Terahertz vortex beam generator carrying orbital angular momentum in both transmission and reflection spaces.

Vortex beam generators carrying orbital angular momentum (OAM) with both transmission and reflection modes has broad application prospects in full-space high data capacity communication and orbital angular momentum multiplexing systems. In this work, we proposed a vanadium dioxide (VO2) assisted metasurface to independently produce and manipulate focused vortex transmission-reflection modes with different number of beams and focal lengths under right-handed circular polarized (RCP) wave incidence. The proposed metasurface generates the diagonal vortex beams, four vortex beams, and focused vortex beam for transmission mode at 1.26THz and reflection mode at 1.06THz by changing phase state of the VO2. Our work may find many potential applications in future high data capacity information multiplexing communication systems.

Transmission and reflection bi-direction terahertz encoding metasurface with a single structure.

Most reported metasurfaces operate in single propagation direction mode (either transmissive mode or reflective mode), which hamper practical application. Here, we proposed a bi-directional operation coding metasurface based on a phase change material of a vanadium dioxide (VO2) assisted metasurface. It can realize a dynamically invertible switch between the transmissive mode or reflective mode in the terahertz regime by changing the external ambient temperature. The proposed structure consists of a silicon column, polyimide dielectric substrate layer, and VO2 film bottom layer. When VO2 is in dielectric state, the designed metasurface possesses the functions of transmission beam splitting and deflection and generates a transmission vortex beam. When VO2 is in metallic state, the proposed metasurface exhibits many functions such as reflection beam splitting, deflection, radar scattering surface (RCS) reduction and reflection vortex beam generation. The proposed metasurface can solve transmissive and reflective bi-direction terahertz encoding regulation. This scheme provides a new method to realize multi-function terahertz devices.

[Research Progress of Non-coding RNA and Endometrial Receptivity].

Endometrial receptivity has become the main cause of in vitro fertilization and pregnancy outcomes in infertile patients,bringing large psychological damage and economic loss to the patients and their family. In recent years,the role of non-coding RNA has increasingly been recognized. The relationship between non-coding RNA and endometrial receptivity is reviewed in this article.

Anterior cervical discectomy versus corpectomy for multilevel cervical spondylotic myelopathy: a meta-analysis.

PURPOSE: This is a meta-analysis to compare the results between anterior cervical discectomy fusion (ACDF) and anterior cervical corpectomy fusion (ACCF) for the patients with multilevel cervical spondylotic myelopathy (MCSM). METHODS: Systematic review and meta-analysis of cohort studies between ACDF with plate fixation and ACCF with plate fixation for the treatment of MCSM. An extensive search of literature was performed in PubMed, Mediline, Embase and the Cochrane library. The following outcome measures were extracted: JOA scores, fusion rate, cervical lordosis (C2-7), complications, blood loss and operation time. Data analysis was conducted with RevMan 5.0. RESULTS: Four cohorts (six studies) involving 258 patients were included in this study. The pooled analysis showed that there was no significant difference in the postoperative JOA score [WMD = -0.14 (-1.37, 1.10), P = 0.83], fusion rate [OR = 0.84 (0.15, 4.86), P = 0.85] between two group. However, there was significant difference in the cervical lordosis [WMD = 3.38 (2.52, 4.23), P < 0.00001], surgical complication rate and instrument related complication rate (P = 0.01, 0.005 respectively), blood loss [WMD = -52.53 (-73.53, -31.52), P < 0.00001], and operation time [WMD = -14.10 (-20.27, -7.93), P < 0.00001]. CONCLUSIONS: As compared with ACCF with plate fixation, ACDF with plate fixation showed no significant differences in terms of postoperative JOA score, fusion rate, but better improved cervical lordosis, lower complication and smaller surgical trauma. As the limitations of small sample and short follow-up in this study, it still could not be identified whether ACDF with plate fixation is more effective and safer than ACCF with plate fixation.

Comparison of unilateral versus bilateral pedicle screw fixation with cage fusion in degenerative lumbar diseases: a meta-analysis.

