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The optic nerve is a viscoelastic solid-like biomaterial. Its normal stress relaxation and creep properties enable the nerve to resist constant strain and protect it from injury. We hypothesized that stress relaxation and creep properties of the optic nerve change after injury. More-over, human brain-derived neurotrophic factor or umbilical cord blood-derived stem cells may restore these changes to normal. To validate this hypothesis, a rabbit model of optic nerve injury was established using a clamp approach. At 7 days after injury, the vitreous body re-ceived a one-time injection of 50 μg human brain-derived neurotrophic factor or 1 × 10(6) human umbilical cord blood-derived stem cells. At 30 days after injury, stress relaxation and creep properties of the optic nerve that received treatment had recovered greatly, with patho-logical changes in the injured optic nerve also noticeably improved. These results suggest that human brain-derived neurotrophic factor or umbilical cord blood-derived stem cell intervention promotes viscoelasticity recovery of injured optic nerves, and thereby contributes to nerve recovery.

Background: Radiation therapy is the method of choice for subjects with inoperable salivary gland malignancies. I-125 brachytherapy, delivering a high radiation dose to a tumor but sparing surrounding normal tissues, is supposed to be ideal modality for the treatment of salivary gland malignancies. We designed a randomised controlled clinical trial to compare the efficacy of I-125 permanent brachytherapy (PBT) versus intensity-modulated radiation therapy (IMRT) for inoperable salivary gland malignancies., Methods/design: In this study, inclusion criteria are subjects with inoperable salivary gland malignancies, aged 18-80 years, have provided informed consent, with at least one measurable tumor focus, be able to survive ≥3 months, Karnofsky performance status ≥60, have adequate hematopoietic function of bone marrow, have normal liver and kidney function, and are willing to prevent pregnancy. Exclusion criteria include a history of radiation or chemotherapy, a history of other malignant tumors in the past 5 years, receiving other effective treatments, participating in other clinical trials, with circulatory metastasis, cognitive impairment, severe cardiovascular and cerebrovascular diseases, acute infection, uncontrolled systemic disease, history of interstitial lungdisease, and being pregnant or breast feeding. The study will be conducted as a clinical, prospective, randomised controlled trial with balanced randomisation (1:1). The planned sample size is 90 subjects. Subjects with inoperable salivary gland malignancies are randomised to receive either I-125 PBT or IMRT, with stratification by tumor size and neck lymph node metastasis. Participants in both groups will be followed up at 2, 4, 6, 9, 12, 15, 18, 21 and 24 months after randomization. The primary outcome is local control rate of the primary site (based on imaging findings and clinical examination, RECIST criteria) in 1 year. Secondary outcomes are progression-free survival, overall survival, quality of life (QOL) measured with the European Organization for Research and Treatment of Cancer QOL Questionnaire (EORTC QLQ-C30 and QLQ-H&N35) of Chinese version, and safety of treatment. Chi-squared test is used to compare the local control rates in both groups. The survival curves are estimated by the Kaplan-Meier method, and log-rank test is used to test the significant difference., Discussion: Only few observational studies have investigated the effect of I-125 PBT on inoperable salivary gland malignancies. To our knowledge, this is the first randomised controlled trial to investigate the efficacy of I-125 PBT for subjects with inoperable salivary gland malignancies, and will add to the knowledge base for the treatment of these subjects., Trial Registration: The study is registered to Clinical Trials.gov ( NCT02048254 ) on Jan 29, 2014.

