The causal associations of circulating lipids with Barrett's Esophagus and Esophageal Cancer: a bi-directional, two sample mendelian randomization analysis.

OBJECTIVE: The causal associations of circulating lipids with Barrett's Esophagus (BE) and Esophageal Cancer (EC) has been a topic of debate. This study sought to elucidate the causality between circulating lipids and the risk of BE and EC. METHODS: We conducted two-sample Mendelian randomization (MR) analyses using single nucleotide polymorphisms (SNPs) of circulating lipids (n = 94,595 - 431,167 individuals), BE (218,792 individuals), and EC (190,190 individuals) obtained from the publicly available IEU OpenGWAS database. The robustness and reliability of the results were ensured by employing inverse-variance weighted (IVW), weighted median, MR-Egger, and MR-PRESSO methods. The presence of horizontal pleiotropy, heterogeneities, and stability of instrumental variables were assessed through MR-Egger intercept test, Cochran's Q test, and leave-one-out sensitivity analysis. Additionally, bidirectional MR and multivariable MR (MVMR) were performed to explore reverse causality and adjust for known confounders, respectively. RESULTS: None of the testing methods revealed statistically significant horizontal pleiotropy, directional pleiotropy, or heterogeneity. Univariate MR analyses using IVW indicated a robust causal relationship between increased triglycerides and BE (odds ratio [OR] = 1.79, p-value = 0.009), while no significant association with EC was observed. Inverse MR analysis indicated no evidence of reverse causality in the aforementioned outcomes. In MVMR analyses, elevated triglycerides (TRG) were significantly and positively associated with BE risk (OR = 1.79, p-value = 0.041). CONCLUSION: This MR study suggested that genetically increased triglycerides were closely related to an elevated risk of BE, potentially serving as a biomarker for the diagnosis of BE in the future.

Association of PLXND1 with a novel subtype of anomalous pulmonary venous return.

Anomalous pulmonary venous return (APVR) is a potentially lethal congenital heart disease. Elucidating the genetic etiology is crucial for understanding its pathogenesis and improving clinical practice, whereas its genetic basis remains largely unknown because of complex genetic etiology. We thus performed whole-exome sequencing for 144 APVR patients and 1636 healthy controls and report a comprehensive atlas of APVR-related rare genetic variants. Novel singleton, loss-of-function and deleterious missense variants (DVars) were enriched in patients, particularly for genes highly expressed in the developing human heart at the critical time point for pulmonary veins draining into the left atrium. Notably, PLXND1, encoding a receptor for semaphorins, represents a strong candidate gene of APVR (adjusted P = 1.1e-03, odds ratio: 10.9-69.3), accounting for 4.17% of APVR. We further validated this finding in an independent cohort consisting of 82 case-control pairs. In these two cohorts, eight DVars were identified in different patients, which convergently disrupt the GTPase-activating protein-related domain of PLXND1. All variant carriers displayed strikingly similar clinical features, in that all anomalous drainage of pulmonary vein(s) occurred on the right side and incorrectly connected to the right atrium, which may represent a novel subtype of APVR for molecular diagnosis. Studies in Plxnd1 knockout mice further revealed the effects of PLXND1 deficiency on severe heart and lung defects and cellular abnormalities related to APVR such as abnormal migration and vascular formation of vascular endothelial cells. These findings indicate the important role of PLXND1 in APVR pathogenesis, providing novel insights into the genetic etiology and molecular subtyping for APVR.

Periodically tunable multimode soliton pulsation in a spatiotemporal mode-locked fiber laser.

Multimode fiber lasers have become a new platform for investigating nonlinear phenomena since the report on spatiotemporal mode-locking. In this work, the multimode soliton pulsation with a tunable period is achieved in a spatiotemporal mode-locked fiber laser. It demonstrates that the pulsation period drops while increasing the pump power. Moreover, it is found that different transverse modes have the same pulsation period, asynchronous pulsation evolution and different dynamical characteristics through the spatial sampling technique and the dispersive Fourier transform technique. To further verify the experimental results, we numerically investigate the influences of the gain and the loss on the pulsation properties. It is found that within a certain parameter range, the pulsation period drops and rises linearly with the increase of the gain and the loss, respectively. The obtained results contribute to understanding the formation and regulating of soliton pulsations in fiber lasers.

