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Tetracyclines are a class of antibiotics that exhibited potent activity against a wide range of Gram-positive and Gram-negative bacteria, yet only five members were isolated from actinobacteria, with two of them approved as clinical drugs. In this work, we developed a genome mining strategy using a TetR/MarR-transporter, a pair of common resistance enzymes in tetracycline biosynthesis, as probes to find the potential tetracycline gene clusters in the actinobacteria genome database. Further refinement using the phylogenetic analysis of chain length factors resulted in the discovery of 25 distinct tetracycline gene clusters, which finally resulted in the isolation and characterization of a novel tetracycline, hainancycline (1). Through genetic and biochemical studies, we elucidated the biosynthetic pathway of 1, which involves a complex glycosylation process. Our work discloses nature's huge capacity to generate diverse tetracyclines and expands the chemical diversity of tetracyclines.

Objective To investigate the method of CT‐guided beacon transponder implantation and precautions after implantation for liver malignant tumor. Methods CT‐guided beacon transponder implantation in three patients with liver malignancies was the first time in China. The operations were performed using Siemens's 16‐row large‐aperture spiral CT and 17‐G guide needles were using for percutaneous liver puncture. Results All three operations were successfully completed. During the operations, the beacon transponders were successfully implanted at predetermined targets next to the lesion in the liver parenchyma, and there was no obvious bleeding, pain or discomfort. All patients underwent localized CT examination on the fifth day after operations. Only one beacon transponder moved slightly, the remaining eight beacon transponders did not move, and the CT images did not have obvious metal artifacts. After the completion of radiotherapy in three patients, the follow‐up CT examination showed no movement of the beacon transponders, and the liver lesions shrank well. However, 3.0 T MRI of the liver showed that the magnetic sensitive artifacts at beacon transponders were more obvious, which affected the observation of local liver tissue. Conclusion CT‐guided liver beacon transponder implantation is safe and feasible. Beacon transponders may move in the liver parenchyma within a short period of time after implantation. Therefore, localized CT examination is recommended to be performed 4 days after the implantation. CT scans after beacon transponder implantation have no obvious metal artifacts. So CT is recommended for follow‐up. However, magnetic resonance sensitive artifacts are more obvious when MRI is performed, which will affect the evaluation of local efficacy and detect new small lesions.

Background This study aimed to compare the efficacy and toxicity of raltitrexed (Saiweijian®) plus cisplatin (SP regimen) and 5‐fluorouracil plus cisplatin (FP regimen) as concurrent chemoradiotherapy (CCRT) in patients with locally advanced nasopharyngeal carcinoma (LA‐NPC). Methods Eligible patients (N = 135) were allocated randomly in a ratio of 1:1 to receive CCRT with either SP or FP. At least 2 cycles of chemotherapy was administrated during radiotherapy. Progression free survival (PFS) was primary endpoint. Secondary endpoints included overall survival (OS), loco‐regional relapse free survival (LRRFS), distant metastasis free survival (DMFS) and toxicity. Results In this study, 68 patients received SP as CCRT, and 67 received FP. Objective responses were noted in 97.1% of the patients in the SP group and in 97.0% of the patients in the FP group (P = 1.00). At the end of a median 36 months follow‐up period, the estimated 3‐year PFS rates were 70.1% for SP and 66.6% for FP, respectively. The 3‐year LRRFS, DMFS and OS rates were 88.9%, 74.7% and 84.0%, respectively, for the SP group, and 92.3%, 71.0% and 73.7%, respectively, for the FP group. Overall, there was no difference between treatment groups with regard to response or survival. The most frequent acute toxicities monitored in both groups were bone marrow suppression, gastrointestinal side effects and oral mucositis (OM). The overall incidence of grade 3‐4 OM in the FP group (47.8%) was higher than in the SP group (11.8%). However, the incidence of other adverse effects observed in both groups was similar (P > .05). Conclusions These data indicate that SP and FP therapies have similar efficacy in treating LA‐NPC. The SP regimen showed a tolerable safety profile along with a lower frequency of severe OM and therefore, an improved life quality. In conclusion, SP was a well tolerated, effective, regimen for LA‐NPC treatment., The incidence of other adverse effects seen in both groups was similar (P > .05).The efficacy of both regimens i.e. SP and FP are found similar. The SP regimen has tolerable safety profile, with a lower incidence of severe OM and consequently, an improved quality of life.

To improve the safety of cryclotrimethylenetrinitramine (RDX), a novel method for the improvement of nano-energetic materials was reported in our research. Based on the mature microcapsule technology, nano-energetic materials are firstly fabricated by using RDX as core material and poly methyl metharylate (PMMA) as shell material via an emulsion polymerization method. The RDX/PMMA nano-composites were characterized by scanning electron microscopy (SEM), Fourier-transform infrared (FT-IR) spectra, X-ray diffraction (XRD), differential scanning calorimetry (DSC) and impact sensitivity test, respectively. The SEM results indicated successful coating of the wall material PMMA on the surface of the core RDX, and the resultant particles by emulsion polymerization were regular solid spherical particles with smooth surface and dense coating layer, more importantly, it exhibits a very uniform particle size distribution with a narrower grain size. The XRD and FT-IR analyses did not show any change in the crystal structure after coating, thus indicating that PMMA could not change the crystal structure of RDX. Moreover, the characteristic height H50 of RDX/PMMA microspheres increased from 24.3 to 39.7 cm, significantly improving the safety performance. According to the DSC analysis, the Tb after core–shell coating increased by about 2 °C, and the Ea increased by 19.07 kJ mol−1, revealing desirable thermal stability. It is obvious that the emulsion polymerization method is an effective desensitization technique to prepare core–shell composite particles for RDX.