In order to establish the quality standard of Berberidis Cortex and improve its quality control level, water, total ash, acid-insoluble ash and alcohol-soluble extract were determined according to procedures recorded in the Chinese Pharmacopoeia (2010 edition). The qualitative and quantitative analyses were performed by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC) methods. The results showed that TLC identification had a good resolution with clear spots. The water content was 8.39%-12.23%; total ash was 4.50%-9.96%; acid-insoluble ash was 0.10%-0.69%, and the alcohol-soluble extraction was 20.62%-37.13%. The average contents of magnoflorine, jatrorrhizine, palmatine, and berberine in Berberidis Cortex were 5.98%, 0.63%, 0.30%, 2.50%, respectively. It was concluded that the developed method was accurate and good in specificity, which can be used for quality control of Berberidis Cortex in the future., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

We selected six tagged single nucleotide polymorphisms (SNPs) in the interleukin 17A (IL-17A) and IL-17F genes, and evaluated the relationship between the six common SNPs and environmental factors in cervical cancer patients. Polymerase chain reaction-restriction fragment length polymorphism was used to detect the IL-17A (rs2275913, rs3748067, and rs3819025) and IL-17F (rs763780, rs9382084, and rs1266828) SNPs. The associations between IL-17A and IL-17F gene polymorphisms and risk of cervical cancer were estimated by conditional logistic regression. Compared with the control subjects, the cervical cancer patients had a lower age at first live birth, a habit of smoking, a family history of cancer, and a greater incidence of human papillomavirus-16 or 18 infections. The logistic regression analysis showed that the variant AA genotype of rs2275913 was associated with a significantly higher risk of cervical cancer than the wild-type GG genotype (OR = 1.99, 95%CI = 1.12-3.50). However, no evidence of the association was observed between rs3748067, rs3819025, rs763780, rs9382084, and rs1266828 polymorphisms and the risk of cervical cancer. We suggest that rs2275913 may play a role in the etiology of cervical cancer. These findings could be helpful in identifying individuals at increased risk of developing cervical cancer.

Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10(6) human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

Objective: To investigate clinical features of distant metastases (DM) and analyze clinicopathologic risk factors associated with DM from salivary gland carcinomas after being treated by surgery combined with 125I internal brachytherapy., Methods: Between October 2001 and March 2010, 197 patients with salivary gland carcinoma were treated by surgery combined with 125I internal brachytherapy and had follow-up for 2 years or more. Univariate and multivariate analyses were performed to evaluate clinicopathologic risk factors that might influence the risk of distant metastases., Results: DM occurred in 28 of 197 patients (14.2%). The commonest site of distant metastases overall was the lung 89.3% (25/28), followed by bones 17.9% (5/28) and liver (4/28). DM developed after an average interval of (44.2±45.8) months from the time of initial diagnosis, and the mean interval was 64 months. The average time to death after the diagnosis of DM was only (9.7±13.4) months, and the mean time was 12 months. The 3-year locoregional control rate and survival rate were 90.8%, and 87.8% respectively,and the 5-year ones 84.0% and 81.0%, respectively. Univariate analyses revealed that the risk of distant metastases was significantly influenced by locoregional tumor failure (F=26.997, P<0.01) and histologic differentiation (F=1.592, P<0.01). Multivariate analysis of freedom from distant metastases revealed that locoregional control (F=29.332, P<0.01) significantly influenced this end point., Conclusion: Salivary gland carcinoma could achieve high local control rate after being treated by surgery combined with 125I internal brachytherapy, and the average interval from diagnosis to DM was prolonged, DM was significantly influenced bylocoregional control.

Objective: To compare the growth of preterm infants fed standard protein-fortified human milk with that containing human milk fortifier (HMF) with a higher-than-standard protein content., Methods: Published articles reporting randomized controlled trials and prospective observational intervention studies listed on the PubMed®, Embase®, CINAHL and Cochrane Library databases were searched using the keywords 'fortifier', 'human milk', 'breastfeeding', 'breast milk' and 'human milk fortifier'. The mean difference with 95% confidence intervals was used to compare the effect of HMF with a higher-than-standard protein content on infant growth characteristics., Results: Five studies with 352 infants with birth weight ≤ 1750 g and a gestational age ≤ 34 weeks who were fed human milk were included in this meta-analysis. Infants in the experimental groups given human milk with higher-than-standard protein fortifier achieved significantly greater weight and length at the end of the study, and greater weight gain, length gain, and head circumference gain, compared with control groups fed human milk with the standard HMF., Conclusions: HMF with a higher-than-standard protein content can improve preterm infant growth compared with standard HMF., (© The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.)

