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A strong shear flow was imposed on the melt of polycarbonate (PC) microfibrils with β-nucleation agent reinforced isotactic polypropylene (iPP) during the melt second flow process, i.e. gas-assisted injection molding (GAIM). A special shell-core structure was formed in the iPP/PC microfibrils with β-nucleation agent (PP/PC/β-NA) composites. A lot of β-transcrystalline and α-transcrystalline superstructures were observed in the skin and sub-skin regions, whereas β-spherulite structures were formed in the gas channel region. There is no doubt that the distinct hierarchical structure has great potential to significantly improve the mechanical performance of the composites, and the experimental results verify this. The results of the mechanical performance testing show that the yield strength of the PP/PC/β-NA composites reached 61.9 MPa, which is 19.7 MPa higher than that of the iPP parts molded by GAIM (G-iPP) (42.2 MPa). The tensile modulus of the PP/PC/β-NA composites (3.3 GPa) increased by 135%, compared to that of G-iPP (1.4 GPa). The high content of β-crystals improved the elongation at break of the composites compared to the iPP/PC microfibril (PP/PC) composites; the elongation at break of the PP/PC/β-NA composites (13%) is over 3 times greater than that of the PP/PC composites (4%).

Graphene quantum dots (GQDs) possess unique properties of graphene and exhibit a series of new phenomena of 0 dimension (D) carbon materials. Thus, GQDs have attracted much attention from researchers and have shown great promise for many applications. Recently, many works focus on GQDs-metal ions and metal nanoparticles (NPs). Although, many researches point out that metal ions and metal NPs have significant effect on photoluminescence (PL) feature of GQDs, mainly focus on PL intensity. Here, for the first time, we reported that metal NPs also affected PL peak position which was dependent on the mix mechanism of metal and GQDs. When GQDs-silver (Ag) composite mixed by physical method and excited at a wavelength of 320 nm, PL peak position of composites first showed blue-shifted then red-shifted with increasing of Ag content. However, if GQDs-Ag composite prepared by chemical method, PL peak position of the composites blue-shifted. Furthermore, the shift of PL peak position of GQDs-Ag prepared both for physical and chemical method displayed excitation-dependent feature. When the excitation wavelength approached to Ag SPR peaks, no obvious PL shift was observed. The mechanism for different PL shifts and the phenomenon of excitation-dependent PL shift as well as the formation mechanism of GQDs-Ag composite by chemical method are discussed in detail in this paper.

Bladder cancer is one of the leading causes of cancer-related death in the world. Prolonged exposure to benzidine is a known cause of bladder cancer. Curcumin has been clinically used in chemoprevention and treatment of cancer. However, it remains unknown whether mitogen-activated protein kinase (MAPK) pathways are involved in curcumin-mediated protection from benzidine-associated promotive effects on bladder cancer. In our study, we found that benzidine increased the proliferation of human bladder cancer T24 cells, triggered transition of the cells from G1 to S phase, elevated the expression of cyclin D1 and proliferating cell nuclear antigen (PCNA) and decreased p21 expression. Meanwhile, exposure of T24 cells to benzidine resulted in activation of extracellular regulated protein kinases 1 and 2 (ERK1/2) pathway as well as activator protein 1 (AP-1) proteins. Treatment with ERK1/2 inhibitor U0126 or curcumin effectively abrogated benzidine-triggered cell proliferation and ERK1/2/AP-1 activation. These results suggested for the first time that curcumin in low concentrations played a protective role in benzidine-induced ERK1/2/AP-1 activation and proliferation of bladder cancer cells, therefore providing new insights into the pathogenesis and chemoprevention of benzidine-associated bladder cancer., (Copyright © 2015 Elsevier GmbH. All rights reserved.)