In marine and ocean engineering area, some underwater cylindrical shell structures or vehicles may approach a free surface (water surface) or a rigid wall (seabed). The existence of the free surface or rigid wall makes the surrounding fluid around the structure an acoustic half-space, causing that the vibroacoustic characteristics of the shell may have much difference from those in an infinite fluid field. In this study, the far-field acoustic radiation of a finite cylindrical shell with an arbitrary, time-harmonic surface velocity distribution positioned within an acoustic semi-space is studied. The Fourier transform method is utilized to express acoustical pressure in the wavenumber domain, and the acoustic boundary effect is considered through the use of the Graf’s addition theorem and the image approach. Then, the relationship between acoustical pressure and the normal velocity on the structure surface is established in the wavenumber domain. Finally, the far-field acoustical pressure could be expressed by the stationary phase method approximately. The accuracy of the present approach is verified by contrast with the boundary element method. It could be observed that there are many similarities between the directivity of the far-field acoustical pressure of the cylindrical shell and the acoustical dipole due to the interference of sound waves. For the case of a rigid wall boundary, a similar interference phenomenon also exists. The present method has the advantages of simpleness and fewer calculations; it can be utilized to rapidly predict the far-field acoustical pressure in an acoustic half-space. Besides, after discussing the multiple scattering effects between the acoustic boundary and the shell, a simpler physical model is successfully put forward to resolve the far-field acoustical pressure of an inclined shell within an acoustic semi-space, assuming that the distance between the shell and the acoustical boundary is larger than a certain value (five-time radiuses in the present study).

Cinnamoyl-containing nonribosomal peptides (CCNPs) are a small group of secondary metabolites with potent biological activities produced by actinobacteria. Two remarkable features in the biosynthesis of CCNPs include the nonribosomal peptide synthases (NRPSs) for assembly of the depsipeptide backbone and the type II polyketide synthases (PKSs) for N-terminal cinnamoyl moiety construction. Here, we present a genome mining approach targeting both NRPS and type II PKS for discovery of new CCNPs, which led to the identification of 51 putative CCNP gene clusters from public bacterial genome databases. After strain prioritization, a novel class of CCNP-type glycopeptides named kitacinnamycins, one of which showing potent activation ability towards the stimulator of interferon genes (STING) protein, was identified. Bioinformatic, genetic and biochemical analysis revealed the use of the NRPS assembly line to form the macrocyclic peptide backbone, followed by a P450 monooxygenase to generate terminal oxidized groups. A glycosyltransferase with relatively broad substrate specificity transfers sugars to the newly generated OH/COOH group. The protein crystallographic study further provided structural insights into this glycosylation. Our results not only demonstrated the feasibility of genome mining and strain prioritization for the discovery of new bioactive natural products but also disclosed the biosynthetic pathway for kitacinnamycins.

Background. Activating transcription factor 6 (ATF6) and receptor-interacting protein 3 (RIP3) are important signaling proteins in endoplasmic reticulum (ER) stress and necroptosis, respectively. However, their regulatory relationship and clinical significance are unknown. We investigate the impact of ATF6 on RIP3 expression, and its role in hepatocyte necroptosis in an acute liver injury model. Methods. In vivo and in vitro experiments were carried out. LO2 cells were treated with thapsigargin (TG). In vivo, male BALB/c mice were treated with carbon tetrachloride (CCl4, 1 mL/kg) or tunicamycin (TM, 2 mg/kg). Then, the impact of ATF6 or RIP3 silencing on liver injury, hepatocyte necroptosis, and ER stress-related protein expression was examined. Results. TG induced ER stress and necroptosis and ATF6 and RIP3 expression in LO2 cells. The knockdown of ATF6 significantly decreased RIP3 expression ( p < 0.05 ) and increased ER stress and necroptosis. The downregulation of RIP3 significantly reduced necroptosis and ER stress ( p < 0.05 ). Similar results were observed in CCl4 or the TM-induced mouse model. The knockdown of ATF6 significantly decreased CCl4-induced RIP3 expression and increased liver injury, necroptosis, and ER stress in mice livers ( p < 0.05 ). In contrast, the downregulation of RIP3 significantly reduced liver injury, hepatocyte necroptosis, and ER stress. Conclusions. Hepatocyte ATF6 has multiple roles in acute liver injury. It reduces hepatocyte necroptosis via negative feedback regulation of ER stress. In addition, ATF6 can upregulate the expression of RIP3, which is not helpful to the recovery process. However, downregulating RIP3 reduces hepatocyte necroptosis by promoting the alleviation of ER stress. The findings suggest that RIP3 could be a plausible target for the treatment of liver injury.

