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Methamphetamine (METH) is well-known as a potent psychostimulant of abuse worldwide. METH administration can cause neurotoxicity and neurodegenerative injury, which are similar to the two prevalent neurodegenerative disorders Alzheimer's disease (AD) and Parkinson's disease (PD). Recent results suggested that METH exposure increased the level of α-synuclein (α-syn) that could be a possible cause of neurotoxicity. However, the mechanism of METH-induced neurodegeneration remains unclear. This study was aimed at examining the effects of glycogen synthase kinase3β (GSK3β), α-syn, and tau on METH-induced neurotoxicity. Our results indicated that P-GSK3β (Tyr216), P-Tau (Ser396), α-syn, and P-α-syn (Ser129) levels were increased after METH administration in dose- and time-dependent manners. Upon inhibiting the GSK3β activity with LiCl or GSK3β-siRNA, these protein expressions were significantly decreased. We observed that LiCl protected the cells from METH-caused cytotoxicity by weakening the cell morphological damage and preventing cell apoptosis and death. We also found that P-GSK3β colocalized with P-Tau and α-syn by the immunofluorescence method. Further, METH disrupted the cellular autophagy by upregulation of LC3-II and P62 proteins, and the cellular autophagy was restored by LiCl and GSK3β-siRNA. The expressions of the α-syn-specific degradative enzyme glucocerebrosidase (GCase) with its regulator lysosomal integral membrane protein type-2 (LIMP-2) decreased inversely with the doses of METH treatment. The GCase inhibitor conduritol-β-epoxide (CβE) increased the α-syn levels, and LiCl restored GCase and LIMP-2 expressions disrupted by the METH treatment. In summary, we conclude that GSK3β plays key roles in METH-induced neurotoxicity and neurodegenerative injury by promoting abnormal protein phosphorylation and α-syn accumulation, blocking the autophagy–lysosomal degradation pathway, and finally leading to cell apoptosis and death. GSK3β may be a potential target to prevent METH-induced neurodegeneration.

The effective removal of aniline and its derivatives from wastewater is very important due to the high toxicity. Adsorption with a high-performance adsorbent is an efficient pathway. A novel activated carbon, ACUF-700, was synthesized using homemade ureaformaldehyde resin as the major carbon source carbonized at 700 °C. ACUF-700 is characterized by surface area analyzer, FTIR, elemental analyzer, and SEM. The adsorption properties of ACUF-700 towards anilines are also investigated by using batch methods. The test results showed that the ACUF-700 possesses higher specific surface area and narrower pore size distribution. In virtue of its developed pore structure and nitrogencontaining chemical groups, the adsorption capacities towards aniline, p-toluidine and p-chloroaniline could reach 95.6, 108.1 and 128.9mg/g, respectively. The adsorption process could be well described by the intra-particle mass transfer diffusion model and Sips model. Besides, ACUF700 was regenerated easily using diluted hydrochloric acid solution as eluent and ACUF700 possesses better reusability.

Nitrogen-containing porous carbons, the 800SP-NH3, were synthesized using sunflower plates as the major carbon source carbonized at 800°C and activated with concentrated aqueous ammonia at the same temperature. The porous carbons were characterized by nitrogen physical adsorption-desorption, surface area analyzer, FT-IR, and SEM. The adsorption properties of the porous carbons towards phenols were also investigated by batch methods. The test results show that the average pore diameter of porous carbon is smaller than 2 nm, and nitrogen-containing chemical groups are formed on its surface. The adsorption capacity for phenol, 4-chlorophenol, and p-nitrophenol is 316.5mg/g, 330.24mg/g and 387.62mg/g due to its developed pore structure and nitrogen-containing chemical groups. The adsorption isotherm data greatly obey the Langmuir model.

