γ-6-Phosphogluconolactone, a Byproduct of the Oxidative Pentose Phosphate Pathway, Contributes to AMPK Activation through Inhibition of PP2A.

The oxidative pentose phosphate pathway (oxiPPP) contributes to cell metabolism through not only the production of metabolic intermediates and reductive NADPH but also inhibition of LKB1-AMPK signaling by ribulose-5-phosphate (Ru-5-P), the product of the third oxiPPP enzyme 6-phosphogluconate dehydrogenase (6PGD). However, we found that knockdown of glucose-6-phosphate dehydrogenase (G6PD), the first oxiPPP enzyme, did not affect AMPK activation despite decreased Ru-5-P and subsequent LKB1 activation, due to enhanced activity of PP2A, the upstream phosphatase of AMPK. In contrast, knockdown of 6PGD or 6-phosphogluconolactonase (PGLS), the second oxiPPP enzyme, reduced PP2A activity. Mechanistically, knockdown of G6PD or PGLS decreased or increased 6-phosphogluconolactone level, respectively, which enhanced the inhibitory phosphorylation of PP2A by Src. Furthermore, γ-6-phosphogluconolactone, an oxiPPP byproduct with unknown function generated through intramolecular rearrangement of δ-6-phosphogluconolactone, the only substrate of PGLS, bound to Src and enhanced PP2A recruitment. Together, oxiPPP regulates AMPK homeostasis by balancing the opposing LKB1 and PP2A.

Quantum squeezing-induced quantum entanglement and EPR steering in a coupled optomechanical system.

We propose a theoretical project in which quantum squeezing induces quantum entanglement and Einstein-Podolsky-Rosen steering in a coupled whispering-gallery-mode optomechanical system. Through pumping the χ(2)-nonlinear resonator with the phase matching condition, the generated squeezed resonator mode and the mechanical mode of the optomechanical resonator can generate strong quantum entanglement and EPR steering, where the squeezing of the nonlinear resonator plays the vital role. The transitions from zero entanglement to strong entanglement and one-way steering to two-way steering can be realized by adjusting the system parameters appropriately. The photon-photon entanglement and steering between the two resonators can also be obtained by deducing the amplitude of the driving laser. Our project does not need an extraordinarily squeezed field, and it is convenient to manipulate and provides a novel and flexible avenue for diverse applications in quantum technology dependent on both optomechanical and photon-photon entanglement and steering.

Effects of gamma-ray irradiation on material and electrical properties of AlN gate dielectric on 4H-SiC.

This article investigates the radiation effects on as-deposited and annealed AlN films on 4H-SiC substrates under gamma-rays. The AlN films are prepared using plasma-enhanced-atomic-layer-deposition on an n-type 4H-SiC substrate. The AlN/4H-SiC MIS structure is subjected to gamma-ray irradiation with total doses of 0, 300, and 600 krad(Si). Physical, chemical, and electrical methods were employed to study the variations in surface morphology, charge transport, and interfacial trapping characteristics induced by irradiation. After 300 krad(Si) irradiation, the as-deposited and annealed samples exhibit their highest root mean square values of 0.917 nm and 1.190 nm, respectively, which is attributed to N vacancy defects induced by irradiation. Under irradiation, the flatband voltage (Vfb) of the as-deposited sample shifts from 2.24 to 0.78 V, while the annealed sample shifts from 1.18 to 2.16 V. X-ray photoelectron spectrum analysis reveals the decomposition of O-related defects in the as-deposited AlN and the formation of Al(NOx)ycompounds in the annealed sample. Furthermore, the space-charge-limits-conduction (SCLC) in the as-deposited sample is enhanced after radiation, while the barrier height of the annealed sample decreases from 1.12 to 0.84 eV, accompanied by the occurrence of the SCLC. The physical mechanism of the degradation of electrical performance in irradiated devices is the introduction of defects like N vacancies and O-related defects like Al(NOx)y. These findings provide valuable insights for SiC power devices in space applications.

Carrier Modulation in 2D Transistors by Inserting Interfacial Dielectric Layer for Area-Efficient Computation.

