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Imatinib mesylate (IM) is highly effective in the treatment of gastrointestinal stromal tumors (GISTs). However, the most of GISTs patients develop secondary drug resistance after 1-3 years of IM treatment. The aim of this study was to explore the IM-resistance mechanism via the multi-scope combined with plasma concentration of IM, genetic polymorphisms and plasma sensitive metabolites.This study included a total of 40 GISTs patients who had been regularly treated and not treated with IM. The plasma samples were divided into three experiments, containing therapeutic drug monitoring (TDM), OCT1 genetic polymorphisms and non-targeted metabolomics. According to the data of above three experiments, the IM-resistant cell line, GIST-T1/IMR cells, was constructed for verification the IM-resistance mechanism.The results of non-targeted metabolomics analysis suggested that the sphingophospholipid metabolic pathway including the SPK1/S1P axis was inferred in IM-insensitive patients with GISTs. A GIST cell line (GIST-T1) was immediately induced as an IM resistance cell model (GIST-T1/IMR) and we found that blocking the signal pathway of SPK1/S1P in the GIST-T1/IMR could sensitize treatment of IM and reverse the IM-resistance.Our findings suggest that IM secondary resistance is associated with the elevation of S1P, and blockage the signaling pathway of SPK1/S1P warrants evaluation as a potential therapeutic strategy in IM-resistant GISTs. The design of this study from blood management, group information collection, IM plasma concentration with different elements, identification of sphingolipid metabolism and lastly verification the function of SPK1/S1P in the IM-resistance GISTs cells.

Objective To investigate the genetic causes of sudden sensorineural hearing loss (SSNHL) patients in China. This study focused on analyzing variations of coding sequence of common genes related to deafness, revealing the molecular pathogenesis of sudden deafness from a genomics perspective, discovering molecular markers associated with the onset of deafness, and then supplying prevention to high-risk populations, classifying disease according to accurate etiology, and choosing a much more precision therapy. Methods We retrospectively analyzed the clinical characteristics of 51 patients diagnosed as SSNHL with vertigo treated in the Chinese PLA General Hospital. In this study, mutation screening of 307 nuclear genes and mitochondrial genome responsible for human or mouse deafness was performed on the 51 cases of unilateral sudden deafness patients with vertigo. Results We identified 51 cases of unilateral sudden deafness, including 2 cases of low-mid frequency hearing impairment, 18 cases of mid-high frequency hearing loss, 11 cases of flat-type hearing loss, and 20 cases of all frequency hearing loss. Among the 51 cases, 8 (15.69%) cases of GJB2 heterozygous variations, 1 (1.96%) case of GJB3 heterozygous variations, 5 (9.8%) cases of SLC26A4 heterozygous variations, 2 (3.92%) cases of COCH heterozygous variations, 14 (27.45%) cases of CDH23 heterozygous variations, 14 (27.45%) cases of OTOF heterozygous variations, 1 (1.96%) case of SLC17A8 heterozygous variations and 2 (3.92%) cases of KCNE1 heterozygous variations. No mtDNA gene variations were identified. Conclusion SSNHL has some relationship with hereditary in Chinese population, but its complex genetic pathogenic mechanisms need further study.

Victim justice sensitivity might be positively associated with envy; however, there is little understanding of the mechanism of this relationship. For the first time, we explored the effect of victim justice sensitivity on envy, and whether this effect is mediated by upward social comparison and moderated by perceived control. A sample of 1570 Chinese undergraduates was collected. The results revealed that victim justice sensitivity was positively associated with envy. Additionally, upward social comparison partially mediated the relationship between victim justice sensitivity and envy, and this mediating effect was further moderated by perceived control. A more positive correlation was found between upward social comparison and envy in individuals with lower levels of perceived control. This finding not only clarities the underlying mechanism but also suggests a potential way of alleviating envy.

