Multishock to Quasi-Isentropic Compression of Dense Gaseous Deuterium-Helium Mixtures up to 120 GPa: Probing the Sound Velocities Relevant to Planetary Interiors.

Shock reverberation compression experiments on dense gaseous deuterium-helium mixtures are carried out to provide thermodynamic parameters relevant to the conditions in planetary interiors. The multishock pressures are determined up to 120 GPa and reshock temperatures to 7400 K. Furthermore, the unique compression path from shock-adiabatic to quasi-isentropic compressions enables a direct estimation of the high-pressure sound velocities in the unexplored range of 50-120 GPa. The equation of state and sound velocity provide particular dual perspectives to validate the theoretical models. Our experimental data are found to agree with several equation of state models widely used in astrophysics within the probed pressure range. The current data improve the experimental constraints on sound velocities in the Jovian insulating-to-metallic transition layer.

NLRP10 ablation protects against ischemia/reperfusion-associated brain injury by suppression of neuroinflammation.

Ischemic stroke leads to neuronal cell death and induces a cascade of inflammatory signals that results in secondary brain damage. Although constant efforts to develop therapeutic strategies and to reveal the molecular mechanism resulting in the physiopathology of this disease, much still remains unclear. Membrane-bound Toll-like receptors (TLRs) and cytosolic nucleotide binding oligomerization domain (NOD)-like receptors (NLRs) are two major families of pattern recognition receptors that initiate pro-inflammatory signaling pathways. In the present study, we explored the role of NLRP10 in regulating inflammatory responses in acute ischemic stroke using the wild type (WT) and NLRP10 knockout (KO) mice by inducing middle cerebral artery occlusion/reperfusion (MCAO) injuries. The study first showed that NLRP10 was over-expressed in the ischemic penumbra of WT mice. Then, the brain infarct volume was significantly decreased, and the moving activity was improved post-MCAO in mice with NLRP10 knockout. Apoptosis was also alleviated by NLRP10-knockout, as evidenced by the decreased number of TUNEL-staining cells. Further, NLRP10 deficiency attenuated the activation of glia cells in hippocampus of mice with MCAO operation. NLRP10 inhibition ameliorated the levels of inflammatory factors in peripheral blood serum and hippocampus of mice after stroke. The activation of toll-like receptor (TLR)-4/nuclear factor-κB (NF-κB) signaling pathways was markedly suppressed by NLRP10 ablation in mice after MCAO treatment. Importantly, inflammasome, including NLRP12, ASC and Caspase-1, induced by MCAO in hippocampus of mice was clearly impeded by the loss of NLRP10. The results above were mainly verified in LPS-incubated astrocytes in the absence of NLRP10. Correspondingly, in LPS-treated astrocytes, NLRP10 knockout-reduced inflammation via impairing TLR-4/NF-κB and NLRP12/ASC/Caspase-1 pathways was evidently restored by over-expressing NLRP10. Therefore, the results above indicated an essential role of NLRP10 in regulating ischemic stroke, presenting NLRP10 as a promising target to protect human against stroke.

11 Long noncoding RNA UCA1 functions as miR-135a sponge to promote the epithelial to mesenchymal transition in glioma.

The dysregulation of long noncoding (lncRNA) UCA1 may play an important role in tumor progression. However, the function in gliomas is unclear. Therefore, this experiment was designed to explore the pathogenesis of glioma based on lncRNA UCA1. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of lncRNA UCA1, miR-135a, and HOXD9 in gliomas tissues. The effect of lncRNA UCA1 and miR-135a on tumor cell proliferation and migration invasiveness was examined by CCK-8 and transwell assays. Target gene prediction and screening, luciferase reporter assay were used to verify downstream target genes of lncRNA UCA1. Expression of E-cadherin, N-cadherin, vimentin, and HOXD9 was detected by RT-qPCR and Western blotting. The tumor changes in mice were detected by in vivo experiments in nude mice. lncRNA UCA1 was highly expressed in glioma tissues and cell lines. lncRNA UCA1 expression was associated with significantly poor overall survival in gliomas. Moreover, lncRNA UCA1 significantly enhanced cell proliferation and migration, and promoted the occurrence of EMT. In addition, lncRNA UCA1 promoted the development of EMT by positively regulating HOXD9 expression as a miR-135a sponge. In vivo experiments indicated that UCA1 exerted its biological functions by modulating miR-135a and HOXD9. In conclusion, lncRNA UCA1 can induce the activation of HOXD9 by inhibiting the expression of miR-135a and promote the occurrence of EMT in glioma.

