[Liujunzi Decoction treats 4NQO-induced esophageal cancer in mice: a study based on serum metabolomics].

This study aims to explore the mechanism of Liujunzi Decoction in the treatment of 4-nitroquinoline-N-oxide(4NQO)-induced esophageal cancer in mice. One hundred mice of 35-45 days were randomized into blank, model, and low-, medium-, and high-concentration(18.2, 36.4, and 54.6 g·kg~(-1), respectively) Liujunzi Decoction groups. The mice in other groups except the blank group had free access to the water containing 100 µg·mL~(-1) 4NQO for 16 weeks for the modeling of esophageal cancer. The mice in the Liujunzi Decoction groups were fed with the diets supplemented with corresponding concentrations of Liujunzi Decoction. The body weight and organ weights were weighed for the calculation of organ indexes. The pathological changes of the esophageal tissue were observed by hematoxylin-eosin(HE) staining. Ultra performance liquid chromatography-mass spectrometry(UPLC-MS/MS) was employed to collect metabolites from mouse serum samples, screen out potential biomarkers, and predict related metabolic pathways. Compared with the blank group, the model group showed decreased spleen and stomach indexes and increased lung, esophagus, and kidney indexes. Compared with the model group, Liujunzi Decoction groups had no significant changes in the organ indexes. The HE staining results showed that Liujunzi Decoction inhibited the invasive growth and cancerization of the esophageal cancer cells. A total of 9 potential biomarkers of Liujunzi Decoction in treating esophageal cancer were screened out in this study, which were urocanic acid, 1-oleoylglycerophosphoserine, 11-deoxy prostaglandin E1, Leu-Glu-Lys-Glu,(±) 4-hydroxy-5E,7Z,10Z,13Z,16Z,19Z-docosahexaenoic acid, ureidosuccinic acid,(2R)-2,4-dihydroxy-3,3-dimethylbutanoic acid, kynurenic acid, and bicyclo prostaglandin E2, which were mainly involved in histidine, pyrimidine, alanine, aspartate, glutamate, pantothenate and tryptophan metabolism and coenzyme A biosynthesis. In summary, Liujunzi Decoction may exert the therapeutic effect on the 4NQO-induced esophageal cancer in mice by regu-lating the amino acid metabolism, inflammation, and immune function.

Tunable longitudinal spin-orbit separation of complex vector modes.

Complex vector modes are opening burgeoning opportunities for a wide variety of applications and therefore the flexible manipulation of their various properties has become a topic of late. As such, in this Letter, we demonstrate a longitudinal spin-orbit separation of complex vector modes propagating in free space. To achieve this, we employed the recently demonstrated circular Airy Gaussian vortex vector (CAGVV) modes, which feature a self-focusing property. More precisely, by properly manipulating the intrinsic parameters of CAGVV modes, the strong coupling between the two constituting orthogonal components can be engineered to undergo a spin-orbit separation along the propagation direction. In other words, while one polarization component focuses at one plane, the other focuses at a different plane. Such spin-orbit separation, which we demonstrated by numerical simulations and corroborated experimentally, can be adjusted on-demand by simply changing the initial parameters of the CAGVV mode. Our findings will be of great relevance in applications such as optical tweezers, to manipulate micro- or nano-particles at two different parallel planes.