PURPOSE: To compare the results between unilateral and bilateral pedicle screw (PS) fixation for the patients with degenerative lumbar diseases. METHODS: A systematic review and meta-analysis of cohort studies were conducted between unilateral PS fixation with cage fusion (unilateral group) and bilateral PS fixation with cage fusion (bilateral group) for the treatment of degenerative lumbar diseases from 1990 to June 2014. An extensive search of studies was performed in PubMed, Mediline, Embase and the Cochrane library. The following outcome measures were extracted: visual analogue scale (VAS), Oswestry disability index (ODI), Short-Form health survey (SF-36), fusion rate, complications, blood loss and operation time. Data analysis was conducted with RevMan 5.0. RESULTS: Eight RCTs involving 545 patients were included in this meta-analysis. The pooled analysis showed that there was no statistically significant difference in terms of the VAS, ODI and SF-36 scores, fusion rate [OR = 0.49 (0.23, 1.04), P = 0.06], complication rate(implant-related complication: P = 0.35, general complication rate: P = 0.71) and blood loss between two groups. However, there was less operation time in the unilateral group compared with bilateral group. Four patients (1.48 %) in unilateral group and one patient (0.36 %) in bilateral group were found cage migration, the difference did not achieve statistical significance (P = 0.213). CONCLUSIONS: As compared to bilateral PS fixation with cage fusion, unilateral PS fixation with cage fusion achieves a similar VAS, ODI and SF-36 scores, fusion rate, complications and smaller surgical trauma. However, it is still uncertain whether unilateral pedicle screw fixation with cage fusion is as effective and safe as bilateral pedicle screw fixation with cage fusion.

Mangiferin activates Nrf2-antioxidant response element signaling without reducing the sensitivity to etoposide of human myeloid leukemia cells in vitro.

AIM: Mangiferin is glucosylxanthone extracted from plants of the Anacardiaceae and Gentianaceae families. The aim of this study was to investigate the effects of mangiferin on Nrf2-antioxidant response element (ARE) signaling and the sensitivity to etoposide of human myeloid leukemia cells in vitro. METHODS: Human HL-60 myeloid leukemia cells and mononuclear human umbilical cord blood cells (MNCs) were examined. Nrf2 protein was detected using immunofluorescence staining and Western blotting. Binding of Nrf2 to ARE was examined with electrophoretic mobility shift assay. The level of NQO1 was assessed with real-time RT-PCR and Western blotting. DCFH-DA was used to evaluate intracellular ROS level. Cell proliferation and apoptosis were analyzed using MTT and flow cytometry, respectively. RESULTS: Mangiferin (50 µmol/L) significantly increased Nrf2 protein accumulation in HL-60 cells, particularly in the nucleus. Mangiferin also enhanced the binding of Nrf2 to an ARE, significantly up-regulated NQO1 expression and reduced intracellular ROS in HL60 cells. Mangiferin alone dose-dependently inhibited the proliferation of HL-60 cells. Mangiferin (50 mol/L) did not attenuate etoposide-induced cytotoxicity in HL-60 cells, and combined treatment of mangiferin with low concentration of etoposide (0.8 µg/mL) even increased the cell inhibition rate. Nor did mangiferin change the rate of etoposide-induced apoptosis in HL-60 cells. In MNCs, mangiferin significantly relieved oxidative stress, but attenuated etoposide-induced cytotoxicity. CONCLUSION: Mangiferin is a novel Nrf2 activator that reduces oxidative stress and protects normal cells without reducing the sensitivity to etoposide of HL-60 leukemia cells in vitro. Mangiferin may be a potential chemotherapy adjuvant.

Oridonin induces NPM mutant protein translocation and apoptosis in NPM1c+ acute myeloid leukemia cells in vitro.