Spatiotemporal dual-periodic soliton pulsation in a multimode fiber laser.

Spatiotemporal mode-locked (STML) fiber lasers have become a new platform for investigating nonlinear phenomena. In this work, spatiotemporal dual-periodic soliton pulsation (SDSP) is firstly observed in an STML fiber laser. It is found that in the SDSP, the long-period pulsations (LPPs) of different transverse modes are synchronous, while the short-period pulsations (SPPs) exhibit asynchronous modulations. The numerical simulation confirms the experimental results and further reveals that the proportion of transverse mode components can manipulate the periods of the LPP and SPP but does not affect the synchronous and asynchronous pulsations of different transverse modes. The obtained results bring the study of spatiotemporal dissipative soliton pulsation into the multi-period modulation stage, which helps to understand the complex spatiotemporal dynamics in STML fiber lasers and discover new dynamics in high-dimensional nonlinear systems.

Identifying nitrate sources and transformations in an agricultural watershed in Northeast China: Insights from multiple isotopes.

Accurate identification of riverine nitrate sources is required for preventing and controlling nitrogen contamination in agricultural watersheds. The water chemistry and multiple stable isotopes (δ15N-NO3, δ18O-NO3, δ2H-H2O, and δ18O-H2O) of the river water and groundwater in an agricultural watershed in China's northeast black soil region were analyzed to better understand the sources and transformations of riverine nitrogen. Results showed that nitrate is an important pollutant that affects water quality in this watershed. Affected by factors such as seasonal rainfall changes and spatial differences in land use, the nitrate concentrations in the river water showed obvious temporal and spatial variations. The riverine nitrate concentration was higher in the wet season than in the dry season, and higher downstream than upstream. The water chemistry and dual nitrate isotopes revealed that riverine nitrate came primarily from manure and sewage (M&S). Results from the SIAR model showed that it accounted for more than 40% of riverine nitrate in the dry season. The proportional contribution of M&S decreased during the wet season due to the increased contribution of chemical fertilizers and soil nitrogen induced by large amounts of rainfall. The δ2H-H2O and δ18O-H2O signatures implied that interactions occurred between the river water and groundwater. Considering the large accumulation of nitrates in the groundwater, restoring groundwater nitrate levels is essential for controlling riverine nitrate pollution. As a systematic study on the sources, migration, and transformations of nitrate/nitrogen in agricultural watersheds in black soil regions, this research can provide a scientific support for nitrate pollution management in the Xinlicheng Reservoir watershed and provide a reference for other watersheds in black soil regions in the world with similar conditions.

Optimizing environmental flow based on a new optimization model in balancing objectives among river ecology, water supply and power generation in a high-latitude river.

Environmental flow plays an important role in maintaining the health of river ecosystems and aquatic habitats. Although ecological regulation of environmental flow has attracted the attention of scientists, managing the world's reservoir-regulated rivers to better meet the needs of human being and ecosystems is a complex social challenge. To address the above issues, we constructed a model for optimizing reservoir operation based on a balance in achieving multi objectives among environmental flow, water supply and power generation (EWP). The model was solved using an intelligent multi-objective optimization algorithm (ARNSGA-III). The developed model was demonstrated in a large reservoir, Laolongkou Reservoir in the Tumen River. The results showed that the reservoir altered environmental flows mainly in terms of flow magnitude, peak, times, duration and frequency, which result in a sharp decrease in spawning fish, and degradation and replacement of vegetation along the channels. In addition, the mutual feedback relationship between the objectives of environmental flows, water supply and power generation is not static, but varies over time and space. The constructed model based on Indicators of Hydrologic Alteration (IHAs) can effectively guarantee the environmental flow at daily scale. In detail, the river ecological benefit increased by 64% in wet year, 68% in normal year, 68% in dry year after optimizing regulation of reservoir, respectively. This study will provide a scientific reference for the optimizing of the management in other rivers affected by dams.

Phage nanoparticle as a carrier for controlling fungal infection.