Vitamin D receptor (VDR) is highly expressed in human and mouse kidneys. Nevertheless, its functions remain obscure. This study investigated the effects of vitamin D3 (VitD3) pretreatment on renal inflammation during lipopolysaccharide (LPS)-induced acute kidney injury. Mice were intraperitoneally injected with LPS. In VitD3 + LPS group, mice were pretreated with VitD3 (25 μg/kg) at 48, 24 and 1 h before LPS injection. As expected, an obvious reduction of renal function and pathological damage was observed in LPS-treated mice. VitD3 pretreatment significantly alleviated LPS-induced reduction of renal function and pathological damage. Moreover, VitD3 pretreatment attenuated LPS-induced renal inflammatory cytokines, chemokines and adhesion molecules. In addition, pretreatment with 1,25(OH)2D3, the active form of VitD3, alleviated LPS-induced up-regulation of inflammatory cytokines and chemokines in human HK-2 cells, a renal tubular epithelial cell line, in a VDR-dependent manner. Further analysis showed that VitD3, which activated renal VDR, specifically repressed LPS-induced nuclear translocation of nuclear factor kappa B (NF-κB) p65 subunit in the renal tubules. LPS, which activated renal NF-κB, reciprocally suppressed renal VDR and its target gene. Moreover, VitD3 reinforced the physical interaction between renal VDR and NF-κB p65 subunit. These results provide a mechanistic explanation for VitD3-mediated anti-inflammatory activity during LPS-induced acute kidney injury.

Background: Regular screening of transfusion-transmissible infections (TTIs), such as human immunodeficiency virus (HIV), hepatitis B and hepatitis C virus (HBV and HCV, respectively), and Treponema pallidum, in blood donors is essential to guaranteeing clinical transfusion safety. This study aimed to determine the seroprevalence of four TTIs among blood donors on Bioko Island, Equatorial Guinea (EG)., Methods: A retrospective survey of blood donors from January 2011 to April 2013 was conducted to assess the presence of HIV, HBV, HCV and T. pallidum. The medical records were analyzed to verify the seroprevalence of these TTIs among blood donations stratified by gender, age and geographical region., Results: Of the total 2937 consecutive blood donors, 1098 (37.39%) had a minimum of one TTI and 185 (6.29%) harbored co-infections. The general seroprevalence of HIV, HBV, HCV and T. pallidum were 7.83%, 10.01%, 3.71% and 21.51%, respectively. The most frequent TTI co-infections were HBV-T. pallidum 60 (2.04%) and HIV-T. pallidum 46 (1.57%). The seroprevalence of HIV, HBV, HCV and T. pallidum were highest among blood donors 38 to 47 years, 18 to 27 years and ≥ 48 years age, respectively (P<0.05). The seroprevalence of TTIs varied according to the population from which the blood was collected on Bioko Island., Conclusions: Our results firstly provide a comprehensive overview of TTIs among blood donors on Bioko Island. Strict screening of blood donors and improved hematological examinations using standard operating procedures are recommended.