AIM: Skewed cytoplasmic accumulation of NPM mutant protein (NPM1c+) is close related to leukemia pathogenesis. The aim of this study was to investigate whether oridonin, a diterpenoid isolated from the Chinese traditional medicine Rabdosia rubescens, was able to interfere with NPM1c+ protein trafficking and induce apoptosis in NPM1c+ acute myeloid leukemia cells in vitro. METHODS: OCI-AML3 cell line harboring a NPM1 gene mutation was examined. Cell growth was detected by MTT assay. Cell apoptosis was evaluated using flow cytometry and Hoechst 33258 staining. The expression and subcellular localization of relevant proteins were detected by Western blot and immunofluorescent staining. The mRNA expression was detected by RT-PCR. RESULTS: Oridonin (2-12 µmol/L) dose-dependently inhibited the viability of OCI-AML3 cells (the IC50 value was 3.27±0.23 µmol/L at 24 h). Moreover, oridonin induced OCI-AML3 cell apoptosis accompanied by activation of caspase-3 and nuclear translocation of NPM1c+ protein. Oridonin did not change the expression of Crm1 (the export receptor for nuclear export signal-containing proteins), but induced nuclear translocation of Crm1. Oridonin markedly increased the expression of nucleoporin98 (Nup98), which had an important role in Crm1-mediated nuclear protein export, and induced nuclear accumulation of Nup98. Furthermore, oridonin markedly increased the expression of p14arf and p53. CONCLUSION: In NPM1c+ leukemia cells, oridonin induces NPM1c+ protein translocation into the nucleus possibly via nuclear accumulation of Crm1; the compound markedly increases p53 and p14arf expression, which may contribute to cell apoptosis.

New targets for the antitumor activity of gambogic acid in hematologic malignancies.

Gambogic acid (GA) is the main active ingredient of gamboge, a brownish to orange dry resin secreted from Garcinia hanburyi, a plant that is widely distributed in nature. Recent in vitro and in vivo studies have demonstrated that GA exerts potent antitumor effects against solid tumors of various derivations, and its antitumor mechanisms have been thoroughly investigated. On the other hand, normal cells remain relatively resistant to GA, indicating a therapeutic window. GA is currently in clinical trials in China. Over the last decade, our laboratory demonstrates that GA exhibits potent anticancer activities against hematological malignancies. This review focuses on the new mechanisms through which GA inhibits proliferation and induces apoptosis in malignant hematological cells. These include the regulation of expression and intracellular positioning of nucleoporin and nucleophosmin; downregulation of steroid receptor coactivator-3 (SRC-3) and its downstream proteins; upregulation of death inducer-obliterator (DIO-1); downregulation of HERG potassium channel; as well as induction of reactive oxygen species (ROS) accumulation.

Betulinic acid inhibits autophagic flux and induces apoptosis in human multiple myeloma cells in vitro.

AIM: To investigate the effects of betulinic acid (BA) on apoptosis and autophagic flux in multiple myeloma cells and the relationship between the two processes. METHODS: The proliferation of human multiple myeloma KM3 cells was measured with MTT assay. FITC/PI double-labeled flow cytometry (FCM) and Hoechst 33258 staining were used to analyze the cell apoptosis. Caspase 3, PARP, Beclin1, LC3-II, and P62 were detected using Western blotting. RESULTS: Treatment of KM3 cells with BA (5-25 µg/mL) suppressed the cell proliferation in time- and dose-dependent manners. The IC(50) values at 12, 24, and 36 h were 22.29, 17.36, and 13.06 µg/mL, respectively. BA treatment dose-dependently induced apoptosis of KM3 cells, which was associated with the activation of caspase 3. However, Z-DEVD-FMK, a specific inhibitor of caspase 3, did not decrease, but rather sensitized the cells to BA-induced apoptosis, suggesting an alternative mechanism involved. On other hand, BA treatment dose-dependently increased the accumulation of LC3-II and P62 in KM3 cells, representing the inhibition of autophagic flux. Furthermore, BA treatment dose-dependently downregulated the expression of Beclin 1, an important inducer of autophagy, in KM3 cells. In the presence of BA, Z-DEVD-FMK induced autophagy and increased the amount of LC3-II in KM3 cells, which may occur via attenuating BA-induced decrease in the level of Beclin 1. Similarly, rapamycin, an autophagy inducer, increased the amount of LC3-II in KM3 cells. In the presence of BA, rapamycin caused further increase in the amount of LC3-II. Furthermore, rapamycin sensitized BA-treated KM3 cells to apoptosis. CONCLUSION: The results demonstrate that BA induces apoptosis and blocks autophagic flux in KM3 cells. Furthermore, in addition to activation of caspase 3, the inhibition of autophagic flux also contributes to the BA-mediated apoptosis of KM3 cells.