Impact of Physician-Coordinated Intensive Follow-Up on Long-Term Medical Costs in Patients with Unstable Angina Undergoing Percutaneous Coronary Intervention.

BACKGROUND: To investigate the impact of professional physician-coordinated intensive follow-up on long-term expenditures after percutaneous coronary intervention (PCI) in unstable angina (UA) patients. METHODS: In this study, there were 669 UA patients who underwent successful PCI and followed up for 3 years, then divided into the intensive follow-up group (N = 337), and the usual follow-up group (N = 332). Patients were provided with detailed discharge information and individualized follow-up schedules. The intensive group received the extra follow-up times and medical consultations, and all patients were followed up for approximately 3 years. RESULTS: At the 3-year mark after PCI, the cumulative major adverse cardiac events (MACE), recurrence of myocardial ischemia, cardiac death, all-cause death and revascularization in the intensive group were lower than in the usual group. Additionally, the proportion of good medication adherence was significantly higher than in the usual group (56.4% vs. 46.1%, p < 0.001). The hospitalization daytime, total hospitalization cost and total medical cost in the intensive group were lower. Multiple linear regression showed that diabetes, hypertension, intensive follow-up and good medication adherence were associated with emergency and regular clinical cost (p < 0.05), the re-hospitalization cost (p < 0.05) and the total medical cost (p < 0.05) of patient care. Intensive follow-up and good adherence were negatively correlated with the cost of re-hospitalization (standardized coefficients = -0.132, -0.128, p < 0.05) and total medical costs (standardized coefficients = -0.072, -0.086, p < 0.05). CONCLUSIONS: Intensive follow-up can reduce MACE, improve medication adherence and save long-term total medical costs, just by increasing the emergency and regular clinical visits cost in UA patients after PCI.

Israeli acute paralysis virus: epidemiology, pathogenesis and implications for honey bee health.

Israeli acute paralysis virus (IAPV) is a widespread RNA virus of honey bees that has been linked with colony losses. Here we describe the transmission, prevalence, and genetic traits of this virus, along with host transcriptional responses to infections. Further, we present RNAi-based strategies for limiting an important mechanism used by IAPV to subvert host defenses. Our study shows that IAPV is established as a persistent infection in honey bee populations, likely enabled by both horizontal and vertical transmission pathways. The phenotypic differences in pathology among different strains of IAPV found globally may be due to high levels of standing genetic variation. Microarray profiles of host responses to IAPV infection revealed that mitochondrial function is the most significantly affected biological process, suggesting that viral infection causes significant disturbance in energy-related host processes. The expression of genes involved in immune pathways in adult bees indicates that IAPV infection triggers active immune responses. The evidence that silencing an IAPV-encoded putative suppressor of RNAi reduces IAPV replication suggests a functional assignment for a particular genomic region of IAPV and closely related viruses from the Family Dicistroviridae, and indicates a novel therapeutic strategy for limiting multiple honey bee viruses simultaneously and reducing colony losses due to viral diseases. We believe that the knowledge and insights gained from this study will provide a new platform for continuing studies of the IAPV-host interactions and have positive implications for disease management that will lead to mitigation of escalating honey bee colony losses worldwide.

Posterior scleral reinforcement combined with patching therapy for pre-school children with unilateral high myopia.

