Methylation- and homologous recombination deficiency-related mutant genes predict the prognosis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is a lung cancer subtype with poor prognosis. We investigated the prognostic value of methylation- and homologous recombination deficiency (HRD)-associated gene signatures in LUAD. METHODS: Data on RNA sequencing, somatic mutations, and methylation were obtained from TCGA database. HRD scores were used to stratify patients with LUAD into high and low HRD groups and identify differentially mutated and expressed genes (DMEGs). Pearson correlation analysis between DMEGs and methylation yielded methylation-associated DMEGs. Cox regression analysis was used to construct a prognostic model, and the distribution of clinical features in the high- and low-risk groups was compared. RESULTS: Patients with different HRD scores showed different DNA mutation patterns. There were 272 differentially mutated genes and 6294 differentially expressed genes. Fifty-seven DMEGs were obtained; the top 10 upregulated genes were COL11A1, EXO1, ASPM, COL12A1, COL2A1, COL3A1, COL5A2, DIAPH3, CAD, and SLC25A13, while the top 10 downregulated genes were C7, ERN2, DLC1, SCN7A, SMARCA2, CARD11, LAMA2, ITIH5, FRY, and EPHB6. Forty-two DMEGs were negatively correlated with 259 methylation sites. Gene ontology and pathway enrichment analysis of the DMEGs revealed enrichment of loci involved in extracellular matrix-related remodeling and signaling. Six out of the 42 methylation-associated DMEGs were significantly associated with LUAD prognosis and included in the prognostic model. The model effectively stratified high- and low-risk patients, with the high-risk group having more patients with advanced stage disease. CONCLUSION: We developed a novel prognostic model for LUAD based on methylation and HRD. Methylation-associated DMEGs may function as biomarkers and therapeutic targets for LUAD. Further studies are needed to elucidate their roles in LUAD carcinogenesis.

Computer-Vision-Based Vibration Tracking Using a Digital Camera: A Sparse-Optical-Flow-Based Target Tracking Method.

Computer-vision-based target tracking is a technology applied to a wide range of research areas, including structural vibration monitoring. However, current target tracking methods suffer from noise in digital image processing. In this paper, a new target tracking method based on the sparse optical flow technique is introduced for improving the accuracy in tracking the target, especially when the target has a large displacement. The proposed method utilizes the Oriented FAST and Rotated BRIEF (ORB) technique which is based on FAST (Features from Accelerated Segment Test), a feature detector, and BRIEF (Binary Robust Independent Elementary Features), a binary descriptor. ORB maintains a variety of keypoints and combines the multi-level strategy with an optical flow algorithm to search the keypoints with a large motion vector for tracking. Then, an outlier removal method based on Hamming distance and interquartile range (IQR) score is introduced to minimize the error. The proposed target tracking method is verified through a lab experiment-a three-story shear building structure subjected to various harmonic excitations. It is compared with existing sparse-optical-flow-based target tracking methods and target tracking methods based on three other types of techniques, i.e., feature matching, dense optical flow, and template matching. The results show that the performance of target tracking is greatly improved through the use of a multi-level strategy and the proposed outlier removal method. The proposed sparse-optical-flow-based target tracking method achieves the best accuracy compared to other existing target tracking methods.

Reversal of the immunosuppressive tumor microenvironment by nanoparticle-based activation of immune-associated cells.

Immunotherapy that activates the host immune system to reverse immunosuppression has emerged as a new generation of cancer treatment in both preclinical studies and clinical trials. Although immunotherapy has shown significant achievements in the treatment of various cancers, it faces challenges that limit its further evolution such as poor permeation and modest responsiveness. The development of nanoparticle drug delivery system has provided an opportunity to overcome these drawbacks and to achieve optimized immunotherapy. Based on the research of our group, we here introduce the new strategies being employed using nanoscale intelligent drug delivery systems to enhance the effects of cancer immunotherapy. We also provide a perspective on the further possible application of nanoparticles in more effective antitumor immunotherapy.

Comprehensive analysis of prognostic and immunological role of basement membrane-related genes in soft tissue sarcoma.