Effect of betulinic acid on the regulation of Hiwi and cyclin B1 in human gastric adenocarcinoma AGS cells.

AIM: To investigate the effect of betulinic acid (BA) on the proliferation, apoptosis and cell cycle of gastric adenocarcinoma cell AGS in vitro and the underlying mechanism. METHODS: The effect of BA on the proliferation of AGS cells was measured by using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium (MTT) assay. Apoptosis was analyzed by using Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) double-labeled flow cytometry (FCM) and Hoechst 33258 staining. The influence of BA on cell cycle of AGS cells was tested by PI staining. Both FCM and reverse transcription-PCR (RT-PCR) technologies were applied to detect the expression of Hiwi and Cyclin B1. RESULTS: BA exhibited significant cell proliferation inhibition, as well as its potency of inducing apoptosis in AGS cells in vitro in a time- and dose-dependent manner. The IC(50) value for 24 h was 18.25 microg/mL (95% confidence interval: 15.16 to 27.31 microg/mL). Cells treated with BA showed increased cell population in G(2)/M phase, with decreased S phase population. The expression of Hiwi and Cyclin B1 was down-regulated in BA-treated AGS cells in a dose-dependent manner. CONCLUSION: BA exerted potent effect on growth inhibition, G(2)/M cell cycle arrest and induction of apoptosis in AGS cells in vitro, possibly associated with the down-regulation of Hiwi and its downstream target Cyclin B1 expression. The potent antitumor capacity of BA suggested that it could be a promising new experimental anticancer agent in human gastric adenocarcinoma treatment.

Complexation of different transition metals with 4,4'-dimethyl-2,2'-bipyridine: Crystal structure, UV spectra and Hirshfeld surfaces.

Four new complexes, [Co(dmbpy)2(dca)2]·CH3OH (1), [Ni(dmbpy)2(dca)2]·CH3OH (2), [Zn(dmbpy)2(dca)2]·(3) and [Cu(dmbpy)2(OH)2]·5H2O (4) (dca=dicyanamide), derived from 4,4'-dimethyl-2,2'-bipyridine (dmbpy) have been synthesized and characterized by elemental analysis, TGA and single-crystal X-ray diffraction. Crystal structures and Hirshfeld surfaces analysis revealed that the complexes 1-3 were mainly supported by OH⋯N, CH⋯N and π⋯π intermolecular interactions, and for complex 4, the uncoordinated water molecules play a key role in the construction of the 3D stacking motif. UV spectrum measurements demonstrate that all of the complexes show typical metal to ligand charge transfer (MLCT) absorption bands between 301 and 306nm. Moreover, after complexation, the absorption maximum bands about intraligand π→π* transitions similarly show slightly red shift compared to dmbpy ligand, consisting with the DFT calculations.

Lattice water molecules tuned spin-crossover for an iron(II) complex with thermal hysteresis.

A new iron(II) complex based on the 4,4'-dimethyl-2,2'-bipyridine ligand [Fe(4,4'-dmbpy)3(ClO4)(SCN)·3H2O (1·3H2O)] has been prepared and characterized. Structural studies and Hirshfeld surface analysis for complex 1·3H2O at three different temperatures (300, 240 and 130 K) are described. The UV-vis absorption spectrum of a water-free sample (1) in methanol solution and magnetic susceptibility measurements for solid-state samples 1·3H2O and 1 revealed that the removal of lattice water molecules from complex 1·3H2O changed the magnetic properties from the low-spin state (1·3H2O) to the complete spin-crossover (1) between 350-220 K with a thermal hysteresis of 7 K, and was accompanied by a colour change from brown to red.

