SND1 Promotes Radioresistance in Cervical Cancer Cells by Targeting the DNA Damage Response.

Background: Radiotherapy is one of the most effective therapeutic strategies for cervical cancer patients, although radioresistance-mediated residual and recurrent tumors are the main cause of treatment failure. However, the mechanism of tumor radioresistance is still elusive. DNA damage response pathways are key determinants of radioresistance. The purpose of this study was to investigate the role and mechanism of SND1 in radioresistance of cervical cancer. Methods: A stable HeLa cell line with SND1 knockout (HeLa-KO) was generated through a modified CRISPR/Cas9 double-nicking gene editing system. The stable CaSki cell lines with SND1 knockdown (CaSki-Ctrl, CaSki-SND1-sh-1, CaSki-SND1-sh-2) were constructed through lentivirus transfection with the pSil-SND1-sh-1 and pSil-SND1-sh-2 plasmids. Results: It was observed that SND1 deficiency significantly increased the radiosensitivity of cervical cancer cells. It was also found that silencing SND1 promotes radiation-induced apoptosis. Significantly, the cells with a loss of SND1 function exhibited inefficient ataxia telangiectasia mutated pathway activation, subsequently impairing DNA repair and G2/M checkpoint arrest. In addition, threonine 103 is an important phosphorylation site of SND1 under DNA damaging stress. Conclusion: Collectively, the results of this study reveal a potent radiosensitizing effect of silencing SND1 or T103 mutation on cervical cancer cells, providing novel insights into potential therapeutic strategies for cervical cancer treatment.

Global Tudor-SN transgenic mice are protected from obesity-induced hepatic steatosis and insulin resistance.

In the current study, we explored the impact of Tudor-staphylococcal nuclease (SN) on obesity induced by a high-fat diet (HFD) in mice, because the functional involvement of Tudor-SN in lipid metabolism in vivo is unknown. HFD-transgenic (Tg) mice exhibited reductions in hepatic steatosis and systemic insulin resistance. There was no difference in hepatic lipid accumulation between chow-fed wild-type (WT) and chow-fed Tg mice; consistently, no difference in activation of the lipogenic pathway was detected. Overactivation of hepatic nuclear sterol regulatory element-binding protein (nSrebp2)-2, the central regulator of cholesterol metabolic proteins, was observed in HFD-Tg livers along with improved cholesterol homeostasis, but no such changes were observed in HFD-WT livers. Consistent results were observed in vitro in α-mouse liver 12 cells treated with palmitate mimicking the HFD state. In addition, global gene analysis indicated that various downstream targets of nSrebp2, were up-regulated in HFD-Tg livers. Moreover, HFD-WT mice displayed islet hypertrophy and suppression of glucose-induced insulin secretion from islets, whereas HFD-Tg mice had normal pancreatic islets. This finding suggests that the improved pancreatic metabolism of HFD-Tg mice is related to the systemic effect of insulin resistance, not to the autonomous influence of pancreatic cells. Tudor-SN is likely to be a key regulator for ameliorating HFD-induced hepatic steatosis and systemic insulin resistance in vivo.-Wang, X., Xin, L., Duan, Z., Zuo, Z., Wang, Y., Ren, Y., Zhang, W., Sun, X., Liu, X., Ge, L., Yang, X., Yao, Z., Yang, J. Global Tudor-SN transgenic mice are protected from obesity-induced hepatic steatosis and insulin resistance.

Histone H3k9 and H3k27 Acetylation Regulates IL-4/STAT6-Mediated Igε Transcription in B Lymphocytes.