ARS2 protein is important to early development and cell proliferation, in which ARS2-CASP8AP2 interaction is implicated. However, the predictive significance of ARS2 in childhood acute lymphoblastic leukemia (ALL) is unknown. Here we evaluate the predictive values of ARS2 expression and combined ARS2 and CASP8AP2 expression in relapse. We showed that ARS2 expression in ALL bone marrow samples at initial diagnosis was markedly lower than that in complete remission (CR). Likewise, the levels of ARS2 expression in the patients suffering from relapse were significantly lower than that of patients in continuous CR. Furthermore, low expression of ARS2 was closely correlated to poor treatment response including poor prednisone response and high minimal residual disease (MRD), and the patients with high MRD (≥10(-4)) and low ARS2 were more subject to relapse. The multivariate analyses for relapse free survival and event free survival revealed that ARS2 expression remained an independent prognostic factor after adjusting other risk factors. In addition, combined assessment of ARS2 and CASP8AP2 expression was more accurate to predict relapse, based on which an algorithm composed of ARS2 and CASP8AP2 expression, prednisone response and MRD (day 78) was proposed. Together, ARS2 and CASP8AP2 expressions can precisely predict high-risk of relapse and ALL prognosis.

Purpose: To explore the connections between Tiam1 and Rac1 expression in renal cell carcinoma (RCC), and its pathological type, grading, invasion and metastasis. Methods: Tiam1 and Rac1 expression was measured in 60 specimens of RCC (including 42 clear cell cases, 12 papillary cases, and 6 chromophobe cases) and a 10-specimen control group using quantum dots IHC labeling, complete with clinical and pathological records, dated 2008 to 2014, were taken from the archives of the Department of Pathology, People’s Hospital of Wuhan University. The expressions of Tiam1 and Rac1 proteins in specimens were measured using immunohistochemical (IHC) and quantum dots-labeling methods to examine their relationships to the clinical and pathological characteristics of RCC. The HIPAS-1000 software was used to quantitatively analyze on the results to obtain absorbance and positive area ratio (PAR) values, and SPSS 15.0 was used to perform single-factor analysis of variance and q verification. Spearman’s rank correlation test is used to verify the correlation between absorbance and PAR of the two proteins. Results: 1. QDs IHC staining. Tiam1 and Rac1 expression is high in RCC, and low in surrounding tissues (P0.05), yet correlate with the differentiation, stage, and lymphatic metastasis of tumors (P

Stem cell-based tissue engineering provides a prospective strategy to bone tissue repair. Bone tissue repair begins at the recruitment and directional movement of stem cells, and ultimately achieved on the directional differentiation of stem cells. The migration and differentiation of stem cells are regulated by nucleoskeletal stiffness. Mechanical properties of lamin A/C contribute to the nucleoskeletal stiffness and consequently to the regulation of cell migration and differentiation. Nuclear lamin A/C determines cell migration through the regulation of nucleoskeletal stiffness and rigidity and involve in nuclear-cytoskeletal coupling. Moreover, lamin A/C is the essential core module regulating stem cell differentiation. The cells with higher migration ability tend to have enhanced differentiation potential, while the optimum amount of lamin A/C in migration and differentiation of MSCs is in conflict. This contrary phenomenon may be the result of mechanical microenvironment modulation.

