[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.

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.

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.

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.

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.

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.

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.

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.

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.

Circulating Soluble ST2 Predicts All-Cause Mortality in Severe Heart Failure Patients with an Implantable Cardioverter Defibrillator.

BACKGROUND: Heart failure (HF) is the terminal stage of all cardiovascular events. Although implantable cardioverter defibrillator (ICD) therapies have reduced mortality among the high-risk HF population, it is necessary to determine whether certain factors can predict mortality even after cardiac device implantation. Growth stimulation expressed gene 2 (ST2) is an emerging biomarker for HF patient stratification in different clinical settings. AIMS: This study aimed to investigate the relationship between baseline soluble ST2 (sST2) levels in serum and the clinical outcomes of high-risk HF patients with device implantation. METHODS: Between January 2017 and August 2018, we prospectively recruited consecutive patients implanted with an ICD for heart failure, with LVEF ≤35% as recommended, and analyzed the basic characteristics, baseline serum sST2, and NT-proBNP levels, with at least 1-year follow-up. All-cause mortality was the primary endpoint. RESULTS: During a 643-day follow-up, all-cause mortality occurred in 16 of 150 patients (10.67%). Incidence of all-cause mortality increased significantly in patients with sST2 levels above 34.98846 ng/ml (16.00% vs. 5.33%, P = 0.034). After adjusting the model (age, gender, device implantation, prevention of sudden death, LVEDD, LVEF, WBC and CLBBB, hsTNT, etiology, and eGFR) and the model combined with NT-proBNP, the risk of all-cause death was increased by 2.5% and 1.9%, respectively, per ng/ml of sST2. The best sST2 cutoff for predicting all-cause death was 43.42671 ng/ml (area under the curve: 0.72, sensitive: 0.69, and specificity: 0.69). Compared to patients with sST2 levels below 43.42671 ng/ml, the risk of all-cause mortality was higher in those with values above the threshold (5.1% vs. 21.2%, P = 0.002). ST2 level ≥43.42671 ng/ml was an independent predictor of all-cause mortality (HR: 3.30 [95% CI 1.02-10.67]). Age (HR: 1.06 [95% CI: 1.01-1.12]) and increased NT-proBNP per 100 (HR: 1.02 [95% CI: 1.01-1.03]) were also associated with all-cause mortality in ICD patients. CONCLUSIONS: sST2 level was associated with risk of all-cause mortality, and a threshold of 43.43 ng/ml showed good distinguishing performance to predict all-cause mortality in patients with severe heart failure, recommended for ICD implantation. Patients with sST2 levels more than 43.42671 ng/ml even after ICD implantation should therefore be monitored carefully.

Benchmarking the effective one-component plasma model for warm dense neon and krypton within quantum molecular dynamics simulation.

The effective one-component plasma (EOCP) model has provided an efficient approach to obtaining many important thermophysical parameters of hot dense matter [J. Clérouin, et al., Phys. Rev. Lett. 116, 115003 (2016)PRLTAO0031-900710.1103/PhysRevLett.116.115003]. In this paper, we perform extensive quantum molecular dynamics (QMD) simulations to determine the equations of state, ionic structures, and ionic transport properties of neon and krypton within the warm dense matter (WDM) regime where the density (ρ) is up to 12 g/cm^{3} and the temperature (T) is up to 100 kK. The simulated data are then used as a benchmark to explicitly evaluate the EOCP and Yukawa models. It is found that, within present ρ-T regime, the EOCP model can excellently reproduce the diffusion and viscosity coefficients of neon and krypton due to the fact that this model defines a system which nearly reproduces the actual physical states of WDM. Therefore, the EOCP model may be a promising alternative approach to reasonably predicting the transport behaviors of matter in WDM regime at lower QMD computational cost. The evaluation of Yukawa model shows that the consideration of the energy level broadening effect in the average atom model is necessary. Finally, with the help of EOCP model, the Stokes-Einstein relationships about neon and krypton are discussed, and fruitful plasma parameters as well as a practical ρ-T-dependent formula of the effective coupling parameter are obtained. These results not only provide valuable information for future theoretical and experimental studies on dense neon and krypton but also reveal the applicability of the EOCP model and the limitation of the Yukawa model in WDM regime and further support the continuing search for a unified description of ionic transport in dense plasma.

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.

Adefovir Dipivoxil plus Chinese Medicine in HBeAg-Positive Chronic Hepatitis B Patients: A Randomized Controlled 48-Week Trial.