Denitrifying phosphorus removal is an attractive wastewater treatment process due to its reduced carbon source demand and sludge minimization potential. In the present study, the metagenome of denitrifying phosphorus removal sludge from a lab-scale anaerobic-anoxic SBR was generated by Illumina sequencing to study the microbial community. Compared with the aerobic phosphorus removal sludge, the denitrifying phosphorus removal sludge demonstrated quite similar microbial community profile and microbial diversity with sludge from Aalborg East EBPR WWTP. Proteobacteria was the most dominant phylum; within Proteobacteria, β-Proteobacteria was the most dominant class, followed by α-, γ-, δ-, and ε-Proteobacteria. The genes involved in phosphate metabolism and biofilm formation reflected the selective pressure of the phosphorus removal process. Moreover, ppk sequence from DPAO was outside the Accumulibacter clusters, which suggested different core phosphorus removal bacteria in denitrifying and aerobic phosphorus removal systems. In a summary, putative DPAO might be a novel genus that is closely related between Accumulibacter and Dechloromonas within Rhodocyclus. The microbial community and metabolic profiles achieved in this study will eventually help to improve the understanding of key microorganisms and the entire community in order to improve the phosphorus removal efficiency of EBPR processes.

Thermal and high speed modulation characteristics are investigated for a unidirectional-emission microdisk laser with a radius of 7 μm surrounded by BCB-cladding layer, with a threshold current of 1.5 mA at the temperature of 287 K. The lasing spectra under different widths of pulsed current are measured to characterize the temperature rise during the pulse period, and the thermal distribution in the microdisk laser is simulated by the finite-element modeling technique. A temperature rise of 25 K is estimated for the microdisk laser biased at 20 mA. Furthermore, small signal modulation response with 3dB bandwidth up to 20 GHz is obtained for the microdisk laser at the biasing current of 18 mA, and eye-diagrams at the modulation bit rates of 20, 25, and 30 GHz are also measured at the temperature of 287 K.

Two new sesquiterpenoids (phellinuins H and I), together with five known compounds, were isolated from cultures of mushroom Phellinus sp. Their structures were elucidated based on comparison of nuclear magnetic resonance and MS data and those reported in the literature. All of these compounds were tested for cytotoxicity against five cancer cell lines (HL-60, SMMC-721, A-549, MCF-7, and SW-480).

Autotrophic nitrifying bacteria have its intrinsic properties including low EPS production, dense colonial structure and slow-growth rate, favoring the sludge filterability improvement. An adsorption-MBR (Ad-MBR) was developed to enrich nitrifier abundance in the MBR chamber by inlet C/N regulation, and its possible positive effect on sludge filterability and underlying mechanisms were investigated. By DNA extraction, PCR amplification and Illumina high-throughput pyrosequencing, the abundance of nitrifying bacteria was accurately quantified. More than 8.29% nitrifier abundance was achieved in Ad-MBR sludge, which was above three times of that in conventional MBR. Regulated C/N ratio and thereafter nitrifier abundance enrichment improved sludge filterability by altering sludge mixture and its supernatant properties, reflected by a good sludge settleability, a low supernatant viscosity and turbidity, a low supernatant organic substances concentration, and a small amount of strong hydrophobic fractional components, thus to profoundly improve sludge filterability and decelerate membrane fouling., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Denitrifying phosphorus removal is an attractive wastewater treatment process due to its reduced carbon source demand and sludge minimization potential. Two lab-scale sequencing batch reactors (SBRs) were operated in alternating anaerobic-anoxic (A-A) or anaerobic-oxic (A-O) conditions to achieve denitrifying enhanced biological phosphate removal (EBPR) and traditional EBPR. No significant differences were observed in phosphorus removal efficiencies between A-A SBR and A-O SBR, with phosphorus removal rates being 87.9% and 89.0% respectively. The community structures in denitrifying and traditional EBPR processes were evaluated by high-throughput sequencing of the PCR-amplified partial 16S rRNA genes from each sludge. The results obtained showed that the bacterial community was more diverse in A-O sludge than in A-A sludge. Taxonomy and β-diversity analyses indicated that a significant shift occurred in the dominant microbial community in A-A sludge compared with the seed sludge during the whole acclimation phase, while a slight fluctuation was observed in the abundance of the major taxonomies in A-O sludge. One Dechloromonas-related OTU outside the 4 known Candidatus "Accumulibacter" clades was detected as the main OTU in A-A sludge at the stationary operation, while Candidatus "Accumulibacter" dominated in A-O sludge.