A novel cellulase-producing actinomycete strain Gxj-6T, isolated from soil in the cold region (Heihe city, Heilongjiang province, the northernmost part of China), subjected to a taxonomic study using a polyphasic approach. In the neighbour-joining phylogenetic tree based on 16S rRNA gene sequences, strain Gxj-6T fell within the clade comprising the type strains of species of the genus Microbispora. 16S rRNA gene sequence similarity studies exhibited that species Gxj-6T was most closely related to Microbispora bryophytorum NEAU-TX2-2T (99.45%), Microbispora fusca NEAU-HEGS1-5T (99.41%), Microbispora camponoti 2C-HV3T (99.31%) and Microbispora rosea subsp. rosea JCM 3006T (98.68%). Organism Gxj-6T contained MK-9(H2) as the predominant ubiquinone and C18:0 10-methyl as the major fatty acid. The major polar lipids of culture Gxj-6T were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside, three unidentified phospholipids, two unidentified glycolipids and two unidentified lipids. The DNA G+C content of strain Gxj-6T was 71.25 mol%. The morphological and chemotaxonomic properties of the strain are also consistent with those members of the genus Microbispora. Combinated with the lower DNA–DNA relatedness values, phenotypic properties, physiology and biochemistry distinctiveness with other recognized species strains, revealed that strain Gxj-6T is separated from other phylogenetically closely species of the genus Microbispora. Therefore, strain Gxj-6T is considered to represent a novel species of the genus Microbispora, for which the name Microbispora cellulosiformans sp. nov. is proposed. The type strain is Gxj-6T (= CGMCC 4.7605T = DSM 109712T).

The Nrf2 (nuclear factor erythroid 2-related factor 2) plays a central role in cell protection against a wide variety of environmental stressors through the Nrf2-Keap1 (Kelch-like ECH-associated protein 1) pathway, but its involvement in modulation of antioxidant system of fish cell is still largely unexplored. The present study focused on the molecular cloning and silencing of the Nrf2 in the fathead minnow muscle cell line (FHM) in response to the oxidative stress induced by H2O2. A full-length cDNA of coding Nrf2 was cloned from FHM cells by RT-PCR and RACE approaches. The obtained cDNA covered 2578 bp with an open reading frame (1770 bp) of encoding 589 amino acids. Sequence alignment and phylogenetic analysis revealed a high degree of conservation (51–86%) among 16 fishes. Based on the cloned Nrf2 sequence, the siRNA-242 of targeting Nrf2 with the best knocking down efficiency was designed and detected. Then, the mRNA levels of Keap1, Nrf2, Maf (musculoaponeurotic fibrosarcoma oncogene), and HO-1 (haemoxygenase-1); the activities of T-SOD (total superoxide dismutase), CAT (catalase), and GSH-PX (glutathione peroxidase); the levels of GSH (glutathione) and MDA (malonaldehyde); and the cell cycle and apoptosis were analyzed to investigate the molecular responses after H2O2 exposure. These results showed a coordinated transcriptional regulation of Keap1, Maf, and HO-1 and antioxidants (T-SOD, GSH, CAT, and GSH-PX) and MDA levels after H2O2 exposure, leading to oxidative damage and apoptosis. These findings provided an insight to understand the mechanisms of Nrf2 against oxidative stress in fish.

Purpose The highly efficient degradation bacteria were selected from the humus from the very cold straw in China for many years to construct the in situ degradation bacteria, and the degradation efficiency of corn straw was determined by process optimization. Methods According to the main components of corn straw, through morphological, physiological, and biochemical screening, three highly efficient complementary degradation strains were selected to construct the compound flora, and the degradation efficiency was analyzed by Fourier transform infrared spectrometer, field emission scanning electron microscope, and X-ray diffractometer. Result The corn straw selected in this paper is mainly composed of cellulose (31.99%), hemicellulose (25.33%), and lignin (14.67%). Through the determination of enzyme activity, strain Streptomyces sp. G1T has high decomposition ability to cellulose and hemicellulose but weak utilization ability to lignin; strain Streptomyces sp. G2T has the strongest decomposition ability to cellulose and hemicellulose among the three strains. The decomposition ability of strain Streptomyces sp. G3T to lignin was the strongest among the three strains. Therefore, by compounding the three strains, the decomposition ability has been greatly improved. The optimal process conditions obtained by single factor and response surface method are as follows: pH is 7, temperature is 30 °C, inoculation amount is 5%, rotational speed is 210 rpm, and the weight loss rate of straw is 60.55% after decomposing for 7 days. A large amount of degradation of corn straw can be seen by Fourier transform infrared spectrometer, field emission scanning electron microscope, and X-ray diffractometer. Conclusion Streptomyces sp. G1T, Streptomyces sp. G2T, and Streptomyces sp. G3T screened from straw humus in very cold areas were used to construct in situ degradation bacteria, which had good straw degradation activity and had the potential to be used for straw treatment in cold areas after harvest. This characteristic makes the complex bacteria become a strong competitive candidate for industrial production, and it is also an effective biotechnology in line with the current recycling of resources.