IL-4 activates STAT6 and causes the subsequent up-regulation of Ig heavy chain germline Igε via chromatin remodeling involved in B lymphocytes development. STAT6 acts as a molecular switch to regulate the higher-order chromatin remodeling via dynamically orchestrating co-activators (CBP/Tudor-SN) and co-repressors (HDAC1/PSF). Here, we demonstrated that STAT6/Tudor-SN/PSF form a complex, balancing the acetylation and deacetylation states to co-regulate IL-4/STAT6 gene transcription. In addition, we confirmed that IL-4 treatment increased the HATs activity in Ramos cells. As "active" markers, the expression of H3K9ac and H3K27ac increased after treatment with IL-4. However, transcriptional repressors such as H3K9me3 and H3K27me3 decreased in response to IL-4 stimulation. Moreover, IL-4 treatment enhanced H3 acetylation at the Igε promoter regions. Our results revealed that the Igε gene transcription is regulated by histone modifications in the IL-4/STAT6 pathway. The study will provide novel insights into the pathogenesis of allergic diseases.

Soliton self-frequency shift and third-harmonic generation in a four-hole As2S5 microstructured optical fiber.

Soliton self-frequency shift (SSFS) and third-harmonic generation (THG) are observed in a four-hole As2S5 chalcogenide microstructured optical fiber (MOF). The As2S5 MOF is tapered to offer an ideal environment for SSFS. After tapering, the zero-dispersion wavelength (ZDW) shifts from 2.02 to 1.61 µm, and the rate of SSFS can be enhanced by increasing the energy density of the pulse. By varying the average input power from 220 to 340 mW, SSFS of a soliton central wavelength from 2.206 to 2.600 µm in the mid-infrared is observed in the tapered segment, and THG at 632 nm is observed in the untapered segment.

Tunable third-harmonic generation in a chalcogenide-tellurite hybrid optical fiber with high refractive index difference.

A chalcogenide-tellurite hybrid optical fiber with a step-index structure is fabricated by the rod-in-tube drawing technique. The core is made of 15Ge-3Ga-12Sb-70S (mol. %) glass, and the cladding is made of 78TeO2-5ZnO-12Li2O-5Bi2O3 (mol. %) glass. The refractive index difference Δn=0.24. Tunable third-harmonic generation from 568 to 869 nm is observed when the optical fiber is pumped by an optical parametric oscillator with the pump wavelength changing from 1700 to 2600 nm.

Tudor-SN, a novel coactivator of peroxisome proliferator-activated receptor γ protein, is essential for adipogenesis.

Adipogenesis, in which mesenchymal precursor cells differentiate into mature adipocytes, is a well orchestrated process. In the present study we identified Tudor-SN as a novel co-activator of the transcription factor peroxisome proliferator-activated receptor γ (PPARγ). We provide the first evidence that Tudor-SN and PPARγ exist in the same complex. Both are up-regulated by the early factor C/EBPß during adipogenesis and significantly influence the regulation of PPARγ target genes in both 3T3-L1 pre-adipocyte and mouse embryonic fibroblasts (MEF) upon exposure to a mixture of hormonal mixture. Moreover, aP2-PPARγ response element (PPRE) interacts with both PPARγ and Tudor-SN, and the gene transcriptional activation of PPRE-luc is enhanced by ectopic expression of Tudor-SN. Deletion of Tudor-SN protein (MEF-KO) affects but does not completely abolish the association of PPARγ and aP2-PPRE. Loss-of-function studies further verified that Tudor-SN is required for adipogenesis, as deletion of Tudor-SN (MEF-KO) impairs dexamethasone, 3-isobutyl-1-methylxanthine, and insulin (DMI)-induced adipocyte differentiation and the expression of PPARγ target genes, such as aP2 and adipsin. Furthermore, H3 acetylation levels were lower in MEF-KO than MEF-WT. Both HDAC1 and HDAC3 are stably associated with PPARγ in MEF-KO, whereas only a small amount of association was observed in MEF-WT after 5 days of treatment during adipogenesis. PPARγ requires various co-activators or co-repressors, which may dynamically associate with and regulate the higher order chromatin remodeling of the promoter region of PPARγ-bound target genes; Tudor-SN is likely one of these co-activators.

Optical parametric gain and bandwidth in highly nonlinear tellurite hybrid microstructured optical fiber with four zero-dispersion wavelengths.