2D materials with atomic thickness display strong gate controllability and emerge as promising materials to build area-efficient electronic circuits. However, achieving the effective and nondestructive modulation of carrier density/type in 2D materials is still challenging because the introduction of dopants will greatly degrade the carrier transport via Coulomb scattering. Here, a strategy to control the polarity of tungsten diselenide (WSe2 ) field-effect transistors (FETs) via introducing hexagonal boron nitride (h-BN) as the interfacial dielectric layer is devised. By modulating the h-BN thickness, the carrier type of WSe2 FETs has been switched from hole to electron. The ultrathin body of WSe2 , combined with the effective polarity control, together contribute to the versatile single-transistor logic gates, including NOR, AND, and XNOR gates, and the operation of only two transistors as a half adder in logic circuits. Compared with the use of 12 transistors based on static Si CMOS technology, the transistor number of the half adder is reduced by 83.3%. The unique carrier modulation approach has general applicability toward 2D logic gates and circuits for the improvement of area efficiency in logic computation.

Photon blockade with a trapped Λ-type three-level atom in asymmetrical cavity.

We propose a scheme to manipulate strong and nonreciprocal photon blockades in asymmetrical Fabry-Perot cavity with a Λ-type three-level atom. Utilizing the mechanisms of both conventional and unconventional blockade, the strong photon blockade is achieved by the anharmonic eigenenergy spectrum brought by Λ-type atom and the destructive quantum interference effect induced by a microwave field. By optimizing the system parameters, the manipulation of strong photon blockade over a wide range of cavity detuning can be realized. Using spatial symmetry breaking introduced by the asymmetry of cavity, the direction-dependent nonreciprocal photon blockade can be achieved, and the nonreciprocity can reach the maximum at optimal cavity detuning. In particular, manipulating the occurring position of nonreciprocal photon blockade can be implemented by simply adjusting the cavity detuning. Our scheme provides feasible access for generating high-quality nonreciprocal single-photon sources.

Direct-detected spectroscopy based on a plasmonic Schottky photodetector and a deep neural network.

Computational algorithms have facilitated the miniaturization of spectrometers, which is essential for on-chip and portable applications. A plasmonic Schottky photodetector provides a filter-free and CMOS-compatible scheme for spectral measurement. In this study, we report on a direct-detected spectral analysis based on an integrated vertically coupled plasmonic nanostructure Schottky photodetector. We demonstrate that the plasmonic Schottky photodetector has a fast response with a -3 dB bandwidth of 600 kHz and a high peak detectivity of 8.65 × 1010 Jones. By designing a deep neural network (DNN), we demonstrate the reconstruction of the unknown spectrum with a mean square error (MSE) of 1.57 × 10-4 at a broad operating wave band of 450-950 nm, using only 20 distinct devices. Moreover, the spectral resolution of the 20 devices can reach to 7 nm. These findings provide a promising route for the development of chip-integrated spectrometers with high spectral accuracy and optical performance.

Optimizing the Schoenemann Reaction for Colorimetric Assays of VX and GD.

The analysis of nerve agents is the focus of chemical warfare agent determination because of their extreme toxicity. A classical chemical colorimetric method, namely, the Schoenemann reaction, has been developed to detect G agents; however, it has not been utilized for VX analysis mainly because of its low peroxyhydrolysis rate. In this study, based on the mechanism of the Schoenemann reaction, a novel rapid quantitative determination method for VX was developed by optimizing the reaction conditions, such as concentrations of peroxide and the indicator, temperature, and reaction time. Using 2 ml 0.5 wt% sodium perborate as the peroxide source, 1 ml 0.1 wt% benzidine hydrochloride as the indicator, and 1 ml acetone as the co-solvent, VX and GD in ethanol or water solutions could be quantitatively analyzed within 15 min at 60°C. Further experiments based on 31P NMR spectroscopy confirmed the existence of a peroxyphosphate intermediate during the GD assay. This quantitative colorimetry system for VX and GD analysis can be developed as a portable device for the water samples in fieldwork applications.

Lysine acetylation activates 6-phosphogluconate dehydrogenase to promote tumor growth.

