Pharmacologically inhibiting phosphoglycerate kinase 1 for glioma with NG52.

Inhibition of glycolysis process has been an attractive approach for cancer treatment due to the evidence that tumor cells are more dependent on glycolysis rather than oxidative phosphorylation pathway. Preliminary evidence shows that inhibition of phosphoglycerate kinase 1 (PGK1) kinase activity would reverse the Warburg effect and make tumor cells lose the metabolic advantage for fueling the proliferation through restoration of the pyruvate dehydrogenase (PDH) activity and subsequently promotion of pyruvic acid to enter the Krebs cycle in glioma. However, due to the lack of small molecule inhibitors of PGK1 kinase activity to treat glioma, whether PGK1 could be a therapeutic target of glioma has not been pharmacologically verified yet. In this study we developed a high-throughput screening and discovered that NG52, previously known as a yeast cell cycle-regulating kinase inhibitor, could inhibit the kinase activity of PGK1 (the IC50 = 2.5 ± 0.2 µM). We showed that NG52 dose-dependently inhibited the proliferation of glioma U87 and U251 cell lines with IC50 values of 7.8 ± 1.1 and 5.2 ± 0.2 µM, respectively, meanwhile it potently inhibited the proliferation of primary glioma cells. We further revealed that NG52 (12.5-50 µM) effectively inhibited the phosphorylation of PDHK1 at Thr338 site and the phosphorylation of PDH at Ser293 site in U87 and U251 cells, resulting in more pyruvic acid entering the Krebs cycle with increased production of ATP and ROS. Therefore, NG52 could reverse the Warburg effect by inhibiting PGK1 kinase activity, and switched cellular glucose metabolism from anaerobic mode to aerobic mode. In nude mice bearing patient-derived glioma xenograft, oral administration of NG52 (50, 100, 150 mg· kg-1·d-1, for 13 days) dose-dependently suppressed the growth of glioma xenograft. Together, our results demonstrate that targeting PGK1 kinase activity might be a potential strategy for glioma treatment.

Defective h-BN sheet embedded atomic metals as highly active and selective electrocatalysts for NH3 fabrication via NO reduction.

NO electrochemical reduction (NOER) is a promising route for the removal of pollutant NO and the production of ammonia. In this work, by means of first-principles computations, we designed a series of single atom catalysts consisting of atomic transition metals anchored onto defective hexagonal boron nitride (h-BN) with boron vacancies (TM@h-BN). Among all nine candidates, our results revealed that Cu@h-BN and Ni@h-BN showed excellent NOER performances with relatively low limiting potentials of 0.23 and 0.31 V, respectively, which are comparable to (or even better than) that of the benchmark Pt catalyst (0.25 V). Moreover, Cu@h-BN and Ni@h-BN can significantly inhibit the competitive hydrogen evolution reaction, suggesting that the promoted ammonia formation is a low-potential and highly selective process.

Theoretical Insights into the Electron Capture Behavior of H2SO4···N2O Complex: A DFT and Molecular Dynamics Study.

Both sulfuric acid (H2SO4) and nitrous oxide (N2O) play a central role in the atmospheric chemistry in regulating the global environment and climate changes. In this study, the interaction behavior between H2SO4 and N2O before and after electron capture has been explored using the density functional theory (DFT) method as well as molecular dynamics simulation. The intermolecular interactions have been characterized by atoms in molecules (AIM), natural bond orbital (NBO), and reduced density gradient (RDG) analyses, respectively. It was found that H2SO4 and N2O can form two transient molecular complexes via intermolecular H-bonds within a certain timescale. However, two molecular complexes can be transformed into OH radical, N2, and HSO4- species upon electron capture, providing an alternative formation source of OH radical in the atmosphere. Expectedly, the present findings not only can provide new insights into the transformation behavior of H2SO4 and N2O, but also can enable us to better understand the potential role of the free electron in driving the proceeding of the relevant reactions in the atmosphere.

Is patellar denervation necessary in total knee arthroplasty without patellar resurfacing?