PURPOSE: Our purpose was to investigate the effect of posterior scleral reinforcement (PSR) combined with patching therapy for pre-school children with unilateral high myopia. METHODS: A total of 32 pre-school children with unilateral high myopia were recruited. They were randomly divided into the PSR and control group, each of which had 16 patients. The patients in the PSR group underwent the simplified PSR surgery followed by rigid gas permeable contact lens wear and traditional patching therapy, while the patients in the control group were only prescribed contact lens wear and patching. Patients were reviewed and the axial length, refraction, best-corrected visual acuity, and stereoscopic vision were respectively examined postoperatively at yearly intervals for three years. RESULTS: The best-corrected visual acuity was significantly higher in the PSR group than that in the control group at any study visit. A statistically significant difference in axial length was found between the PSR group (27.38 ± 1.30 mm) and the control group (28.29 ± 0.74 mm) at the postoperative three-year (p = 0.03) time point. There was a statistical difference in refractive error between the PSR group (-13.13 ± 2.55 D) and the control group (-15.42 ± 1.83 D) at 3-year follow-up. No significant difference was found between the two groups with respect to the stereoscopic vision by the end of follow-up at 3 years (p =0.103). CONCLUSIONS: PSR combined with the patching therapy has the potential to arrest the progression of high myopia and to help the treatment for amblyopia.

[Regulating effect of N-acetyl-seryl-aspartyl-lysyl-proline on activation of c-jun N-terminal kinase pathway in rats with silicosis].

OBJECTIVE: To investigate the regulatory effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the activation of c-jun N-terminal kinase (JNK) signal transduction pathway and its role in silicotic fibrosis. METHODS: A rat model of silicosis was developed by intratracheal instillation. Sixty rats were randomly divided into 4-week control group (n = 10), 8-week control group (n = 10), 4-week silicosis model group (n = 10), 8-week silicosis model group (n = 10), AcSDKP treatment group (n = 10), and AcSDKP prevention group (n = 10). The content of hydroxyproline in lung tissue was measured using a p-dimethylaminoben-zaldehyde reagent; the expression levels of transforming growth factor (TGF)-beta 1 (TGF-ß1), phospho-JNK, JNK, and c-jun in lung tissue were measured by Western blot. The lung fibroblasts from neonatal rats were cultured, and the 4th generation of cells were used in the experiment; these cells were divided into control group, TGF-ß1 stimulation group, SP600125 intervention group, and AcSDKP intervention group. The distributions of phospho-JNK and c-jun in lung fibroblasts were observed by immunocytochemistry; the expression levels of type I collagen and type III collagen in lung fibroblasts were measured by Western blot. RESULTS: The expression levels of TGF-ß1, phospho-JNK, and c-jun and the content of hydroxyproline in the AcSDKP treatment group were 70.60%, 78.03%, 79.85%, and 71.28%, respectively, of those in the 4-week silicosis model group (P < 0.05) and 77.99%, 66.73%, 69.94%, and 64.82%, respectively, of those in the 8-week silicosis model group (P < 0.05); the expression levels of TGF-ß1, phospho-JNK, and c-jun and the content of hydroxyproline in the AcSDKP prevention group were 84.56%, 61.18%, 64.73%, and 74.96%, respectively, of those in the 8-week silicosis model group (P < 0.05). The expression levels of phospho-JNK and c-jun in the AcSDKP intervention group were 54.59% and 55.56%, respectively, of those in the TGF-ß1 stimulation group; the expression levels of type I collagen and type III collagen in the AcSDKP intervention group were 79.9% and 84.4%, respectively, of those in the TGF-ß1 stimulation group (P < 0.05). CONCLUSION: AcSDKP exerts anti-silicotic fibrosis effect probably by inhibiting the activation of JNK signal transduction pathway mediated by TGF-ß1 and the deposition of interstitial collagen.

The effect of annulus fibrosus incision and foraminoplasty on lumbar biomechanics in percutaneous endoscopic lumbar discectomy: a finite element analysis.

The objective of this study was to analyze the effects of annulus fibrosus incision and foraminoplasty on lumbar biomechanics during posterior lateral approach translaminar percutaneous endoscopic lumbar discectomy (PELD) using a lumbar 4/5 segment model and three-dimensional finite element analysis (FEA). We created a model of the L4 to L5 segment and performed simulated foraminoplasty, annulus fibrosus incision, and a combined operation. The models were tested under six working conditions, and we recorded the deformation and equivalent strain/stress of each group. Results showed that foraminoplasty can affect the stability and rotation axis of the segment during rotation without significantly impacting discal stress. Conversely, annulus fibrosus incision significantly increases discal stress except for when the patient is doing a forward flexion movement. We recommend that surgical maneuvers minimize the removal and destruction of the annulus fibrosus and that rotation movements are avoided during the short-term recovery period following PELD surgery.

