Protein tyrosine phosphatase Meg2 dephosphorylates signal transducer and activator of transcription 3 and suppresses tumor growth in breast cancer

INTRODUCTION: Signal transducer and activator of transcription 3 (STAT3) is over-activated or phosphorylated in breast cancers. The hyper-phosphorylation of STAT3 was attributed to either up-regulated phosphorylation by several tyrosine-kinases or down-regulated activity of phosphatases. Although several factors have been identified to phosphorylate STAT3, it remains unclear how STAT3 is dephosphorylated by PTPMeg2. The aim of this study was to determine the role of PTPMeg2 as a phosphatase in regulation of the activity of STAT3 in breast cancers. METHODS: Immunoprecipitation assays were used to study the interaction of STAT3 with PTPMeg2. A series of biochemistry experiments were performed to evaluate the role of PTPMeg2 in the dephosphorylation of STAT3. Two breast cancer cell lines MCF7 (PTPMeg2 was depleted as it was endogenously high) and MDA-MB-231 (PTPMeg2 was overexpressed as it was endogenously low) were used to compare the level of phosphorylated STAT3 and the tumor growth ability in vitro and in vivo. Samples from breast carcinoma (n = 73) were subjected to a pair-wise Pearson correlation analysis for the correlation of levels of PTPMeg2 and phosphorylated STAT3. RESULTS: PTPMeg2 directly interacts with STAT3 and mediates its dephosphorylation in the cytoplasm. Over-expression of PTPMeg2 decreased tyrosine phosphorylation of STAT3 while depletion of PTPMeg2 increased its phosphorylation. The decreased tyrosine phosphorylation of STAT3 is coupled with suppression of STAT3 transcriptional activity and reduced tumor growth in vitro and in vivo. Levels of PTPMeg2 and phosphorylated STAT3 were inversely correlated in breast cancer tissues (P = 0.004). CONCLUSIONS: PTPMeg2 is an important phosphatase for the dephosphorylation of STAT3 and plays a critical role in breast cancer development

A Novel Memory-hard Password Hashing Scheme for Blockchain-based Cyber-physical Systems

There has been an increasing interest of integrating blockchain into cyber-physical systems (CPS). The design of password hashing schemes (PHSs) is in the core of blockchain security. However, no existing PHS seems to meet both the requirements of sufficient security and small code size for blockchain-based CPSs. In this article, a novel memory-hard PHS based on the classic PBKDF2 is proposed. Evaluation results show that the proposed scheme is promising for blockchain-based CPS, as it manages to provide enhanced security in comparison to PBKDF2 with limited increase in code size.</jats:p

Revealing the Effects of Water Imbibition on Gas Production in a Coalbed Matrix Using Affected Pore Pressure and Permeability

The effect of water imbibition on characteristics of coalbed methane reservoirs, such as permeability, gas occurrence state, and gas production, is controversial. According to the mechanism of imbibition, gas and water distribution in blind pores is reconfigured during the fracturing process. Therefore, a new comprehensive model of pore pressure and permeability, based on the perfect gas equation and the weighted superposition of viscous flow and Knudsen diffusion, was established for micro- and nanoscale blind pores during water drainage. Using the numerical simulation module in the Harmony software, the effects of imbibition on coal pore pressure, permeability, and gas production were analyzed. The results showed that (1) water imbibition can increase pore pressure and reduce permeability, and (2) water imbibition is not always deleterious to gas production and estimated ultimate reserve (EUR), when the imbibition is constant, the thicker water film is deleterious to coalbed methane wells; when the thickness of water film is constant, more imbibition is beneficial to gas production and EUR. This research is beneficial to optimize the operation of well shut-ins after fracturing and provides methods for optimizing key parameters of gas reservoirs and insights into understanding the production mechanism of coalbed methane wells

Coal Facies and Its Effects on Pore Characteristics of the Late Permian Longtan Coal, Western Guizhou, China

