Decreased expression of GBA3 correlates with a poor prognosis in hepatocellular carcinoma patients.

Beta-glucosidase (GBA), also known as acid ß-glucosidase, exhibits an activity of glucosylceramidase (EC 3.2.1.45). Three main isoforms of ß-glucosidases have been identified in mammals: GBA1, GBA2, and GBA3. The deficiency of these enzymes leads to glucosylceramide accumulation, resulting in Gaucher's disease. The present study is focused on the cytosolic ß-glucosidase, GBA3, and its relationship with hepatocellular carcinoma (HCC). The expression of GBA3 mRNA in HCC was evaluated first using the TCGA database, and then by immunohistochemistry using tissue microarrays of 328 clinically characterized HCC samples and 151 non-tumor liver controls. Moreover, the presence of a correlation between GBA3 expression and clinicopathological characteristics of patients was examined. The obtained results indicated that the expression of GBA3 mRNA was significantly lower in HCC than in the adjacent non-tumor liver tissues. The expression of GBA3 was inversely related to the number of tumors (p=0.041), tumor size (p<0.001), Edmondson grade (p=0.007), microvascular invasion (p=0.049), patient status (p<0.001), and α-fetoprotein level (p<0.001). Patients exhibiting low GBA3 expression had a shorter survival time than those with high expression (p<0.001). In conclusion, the decreased GBA3 expression is strongly associated with a poor prognosis in HCC patients, and GBA3 may be a potential therapeutic target for HCC.

Liver Tissue-related Metabolic Mechanism of Different Infusion Volumes for Hemorrhagic Shock.

OBJECTIVES: To investigate the curative effects of various infusion volumes on liver-related metabolic mechanism in the treatment of hemorrhagic shock. METHODS: A severe hemorrhagic shock rabbit model was established in 30 rabbits. The rabbits were randomly divided into three groups： non-infusion group （A）, conventional infusion group （B）, and excessive infusion group （C） （n=10 in each group）. Taking group B as the control, groups A and C were observed for the damage of non-infusion and excessive infusion, respectively. The outcomes in the three groups and their relations with liver tissue metabolism changes were analyzed with gas chromatograph-mass spectrometer （GC-MS）. RESULTS: The mortality in groups A, B, and C group were 80%, 0%, and 70%, respectively. The liver tissue metabolic profile in group B showed statistically significant difference compared with that in groups A and B. In group C, the levels of 21 metabolites were lower than those in group B, and the levels of 8 metabolites were lower than those in group A. The relative contents of various metabolites were correlated with infusion volumes, and the succinic acid content was associated with death events （P<0.05）. CONCLUSIONS: The conventional infusion has significant curative effect on hemorrhagic shock. The metabolites of liver tissues with excessive infusion are generally decompensated and have longer survival time than those in non-infusion group, which may caused by the excessive infusion-induced blood volume increase after hemorrhagic shock. Tissue fluid dilution is an important cause of death.

Pedigrees of infertile Chinese men with Y chromosome microdeletions derived from natural transmission and de novo mutation.

Y chromosome microdeletions can cause male infertility and are classified as natural transmission and de novo mutations. To examine the source of these deletions in Chinese men and to provide a theoretical and laboratory basis for genetic counseling, patients from Northeast China with primary male infertility (N = 22) and their fathers were investigated. Karyotype analysis was performed on peripheral blood lymphocytes using standard G-banding. Multiplex polymerase chain reaction amplification using 18 specific sequence-tagged sites was selected to detect Y chromosome microdeletions. De novo mutations were observed in 17 father-son pairs, leading to a mutation rate of 77.27% (17/22), while the vertical transmission of Yq AZFc microdeletions was detected in 5 cases of the families investigated (29.41%, 5/17). There were no statistically significant differences between vertically transmitted and de novo mutations in men with AZFc deletions regarding age, testicular volume, and reproductive hormone levels. Most Y chromosome microdeletions in men from Northeast China are the result of de novo mutations via natural conception, and men with Yq AZFc deletions showed no clear differences between vertical transmission and de novo mutations.