Biomechanical Study of Minimally Invasive Nonfusion Surgery for Treatment of Disc Herniation Associated with Adjacent Segment Disease: A Finite Element Analysis.

OBJECTIVE: We explored the biomechanical changes of 2 conventional minimally invasive nonfusion surgical methods for treating disc herniation in adjacent segment disease using 3-dimensional finite element analysis. METHODS: A model comprising L3 to the sacrum was validated and used to establish an L4-L5 fusion model, and an adjacent segment disease (ASD) model was developed by modifying the material properties of the intervertebral discs. The ASD model was used to simulate 2 conventional minimally invasive nonfusion surgical methods, which resulted in the creation of 2 postoperative models (M1 and M2). The range of motion and the equivalent stress for each model were recorded under 6 different working conditions. The data are descriptive and were analyzed comparatively under a normal load. RESULTS: Compared with the ASD group, the range of motion of the adjacent segment in the M1 and M2 groups remained unaffected. However, significant Von-Mises stress changes were found in the annulus fibrosus and nucleus pulposus (NP), especially during extension, ipsilateral bending, and rotation. Stress in the NP also shifted toward the surgical incision in the annulus fibrosus during these movements. The maximum Von-Mises stress in the NP of the cephalic segment increased more than did that of the caudal segment. CONCLUSIONS: Minimal nonfusion surgery for ASD might not affect adjacent segment stability significantly. Nonetheless, it can lead to segmental degeneration deterioration and postoperative recurrence. The cephalic segment is affected more than the caudal segment. Therefore, consideration of disc degeneration and appropriate selection of surgical methods for ASD are crucial.

Enhancement patterns of potassium on nitrogen transport and functional genes in cotton vary with nitrogen levels.

The application of potassium (K) in conjunction with nitrogen (N) has been shown to enhance N use efficiency. However, there is still a need for further understanding of the optimal ratios and molecular regulatory mechanisms, particularly in soil-cotton systems. Here, a field trial was conducted, involving varying rates of N and K, alongside pot and hydroponic experiments. The objective was to assess the impact of N-K interaction on the absorption, transport and distribution of N in cotton. The results showed that K supply at 90 and 240 kg ha-1 had a beneficial impact on N uptake and distribution to both seed and lint, resulting in the highest N use efficiency ranging from 22% to 62% and yield improvements from 20% to 123%. The increase in stem and root diameters, rather than the quantify of xylem vessels and phloem sieve tubes, facilitated the uptake and transport of N due to the provision of K. At the molecular level, K supply upregulated the expression levels of genes encoding GhNRT2.1 transporter and GhSLAH3 channel in cotton roots to promote N uptake and GhNRT1.5/NPF7.3 genes to transport N to shoot under low-N conditions. However, under high-N conditions, K supply induced anion channel genes (GhSLAH4) of roots to promote N uptake and genes encoding GhNRT1.5/NPF7.3 and GhNRT1.8/NPF7.2 transporters to facilitate NO3- unloading from xylem to mesophyll cell in high-N plants. Furthermore, K supply resulted in the upregulation of gene expression for GhGS2 in leaves, while simultaneously downregulating the expression of GhNADH-GOGAT, GhGDH1 and GhGDH3 genes in high-N roots. The enzyme activities of nitrite reductase and glutamine synthetase increased and glutamate dehydrogenase decreased, but the concentration of NO3- and soluble protein exhibited a significant increase and free amino acid decreased in the shoots subsequent to K supply.

[Distribution Characteristics and Risk Assessment of Microplastics in Soil in Danjiangkou Reservoir Area of South-to-North Water Diversion Project].

To explore the occurrence characteristics and influencing factors of microplastics in soil in the Danjiangkou Reservoir area, this study collected soil samples from orchards, dryland, paddy fields, and wetland and identified microplastics in soil via density sorting, microscope observation, and Raman spectrometry. The results showed that microplastics were detected in 64 samples collected in the study area, and the abundance ranged from 645 to 15161 n·kg-1. The spatial distribution of microplastics in the bottom of the reservoir was higher than those in the middle and head of the reservoir, and the abundance of microplastics in the surface soil(0-20 cm) was significantly lower than that in the bottom soil(20-40 cm). The main types of microplastics were polypropylene(26.4%) and polyamide(20.2%), the particle size was mainly concentrated between 50-500 µm(75%), and the common shape was fragments(66.2%). Correlation analysis showed that soil microplastic abundance was closely related to land use, distance from water and housing, population density, and soil properties. From the perspective of microplastic pollution risk, 72.1% of the region's microplastic polymer risk index was at level Ⅲ and level Ⅳ, and there was a certain risk of microplastic pollution in the Danjiangkou Reservoir area. The results of this study can provide support for risk assessment of microplastics.