Although the oxidative pentose phosphate pathway is important for tumor growth, how 6-phosphogluconate dehydrogenase (6PGD) in this pathway is upregulated in human cancers is unknown. We found that 6PGD is commonly activated in EGF-stimulated cells and human cancer cells by lysine acetylation. Acetylation at K76 and K294 of 6PGD promotes NADP(+) binding to 6PGD and formation of active 6PGD dimers, respectively. Moreover, we identified DLAT and ACAT2 as upstream acetyltransferases of K76 and K294, respectively, and HDAC4 as the deacetylase of both sites. Expressing acetyl-deficient mutants of 6PGD in cancer cells significantly attenuated cell proliferation and tumor growth. This is due in part to reduced levels of 6PGD products ribulose-5-phosphate and NADPH, which led to reduced RNA and lipid biosynthesis as well as elevated ROS. Furthermore, 6PGD activity is upregulated with increased lysine acetylation in primary leukemia cells from human patients, providing mechanistic insights into 6PGD upregulation in cancer cells.

Microscopies Enabled by Photonic Metamaterials.

In recent years, the biosensor research community has made rapid progress in the development of nanostructured materials capable of amplifying the interaction between light and biological matter. A common objective is to concentrate the electromagnetic energy associated with light into nanometer-scale volumes that, in many cases, can extend below the conventional Abbé diffraction limit. Dating back to the first application of surface plasmon resonance (SPR) for label-free detection of biomolecular interactions, resonant optical structures, including waveguides, ring resonators, and photonic crystals, have proven to be effective conduits for a wide range of optical enhancement effects that include enhanced excitation of photon emitters (such as quantum dots, organic dyes, and fluorescent proteins), enhanced extraction from photon emitters, enhanced optical absorption, and enhanced optical scattering (such as from Raman-scatterers and nanoparticles). The application of photonic metamaterials as a means for enhancing contrast in microscopy is a recent technological development. Through their ability to generate surface-localized and resonantly enhanced electromagnetic fields, photonic metamaterials are an effective surface for magnifying absorption, photon emission, and scattering associated with biological materials while an imaging system records spatial and temporal patterns. By replacing the conventional glass microscope slide with a photonic metamaterial, new forms of contrast and enhanced signal-to-noise are obtained for applications that include cancer diagnostics, infectious disease diagnostics, cell membrane imaging, biomolecular interaction analysis, and drug discovery. This paper will review the current state of the art in which photonic metamaterial surfaces are utilized in the context of microscopy.

Pretreatment Method for Chloramine-T Decon Sample Before GC Analysis of HD and VX.

Chloramine-T, especially its solution in weak acidity, is one of the decontaminants for chemical warfare agents (CWAs), HD, and VX. A high CWAs recovery from decontamination (decon) sample via pretreatment was essential for evaluating decontamination effects. This paper performed experiments to optimize pretreatment methods to extract residual CWAs from chloramine-T decon samples before GC analysis. Effects of two neutralization methods, destroying decon activity by 15% Na2SO3 or decreasing decon activity by 3% NH3·H2O or 4% NaOH, were studied. Results showed they were all suitable for the HD decon sample, but only 4% NaOH was ideal for the VX decon sample. As for extractant, compared with dichloromethane, petroleum ether was more suitable for recovering CWAs from decon samples. A high recovery above 80% could be obtained for HD and VX samples ranging from 10 mg/L to 10,000 mg/L when optimized neutralization and extraction methods were simultaneously carried out.

Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III-IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial.