Objective P2 receptors have been implicated in the release of neurotransmitter and pro-inflammatory cytokines due to their response to neuroexcitatory substances in the microglia. Dorsal horn P2Y12 and P2Y13 receptors are involved in the development of pain behavior induced by peripheral nerve injury. However, it is not known whether P2Y12 and P2Y13 receptors activation is associated with the expression and the release of interleukin-1B (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) in cultured dorsal spinal cord microglia. For this reason, we examined the effects of ADPβs (ADP analog) on the expression and the release of IL-1β, IL-6, and TNF-α. Methods and results In this study, we observed the effect of P2Y receptor agonist ADPβs on the expression and release of IL-1β, IL-6 and TNF-α by using real-time fluorescence quantitative polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). ADPβs induced the increased expression of Iba-1, IL-1β, IL-6 and TNF-α at the level of messenger RNA (mRNA). ADPβs-evoked increase in Iba-1, IL-1β, IL-6 and TNF-α mRNA expression was inhibited only partially by P2Y12 receptor antagonist MRS2395 or P2Y13 receptor antagonist MRS2211, respectively. Similarly, ADPβs-evoked release of IL-1β, IL-6 and TNF-α was inhibited only partially by MRS2395 or MRS2211. Furthermore, ADPβs-evoked increased expression of Iba-1, IL-1β, IL-6 and TNF-α mRNA, and release of IL-1β, IL-6 and TNF-α were nearly all blocked after co-administration of MRS2395 plus MRS2179. Further evidence indicated that P2Y12 and P2Y13 receptor-evoked increased gene expression of IL-1β, IL-6 and TNF-α were inhibited by Y-27632 (ROCK inhibitor), SB203580 (P38MAPK inhibitor) and PDTC (NF-κb inhibitor), respectively. Subsequently, P2Y12 and P2Y13 receptor-evoked release of IL-1β, IL-6 and TNF-α, were also inhibited by Y-27632, SB203580 and PDTC, respectively. Conclusion These observations suggest that P2Y12 and P2Y13 receptor-evoked gene expression and release of IL-1β, IL-6 and TNF-α are associated with ROCK/P38MAPK/NF-κb signaling pathway.

Objectives CREBBP alterations are associated with many diseases including leukaemia. However, CREBBP expression and its clinical relevance in paediatric acute lymphoblastic leukaemia have not been elucidated. Methods We studied CREBBP mRNA expression in 349 patients treated with either the BCH-2003 or CCLG-2008 protocol. Using a receiver operating characteristic curve, patients were divided into low- or high-CREBBP. The association among clinicobiological characteristics, outcomes, and CREBBP level was analysed. Results Low expression of CREBBP ( 10−2) after induction. We found significantly poorer event-free survival (EFS) and overall survival (OS) in low-CREBBP group whether administered BCH-2003 or CCLG-2008. Low-CREBBP was an inferior independent prognostic factor in BCH-2003; patients with low-CREBBP had better outcomes on an intermediate-risk regimen than a standard-risk regimen involving the CCLG-2008 protocol. Patients stratified to high-risk with low-CREBBP had the worst EFS and OS. Conclusions These findings indicate that low-CREBBP is predictive of unfavourable outcomes; thus, a more intensive treatment protocol is necessitated for standard-risk patients with insufficient CREBBP and that a specific target therapy is necessitated for high-risk patients. This article is protected by copyright. All rights reserved.

High-dose methotrexate (HDMTX) plays an important role in the treatment of acute lymphoblastic leukemia (ALL) although there is great inter-patient variability in the efficacy and toxicity of MTX. The relationship between polymorphisms in genes encoding MTX transporters and MTX response is controversial. In the present study, 322 Chinese children with standard- and intermediate-risk ALL were genotyped for 12 polymorphisms. SLCO1B1 rs10841753 showed a significant association with plasma MTX levels at 48 h (P = 0.017). Patients who had the ABCB1 rs1128503 C allele had longer duration of hospitalization than did those with the TT genotype (P = 0.006). No association was found between oral mucositis and any polymorphism. Long-term outcome was worse in patients with the SLCO1B1 rs4149056 CC genotype than in patients with TT or TC (5-year event-free survival [EFS] 33.3 ± 19.2% vs. 90.5 ± 1.7%, P < 0.001), and was worse in patients with the SCL19A1 rs2838958 AA genotype than in patients with AG or GG (5-year EFS 78.5 ± 4.6% vs. 92.2 ± 1.8%, P = 0.008). Multiple Cox regression analyses revealed associations of minimal residual disease (MRD) at day 33 (hazard ratio 3.458; P = 0.002), MRD at day 78 (hazard ratio 6.330; P = 0.001), SLCO1B1 rs4149056 (hazard ratio 12.242; P < 0.001), and SCL19A1 rs2838958 (hazard ratio 2.324; P = 0.019) with EFS. Our findings show that polymorphisms in genes encoding MTX transporters substantially influence the kinetics and response to HDMTX therapy in childhood ALL.