Taxonomy and epidemiology of Mucor irregularis, agent of chronic cutaneous mucormycosis.

Mucormycosis usually presents as a progressive infection with significant angio-invasion. Mucormycosis due to Mucor irregularis (formerly Rhizomucor variabilis var. variabilis), however, is exceptional in causing chronic cutaneous infection in immunocompetent humans, ultimately leading to severe morbidity if left untreated. More than 90 % of the cases known to date were reported from Asia, mainly from China. The nearest neighbour of M. irregularis is the saprobic species M. hiemalis. The aim of this study was to evaluate the taxonomic position, epidemiology, and intra- and inter-species diversity of M. irregularis based on 21 strains (clinical n = 17) by multilocus analysis using ITS, LSU, RPB1 and RPB2 genes, compared to results of cluster analysis with amplified fragment length polymorphism (AFLP) data. By combining MLST and AFLP analyses, M. irregularis was found to be monophyletic with high bootstrap support, and consisted of five subgroups, which were not concordant in all partitions. It was thus confirmed that M. irregularis is a single species at 96.1-100 % ITS similarity and low recombination rates between populations. Some geographic structuring was noted with some localised populations, which may be explained by limited air-dispersal. The natural habitat of the species is likely to be in soil and decomposing plant material.

Simulations of neutral beam injection and ion cyclotron resonance heating synergy in high power EAST scenarios.

The EAST plasmas heated with deuterium neutral beam injection and ion cyclotron resonance heating (ICRH) have been simulated by the TRANSP code. The analysis has been conducted using the full wave solver TORIC5, the radio frequency (RF)-kick operator, and NUBEAM to model the RF heating effects on fast ion velocity distribution. In this work, we present several simulated results compared with experiments for high power EAST scenarios, indicating that the interactions between ICRH and fast ions can significantly accelerate fast ions, which are confirmed by the increased neutron yield and broadened neutron emission spectrum measurements.

Post-pleistocene demographic history of the North Atlantic endemic Irish moss Chondrus crispus: glacial survival, spatial expansion and gene flow.

Range expansions and gene flow as micro-evolutionary processes played a leading role in the population demographic history of marine organisms. Herein, we sequenced partial mtDNA Cox1 gene from 26 assigned geographical populations to understand how Irish moss (Chondrus crispus) responded to severe climatic oscillations during the Pleistocene glaciations and contemporary forces such as gene flow. Phylogeographic patterns indicated that haplotype frequency distributions were strongly skewed, with nearly half found only in single samples and thus restricted to a single population. Analysis of molecular variance revealed that most of the variation was within populations with no significant genetic structuring on either side of the Atlantic. Demographic analyses indicated that ISI (Irish Sea and Ireland) and NS (the North Sea) areas experienced a slight trend of increase in population size over time, whereas EC (the English Channel) area experienced expansion beginning approximately 170,000-360,000 BP. The observed complex genetic pattern of C. crispus is consistent with a scenario of multiple unrelated founding events by survival of this species in at least three putative Pleistocene refugia along the European coastline, and subsequent trans-Atlantic dispersal combined with contiguous northward population expansion predating the LGM and geographically gene flow.

[Research progress of liposome drug delivery system in stomatology].

Liposomes are spherical vesicles with bilayer membrane structure spontaneously formed by phospholipids dispersed in an aqueous medium. Liposomes are excellent drug carrier with amphiphilic properties. Liposomes have good biocompatibility, biodegradability and no immunogenicity. Liposomes can achieve the delivery of the drug, enhance the solubility, improve the stability, reduce the toxic effect of the drug, and improve the therapeutic effect of the loaded drug. In recent years, liposome drug delivery systems have been widely used in dentistry. This article reviews the application of liposome drug delivery systems in caries, dental pulp diseases, periodontitis, implantation, oral anesthesia and oral candidiasis.

A compact stilbene crystal neutron spectrometer for NBI-heated plasma neutron diagnostics at EAST.