Increasing evidence demonstrates that reactive oxygen species plays important roles in sepsis-induced acute kidney injury. This study investigated the effects of VitD3 pretreatment on renal oxidative stress in sepsis-induced acute kidney injury. Mice were intraperitoneally injected with lipopolysaccharide (LPS, 2.0mg/kg) to establish an animal model of sepsis-induced acute kidney injury. In VitD3+LPS group, mice were orally pretreated with three doses of VitD3 (25 μg/kg) at 1, 24 and 48 h before LPS injection. As expected, oral pretreatment with three daily recommended doses of VitD3 markedly elevated serum 25(OH)D concentration and efficiently activated renal VDR signaling. Interestingly, LPS-induced renal GSH depletion and lipid peroxidation were markedly alleviated in VitD3-pretreated mice. LPS-induced serum and renal nitric oxide (NO) production was obviously suppressed by VitD3 pretreatment. In addition, LPS-induced renal protein nitration, as determined by 3-nitrotyrosine residue, was obviously attenuated by VitD3 pretreatment. Further analysis showed that LPS-induced up-regulation of renal inducible nitric oxide synthase (inos) was repressed in VitD3-pretreated mice. LPS-induced up-regulation of renal p47phox and gp91phox, two NADPH oxidase subunits, were normalized by VitD3 pretreatment. In addition, LPS-induced down-regulation of renal superoxide dismutase (sod) 1 and sod2, two antioxidant enzyme genes, was reversed in VitD3-pretreated mice. Finally, LPS-induced tubular epithelial cell apoptosis, as determined by TUNEL, was alleviated by VitD3 pretreatment. Taken together, these results suggest that VitD3 pretreatment alleviates LPS-induced renal oxidative stress through regulating oxidant and antioxidant enzyme genes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency and hemoglobinopathies were the inherited conditions found mostly in African. However, few epidemiological data of these disorders was reported in Equatorial Guinea (EQG). This study aimed to assess the prevalence and healthy effects of G6PD deficiency and hemoglobinopathies among the people on malaria endemic Bioko Island, EQG., Materials and Methods: Blood samples from 4,144 unrelated subjects were analyzed for G6PD deficiency by fluorescence spot test (FST), high-resolution melting assay and PCR-DNA sequencing. In addition, 1,186 samples were randomly selected from the 4,144 subjects for detection of hemoglobin S (HbS), HbC, and α-thalassemia deletion by complete blood count, PCR-DNA sequencing and reverse dot blot (RDB)., Results: The prevalence of malaria and anemia was 12.6% (522/4,144) and 32.8% (389/1,186), respectively. Overall, 8.7% subjects (359/4,144) were G6PD-deficient by FST, including 9.0% (249/2,758) males and 7.9% (110/1,386) females. Among the 359 G6PD-deficient individuals molecularly studied, the G6PD A- (G202A/A376G) were detected in 356 cases (99.2%), G6PD Betica (T968C/A376G) in 3 cases. Among the 1,186 subjects, 201 cases were HbS heterozygotes, 35 cases were HbC heterozygotes, and 2 cases were HbCS double heterozygotes; 452 cases showed heterozygous α-thalassemia 3.7 kb deletion (-α3.7 kb deletion) and 85 homozygous - α3.7 kb deletion. The overall allele frequencies were HbS 17.1% (203/1186); HbC, 3.1% (37/1186); and -α3.7 kb deletion 52.4% (622/1186), respectively., Conclusions: High G6PD deficiency in this population indicate that diagnosis and management of G6PD deficiency is necessary on Bioko Island. Obligatory newborn screening, prenatal screening and counseling for these genetic disorders, especially HbS, are needed on the island.

Apolipoprotein E (APOE) gene polymorphism can affect APOE gene transcription, serum lipid levels and repair of tissue damage, which could place individuals at serious risk of cardiovascular disease or certain infectious diseases. Recently, high-resolution melting (HRM) analysis was reported to be a simple, inexpensive, accurate and sensitive method for the genotyping or/and scanning of rare mutations. For this reason, an HRM analysis was used in the present study for APOE genotyping in the Southern Chinese Han and African Fang populations. A total of 100 healthy Southern Chinese Han and 175 healthy African Fang individuals attended the study. Polymerase chain reaction-DNA sequencing was used as a reference method for the genotyping of these samples. The six APOE genotypes could all be rapidly and efficiently identified by HRM analysis, and 100% concordance was found between the HRM analysis and the reference method. The allele frequencies of APOE in the Southern Chinese Han population were 7.0, 87.5 and 5.5% for ɛ2, ɛ3 and ɛ4, respectively. In the African Fang population, the allele frequencies of APOE were 24.3, 65.7 and 10.0% for ɛ2, ɛ3 and ɛ4, respectively. A statistically significant difference was found between the allele frequencies between the populations (P<0.05). In conclusion, the present study revealed the molecular characterization of APOE gene polymorphism in the Han population from the Chaozhou region of Southern China and the Fang population from Equatorial Guinea. The findings of the study indicated that HRM analysis could be used as an accurate and sensitive method for the rapid screening and identification of APOE genotypes in prospective clinical and population genetic analyses.

Objective: To determine the value of blink reflex in early diagnosis and prognosis evaluation of Bell palsy., Methods: Blink reflex and facial nerve conduction were examined in 58 patients with Bell palsy within one week after symptom onset. The patients without response of R1 , R2 and R2 ' waves were classified as complete efferent retardarce (Group A, 30 cases), and those with response of R1 , R2 and R2 ' waves were classified as incomplete efferent anomalies (Group B, 28 cases). The clinical outcomes after three months of systemic therapy were evaluated using the House-Blackmann (H-B) scale., Results: Efferent anomalies of blink reflex occurred in ail of the 58 patients. Abnormal results of facial nerve conduction appeared in 23 (39. 7%) patients. The three months therapy was effective in 93% patients in Group B and 70% patients in Group A (P<0. 05)., Conclusion: Blink reflex can play a significant role in early diagnosis and prognosis evaluation of Bell palsy.