To improve foam expansion and the stability of the foamed gel selected as the starting point, three foaming agents with relatively higher foam expansion and three foam stabilizers were used to determine optimum gradient and composition of the gel. Sodium laurate and dodecyl trimethyl ammonium bromide at a proportion of 2:3 were observed to produce the desirable foaming property and also created the largest foaming volume after the addition of 0.2% polyethylene glycol as the foam stabilizer. Different concentrations of gelatinizing and cross-linking agents were added to the foamed gel containing the foaming agent and the foam stabilizer. The most suitable ratio of the gelatinizing agent and the cross-linking agent determined on the basis of volume of foam dewatering after the addition of foam stabilizer for 6 h was 0.6%:0.5%. The resulting foamed gel was evaluated for rheological and plugging properties and a decrease in the viscosity of the gel and better plugging effect on coal seam were observed.

Background. The tumor volume of high-grade glioma (HGG) after surgery is usually determined by contrast-enhanced MRI (CE-MRI), but the clinical target volume remains controversial. Functional magnetic resonance imaging (multimodality MRI) techniques such as magnetic resonance perfusion-weighted imaging (PWI) and diffusion-tensor imaging (DTI) can make up for CE-MRI. This study explored the survival outcomes and failure patterns of patients with HGG by comparing the combination of multimodality MRI and CE-MRI imaging with CE-MRI alone. Methods. 102 patients with postoperative HGG between 2012 and 2016 were included. 50 were delineated based on multimodality MRI (PWI, DTI) and CE-MRI (enhanced T1), and the other 52 were delineated based on CE-MRI as control. Results. The median survival benefit was 6 months. The 2-year overall survival, progression-free survival, and local–regional control rates were 48% vs. 25%, 42% vs. 13.46%, and 40% vs. 13.46% for the multimodality MRI and CE-MRI cohorts, respectively. The two cohorts had similar rates of disease progression and recurrence but different proportions of failure patterns. The univariate analysis shows that characteristics of patients such as combined with epilepsy, the dose of radiotherapy, the selection of MRI were significant influence factors for 2-year overall survival. However, in multivariate analyses, only the selection of MRI was an independent significant predictor of overall survival. Conclusions. This study was the first to explore the clinical value of multimodality MRI in the delineation of radiotherapy target volume for HGG. The conclusions of the study have positive reference significance to the combination of multimodality MRI and CE-MRI in guiding the delineation of the radiotherapy target area for HGG patients.

Two homologous meroterpenoid gene clusters consisting of contiguous genes encoding polyketide synthase (PKS), prenyltransferase (PT), terpenoid cyclase (TC) and other tailoring enzymes were identified from two phylogenetically distinct fungi through computational analysis. Media optimization guided by reverse-transcription PCR (RT-PCR) enabled two strains to produce eight new and two known meroterpenoids (1-10). Using gene inactivation, heterologous expression, and biochemical analyses, we revealed a new polyketide-terpenoid assembly line that utilizes a pair of PKSs to synthesize 2,4-dihydroxy-6-alkylbenzoic acid, followed by oxidative decarboxylation, farnesyl transfer, and terpene cyclization to construct the meroterpenoid scaffold. In addition, two of the isolated meroterpenoids (3 and 17 d) showed immunosuppressive bioactivity. Our work reveals a new strategy for meroterpenoid natural products discovery, and reveals the biosynthetic pathway for compounds 1-10.

Background: This study aimed to compare concurrent chemoradiotherapy (CCRT) plus cetuximab (C) with CCRT alone in locoregionally advanced nasopharyngeal carcinoma(NPC). Methods: A total of 682 locoregionally advanced NPC patients who had undergone chemoradiotherapy with or without cetuximab were included. Propensity score-matching method was used to match patients. Progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) were compared between the two treatment arms. Results: After matching, 225 patients were identified for the analysis. Compared to CCRT, CCRT plus C was associated with significantly improved 3-year PFS (83.7% vs 71.9%, P = 0.036), LRFS (98.6% vs 90.2%, P = 0.034) but not OS (91.4% vs 85.4%, P = 0.117). Among patients with T4 and/or N3 category, CCRT plus C significantly prolonged 3-year PFS (81.0% vs 61.4%, P = 0.022) and increased 3-year OS (88.0% vs 77.9%, P = 0.086). No significant differences were observed between CCRT plus C and CCRT alone groups with regard to 3-year PFS, OS, LRFS and DMFS rates in stage III patients. Acute oral and oropharyngeal mucositis during radiotherapy were more common in the CCRT plus C than that in CCRT, but late toxicities were comparable. Conclusions: This study reveals that patients with locoregionally advanced NPC could benefit from the addition of cetuximab to CCRT, and this therapeutic gain mainly originated from T4 and/or N3 subgroup although suffering more acute moderate to severe toxicities.

Hainan Island is the second largest island and one of the most famous tourist destinations in China, but sediment contamination by trace metals in coastal areas is a major issue. However, full-scale risk assessments of trace metal-polluted coastal sediments are lacking. In this study, coastal surface sediments from 474 geographical locations covering almost the entire island were collected to identify risk-related variables. Controlling factors and possible sources of trace metals were identified, and the toxicity effects were carefully evaluated. Our results suggest that trace-metal pollution in coastal sediments, which was mainly caused by Pb, Zn and Cu emissions, has primarily resulted from industrial sewage and shipping activities and has threatened the offshore ecosystem of Hainan Island and warrants extensive consideration. This is the first study that has systematically investigated trace metal-polluted coastal sediments throughout the entirety of Hainan Island and provides solid evidence for sustainable marine management in the region.