Objective This research was aimed to investigate the correct dose of nitrite that would act as a protection against the ischemic effects induced by acute myocardial infarction (AMI). Methods Mice were randomly divided into a sham-operation group (sham), an AMI operation group (AMI), and a nitrite pretreatment+AMI operation group (N+AMI). Seven days before the AMI operation, mice in the N+AMI group were pretreated with sodium nitrite in drinking water. Results One week after the AMI operation, serum lactate dehydrogenase (LDH) and creatine kinase (CK) activities in both AMI and N+AMI group were significantly higher than those in the sham group, but there were no significant differences between AMI and N+AMI mice. Contents of inducible nitric oxide synthase (iNOS) in the noninfarct area of the left ventricle in the N+AMI mice were significantly higher than those in the AMI mice, with no difference in the infarct area. Coagulation necrosis in the cardiomyocytes was observed in both AMI and N+AMI mice; however, it was less severe in the N+AMI mice. Western blot analyses showed that nitrite pretreatment resulted in up-regulation of antiapoptotic factors Bcl-2 and p21waf1/cip1 signal proteins, but down-regulation of the proapoptotic factor Bax signal protein. Furthermore, nitrite pretreatment also showed significant alleviation of AMI-induced signal protein expressions of inflammatory factors of NF-K B and oxidative factors of Hsp 70 and HO-1. Conclusion These results suggest that nitrite show certain protective effects against the ischemic effects induced by AMI in mice, which might be attributed to the synthesis of NO induced by iNOS through up-regulation of antiapoptotic factors and down-regulation of proapoptotic and inflammatory factors.

In this paper, a highly porous metal–organic framework (MOF) based on iron (III) trimesate (MIL-100 (Fe)) was applied to the adsorption of a harmful anionic dye, acid orange 7 (AO7), from aqueous solution. The influences of various factors on the adsorption as well as adsorption kinetics and isotherms were investigated. It was found that a relatively low pH value was favorable for the adsorption. The high dosage of the adsorbent led to a high decolorization rate, but a low adsorption quantity. The adsorption kinetics obeyed the pseudo-second-order kinetic model and the adsorption isotherms followed the Langmuir mode. The driving force of the adsorption was an entropy effect rather than an enthalpy change. The adsorption mechanism may be explained with a simple electrostatic interaction between AO7 aqueous solution and the adsorbent. The adsorption capacities of MIL-100 (Fe) are much higher than those of an activated carbon. Finally, it can be suggested that (MOFs) having high porosity and large pore size can be potential adsorbents to remove harmful AO7 in contaminated water.

Methamphetamine (MA) is a highly abused amphetamine‑like psychostimulant. At present, the mechanisms underlying MA‑induced cardiotoxicity are poorly understood. The cardiotoxic effects have yet not been clearly elucidated with respect to the apoptotic pathway. Insulin‑like growth factor binding protein‑5 (IGFBP5) is important for cell growth control and the induction of apoptosis. The aim of the present study was to analyze whether IGFBP5 is involved in MA‑induced apoptosis as a novel target. MA‑induced apoptosis was observed in neonatal rat ventricular myocytes (NRVMs) in a concentration‑dependent manner using a terminal deoxyribonucleotide transferase‑mediated dUTP nick end‑labeling assay. Using reverse transcription polymerase chain reaction and western blotting, MA was demonstrated to induce concentration‑dependent increases in the expression of IGFBP5. Silencing IGFBP5 with small interfering RNA significantly reduced apoptosis and suppressed the expression of caspase‑3 in NRVMs following treatment with MA. To the best of our knowledge, the present study provided the first evidence suggesting that IGFBP5 is a potential therapeutic target in MA‑induced apoptosis in vitro, providing a foundation for future in vivo studies.