Enhanced tolerance to NaCl and LiCl stresses by over-expressing Caragana korshinskii sodium/proton exchanger 1 (CkNHX1) and the hydrophilic C terminus is required for the activity of CkNHX1 in Atsos3-1 mutant and yeast.

Sodium/proton exchangers (NHX antiporters) play important roles in plant responses to salt stress. Previous research showed that hydrophilic C-terminal region of Arabidopsis AtNHX1 negatively regulates the Na(+)/H(+) transporting activity. In this study, CkNHX1 were isolated from Caragana korshinskii, a pea shrub with high tolerance to salt, drought, and cold stresses. Transcripts of CkNHX1 were detected predominantly in roots, and were significantly induced by NaCl stress in stems. Transgenic yeast and Arabidopsisthalianasos3-1 (Atsos3-1) mutant over-expressing CkNHX1 and its hydrophilic C terminus-truncated derivative, CkNHX1-ΔC, were generated and subjected to NaCl and LiCl stresses. Expression of CkNHX1 significantly enhanced the resistance to NaCl and LiCl stresses in yeast and Atsos3-1 mutant. Whereas, compared with expression of CkNHX1, the expression of CkNHX1-ΔC had much less effect on NaCl tolerance in Atsos3-1 and LiCl tolerance in yeast and Atsos3-1. All together, these results suggest that the predominant expression of CkNHX1 in roots might contribute to keep C. korshinskii adapting to the high salt condition in this plant's living environment; CkNHX1 could recover the phenotype of Atsos3-1 mutant; and the hydrophilic C-terminal region of CkNHX1 should be required for Na(+)/H(+) and Li(+)/H(+) exchanging activity of CkNHX1.

Transport properties of a quasisymmetric binary nitrogen-oxygen mixture in the warm dense regime.

Transport properties of mixtures in the warm dense matter (WDM) regime play an important role in natural astrophysics. However, a physical understanding of ionic transport properties in quasisymmetric liquid mixtures has remained elusive. Here, we present extensive ab initio molecular dynamics (AIMD) simulations on the ionic diffusion and viscosity of a quasisymmetric binary nitrogen-oxygen (N-O) mixture in a wide warm dense regime of 8-120 kK and 4.5-8.0 g/cm^{3}. Diffusion and viscosity of N-O mixtures with different compositions are obtained by using the Green-Kubo formula. Unlike asymmetric mixtures, the change of proportions in N-O mixtures slightly affects the viscosity and diffusion in the strong-coupling region. Furthermore, the AIMD results are used to build and verify a global pseudo-ion in jellium (PIJ) model for ionic transport calculations. The PIJ model succeeds in reproducing the transport properties of N-O mixtures where ionization has occurred, and provides a promising alternative approach to obtaining comparable results to AIMD simulations with relatively small computational costs. Our current results highlight the characteristic features of the quasisymmetric binary mixtures and demonstrate the applicability of the PIJ model in the WDM regime.

Activation of P2X4 receptor exacerbates acute brain injury after intracerebral hemorrhage.

INTRODUCTION: Intracerebral hemorrhage (ICH) accounts for 10%-15% of all strokes and culminates in high mortality and disability. After ICH, brain injury is initiated by the mass effect of hematoma, followed by secondary cytotoxic injury from dying brain cells, hematoma disintegration, and cascading brain immune response. However, the molecular mechanism of secondary cytotoxic brain injury in ICH is not completely understood. The sensitive purinergic receptor, P2X4 receptor (P2X4R), was known to recognize extracellular free ATP released by dying cells during tissue injury. AIMS: In this study, we aim to understand the role of P2X4R in acute brain injury triggered by ICH. RESULTS: In this study, we found that the sensitive purinergic receptor, P2X4R, was upregulated in the brain of patients with ICH as well as in a mouse model of ICH induced by collagenase injection. P2X4R blockage with the specific inhibitor 5-BDBD attenuated brain injury in ICH mice by significantly reducing brain edema, blood-brain barrier leakage, neural death, and ultimately acute neurodeficits. Further study indicated that the protective effect of P2X4R inhibition is related to decreased pro-inflammatory activity of microglia and recruitment of peripheral immune cells into the hemorrhagic brain. CONCLUSIONS: These results suggest that the P2X4 receptor is activated by ICH stimuli which worsen brain injury following ICH.