Stilbene crystal detectors are widely used as fast neutron measurement tools based on recoil proton detection, such as liquid scintillators. A compact stilbene crystal neutron spectrometer (CSCNS) has been installed at the Experimental Advanced Superconducting Tokamak (EAST) to obtain information on fuel ions produced in the plasma core because of its merits of good n/γ discrimination capability, high detection efficiency, and fast response. For the first time, CSCNS has been used for neutron emission spectroscopy measurements in EAST plasmas with neutral beam injection (NBI) heating. The CSCNS has the same horizontal line of sight as the time-of-flight enhanced diagnostics neutron spectrometer. Under NBI heating scenarios, the time trace of the neutron yield monitored by the CSCNS is similar to the one monitored by a standard 235U fission chamber. The experimental pulse height spectra are also similar to the simulated ones generated by folding the simulated neutron energy spectrum with the detector response functions. These results demonstrate the capability of the CSCNS for neutron diagnostics and the study of fast-ion physics in EAST.

Neutron emission and fast ion simulation for high performance long pulses at EAST.

Neutron emission spectroscopy and neutron yield measurements are important for high neutral beam injection (NBI) power heating at the Experimental Advanced Superconducting Tokamak (EAST). The neutron yields mainly depend on the deposition from NBI to the deuterium plasmas in the EAST. We have recently used TRANSP with time dependent diagnostic results to simulate the transport process of 30 s long pulse deuterium plasma discharges in the EAST, obtaining the time dependent fast ion distribution, neutron emission spectrum, and total neutron emission rate. Combined with the time trace of the result measured by a standard 235U fission chamber, the effects of different configurations of NBI heating in EAST fusion plasmas have been evaluated.

Mutation L437P in the 2B domain of keratin 1 causes diffuse palmoplantar keratoderma in a Chinese pedigree.

Diffuse palmoplantar keratoderma (DPPK) is an autosomal dominant genodermatosis characterized by uniform hyperkeratosis of the palm and sole epidermis. This disorder can be caused by mutations in the genes keratin 1, keratin 9, keratin 16, desmoglein 1 and plakoglobin. Here we present a DPPK Chinese pedigree and identify the aetiology as a novel missense mutation, L437P, located in a highly conserved helix motif in domain 2B of KRT1. Functional analysis shows that overexpression of the L437P mutant in cultured cells leads to abnormal intermediate filament networks and filament aggregation. This gain-of-function mutation highlights the role of domain 2B in mediating filament assembly.

Development of gamma ray spectrometer with high energy and time resolutions on EAST tokamak.

A new gamma ray spectrometer with high energy and time resolutions has been developed and installed on the EAST tokamak to study fast ion and runaway electron behaviors. The spectrometer is based on a LaBr3(Ce) scintillator detector and a fully digital data acquisition system that is based on a digitizer with digital pulse processing algorithms. The energy resolution of the spectrometer is about 3.9% at 662 keV, and the spectrometer can operate stably at a counting rate as high as 1 MHz, monitored by using a light emitting diode monitoring system. The measured gamma ray spectrum is simulated based on Geant4 and unfolded with the high-resolution boosted Gold deconvolution algorithm, aiming at reconstructing the energy distribution functions of fast ions and runaway electrons.

Cisplatin induces apoptosis of hepatocellular carcinoma LM3 cells via down-regulation of XIAP.

OBJECTIVE: Cisplatin is an important anti-cancer drug. However, the molecular mechanism of cisplatin on inhibition of the proliferation of liver cancer cells is unclear. Thus, we aimed to investigate the regulatory role of cisplatin on the growth and apoptosis of hepatoma LM3 cells. MATERIALS AND METHODS: LM3 cells were treated with cisplatin (2 µmol/L) for 48 h. MTT assay, flow cytometry, and caspase-3 activity assay were used to detect the growth, proliferation and apoptosis of LM3 cells. Western blot was applied to detect the expression of the inhibitor of apoptosis protein, XIAP. siRNA was used to knockdown the level of XIAP followed by cisplatin (2 µmol/L) treatment, and then the apoptosis of LM3 cells was measured. RESULTS: The treatment of cisplatin significantly inhibited the growth but induced the apoptosis of LM3 cells. Cisplatin also downregulated the expression of XIAP. The downregulation of XIAP by using siRNA enhanced the apoptosis of LM3 cells induced by cisplatin. CONCLUSIONS: Downregulation of XIAP enhanced the proapoptotic effect of cisplatin on LM3 cells, suggesting that XIAP might be used as a potential target in the treatment of liver cancer.