BACKGROUND: Cisplatin-based induction chemotherapy plus concurrent chemoradiotherapy in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma has been recommended in the National Comprehensive Cancer Network Guidelines. However, cisplatin is associated with poor patient compliance and has notable side-effects. Lobaplatin, a third-generation platinum drug, has shown promising antitumour activity against several malignancies with less toxicity. In this study, we aimed to evaluate the efficacy of lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy over a cisplatin-based regimen in patients with locoregional, advanced nasopharyngeal carcinoma. METHODS: In this open-label, non-inferiority, randomised, controlled, phase 3 trial done at five hospitals in China, patients aged 18-60 years with previously untreated, non-keratinising stage III-IVB nasopharyngeal carcinoma; Karnofsky performance-status score of at least 70; and adequate haematological, renal, and hepatic function were randomly assigned (1:1) to receive intravenously either lobaplatin-based (lobaplatin 30 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) or cisplatin-based (cisplatin 100 mg/m2 on days 1 and 22, and fluorouracil 800 mg/m2 on days 1-5 and 22-26 for two cycles) induction chemotherapy, followed by concurrent lobaplatin-based (two cycles of intravenous lobaplatin 30 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) or cisplatin-based (two cycles of intravenous cisplatin 100 mg/m2 every 3 weeks plus intensity-modulated radiotherapy) chemoradiotherapy. Total radiation doses of 68-70 Gy (for the sum of the volumes of the primary tumour and enlarged retropharyngeal nodes), 62-68 Gy (for the volume of clinically involved gross cervical lymph nodes), 60 Gy (for the high-risk target volume), and 54 Gy (for the low-risk target volume), were administered in 30-32 fractions, 5 days per week. Randomisation was done centrally at the clinical trial centre of Sun Yat-sen University Cancer Centre by means of computer-generated random number allocation with a block design (block size of four) stratified according to disease stage and treatment centre. Treatment assignment was known to both clinicians and patients. The primary endpoint was 5-year progression-free survival, analysed in both the intention-to-treat and per-protocol populations. If the upper limit of the 95% CI for the difference in 5-year progression-free survival between the lobaplatin-based and cisplatin-based groups did not exceed 10%, non-inferiority was met. Adverse events were analysed in all patients who received at least one cycle of induction chemotherapy. This trial is registered with the Chinese Clinical Trial Registry, ChiCTR-TRC-13003285 and is closed. FINDINGS: From June 7, 2013, to June 16, 2015, 515 patients were assessed for eligibility and 502 patients were enrolled: 252 were randomly assigned to the lobaplatin-based group and 250 to the cisplatin-based group. After a median follow-up of 75·3 months (IQR 69·9-81·1) in the intention-to-treat population, 5-year progression-free survival was 75·0% (95% CI 69·7-80·3) in the lobaplatin-based group and 75·5% (70·0 to 81·0) in the cisplatin-based group (hazard ratio [HR] 0·98, 95% CI 0·69-1·39; log-rank p=0·92), with a difference of 0·5% (95% CI -7·1 to 8·1; pnon-inferiority=0·0070). In the per-protocol population, the 5-year progression-free survival was 74·8% (95% CI 69·3 to 80·3) in the lobaplatin-based group and 76·4% (70·9 to 81·9) in the cisplatin-based group (HR 1·04, 95% CI 0·73 to 1·49; log-rank p=0·83), with a difference of 1·6% (-6·1 to 9·3; pnon-inferiority=0·016). 63 (25%) of 252 patients in the lobaplatin-based group and 63 (25%) of 250 patients in the cisplatin-based group had a progression-free survival event in the intention-to-treat population; 62 (25%) of 246 patients in the lobaplatin-based group and 58 (25%) of 237 patients in the cisplatin-based group had a progression-free survival event in the per-protocol population. The most common grade 3-4 adverse events were mucositis (102 [41%] of 252 in the lobaplatin-based group vs 99 [40%] of 249 in the cisplatin-based group), leucopenia (39 [16%] vs 56 [23%]), and neutropenia (25 [10%] vs 59 [24%]). No treatment-related deaths were reported. INTERPRETATION: Lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy resulted in non-inferior survival and fewer toxic effects than cisplatin-based therapy. The results of our trial indicate that lobaplatin-based induction chemotherapy plus concurrent chemoradiotherapy might be a promising alternative regimen to cisplatin-based treatment in patients with locoregional, advanced nasopharyngeal carcinoma. FUNDING: National Science and Technology Pillar Program, International Cooperation Project of Science and Technology Program of Guangdong Province, Planned Science and Technology Project of Guangdong Province, and Cultivation Foundation for the Junior Teachers at Sun Yat-sen University. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

The key amino acids of E protein involved in early flavivirus infection: viral entry.