BACKGROUND: Soft tissue sarcoma (STS) represents highly multifarious malignant tumors that often occur in adolescents and have a poor prognosis. The basement membrane, as an ancient cellular matrix, was recently proven to play a vital role in developing abundant tumors. The relationship between basement membrane-related genes and STS remains unknown. METHODS: Consensus clustering was employed to identify subgroups related to differentially expressed basement membrane-related genes. Cox and least absolute shrinkage and selection operator regression analyses were utilized to construct this novel signature. Then, we established a nomogram and calibration curve, including the risk score and available clinical characteristics. Finally, we carried out functional enrichment analysis and immune microenvironment analysis to investigate enriched pathways and the tumor immune microenvironment related to the novel signature. RESULTS: A prognostic predictive signature consisting of eight basement membrane-related genes was established. Kaplan-Meier survival curves demonstrated that the patients in the high-risk group had a poor prognosis. Independent analysis illustrated that this risk model could be an independent prognostic predictor. We validated the accuracy of our signature in the validation data set. In addition, gene set enrichment analysis and immune microenvironment analysis showed that patients with low-risk scores were enriched in some pathways associated with immunity. Finally, in vitro experiments showed significantly differential expression levels of these signature genes in STS cells and PSAT1 could promote the malignant behavior of STS. CONCLUSIONS: The novel signature is a promising prognostic predictor for STS. The present study may improve the prognosis and enhance individualized treatment for STS in the future.

Study on synergistic inhibition and mechanism of flotation separation of fluorite and calcite by tannin and sodium humate.

At present, the separation technology of fluorite and calcite is still immature, and the research in this paper can promote the improvement of the separation technology of fluorite and calcite. The selective inhibition mechanism of tannin and humate sodium on calcite was studied by means of actual ore flotation test, single mineral flotation test, Zeta potential measurement and FT-IR spectroscopy. The results show that the mixture of tannin and sodium humate inhibitor has a good inhibitory effect on carbonate under weak alkaline condition. The reaction products of sodium humate, tannin and calcium ions in solution interact with organic compounds adsorbed on the surface of calcite, forming multilayer adsorption on the surface of calcite, making calcite more hydrophilic. Based on density functional theory, Materials Studio (MS) was used to calculate the relevant adsorption energy, and the result was as follows: (a) compared with fluorite, tannin and humate sodium molecules are more easily adsorbed on the surface of calcite. (b) Compared with calcite alone adsorption of tannin molecules or sodium humate molecules, the adsorption state will be more stable, and the effect of tannin and sodium humate synergistic inhibition of calcite is better than the effect of inhibition alone. Therefore, using tannin and sodium humate as a combination inhibitor can effectively separate fluorite and calcite, which will promote the development and utilization of fluorite ore in industry.

Traceability of chemicals from Tripterygium Wilfordii Hook. f. in raw honey and the potential synergistic effects of honey on acute toxicity induced by celastrol and triptolide.

The object of this study was to trace TwHf-derived toxins in raw honey and clarify their acute toxic effect related to the addition of honey or sugars. TwHf flowers, raw honey from TwHf planting base and from beekeepers in high-risk area were detected using LC-MS/MS. The results revealed five target toxins were detected in TwHf flowers; only celastrol was detected in one raw honey sample, as a food safety risk factor, celastrol had been traced back to TwHf flowers from raw honey. In a series of acute toxic tests on zebrafish, toxification effects were observed when honey, mimic honey or sugar was mixed with toxins. The degree of toxicity varied among various sugar-based solutions. At the same mass concentration, they follow this order: raw honey/mimic honey > glucose > fructose. The main toxic target organs of triptolide and celastrol with honey were the heart and liver.

Genetic variants in IL1A and IL1B contribute to the susceptibility to 2009 pandemic H1N1 influenza A virus.