OBJECTIVE: To evaluate the effects of a 48-week course of adefovir dipivoxil (ADV) plus Chinese medicine (CM) therapy, namely Tiaogan Jianpi Hexue () and Tiaogan Jiedu Huashi () fomulae, in hepatitis B e antigen (HBeAg)-positive Chinese patients. METHODS: A total of 605 HBeAg-positive Chinese CHB patients were screened and 590 eligible participants were randomly assigned to 2 groups in 1:1 ratio including experimental group (EG, received ADV plus CM) and control group (CG, received ADV plus CM-placebo) for 48 weeks. The major study outcomes were the rates of HBeAg and HBV-DNA loss on week 12, 24, 36, 48, respectively. Secondary endpoints including liver functions (enzymes and bilirubin readings) were evaluated every 4 weeks at the beginning of week 24, 36, and 48. Routine blood, urine, and stool analyses in addition to electrocardiogram and abdominal B scan were monitored as safety evaluations. Adverse events (AEs) were documented. RESULTS: The combination therapy demonstrated superior HBeAg loss at 48 weeks, without additional AEs. The full analysis population was 560 and 280 in each group. In the EG, population achieved HBeAg loss on week 12, 24, 36, and 48 were 25 (8.90%), 34 (12.14%), 52 (18.57%), and 83 (29.64%), respectively; the equivalent numbers in the CG were 20 (7.14%), 41 (14.64%), 54 (19.29%), and 50 (17.86%), respectively. There was a statistically significant difference between these group values on week 48 (P<0.01). No additional AEs were found in EG. Subgroup analysis suggested different outcomes among treatment patterns. CONCLUSION: Combination of CM and ADV therapy demonstrated superior HBeAg clearance compared with ADV monotherapy. The finding indicates that this combination therapy may provide an improved therapeutic effect and safety profile (ChiCTR-TRC-11001263).

New possible candidate structure for phase IV of solid hydrogen.

It has been proved in experiments that there are at least five phases of solid hydrogen at high pressure, however, only the structure of phase I has been absolutely determined. We revisited the phase space of solid hydrogen in the pressure range of 200-500 GPa using the particle swarm optimization technique combined with first-principles simulations. A novel orthorhombic structure named Ama2 is proposed as a possible candidate structure for phase IV. The Ama2 structure is a 'mixed structure' with two different types of layers and is distinctly different from the previously reported Pc structure. Enthalpies and Gibbs free energies show that Ama2 and Pc are competitive in the pressure region of phase IV. Nevertheless, the Raman and infrared vibron frequencies of Ama2 calculated by using density functional perturbation theory based on first-principles lattice dynamics show a better agreement with the experimental measurements than those of the Pc structure. And the pressure dependence of these low-frequency Raman vibrons of Ama2 obtained from the first-principles molecular dynamics simulation shows a steeper slope, which resolves the long-standing issue of large discrepancies between the calculated Raman frequencies and the experimental ν 1 [P. Loubeyre, F. Occelli and P. Dumas, Phys. Rev. B: Condens. Matter Mater. Phys., 2013, 87, 134101 and C. S. Zha, R. E. Cohen, H. K. Mao and R. J. Hemley, Proc. Natl. Acad. Sci. U.S.A., 2014, 111, 4792]. Structural and vibrational analyses show that the hydrogen molecules in the weakly bonded molecular layer of Ama2 form distorted hexagonal patterns, and their vibration can be used to explain the experimental ν 1 vibron. It is found that the weakly bonded layer is almost the same as the layers in the C2/c structure. This confirms the experimental conclusion [P. Loubeyre, F. Occelli and P. Dumas, Phys. Rev. B: Condens. Matter Mater. Phys., 2013, 87, 134101] that the ordering of hydrogen molecules in the weakly bonded molecular layers of the 'mixed structure' for phase IV is similar to that in the layers of the C2/c structure.

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.

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.

Equation of state, ionic structure, and phase diagram of warm dense krypton.