Flaviviruses are enveloped viruses that infect multiple hosts. Envelope proteins are the outermost proteins in the structure of flaviviruses and mediate viral infection. Studies indicate that flaviviruses mainly use envelope proteins to bind to cell attachment receptors and endocytic receptors for the entry step. Here, we present current findings regarding key envelope protein amino acids that participate in the flavivirus early infection process. Among these sites, most are located in special positions of the protein structure, such as the α-helix in the stem region and the hinge region between domains I and II, motifs that potentially affect the interaction between different domains. Some of these sites are located in positions involved in conformational changes in envelope proteins. In summary, we summarize and discuss the key envelope protein residues that affect the entry process of flaviviruses, including the process of their discovery and the mechanisms that affect early infection.

Binding of the Duck Tembusu Virus Protease to STING Is Mediated by NS2B and Is Crucial for STING Cleavage and for Impaired Induction of IFN-ß.

Duck Tembusu virus (DTMUV) is a newly emerged causative agent of avian disease. The protease-dependent immune evasion of flaviviruses has been reported; however, the molecular details of this process are unclear. In this study, we found that DTMUV nonstructural protein 2B-3, a NS2B3 protease, can inhibit IFN-ß production. DTMUV NS2B3 inhibited RIG-I-, MDA5-, MAVS-, and STING-directed IFN-ß transcription, but not TBK1- and IRF7-mediated induction of IFN-ß. Further analysis showed that DTMUV NS2B3 could cleave duck STING (duSTING); the cleavage was dependent on the protease activity of NS2B3. Moreover, the STING cleavage event occurred in a not-strictly-species-specific manner. The scissile bond of duSTING cleaved by NS2B3 was mapped between the R84 and G85 residues. The ability of NS2B3 to reduce duSTING cleavage-resistant mutant-mediated IFN-ß, and ISG production was significantly reduced, demonstrating that duSTING cleavage is essential for NS2B3-induced suppression of type I IFN responses. Remarkably, the binding of NS2B3 to duSTING, which is a prerequisite for cleavage, was found to depend on NS2B, but not NS3, the cofactor of the enzyme. Unexpectedly, we found that the region between aa residues 221-225 of duSTING, distal from the site of the scissile bond, was essential for the binding of NS2B3 to duSTING and/or the cleavage of duSTING by NS2B3. Thus, we identified the molecular mechanism by which DTMUV subverts the host innate immunity using its protease. More importantly, our study provides insight into NS2B3-mediated STING cleavage events in general.

Neoadjuvant dose-modified docetaxel in squamous cell carcinoma of the head and neck: A phase 3 study.

OBJECTIVE: To evaluate the efficacy and safety of dose-modified docetaxel plus cisplatin and 5-fluorouracil (TPF) in Chinese patients with squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: This Phase III, open-label, multi-center study included Chinese adults with previously untreated TNM Stage III or IV SCCHN (NCT00995293). Patients were randomized (1:1) to induction chemotherapy with TPF (docetaxel 60 mg/m2 and cisplatin 60 mg/m2 on day 1 and 5-FU 750 mg/m2  per day continuous IV infusion on days 1-5) or PF (cisplatin 75 mg/m2 on day 1 and 5-FU 750 mg/m2  per day on days 1-5) every 3 weeks for 3-4 cycles. The primary endpoint was progression-free survival (PFS). RESULTS: Median PFS in the TPF (n = 108) and PF (n = 111) groups was 400 days and 342 days (HR = 0.75; 95% CI, 0.53─1.06; p = .227), respectively. Overall response rate was higher for TPF versus PF (76.3% vs. 52.9%; p = .001), although this equalized following radiotherapy (75.0% vs. 73.9%). In the TPF and PF groups, ≥1 treatment-emergent adverse event was experienced by 104 (94.5%) and 110 (93.2%) patients, respectively. CONCLUSION: Adding dose-modified docetaxel to PF did not significantly improve PFS but may increase anti-tumor activity in Chinese patients with locally advanced SCCHN.

Melatonin attenuates nicotine-induced autophagy and neurological changes by decreasing the production of reactive oxygen species.