The latest research progress on minimally invasive treatments for hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer-related death worldwide. Due to the high prevalence of hepatitis B virus (HBV) infection in China, the incidence of HCC in China is high, and liver cirrhosis caused by chronic hepatitis also brings great challenges to treatment. This paper reviewed the latest research progress on minimally invasive treatments for HCC, including percutaneous thermal ablation and new nonthermal ablation techniques, and introduced the principles, advantages, and clinical applications of various therapeutic methods in detail. DATA SOURCES: The data of treatments for HCC were systematically collected from the PubMed, ScienceDirect, American Chemical Society and Web of Science databases published in English, using "minimally invasive" and "hepatocellular carcinoma" or "liver cancer" as the keywords. RESULTS: Percutaneous thermal ablation is still a first-line strategy for the minimally invasive treatment of HCC. The effect of microwave ablation (MWA) on downgrading treatment before liver transplantation is better than that of radiofrequency ablation (RFA), while RFA is more widely used in the clinical practice. High-intensity focused ultrasound (HIFU) is mainly used for the palliative treatment of advanced liver cancer. Electrochemotherapy (ECT) delivers chemotherapeutic drugs to the target cells while reducing the blood supply around HCC. Irreversible electroporation (IRE) uses a microsecond-pulsed electric field that induces apoptosis and necrosis and triggers a systemic immune response. The nanosecond pulsed electric field (nsPEF) has achieved a good response in the ablation of mice with HCC, but it has not been reported in China for the treatment of human HCC. CONCLUSIONS: A variety of minimally invasive treatments provide a sufficient survival advantage for HCC patients. Nonthermal ablation will lead to a new wave with its unique advantage of antitumor recurrence and metastasis.

Experimental generation of arbitrary abruptly autofusing Circular Airy Gaussian vortex vector beams.

Complex vector modes represent a general state of light nonseparable in their spatial and polarization degrees of freedom, which have inspired a wide variety of novel applications and phenomena, such as their unexpected propagation behaviour. For example, they can propagate describing periodic polarization transitions, changing from one vector beam to another. Here, we put forward a novel class of vector modes with the capability to experience an abruptly autofocusing behaviour. To achieve such beams, we encode the spatial degree of freedom in the Circular Airy Gaussian vortex (CAGV) beams. We demonstrate the experimental generation of arbitrary CAGV vector beams and evince some of their properties, such as a rotation of intermodal phase. We anticipate that the fascinating properties of theses modes will prompt the development of novel applications associated to their autofocusing behaviour and polarization distribution.

Polarisation-insensitive generation of complex vector modes from a digital micromirror device.

In recent time there has been an increasing amount of interest in developing novel techniques for the generation of complex vector light beams. Amongst these, digital holography stands out as one of the most flexible and versatile with almost unlimited freedom in the generation of scalar and complex vector light fields featuring arbitrary polarisation distributions and spatial profiles. In this manuscript we put forward a novel technique, which relies on the polarisation-insensitive attribute of Digital Micromirror Devices (DMDs). In a prior work where we outlined a new detection scheme based on Stokes projections we alluded to this technique. Here we outline the creation process in full, providing all the details for its experimental implementation. In addition, we fully characterise the performance of such technique, providing a quantitative analysis of the generated modes. To this end, we experimentally reconstruct the transverse polarisation distribution of arbitrary vector modes and compare the ellipticity and flatness of the polarisation ellipses with theoretical predictions. Further, we also generate vector modes with arbitrary degrees of non-separability and determine their degree of concurrence comparing this to theoretical predictions.

Endoplasmic reticulum stress and destruction of pancreatic ß cells in type 1 diabetes.

Type 1 diabetes (T1D) results from dysfunction of pancreatic islets ß cells. Recent studies supported that endoplasmic reticulum (ER) stress takes an important role in pancreatic ß cell excessive loss, resulting in T1D. Here, we aimed to review the relationship between ER stress and T1D. Additionally, we also reviewed the potential mechanisms underlying ER stress mediated T1D. Studies have shown that severe ER stress is directly involved in the pancreatic ß cells destruction and pathogenesis of T1D. ER stress plays a key part in pancreatic ß cells and T1D, which will help in developing new effective therapeutics for T1D.

Does the structure of light influence the speckle size?

It is well known that when a laser is reflected from a rough surface or transmitted through a diffusive medium, a speckle pattern will be formed at a given observation plane. An important parameter of speckle is its size, which for the case of homogeneous illumination, well-known relations for its computation have been derived. This is not the case for structured light beams of non-homogeneous intensity and phase distribution. Here, we propose and demonstrate, using Hermite- and Laguerre-Gaussian light modes, that the mean size of the speckle generated by these structured light beams can be measured assuming a homogeneous illumination. We further provide with mathematical expressions that relate the speckle size to the generalised definition of "spot size". To reinforce our assessment, we compare the mean speckle size generated by structured light modes with that generated by wave fronts of constant phase and amplitude and show that in both cases the mean speckle size is almost identical. Our findings reveal a fundamental property of speckle, which will be of great relevance in many speckle-based applications and will pave the way towards the development of novel applications.