Myelodysplastic syndromes (MDSs) are stem cell disorders with risk of transformation to acute myeloid leukemia (AML). Gene expression profiling reveals transcriptional expression of GLI1, of Hedgehog (Hh) signaling, in poor-risk MDS/AML. Using a murine model of MDS we demonstrated that constitutive Hh/Gli1 activation accelerated leukemic transformation and decreased overall survival. Hh/Gli1 activation resulted in clonal expansion of phenotypically defined granulocyte macrophage progenitors (GMPs) and acquisition of self-renewal potential in a non-self-renewing progenitor compartment. Transcriptome analysis of GMPs revealed enrichment in gene signatures of self-renewal pathways, operating via direct Gli1 activation. Using human cell lines we demonstrated that in addition to canonical Hh signaling, GLI1 is activated in a Smoothened-independent manner. GLI1 knockdown or inhibition with GANT61 resulted in decreased proliferation and clonogenic potential. Our data suggest that GLI1 activation is frequent in MDS during disease progression and inhibition of GLI1 is an attractive therapeutic target for a subset of patients.

This paper presents a compact quintic spline reconstruction for finite volume method on non-uniform structured grids. The primitive function of a dependent variable is reconstructed by a piece-wise quintic polynomial by requiring the derivatives up to fourth order being continuous at the cell interfaces. This procedure results in a block tridiagonal system of linear equations which can be solved efficiently by incorporating certain boundary closure relations. There are some distinct features in the quintic spline reconstruction. Firstly, the reconstruction stencil is compact; Secondly, the reconstruction can be applied on arbitrary non-uniform grids; and finally, the reconstruction is continuous at cell interface without the need of a Riemann solver. To stabilize the scheme, the sixth order artificial viscosity is introduced. The quintic spline reconstruction achieves sixth-order accuracy on uniform grids without artificial viscosity and fifth-order accuracy on both uniform and non-uniform grids when artificial viscosity is added. The splined scheme is blended with shock-capturing WENO scheme to suppress non-physical oscillations near discontinuities. Numerical results demonstrate the accuracy, robustness and efficiency of the proposed scheme.

The ossicles represent one of the most fundamental morphological features in evolutionary biology of the mammalians. The mobile ossicular morphology abnormalities result in the severe conductive hearing loss. Development and patterning of the middle ear malformation depend on genetic and environmental causes. However, the genetic basis for the risk of congenital ossicle malformation is poorly understood. We show here nine affected individuals in a Chinese pedigree who had bilateral conductive hearing loss with ptosis. We performed whole-genome sequencing and array comparative genomic hybridization (CGH) analysis on DNA samples from the Chinese pedigree. We confirmed the presence of a novel 60 kb heterozygous deletion in size, encompassing SIX2 in our family. Mutation screening in 169 sporadic cases with external ear and middle ear malformations identified no pathogenic variant or polymorphism. We suggest SIX2 haploinsufficiency as a potential congenital factor could be attributed to developmental malformation of the middle ear ossicles and upper eyelid. To the best of our knowledge, this is the first report to provide a description of copy number variation in the SIX2 gene resulting in syndromic conductive hearing loss.

Auditory neuropathy spectrum disorder is a unique group of hearing dysfunctions characterized by preserved outer hair cell function and abnormal neural conduction of the auditory pathway. However, the pathogenic mechanism underlying this disorder is not clear. We therefore performed a systematic review of genetic mouse models with different gene mutations to provide a valuable tool for better understanding of the process and the possible molecular mechanisms. Of the 18 articles retrieved, nine met the required criteria. All biochemical, histological, and electrophysiological results were recorded for each of the mouse models, as was the transgenic technology. This review provides a summary of different mouse models that may play an important role in the diagnosis and management of auditory neuropathy spectrum disorder in the future.

We compared the enhancement of photoactivity of transition metal ion (1 mol% Fe, Cu, Mn, and Zn) doped CeO2 nanocatalysts, and examined the effects of oxygen vacancies and the valence of the doped ions. The nanocatalysts were synthesized using a coprecipitation method and were characterized by x-ray diffraction, scanning electron microscopy, transmission electron microscopy, Brunauer–Emmett–Teller isotherm methods and Raman spectroscopy. The photocatalytic activities of these catalysts were tested using aqueous Rhodamine B (RhB) degradation under UV irradiation. The spherical CeO2 nanocatalysts had a mesoporous structure and ∼15 nm average particle size. The catalytic activity was closely related to the oxygen vacancies and the valence of the doped ions. An increase in oxygen vacancies of doped CeO2 decreased the photocatalytic activity. The photocatalytic activities of the catalysts decreased in the order: 1 mol% Fe > Cu > Mn > Zn > undoped CeO2. The 1 mol% Fe doped CeO2 degraded ∼92.6% of the RhB after 3 h of irradiation, and the degradation obeyed pseudo-first-order kinetics. Liquid chromatography–mass spectrometry indicated that the photodegradation of RhB was a stepwise oxidation process. Under continuous oxidation, over a long reaction time, the RhB was completely oxidized to its final products, such as water and carbon dioxide.