This study was designed to improve the traditional scouring procedure using a solution of sodium silicate, sodium carbonate, H2O2, surfactant etc. as a refining agent for degumming machine-drawn raw silk sheet (RSS) and raw silk from the cocoon shell of the silkworm Bombyx mori. The RSS was scoured firstly in strongly alkaline electrolyzed water (SAEW, pH ≥ 11.5) consisting mainly of hydroxyl ions by boiling for 30 min and then treated by the traditional scouring procedure (without alkaline compounds), resulting in refined silk floss. The recycled SAEW containing sericin was separated by ultrafiltration into a retentate with a range of high molecular mass values accounting for 10% (w/w) of the cocoon shell and the filtrate was separated by nanofiltration into a purified H2O filtrate and a retentate containing oligopeptides and free amino acids, which can be used directly as food additives or in biological growth media. The ultrafiltration retentate was hydrolyzed by papain under three different conditions into three groups of sericin peptides with high, middle or low molecular mass. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and gel permeation high-performance liquid chromatography (GP-HPLC) showed the molecular mass of these sericin peptides was in the range 0.2–60, 0.2–30 and 0.2–15 kDa. These clean products have a variety of applications, including coating materials for surface modification, cell culture media and food additives. The procedure described here could be applied to the manufacture of silk floss quilts and the process of refining raw silk, which results in three clean products of the silk protein fibroin (i.e. stripped of sericin) and reduces environmental pollution from scouring waste containing sericin.

This study focused on the carboxylation method on multiwalled carbon nanotube (MWCNT) structure and property. The applicability of a novel adsorbent, the SA/MWCNT-CTS composite were obtained by controlling the reaction conditions. The SA/MWCNT-CTS composite was applied to the absorption of methyl orange (MO) from simulated dye wastewater .Adsorption dynamics and thermodynamics of SA/MWCNT-CTS microspheres were examined by UV-visible spectroscopy, and the associated adsorption mechanism was preliminarily investigated. Changes in the absorbance, throw ratio, conductivity, and the pH value of MO solution of MO solution during adsorption by SA/MWCNT-CTS microspheres were also studied. Results showed that the prepared SA/MWCNT-CTS microspheres retained excellent inherent chemical stability and had strong MO adsorption capacity. CS contains many hydroxyl groups, which are involved in the adsorption of organic dye. The adsorption process had a negative value of free energy change (∆G0); therefore, the process was a spontaneous reaction. At lower MO equilibrium concentrations, the SA/MWCNT-CTS microspheres had a greater capacity for adsorption.

Chitosan (CS) microspheres were successfully prepared via emulsion polymerization using biodegradable chitosan as raw material and glutaraldehyde as crosslinking agent. Micron-scale monodisperse CS microspheres were then obtained by controlling the reaction conditions. Simulated dye wastewater, containing methyl orange (MO), was examined for the adsorption dynamics and thermodynamics of CS microspheres by UV–vis spectroscopy, and the associated adsorption mechanism was preliminarily investigated. Changes in the absorbance, throw ratio, conductivity, and dissolved oxygen content of MO solution during adsorption by CS microspheres were studied, and the chemical structures of CS microspheres before and after MO adsorption were characterized by Fourier transform-infrared spectroscopy. Results showed that the prepared CS microspheres retained excellent inherent chemical stability and had strong MO adsorption capacity. CS contains many hydroxyl groups, which are involved in the adsorption of organic dye. The adsorption process had a negative value of free energy change (Δ G °); therefore, the process was a spontaneous reaction. At lower MO equilibrium concentrations, the CS microspheres had a greater capacity for adsorption.

A novel noncentrosymmetric coordination polymer, namely, [Cd2L(H2O)2]·solvent (1) (H4L = tetrakis[4-(carboxyphenyl)oxamethyl]methane acid), has been successfully solvothermally synthesized and characterized by signal-crystal X-ray diffraction, IR spectra, element analysis, powder X-ray diffraction and thermogravimetric analysis. The structure study shows that 1 exhibits a 3D framework based on 1D carboxylate-metal chains. Furthermore, 1 contains three types of helical chains along the c axis. From a topological perspective, 1 can be reduced to a new self-catenated binodal (4,6)-connected (66)(615) topology. In addition, the second-order nonlinear optical and fluorescent properties of 1 have also been investigated.