Real-time Stokes polarimetry using a digital micromirror device.

Stokes polarimetry (SP) is a powerful technique that enables spatial reconstruction of the state of polarization (SoP) of a light beam using only intensity measurements. A given SoP is reconstructed from a set of four Stokes parameters, which are computed through four intensity measurements. Since all intensities must be performed on the same beam, it is common to record each intensity individually, one after the other, limiting its performance to light beams with static SoP. Here, we put forward a novel technique to extend SP to a broader set of light beams with dynamic SoP. This technique relies on the superposition principle, which enables the splitting of the input beam into identical copies, allowing the simultaneous measurement of all intensities. For this, the input beam is passed through a multiplexed digital hologram displayed on a polarization-insensitive Digital Micromirror Device (DMD) that grants independent and rapid (20 kHz) manipulation of each beam. We are able to reliably reconstruct the SoP with high fidelity and at speeds of up to 27 Hz, paving the way for real-time polarimetry of structured light.

In situ detection of a cooperative target's longitudinal and angular speed using structured light.

Laser remote sensing represents a powerful tool that enables the accurate measurement of the speed of moving targets. Crucially, most sensing techniques are two-dimensional (2D) and only enable direct determination of the speed along the line of sight. Here we put forward a novel three-dimensional technique that enables the direct and simultaneous measurement of both the longitudinal and angular speed of cooperative targets. This technique is based on the use of complex vector light beams, whose polarization and spatial degree of freedom are coupled in a non-separable way. We present evidence of our technique by performing a proof-of-principle experiment.

Numb confers to inhibit epithelial mesenchymal transition via ß-catenin/Lin28 signaling pathway in breast cancer.

OBJECTIVES: This study aimed to investigate role of Numb in the epithelial mesenchymal transition (EMT) of breast cancer. METHODS: Numb and ß-catenin were inhibited in MCF-7 cells using sh-RNA and overexpressed in T47D cells by pcDNA3.0-Numb, pcDNA3.0-ß-catenin. Cell proliferation, invasion and migration were evaluated using MTT and Transwell assay, respectively. ß-catenin, Lin28, and EMT related markers were determined using qRT-PCR and Western Blotting. RESULTS: Knockdown of Numb significantly promoted the proliferation, invasion and migration of MCF-7 cells, further increased the expression of ß-catenin, Lin28, Snail-1, and N-cadherin, as well as decreased E-cadherin. In T47D cells transfected with pcDNA3.0-Numb, the results were quite the reverse. CONCLUSIONS: Knockdown of Numb could promote the EMT of breast cancer cells via ß-cateni/Lin28 signaling pathway.

LIGHT/IFN-γ triggers ß cells apoptosis via NF-κB/Bcl2-dependent mitochondrial pathway.

LIGHT recruits and activates naive T cells in the islets at the onset of diabetes. IFN-γ secreted by activated T lymphocytes is involved in beta cell apoptosis. However, whether LIGHT sensitizes IFNγ-induced beta cells destruction remains unclear. In this study, we used the murine beta cell line MIN6 and primary islet cells as models for investigating the underlying cellular mechanisms involved in LIGHT/IFNγ - induced pancreatic beta cell destruction. LIGHT and IFN-γ synergistically reduced MIN6 and primary islet cells viability; decreased cell viability was due to apoptosis, as demonstrated by a significant increase in Annexin V(+) cell percentage, detected by flow cytometry. In addition to marked increases in cytochrome c release and NF-κB activation, the combination of LIGHT and IFN-γ caused an obvious decrease in expression of the anti-apoptotic proteins Bcl-2 and Bcl-xL, but an increase in expression of the pro-apoptotic proteins Bak and Bax in MIN6 cells. Accordingly, LIGHT deficiency led to a decrease in NF-κB activation and Bak expression, and peri-insulitis in non-obese diabetes mice. Inhibition of NF-κB activation with the specific NF-κB inhibitor, PDTC (pyrrolidine dithiocarbamate), reversed Bcl-xL down-regulation and Bax up-regulation, and led to a significant increase in LIGHT- and IFN-γ-treated cell viability. Moreover, cleaved caspase-9, -3, and PARP (poly (ADP-ribose) polymerase) were observed after LIGHT and IFN-γ treatment. Pretreatment with caspase inhibitors remarkably attenuated LIGHT- and IFNγ-induced cell apoptosis. Taken together, our results indicate that LIGHT signalling pathway combined with IFN-γ induces beta cells apoptosis via an NF-κB/Bcl2-dependent mitochondrial pathway.

