[High throughput-targeted sequencing panel for exploring radiosensitivity associated genes in esophageal squamous cell carcinoma].

Objective: To explore radiosensitivity-associated genes in esophageal squamous cell carcinoma by targeted sequencing panel. Methods: The peripheral blood from 22 esophageal squamous cell carcinoma (ESCC) patients received radiotherapy alone were collected, respectively. The genomic DNA (gDNA) of peripheral blood was extracted and used to create a library of gDNA restriction fragments. The gDNA restriction fragments were hybridized to the HaloPlex probe capture library, which comprises 356 cancer genes selected from the Catalogue of Somatic Mutations in Cancer (Cosmic) database of 2011 updated edition. The sequencing data were aligned by the Genome Analysis Toolkit GATK (version 3.0) and Picar. The single nucleotide polymorphism and inserted-deletion (SNP/InDel) variations were annotated by online database. The pathway enrichment was analyzed by Ingenuity Pathway analysis (IPA). Moreover, according to the short-period curative effect, 22 patients were divided into two groups: the radiation- sensitivity group (CR+ PR) and the radiation-resistant group (PD+ SD). The nonsynonymous mutation sites were statistically analyzed and the genes associated with radiosensitivity of ESCC were screened. Results: More than 97% sequencing reads were aligned to human genome reference sequence and more than 90% sequencing reads were the target sequences. SNP/InDel database annotation results showed that the mutations of 22 cases mainly distributed in exons, and the mutant types were mainly missense and synonymous single nucleotide variant (SNV). There were 23 genes of high-frequency mutation associated with esophageal cancer. Pathway enrichment by IPA showed that 3 pathways were associated with the development of esophageal cancer, which were roles of BRCA1 in DNA damage response pathway, DNA double-strand break repair by non-homologous end joining pathway and ATM signaling pathway. According to the curative effect, five genes including mismatch repair system component (PMS1), fibronectin 1(FN1), mutL homolog 1 (MLH1), B-Raf proto-oncogene, serine/threonine kinase (BRAF), patched 1 (PTCH1) and cytochrome P450 family 2 subfamily C member 19 (CYP2C19) were associated with radiosensitivity of ESCC patients.Moreover, the PTCH1 was mutated in all of 22 ESCC patients, while the variations of rs199476092 and rs202111971 sites of PTCH1 were only identified in the radiation-resistant group. Conclusions: We find that the variations of rs199476092 and rs202111971 in the encoding region of PTCH1 gene are significantly associated with radiosensitivity of ESCC patients.

Effects of γ-ray irradiation on optical absorption and laser damage performance of KDP crystals containing arsenic impurities.

The effects of γ-irradiation on potassium dihydrogen phosphate crystals containing arsenic impurities are investigated with different optical diagnostics, including UV-VIS absorption spectroscopy, photo-thermal common-path interferometer and photoluminescence spectroscopy. The optical absorption spectra indicate that a new broad absorption band near 260 nm appears after γ-irradiation. It is found that the intensity of absorption band increases with the increasing irradiation dose and arsenic impurity concentration. The simulation of radiation defects show that this absorption is assigned to the formation of AsO44⁻ centers due to arsenic ions substituting for phosphorus ions. Laser-induced damage threshold test is conducted by using 355 nm nanosecond laser pulses. The correlations between arsenic impurity concentration and laser induced damage threshold are presented. The results indicate that the damage performance of the material decreases with the increasing arsenic impurity concentration. Possible mechanisms of the irradiation-induced defects formation under γ-irradiation of KDP crystals are discussed.

Diode-pumped 1988-nm Tm:YAP laser mode-locked by intracavity second-harmonic generation in periodically poled LiNbO3.

We report a diode-pumped intracavity second-harmonic generation mode-locked solid-state Tm:YAP laser operating at 1988 nm using a periodically poled congruent LiNbO3 as the nonlinear crystal. The threshold of continuous wave mode locking is 11.6 W. The maximum output power is 1.67 W, while the shortest pulse obtained is 4.7 ps at a repetition rate of 97.09 MHz.