A mass of nanocarriers have been exploited and utilized for prevention of fungi, including organic nanomaterials, inorganic nanoparticles, polypeptides, and viruses. Due to biological safety and flexible genetic engineering property, bacteriophages, as bionanoparticles, are widely used in the diagnosis and treatment of microorganisms, which can be easily loaded with proteins and drugs. In particular, random DNAs can be inserted into the genome of phage by phage display technology, and it is possible to obtain the peptide/antibody targeting fungi from phage library. Meanwhile, phages displaying specific peptides are able to conjugate with other nanoparticles, which have both characteristics of peptides and nanomaterials, and have been used for precise detection of fungi. Additionally, phage nanomaterials as carriers can reduce the toxicity of drugs, increase the time of drug circulation, stimulate the immune response, and have an anti-fungal effect by itself. In this review, we summarize the recent applications of bacteriophages on the study of fungi. The improvement of our understanding of bacteriophage will supply new tools for controlling fungal infections. These phage libraries were used to pan the specific peptides for diagnosis, prevention, and treatment of fungi. KEY POINTS: • System fungal infection has no significant clinical symptoms; it is important to develop vaccine, diagnosis, and therapeutic agents to reduce mortality; phage is an ideal carrier for vaccine and drug to stimulate immune response and improve the efficiency of drug, and also can improve the sensitivity of detection • This review summarized recent studies on phage-based fungal vaccine and threw light on the developing therapeutic phage in the treatment of fungal infection.

FastProNGS: fast preprocessing of next-generation sequencing reads.

BACKGROUND: Next-generation sequencing technology is developing rapidly and the vast amount of data that is generated needs to be preprocessed for downstream analyses. However, until now, software that can efficiently make all the quality assessments and filtration of raw data is still lacking. RESULTS: We developed FastProNGS to integrate the quality control process with automatic adapter removal. Parallel processing was implemented to speed up the process by allocating multiple threads. Compared with similar up-to-date preprocessing tools, FastProNGS is by far the fastest. Read information before and after filtration can be output in plain-text, JSON, or HTML formats with user-friendly visualization. CONCLUSIONS: FastProNGS is a rapid, standardized, and user-friendly tool for preprocessing next-generation sequencing data within minutes. It is an all-in-one software that is convenient for bulk data analysis. It is also very flexible and can implement different functions using different user-set parameter combinations.

Analysis and inspection techniques for mouse liver injury based on terahertz spectroscopy.

At present, researchers are exploring biological tissue detection method using terahertz techniques. In this paper, techniques to inspect mouse liver injury by using terahertz spectroscopy were studied. The boxplots were applied to remove abnormal data, and the maximal information coefficient was employed to select crucial features from the absorption coefficient and refractive index spectra. Random Forests and AdaBoost were applied to recognize different levels of liver injury. We found that AdaBoost had better performance on low-level injury classification. This work suggests that terahertz techniques have the potential to detect liver injury at an early stage and evaluate liver treatment strategies.

Mechanical Respond and Failure Mode of Large Size Honeycomb Sandwiched Composites under In-Plane Shear Load.

The present work focuses on the in-plane shear respond and failure mode of large size honeycomb sandwich composites which consist of plain weave carbon fabric laminate skins and aramid paper core. A special size specimen based on a typical element of aircraft fuselage was designed and manufactured. A modified in-plane shear test method and the corresponding fixture was developed. Three large size specimens were tested. The distributed strain gauges were used to monitor the mechanical response and ultimate bearing capacity. The results show that a linear respond of displacement and strain appears with the increase of the load. The average shear failure load reaches 205.68 kN with the shear failure occurring on the face sheet, and the maximum shear strain monitored on the composite plate is up to 16,115 µÎµ. A combination of theoretical analysis and finite element method (FEM) was conducted to predict the shear field distribution and the overall buckling load. The out-of-plane displacement field distribution and in-plane shear strain field distribution under the pure shear loading were revealed. The theoretical analysis method was deduced to obtain the variation rule of the shear buckling load. A good agreement was achieved among the experiment, theoretical analysis, and FEM results. It can be concluded that the theoretical analysis method is relatively conservative, and the FEM is more accurate in case of deformation and strain. The results predicted by h element and p element methods are very close. The results of the study could provide data support for the comprehensive promotion of the design and application of honeycomb sandwich composites.