PURPOSE: To conduct a meta-analysis with randomized controlled trials (RCTs) published in full text to determine the effectiveness of patellar denervation (PD) in primary total knee arthroplasty (TKA). METHODS: Literature search was performed in PubMed, Embase, Web of Science and Cochrane Library for information from the earliest date of data collection to February 2015. RCTs comparing the benefits and risks of PD with those of no patellar denervation (NPD) in primary TKAs were included. Statistical heterogeneity was quantitatively evaluated by X(2) test with the significance set P < 0.10 or I (2) > 50 %. RESULTS: Six RCTs consisting of 751 patients were included. The incidences of AKP in PD group and NPD group were 38.3 % (90/235) and 46.3 % (107/231), respectively. Meta-analysis showed significant prevention effect of PD on the incidence of AKP (OR 0.65; 95 % CI 0.42, 1.00; P = 0.05) without significant heterogeneity (I (2) = 44 %, P = 0.15). Our results also indicated that PD was significantly associated with better American Knee Society knee (WMD = 2.50; 95 % CI 0.34, 4.67; P = 0.02) and functional scores (WMD = 4.07; 95 % CI 1.34, 6.80; P = 0.0003) and range of motion (ROM) (WMD = 4.27; 95 % CI 1.95, 6.60; P = 0.0003) compared with NPD. However, there was no significant difference between the two groups no matter in Oxford knee score, patellar score or visual analogue scale at any other time. Complications and revisions did not differ significantly between the two groups. CONCLUSION: This meta-analysis showed that PD in TKAs without patellar resurfacing, compared with NPD, could prevent the incidence of post-operative AKP and improve clinical outcome in KSS and post-operative ROM. Based on the above results, PD was a safe procedure with no significant complications and revision or re-operations. LEVEL OF EVIDENCE: Therapeutic study, Level II.

[TG-fTIR study of the thermal-conversion properties of holo-cellulose derived from woody biomass].

Thermal-conversion properties of cellulose, hemi-cellulose and holo-cellulose derived from woody biomass were studied using TG-FTIR, and also compared to those of avicel cellulose and xylan. 3-D diffusion model was applied to calculate the kinetic parameters of thermal-conversion reaction of biomass materials, such as the activation energy, pre-exponential factors, etc, which showed good regression results. With the analysis of three-dimensional IR spectra of gas products, featured peaks of HzO, CO, CO2, CH4, and oxygenates were obviously observed where showing up with the maximum weight-loss rate in DTG curves. The possible forming routes of major gaseous products were analyzed and discussed. The order of releasing amounts for gaseous productions was approximately as CO2 > H2O > CO CH4. Based on the comprehensive understanding and comparative analysis of the whole results, it is concluded that the thermal conversion process of holo-cellulose was the result of interaction between cellulose and hemi-cellulose under the dominant role of cellulose.

[Analysis of pyrolysis process and gas evolution rule of larch wood by TG-FTIR].

The weight-loss character and gas evolution rule of larch wood at different heating rates were investigated by TG-FTIR (thermogravimetric analyzer coupled to a Fourier transform infrared spectrometer), and the results were compared with those of larch wood model-component mixture. The main weight-loss area of larch wood was wider than larch wood model-component mixture, and the residual char yield of larch wood (18.97%) was lower than larch wood model-component mixture (29.83%). During the pyrolysis process, the activation energy of larch wood model-component mixture was higher than the larch wood's in the low-temperature region, but there was little difference between the two segments in high temperature region. Larch wood came through several stages of water extraction, main component decomposition, charring during its pyrolysis process, and gas precipitation mainly happening at near 375 degrees C. The order of main gas products generated from the larch wood pyrolysis reaction was CO2 > H2O > CH4 > CO, and the gas product yield was significantly increased when the heating rate increased. The larch wood model-component mixture had the similar basic rules of producing gas to larch wood, but the former had relatively higher precipitation density than the latter.

Inhibition of the P53/P21 Pathway Attenuates the Effects of Senescent Nucleus Pulposus Cell-Derived Exosomes on the Senescence of Nucleus Pulposus Cells.