Control of postharvest grey mould decay of nectarine by tea polyphenol combined with tea saponin.

UNLABELLED: The control efficacy of tea polyphenol (TP) in combination with tea saponin (TS) against nectarine grey mould decay caused by Botrytis cinerea and the underlying mechanism were investigated. The in vitro experiments showed that both TP and TS inhibited the mycelial growth in a dose-dependent manner, and their combinations exhibited synergistic antifungal interactions with the synergistic ratios (SR) exceeding 1·5. The in vivo experiments showed that disease incidence and lesion diameter of grey mould of inoculated fruit were significantly lowered after being treated with the combination of TP and TS; furthermore, the activities of phenylalanine ammonia-lyase (PAL), peroxidase (POD), polyphenol oxidase (PPO), chitinase and ß-1,3-glucanase of inoculated fruit as well as the contents of total phenolic and lignin were significantly induced, the respiration rate of inoculated fruit was significantly decreased and therefore the quality decrease was accordingly retarded. These results revealed that TP in combination with TS could control grey mould of inoculated nectarines and their mechanism of action might be attributed to their active components, the induction of defensive system and the regulation of respiration. SIGNIFICANCE AND IMPACT OF THE STUDY: This study demonstrates that the combination of TP and TS has exhibited synergistic antifungal interactions against Botrytis cinerea, and it suggests that their combination may be useful and effective agents for the control of nectarine grey mould decay. Such natural products therefore represent a promising alternative to synthetic fungicides in the control of nectarine postharvest diseases.

Space-efficient optical computing with an integrated chip diffractive neural network.

Large-scale, highly integrated and low-power-consuming hardware is becoming progressively more important for realizing optical neural networks (ONNs) capable of advanced optical computing. Traditional experimental implementations need N2 units such as Mach-Zehnder interferometers (MZIs) for an input dimension N to realize typical computing operations (convolutions and matrix multiplication), resulting in limited scalability and consuming excessive power. Here, we propose the integrated diffractive optical network for implementing parallel Fourier transforms, convolution operations and application-specific optical computing using two ultracompact diffractive cells (Fourier transform operation) and only N MZIs. The footprint and energy consumption scales linearly with the input data dimension, instead of the quadratic scaling in the traditional ONN framework. A ~10-fold reduction in both footprint and energy consumption, as well as equal high accuracy with previous MZI-based ONNs was experimentally achieved for computations performed on the MNIST and Fashion-MNIST datasets. The integrated diffractive optical network (IDNN) chip demonstrates a promising avenue towards scalable and low-power-consumption optical computational chips for optical-artificial-intelligence.

High resolution characterization of modifications in fused silica after exposure to low fluence 355 nm laser at different repetition frequencies.

We report on the characterization of modifications in fused silica after exposure to low fluence (2 J/cm2) 355 nm laser at repetition frequencies of 1 Hz, 5 Hz and 10 Hz. Synchrotron based XRF spectroscopy is employed to study concentration variation of metal inclusions in the surface layer. Positron annihilation lifetime spectroscopy is used to probe atomic size defects variation in bulk silica. FT-IR is used to characterize changes of bond length and angle of Si-O-Si covalent bond of irradiated silica. Compared to the basic frequency, the big loss of cerium and iron concentration, the size enlargement of vacancy cluster and the decrease of Si-O-Si covalent bond length after 10 Hz laser irradiation are illustrated by our data. These tiny modifications provide important data to investigate laser damage mechanism.

An optical neural chip for implementing complex-valued neural network.

