces FⅧ antibodies that seriously affect the treatment effect. In this paper, we review the present status, research progress and main problems of the long-acting recombinant factor Ⅷ.

Hemophilia B is an X chromosome linked hereditary hemorrhagic disease, which is caused by the lose function mutation of factor IX (FIX), and significantly affects the patients' lifespan and life quality. The severity of hemophilia B depends on the FIX level in the plasma. By referring to the relevant literatures, we reviewed and summarized hemophilia B replacement therapies. Specifically, we focus on recombinant factor IX products on the market and those in the pipeline, especially on the long-acting factor IX drugs, to provide the basis for researches of new hemophilia B drugs.

We established methods to isolate human amniotic fluid-derived progenitor cells (hAFPCs), and analyze the ability of hAFPCs to secrete human coagulation factor IX (hFIX) after gene modification. The hAFPCs were manually isolated by selection for attachment to gelatin coated culture dish. hFIX cDNA was transfected into hAPFCs by using a lentiviral vector. The hFIX protein concentration and activity produced from hAFPCs were determined by enzyme-linked immunosorbent assay (ELISA) and clotting assay. The isolated spindle-shaped cells showed fibroblastoid morphology after three culture passages. The doubling time in culture was 39.05 hours. Immunocytochemistry staining of the fibroblast-like cells from amniotic fluid detected expression of stem cell markers such as SSEA4 and TRA1-60. Quantitative PCR analysis demonstrated the expression of NANOG, OCT4 and SOX2 mRNAs. Transfected hAFPCs could produce and secrete hFIX into the culture medium. The observed concentration of secreted hFIX was 20.37% +/- 2.77% two days after passage, with clotting activity of 16.42% +/- 1.78%. The amount of hFIX:Ag reached a plateau of 50.35% +/- 5.42%, with clotting activity 45.34% +/- 4.67%. In conclusion, this study established method to isolate and culture amniotic fluid progenitor cells. Transfected hAFPCs can produce hFIX at stable levels in vitro, and clotting activity increases with higher hFIX concentration. Genetically engineered hAFPC are a potential method for prenatal treatment of hemophilia B.

To compare the regulation effects by different promoters on bovine prolactin gene expression in different cell lines, three recombinant bovine prolactin expression vectors were constructed using different promoters, i.e., CMV promoter, bovine prolactin gene promoter and goat beta-casein gene promoter, respectively named pCMV, pPRLP and pP1A3, which were transfected into two cell lines, mouse pituitary tumor cell strain (AtT20) and mouse mammary epithelial cell strain (HC11), respectively. RT-PCR and real-time RT-PCR were used to investigate the expression level of the above three vectors in both cell lines, pCMV vector was effectively expressed in both cell lines, pPRLP vector had a similar expression level to that of pCMV in both cell lines, pP1A3 was expressed in HC11 but not in AtT20. pP1A3 was tissue-specific to mammary gland, pPRLP was able to express with a significant level in pituitary and mammary glands, while its tissue-specific characteristics in other tissues need further investigation.

Objective: To investigate the expression of human specific proteins in liver tissue obtained from goats engrafted with human hematopoietic stem cells (hHSC)., Methods: hHSCs derived from cord blood were transplanted into fetal goats for production of chimerism. Liver specimens were obtained from four 10-month-old chimeric goats and examined for their reactivity with monoclonal antibodies against human antigens: proliferating cell nuclear antigen (PCNA) and hepatocyte specific antigen (HSA). The presence of human HSA positive cells in the goat liver tissue was determined by fluorescence assisted cell sorting (FACS). The expression of human hepatocyte nuclear factor (hHNF-3beta) and human serum albumin (hALB) mRNAs was determined by RT-PCR. Meanwhile, FISH experiment was also performed to detect the human cells in the chimeric livers with the probe of human p17H8., Results: Successful engraftment was confirmed by the detection of human blood cell chimerism in the circulation of the transplanted goats. Human PCNA and HSA were found in liver specimens of transplanted goats but not of normals. FACS analysis showed the presence of human HSA positive cells in the liver of chimeric goats. RT-PCR results demonstrated that hHNF-3beta and hALB mRNAs were specifically expressed in liver tissues of chimeric goats. FISH experiment showed two positive hybridized signals in some liver cells of the chimeric goats, indicating that human liver-like cells were present there., Conclusion: Goats engrafted with hHSC are capable to produce chimeric livers. Growth and propagation of human cells in the liver tissue of such transplanted goats were possible. Particularly, the human liver-like cells in chimeric goat livers had transcriptional activity specific to human hepatocytes.

Objective: To establish a human/goat hematopoietic stem cell (HSC) xenogeneic transplant model and to probe the engraftment, expansion and differentiation of human HSC in vivo., Methods: Human HSCs were isolated from human umbilical cord blood and 1 x 10(5) human HSCs were in utero transplanted into 50 fetal goats at the 55 - 65 the gestation days. The engraftment, expansion and differentiation of human HSCs in goats were determined by FACS analysis, PCR and PCR-Southern blot hybridization at various intervals after birth., Results: Hematopoietic chimerism occurred certainly in 35 of 39 live-born recipients. On average, The proportion of human hematopoietic cells in goat blood was 1% approximately 3% and remained phenotypically stable for at least 10 months. The human hematopoietic cells circulated in goat blood expressed CD34, CD14, CD20 and glycophorin A (GPA) but did not express CD3, CD4, CD7, CD8 and CD56 or expressed them at a very low level., Conclusion: The number of human HSC can be effectively expanded 1 000 - 10 000 fold. Human HSCs in goats undergo a limited differentiation. Our human/goat HSC xenogeneic model provides a useful way for the investigation of HSC transplantation, expansion and differentiation in vivo.