The nanocrystalline xCuFe2O4/CuO (x ≤ 50 %) composite microfibers with a fiber diameter about 0.5–2 μm, length of tens to hundreds of micrometers were prepared by the sol–gel process. The content of CuFe2O4 on the magnetic and electrochemical properties of CuFe2O4/CuO composite microfibers was investigated. The microfibers were characterized by X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscopy, vibrating sample magnetometer and X-ray photoelectron spectroscopy analysis. At the calcination temperature of 900 °C, with a content of copper ferrite phase about 10 %, the optimized porous composite microfibers are obtained. These composite microfibers show a typical soft magnetic property, and the specific saturation magnetization is related to the calcination temperature as well as CuFe2O4 content, with a steady M r/M s value of 0.64 at CuFe2O4 content (x) range from 10 to 50 %. The electrochemical properties of the as-prepared microfibers were investigated by cyclic voltammetry method, and the results show these composite microfibers are good electrode materials for supercapacitors. The 10 % CuFe2O4/CuO composite microfibers have the highest specific capacity of 81.7 F/g, with almost no decay after 200 cycles.

In order to construct the recombinant plasmid of pIRES-ORF81, the nucleic acid isolated from Koi herpes virus-CJ (KHV-CJ) strains was used as a template to insert the ORF81 gene fragments amplified by PCR into the pIRES-neo, a kind of eukaryotic expression vector. Using Western blotting analysis, it was verified that ORF81 gene protein can be expressed correctly by pIRES-ORF81, after MFC cells were transfected. The recombinant plasmid pIRES-ORF81 was set into three immunization dose gradients: 1, 10, and 50 μg/carp. Empty plasmid group, PBS group, and blank control group were set simultaneously. Giving intramuscular injections to healthy carps with an average body mass of 246 ± 20 g, indirect ELISA was used to regularly determine antibody levels after three times immunization injection. Neutralizing antibodies were detected by neutralization assay. The results of inoculation tests showed that the pIRES-ORF81 recombinant plasmid can induce the production of carp-specific antibodies. The differences of immune effect between the three different doses of immune gradients were not significant (P > 0.05), but they can induce the production of neutralizing antibodies. After 25 d of inoculation, carp mortality of pIRES-neo empty vector treatment groups was 85%, while the carp mortality of eukaryotic expression recombinant plasmid pIRES-ORF81 injected with three different doses of immune gradients was 20, 17.5, and 12.5%, respectively. Differences in comparison to the control group were highly significant (P < 0.01). However, histopathological section of immunohistochemistry organization revealed no significant changes. It demonstrated that the DNA vaccine pIRES-ORF81 constructed in the experiment displayed a good protective effect against KHV, which had the potential to industrial applications.

To decipher the phenotype and genotype of a Chinese family with autosomal dominant non-syndromic hearing loss (ADNSHL) and a novel dominant missense mutation in the GJB2 gene (DFNA3), mutation screening of GJB2 was performed on the propositus from a five-generation ADNSHL family through polymerase chain reaction amplification and Sanger sequencing. The candidate variation and the co-segregation of the phenotype were verified in all ascertained family members. Targeted genes capture and next-generation sequencing (NGS) were performed to explore additional genetic variations. We identified the novel GJB2 mutation c.524C > A (p.P175H), which segregated with high frequency and was involved in progressive sensorineural hearing loss. One subject with an additional c.235delC mutation showed a more severe phenotype than did the other members with single GJB2 dominant variations. Four patients diagnosed with noise-induced hearing loss did not carry this mutation. No other pathogenic variations or modifier genes were identified by NGS. In conclusion, a novel missense mutation in GJB2 (DFNA3), affecting the second extracellular domain of the protein, was identified in a family with ADNSHL.