Extensive quantum molecular dynamics (QMD) simulations are performed to determine the equation of state, sound velocity, and phase diagram of middle-Z krypton in a warm dense regime where the pressure (P) is up to 300 GPa and the temperature is up to 60 kK. The shock wave experimental data are used to validate the present theoretical models. It is found that, within the regime of the current density (ρ) and temperature (T), sound velocity can effectively discriminate differences between different theoretical models, and therefore it is more suitable as a benchmark to verify the practicability of models. The QMD-simulated results of the ionic structures and electronic properties imply the occurrence of two kinds of phase transitions, including transition from a solidlike to fluid state and that from an insulator to conductive fluid in this T-P regime. The calculated electrical conductivities confirm that the metallization transition occurs at about 60 GPa and 17.5 kK along the principal Hugoniot. With the help of simulation results and experimental data, a comprehensive phase diagram for krypton is constructed by using the solid-fluid and insulator-metal fluid phase boundaries, which fills the gap of the experimental work [Proc. Natl. Acad. Sci. USA 112, 7925 (2015)PNASA60027-842410.1073/pnas.1421801112]. These results will provide an instructive basis for the experimental investigations of rare gases over a wide T-P range.

Inhibition of activator protein 1 attenuates neuroinflammation and brain injury after experimental intracerebral hemorrhage.

AIMS: Intracerebral hemorrhage (ICH) is a devastating type of stroke without specific treatment. Activator protein 1 (AP-1), as a gene regulator, initiates cytokine expression in response to environmental stimuli. In this study, we investigated the relationship between AP-1 and neuroinflammation-associated brain injury triggered by ICH. METHODS: Intracerebral hemorrhage mice were developed by autologous blood or collagenase infusion. We measured the dynamics of AP-1 in mouse brain tissues during neuroinflammation formation after ICH. The effects of the AP-1 inhibitor SR11302 on brain injury and neuroinflammation as well as the underlying mechanisms were investigated in vivo and in vitro. RESULTS: AP-1 was significantly upregulated in mouse brain tissue as early as 6 hours after ICH, accompanied by elevations in proinflammatory factors, including interleukin (IL)-6, IL-1ß, and tumor necrosis factor (TNF)-α. Inhibition of AP-1 using SR11302 reduced neurodeficits and brain edema at day 3 after ICH. SR11302 ablated microglial IL-6 and TNF-α production and brain-infiltrating leukocytes in ICH mice. In addition, SR11302 treatment diminished thrombin-induced production of IL-6 and TNF-α in cultured microglia. CONCLUSIONS: Inhibition of AP-1 curbs neuroinflammation and reduces brain injury following ICH.

Global brain inflammation in stroke.

Stroke, including acute ischaemic stroke and intracerebral haemorrhage, results in neuronal cell death and the release of factors such as damage-associated molecular patterns (DAMPs) that elicit localised inflammation in the injured brain region. Such focal brain inflammation aggravates secondary brain injury by exacerbating blood-brain barrier damage, microvascular failure, brain oedema, oxidative stress, and by directly inducing neuronal cell death. In addition to inflammation localised to the injured brain region, a growing body of evidence suggests that inflammatory responses after a stroke occur and persist throughout the entire brain. Global brain inflammation might continuously shape the evolving pathology after a stroke and affect the patients' long-term neurological outcome. Future efforts towards understanding the mechanisms governing the emergence of so-called global brain inflammation would facilitate modulation of this inflammation as a potential therapeutic strategy for stroke.

Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B: Study Protocol for a Multi-Center, Double-Blind Randomized-Controlled Trial.

BACKGROUND: The domestic prevalence of chronic hepatitis B (CHB) in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot(s)ide analogues (NUCs) anti-hepatitis B virus (HBV) therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine (CHM) is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule (, TGYP) or Tiaogan-Jianpi-Jiedu Granule (, TGJPJD) plus entecavir tablet (ETV) was superior over ETV monotherapy in enhancing HBeAg loss rate. METHODS: The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1:1 ratio via central randomization system: experimental group (EG) and control group (CG). Subjects in EG received CM formulae (TGYP or TGJPJD, 50 g per dose, twice daily) plus ETV tablet (or ETV placebo) 0.5 mg per day in the first 24 weeks (stage 1), and CHM granule plus ETV tablet (0.5 mg per day) from week 25 to 108 (stage 2). Subjects in CG received CHM Granule placebo plus ETV tablet (0.5 mg per day) for 108 weeks throughout the trial. The assessments of primary outcomes (HBV serum markers and HBV-DNA) were conducted by a third-party College of American Pathologists (CAP) qualified laboratory. Adverse effects were observed in the hospitals of recruitment. DISCUSSION: The study was designed to compare the curative effect of CM plus ETV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as "a valuable endpoint". We believe this trial could provide a reliable status for patients' "journey" towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry (No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23).