A significant amount of research on the vibration and sound radiation of the cylindrical shell has been carried out and reported. The cylindrical shell was usually assumed to be submerged in an infinite fluid. However, the fluid region surrounding the cylindrical shell is bounded. Free vibration and forced vibration characteristics of finite cylindrical shells semi-submerged are studied in this paper, based on energy functional variational principle. The combined form of the triangular series and the Fourier series is used for the displacement of the cylindrical shell, then the orthogonality can be used to eliminate the other two directions after the variation, and only the radial displacement is kept. The relationships between the amplitudes of fluid load and the amplitudes of the radial displacement are established by the orthogonal processing of the continuous conditions of the solid-liquid coupling contact surface and the boundary conditions of the free liquid surface. Finally, the fluid structure coupling control equation is obtained. The results show that the method is correct and effective, in addition, providing a new thought for solving similar problem.

Background: Chinese perch, Siniperca chuatsi (Basilewsky), is one of the most commercially important cultured fishes in China. In the present study, a high-density genetic linkage map of Chinese perch was constructed by genotyping-by-sequencing (GBS) technique with an F1 mapping panel containing 190 progenies. Result: A total of 2328 SNPs were assigned to 24 linkage groups (LGs), agreeing with the chromosome haploid number in this species (n = 24). The sex-averaged map covered 97.9% of the Chinese perch genome, with the length of 1694.3 cM and a marker density of 0.7 cM/locus. The number of markers per LG ranged from 57 to 222, with a mean of 97. The length of LGs varied from 43.2 cM to 108.2 cM, with a mean size of 70.6 cM. The recombination rate of females was 1.50 : 1, which was higher than that of males. In order to better understand the distribution pattern of segregation distortion between the two sexes of Chinese perch, the skewed markers were retained and used to reconstruct the sex-specific maps. The 16 SDRs were identified on 10 LGs of the female map, while 12 SDRs on 8 LGs of the male map. Among these LGs, 6 LGs matched between the sex-specific maps. Conclusion: This high-density linkage map could provide a solid basis for identifying QTLs associated with economically important traits, and for implementing marker-assisted selection breeding of Chinese perch.

Background In March 2009, the first reported case infected with influenza A (H1N1) virus was identified in Mexico. The World Health Organization officially declared the outbreak to be a pandemic on June 11, 2009. The objective of this study was to evaluate the efficacy and safety of traditional Chinese medicine (TCM) in the treatment of influenza A (H1N1) infection. Methods We electronically and manually searched electronic databases, reference lists, and conference compilations to identify randomized clinical trials that compared the treatment of influenza A (H1N1) using TCM with a control group receiving oseltamivir or antivirus therapy. The Jadad score was used to assess trial quality. Duration of viral shedding, time to defervescence, and effective rate were taken as outcome measurements; additionally, heterogeneity analysis and meta-analysis were performed. Results A total of 30 studies were included in our investigation, and these studies together included 3444 cases. Based on the Jadad score, each of these studies were divided as follows: high-quality studies (n = 3), medium-quality studies (n = 2), and low quality studies (n = 25). A meta analysis was performed, which indicated that the time to defervescence between the TCM treatment group and the control group was statistically significant, the duration of viral [Influenza A (H1N1)] shedding in the integrated Chinese and Western medicine subgroups was statistically significant, but it was not statistically significant between the two groups, the effective rate between the two groups was not statistically significant. A total of 18 studies described adverse drug reactions. Conclusion The results of our study indicated that the mean time to defervescence in the TCM treatment group was less than noted in the control group, and that the duration of viral [Influenza A (H1N1)] shedding in the integrated Chinese and Western medicine subgroups was less than that noted in the control group. However, the available evidence does not consider the fact that the difference in duration of viral shedding and effective rate between the two groups was statistically similar. No obvious adverse events were reported in the included studies.

Activation of inflammasomes involves multi-protein assembly and activation of inflammatory caspase and maturation of pro-inflammatory cytokines interleukin-1β(IL-1β) and interleukin-18(IL-18). Among those types of inflammasomes, NOD (nucleotide binding oligomerization domain)-like receptors(NLRP3) is the most studied inflammasome which involves in amount of human inflammatory and autoimmune diseases. Therefore, targeting on NLRP3 inflammasome has been one of the promising methods for treatment of diseases. In this review, we focused on the studies in the latest five years on the mechanisms of NLRP3 inflammasome regulation which mainly including NLRP3 priming, three protein complex assembly and regulation of NLRP3 inflammasome activation by endogenous metabolic compounds, iron flux, subcellular structure, other types of cells and small molecular compounds. Better understanding of NLRP3 inflammasome will be benefit for potential drug target and treatment of NLRP3 inflammasome-associated diseases.