BACKGROUND: Host genetic variations may contribute to disease susceptibility of influenza. IL-1A and IL-1B are important inflammatory cytokines that mediate the inflammation and initiate the immune response against virus infection. In this study, we investigated the relationship between single-nucleotide polymorphisms (SNPs) of Interleukin-1A (IL-1A) and Interleukin-1B (IL-1B) and the susceptibility to 2009 pandemic A/H1N1 influenza (A(H1N1)pdm09). 167 patients whom were confirmed with A(H1N1)pdm09 and 192 healthy controls were included in this study. Four SNPs (rs1304037, rs16347, rs17561, rs2071373) in IL1A gene and three SNPs (rs1143623, rs3917345, rs1143627) in IL1B gene were genotyped by using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry platform, and the associations of the genetic variants of IL-1 with susceptibility to A(H1N1)pdm09 were then assessed. RESULTS: The polymorphisms of rs17561 in IL1A gene and rs1143627 in IL1B gene were found to be associated with susceptibility to A(H1N1)pdm09 with P values of 0.003 (OR 2.08, 95% CI 1.27-3.41) and 0.002 (OR 1.62 , 95% CI 1.20-2.18), respectively. However, no significant difference in allelic frequency was observed for other SNPs between cases and controls. CONCLUSIONS: This study provides a new insight into pathogenesis of A(H1N1)pdm09, suggesting that genetic variants of IL-1A and IL-1B may exert a substantial impact on the susceptibility of A(H1N1)pdm09 virus infection.

[Quantization determination study of micro-Raman spectroscopy of methemoglobin induced by sodium nitrite].

In the present study, Raman spectral characteristics of methemoglobin (MetHb) induced by sodium nitrite (NaNO2) were investigated. Hemoglobin (Hb) was oxidated to MetHb with NaNO2, the Raman spectral specific changes of MetHb was studied by determining the Raman spectral changes of methemoglobin/total hemoglobin of different ratios, and the Raman intensities of methemoglobin/total hemoglobin of different ratios at 1 586, 1 605 and 1 637 cm(-1) were linearly fitted to realize its quantitative detection. The results show that the completely oxidized MetHb can be obtained when the molar ratio of NaNO2 to Hb is 3.5 : 1 whose Raman characteristic peaks are at around 499, 1 340, 1 562 and 1 622 cm(-1), and that the linear fitting correlation coefficients R2 of the Raman intensities of methemoglobin/total hemoglobin of different ratios at 1 586, 1 605 and 1 637 cm(-1) are 0.972 84, 0.997 97 and 0.991 26 respectively, which shows a good linear relationship. This study indicates that the Raman spectrums of MetHb induced by NaNO2 have characteristic differences when compared with normal Hb, that the locations and intensities of Raman characteristic peaks change correspondingly with the alterations of the ratios of methemoglobin/total hemoglobin, and that there are linear correlations between the ratios and their corresponding Raman intensities, which would provide theoretical bases for the clinical Raman spectral detection and quantitative study of methemoglobinemia.

[Raman spectroscopy study of the effect of H+ on the oxygen affinity capacity of hemoglobin].

The hemoglobin was extracted from the blood which was provided by the healthy volunteers and the impact of the pH on hemoglobin oxygen binding capacity was studied with microscopic Raman spectroscopy. The results indicated that: under the excitation light of 514.5 nm, with the reducing of the oxygen partial pressure (PO2), the Raman peak intensity at 1 375, 1 562, 1 585 and 1 638 cm(-1) of the control hemoglobin (pH 7.4) reduced gradually, among which, the change of the 1 375 and 1 638 cm(-1) were the most significant and had a good relevance with the PO2. The curves were plotted by regarding the PO2 as the x-axis and the Raman absolute intensity as the y-axis, and the relationship between hemoglobin Raman absolute intensity of the 1 375 and 1 638 cm(-1) and their related PO2 levels when the pH was 5.7, 7.4 and 8.0 respectively were analyzed. The data was well linear fitted and the fitting equation was obtained. The relationship of the slope (Raman intensity/PO2 level) among them were K8.0 > K7.4 > K5.7, indicating that the lower the pH, the easier the release of the oxygen molecules. It was showed that the Raman spectroscopy technique could be used to detect the oxygen binding rate of hemoglobin quantitatively, and the effect of the PH on oxygen binding state of hemoglobin could be observed, which could provide a new method and make a foundation for the monitoring of the PO2 levels in the blood, as well as the research on the regulatory factors of the blood oxygen affinity, such as H+ and CO2.

[Observation of intraoperative lower limb blood flow of infrarenal aortic occlusion].

