ExtHT: A hybrid tracing method for cyber-attacks in power industrial control systems.

Tracing the sources of cyber-attacks in Power Industrial Control Systems (PICS) can help the defense systems to block the attacks, and support the decision of the grid control policies. However, there has been no work on the cyber-attack source traceback for PICS, and the methods for the Internet are not suitable for PICS in terms of fineness, real-time performance, and supporting communication protocols. Therefore, a method for tracing cyber-attacks in PICS is proposed. First, the communication network architecture of PICS and the cyber security threats to PICS are analyzed. Then, an extended hybrid tracing method (ExtHT) based on packet marking and packet logging is proposed. This method involves all the devices working at the data link layer and upper layers to achieve more fine-grained attack tracing. At the same time, taking the costs of attack tracing into consideration, a coarse-grained tracing mode is presented to improve the tracing speed. In addition, a log database optimization scheme is provided to reduce storage costs. To facilitate the application of this method in practice, a cyber-attack source tracing system and its deployment architecture are designed for PICS. Further, the applicability and limitations of ExtHT are analyzed, theory ratiocinations are given to justify our ExtHT, and the performance of our ExtHT is compared with that of existing mainstream methods. Finally, two cyber-attack scenarios against PICS are constructed and the feasibility of ExtHT is verified on them.

Decreased microRNA-182-5p helps alendronate promote osteoblast proliferation and differentiation in osteoporosis via the Rap1/MAPK pathway.

Osteoporosis (OP) is a serious health problem that contributes to osteoporotic structural damage and bone fragility. MicroRNAs (miRNAs) can exert important functions over bone endocrinology. Therefore, it is of substantial significance to clarify the expression and function of miRNAs in bone endocrine physiology and pathology to improve the potential therapeutic value for metabolism-related bone diseases. We explored the effect of microRNA-182-5p (miR-182-5p) on osteoblast proliferation and differentiation in OP rats after alendronate (ALN) treatment by targeting adenylyl cyclase isoform 6 (ADCY6) through the Rap1/mitogen-activated protein kinase (MAPK) signaling pathway. Rat models of OP were established to observe the effect of ALN on OP, and the expression of miR-182-5p, ADCY6 and the Rap1/MAPK signaling pathway-related genes was determined. To determine the roles of miR-182-5p and ADCY6 in OP after ALN treatment, the relationship between miR-182 and ADCY6 was initially verified. Osteoblasts were subsequently extracted and transfected with a miR-182-5p inhibitor, miR-182-5p mimic, si-ADCY6 and the MAPK signaling pathway inhibitor U0126. Cell proliferation, apoptosis and differentiation were also determined. ALN treatment was able to ease the symptoms of OP. miR-182-5p negatively targeted ADCY6 to inhibit the Rap1/MAPK signaling pathway. Cells transfected with miR-182 inhibitor decreased the expression of ALP, BGP and COL I, which indicated that the down-regulation of miR-182-5p promoted cell differentiation and cell proliferation and inhibited cell apoptosis. In conclusion, the present study shows that down-regulated miR-182-5p promotes the proliferation and differentiation of osteoblasts in OP rats through Rap1/MAPK signaling pathway activation by up-regulating ADCY6, which may represent a novel target for OP treatment.

Effects of MicroRNA-206 on Osteosarcoma Cell Proliferation, Apoptosis, Migration and Invasion by Targeting ANXA2 Through the AKT Signaling Pathway.

BACKGROUND/AIMS: This study aimed to investigate the mechanism by which microRNA-206 (miR-206) affects the proliferation, apoptosis, migration and invasion of osteosarcoma (OS) cells by targeting ANXA2 via the AKT signaling pathway. METHODS: A total of 132 OS tissues and 120 osteochondroma tissues were examined in this study. The targeting relationship between miR-206 and ANXA2 was verified with a dual-luciferase reporter assay. The miR-206 expression and ANXA2, AKT, PARP, FASN, Survivin, Bax, Mcl-1 and Bcl-1 mRNA and protein expression in the above two groups were examined by qRT-PCR and western blotting. The cultured OS cells were divided into 6 groups: a blank group, negative control (NC) group, miR-206 mimic group, miR-206 inhibitor group, si-ANXA2 group and miR-206 inhibitor + si-ANXA2 group. Cell cycle and apoptosis were assessed by flow cytometry, cell migration was examined with a wound-healing assay, and cell invasion was assessed with a Transwell assay. Pearson correlation analysis was used to determine the correlation between ANXA2 mRNA expression and miR-206 expression in OS. RESULTS: OS tissues exhibited increased mRNA and protein expression of ANXA2, AKT, PARP, FASN, Survivin, Mcl-1 and Bcl-2; decreased miR-206 expression; and decreased Bax mRNA and protein expression. ANXA2 mRNA expression was strongly negatively correlated with miR-206 expression in OS. ANXA2 was found to be a miR-206 target gene. In the miR-206 mimic group and the si-ANXA2 group, the mRNA and protein expression of ANXA2, AKT, PARP, FASN, Survivin, Mcl-1 and Bcl-1 decreased markedly, cell proliferation was inhibited, apoptosis was promoted, higher cell growth in G1 phase and decreased growth in S phase was detected, and decreased cell migration and invasion were observed compared with those in the blank group. CONCLUSION: The current results demonstrate that miR-206 overexpression inhibits OS cell proliferation, migration and invasion and promotes apoptosis through targeting ANXA2 by blocking the AKT signaling pathway.