Complex-valued neural networks have many advantages over their real-valued counterparts. Conventional digital electronic computing platforms are incapable of executing truly complex-valued representations and operations. In contrast, optical computing platforms that encode information in both phase and magnitude can execute complex arithmetic by optical interference, offering significantly enhanced computational speed and energy efficiency. However, to date, most demonstrations of optical neural networks still only utilize conventional real-valued frameworks that are designed for digital computers, forfeiting many of the advantages of optical computing such as efficient complex-valued operations. In this article, we highlight an optical neural chip (ONC) that implements truly complex-valued neural networks. We benchmark the performance of our complex-valued ONC in four settings: simple Boolean tasks, species classification of an Iris dataset, classifying nonlinear datasets (Circle and Spiral), and handwriting recognition. Strong learning capabilities (i.e., high accuracy, fast convergence and the capability to construct nonlinear decision boundaries) are achieved by our complex-valued ONC compared to its real-valued counterpart.

Effect of miR-26a targeting GSK-3ß/ß-catenin signaling pathway on myocardial apoptosis in rats with myocardial ischemia-reperfusion.

OBJECTIVE: The aim of this study was to evaluate the effect of micro ribonucleic acid (miR)-26a on myocardial ischemia-reperfusion (I/R) injury in rats and to explore its potential mechanism. Our findings might help to provide references for clinical prevention and treatment of myocardial I/R. MATERIALS AND METHODS: A total of 60 male Sprague-Dawley (SD) rats were randomly divided into three groups using a random number table, including: Control group (n=20), I/R group (n=20) and I/R + miR-26a siRNA group (n=20). I/R model was established via recanalization after ligation of left anterior descending coronary artery (LAD). The model of miR-26a knockdown was established in rats of I/R + miR-26a siRNA group via tail intravenous injection of miR-26a siRNA. Ejection fraction (EF%) and fractional shortening (FS%) of rats in each group were detected via echocardiography. The infarction area of each group was detected via 2,3,5-triphenyltetrazolium chloride (TTC) assay. Subsequently, morphological changes in myocardial cells of each group were detected via hematoxylin-eosin (H&E) staining. Myocardial apoptosis level was measured via terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay. At the same time, the expression levels of pro-apoptotic proteins Bcl-2 associated X protein (Bax) and cleaved (C)-caspase3 in myocardial tissues of the three groups were determined using Western blotting. Finally, the effects of miR-26a knockdown on the expressions of glycogen synthase kinase (GSK)-3ß/ß-catenin signaling pathway-related proteins were detected via Western blotting and immunohistochemistry. RESULTS: The expression of miR-26a in myocardial tissues of I/R group increased significantly when compared with that in Control group (p<0.05). Knockdown of miR-26a significantly improved cardiac insufficiency caused by I/R, which also obviously increased both EF% and FS% in rats (p<0.05). In addition, knockdown of miR-26a significantly inhibited myocardial infarction caused by I/R injury, and reduced infarction area from (43.08±2.43) to (21.54±1.82) (p<0.05). The results of H&E staining revealed that in I/R + miR-26a siRNA group, myofilaments were arranged more orderly, the degree of degradation and necrosis was significantly lower, and cellular edema was significantly alleviated when compared with I/R group. Subsequent TUNEL staining demonstrated that rats in I/R + miR-26a siRNA group showed a remarkably lower level of myocardial apoptosis than I/R group (p<0.05). Meanwhile, the protein expression levels of Bax and C-caspase3 were remarkably declined in I/R + miR-26a siRNA group (p<0.05). Furthermore, the results of Western blotting showed that miR-26a siRNA could significantly reverse the inhibition of GSK-3ß/ß-catenin signaling pathway induced by I/R injury (p<0.05). CONCLUSIONS: Knockdown of miR-26a could significantly improve I/R-induced myocardial injury and promote cardiac function in rats. The possible underlying mechanism might be related to targeted regulation of miR-26a on GSK-3ß/ß-catenin signaling pathway. Therefore, miR-26a was expected to be a new therapeutic target for myocardial I/R injury.