OBJECTIVE: To summarize the surgical therapy and profiles of lower limb blood flow during surgery for chronic infrarenal aortic occlusion. METHODS: A total of 36 patients of chronic infrarenal aortic occlusion underwent surgical procedures at our department from 2004 to 2011. Their clinical data were analyzed. Several methods were applied at different time points during surgery to observe the lower limb blood flow. RESULTS: SaO2, waveforms of dorsalis pedis artery and posterior tibial artery changed dramatically at different time points during surgery. Before and after blood occlusion, the SaO2 was 82% ± 6% and 23% ± 4% respectively, 1min after unclamped and after abdomen-closing, the SaO2 increased to 66% ± 5% and 88% ± 8% respectively. CONCLUSION: Doppler blood flow and blood oxygen saturation monitors are simple, non-invasive and objective detection methods for lower limb blood flow. A combination of both methods can improve the safety of surgery. Keeping the limbs warm and uses of spasmolytic drugs can facilitate the recovery of postoperative blood flow of lower limbs.

[Chromaticity and optical spectrum colorimetry of the tongue color in different syndromes of primary hepatic carcinoma].

OBJECTIVE: In this study, the optical data of tongue color of different syndromes in primary hepatic carcinoma (PHC) were detected by optical spectrum colorimetry, and the chromaticity of tongue color was compared and analyzed. The tongue color characteristics of different syndromes in PHC and the relationship between different syndromes and tongue color were also investigated. METHODS: Tongue color data from 133 eligible PHC patients were collected by optical spectrum colorimetry and the patients were divided into 4 syndrome groups according to their clinical features. The syndrome groups were liver depression and spleen deficiency (LDSD), accumulation of damp-heat (ADH), deficiency of liver and kidney yin (DLKY), and qi stagnation and blood stasis (QSBS). The variation characteristics of chromaticity coordinates, dominant wavelength, excitation purity and the distribution in the International Commission on Illumination (CIE) LAB uniform color space were measured. At the same time, the differences of overall chromatism, clarity, chroma, saturation and hue were also calculated and analyzed. RESULTS: PHC patients in different syndrome groups exhibited differences in chromaticity coordinates. The dominant wavelength of QSBS was distinctly different from that of the other 3 syndromes. Excitation purity in the syndromes of LDSD, ADH and DLKY showed gradual increases (P<0.01). Different syndromes in the CIE LAB color three-dimensional space showed differences in tongue color distribution areas. The CIE hue-angle value of QSBS was negative, and different from that of the other 3 syndromes (P<0.01). CIE chroma in the syndromes of LDSD, ADH and DLKY showed gradual increases (P<0.01), the same as excitation purity. In the comparison of chromatism, tongue color variations in different syndromes were quantified by human observation. CONCLUSION: This study shows that tongue color diagnosis according to the syndrome classifications of traditional Chinese medicine can be quantified with optical spectrum colorimetry technology. Different syndromes in PHC exhibit distinct chromatisms of tongue color through the calculation and analysis of chromaticity parameters of CIE, combined with colorimetric system and CIE LAB color space, and these are consistent with the characteristics of clinical tongue color. Applying optical spectrum colorimetry technology to tongue color differentiation has the potential to serve as a reference point in standardizing traditional Chinese medicine syndrome classification in PHC.

DNA: Deeply Supervised Nonlinear Aggregation for Salient Object Detection.

Recent progress on salient object detection mainly aims at exploiting how to effectively integrate multiscale convolutional features in convolutional neural networks (CNNs). Many popular methods impose deep supervision to perform side-output predictions that are linearly aggregated for final saliency prediction. In this article, we theoretically and experimentally demonstrate that linear aggregation of side-output predictions is suboptimal, and it only makes limited use of the side-output information obtained by deep supervision. To solve this problem, we propose deeply supervised nonlinear aggregation (DNA) for better leveraging the complementary information of various side-outputs. Compared with existing methods, it: 1) aggregates side-output features rather than predictions and 2) adopts nonlinear instead of linear transformations. Experiments demonstrate that DNA can successfully break through the bottleneck of the current linear approaches. Specifically, the proposed saliency detector, a modified U-Net architecture with DNA, performs favorably against state-of-the-art methods on various datasets and evaluation metrics without bells and whistles.

Epidemiological and clinical features of 308 hospitalized patients with novel 2009 influenza A (H1N1) virus infection in China during the first pandemic wave.