Velocity-space sensitivity of the compact neutron emission spectrometers at EAST.

Several compact neutron spectrometers are now installed at EAST (Experimental Advanced Superconducting Tokamak) to obtain information on fuel ions produced in the core of the plasma. In this paper, a stilbene crystal neutron spectrometer and an EJ301 liquid scintillator neutron spectrometer with n-γ discrimination capability will be discussed. Both spectrometers have a horizontal line of sight, while at different positions. In the last few experiment campaigns at EAST, they all proved to be reliable diagnostics for auxiliary heated D-D plasmas. Taking the response function simulated by dedicated Geant4 models into consideration, the velocity-space sensitivities given by the instrument-specific weight function of the beam-thermal part of neutron energy spectra in D-D plasmas are derived for both spectrometers with the Genesis code. This method makes it possible to directly relate the contribution of different deuteron velocity space regions to events in each channel of the neutron spectrum measured by the two instruments: http://rsi-htpd.peerx-press.org/.

Velocity-space sensitivity of time-of-flight neutron spectrometer at EAST in deuterium plasma.

The Time-Of-Flight Enhanced Diagnostics (TOFED) neutron spectrometer with a double-ring structure has been installed at the Experimental Advanced Superconducting Tokamak (EAST) to perform advanced neutron emission spectroscopy diagnosis for deuterium plasma. In order to reduce the random coincidence from the background neutrons and gamma-rays, TOFED was moved outside the experimental hall and placed in the newly-built nuclear diagnostics laboratory in 2017. In this paper, the instrument-specific weight functions of TOFED are derived by taking the instrument response matrix and the radial line of sight in this new layout into consideration. The results show that the instrument is predominantly sensitive to counter-passing particles in the region where time-of-flights < 69.4 ns, while events at higher time-of-flights (corresponding lower neutron energies) are mostly representative of co-passing ions. The instrument-specific weight functions express the relationship between data in a given channel of the spectrum and the velocity space region that contributes to that. The results can be applied for energetic particle physics studies at EAST, in particular to compare data from different diagnostic techniques.

Schisandrin B attenuates the inflammatory response, oxidative stress and apoptosis induced by traumatic spinal cord injury via inhibition of p53 signaling in adult rats.

Schisandrin B is an active monomer of the Chinese magnolia vine (Schisandra chinensis) that can reduce transaminase activity in liver cells, inhibit lipid peroxidation, enhance antioxidant status, has protective effects in the liver and has antitumor effects. The present study investigated the potential protective effects of schisandrin B on the p53 signaling pathway in attenuating the inflammatory response, oxidative stress and apoptosis induced by traumatic spinal cord injury (TSCI) in adult rats. Behavioral examination, inclined plate test and spinal cord water content were used to evaluate the protective effect of schisandrin B in TSCI rats. The expression levels of superoxide dismutase (SOD), malondialdehyde (MDA), nuclear factor (NF)­κB subunit p65 and tumor necrosis factor (TNF)­α were examined using ELISA kits. Western blot analysis was performed to analyze the protein expression of caspase­3 and phosphorylated (p)­p53 in TSCI rats. In the present study, schisandrin B improved behavioral examination results and the maximum angle of inclined plate test, and inhibited spinal cord water content in rats with TSCI. Notably, schisandrin B reduced the activation of traumatic injury­associated pathways, including SOD, MDA, NF­κB p65 and TNF­α, in TSCI rats. In addition, schisandrin B suppressed the TSCI­induced expression of caspase­3 and p­p53 in TSCI rats. These results indicated that schisandrin B may attenuate the inflammatory response, oxidative stress and apoptosis in TSCI rats by inhibiting the p53 signaling pathway in adult rats.