The expression and clinical significance of miRNA-99a and miRNA-224 in non-small cell lung cancer.

OBJECTIVE: To investigate the expression and clinical significance of miRNA-99a and miRNA-224 in the serum of patients with non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: 83 patients with NSCLC, who were diagnosed and treated in our hospital from January 2014 to September 2017, were included in the experiment group. 79 patients, who made health check up, were included in the control group. The quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) technique was used to test the expressions of miRNA-99a and miRNA-224 in the serum of the patients in the two groups, and the relationship between the expression levels of miRNA-99a and miRNA-224 and the clinicopathological features of the patients with NSCLC was analyzed; the correlation between the expression of miRNA-99a and the expression of miRNA-224 in NSCLC was also analyzed. RESULTS: The expression level of miRNA-99a in the patients with NSCLC was significantly lower than that in the patients in the normal control group; the differences were statistically significant (p<0.001). The expression level of miRNA-224 in the patients with NSCLC was markedly higher than that in the patients in the normal control group; the differences were statistically significant (p<0.001). The expression level of miRNA-99a in the patients with NSCLC was remarkably correlated with pathological stage, the presence or absence of lymph node metastasis and tissue differentiation (p<0.001). The expression level of miRNA-224 in the patients with NSCLC was significantly correlated with pathological stage, the presence or absence of lymph node metastasis and pathological grade (p<0.001). The results of partial correlation analysis showed that the expression levels of miRNA-99a and miRNA-224 were negatively correlated with each other in NSCLC (r=-0.985, p<0.001). CONCLUSIONS: MiRNA-99a and miRNA-224 may be involved in the development and progression of NSCLC. MiRNA-99a is associated with NSCLC pathological stage, lymph node metastasis and tissue differentiation, while miRNA-224 is associated with NSCLC pathological stage, lymph node metastasis and pathological grade. MiRNA-99a and miRNA-224 can be used as clinical monitoring indicators for NSCLC.

[Expression of Oct4 and Sox2 and their clinical significance in tongue squamous cell carcinoma].

Objective: To investigate Oct4 and Sox2 protein expression in tongue squamous cell carcinoma (TSCC) and the relationships between the expressions of Oct4 and Sox2 and clinical pathological characteristics and survival of patients. Methods: The paraffin imbedded tissue specimens of 51 patients with histologically confirmed TSCC were included. Immunohistochemistry was employed to detect the protein expression of Oct4 and Sox2 in 51 TSCC tissue samples. The protein expression levels of Oct4 and Sox2 and their relationships with both clinicopathological features and survival of patients with TSCC were evaluated. Results: In 51 TSCC cases,positive expressions of Oct4 and Sox2 were mainly located in the nucleus of tumor cells. The expression of Oct4 was strongly positive in 27 cases (53%), weakly positive in 16 (31%) and negative in 8 (16%), whereas that of Sox2 was strongly positive in 25 cases (49%), weakly positive in 22 (43%) and negative in 4 (8%). Oct4 and Sox2 expression levels were significantly correlated with the histological grade of TSCC (P=0.004, P=0.006, respectively), not correlated with age, gender, T stage, tobacco smoking and alcohol consumption status (P>0.05), but Oct4 expression level was significantly associated with lymph node metastasis (P=0.001). Sox2 expression level was not associated with lymph node metastasis (P>0.05). The expression of Sox2 was significantly correlated with Oct4 (P<0.001). Oct4 and Sox2 expression was associated with poor overall survival of patients with TSCC (P=0.001, P=0.002, respectively), cases with higher Oct4 and Sox2 expression had the poorest overall survival (P<0.001). Sox2 expression and lymph node metastasis were independent prognostic factors of overall survival in patients with TSCC (P=0.02, P=0.001, respectively). Conclusions: Sox2 had independent prognostic effects on overall survival, suggesting that Sox2 expression may be an usefull indicator for predicting the prognosis of patients with TSCC.