[Clinical research of timing of application of antibiotics in septic shock of pediatric patients].

OBJECTIVE: To investigate the value of timing of antibiotics in pediatric septic shock. METHODS: Eighty children with septic shock treated with bundle treatment in Department of Critical Care Medicine were retrospectively analyzed. Eighty children with septic shock were divided into observation group (n=40, anti-infection therapy within 1 hour after admission) and control group (n=40, anti-infection therapy 1-6 hours after admission). The contents of lactate, C-reaction protein (CRP) and procalcitonin (PCT) were compared between two groups at admission and 24 hours and 72 hours after admission. RESULTS: Lactate in the observation group was significantly lower than that of the control group within the first 24 hours after admission (8.65 ± 2.84 mmol/L vs. 11.75 ± 3.20 mmol/L, P<0.01). CRP in the observation group was significantly lower than that of the control group 24 hours and 72 hours after admission (66.25 ± 8.55 mg/L vs. 91.77 ± 7.71 mg/L, 22.03 ± 7.46 mg/L vs. 50.11 ± 7.30 mg/L, both P<0.01). PCT in the observation group was significantly lower than that of the control group 72 hours after admission (0.67 ± 0.31 µg/L vs. 1.16 ± 0.25 µg/L, P<0.01). Time for shock recovery in the observation group was significantly shorter than that of the control group (6.80 ± 3.70 hours vs. 12.80 ± 3.63 hours, P<0.05), but no statistical difference in mortality rate between groups was found [5% (2/40) vs. 10% (4/40), P>0.05]. CONCLUSION: With the early empirical anti-infection treatment in pediatric septic shocked patients, time for recovery from shock can be shortened and successful rate of resuscitation can be improved.

Leukemia-associated translocation products able to activate RAS modify PML and render cells sensitive to arsenic-induced apoptosis.

Since the 19th century, arsenic (As2O3) has been used in the treatment of chronic myelogenous leukemia (CML) characterized by the t(9;22) translocation. As2O3 induces complete remissions in patients with acute promyelocytic leukemia. The response to As2O3 is genetically determined by the t(15;17)-or the t(9;22)-specific fusion proteins PML/RARalpha or BCR/ABL. The PML portion of PML/RARalpha is crucial for the sensitivity to As2O3. PML is nearly entirely contained in PML/RARalpha. PML is upregulated by oncogenic RAS in primary fibroblasts. The aberrant kinase activity of BCR/ABL leads to constitutive activation of RAS. Therefore, we hypothesized that BCR/ABL could increase sensitivity to As2O2-induced apoptosis by modifying PML expression. To disclose the mechanism of As2O3-induced apoptosis in PML/RARalpha- and BCR/ABL-expressing cells, we focused on the role of PML for As2O3-induced cell death. Here we report that (i) sensitivity to As2O3-induced apoptosis of U937 cells can be increased either by overexpression of PML, or by conditional expression of activated RAS; (ii) also the expression of the t(8;21)-related AML-1/ETO increased sensitivity to As2O3-induced apoptosis; (iii) both BCR/ABL and AML-1/ETO activated RAS and modified the PML expression pattern; (iv) the expression of either BCR/ABL or AML-1/ETO rendered U937 cells sensitive to interferon alpha-induced apoptosis. In summary, these data suggest a crucial role of factors able to upregulate PML for As2O2-induced cell death.

[Preliminary study on the molecular mechanism of K562 cell apoptosis induced by As2S2].