Genes encoding the biotin carboxylase subunit of acetyl-CoA carboxylase from Brassica napus and parental species: cloning, expression patterns, and evolution.

Comparative genomics is a useful tool to investigate gene and genome evolution. Biotin carboxylase (BC), an important subunit of heteromeric acetyl-CoA carboxylase (ACCase) that is a rate-limiting enzyme in fatty acid biosynthesis in dicots, catalyzes ATP, biotin carboxyl carrier protein, and CO2 to form carboxybiotin carboxyl carrier protein. In this study, we cloned four genes encoding BC from Brassica napus L. (namely BnaC.BC.a, BnaC.BC.b, BnaA.BC.a, and BnaA.BC.b), and two were cloned from each of the two parental species Brassica rapa L. (BraA.BC.a and BraA.BC.b) and Brassica oleracea L. (BolC.BC.a and BolC.BC.b). Sequence analyses revealed that in B. napus the genes BnaC.BC.a and BnaC.BC.b were from the C genome of B. oleracea, whereas BnaA.BC.a and BnaA.BC.b were from the A genome of B. rapa. Comparative and cluster analysis indicated that these genes were divided into two major groups, BnaC.BC.a, BnaA.BC.a, BraA.BC.a, and BolC.BC.a in group-1 and BnaC.BC.b, BnaA.BC.b, BraA.BC.b, and BolC.BC.b in group-2. The divergence of group-1 and group-2 genes occurred in their common ancestor 13-17 million years ago (MYA), soon after the divergence of Arabidopsis and Brassica (15-20 MYA). This time of divergence is identical to the previously reported triplicated time of paralogous subgenomes of diploid Brassica species and the divergence date of group-1 and group-2 genes of α-carboxyltransferase, another subunit of heteromeric ACCase, in Brassica. Reverse transcription PCR revealed that the expression level of group-1 and group-2 genes varied in different organs, and the expression patterns of the two groups of genes were similar in different organs, except in flower. However, two paralogs of group-2 BC genes from B. napus could express differently in mature plants tested by generating BnaA.BC.b and BnaC.BC.b promoter-ß-glucuronidase (GUS) fusions. The amino acid sequences of proteins encoded by these genes were highly conserved, except the sequence encoding predicted plastid transit peptides. The plastid transit peptides on the BC precursors of Brassica (71-72 amino acid residues) were predicted based on AtBC protein, compared, and confirmed by fusion with green fluorescent protein. Our results will be helpful in elucidating the evolution and the regulation of ACCase in the genus Brassica.

Influence of KDR Genetic Variation on the Efficacy and Safety of Patients with Chemotherapy Refractory Metastatic CRC Who Received Apatinib Treatment.