Isoalantolactone induces apoptosis through reactive oxygen species-dependent upregulation of death receptor 5 in human esophageal cancer cells.

Esophageal cancer is the eighth most prevalent cancer and has high mortality in our society. Isoalantolactone, extracted from Inula helenium L, has shown potent anticancer effects on a variety of cancers. However, its effect on human esophageal cancer, and the underlying molecular mechanism, remain to be investigated. In the present study, we demonstrated that isoalantolactone induced apoptosis in esophageal cancer cells. Treatment with isoalantolactone activated caspases-3, -7, and -10, and upregulated death receptor (DR)5. Furthermore, DR5 knockdown partially reversed the effect of isoalantolactone. These results indicated the extrinsic apoptosis was induced by isoalantolactone. In addition, intracellular reactive oxygen species (ROS) were significantly elevated after treatment with isoalantolactone. N-Acetylcysteine, an ROS scavenger, blocked both the apoptosis and decreased cell viability caused by isoalantolactone. In vivo, significant suppression of tumor growth by isoalantolactone was observed in an ECA109 cell xenograft mouse model. Isoalantolactone showed no obvious adverse effects on mouse weight and histology of heart, liver, spleen, lung, and kidney. In conclusion, our results revealed that isoalantolactone induced apoptosis through the extrinsic pathway via upregulation of DR5 and elevation of ROS in human esophageal cancer cells. Isoalantolactone, therefore, could be a potential candidate in developing anticancer agents for esophageal cancer patients.

Application of Least-Squares Support Vector Machines for Quantitative Evaluation of Known Contaminant in Water Distribution System Using Online Water Quality Parameters.

In water-quality, early warning systems and qualitative detection of contaminants are always challenging. There are a number of parameters that need to be measured which are not entirely linearly related to pollutant concentrations. Besides the complex correlations between variable water parameters that need to be analyzed also impairs the accuracy of quantitative detection. In aspects of these problems, the application of least-squares support vector machines (LS-SVM) is used to evaluate the water contamination and various conventional water quality sensors quantitatively. The various contaminations may cause different correlative responses of sensors, and also the degree of response is related to the concentration of the injected contaminant. Therefore to enhance the reliability and accuracy of water contamination detection a new method is proposed. In this method, a new relative response parameter is introduced to calculate the differences between water quality parameters and their baselines. A variety of regression models has been examined, as result of its high performance, the regression model based on genetic algorithm (GA) is combined with LS-SVM. In this paper, the practical application of the proposed method is considered, controlled experiments are designed, and data is collected from the experimental setup. The measured data is applied to analyze the water contamination concentration. The evaluation of results validated that the LS-SVM model can adapt to the local nonlinear variations between water quality parameters and contamination concentration with the excellent generalization ability and accuracy. The validity of the proposed approach in concentration evaluation for potassium ferricyanide is proven to be more than 0.5 mg/L in water distribution systems.

MicroRNA-200c and microRNA- 141 are regulated by a FOXP3-KAT2B axis and associated with tumor metastasis in breast cancer.

BACKGROUND: Members of the microRNA (miR)-200 family, which are involved in tumor metastasis, have potential as cancer biomarkers, but their regulatory mechanisms remain elusive. METHODS: We investigated FOXP3-inducible breast cancer cells, Foxp3 heterozygous Scurfy mutant (Foxp3 sf/+ ) female mice, and patients with breast cancer for characterization of the formation and regulation of the miR-200 family in breast cancer cells and circulation. Participants (259), including patients with breast cancer or benign breast tumors, members of breast cancer families, and healthy controls, were assessed for tumor and circulating levels of the miR-200 family. RESULTS: First, we identified a FOXP3-KAT2B-miR-200c/141 axis in breast cancer cells. Second, aging Foxp3 sf/+ female mice developed spontaneous breast cancers and lung metastases. Levels of miR-200c and miR-141 were lower in Foxp3 sf/+ tumor cells than in normal breast epithelial cells, but plasma levels of miR-200c and miR-141 in the Foxp3 sf/+ mice increased during tumor progression and metastasis. Third, in patients with breast cancer, the levels of miR-200c and 141 were lower in FOXP3 low relative to those with FOXP3 high breast cancer cells, especially in late-stage and metastatic cancer cells. The levels of miR-200c and miR-141 were higher in plasma from patients with metastatic breast cancer than in plasma from those with localized breast cancer, with benign breast tumors, with a family history of breast cancer, or from healthy controls. Finally, in Foxp3 sf/+ mice, plasma miR-200c and miR-141 appeared to be released from tumor cells. CONCLUSIONS: miR-200c and miR-141 are regulated by a FOXP3-KAT2B axis in breast cancer cells, and circulating levels of miR-200c and miR-141 are potential biomarkers for early detection of breast cancer metastases.