A four-wavelength microdisk laser array laterally coupled with a bus waveguide is demonstrated numerically and experimentally. The coupled-mode characteristics as well as scattering loss in the bus waveguide caused by the connected microdisks are simulated by a 2D finite-difference time-domain technique. An AlGaInAs/InP microdisk laser array with circular radii of 10.1, 10.2, 10.3, and 10.4 μm is designed and fabricated by common photolithography and an inductively coupled-plasma etching technique. Continuous-wave electrically injected operation is realized at room temperature with the lowest threshold current of 3 mA. Four-wavelength lasing operation is realized with wavelength intervals of 3-4 nm and side mode suppression ratios larger than 25 dB. Finally, the influences of heating effect and thermal cross talk on lasing mode wavelength tuning are investigated experimentally.

Aerobic methane-oxidation coupled to denitrification (AME-D) process was successfully achieved in a membrane biofilm reactor (MBfR). PVDF membrane was employed to supply the methane and oxygen for biofilm, which was coexistence of methanotrophs and denitrifier. With a feeding NO3(-)-N of 30 mg/L, up to 97% nitrate could be removed stably. The oxygen ventilation modes impacted the denitrification performance remarkably, resulting in different nitrate removal efficiencies and biofilm microorganism distribution. The biofilm sludge showed a high resistance to the DO inhibition, mainly due to the co-existing methanotroph being capable of utilizing oxygen perferentially within biofilm, and create an anoxic micro-environment. The denitrification of both nitrate and nitrite by biofilm sludge conformed to the Monod equation, and the maximum specific nitrate utilization rate (k) ranged from 1.55 to 1.78 NO3(-)-N/g VSS-d. The research findings should be significant to understand the considerable potential of MBfR as a bioprocess for denitrification., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Vertical radiation loss and far-field pattern are investigated for microcylinder lasers by 3D FDTD simulation and experimentally. The numerical results show that an output waveguide connected to the microcylinder resonator can result in additional vertical radiation loss for high Q coupled modes and affect the far field pattern. The vertical radiation loss can be controlled by adjusting the up cladding layer thickness. Furthermore, two lobes of vertical far-field patterns are observed for a 15-μm-radius microcylinder laser connected with an output waveguide, which confirms the vertical radiation loss.

Pitching ratio has been reported to impact not only on the primary metabolism, but also the secondary metabolism. Comparative metabolomics was used to explore the metabolic responses of Streptomyces lydicus E9 to pitching ratios (1, 10, and 30%, v/v). We identified more than 120 metabolites involved in glycolysis, tricarboxylic acid cycle, and amino acid and secondary metabolism, of which there are significant differences in the quantified 32 metabolites under different pitching ratios by gas chromatography coupled to time-of-flight mass spectrometry. The intracellular levels of most amino acids (e.g., valine, alanine, and isoleucine) declined with the increases of pitching ratios. Especially, the relative abundances of glutamate and proline were not only decreased with the increases of pitching rations, but also had much low level at stages II and III, which might be related to the significant enhancement in streptolydigin of S. lydicus E9 under 30% high pitching ratio. Moreover, principal component analysis revealed that eight metabolites, including glucopyranoside, maltose, cAMP, glycine, proline, lysine, isoleucine, and valine, were considered as potential biomarkers to distinguish the influences of pitching ratios on streptolydigin production. Further investigations demonstrated that the additions of exogenous glutamate and proline (100 mgL⁻¹) enhanced significantly the accumulation of streptolydigin, indicating that glutamate was the synthetic precursor of streptolydigin, while proline in S. lydicus E9 was converted into glutamate and consequently improved streptolydigin biosynthesis. Therefore, these findings provide new insights into the amino acid responses of S. lydicus E9 to pitching ratios and provide potential strategies to improve streptolydigin production.