Purpose: The aim of this study was to explore the mechanism of neurological changes underlying the toxicity of nicotine.Materials and methods: Rat pheochromocytoma 12 (PC12) cells and human neuroglia (HM) cells were used. The ROS levels of the cells were detected by the FACScan. Autophagy flux was monitored by a tandem monomeric RFP-GFP-tagged LC3 lentivirus. The autophagic proteins LC3, SQSTM1/p62 and Beclin1 were detected by western blot assay. In order to evaluate the effects of nicotine and melatonin on the morphological changes of neurons, primary cortical neurons were obtained and immunocytochemistry of TUBB3 tubulin were conducted.Results: Nicotine increased the levels of reactive oxygen species (ROS) in PC12 and HM cells in a concentration-dependent manner. Microscopy showed increased autophagic flux in nicotine-treated PC12 cells. Subsequent western blotting results showed that nicotine induced increase in the levels of LC3B-II and Beclin1, and decreased SQSTM1/p62 in a concentration-dependent manner. Finally, nicotine treatment reduced the length of TUBB3-positive axons and dendrites. Melatonin, a mitochondrially targeted antioxidant, reduced the ROS level, and blocked autophagy activation and the morphologic structural changes induced by nicotine.Conclusions: Our results suggested that the role of nicotine in neuronal toxicity maybe through the induction of ROS and the subsequent activation of autophagy. These effects could be restored by melatonin.

[Roles of G protein-coupled receptor 30 in the effects of genistein on apoptosis and cell cycle in human thyroid squamous cells SW579].

OBJECTIVE: Investigate the estrogen receptor expression in human thyroid squamous cell carcinoma SW579 and the effects of genistein on the apoptosis and cycle of SW579 and its mechnism. METHODS: The real-time PCR was applied to detect the expression of estrogen receptor(ER)α、ERß and G protein-coupled receptor(GPR)30 in human thyroid squamous cell line SW579; MTT was used to test the effect of genistein on cell proliferation in the SW579 cells before and after blocking GPR30; flow cytometry was explorited to measure the effect of genistein on the cell cycle and apoptosis in the SW579 was detected before and after blocking GPR30. RESULTS: The high concentration of genistein promoted the expression of ERß and GPR30 in the SW579 cells, but ERα was not expressed. The specific blocking of GPR30, the cell proliferation was aboviously inhibited by genistein in the SW579 cells and the cell apoptosis was markedly promoted after the GPR30 was blocked; The cell cycle was mainly blocked in G_2/M phase. CONCLUSION: Genistein can obiviously promote the cell proliferation in the SW579 cells, which may be related to the action of GPR30.

Heparin sulfate is the attachment factor of duck Tembus virus on both BHK21 and DEF cells.

BACKGROUND: Duck tembusu virus (DTMUV, genus Flaviviruses, family Flaviviridae) is an emerging flavivirus that can infect a wide range of cells and cell lines in vitro, though the initial step of virus invasion remains obscure. METHODS: In this study, drug treatments that including heparin, chondroitin sulfate, heparinase I, chondroitinase ABC and trypsin were applied to detect the influence of DTMUV absorption, subsequently, the copy number of viral genome RNA was analyzed by quantitative real-time PCR. The inhibition process of viral absorption or entry by heparin was determined by western blotting, and the cytotoxicity of drug treated cells was detected by cell counting kit-8. RESULTS: We found that the desulfation of glycosaminoglycans (GAGs) with sodium chlorate had a significant effect on the adsorption of DTMUV in both BHK21 and DEF cells. Based on this result, we incubated cells with a mixture of DTMUV and GAGs competition inhibitors or pre-treated cells with inhibitors, after incubation with the virus, the NS5 expression of DTMUV and viral titers were detected. The data suggested that heparin can significantly inhibit the absorption of DTMUV in a dose dependent manner but not at the step of viral entry in BHK21 and DEF cells. Meanwhile, heparinase I can significantly inhibit DTMUV attachment step. CONCLUSIONS: Our results clearly proved that heparin sulfate plays an important role in the first step of DTMUV entry, viral attachment, in both BHK21 and DEF cells, which sheds light on the entry mechanism of DTMUV.

[Effects of genistein on proliferation and invasion of human thyroid squamous cell carcinoma SW579 cells].