Neutron emission spectroscopy of DT plasmas at enhanced energy resolution with diamond detectors.

This work presents measurements done at the Peking University Van de Graaff neutron source of the response of single crystal synthetic diamond (SD) detectors to quasi-monoenergetic neutrons of 14-20 MeV. The results show an energy resolution of 1% for incoming 20 MeV neutrons, which, together with 1% detection efficiency, opens up to new prospects for fast ion physics studies in high performance nuclear fusion devices such as SD neutron spectrometry of deuterium-tritium plasmas heated by neutral beam injection.

Response function of single crystal synthetic diamond detectors to 1-4 MeV neutrons for spectroscopy of D plasmas.

A Single-crystal Diamond (SD) detector prototype was installed at Joint European Torus (JET) in 2013 and the achieved results have shown its spectroscopic capability of measuring 2.5 MeV neutrons from deuterium plasmas. This paper presents measurements of the SD response function to monoenergetic neutrons, which is a key point for the development of a neutron spectrometer based on SDs and compares them with Monte Carlo simulations. The analysis procedure allows for a good reconstruction of the experimental results. The good pulse height energy resolution (equivalent FWHM of 80 keV at 2.5 MeV), gain stability, insensitivity to magnetic field, and compact size make SDs attractive as compact neutron spectrometers of high flux deuterium plasmas, such as for instance those needed for the ITER neutron camera.

Measurement and simulation of the response function of time of flight enhanced diagnostics neutron spectrometer for beam ion studies at EAST tokamak.

The 2.5 MeV TOFED (Time-Of-Flight Enhanced Diagnostics) neutron spectrometer with a double-ring structure has been installed at Experimental Advanced Superconducting Tokamak (EAST) to perform advanced neutron emission spectroscopy diagnosis of deuterium plasmas. This work describes the response function of the TOFED spectrometer, which is evaluated for the fully assembled instrument in its final layout. Results from Monte Carlo simulations and dedicated experiments with pulsed light sources are presented and used to determine properties of light transport from the scintillator. A GEANT4 model of the TOFED spectrometer was developed to calculate the instrument response matrix. The simulated TOFED response function was successfully benchmarked against measurements of the time-of-flight spectra for quasi-monoenergetic neutrons in the energy range of 1-4 MeV. The results are discussed in relation to the capability of TOFED to perform beam ion studies on EAST.

[Determination of amikacin by single oscillopolarography in the presence of formaldehyde].

The singlescan oscillopolarographic behavior of formaldehyde derivative of amikacin (AMK) in the medium of Britton-Robinson buffer solution (pH 8.0) has been studied and the mechanism of its electrode process has been discussed. Under optimum conditions, the peak current increases linearly with the increase of AMK concentration in the range of 6.0 x 10(-7)-5.0 x 10(-5) mol.L-1 and its correlation coefficient is 0.9988. The detection limit is 2.4 x 10(-7) mol.L-1. This method has been applied to the determination of trace AMK in samples of its injection, urine and blood serum without pretreatment. Its recovery was 90%-100% and the relative standard deviation was less than 4.1%.

Design of a magnetic shielding system for the time of flight enhanced diagnostics neutron spectrometer at Experimental Advanced Superconducting Tokamak.

The novel neutron spectrometer TOFED (Time of Flight Enhanced Diagnostics), comprising 90 individual photomultiplier tubes coupled with 85 plastic scintillation detectors through light guides, has been constructed and installed at Experimental Advanced Superconducting Tokamak. A dedicated magnetic shielding system has been constructed for TOFED, and is designed to guarantee the normal operation of photomultiplier tubes in the stray magnetic field leaking from the tokamak device. Experimental measurements and numerical simulations carried out employing the finite element method are combined to optimize the design of the magnetic shielding system. The system allows detectors to work properly in an external magnetic field of 200 G.