The coal facies and their effects on the coal pore characteristics of the Late Permian Longtan Formation, western Guizhou, were studied, using diverse experiments of macerals and minerals compositions, vitrinite reflectance, and pore characteristics. The results show that five coal facies exist in studied samples, and they are shallow-water covered forest peat swamp facies, moist forest peat swamp facies, dry forest peat swamp facies, low peat swamp facies, and wet land herbaceous peat swamp facies. Among them, the moist forest peat swamp facies accounts for the largest proportion, followed by the shallow-water covered forest peat swamp and dry forest peat swamp facies. The order of pore development degree is identical with the order of moist forest peat swamp facies coal > shallow-water covered forest peat swamp facies coal > dry forest peat swamp facies coal. In contrast to shallow-water covered forest peat swamp facies and dry forest peat swamp facies samples, moist forest peat swamp facies samples have higher porosity and larger pore size. Coal facies play an important role in controlling the pore structure of coal reservoir, which have more effect on pore size distribution than coal rank for the samples in this study

The pharmacokinetics of buserelin after intramuscular administration in pigs and cows

Abstract Background Buserelin is a luteinizing hormone releasing hormone (LHRH) agonist used for the treatment of hormone-dependent diseases in males and females. However, the pharmacokinetics of buserelin in pigs and cows are not fully understood. This study was designed to develop a sensitive method to determine the concentration of buserelin in blood plasma and to investigate the pharmacokinetic parameters after intramuscular (i.m.) administration in pigs and cows. Results A sensitive and rapid stability method based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was developed. The pharmacokinetic parameters of buserelin after i.m. administration were studied in five pigs and five cows at a single dose of 1 mg per pig and 3 mg per cow. The plasma kinetics were analyzed by WinNonlin 8.1.0 software using a non-compartmental model. The mean concentration area under the curve (AUC0-t) was 25.02 ± 6.93 h × ng/mL for pigs and 5.63 ± 1.86 h × ng/mL for cows. The maximum plasma concentration (Cmax) and time to reach the maximum concentration (tmax) were 10.99 ± 2.04 ng/mL and 0.57 ± 0.18 h for pigs and 2.68 ± 0.36 ng/mL and 1.05 ± 0.27 h for cows, respectively. The apparent volume of distribution (Vz) in pigs and cows was 80.49 ± 43.88 L and 839.88 ± 174.77 L, respectively. The elimination half-time (t1/2), and clearance (CL) were 1.29 ± 0.40 h and 41.15 ± 11.18 L/h for pigs and 1.13 ± 0.3 h and 545.04 ± 166.40 L/h for cows, respectively. No adverse effects were observed in any of the animals. Conclusion This study extends previous studies describing the pharmacokinetics of buserelin following i.m. administration in pigs and cows. Further studies investigating other factors were needed to establish therapeutic protocol in pigs and cows and to extrapolate these parameters to others economic animals. </jats:sec

Disrupted grey matter network morphology in pediatric posttraumatic stress disorder

Introduction: Disrupted topological organization of brain functional networks has been widely observed in posttraumatic stress disorder (PTSD). However, the topological organization of the brain grey matter (GM) network has not yet been investigated in pediatric PTSD who was more vulnerable to develop PTSD when exposed to stress. Materials and methods: Twenty two pediatric PTSD patients and 22 matched trauma-exposed controls who survived a massive earthquake (8.0 magnitude on Richter scale) in Sichuan Province of western China in 2008 underwent structural brain imaging with MRI 8–15 months after the earthquake. Brain networks were constructed based on the morphological similarity of GM across regions, and analyzed using graph theory approaches. Nonparametric permutation testing was performed to assess group differences in each topological metric. Results: Compared with controls, brain networks of PTSD patients were characterized by decreased characteristic path length (P = 0.0060) and increased clustering coefficient (P = 0.0227), global efficiency (P = 0.0085) and local efficiency (P = 0.0024). Locally, patients with PTSD exhibited increased centrality in nodes of the default-mode (DMN), central executive (CEN) and salience networks (SN), involving medial prefrontal (mPFC), parietal, anterior cingulate (ACC), occipital and olfactory cortex and hippocampus. Conclusions: Our analyses of topological brain networks in children with PTSD indicate a significantly more segregated and integrated organization. The associations and disassociations between these grey matter findings and white matter (WM) and functional changes previously reported in this sample may be important for diagnostic purposes and understanding the brain maturational effects of pediatric PTSD. Keywords: Pediatric PTSD, Topological organization, Graph theory, Brain network, MRI, Psychoradiolog