The extracellular signal-regulated kinase (ERK) is one of the three major types of mitogen-activated protein kinases. Previous studies showed that ERKs mediate various signaling pathways for cell proliferation, differentiation, survival and transformation in mammals. In the present study, we use goldfish as a model system and demonstrate that ERK kinases play important roles in promoting embryonic survival and regulate development of eye and trunk in vertebrates. ERKs are highly expressed in multiple tissues including lens epithelial cells, lens fiber cells, retina, brain, muscle and heart of adult goldfish. Injection of the dominant negative ERK mutant (DNM-ERK) into the fertilized eggs of goldfish significantly inhibited ERK activity at blastula stage, and completely blocked ERK activity at gastrula and later stages. As a result, the blastula cells were induced into apoptosis, and majority of the injected embryos were lethal at embryonic stages. At the molecular level, inhibition of ERK activity by DNM-ERKs suppressed phosphorylation of Bad at Ser-112 to promote apoptosis. Similar results were observed when MEK activity was inhibited by U0126 treatment. The survived embryos display significant abnormality in the phenotypes of both eye and trunk. Associated with the abnormality in the eye development, phosphorylation in Pax-6 and expression of HSF4 were significantly decreased and expression of the β-crystallin gene was also downregulated. These results provide novel information regarding the roles of ERKs in regulating vertebrate development.

Defected circular resonators laterally confined by a metal layer with a flat side as an emitting window are numerically investigated based on the boundary element method for realizing unidirectional emission microlasers. The results indicate that Fabry-Pérot (FP) modes become high Q confined modes in the defected circular resonator with a metallic layer. The mode coupling between the FP mode and chaotic-like mode can result in high Q confined mode for unidirectional emission with a narrow far field pattern.

The genetic bases of demographic changes and artificial selection underlying domestication are of great interest in evolutionary biology. Here we perform whole-genome sequencing of multiple grey wolves, Chinese indigenous dogs and dogs of diverse breeds. Demographic analysis show that the split between wolves and Chinese indigenous dogs occurred 32,000 years ago and that the subsequent bottlenecks were mild. Therefore, dogs may have been under human selection over a much longer time than previously concluded, based on molecular data, perhaps by initially scavenging with humans. Population genetic analysis identifies a list of genes under positive selection during domestication, which overlaps extensively with the corresponding list of positively selected genes in humans. Parallel evolution is most apparent in genes for digestion and metabolism, neurological process and cancer. Our study, for the first time, draws together humans and dogs in their recent genomic evolution.

Aim: To explore the relationship between the expression of hemeoxygenase-1 (HO-1) and the dopaminergic system impairment in MPTP-treated SAMP8 mice., Methods: 6-month-old male SAMP8 mice received MPTP (20 mg/kg) subcutaneous injection at 2-h intervals for 4 times, and the control group was treated with an equal volume of normal saline. Mice were sacrificed at 6 h, 24 h, 3 d and 8 d after the first injection for the detection of the changes of tyrosine hydroxylase (TH) and HO-1 in the nigrostriatal system by immunohistochemistry and Western blotting., Results: TH-positive neuronal loss was visible at 6 h (14.23%, P<0.05), 24 h (23.85%, P<0.01), 3 d (36.77%, P<0.001), and 8 d (45.90%, P<0.001), and the significant progression of dopaminergic neuronal loss occurred most prominently in the MPTP group from 24 h to 3 d (24 h vs 3 d, P<0.05). There was a significant decrease of striatal TH immunoreactive cells in the MPTP group (P<0.05). Additionally, HO-1 positive cells were detected in striatum just only at 3 d, with the increase of HO-1 protein expression in MPTP groups. Western blot analysis showed no change of HO-1 protein levels in the midbrain after MPTP treatment compared to those of the normal saline group., Conclusion: MPTP caused the loss of dopaminergic neuron number and the decrease of TH protein levels in SAMP8 mice. The up-regulation of HO-1 was ephemeral, and its effects related with Parkinson's disease was limited in this study.