The parametric amplification gain and bandwidth in highly nonlinear tellurite hybrid microstructured optical fiber (HMOF) are simulated based on four wave mixing process. The fiber core and cladding materials are made of TeO(2)­Li(2)O­WO(3)­MoO(3)­Nb(2)O(5) and TeO(2)­ZnO­Na(2)O­P(2)O(5) glass, respectively. The fiber has four zero-dispersion wavelengths and the chromatic dispersion is flattened near the zerodispersion wavelengths. A broad gain bandwidth as wide as 1200 nm from 1290 to 2490 nm can be realized in the near infrared window by using a tellurite HMOF as short as 25 cm.

MicroRNA-127 is downregulated by Tudor-SN protein and contributes to metastasis and proliferation in breast cancer cell line MDA-MB-231.

Tudor-SN is a multifunctional protein that is highly expressed in multiple cancers including breast cancer. Tudor-SN, as a component in RNA-induced splicing complex, was recently reported to regulate gene expression in a microRNA (miRNA)-dependent manner, such as let-7, miR-34a and miR-221. However, how Tudor-SN is associated with cancer development still remains largely elusive. In the present study, we explored the role of Tudor-SN in breast cancer. Stable knockdown of endogenous Tudor-SN, performed on the breast cancer cell line MDA-MB-231 by small hairpin RNA expression vectors, suppressed the in vitro migration and invasion ability of the metastatic breast cancer cell line. Interestingly, we found Tudor-SN as a miRNA regulator according to microarray analysis, and further identified that Tudor-SN negatively regulated the expression of miR-127, and consequently increased the expression of the proto-oncogene BCL6 which was a convincing target of miR-127. Moreover, overexpression of miR-127 reduced the in vitro migration and proliferation ability of breast cancer cell MDA-MB-231. Collectively, our results suggested a novel mechanism that Tudor-SN promoted metastasis and proliferation of breast cancer cells via downregulating the miR-127 expression.

Supercontinuum generation from a multiple-ring-holes tellurite microstructured optical fiber pumped by a 2 µm mode-locked picosecond fiber laser.

Supercontinuum (SC) generation from a highly nonlinear tellurite microstructured optical fiber with multiple rings of holes was demonstrated by pumping with a 2 µm mode-locked picosecond fiber laser. The chromatic dispersion of the fiber was measured with a homemade white-light spectral interferometer in a wide wavelength range and agreed with the theoretical calculation. Although the pumped wavelength was far from the zero dispersion wavelength, with flat dispersion profile of the fiber in the anomalous dispersion, the SC could be expanded from 650 to 2850 nm with launched pulse energy of several hundred picojoules. Simulations of SC generation agreed with the experimental results.

Mid-infrared supercontinuum generation in a suspended-core As2S3 chalcogenide microstructured optical fiber.

We demonstrate the supercontinuum (SC) generation in a suspended-core As(2)S(3) chalcogenide microstructured optical fiber (MOF). The variation of SC is investigated by changing the fiber length, pump peak power and pump wavelength. In the case of long fibers (20 and 40 cm), the SC ranges are discontinuous and stop at the wavelengths shorter than 3500 nm, due to the absorption of fiber. In the case of short fibers (1.3 and 2.4 cm), the SC ranges are continuous and can extend to the wavelengths longer than 4 µm. The SC broadening is observed when the pump peak power increases from 0.24 to 1.32 kW at 2500 nm. The SC range increases with the pump wavelength changing from 2200 to 2600 nm, corresponding to the dispersion of As(2)S(3) MOF from the normal to anomalous region. The SC generation is simulated by the generalized nonlinear Schrödinger equation. The simulation includes the SC difference between 1.3 and 2.4 cm long fiber by 2500 nm pumping, the variation of SC with pump peak power in 2.4 cm long fiber, and the variation of SC with pump wavelength in 1.3 cm long fiber. The simulation agrees well with the experiment.

A simple all-solid tellurite microstructured optical fiber.