OBJECTIVES: To investigate the epidemiological and clinical features of 308 hospitalized patients suffering from infection with novel H1N1 influenza virus in China from May to August 2009, and to examine the effects of oseltamivir treatment for mild cases. METHODS: Information on H1N1 influenza patients confirmed by real-time RT-PCR assay was gathered and analyzed from an influenza surveillance system, including demographic features, clinical symptoms and signs, therapeutic regimen, and duration of fever and virus shedding. RESULTS: The clinical course of infected individuals appeared mild. Mainly young adults were affected. Most cases had low or mid-level fever, cough, headache, rhinorrhoea, and sore throat. Few patients had vomiting (1.3%) and diarrhea (3.9%). Oseltamivir treatment did not shorten the duration of fever. Furthermore, early oseltamivir treatment as well as early conventional supportive treatment without antiviral drugs contributed to a reduction in the duration of virus shedding. CONCLUSIONS: In the first pandemic wave, novel H1N1 virus caused disease primarily in adults, causing mild febrile illness. Mildly ill patients cleared the virus rapidly even in the absence of oseltamivir treatment.

[Application and evaluation of a pseudotyped virus assay for screening herbs for anti-H5N1 avian influenza virus].

OBJECTIVE: To establish a method based on a pseudotyped virus assay for screening drugs for anti-H5N1 avian influenza virus, and then to evaluate anti-virus activity of traditional Chinese herbal compounds with the function of purgation, detoxification, cooling the blood and reinforcing the healthy qi based on seropharmacology. METHODS: Pseudotyped viruses expressing H5N1 virus hemagglutinin were constructed. Herb-medicated sera were prepared by feeding Wistar rats traditional Chinese herbal compounds. Then inhibitory effects of different drug-medicated sera against pseudotyped virus were evaluated based on incubating serum with pseudotyped viruses or target cells such as Madin-Darby canine kidney cells and human embryonic kidney cell line 293T cells, and the expression of hemagglutinin (HA) protein was detected by flow cytometry. RESULTS: Pseudotyped virus could be neutralized by specific 2B4 monoclonal antibody at doses of 50 µL (500 µg), 25 µL (250 µg) and 12.5 µL (125 µg), which showed that it was a feasible assay to screen drugs. No significant difference was observed in inhibition against H5N1 pseudotyped virus between herb-medicated sera and control serum (P>0.05), meanwhile, the herb-medicated sera also could not inhibit HA expression. CONCLUSION: Pseudotyped virus assay is a safe, effective, and exact method for screening anti-H5N1 avian influenza virus herbs, and herb-medicated sera prepared by administration of herbs with the function of purgation, detoxification, cooling the blood and reinforcing the healthy qi do not contain active ingredient or monomer which can inhibit HA and sialic acid-α 2,3-galatose.

Analysis on Mitigation of Visually Induced Motion Sickness by Applying Dynamical Blurring on a User's Retina.

Visually induced motion sickness (MS) experienced in a 3D immersive virtual environment (VE) limits the widespread use of virtual reality (VR). This paper studies the effects of a saliency detection-based approach on the reduction of MS when the display on a user's retina is dynamic blurred. In the experiment, forty participants were exposed to a VR experience under a control condition without applying dynamic blurring, and an experimental condition applying dynamic blurring. The experimental results show that the participants under the experimental condition report a statistically significant reduction in the severity of MS symptoms on average during the VR experience compared to those under the control condition, which demonstrates that the proposed approach may alleviate visually induced MS in VR and enable users to remain in a VE for a longer period of time.

Do the mutations of C1GALT1C1 gene play important roles in the genetic susceptibility to Chinese IgA nephropathy?