Laser Ablation of 6H-SiC Single Crystals and Spectral Characterization.

Laser micromachining has proven to be a useful tool for precision processing of semiconductors. For Silicon Carbide (SiC) single crystals, ablation with ultraviolet wavelength laser could lead to the maximum absorption efficiency of incident energy. In this paper, laser ablations were performed on 6H-SiC single crystals through a 355 nm solid state laser. Different confining media were also employed to find the optimal processing condition. The surface of SiC after laser ablation was characterized by Raman spectroscopy. Amorphous silicon and nanocrystalline graphite were found to be the main compositions left. For SiC wafers ablation in air, the amorphous silicon exhibited mainly around rather than inside the ablated crater. However, the amorphous silicon showed opposite spatial distribution features for samples processing under liquid. Through analysis of the compositions left on the ablated surface, the ablation mechanism was investigated from another point of view. For liquid confined laser processing,previous studies mainly concentrate on the thickness and viscosity of the liquids, little information has been done on the reducibility of liquids. To investigate the influence of liquid reducibility, the surface morphology and oxygen content of ablation under different confining media were checked by confocal laser scanning microscopy and energy dispersive spectroscopy. Results showed that the reducibility of confining liquid also played a vital role in the ablation process under liquid. Utilizing liquids with deoxidizing ability as confining media will result in a remarkable reduction of surface oxygen content and a more regular morphology.

STAT1-mediated down-regulation of Bcl-2 expression is involved in IFN-γ/TNF-α-induced apoptosis in NIT-1 cells.

Tumor necrosis factor (TNF)-α and interferon (IFN)-γ are the major pro-inflammatory cytokines involved in beta-cell destruction. The fate of islet beta-cells in the cytokine-induced intrinsic mitochondrial apoptotic pathway is determined by the interaction between members of the Bcl-2 family. However, the mechanism through which beta-cell apoptosis is regulated remains unclear. In this study, we treated the murine beta-cell line NIT-1 with TNF-α and IFN-γ and then investigated the regulation of signal transducer and activator of transcription-1 (STAT-1) and expression of the members of the Bcl-2 family in this apoptotic pathway. Results showed that TNF-α and IFN-γ synergistically reduced NIT-1 cell viability. In addition, the decrease in cell growth was due to apoptosis as shown by apoptotic body formation, detected by confocal laser microscope, and a significant increase in Annexin-Vup(+) cell percentage, detected by flow cytometry. Combination treatment with TNF-α and IFN-γ caused a remarkable increase in the release of cytochrome c, and in the activation of caspase-9 and caspase-3, as well as, an obvious enhancement in STAT-1 phosphorylation; the treatment, however, resulted in the down-regulation in Bcl-2 expression. The enhancement in STAT-1 activity and a down-regulation in Bcl-2 expression was also observed in MIN6 cells, another murine beta-cell derived line, after cells exposure to the combination of TNF-α and IFN-γ treatment. Knockdown of STAT-1 gene expression by siRNA or inhibition of STAT-1 activation with fludarabine reversed Bcl-2 down-expression and led to a significant decrease in apoptosis in TNF-α- and IFN-γ-treated NIT-1 cells. Taken together, our results suggest that STAT1-mediated down-regulation of Bcl-2 is involved in NIT-1 cell apoptosis induced by combination treatment with TNF-α and IFN-γ.

Synthesis of stable ACC using mesoporous silica gel as a support.