A simple all-solid tellurite microstructured optical fiber which has only one layer of high-index rods in the cladding is proposed and fabricated in the paper. The core and the cladding with the low index are made from the TeO(2)-ZnO-Na(2)O-La(2)O(3) glass, and the high-index rods are made from the TeO(2)-Li(2)O-WO(3)-MoO(3)-Nb(2)O(5) glass. The guiding regime in this fiber can be explained by ARROW model. The fiber can support the near- and mid-infrared light transmitting in the core within the transmission bands while the all-solid silica microstructured optical fiber cannot. When the pump light is outside the transmission bands, the light will transmit in six TLWMN rods.

Suppression of stimulated Brillouin scattering in all-solid chalcogenide-tellurite photonic bandgap fiber.

A new way to suppress stimulated Brillouin scattering by using an all-solid chalcogenide-tellurite photonic bandgap fiber is presented in the paper. The compositions of the chalcogenide and the tellurite glass are As(2)Se(3) and TeO(2)-ZnO-Li(2)O-Bi(2)O(3). The light and the acoustic wave are confined in the fiber by photonic bandgap and acoustic bandgap mechanism, respectively. When the pump wavelength is within the photonic bandgap and the acoustic wave generated by the pump light is outside the acoustic bandgap, the interaction between the optical and the acoustic modes is very weak, thus stimulated Brillouin scattering is suppressed in the photonic bandgap fiber.

Flat and broadband supercontinuum generation by four-wave mixing in a highly nonlinear tapered microstructured fiber.

We have demonstrated broad supercontinuum (SC) generation by using a highly nonlinear tapered tellurite microstructured fiber pumped by a 15-ps-pulsed laser with the peak power of 375 W. The fiber is characterized with a short section with a large diameter followed by a long section with a small diameter. The SC was mainly generated in the last 30-cm-long section which had a core diameter of 0.9 µm and a zero dispersion wavelength around the pump wavelength. Such a core size and a dispersion profile were chosen to ensure the SC was mainly broadened by phase matched four-wave mixing. The SC spans from UV to mid IR. The 10 dB spectrum is from 780 to 1890 nm. The input peak power is much lower than conventionally adopted in the picosecond regime. The constructed SC light source is cost-effective, since neither femtosecond pulsed laser nor high power picosecond pulsed laser is adopted.

Supercontinuum generation in short tellurite microstructured fibers pumped by a quasi-cw laser.

We investigate supercontinuum (SC) generation in highly nonlinear tellurite microstructured fibers pumped by a continuous wave (cw)/quasi-cw laser. We investigate two types of tellurite fibers. One type has the constant core diameter, and the other type has a longitudinally varying core diameter. For the fibers with a constant core diameter, when pumped in the anomalous dispersion region, the SC is symmetric in a fiber that has a zero dispersion wavelength close to the pump wavelength. For the fibers with a longitudinally varying diameter, the calculated phase-matching conditions show that they have a broad wavelength range of dispersive waves, and therefore the measured SC spectrum can be broader than one octave. In this work, the fiber lengths are as short as several tens of centimeters, and the pump power is in the watt level.

Directly draw highly nonlinear tellurite microstructured fiber with diameter varying sharply in a short fiber length.

We demonstrate theoretically and experimentally that it is feasible to draw the microstructured fiber with longitudinally varying diameter (FLVD) whose diameter varies sharply in a short fiber length. It is elucidated that during the fiber drawing process the tension is linearly proportional to the natural logarithm of the fiber drawing speed. As a result, the tension is not so sensitive to the fiber diameter. Moreover, this sensitivity can be decreased by using a large diameter ratio of preform to fiber. Owing to the low sensitivity the FLVD with diameter varying sharply in a short fiber length can be drawn directly from the preform. Additionally we show that the microstructural geometry of FLVD does not depend on the varying diameter. The deformation in microstructural geometry is determined by the fiber segment with the smallest diameter. We fabricate a FLVD of which the diameter decreases by 75% in a fiber length of 10 cm. By using this fiber we demonstrate the 600-1800 nm supercontinuum (SC) generation and the 532 nm second harmonic generation pumped by a picosecond fiber laser. The SC spectra by the conventional fibers with the largest and the smallest diameters of the FLVD are also shown, respectively. The comparisons show that the FLVD has the broadest SC spectrum due to its high nonlinearity, varying dispersion, and high damage threshold.