[Impact of allergic airway diseases on risk of attention deficit hyperactivity disorder in school-age children].

Objective: To investigate the impact of allergic airway diseases on the risk of attention deficit hyperactivity disorder (ADHD) in school-age children. Method: Used stratified cluster sampling method, school-age children in first to sixth grade in primary schools in 9 randomly selected cities including Shanghai, Guangzhou, Xi'an, and Wuhan were enrolled in the study. Interview of parents with questionnaires, which included school-age individual and family social environment questionnaire (including history of diagnosed ADHD, allergic rhinitis, and bronchial asthma) and Children's Sleep Habits Questionnaire (CSHQ), were finished and collected during November to December in 2005.Diagnosed allergic rhinitis and asthma by specialist were independent variables and divided into following three categories as no allergic diseases (neither allergic rhinitis nor asthma), single allergic disease (allergic rhinitis or asthma), and combined allergic diseases (allergic rhinitis and asthma). Diagnosed ADHD as dependent variable, binary logistic regress model was used to analyze the risks of ADHD in school-age children. Result: Totally 23 791 questionnaires were handed out, while 22 018 were collected. The children had an average age of (8.8±1.8) years, within which 10 869 were male, and 11 021 were female. The risk ratios of ADHD were 2.197 (95%CI: 1.823-2.648) and 3.150 (95%CI: 2.082-4.760) in children with single allergic disease and combined allergic diseases separately. There was no significant difference after adjusting for the factor of sleep habits, as the risk ratios were 2.055 (95%CI: 1.683-2.508) and 3.140 (95%CI: 2.061-4.784) in children with single and combined allergic airway disease separately. Conclusion: Allergic rhinitis and bronchial asthma increased the risk of ADHD, not depending on sleep habits. Hence, allergic airway diseases could be independent risk factors of ADHD.

Fine structure of the acinar and duct cell components in the parotid and submandibular salivary glands of the rat: a TEM, SEM, and HRSEM study.

Parenchymal and stromal components of the rat parotid and submandibular glands were examined by conventional and high resolution scanning electron microscopy (HRSEM). Freeze-fractured specimens were subjected to HCl and NaOH extraction procedures to better differentiate connective tissue and cellular components. In addition, the internal three-dimensional morphology of the secretory acinar cells and duct cells was revealed by maceration with a dilute osmium tetroxide solution to selectively remove some of the cytoplasmic components. SEM and HRSEM examination of the HCl-treated samples of both glands revealed a fine filamentous network immediately surrounding each acinus. Coarser bundles of collagen that linked neighboring acini were also observed. NaOH-extracted samples selectively removed the cellular components and showed more clearly the three-dimensional structure of the connective-tissue stroma. A dense-collagenous network surrounded each lobule while more internal regions consisted of a honeycomb-like pattern of evacuated spaces previously occupied by secretory acini. These spaces were smoothened in appearance and often interconnected. Apically-located secretory granules and profiles of the rough endoplasmic reticulum and Golgi apparatus in perinuclear regions were encountered in the acinar and duct cells of macerated samples by HRSEM. In addition, a phenylephrine-induced experimental condition performed in some rats resulted in a significant increase in secretory granule size and density of the serous cells.

Investigation of allotypes of HLA class III (C2, BF and C4) in patients with schizophrenia.

The allotypes of HLA Class III (C2, BF and C4) in 60 patients with schizophrenia were investigated. Significantly higher frequencies of BF*F, BF*SO7 and C4A*4 in patients were found as compared with those of the normal controls. The relative risks (RR) of the three allotypes to schizophrenia were 1.81, 7.79 and 4.18 and the etiologic fraction (EF) were 0.086, 0.060 and 0.042, respectively. There were no significant changes of C2 allotypes.

Suppression of Frizzled-2-mediated Wnt/Ca²âº signaling significantly attenuates intracellular calcium accumulation in vitro and in a rat model of traumatic brain injury.