Effects of gambogic acid on the activation of caspase-3 and downregulation of SIRT1 in RPMI-8226 multiple myeloma cells via the accumulation of ROS.

Multiple myeloma (MM) is the second most commonly diagnosed hematologic malignancy. Although new drugs, including bortezomib and lenalidomide, have improved the treatment landscape for MM patients, MM remains incurable. Therefore, screening for novel anti-myeloma drugs is necessary. Gambogic acid (GA), the main active ingredient of gamboges secreted from the Garcinia hanburryi tree, has been reported to exhibit potent anticancer activity in certain solid tumors and hematological malignancies, while there are few studies that are available concerning its effects on MM cells. In the present study, we investigated the anticancer activity of GA on the MM RPMI-8226 cells and further studied the underlying mechanisms by which GA affected the cells. RPMI-8226 cells were cultured and the effect of GA on cell proliferation was analyzed using MTT assay. Hoechst 33258 staining was used to visualize nuclear fragmentation, and reactive oxygen species (ROS) levels were detected. GA was found to have a significant, dose-dependent effect on growth inhibition and apoptosis induction in RPMI-8226 cells. This activity is associated with the accumulation of ROS, which contributes to the activation of caspase-3 and the cleavage of poly (ADP-ribose) polymerase (PARP), accompanied with apoptosis in RPMI-8226 cells treated with GA. Mammalian SIRT1, as the closest homolog of the yeast Sir2, was extensively involved in regulating cell processes, including cell senescence, aging and neuronal protection, as well as having anti-apoptotic properties. Moreover, SIRT1 overexpression has been shown to protect cancer cells from chemotherapy and ionizing radiation. In the present study, we demonstrated that GA has the potential to downregulate the expression of SIRT1 via ROS accumulation. In conclusion, our study found that GA is able to induce apoptosis in RPMI-8226 cells via ROS accumulation followed by caspase-3 activation, PARP cleavage and SIRT1 downregulation. These results suggest that GA may have the potential to not only induce apoptosis in MM cells, but also to decrease the relapse rate of MM.

[Effect of betulinic acid on inducing apoptosis of human multiple myeloma cell line RPMI-8226].

The aim of this study was to investigate the effect of betulinic acid on inducing apoptosis of human multiple myeloma RPMI-8226 cell line. The inhibitory effect of betulinic acid on proliferation and its inducing apoptosis effect, influence on cell cycle and induced morphological changes of RPMI-8226 were evaluated by MTT, flow cytometry Annexin-V/PI double staining, flow cytometry with PI staining and fluorescence microscopy with Hoechst33258 staining, respectively. The transcription level changes of bcl-xl gene and caspase 3 which are two kinds of apoptosis related protein gene were determined by RT-PCR. The results showed that within a certain range of concentration (0, 5, 10, 15, 20 microg/ml), IC50 of betulinic acid to RPMI-8226 at 24 hours was 10.156+/-0.659 microg/ml, while the IC50 at 48 hours was 5.434+/-0.212 microg/ml, and its inhibiting effect on proliferation of RPMI-8226 showed both time-and dose-dependent manners. Flow cytometry with Annexin-V/PI double staining revealed that apoptotic rate of RPMI-8226 cells increased as betulinic acid concentration increased. Flow cytometry with PI staining showed that the ratio of cells in G0/G1 phase increased, while it in S phase decreased, and ratio of cells at G2/M phase did not present a significant change. Morphological differences were typical and obvious between cells in treated and control groups under fluorescence microscope using Hoechst33258 staining. RT-PCR detection of caspase 3 gene indicated that its transcription level showed an increasing trend as the concentration of betulinic acid increased, while the bcl-xl showed the opposite trend. It is concluded that the betulinic acid can induce apoptosis of RPMI-8226 within a certain range of concentration in a time- and dose-dependent manners. This phenomenon may be related to the transcriptional level increase of caspase 3 gene and decrease of bcl-xl. Betulinic acid also affects G1/S in cell cycle which arrests cells at phase G0/G1.