BACKGROUND: The aim of the present study was to investigate the influence of kinase insert domain containing receptor (KDR) genetic variation on the efficacy of treatment and safety of patients with chemotherapy-refractory metastatic colorectal cancer (CRC) receiving apatinib. METHODS: A total of 108 patients with chemotherapy refractory metastatic CRC who were treated with apatinib participated in this study retrospectively. Efficacy of the patients' treatment was evaluated. Prognosis was carried out and safety profile was documented, respectively. Blood specimens and peripheral blood mononuclear cells (PBMC) of the patients were obtained for the analysis of genetic variation and KDR gene mRNA expression, respectively. The association between genotype status and clinical outcomes was presented. RESULTS: Objective response rate (ORR) and disease control rate (DCR) of the 108 patients with metastatic CRC receiving apatinib treatment were 5.6% and 69.4%, respectively. Survival analysis results exhibited that the median progression-free survival (PFS) and overall survival (OS) of the 108 patients with metastatic CRC was 3.6 months (95% confidence interval (CI): 3.03-4.17 months) and 8.9 months (95% CI: 7.57-10.23 months), respectively. Subsequently, the analysis of KDR genetic variation indicated that rs2071559 was of clinical significance. The minor allele frequency of rs2071559 was 0.22 and the genotype status corresponded with Hardy-Weinberg equilibrium (P=0.949). Prognosis analysis in a dominant inheritance manner through the combination of patients with TC and CC genotype showed that the median PFS of patients with TT genotype and TC/CC genotype was 4.1 and 3.0 months, respectively (P=0.012). Furthermore, the median OS of patients with the two genotypes was 10.5 and 6.1 months, respectively (P=0.007). Additionally, multivariate Cox regression analysis of OS showed that TC/CC genotype was an independent factor for OS (Hazard ratio (HR)=0.65, P=0.021). Interestingly, mRNA expression analysis suggested that the mRNA expression of KDR in PBMC differed significantly according to rs2071559 genotype status (P<0.001). CONCLUSION: Apatinib demonstrated a potentially superior clinical outcome for patients with chemotherapy-refractory metastatic CRC. KDR polymorphism rs2071559 could be used as a potential biomarker for the prognosis evaluation of patients with CRC receiving apatinib therapy.

CRISPR/Cas9 mediated knockout of Amyellow-y gene results in melanization defect of the cuticle in adult Apis mellifera.

Visible genetic markers are critical to gene function studies using genome editing technology in insects. However, there is no report about visible phenotypic markers in Apis mellifera, which extremely influences the application of genomic editing in honey bees. Here, we cloned and characterized the Amyellow-y gene in A. mellifera. Stage expression profiles showed that Amyellow-y gene was highly expressed in 2-, 4-day-old pupae, and newly emerged bees, and a high expression level was detected in the leg, thorax, wing and sting. To understand its functional role in pigmentation, Amyellow-y edited honeybees were created using CRISPR/Cas9, and it was found that the black pigment was decreased in the cuticle of mosaic workers and mutant drones. In particular, mutant drones manifested an overall appearance of yellowish cuticle in the body and appendages, including antennae, wings and legs, indicating that mutagenesis induced by disruption of Amyellow-y with CRISPR/Cas9 are heritable. Furthermore, the expression levels of genes associated with melanin pigmentation was investigated in mutant and wild-type drones using quantitative reverse transcription PCR. Transcription levels of Amyellow-y and aaNAT decreased markedly in mutant drones than that in wild-type ones, whereas laccase 2 was significantly up-regulated. Our results provide the first evidence, to our knowledge, that CRISPR/Cas9 edited G1 mutant drones of A. mellifera have a dramatic body pigmentation defect that can be visualized in adults, suggesting that Amyellow-y may serve as a promising visible phenotypic marker for genome editing in honey bees.

Genes encoding the alpha-carboxyltransferase subunit of acetyl-CoA carboxylase from Brassica napus and parental species: cloning, expression patterns, and evolution.

Heteromeric acetyl coenzyme A carboxylase (ACCase), a rate-limiting enzyme in fatty acid biosynthesis in dicots, is a multi-enzyme complex consisting of biotin carboxylase, biotin carboxyl carrier protein, and carboxyltransferase (alpha-CT and beta-CT). In the present study, four genes encoding alpha-CT were cloned from Brassica napus, and two were cloned from each of the two parental species, B. rapa and B. oleracea. Comparative and cluster analyses indicated that these genes were divided into two major groups. The major divergence between group-1 and group-2 occurred in the second intron. Group-2 alpha-CT genes represented the ancestral form in the genus Brassica. The divergence of group-1 and group-2 genes occurred in their common ancestor 12.96-17.78 million years ago (MYA), soon after the divergence of Arabidopsis thaliana and Brassica (15-20 MYA). This time of divergence is identical to that reported for the paralogous subgenomes of diploid Brassica species (13-17 MYA). Real-time reverse transcription PCR revealed that the expression patterns of the two groups of genes were similar in different organs, except in leaves. To better understand the regulation and evolution of alpha-CT genes, promoter regions from two sets of orthologous gene copies from B. napus, B. rapa, and B. oleracea were cloned and compared. The function of the promoter of gene Bnalpha-CT-1-1 in group-1 and gene Bnalpha-CT-2-1 in group-2 was examined by assaying beta-glucuronidase activity in transgenic A. thaliana. Our results will be helpful in elucidating the evolution and regulation of ACCase in oilseed rape.