OBJECTIVE: The purpose of this paper is to investigate the effects of senescent nucleus pulposus cell (NPC)-derived exosomes (SNPC-Exo) and the roles of the P53/P21 pathway on the senescence of NPC. METHODS: The senescent phenotypes of NPC were induced by interleukin-1ß treatment. SNPC-Exo was extracted from the culture medium of senescent NPC and purified by differential centrifugation. The structure of SNPC-Exo was identified by transmission electron microscopy and western blot analysis was used to determine the exosomal marker proteins CD63 and Tsg101. Western blot analysis was performed to determine the relative expression levels of P16, P21, and P53 in NPC. Senescence-associated ß-galactosidase (SA-ß-gal) staining was used to stain the senescent NPC and a phase contrast microscope was used to observe and count the SA-ß-gal staining of NPC. The proliferation of SNPC-Exo-treated NPC was assessed using growth curve analysis and the colony formation assay. The cell cycle of SNPC-Exo-treated NPC was determined by flow cytometry. NPC were transfected with siRNA to knock down P53 and P21 expression. RESULTS: Interleukin-1ß-treated NPC had a higher percentage of SA-ß-gal positive cells (45%) than the control group (20%) and showed an increase in the relative expression of P16, P21, and P53 (P < 0.05). SNPC-Exo were positive for exosomal marker protein CD63 and Tsg 101 and negative for calnexin, and successfully internalized as previously described. SNPC-Exo-treated NPC showed an increase in the relative expression of P21 and P53 (P < 0.05). Compared with the control group, the SNPC-Exo-treated NPC showed a lower growth rate (3 times lower on the 5th day and 2 times lower on the 7th day), fewer colony-forming units (12.0%), and a higher percentage of SA-ß-gal-positive NPC (50.0%). The SNPC-Exo-treated NPC contained more G1 phase cells (68.0%) and fewer S phase (15.5%) cells than the control group (53.0% in G1 phase, 33.5% in S phase). The expression of P21 and P53 significantly decreased in SNPC-exo-treated NPC after siRNA transfection (P < 0.05), followed by a higher growth rate (2 times higher on the 5th day and 1.5 times higher on the 7th day) and lower percentage of SA-ß-gal-positive NPC (22.5%). Moreover, the inhibition of the P53/P21 pathway promoted the SNPC-Exo-treated NPC to enter the S phase (from 15.5% to 25.3%). CONCLUSION: The inhibition of the P53/P21 pathway attenuated the senescence of NPC induced by SNPC-Exo.

Two new diterpenoids with their antiproliferative activities from the supercritical fluid extraction of Croton crassifolius root.

Supercritical fluid extraction was applied to obtain the lower polarity extracts from Croton crassifolius roots, and chemical investigation of which led to the isolation and identification of two new diterpenoids, named crassifolius P (1) and crassifolius Q (2). In vitro anti-proliferative activities of compounds 1 and 2 on A549, Hep-G2 and Hela tumor cell lines were evaluated. The two new compounds exhibited obvious selectivity to tumor cells with IC50 values ranging from 20.43 ± 1.18 µM to 25.72 ± 1.32 µM.

[Interventional treatment of idiopathic long-segment occlusion of infrahepatic inferior vena cava complicated with thrombosis].

OBJECTIVE: To evaluate the efficacy of interventional treatment of idiopathic long-segment occlusion of infrahepatic inferior vena cava (IVC) complicated with thrombosis. METHODS: Fourteen patients with idiopathic long-segment occlusion of infrahepatic IVC complicated with thrombosis underwent endovascular recanalization. All procedures were performed under local anesthesia via internal jugular vein in combination with a unilateral femoral approach. First catheter-directed urokinase thrombolysis was performed. Then the occlusion of IVC was treated with balloon angioplasty and/or stent placement. RESULTS: Iliocavogram demonstrated an occlusion of IVC from intrahepatic segment to infrarenal segment in 3 patients and an occlusion of infrahepatic IVC above renal veins in 11 patients. Thrombosis was located in IVC (n = 14) and extended to iliofemoarl veins (n = 12). Technical success was achieved in 12 patients. IVCs were recanalized successfully. Complete or partial thrombus removal was accomplished in 8 and 4 cases, respectively. Recanalization failure occurred in 2 patients. No rethrombosis occurred over a mean follow-up of 12 +/- 6 months (range: 1 - 36). And an asymptomatic restenosis of IVC was diagnosed by duplex scanning. CONCLUSION: Interventional treatment of idiopathic long-segment occlusion of infrahepatic IVC complicated with thrombosis is a safe and effective method.