Traumatic brain injury (TBI) can dramatically increase levels of intracellular calcium (Ca²âº). The association between Wnt5a/Frizzled-2 (wingless-type mouse mammary tumor virus integration site family member 5a/Fzd2) signaling and Ca²âº cellular homeostasis in lower vertebrates has been well documented. However, little is known about Wnt5a/Fzd2 signaling in mammalian nerve cells, or whether Ca²âº accumulation after TBI is mediated through this pathway. We hypothesized that an activated Wnt5a/Fzd2 pathway following TBI may play a role in Ca²âº overloading. To elucidate the influence of Fzd2 and the Wnt5a signal transduction pathway on an increase in intracellular Ca²âº, we assessed the expression of Wnt5a/Fzd2 in rat hippocampal cells both in vitro and in vivo. We found that transfection of the rat Fzd2 gene in rat neonatal hippocampal astrocytes significantly increased gene expressions of both Wnt5a and Fzd2 by fourfold when compared to non-transfected cells (P<0.01 in both cases). Expressions of the proteins Wnt5a and Fzd2 were significantly increased approximately two- and threefold, respectively, when compared to non-transfected control cells (P<0.01 in both cases). Moreover, intracellular Ca²âº, as manifested by the fluorescent intensity of the intracellular Ca²âº indicator Fluo-3/AM, was significantly increased by 1.75-fold (P<0.01). The blocking of Fzd2 signaling using Stealth RNAi markedly inhibited the elevated gene and protein expression of Wnt5a in the transfected cells by two- and fourfold, respectively (P<0.01), and suppressed intracellular Ca²âº by 1.5-fold (P<0.01). Furthermore, in vivo, we demonstrated that TBI-induced dramatic upregulation of gene and protein expression of Wnt5a/Fzd2 by two- and fivefold (P<0.01) in injured hippocampi, and intracellular Ca²âº increased in isolated injured hippocampal cells. Whereas, the in vivo blocking of Fzd2 signaling by hippocampal delivery of Stealth RNAi and Invivofectamine significantly suppressed the increased gene and protein expression of Wnt5a and Fzd2 induced by TBI by 1- to 3.5-fold (P<0.01) and also inhibited Ca²âº accumulation by 1.5-fold (P<0.01). These findings demonstrated that the Wnt5a/Fzd2 signaling pathway contributed to increasing intracellular Ca²âº in nerve cells under physiological and pathological conditions. Furthermore, our findings provide evidence that specifically expressed components of this signal pathway, such as Wnt5a and Fzd2, are potential therapeutic targets following brain trauma.

Cellular immunologic response to primary cryoablation of C6 gliomas in rats.

The immunological consequences of cryoablation for gliomas are largely unknown. cryoablation is an attractive therapeutic option for tumors due to its minimally invasive nature. cryoablation is also potentially immunogenic. With an aim to explore changes in cellular immunity following argon-helium cryosurgery, we established Wistar rat models bearing subcutaneous C6 glioma and divided the rats into the normal control (30 rats), sham-operated (33 rats), surgical resection (30 rats), and cryosurgery (33 rats) groups with corresponding treatments. The tumor cell morphology was observed, and changes in the T lymphocyte subset and NK lymphocyte subset and the ratio of Th1/Th2 were assessed with flow cytometry following the cryosurgery. The results showed that subcutaneous tumor implantation was successful in all cases and this was confirmed histologically. Compared with surgical resection that caused significant reduction in CD3(+), CD4(+), CD14(+), CD16+56 cell percentages, cryosurgery resulted in significantly increased percentages of CD3(+), CD4(+), CD14(+), CD16+56 cells (P < 0.05) with a increase of the Th1/Th2 ratio 7 days after the operation. These results demonstrate that in addition to tumor cell destruction, cryosurgery also results in enhanced cellular immunity, suggesting the great potential of argon-helium cryosurgery in clinical management of gliomas.