Objective: To explore the association between parental genetic polymorphism of methylenetetrahydrofolate reductase (MTHFR) 677C/T and occurrence of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in offspring in Shandong Province., Methods: MTHFR genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Parents of 89 NSCL/P patients treated at Qilu Hospital from August, 2006 to August, 2008 and those of 64 healthy children were recruited in this case-control study., Results: Frequencies of T and C alleles in mothers of patients and healthy children were 65.73% and 46.09%, and 34.27% and 53.91%, respectively (Chi-square=13.663, P<0.01). Offspring whose mothers had T alleles were 2.243 times more likely to develop NSCL/P (95%CI: 1.408-3.572). Frequencies of T and C alleles in fathers of patients and healthy children were 62.92% and 55.47%, and 37.08% and 44.53%, respectively (Chi-square=2.222, P>0.05). The chance for parents of the patient and control groups to bear an affected fetus carrying homozygous mutations were 43% and 29%, respectively (P>0.05)., Conclusion: In Shandong Province, maternal genotype for the MTHFR 677C/T polymorphism has a significant impact on the occurrence of NSCL/P in their offspring, whilst paternal genotype for this polymorphism may not be a risk factor for NSCL/P in their offspring.

We demonstrate wide-angle emission and single mode operation in deformed circular microlasers with a flat side. The mode characteristics of a metallic confined deformed circular resonator with a flat side are investigated by finite-difference time-domain simulation. The numerical results indicate that this structure is suitable to realize wide-angle emission. Furthermore, metallic confined deformed circular microlasers with a flat side are fabricated using common photolithography and inductively coupled-plasma etching techniques. A continuous-wave single-mode operation with a side mode suppression ratio of 25 dB is achieved at an injection current of 4 mA for an 8 μm radius microlaser with a flat side. Additionally, wide angle emission over 120° is observed from the far-field pattern.

We experimentally investigate the coherence of a single mode InAlGaAs/InP cylindrical microlaser with two output waveguides. For a cylindrical microlaser with a radius of 15 μm and two 2 μm-wide output waveguides, single mode operation with a side mode suppression ratio of 30 dB is realized, and a far-field interferometric pattern similar to a Young's interferometer is observed. The results indicate that the microlasers with two output waveguides can be used as the light source for an optical sensor by monitoring the phase change of the output emission from one port versus that of the other port.

Optical bistability is realized in GaInAsP/InP coupled-circular resonator microlasers, which are fabricated by planar technology. For a coupled-circular resonator microlaser with the radius of 20 μm and a 2 μm-wide bus waveguide, hysteresis loops are observed for the output power coupling into an optical fiber versus the cw injection current at room temperature. The laser output spectra of the upper and lower states of the hysteresis loop indicate that the bistability is related to mode competitions. The optical bistability can be explained as the mode competition between the symmetry and antisymmetry coupled modes relative to the bus waveguide.

Proteinases play a critical role in developmental homeostasis and in response to environ-mental stimuli. Our present research reports that a new cysteine protease, NtCP56, is involved in the development of pollen grains in Nicotiana tabacum L. The NtCP56 gene, which encodes a protein of 361 amino acid residues with a calculated molecular mass of 40 kDa, is strongly expressed in anthers. The recombinant NtCP56 showed a high activity towards casein. Kinetic analysis revealed a K(m) of 2.20 mg ml(-1) and V(max) of 11.07 microg ml(-1) min(-1). The recombinant NtCP56 retained more than 50% of its maximum enzymatic activity from 20 degrees C to 60 degrees C with an optimum Tm range of 30-50 degrees C. The enzyme had a maximum activity at approximately pH 6.5. Suppression of the NtCP56 gene in anti-sense transgenic tobaccos resulted in the sterility of pollen grains. Our data indicated that, as a cysteine protease, NtCP56 might play an important role in pollen development.