Objective To evaluate cell-free DNA (cfDNA) in plasma as a promising biomarker for lymphoma, altered levels of cfDNA and its association with clinical parameters are investigated in patients suffered from lymphomas. Methods Peripheral blood specimens were collected from 60 patients with lymphoma during initial diagnosis and those of another 107 patients with lymphoma during treated stage were also collected, 93 healthy volunteers were selected as control group. Quantitative PCR was used to detect cfDNA level in each group, cfDNA level in different groups was analyzed to understand its relationship with lymphoma patients' clinical features. After correlation analysis between cfDNA and clinical characteristics, Receiver operator characteristic curve was performed to analyze sensitivity and specificity of cfDNA and LDH . Results cfDNA concentration and integrity in initial stage of lymphoma patients were significantly higher than those in treated stage, and cfDNA concentration in treated phase was significantly higher than cfDNA concentration in control group. There was no significant difference in cfDNA integrity at treated stage compared with control group. There was no significant correlation between patient's age, gender, extranodal invasion and lymphoma pathological type and cfDNA concentration and integrity; In contrast, there was a significant correlation between ECOG score, LDH content, Ann Arbor stage, IPI, B-symptoms , Ki-67 expression and radiotherapy and cfDNA concentration and integrity, both at the time of initial diagnosis and treated stage. cfDNA concentration detection is an optimal diagnostic indicator, followed by cfDNA integrity detection, the sensitivity and specificity of both are superior to the traditional LDH detection. Conclusion cfDNA level is significantly increased in lymphomas patient plasma and may help lymphoma screening. cfDNA level may serve as a potential indicator of lymphomas treatment efficacy.

Non-small-cell lung cancer (NSCLC) is a common disease threatening the health of humankind. It has a low survival rate and a poor prognosis. Under normal circumstances, tumor infiltrating lymphocytes (TILs) play the main role in the antitumor process, but studies in recent years have found that NSCLC is capable of releasing various immunosuppressive factors, inducing the TILs to exhibit high expression of immune inhibitory receptors and relevant immunosuppressive factors. They can not only activate their own signal pathways but also block those of TILs, which causes inefficiency of tumor destruction. Researchers have now developed targeted drugs that specifically bind to immunosuppression receptors. By blocking signal transmission of immune inhibitory receptors, restraint on T lymphocytes can be released to recover antitumor role. Further research and understanding of the immunosuppression signal pathways of NSCLC are of significant importance to promote the development of immune-targeted drugs and the formulation of new treatment plans. This paper summarizes the immunosuppressive mechanisms of multiple important and newly discovered immune inhibitory receptors on T lymphocytes and immunosuppressive factors released by NSCLC cells, and their influence on patients' survival rate and prognosis. Further laboratory and clinical studies on immune-targeted drugs for primary NSCLC are needed to provide more evidence.

MiR-145 is downregulated and functions as a tumor suppressor in many malignancies. In this study, the biological function, molecular mechanism, and direct target genes of miR-145 in nasopharyngeal carcinoma (NPC) cells were investigated. Cell survival was detected by cell viability assay, and cell cycle was determined through flow cytometry. Invasion and migration of NPC cells were examined using cell invasion and wound healing assays, respectively. A disintegrin and metalloproteinase 17 (ADAM17) was verified as the target of miR-145 through luciferase reporter assay, qRT-PCR, and Western blot analysis. In NPC cell lines, miR-145 expression was significantly downregulated and ADAM17 protein expression was upregulated. ADAM17 was downregulated at the post-transcriptional level by miR-145 via the binding site of ADAM17-3'UTR. Transfection with miR-145 mimic suppressed cell growth and induced cell cycle arrest in the G0/G1 phase by upregulating key G0/G1 phase regulators, namely, p53 and p21. MiR-145 also inhibited cellular migration and invasion through targeting ADAM17 involving the regulation of EGFR and E-cadherin. Knockdown of ADAM17 elicited similar effects to that of miR-145 on NPC cells. This study reveals that miR-145 suppressed the invasion and migration of NPC cells by targeting ADAM17. Thus, miR-145 could be a therapeutic target for NPC.

Epithelial-mesenchymal transition (EMT) is associated with invasion and metastasis of cancer cells. High-mobility group AT-hook 2 (HMGA2) has been found to play a critical role in EMT in a number of malignant tumors. However, whether HMGA2 regulates the EMT in human nasopharyngeal carcinoma (NPC) is unclear.The aim of this study was to investigate the effect and mechanism of HMGA2 in inducing invasion and migration in NPC.In NPC tissues samples, the association of HMGA2 mRNA expression with clinicopathological characteristics were estimated by real-time quantitative RT-PCR(qRT-PCR). In vitro, following the silencing of HMGA2 in CNE-1 and CNE-2 cell lines, the viability and metastatic ability were analyzed using Cell Counting Kit-8 (CCK8), colony formation assay, and transwell assay. EMT and transforming growth factor-beta (TGFβ)/Smad3 signaling pathway-related protein expression changes were evaluated using western blot.HMGA2 was upregulated in NPC cell lines and clinical specimens (P0.01), and HMGA2 expression correlated significantly with metastasis (P = 0.02) and disease-free survival of NPC (hazard ratio: 3.52; 95% confidence interval: 1.34-7.79; P = 0.01). In addition, following in vitro knockdown of HMGA2, the aggressiveness of cells was markedly inhibited, Vimentin and Snail level was downregulated and E-cadherin expression was upregulated. Moreover, the expression of key proteins TGFβRII and p-Smad3 of the TGFβ/Smad3 signaling pathway was inhibited by the downregulation of HMGA2.HMGA2 might maintain EMT-induced invasion and migration through the TGFβ/Smad3 signaling pathway in NPC cell lines.