Five-order SRSs and supercontinuum generation from a tapered tellurite microstructured fiber with longitudinally varying dispersion.

We try to obtain stable supercontinuum (SC) generation with broad bandwidth under relative simple pump conditions. We use a 1.3-m-long highly nonlinear tellurite microstructured fiber and pump it by a 15 ps 1064 nm fiber laser. One segment of the fiber is tapered from a core diameter of 3.4 µm to 1.3 µm. For the first time five-order stimulated Raman scatterings (SRSs) are observed for soft glass fibers. SC covering 730-1700 nm is demonstrated with the pump-pulse-energy of several nJ. The mechanisms of SC broadening are mainly SRS, self-phase modulation (SPM) and cross phase modulation (XPM). The tapered segment has two advantages. Firstly it increases the nonlinearity of fiber by several times. Secondly, it acts as a compensation for the dispersion of the untapered segment, and mitigates the walk-off between pump pulse and SRS peaks.

Structural and up-conversion luminescence properties in Tm3+/Yb3+-codoped heavy metal oxide-halide glasses.

Tm3+/Yb3+-codoped heavy metal oxide-halide glasses have been synthesized by conventional melting and quenching method. Structural properties were obtained based on the Raman spectra, indicating that halide ion has an important influence on the phonon density and maximum phonon energy of host glasses. Intense blue and weak red emissions centered at 477 and 650 nm, corresponding to the transitions 1G4-->3H6 and 1G4-->3H4, respectively, were observed at room temperature. The possible up-conversion mechanisms are discussed and estimated. With increasing halide content, the up-conversion luminescence intensity and blue luminescence lifetimes of Tm3+ ion increase notably. Our results show that with the substitution of halide ion for oxygen ion, the decrease of phonon density and maximum phonon energy of host glasses both contribute to the enhanced up-conversion emissions.

Intense blue up-conversion luminescence in Tm3+/Yb3+ codoped oxyfluoride glass-ceramics containing beta-PbF2 nanocrystals.

Up-conversion luminescence properties of a Tm3+/Yb3+ codoped oxyfluoride glass-ceramics under 980 nm excitation are investigated. Intense blue emission centered at 476 nm, corresponding to 1G4-->3H6 transitions of Tm3+ was simultaneously observed in the transparent oxyfluoride glass ceramics at room temperature. The intensity of the blue up-conversion luminescence in a 1 mol% YbF3-containing glass-ceramic was found to be about 40 times stronger than that in the precursor oxyfluoride glass. The reason for the intense Tm3+ up-conversion luminescence in the oxyfluoride glass-ceramics is discussed. The dependence of up-conversion intensities on excitation power and possible up-conversion mechanism are also evaluated.

Up-conversion luminescence analysis in ytterbium-sensitized erbium-doped oxide-halide tellurite and germanate-niobic-lead glasses.

Ytterbium-sensitized erbium-doped oxide-halide tellurite and germanate-niobic-lead glasses have been synthesized by conventional melting method. Intense green and red emissions centered at 525, 546 and 657 nm, corresponding to the transitions 2H11/2-->4I15/2, 4S3/2-->4I15/2 and 4F9/2-->4I15/2, respectively, were simultaneously observed at room temperature in these glasses. The quadratic dependence of the 525, 546 and 657 nm emissions on excitation power indicates that a two-photon absorption process occurs. Tellurite glass showed a weaker up-conversion emission than germanate-niobic-lead glass, which is inconsistent with the prediction from the difference of maximum phonon energy between tellurite and germanate-niobic-lead glasses. In this paper, Raman spectroscopy was employed to investigate the origin of the difference in up-conversion luminescence in the two glasses. Compared with phonon side-band spectroscopy, Raman spectroscopy extracts more information including both phonon energy and phonon density. Our results reveal that the phonon density and the maximum phonon energy of host glasses are both important factors in determining the up-conversion efficiency.