2-Hydroxydiplopterol, a new cytotoxic pentacyclic triterpenoid from the halotolerant fungus Aspergillus variecolor B-17.

A new hopane type pentacyclic triterpenoid, 2-hydroxydiplopterol (1) has been isolated from the metabolites produced by the halotolerant fungal strain Aspergillus variecolor B-17. The structure of 1 was determined by spectroscopic methods and single crystal X-Ray diffraction analysis. 2-Hydroxydiplopterol (1) exhibited cytotoxicity against K562 cells with an IC50 value of 22 microM.

Cytotoxic alkaloids and antibiotic nordammarane triterpenoids from the marine-derived fungus Aspergillus sydowi.

Three new diketopiperazine alkaloids, 6-methoxyspirotryprostatin B (1), 18-oxotryprostatin A (2), and 14-hydroxyterezine D (3), with an oxaspiro[4.4]lactam moiety, 14-norpseurotin A (4), and the 29-nordammarane triterpenoid 6beta,16beta-diacetoxy-25-hydroxy-3,7-dioxy-29-nordammara-1,17(20)-dien-21-oic acid (5), as well as 12 known compounds (6- 17), were isolated from the ethyl acetate extract of a marine-derived fungal strain, Aspergillus sydowi PFW1-13. The structures of compounds 1- 5 were elucidated by comprehensive spectroscopic analysis. Compounds 1- 3 exhibit weak cytotoxicity against A-549 cells, with IC 50 values of 8.29, 1.28, and 7.31 microM, respectively. Compound 1 also shows slight cytotoxicity against HL-60 cells, with an IC 50 value of 9.71 microM. Compounds 4 and 5 display significant antimicrobial activities against Escherichia coli, Bacillus subtilis, and Micrococcus lysoleikticus with MICs of 3.74, 14.97, and 7.49 microM and 10.65, 5.33, and 10.65 microM, respectively.

[Study on spectroscopic properties of CuO nanoparticles].

The precursor Cu2 (NO3)(OH)3 was synthesized by homogeneous precipitation processing in ethanol-water(phi, 1 : 1) mixed solvent system using (CH2)6N4 as host-precipitates. CuO nanoparticles were prepared by heating Cu2 (NO3)(OH)3 at different temperatures. XRD, FTIR, XPS, FT-Raman and UV-Vis absorption spectra techniques were applied to investigated spectrum properties of CuO nanoparticles. All of the obtained samples were indicated to be monoclinic CuO under XRD measurement. Consistent with the XRD results, the XPS method also revealed that the atomic ratio of Cu to O in our samples was 1 : 1. With the increase in the calcinations temperature, the crystal of CuO grew up, the FTIR patterns revealed that the absorption of Cu-O and -OH bond in CuO nanoparticles blue-shifted and red-shifted at the same time, XPS spectrum indicated that the content of surface oxygen decreased, and the FT-Raman spectrum showed that the Raman scattering peak broadened with the decrease in the nano-CuO diameter; UV-Vis adsorption spectroscopy revealed that CuO has a wide adsorption peak at -350 nm, and the absorption edge blue-shifted with the size decreasing.

Epigenetic and genetic alterations of PTEN in hepatocellular carcinoma.

AIM: To investigate the roles of epigenetic and genetic alterations of the phosphatase and tensin homologue on chromosome 10 gene (PTEN) in carcinogenesis and the development of hepatocellular carcinomas (HCC). METHODS: A total of 56 cases of HCC tissues and six liver cell lines were studied for the expression of PTEN by immunohistochemistry and Western blot analysis. The PTEN gene mutations in exon5 and exon8 were detected by a combination of single-strand conformation polymorphism (SSCP) analysis and DNA sequencing. Methylation-specific PCR (MSP) was used to identify PTEN promoter methylation. RESULTS: Of the 56 cases of HCC, 24 (42.9%) expressed the PTEN protein. All surrounding liver tissues of the hepatoma (32 cases) were positive for PTEN. Of the six cell lines, three liver cancer cell lines showed a low expression of PTEN. Five mutations of 56 HCC samples were detected. All of them were located at intron4. No mutation was found in exon5 and exon8. After MSP analysis, we found nine cases of PTEN promoter methylation in 56 specimens (16.1%). However, no CpG island of PTEN was found to be methylated in all six liver cell lines. CONCLUSION: The level of PTEN protein was altered in part of the HCC. The downregulation of PTEN expression may not be mainly associated with the PTEN mutations, but partly due to PTEN promoter methylation and other epigenetic regulation.