[Effect of N-acetyl-seryl-aspartyl-lysyl-proline on regulation of expression of ras-raf-ERK1/2 signal transduction pathway in lung of rats with silicosis].

OBJECTIVE: to investigate the effect of N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) on the expressions of c-Raf, ERK1/2 and TGF-ß1 in the lung of rats with silicosis, thus to investigate the regulating of AcSDKP on the Ras-Raf-ERK1/2 signal transduction pathway. METHODS: rats were instilled with silica through trachea as silicotic models and administered AcSDKP in the experiment. Rats were divided into 6 groups randomly, 10 rats in each group: Control 1 and 2 of silicotic model: each rat was intratracheally instilled with 1.0 ml normal sodium and was killed after 4 or 8 weeks; Silicotic model 1 and Silicotic model 2: each rat was intratracheally instilled with 1ml silica suspension and was killed after 4 or 8 weeks; Anti-fibrosis treatment of AcSDKP: after each rat was intratracheally instilled with 1ml silica suspension for 4 weeks, AcSDKP 800 microg × kg(-1) × d(-1) was administered into every rat and rats were killed at the eighth week; Preventing fibrosis treatment of AcSDKP: after AcSDKP 800 microg × kg(-1) × d(-1) was administered into every rat for 48 hours, each rat was intratracheally instilled with 1.0 ml silica suspension and rats were killed at the eighth week. The expression of c-Raf, phospho-c-Raf, ERK1/2, phospho-ERK1/2 and TGF-ß1 was measured by immunohistochemistry and western blot assay. RESULTS: compared with the corresponding control groups, the expressions of phospho-c-Raf, phospho-ERK1/2 and TGF-ß1 increased in the lung tissue of the silicotic models. Compared with the corresponding model groups, after administration AcSDKP, the expressions of phospho-c-Raf, phospho-ERK1/2 and TGF-ß1 in the lung tissue reduced obviously. In anti-fibrosis treatment of AcSDKP group, expressions of phospho-c-Raf, phospho-ERK1/2 and TGF-ß1 decreased to 52.25%, 51.72% and 67.74% compared with those of the silicotic model 1, and expressions of phospho-c-Raf, phospho-ERK1/2 and TGF-ß1 decreased to 49.37%, 55.76%, 65.63% compared with those of the silicotic model 2; In preventing fibrosis treatment of AcSDKP group, expressions of phospho-c-Raf, phospho-ERK1/2 and TGF-ß1 decreased to 54.64%, 55.76% and 78.91% compared with those of the silicotic model 2 (P < 0.05) while the expressions of c-Raf and ERK1/2 were not different significantly among each groups. CONCLUSION: AcSDKP possibly plays an important role in anti-silicotic fibrosis by blocking the TGF-ß-induced Ras-Raf-ERK1/2 signal transduction pathway.

LncRNA TDRG1 promotes the aggressiveness of gastric carcinoma through regulating miR-873-5p/HDGF axis.

Gastric carcinoma (GC) is still one of the most common digestive system neoplasms and the primary reason for malignant cancer-associated death. Long non-coding RNAs (lncRNAs) have been reported to play critical roles in GC progression. In this study, we demonstrated that lncRNA testis development-related gene 1 (TDRG1) is markedly upregulated in clinical GC tissues and GC cells. High level of lncRNA TDRG1 correlates with the metastasis and prognosis of patients with GC. Overexpression of lncRNA TDRG1 promotes GC growth and metastatic-related traits in vitro and in vivo, and silencing TDRG1 causes opposite results. We future find that TDRG1 is inversely associated with miR-873-5p and positively modulates the expression of hepatoma-derived growth factor (HDGF), a functional target gene of miR-873-5p. Finally, lncRNA TDRG1 regulates the progression of GC through regulating miR-873-5p/HDGF pathway. Taken together, our data uncover the crucial function of TDRG1-miR-873-5p-HDGF axis in human gastric cancer.