OBJECTIVE: To study the effect and mechanism of genistein on the proliferation, adhesion, invasion and migration of SW579 cells. METHODS: MTT assay was used to detect the effect of genistein on cell proliferation of the thyroid carcinoma cell line( SW579). Cell-matrix adhesion and transwell invasion assay were used to measure the impact of genistein on the cell adhesion, invasion and migration. Real-time PCR assay was used to detect the effect of genistein on the level of MMP2 mRNA. RESULTS: Compared with the control groups, genistein treated groups can significantly promote the proliferation of SW579 cells. However, genistein can obiviously inhibited the adhesion, invasion and migartion of SW579 cells. And genistein can dramatically decreased MMP2 mRNA expression in SW579 cells. CONCLUSION: In the study, genistein could effectively inhibit the invasion and migration ability of the SW579 cells in vitro, and the reduction of MMP-2 expression may play an important role in this process.

[The change of cancer-related genes expression profile in Nthy-ori-3-1 cell induced by the pesticide amitrole].

OBJECTIVE: To explore the possible mechanism of amitrole causing thyroid tumor in Nthy-ori-3-1 cell by differential expression microarray analysis. METHODS: After the Nthy-ori-3-1cells were treated with 1 ~ 100 g / m L amitrole for 24 h, and the effect of amitrole on the proliferation of the cells was detected by MTT assay. Then cells were treated with 100 g / m L amitrole for 24 h, and the differential expression microarray was tested. The microarray results was analyzed by GO analysis and pathway analysis. The microarray results were verified by real-time quantitative PCR. RESULTS: MTT results showed that amitole had no significant effect on the proliferation of Nthy-ori-3-1 cells. Microarray results showed that 90( 55 up-regulated, 35 down regulated) genes were significantly changed. GO analysis showed that 43( 37 up-regulated, 6 down-regulated) of the 90 changed genes were related to biological processes, and 42( 37 up-regulated, 5down-regulated) were related to molecular function, and 44( 38 up-regulated, 6 downregulated) were related to cell components. Pathway results showed that 44 signalingpathways were influenced by the differentially expressed genes, and 10 of them were closely related to tumor. The qRT-PCR results were consistent with microarray results. wnt5 b, arnt2 and bmp2 genes were significantly related with multiple tumor-associated pathways. CONCLUSION: Amitrole may cause thyroid tumor by multiple signaling pathways, and bmp2, arnt2 and wnt5 b may beits major target genes.

Prognostic Value of Cervical Nodal Necrosis in Nasopharyngeal Carcinoma: Analysis of 1800 Patients with Positive Cervical Nodal Metastasis at MR Imaging.

PURPOSE: To evaluate the prognostic value of cervical nodal necrosis (CNN) in patients with nasopharyngeal carcinoma (NPC) with magnetic resonance (MR) imaging. MATERIALS AND METHODS: This was an institutional review board-approved retrospective study of 1800 patients with newly diagnosed stage T1, 4N1, 3M0 NPC who were treated with definitive radiation therapy, with or without chemotherapy, between January 2007 and December 2009; the requirement to obtain informed consent was waived. MR images were reviewed to assess lymph node status, and patients were divided into CNN and non-CNN groups. The overall survival, disease-free survival, regional relapse-free survival (RRFS), and distant metastasis-free survival (DMFS) were calculated with the Kaplan-Meier method, and differences were compared by using the log-rank test. RESULTS: The incidence of CNN was 44.0% (792 of 1800). After the median follow-up period of 53 months, the 5-year overall survival, disease-free survival, RRFS, and DMFS rates of the CNN and non-CNN groups were 78.8% and 91.8%, 78.2% and 91.2%, 78.6% and 91.8%, and 78.4% and 91.6%, respectively (for all rates, P < .001). The distant metastasis rate was 18.7% (148 of 792) for the CNN group versus 4.6% (46 of 1008) for the non-CNN group (P < .01). Subgroup analysis revealed similar survival outcomes between stage N1 disease with CNN and stage N2 disease without CNN, stage N2 disease with CNN, and stage N3 disease regardless of CNN. CNN, T stage, N stage, age older than 44 years, and male sex were significant independent negative prognostic factors for overall survival, disease-free survival, RRFS, and DMFS. CONCLUSION: CNN is an independent negative prognostic factor in patients with NPC, and it may be appropriate to investigate whether N stage should be upgraded by one level in patients with CNN.