Three novel, structurally unique spirocyclic alkaloids from the halotolerant B-17 fungal strain of Aspergillus variecolor.

During our search for novel antitumor lead compounds from microorganisms living under extreme conditions, three novel alkaloids, variecolortides A-C (1-3), were isolated from the mycelia of the halotolerant fungal strain Aspergillus variecolor B-17. The new compounds were found to share an unprecedented 'spiro-anthronopyranoid diketopiperazine' structure, with a stable hemiaminal function, as corroborated by in-depth NMR-spectroscopic and mass-spectrometric analyses, as well as by a single-crystal X-ray analysis of 1. All compounds were shown to exhibit weak cytotoxic and antioxidant activities.

Isocoumarin Derivatives from the Sea Squirt-derived Fungus Penicillium stoloniferum QY2-10 and the Halotolerant Fungus Penicillium notatum B-52.

Two isocoumarin derivatives, stoloniferol A (1) and B (2), a known 5alpha, 8alpha-epidioxy-23-methyl-(22E, 24R)-ergosta-6, 22-dien-3beta-ol (3), and a known dihydrocitrinone (4) were isolated from the ethyl acetate extract of the sea squirt-derived fungus, Penicillium stoloniferum QY2-10, and a halophilic fungus, Penicillium notatum B-52, respectively. Their structures were elucidated by spectroscopic methods and optical rotation. The stereochemistry of 2 was determined on the basis of different NOE experiments and chemical transformation. Compound 3 showed cytotoxicity against P388 cells, with an IC50 value of 4.07 microM.

Research into care quality criteria for long-term care institutions.

The purpose of this paper was to determine the criteria that reflect the quality of care provided by long-term care institutions. Research was conducted using a two-step procedure that first utilized the SERVQUAL model with Fuzzy Delphi Method to establish the proper criteria by which service quality could be measured. A total of 200 questionnaires were mailed to expert respondents, of which 89 were returned and 77 deemed valid for use in this study. We then applied the Multi-Criteria Decision Making Process to determine the degree of importance of each criterion to long-term care institution service quality planning work. Secondly, 200 questionnaires were distributed and 74 valid responses were returned. Based on the 5 SERVQUAL model constructs, this study found 17 of the 28 criteria, to be pertinent to nursing care quality, with those in the Responsiveness and Empathy domains being the ones most critical.

1,6-Dihydr-oxy-3-hydroxy-methyl-8-methoxy-anthracene-9,10-dione monohydrate.

The title compound, C(16)H(12)O(6)·H(2)O, isolated from the halotolerant fungus Aspergillus variecolor B-17, is also known as questinol monohydrate. In the crystal structure, O-H⋯O hydrogen bonds link the mol-ecules, forming a three-dimensional network. π-π stacking inter-actions consolidate the supra-molecular structure [the shortest inter-planar distances are 3.456 (3), 3.366 (4) and 3.382 (4) Å].

[Evaluation on schistosomiasis control effect of the intervention measures adapted to the ecological environment changes in Jiang Han Plain due to establishment of the Three Gorges dam].