BACKGROUND: The deficiency of beta1,3 galactose in hinge region of IgA1 molecule played a pivotal role in pathogenesis of IgA nephropathy (IgAN). Cosmc, encoded by C1GALT1C1 gene, was indispensable to beta1,3 galactosylation of IgA1. We designed a serial study to investigate the relationship between the mutations of C1GALT1C1 gene and the genetic susceptibility to IgAN. METHODS: Nine hundred and thirty-eight subjects, including 661 patients with IgAN and 277 healthy controls were enrolled in the study. Firstly, single nucleotide polymorphisms (SNPs) in the promoter region of C1GALT1C1 gene were screened. Then the c.-347-190G>A was analyzed by PCR-restriction fragment length polymorphism (PCR-RFLP) for further case-control association analysis. Secondly the somatic mutations of DNAs from peripheral blood B lymphocytes were detected in 15 patients and 7 normal controls. RESULTS: No significant association was observed between the different alleles or genotypes of c.-347-190G>A and IgAN. The patients with different genotypes of C1GALT1C1 gene did not significantly associate with clinical manifestations, including hematuria, proteinuria, and serum creatinine of patients with IgAN. There was no somatic mutation detected in total 202 clones of 22 individuals. CONCLUSION: The c.-347-190G>A polymorphism and the somatic mutation of encoding region of C1GALT1C1 gene were not significantly related to the genetic susceptibility to IgAN in Northern Chinese population.

[Diagnosis and prediction of lung cancer through different classification techniques with tumor markers].

OBJECTIVE: To study which classification model was most suitable for establishing a multi-tumor markers lung cancer prediction model, through established logistic regression model, decision trees model and artificial neural network model. METHODS: RIA analysis, ELISA, spectrophotometry, high-performance liquid chromatography (HPLC) and atomic absorption spectrometry were used to measure the serum CEA, CA125, gastrin, NSE, beta2-MG, Sil-6 receptors, sialic acid, nitric oxide, Cu, Zn, Ca and the pseudo-urine nucleoside of urine samples in lung cancer patients, benign lung disease patients and healthy controls. The lung cancer diagnosis models were established by logistic regression analysis, decision tree analysis and artificial neural network training. RESULTS: The diagnosis sensitivities of the logistic regression analysis, decision tree analysis and artificial neural network model with 12 tumor markers in lung cancer were 94.00%, 100.00% and 100.00%; the specificity were 100.00%, 98.89% and 100.00%; the total accurate 94.29%, 95.00% and 90.00%, respectively. CONCLUSION: The results of three classification models with 12 tumor markers in diagnosis of lung cancer are ideal. Especially the C5.0 decision tree model and the artificial neural network model are more suitable for the prediction and diagnosis of the lung cancer.

Electric Field-Assisted In Situ Precise Deposition of Electrospun γ-Fe2O3/Polyurethane Nanofibers for Magnetic Hyperthermia.

A facial electrospinning method of in situ precise fabricating magnetic fibrous membrane composed of polyurethane (PU) nanofibers decorated with superparamagnetic γ-Fe2O3 nanoparticles with simultaneous heat generation in response to alternating magnetic field (AMF) is reported. In this method, a conical aluminum auxiliary electrode is used to regulate the electrostatic field and affect the process of electrospinning for the in situ rapid and precise deposition of electrospun γ-Fe2O3/PU fibers. The auxiliary conical electrode can extend the jet stabilization zone of the precursor solution four times longer than that of without auxiliary electrode, which can achieve the precise control of the fiber deposition area. Moreover, the electrospun composite fibrous membranes show a rapid temperature increase from room temperature to 43 °C in 70 s under the AMF, which exhibits faster heating rate and higher heating temperature compared to the samples fabricated without the assist of the auxiliary electrode. The present results demonstrate that the in situ precise electrospinning with the help of an auxiliary conical electrode has the potential as a manipulative method for preparing magnetic composite fibers as well as magnetic hyperthermia of cancer therapy.

Electrically Conductive TPU Nanofibrous Composite with High Stretchability for Flexible Strain Sensor.

Highly stretchable and electrically conductive thermoplastic polyurethane (TPU) nanofibrous composite based on electrospinning for flexible strain sensor and stretchable conductor has been fabricated via in situ polymerization of polyaniline (PANI) on TPU nanofibrous membrane. The PANI/TPU membrane-based sensor could detect a strain from 0 to 160% with fast response and excellent stability. Meanwhile, the TPU composite has good stability and durability. Besides, the composite could be adapted to various non-flat working environments and could maintain opportune conductivity at different operating temperatures. This work provides an easy operating and low-cost method to fabricate highly stretchable and electrically conductive nanofibrous membrane, which could be applied to detect quick and tiny human actions.