This retrospective study aims to examine the association of plasma Epstein-Barr virus- (EBV-) DNA levels with the tumor volume and prognosis in patients with locally advanced nasopharyngeal carcinoma (NPC). A total of 165 patients with newly diagnosed locally advanced NPC were identified from September 2011 to July 2012. EBV-DNA was detected using fluorescence quantitative polymerase chain reaction (PCR) amplification. The tumor volume was calculated by the systematic summation method of computer software. The median copy number of plasma EBV-DNA before treatment was 3790 copies/mL. The median gross tumor volume of the primary nasopharyngeal tumor (GTVnx), the lymph node lesions (GTVnd), and the total GTV before treatment were 72.46, 23.26, and 106.25 cm3, respectively; the EBV-DNA levels were significantly correlated with the GTVnd and the total GTV (P<0.01). The 2-year overall survival (OS) rates in patients with positive and negative pretreatment plasma EBV-DNA were 100% and 98.4% (P=1.000), and the disease-free survival (DFS) rates were 94.4% and 80.8% (P=0.044), respectively. These results indicate that high pretreatment plasma EBV-DNA levels in patients with locally advanced NPC are associated with the degree of lymph node metastasis, tumor burden, and poor prognosis.

Objectives The purpose of this study was to investigate the relationship between huntingtin-associated protein1 (HAP1) gene and radiation therapy of breast cancer cells. Methods HAP1 gene was transfected into breast cancer MCF-7 cells, which was confirmed by quantitative reverse transcription-polymerase chain reaction analysis (qRT-PCR) and Western blot in vitro. The changes of cell radiosensitivity were assessed by colony formation assay. Apoptosis were examined by flow cytometry. The expressions of two radiation-induced genes were evaluated by Western blot. Tumor growth was investigated in nude mice xenograft models in vivo. Results Our data showed that HAP1 gene expression was significantly increased in HAP1-transfected MCF-7 cells in comparison with the parental cells or negative control cells. The survival rate in MCF-7/HAP1 cells was significantly decreased after irradiation (0, 2, 4, 6, 8 Gy), compared to cells in MCF-7 and MCF-7/Pb groups in vitro. HAP1 gene increased apoptosis in MCF-7 cells after irradiation. Additionally, the tumor volume and weight in MCF-7/HAP1 + RT group were observably lower than in MCF-7/HAP1 group and MCF-7/Pb + RT group. Conclusion The present study indicated that HAP1 gene expression was related to the radiosensitivity of breast cancer cells and may play an important role in the regulation of cellular radiosensitivity.

Intensity-modulated radiotherapy (IMRT) has been applied in nasopharyngeal carcinoma (NPC) for nearly twenty years, while little is known about the ten-year survival outcomes. This study aimed at evaluating the 10-year survival outcomes for patients with NPC receiving IMRT.Data on 614 patients with newly diagnosed, non-disseminated NPC treated by IMRT between 2004 and 2008 were retrospectively reviewed. Survival outcomes stratified by tumor stage were compared.The median follow-up duration was 112.7months (range, 7.6-156.8months) for the entire cohort. The 10-year local relapse-free survival rates for T1, T2 and T3 were 94.2%, 92.5% and 91.4% (P0.05), respectively, and significantly higher than that of T4 disease (79.3%, P0.05 for all rates). As N category increased from N0 to N3, the 10-year distant metastasis-free survival rates significantly decreased accordingly (P0.01 for all rates). Furthermore, the 10-year overall survival rates were 100%, 87.1%, 75.5% and 55.6% for stage I, II, III and IV, respectively (P0.05 except stage I and II). Multivariate analysis established tumor stage and age as independent prognostic factors. Late toxicities were assessable for 495 (80.6%) patients and most were Grade I/II damages. Xerostomia (387 of 489, 79.1%) and hearing impairment (212 of 495, 42.8%) remained the most troublesome.IMRT could achieve satisfactory survival outcomes for NPC patients with acceptable late toxicities. However, distant control still remains poor, especially for patients with N3 disease.

The purpose of this paper is to demonstrate a substructure-based method dealing with the optimal material layout of the aircraft wing structure system. In this method, the topology optimization design domain of the aircraft wing is divided into multiple subordinate topological units which are called substructure. The material layout of each subordinate topology design unit is found for maximizing the total stiffness under a prescribed material usage constraint by using the Solid Isotropic Microstructures with Penalization (SIMP) method. Firstly, the proposed method is implemented to find the optimal material layouts of a high aspect-ratio I-beam. Different division ways and material constraints of the substructure have proven important influence on the total stiffness. The design formulation is applied to the optimization of an aircraft wing. Compared with the traditional one, the proposed method can find a reasonable and clearer material layout of the wing, especially material piled up near the fixed end is pushed toward the tip or the middle of the wing. The optimized design indicates the proposed method can enhance the guidance of topology optimization in finding reasonable stiffener layouts of wing structure.

With a bridge which appearing disease cause a insufficient carrying capacity as background, this paper used bridge finite element analysis software combined with field loading test to analyze Prestressed Carbon Fiber Plate reinforcement effect .The results show that the reinforcement method has a remarkable effect in improving the structure stiffness and the natural frequency of vibration , improving the carrying capacity of old bridge and overall security.