CD24 is a genetic modifier for risk and progression of prostate cancer.

CD24 plays an oncogenic role in the onset and progression of various human cancers, including prostate cancer. In the present study, we identified two linkage disequilibrium blocks with four recombination hotspot motifs in human CD24 locus. To elucidate whether genetic variants of CD24 are associated with susceptibility to prostate cancer and its disease status, we conducted a case-control association study with two P170 C/T and P-534 A/C polymorphisms of CD24 in 590 patients with prostate cancer and 590 healthy controls. A significant increased risk of prostate cancer was found in men with the P170T/T genotype over the P170C/C genotype (odd ratio = 1.74, 95% confidence interval = 1.16-2.63, P = 0.008), and in men with the P-534C/C genotype over the P-534A/A genotype (odd ratio = 1.47, 95% CI = 1.18-2.26, P = 0.003). Cochran-Armitage trend analysis showed that the P170T allele was significantly correlated with an increased risk of prostate cancer progression (P = 0.029, trend between genotypes and stages) and this observation was also validated in an independent sample cohort. Next, we found that tumors with P170T or P-534C alleles had more twofold increased protein expressions of CD24 as compared to those with P170C or P-534A alleles, respectively. Likewise, tumors with a combination of P170T/T and P-534C/C genotypes were associated with a high mRNA level of CD24. Our data suggest a significant association of CD24 genetic variants with prostate cancer onset and progression, which provides new insight into molecular genetics of prostate cancer; however, these findings need to be validated in multiple independent cohorts. © 2016 Wiley Periodicals, Inc.

In situ detection of water quality contamination events based on signal complexity analysis using online ultraviolet-visible spectral sensor.

The contaminant detection in water distribution systems is essential to protect public health from potentially harmful compounds resulting from accidental spills or intentional releases. As a noninvasive optical technique, ultraviolet-visible (UV-Vis) spectroscopy is investigated for detecting contamination events. However, current methods for event detection exhibit the shortcomings of noise susceptibility. In this paper, a new method that has less sensitivity to noise was proposed to detect water quality contamination events by analyzing the complexity of the UV-Vis spectrum series. The proposed method applied approximate entropy (ApEn) to measure spectrum signals' complexity, which made a distinction between normal and abnormal signals. The impact of noise was attenuated with the help of ApEn's insensitivity to signal disturbance. This method was tested on a real water distribution system data set with various concentration simulation events. Results from the experiment and analysis show that the proposed method has a good performance on noise tolerance and provides a better detection result compared with the autoregressive model and sequential probability ratio test.

Online Classification of Contaminants Based on Multi-Classification Support Vector Machine Using Conventional Water Quality Sensors.

Water quality early warning system is mainly used to detect deliberate or accidental water pollution events in water distribution systems. Identifying the types of pollutants is necessary after detecting the presence of pollutants to provide warning information about pollutant characteristics and emergency solutions. Thus, a real-time contaminant classification methodology, which uses the multi-classification support vector machine (SVM), is proposed in this study to obtain the probability for contaminants belonging to a category. The SVM-based model selected samples with indistinct feature, which were mostly low-concentration samples as the support vectors, thereby reducing the influence of the concentration of contaminants in the building process of a pattern library. The new sample points were classified into corresponding regions after constructing the classification boundaries with the support vector. Experimental results show that the multi-classification SVM-based approach is less affected by the concentration of contaminants when establishing a pattern library compared with the cosine distance classification method. Moreover, the proposed approach avoids making a single decision when classification features are unclear in the initial phase of injecting contaminants.