The magnetic, nanocrystalline Fe0.2(Co20Ni80)0.8 alloy porous microfibers were prepared by the citrate gel thermal decomposition and reduction process. The morphology, chemical composition, microstructure, and magnetic properties of the microfibers were investigated by X-ray diffraction, field emission scanning electron microscopy, energy-dispersive X-ray, Brunauere–Emmette–Teller, and vibration sample magnetometer. The as-prepared magnetic, nanocrystalline Fe0.2(Co20Ni80)0.8 porous microfibers consisting of about 48 nm grains are characterized by diameters of 1–4 μm, specific surface area of 17.73 m2/g, and specific magnetization of 196.7 Am2/kg. The arsenic(V) absorption on these magnetic Fe0.2(Co20Ni80)0.8 porous microfibers at room temperature was determined by the ICP-AES measurement of arsenic(V) in aqueous solution. The results show that the pseudo-first-order kinetic model is consistent with the arsenic(V) adsorption process and a good correlation coefficient (R 2 = 0.9862). By comparing among the Langmuir, Freundlich, Temkin, and Redlich–Peterson models for adsorption isotherms of arsenic(V) onto the magnetic Fe0.2(Co20Ni80)0.8 porous microfibers at room temperature, the Freundlich model and Redlich–Peterson model can be used to evaluate the arsenic(V) adsorption isotherm at room temperature. The arsenic(V) equilibrium absorbance of the magnetic Fe0.2(Co20Ni80)0.8 porous microfibers is up to 1.9 mg/g when the initial arsenic(V) concentration is 1.0 mg/L in aqueous solution.

This study was conducted to evaluate the effect of ethanolic extract of propolis (EEP) on growth performance and plasma biochemical parameters of rainbow trout (Oncorhynchus mykiss). Graded levels of EEP [0 (control), 1, 2, and 4 g kg(-1) diet] were fed to trout juveniles (mean weight 7.73 ± 0.17 g) for 10 weeks. Dietary EEP supplementation regardless of inclusion level significantly improved the specific growth rate of fish. Similarly, supplemental EEP generally improved the feed efficiency ratio and protein efficiency ratio, but no significant differences were observed between the 1 g kg(-1) EEP group and the control group. In addition, dietary EEP supplementation generally increased the plasma superoxide dismutase, lysozyme, total antioxidant capacity, glutathione peroxidase, and catalase activities, but decreased the plasma malondialdehyde level. The plasma triglycerides level was significantly lower in the 1 or 4 g kg(-1) EEP group as compared with the control group. Dietary EEP supplementation generally decreased the plasma aspartate aminotransferase and alanine aminotransferase activities, but increased the hepatic aspartate aminotransferase and alanine aminotransferase activities. These results indicate the potential to use the EEP as a growth promoter, hepatoprotective agent, and immunostimulant for rainbow trout.

We report a novel mutation (erlong, erl) of the cadherin 23 (Cdh23) gene in a mouse model for DFNB12 characterized by progressive hearing loss beginning from post-natal day 27 (P27). Genetic and sequencing analysis revealed a 208T>C transition causing an amino acid substitution (70S-P). Caspase expression was up-regulated in mutant inner ears. Hearing was preserved (up to 35-dB improvement) in pan-caspase inhibitor Z-VAD-FMK-treated mutants compared to untreated mutants (P < 0.05). Outer hair cell (OHC) loss in the cochleae of Z-VAD-FMK-treated mutants was significantly reduced compared to those of untreated mice. Thus, the erl mutation can lead to hearing loss through apoptosis. This is the first genetic mouse model of hearing loss shown to respond to otoprotective drug therapy. The short interval from initial hearing loss to deafness (P27-P90) makes this model ideal for screening and validating otoprotective drugs.

Magnetic Ni0.5Zn0.5Fe2O4 nanoparticles were prepared by the rapid combustion process and their microstructure and magnetic properties were investigated by XRD, SEM, EDX, and VSM. The as-prepared magnetic Ni0.5Zn0.5Fe2O4 nanoparticles were characterized with about 16 nm grains and specific magnetization of 46.0 Am2/kg. The adsorption kinetics and adsorption isotherms of methyl blue onto the magnetic Ni0.5Zn0.5Fe2O4 nanoparticles at room temperature were investigated. The kinetics data related to the adsorption of methyl blue from aqueous solutions are in good agreement with the pseudo-second-order kinetic model in a range of initial concentration of 50–300 mg/L. By comparison of the Langmuir, Freundlich, Temkin and Redlich–Peterson models for adsorption isotherms of methyl blue, the Temkin model (correlation coefficient R 2 = 0.9912) and Redlich–Peterson model (correlation coefficient R 2 = 0.9963) can be used to evaluate the methyl blue adsorption isotherm at room temperature. The adsorption capacity of methyl blue onto magnetic Ni0.5Zn0.5Fe2O4 nanoparticles reaches the maximum value at pH 3.