OBJECTIVE: To evaluate the effect of the intervention measures for schistosomiasis control adapted to the ecological environment changes in Jiang Han plain caused by the establishment of the Three Gorges Dam. METHODS: Four villages in Qianjiang City were selected to implement paddy-upland rotation, crawfish-paddy alternation, water control and soil improvement, and adjusting agricultural structure to rebuild the waterlogging low yielding land and to change the snail habitat environment respectively. The snail habitat area, mean density of living snails and prevalence of schistosomiasis in human and cattle were compared with those of the control villages. Miracidia hatching methods were used to examine the prevalence in human and cattle. RESULTS: In the four experimental villages, the snail-ridden area decreased by 100%, 51.35%, 62.16% and 87.88% respectively; mean density of living snails decreased by 100%, 69.41%, 52.30% and 75.77%, with a t value of 9.37, 4.91, 2.31 and 9.16, I'<0.01. Human prevalence of schistosomiasis in 2005 in village with crawfish-paddy alteration decreased significantly than control (chi2=39.84, I'<0.01); decreased by 73.10% in village with water control and soil improvement in 1990 than in 1987 (chi2=236.10, P<0.01). CONCLUSION: Implementation of the four intervention measures reaches a remarkable benefit in reforming snail habitat and protecting environment, which can be recommended to the inner embankment type endemic regions.

Adding nickel formate in alkali lignin to increase contents of alkylphenols and aromatics during fast pyrolysis.

The composition of pyrolysis vapors obtained from alkali lignin pyrolysis with the additive of nickel formate was examined using the pyrolysis gas chromatography-mass spectrometry (Py-GC/MS). Characterization of bio-chars was performed using X-ray diffraction (XRD). Results showed that the nickel formate significantly increased liquid yield, simplified the types of alkali lignin pyrolysis products and increased individual component contents. The additive of nickel formate increased contents of alkylphenols and aromatics from alkali lignin pyrolysis. With an increase in temperature, a greater amount of the relative contents can be achieved. The nickel formate was thermally decomposed to form hydrogen, resulting in hydrodeoxygenation of alkali lignin during pyrolysis. It was also found that Ni is in favor of producing alkylphenols. The analysis based on the experimental result provided evidences used to propose reaction mechanism for pyrolysis of nickel formate-assisted alkali lignin.

[Mutations of tumor suppressor gene PTEN mutations in hepatocellular carcinoma and its implications in tumor proliferation and apoptosis].

OBJECTIVE: To study mutations of tumor suppressor gene PTEN in human hepatocellular carcinomas and its effects on the proliferation and apoptosis of hepatocellular carcinoma cell line HHCC. METHODS: (1) PCR-SSCP and sequence analysis were used to detect the mutations of the 5th and 8th exon of PTEN in 42 cases of human primary hepatocellular carcinoma. (2) Eukaryotic expression vectors of the wild-type (pEGFP-wt-PTEN) and the mutant type (pEGFP-PTEN, G129R) of PTEN were constructed. Lipofectamine 2000 mediated gene transfection was used to transfect hepatocellular carcinoma cell line HHCC, in which the PTEN protein is not expressed. Culture medium containing G418 was used to select stable transfectants. MTT colorimetry was used to analyze the proliferation ability of selected cell lines. Naive HHCC cells and HHCC cells transfected with empty vector (pEGFP-C1) served as controls. (3) TNF-alpha was used to induce apoptosis of selected cell clones. RESULTS: (1) Point mutation involving the 5th exon of PTEN was detected in 4 of 42 primary hepatocellular carcinomas. (2) Compared with the control groups, the proliferation of hepatocellular carcinoma cells was significantly inhibited by the transfection of wild-type PTEN gene, while the transfection with mutant PTEN construct did not significantly change the proliferation. (3) The apoptosis indices of cells transfected with the wild-type and the mutant PTEN genes were 13.8% and 8.1% respectively. Compared with the control, the apoptosis index of HHCC cell transfected by the wild type PTEN was significantly lower (P < 0.05). There were no significant differences between HHCC cells transfected with mutated PTEN gene and the control (P > 0.05). The expression of internal 473-phosphorylated Akt of HHCC was weak, but was enhanced when the cells treated with TNF-alpha. However, it was down regulated by the wild type PTEN. CONCLUSIONS: (1) First time report that PTEN mutations can be found in 9.5% human primary hepatocellular carcinomas. (2) The expression of the wild-type PTEN can suppress the proliferation of HHCC cells, and such suppression was lost when PTEN gene was mutated. (3) PTEN inhibition of the proliferation and the enhancement of apoptosis of hepatocellular carcinoma cells is likely related to a down-regulation of the TNF-alpha induced activation of protein kinase Akt pathway.