Striatal-enriched tyrosine phosphatase (STEP) is an important regulator of neuronal synaptic plasticity, and its abnormal level or activity contributes to cognitive disorders. One crucial downstream effector and direct substrate of STEP is extracellular signal-regulated protein kinase (ERK), which has important functions in spine stabilisation and action potential transmission. The inhibition of STEP activity toward phospho-ERK has the potential to treat neuronal diseases, but the detailed mechanism underlying the dephosphorylation of phospho-ERK by STEP is not known. Therefore, we examined STEP activity toward para-nitrophenyl phosphate, phospho-tyrosine-containing peptides, and the full-length phospho-ERK protein using STEP mutants with different structural features. STEP was found to be a highly efficient ERK tyrosine phosphatase that required both its N-terminal regulatory region and key residues in its active site. Specifically, both kinase interaction motif (KIM) and kinase-specific sequence of STEP were required for ERK interaction. In addition to the N-terminal kinase-specific sequence region, S245, hydrophobic residues L249/L251, and basic residues R242/R243 located in the KIM region were important in controlling STEP activity toward phospho-ERK. Further kinetic experiments revealed subtle structural differences between STEP and HePTP that affected the interactions of their KIMs with ERK. Moreover, STEP recognised specific positions of a phospho-ERK peptide sequence through its active site, and the contact of STEP F311 with phospho-ERK V205 and T207 were crucial interactions. Taken together, our results not only provide the information for interactions between ERK and STEP, but will also help in the development of specific strategies to target STEP-ERK recognition, which could serve as a potential therapy for neurological disorders. Regulation of phospho-ERK by STEP underlies important neuronal activities. A detailed enzymologic characterisation and cellular studies of STEP revealed that specific residues in KIM and active site mediated ERK recognition. Structural differences between the KIM-ERK interfaces and the active site among different ERK phosphatases could be targeted to develop specific STEP inhibitor, which has therapeutic potential for neurological disorders. PKA, protein kinase A & NGF, nerve growth factor., (© 2013 International Society for Neurochemistry.)

Objectives: To evaluate the changes of the position of medulla oblongata and cerebellum following posterior fossa decompression (PFD), and to investigate their influences on the prognosis of the syringomyelia in adolescents with Chiari malformation (CM)., Methods: A retrospective review was performed on all CM patients between September 2006 and September 2011. A subset of 46 patients, including 25 male and 21 female patients, was finally enrolled according to the inclusion criteria. The initial age and duration of follow-up averaged 13.9 years (range, 10-17 years) and 13 months (range, 6-52 months), respectively. On mid-sagittal MRI, the following parameters were evaluated pre- and postoperatively (follow-up ≥ 6 months): the longitudinal and transverse position of bulbopontine sulcus, the fourth ventricle vertex, the lower extreme of cerebella tonsil, the cervico-medullary angle, the maximal syrinx/cord(S/C) ratio and the syrinx length. Changes in these parameters were analysed using the paired samples t test, and for these reaching statistical significances, an additional bivariate correlation analysis was performed to investigate their relation with syrinx resolution., Results: At the latest follow-up, upward shifting of the bulbopontine sulcus was observed in 31 patients(67.4%), with upward shifting of the lower extreme of cerebella tonsil presenting in 35 patients(76.0%). The maximal S/C ratio and the syrinx length were significantly improved postoperatively (t = 7.114 and 7.816, P = 0.000).Significant resolution of the syrinx was demonstrated in 40 patients(86.9%), and more specifically, the average improvement rates of the maximal S/C ratio and the syrinx length were 32% ± 30%and 43% ± 33%, respectively. In addition, the bivariate correlation analysis revealed that syrinx resolution was significantly correlated with the upward shifting of the bulbopontine sulcus (r = 0.332, P = 0.027) and lower extreme of cerebella (r = 0.298, P = 0.044) ., Conclusion: The upward shifting of the bulbopontine sulcus and the lower extreme of cerebella tonsil might be implicated in the mechanisms of postoperative syrinx resolution.