Two coupling models, the fluid-structure coupling and the acoustic-structure coupling, have been studied in this paper, in order to describe the free vibration of a fluid-filled cylindrical shell under internal pressure from two different angles. For both models, a new approach to solve the characteristic equation is presented, using the Galerkin method to obtain the natural frequency of each mode. The comparison shows the results of two models are in good agreement. Although the two models are based on different mechanical theories, the mathematic essences are confirmed to be the same, both derived from Bessel functions.

As the span became longer and the accumulation of service period of bridges, the problem that deflection of main span has also clearly emerged. To reduce long term deflection of large-span prestressed concrete continuous rigid frame bridges, tendon group-additional bending moment influence matrix method is proposed to optimize the design of prestressed reinforcement. Based on elasticity assumption, an optimum prestressed tendon arrangement can be derived by least square method. The new design is tested to be effective considering shrink and creep effect which fulfills the practical application.

Anti-seismic property was essential in the progress of bridge designing and construction due to destructive power of earthquake disaster and increasing span of bridge. This paper elaborated theory method of analysis, taking five spans continuous cable-stayed bridge which was half floating system as an engineering background, and using method of special finite element analysis to calculating dynamic characteristics and seismic response respectively which also considered longitudinal limit damping and stiffness of cable under longitudinal, transverse, vertical and three-dimensional seismic oscillation. Fundamental frequency of cable-stayed bridge was affected significantly with considering longitudinal limit damping, so connection measures would be determined reasonably in designing and analyzing anti-seismic property of long-span cable-stayed bridge. When response spectrum analysis was adopted, longitudinal and vertical displacement were larger than lateral displacement under longitudinal seismic oscillation, lateral seismic oscillation only affected the structural lateral displacement, and vertical seismic oscillation affected vertical and longitudinal displacement.

This study aims to evaluate the radiosensitization effect of nedaplatin on nasopharyngeal carcinoma (NPC) cell lines with different Epstein-Barr virus (EBV) status. Human NPC cell lines CNE-2 (EBV-negative) and C666 (EBV-positive) were treated with 0–100 μg/mL nedaplatin, and inhibitory effects on cell viability and IC50were calculated by MTS assay. We assessed changes in radiosensitivity of cells by MTS and colony formation assays, and detected the apoptosis index and changes in cell cycle by flow cytometry. MTS assay showed that nedaplatin caused significant cytotoxicity in CNE-2 and C666 cells in a time- and dose-dependent manner. After 24 h, nedaplatin inhibited growth of CNE-2 and C666 cells with IC50values of 34.32 and 63.69 μg/mL, respectively. Compared with radiation alone, nedaplatin enhanced the radiation effect on both cell lines. Nedaplatin markedly increased apoptosis and cell cycle arrest in G2/M phase. Nedaplatin radiosensitized human NPC cells CNE-2 and C666, with a significantly greater effect on the former. The mechanisms of radiosensitization include induction of apoptosis and enhancement of cell cycle arrest in G2/M phase.

Aim: This article aimed to determine treatment compliance, acute toxicities and the short-term curative effects of combining cetuximab with chemoradiation following induction chemotherapy of locoregionally advanced nasopharyngeal carcinoma (NPC). Materials & methods: A total of 21 patients with locoregionally advanced NPC were scheduled to receive one cycle of induction chemotherapy followed by intensity-modulated radiotherapy, weekly administration of cetuximab and concurrent chemotherapy (at least two cycles with a limit of six). Results: All 21 patients completed the planned radiotherapy, 14 patients (67%) without treatment breaks, and 20 patients (95.2%) completed the planned cetuximab therapy. Grade 4 toxicities included leukopenia (seven patients; 33.4%), neutropenia (three patients; 14.3%), thrombocytopenia (one patient; 4.8%) and acneiform rash (one patient; 4.8%). Over a median follow-up period of 13 months (range: 3–23 months), the local, regional and distant control rates were 100, 100 and 95.2%, respectively. Conclusion: Cetuximab in combination with intensity-modulated radiotherapy and chemoradiation is a feasible strategy against locoregionally advanced NPC. Preliminary survival data are encouraging compared with historic data.

Purpose To investigate the prognosis of three subgroups of locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiotherapy and platinum-based chemotherapy. Patients and methods Hundred and eighty-one consecutive patients with locoregionally advanced untreated nasopharyngeal carcinoma were retrospectively divided into three subgroups: locally advanced group (T3-4N0-1M0), regionally advanced group (T1-2N2-3M0) and the mixed group (T3-4N2-3M0). They were all treated with definitive intensity-modulated radiotherapy and platinum-based chemotherapy. Their prognosis were investigated and compared. Multivariate analysis was applied to identify the independent risk factors of study endpoints. Results The 3-year locoregional control rates for locally advanced group, regionally advanced group, and the mixed group were 91.5%, 90.6% and 84.3% respectively, no significant difference was observed ( P = 0.656, P = 0.429). The 3-year distant metastasis-free survival rates were 89.6%, 75.7% and 76.3%, respectively. The distant metastasis-free survival rate of the locally advanced group was significantly higher than the other two subgroups ( P = 0.028, P = 0.028). The 3-year progression-free survival rates were 85.5%, 67.9% and 67.1% respectively with significance also favoring the locally advanced group ( P = 0.043, P = 0.023). Nodal stage and the performance status were the independent risk factors of distant metastasis in the observed period. Conclusions In the context of intensity-modulated radiotherapy and platinum-based chemotherapy, the locally advanced group had a better prognosis compared with the regionally advanced group and the mixed group. Treatment stratification may be based on nodal stage.