Stable amorphous calcium carbonate supported by mesoporous silica gel was successfully synthesized. The silica gel support is prepared through the hydrolytic polycondensation of ethyl silicate under suitable conditions. Laser scanning confocal microscopy (LSCM) observations reveal that the morphology of the products is branched with cruciform-like and flower-like structure. Raman spectroscopic analysis and scanning electron microscopy (SEM) observation of the products confirm the combination of stable amorphous calcium carbonate (ACC) nanoparticles and mesoporous silica gel. A possible growth mechanism for the branched structure has been proposed. Results indicate potential application of this work to ACC storage, crystal engineering, biomimetic synthesis, etc.

C5a stimulates the proliferation of breast cancer cells via Akt-dependent RGC-32 gene activation.

Complement system activation contributes to various immune and inflammatory diseases, as well as cancers.However, the role of complement activation in the proliferation of cancer cells is not clear. In the present study, we investigated the consequences of complement activation on the proliferation of breast cancer cells and its possible mechanisms. We focused our study on the potential roles of the anaphylatoxins C3a and C5a in the proliferation of human breast cancer, as two important immune mediators generated after complement activation. Our study revealed that C5a stimulation, but not C3a, enhanced the proliferation of human breast cancer cells in vitro. Moreover, the expression of response gene to complement 32 (RGC-32) was pronounced in breast cancer cells in response to C5a stimulation. Notably, blockade of the C5a receptor markedly reduced the expression of RGC-32 and the proliferation of breast cancer cells stimulated by C5a. Meanwhile, silencing of RGC-32 expression reduced the proliferation of breast cancer cells induced by C5a treatment. Further investigation revealed that Akt activation was involved in C5a-induced RGC-32 expression and breast cancer cell proliferation. In conclusion, the present study indicates that C5a may promote the proliferation of breast cancer cells through Akt1 activation of the RGC-32 gene.

[Effects of diterpene phenol extract of Rosmarinus officinalis on TGFbeta1 and mRNA expressions of its signaling pathway molecules in the lung tissue of pulmonary fibrosis rats].

OBJECTIVE: To investigate the regulative mechanism of the diterpene phenol extract of Rosmarinus Officinalis (DERO) on the imbalance of collagen metabolism of the lung tissue in pulmonary fibrosis rats. METHODS: Fifty healthy Sprague-Dawley rats were randomly divided into the normal saline group (NS), the bleomycin-induced lung injury group (BLM), the low dose DERO group (at the daily dose of 50 mg/kg), the moderate dose DERO group (at the daily dose of 100 mg/kg), and the high dose DERO group (at the daily dose of 200 mg/kg), 10 in each group (abbreviated as DERO 1, 2, 3, respectively). The pulmonary fibrosis rat model was prepared by disposable intratracheal instillation of bleomycin. DERO was administered by gastrogavage as intervention during the repairing process of lung injury. On the morning of the 29th day, the rats' lung tissue was extracted. The karyocyte number, collagen protein, type I collagen (collagen I) and transforming growth factor-beta type II receptor (TGFbetaR II), Smad4 mRNA expressions were semi-quantitatively determined using tissue microarray, HE staining, collagen fiber dyeing, immunohistochemical assay, and in situ hybridization. Using real-time fluorescent quantification RT-PCR, the mRNA expression of transforming growth factor-beta1 (TGF-beta1) were detected. RESULTS: Compared with the NS group, the collagen deposition of the lung tissue was obvious and the inflammatory infiltration was more severe in the BLM group (P < 0.05, P < 0.01). There was no statistical difference in the aforesaid 4 indices between the DERO1 group and the BLM group (P > 0.05). The collagen deposition and the inflammatory infiltration were obviously alleviated in the DERO2 and DERO3 groups (P < 0.05, P < 0.01). Compared with the NS group, the mRNA expressions of collagen-I, TGF-beta1 R II, Smad4, and TGF-beta1 were obviously up-regulated in the BLM group (P < 0.05, P < 0.01). Compared with the BLM group, the aforesaid four indices were not statistically changed in the DERO1 group (P > 0.05). But the mRNA expressions of collagen-I, TGF-beta1 R II, Smad4, and TGF-beta1 were obviously downregulated in the DERO2 and DERO3 groups (P < 0.05, P < 0.01). But the down-regulation of Smad4 expression was not obvious in the DERO2 and the DERO3 groups (P > 0.05). Compared with the DERO1 group, the mRNA expressions of collagen-I, TGF-beta1, R II, TGFbeta1 were all obviously lower in the DERO2 and the DERO3 groups (P < 0.05). But there was no statistical difference in the aforesaid 4 indices between the DERO2 group and the DERO3 group (P > 0.05). CONCLUSIONS: DERO could regulate imbalanced collagen metabolism of pulmonary fibrosis. It could inhibit excessive deposition of collagen fibers, especially excessive deposition of collagen- I. Its mechanisms might be realized by inhibiting up-regulation of TGF-beta1 and TGFbetaR II mRNA expressions, thus interfering the activation of TGF-beta-Smad signaling pathway on target genes, especially on type I procollagen target gene.