OBJECTIVE: To investigate the apoptotic inducing effect of As(2)S(2) on K562 cells. METHODS: The apoptotic inducing effect of As(2)S(2) on K562 cells was determined by flow cytometry, DNA fragmentation analysis and morphology observation. Expression of protein was determined by Western-blot. RT-PCR was used to evaluate changes in gene expression. RESULTS: Apoptosis of K562 cells was induced by 48 - 72 h exposure to 5 micromol/L As(2)S(2). Apoptosis was induced in (34.4 +/- 3.3)% treated cells by 72 h exposure to 3 micro mol/L As(2)S(2), in (21.8 +/- 3.6)% treated cells by 48 h exposure to 5 micromol/L As(2)S(2) and in (46.0 +/- 5.2)% treated cells by 72 h exposure to As(2)S(2) at the same concentration. With 5 micromol/L As(2)S(2), the protein level of Bcr-Abl and JAK2 decreased, while bax expression was upregulated and c-myc was downregulated both in protein and mRNA level. The activity of caspase 3 in K562 cells was increased by As(2)S(2). As(2)S(2) also induced apoptosis of fresh mononuclear cells derived from chronic myelogenous leukemia (CML) patients. CONCLUSION: As(2)S(2) can induce apoptosis of CML cells. The decline of Bcr-Abl may play an important role. The upregulation of bax, increase of the activity of caspase 3, downregulation of c-myc and decrease of JAK2 may also be involved in the mechanism.

[Synergism of As2S2 and STI 571 in inducing apoptosis of K562 cells].

OBJECTIVE: To investigate the synergistic effect of As(2)S(2) and STI 571 on K562 cells and its mechanism. METHODS: The inhibitive effect of As(2)S(2) on the proliferation of K562 cells was determined by cell number count. Cell apoptosis was assessed by flow cytometry, DNA fragmentation and morphology. Protein expression was determined by Western-blot and gene expression by RT-PCR. RESULTS: As(2)S(2) could significantly inhibit the proliferation and induce apoptosis of K562 cells in a dose and time-dependent manner at concentrations from 1 micromol/L to 5 micromol/L for 24 approximately 72 h. 34.4%, 21.8% and 46.0% of the treated-cells displayed apoptosis at 3 micro mol/L for 72 h, 5 micromol/L for 48 h and 5 micromol/L for 72 h, respectively. Compared to treatment with STI571 (0.25 approximately 1.00 micromol/L) or As(2)S(2) (1 approximately 5 micromol/L) alone, treatment of K562 cells with As(2)S(2) and STI571 combination induced more cell apoptosis. (18.4 +/- 1.4)% and (15.8 +/- 1.2)% cells underwent apoptosis at 1 micromol/L STI571 for 48 h and 5 micromol/L As(2)S(2) for 48 h, respectively, and (40.6 +/- 2.0)% cells did in combination treatment (P < 0.05). For U937 cells, the percentages of apoptotic cells were (6.0 +/- 1.1)% at 1 micromol/L STI571 for 48 h, (4.5 +/- 1.2)% at 5 micromol/L As(2)S(2) for 48 h, and (7.3 +/- 1.0)% in combination treatment. As(2)S(2) decreased the bcr-abl fusion protein expression and PTK activity of c-abl and bcr-abl, but not for bcr-abl expression. CONCLUSION: Combination treatment with As(2)S(2) and STI 571 induced more apoptosis of K562 cells. The reduction of PTK activity may be involved in the mechanisms.

Apoptotic effect of As2S2 on K562 cells and its mechanism.

AIM: To investigate the apoptotic effect of As2S2 on K562 cells and its mechanism. METHODS: The effect of As2S2 on proliferation of K562 cells was determined by counting the number of cells. Apoptosis was assessed by flow cytometry, DNA fragmentation analysis, and morphology observation. Expression of protein was determined by Western blot. RT-PCR was used to evaluate changes in gene expression. RESULTS: As2S2 greatly inhibited the proliferation and induced apoptosis of K562 cells in a concentration- and time-dependent manner at the concentration range of 1-5 micromol/L during 24-72 h. Viable cells were decreased to approximately 71 % of control at the concentration of 5 micromol/L after 48-h incubation, 31.4 % after 72-h incubation, and 45.4 % at 3 micromol/L after 72-h incubation. At 3 micromol/L for 72 h, 5 micromol/L for 48 h, and 5 micromol/L for 72 h, the apoptosis rate were 34.4 %, 21.8 %, and 46 % of the treated-cells, respectively. As2S2 decreased the Bcr-Abl fusion protein and protein tyrosine kinase (PTK) activity of c-abl and Bcr-Abl, but it did not change the transcription of bcr-abl assayed. As2S2 also induced apoptosis in fresh mononuclear cells derived from chronic myelogenous leukemia (CML) patients. CML Ph+ leukemia cells were more sensitive to the apoptotic effect of As2S2 than Ph- mononuclear cells (P<0.05). CONCLUSION: As2S2 inhibited the proliferation and induced apoptosis in K562 and fresh CML mononuclear cells. The decline of the Bcr-Abl protein and its PTK activity may play an important role in the apoptotic effect of As2S2. As2S2 may be a useful agent for the treatment of CML.