Aluminum matrix composites reinforced by silicon carbide particles (SiCp/Al) were prepared using microwave sintering. The hardness, bending strength and compression strength of sintered composites had been measured. The results showed that SiCp/Al composite can be sintered by microwave in very short time. The oxidation or plating copper in silicon carbide surface can improve the mechanical properties of composites.

Variation in the pore structure of eucalyptus fibre during recycling was investigated using low-temperature nitrogen adsorption, atomic force microscopy (AFM), and fractal geometry. The Brunauer- Emmett-Teller (BET) surface area of the fibre fell to 55.1% of the original value after the first cycle, and to 49.0% after the second cycle, ultimately declining to 35.0% after the fourth. The Barret-Joyner- Halenda (BJH) adsorption cumulative pore volume fell to 38.4% of the original by the fourth. After four cycles, the average pore diameter fell to 82% of the original. AFM tests showed that the pore structure in fibre expressed high self-similarity in statistics, and the pore structure in the fibre could be regarded as a fractal. Fractal geometry analysis of the results showed that the fractal dimension of eucalyptus virgin fibre is 2.954. With the number of process cycles increasing, the fractal dimension fell to a minimum of 2.886 after four cycles. The water retention value (WRV) of the fibre was proportional to the fractal dimension and the crystallinity of fibre.

A 21-kDa heteropolysaccharide, coded as GFPS1b, was obtained from the cultured mycelia of Grifola frondosa GF9801 by hot-water extraction, ethanol precipitation, and fractioned by DEAE Sepharose Fast-flow, followed by the purification with Sephadex G-100 column chromatography using an AKTA purifier. It exhibited more potent anti-proliferative activity on MCF-7 cells than other polysaccharide fractions. GFPS1b was an acidic polysaccharide with approximately 16.60% protein and 4.3% uronic acid. Gas chromatography of absolute acid hydrolysate of GFPS1b suggested that it was composed of D-glucose, D-galactose, and L-arabinose with a molar ratio of 4:2:1. Periodate oxidation, Smith degradation, partial acid hydrolyzation, methylation analysis, FT-IR, and (1)H, (13)C NMR spectroscopy analysis revealed that GFPS1b had a backbone consisting of alpha-(1-->4)-linked D-galacopyranosyl and alpha-(1-->3)-linked D-glucopyranosyl residues substituted at O-6 with glycosyl residues composed of alpha-L-arabinose-(1-->4)-alpha-D-glucose (1--> linked residues.

The aim of this study was to examine the relationship between genetic polymorphisms in DNA ligase 1 (LIG1) and non-small cell lung cancer (NSCLC) susceptibility and radiosensitivity in a Chinese population. This was a case-control study that included 352 NSCLC patients and 448 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism analysis was conducted to detect HaeIII polymorphisms in exon 6 of the LIG1 gene in this popula-tion. This information was used to observe the effects of radiation in pa-tients with different genotypes in order to determine the genotypes as-sociated with radiosensitivity. The CC genotype and C allele frequency were significantly higher in the NSCLC group than in the control group (P = 0.012 and P = 0.023, respectively). The relative risk of experienc-ing NSCLC was 2.55 [95% confidence interval (CI), 1.12-3.98] for CC homozygous patients and 0.87 (95%CI, 0.46-1.88) for AA homozygous patients. Analysis of LIG1 genetic polymorphisms and radiosensitiv-ity of NSCLC patients showed that AA homozygous patients were sig-nificantly more radiosensitive than the control group (AA vs AC, P = 0.014; AA vs CC, P < 0.001; AC vs CC, P = 0.023). Therefore, the LIG1 CC genotype was associated with susceptibility to NSCLC, and the AA genotype demonstrated increased radiosensitivity compared to the AC and CC genotypes.

You-You Xia,1,* Li Yin,2,* Hao Tian,1 Wen-Jie Guo,2 Ning Jiang,2 Xue-Song Jiang,2 Jing Wu,1 Meng Chen,1 Jian-Zhong Wu,3 Xia He2 1The Fourth Clinical Medical College of Nanjing Medical University, 2Department of Radiation Oncology, 3Research Center of Clinical Oncology, The Affiliated Jiangsu Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China *These authors contributed equally tothis paper Objective: High-mobility group protein 2 (HMGA2) and epithelial–mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis. However, the clinical significance of HMGA2 and its relationship with EMT markers in nasopharyngeal carcinoma (NPC) is unclear. This study aimed to assess the clinicopathological significance and prognostic value of HMGA2, E-cadherin, and vimentin in NPC. Methods: Using immunohistochemistry, HMGA2, E-cadherin, and vimentin expression levels were evaluated in NPC (n=124) and non-tumoral inflammatory nasopharynx (n=20) tissues. The association of HMGA2 and EMT markers with clinicopathological characteristics and relationships between the protein levels and overall survival were analyzed.Results: Compared with non-tumorous tissues, HMGA2 and vimentin levels were markedly increased in NPC tissues, whereas decreased E-cadherin levels were observed (P