Fusion gene expression, a kind of chromosome rearrangement mode, has been strongly linked to prostate cancer diagnosis and prognosis as well as to the Gleason score and the American Joint Committee on Cancer stage assessment. In combination with traditional methods for locating fusion genes and scoring their association with cancer cell growth, proliferation, and invasion through the basement membrane, the emerging high-throughput sequencing technologies offer a panorama of fusion genes in a genome and facilitate the discovery of new fusion modes. We describe here a method for using single-end reads to analyze fusion gene expression in prostate tumors. We obtained the fusion gene expression profiling of prostate tumors, clustered them into several biological pathways, highlighted three "rediscovered" fusion genes (TMPRSS2-ERG, KLK2, and KLK3) and proved the reliability of our method.

Protein phosphorylation is an important post-translational modification that regulates almost every aspect of signal transduction in cells. Activation of the mitogen-activated protein kinase (MAPK) family kinase extracellular signal-regulated kinase (ERK) is a point of convergence for many cellular activities in response to external stimulation. With stimuli, ERK activity is significantly increased by the phosphorylation of Thr202 and Tyr204 at its activation loop. Downregulation of ERK phosphorylation at these two sites by several phosphatases, such as protein phosphatase 2A, HePTP and MAPK phosphatase 3, is essential for maintaining appropriate ERK function in different cellular processes. However, it is unknown whether metal-dependent protein phosphatase (PPM) family phosphatases directly dephosphorylate ERK. In this study, we found that PPM1A negatively regulated ERK by directly dephosphorylating its pThr202 position early in EGF stimulation. Additional kinetic studies revealed that key residues participated in phospho-ERK recognition by PPM1A. Importantly, PPM1A preferred the phospho-ERK peptide sequence over a panel of other phosphopeptides through the interactions of basic residues in the active site of PPM1A with the pThr-Glu-pTyr motif of ERK. Whereas Lys165 and Arg33 were required for efficient catalysis or phosphosubstrate binding of PPM1A, Gln185 and Arg186 were determinants of PPM1A substrate specificity. The interaction between Arg186 of PPM1A and Glu203 and pTyr204 of phospho-ERK was identified as a hot-spot for phospho-ERK-PPM1A interaction., (© 2013 The Authors Journal compilation © 2013 FEBS.)

The heavy metal cadmium is a non-degradable pollutant. By screening the effects of a panel of metal ions on the phosphatase activity, we unexpectedly identified cadmium as a potent inhibitor of PPM1A and PPM1G. In contrast, low micromolar concentrations of cadmium did not inhibit PP1 or tyrosine phosphatases. Kinetic studies revealed that cadmium inhibits PPM phosphatases through the M1 metal ion binding site. In particular, the negative charged D441 in PPM1G specific recognized cadmium. Our results suggest that cadmium is likely a potent inhibitor of most PPM family members except for PHLPPs. Furthermore, we demonstrated that cadmium inhibits PPM1A-regulated MAPK signaling and PPM1G-regulated AKT signaling potently in vivo. Cadmium reversed PPM1A-induced cell cycle arrest and cadmium insensitive PPM1A mutant rescued cadmium induced cell death. Taken together, these findings provide a better understanding of the effects of the toxicity of cadmium in the contexts of human physiology and pathology.

Objective: To explore the profile of false memory in aMCI (amnesia mild cognitive impairment) and to elucidate the neuropsychological mechanism of false memory., Methods: False memory provoked by pictures and feeling-of-knowing (FOK) test in episodic memory (EM) were conducted in 25 aMCI patients at our hospital from October 2009 to May 2010. And 25 age and education level-matched healthy patients were recruited into the healthy control (HC) group., Results: As compared with HC group, the rate of false memory was higher in the aMCI group. The rate of false memory in recall stage was 26% ± 7% and that of questionnaire stage 28% ± 12%. And the difference between two group was significant (t = 14.437, 7.597, P < 0.05). The FOK-EM of correct judgment and false recognition in the aMCI group (41% ± 10%) was higher than the HC group. And the difference was significant (t = 4.207, P < 0.05). The rates of false memory in recall and questionnaire stages were positively correlated with FOK-EM in aMCI group (r = 0.563, 0.705, P < 0.01)., Conclusion: The aMCI patients tend to have more false memory provoked by pictures. The deficit of memory monitoring in aMCI may be the foundation of false memory.