Potassium permanganate was selected as oxidant to treat cashmere fiber. Through fuzz mathematics method, the optimum treating condition of cashmere for potassium permanganate was got: temperature 50°C, time 20min, potassium permanganate 3g/L, pH 3; Through the fiber whiteness based on test result, optimum reduction conditions after potassium permanganate treatment was as following: Temperature 45°C, time 10min, sodium sulfite 30g/L, HAc 2%. Through test of felting, tensile property, compression property, it is obtained that potassium permanganate was suitable to oxidizing cashmere. After cashmere fibers were treated in optimum conditions, the strength of processing cashmere fiber decreases slightly, and the elongation and 15 second elasticity of compression recovery rate increases certainly.

Methamphetamine (MA) is a psychostimulant. MA may induce numerous cardiotoxic effects, leading to cardiac arrhythmias, heart failure, eventually leading to sudden cardiac death. The deleterious effects of methamphetamine work in tandem to disrupt the coordinated electrical activity of the heart and have been associated with life-threatening cardiac arrhythmias. Remodeling of ion channels is an important mechanism of arrhythmia. Although arrhythmogenic remodeling involves alterations in ion channel expression, it is yet unknown whether MA induced electrical remodeling by affecting gene expression, and whether the changes in protein expression are paralleled by alterations in mRNA expression. Our study focused on the expression of ion channels which were correlated to the electrical remodeling caused by MA. We used RT-PCR and western blot to assess of the transcript and translate levels of ion channel subunits, including Ito: kv1.4, kv1.7, kv3.4, kv4.2; IK1: kir2.1, kir2.2, kir2.3, kir2.4; and ICa-l: Ca(2+)α1, Ca(2+)β, respectively. The reversible effect of these changes after MA withdrawal was also evaluated. MA caused decrease in mRNA and protein levels in all ion channel subunits in vitro and also in vivo, is at this work. The kv3.4 and all 4 subunits of Kir2.0 family showed significant decrease than the other genes. Most of the channel subunit expression started to reverse after MA withdrawal for 4 weeks and significantly reverse in all of the channel subunits after MA withdrawal for 8 weeks. We found that CACNA1C and Kir2.0 family showed lower recoverability than the others after MA withdrawal for 8 weeks. The reduction of the ion channel expression levels may be the molecular mechanism that mediates the electrical remodeling caused by methamphetamine.

Mulberry raw silk is composed of sericin and fibroin and must be soaked before it is reeled. In this paper, the effect of soaking temperature and soaking time in clean water on mechanical properties and appearance of mulberry silk is studied. When soaking time is 40 min and soaking temperature is 55 °C, the resulting silk can satisfied with further operation.

Background Interphase fluorescence in situ hybridization (FISH) of bone marrow cells has been confirmed to be a direct and valid method to assess the v-myc avian myelocytomatosis viral oncogene neuroblastoma derived homolog (MYCN) amplification in patients with bone marrow metastatic neuroblastoma. MYCN amplification alone, however, is insufficient for pretreatment risk stratification. Chromosome band 11q23 deletion has recently been included in the risk stratification of neuroblastoma. In the present study, we aimed to evaluate the biological characteristics and prognostic impact of 11q23 deletion and MYCN amplification in patients with bone marrow metastatic neuroblastoma. Methods We analyzed the MYCN and 11q23 statuses of 101 patients with bone marrow metastatic neuroblastoma using interphase FISH of bone marrow cells. We specifically compared the biological characteristics and prognostic impact of both aberrations. Results MYCN amplification and 11q23 deletion were seen in 12 (11.9%) and 40 (39.6%) patients. The two markers were mutually exclusive. MYCN amplification occurred mainly in patients with high lactate dehydrogenase (LDH) and high neuron-specific enolase (NSE) levels (both P