Interleukin-2 gene polymorphisms and prognosis of breast cancer.

Breast cancer is the most common malignancy in women. Interleukin-2 (IL-2) plays a key role in the proliferation of T cells and natural killer cells. It has been reported that polymorphisms in the IL-2 gene are associated with various cancers. The aim of this study was to examine the effect of polymorphisms in the IL-2 gene on the development of breast cancer in the Chinese population. IL-2-330T/G and +114T/G polymorphisms were assessed in 638 breast cancer cases and 682 age-matched healthy controls. Data were analyzed using the chi-square test. Results showed that individuals with -330TG genotype and -330GG genotype had significantly increased susceptibility to breast cancer (Odds ratio [OR]=1.42, 95% confidence interval [CI]: 1.10-1.79, p=0.0021 and OR=2.26, 95%CI: 1.53-3.30, p<0.0001). The +114T/G polymorphism did not show any correlation with breast cancer. In addition, when analyzing the survival time of breast cancer patients with IL-2-330T/G polymorphism, cases with a -330G allele had significantly shorter survival time compared with wild-type patients (p=0.002). These results suggested that polymorphism in the IL-2 gene was associated with increased susceptibility to breast cancer and could be used as a prognostic marker for this malignancy.

Dickkopf-1 as a novel predictor is associated with risk stratification by GRACE risk scores for predictive value in patients with acute coronary syndrome: a retrospective research.

OBJECTIVE: Dickkopf-1 (DKK-1), a major regulator of the Wnt pathway, plays an important role in cardiovascular disease. However, no study has evaluated the association of DKK-1 and acute coronary syndrome (ACS). We investigated this association and whether the Global Registry of Acute Coronary Events (GRACE) hospital-discharge risk score predicting major adverse cardiac events (MACE) can be improved by adding the DKK-1 value. METHODS: We enrolled 291 patients (46 with ST-segment elevation myocardial infarction [STEMI] and 245 with non-ST elevated ACS [NSTE-ACS]) who were divided into groups by tertiles of baseline plasma DKK-1 level measured by ELISA. The GRACE risk score was calculated and predictive value alone and together with DKK-1 and/or high-sensitivity C-reactive protein (hs-CRP) level were assessed, respectively. RESULTS: Compared with patients with NSTE-ACS, those with STEMI had higher plasma DKK-1 level at baseline (P = 0.006). Plasma DKK-1 level was correlated with hs-CRP level (r = 0.295, P<0.001) and was greater with high than intermediate or low GRACE scores (P = 0.002 and P<0.001, respectively). We found 44 (15.1%) MACEs during a median 2-year follow-up. DKK-1 levels were higher for patients with than without events (P<0.001). The rate of MACE increased with increasing DKK-1 level (P<0.001). The area under the receiver operating characteristic curve for GRACE score with MACE was 0.524 and improved to 0.791 with the addition of hs-CRP level, 0.775 with the addition of DKK-1 level and 0.847 with both values added. CONCLUSIONS: DKK-1 is an independent predictor of long-term MACE of patients with ACS. The long-term predictive ability of post-discharge GRACE score may be enhanced by adding DKK-1 level.