Targeting CD133(+) laryngeal carcinoma cells with chemotherapeutic drugs and siRNA against ABCG2 mediated by thermo/pH-sensitive mesoporous silica nanoparticles.

Mesoporous silica nanoparticles (MSNs) represent a new form of drug nanocarrier with thermo/pH-coupling sensitivity and site-specificity. CD133(+) Hep-2 laryngeal cancer cells are responsible for multidrug resistance due to elevated expression of ABCG2. Since positively charged nanoparticles could easily uptake nucleic acids, we examined the possibility of using this new drug delivery system to simultaneously deliver different chemotherapeutic drugs and siRNA targeting ABCG2. Our results demonstrated that both antitumor drugs and siRNA against ABCG2 were successfully delivered into CD133(+) cancer cells by loaded MSNs. Down-regulation of ABCG2 significantly enhanced the efficacy of chemotherapeutic drug-induced apoptosis in laryngeal carcinoma cells. Furthermore, the chemotherapeutic drug and siRNA loaded nanoparticles inhibited tumor growth in vivo in a laryngeal cancer mouse model.

Costunolide Induces Apoptosis through Generation of ROS and Activation of P53 in Human Esophageal Cancer Eca-109 Cells.

Costunolide is a sesquiterpene lactone, which possesses potent anti-cancer properties. However, there is little report about its effects on esophageal cancer. In our study, we investigated the effects of costunolide on the cell viability, cell cycle, and apoptosis in human esophageal cancer Eca-109 cells. It was found that costunolide inhibited the growth of Eca-109 cells in a dose-dependent manner, which was associated with the loss of mitochondrial membrane potential (Δψm ) and the production of ROS. Costunolide induced apoptosis of Eca-109 cells as well as cell cycle arrest in G1/S phase by upregulation of P53 and P21. Costunolide triggered apoptosis in esophageal cancer cells via the upregulation of Bax, downregulation of Bcl-2, and significant activation of caspase-3 and poly ADP-ribose polymerase. These effects were markedly abrogated when cells were pretreated with N-acetylcysteine, a specific reactive oxygen specie inhibitor. These results suggest that costunolide is a potential candidate for the treatment of esophageal cancer.

Comparison of chelates for enhancing Ricinus communis L. phytoremediation of Cd and Pb contaminated soil.

We studied chelate effects on castor bean (Ricinus communis L.) growth. These effects included Cd and Pb accumulation in plant tissues and the chemical behavior of Cd and Pb in the plant rhizosphere and non-rhizosphere. Tests were conducted in a glasshouse using the rhizobag method. Two castor bean cultivars (Zibo-3 and Zibo-9) were grown in soil contaminated with 3.53mg/kg Cd and 274mg/kg Pb. The soil was treated with citric acid (CA), ethylenediamine disuccinic acid (EDDS) or ethylenediamine tetraacetic acid (EDTA) (5mmol/kg). EDDS-treated soil produced 28.8% and 59.4% greater biomass for Zibo-3 and Zibo-9 respectively. In contrast, CA and EDTA inhibited the growth of the two cultivars. Zibo-9 had greater tolerance than Zibo-3 to chelate toxicity. Based on Cd and Pb plant uptake, EDDS could substitute for EDTA for phytoremediation of Cd in soil. EDTA was the most effective of the three chelates for Pb phytoremediation but it is less suitable for field use due to toxicology environmental persistence. Acid extractable Cd and Pb in the rhizosphere or reducible Cd and Pb in the non-rhizosphere of soil were the main influences on Cd and Pb accumulation in castor bean.

Cepharanthine induces apoptosis through reactive oxygen species and mitochondrial dysfunction in human non-small-cell lung cancer cells.

Cepharanthine is a medicinal plant-derived natural compound which possesses potent anti-cancer properties. However, there is little report about its effects on lung cancer cells. In this study, we investigated the effects of cepharanthine on the cell viability and apoptosis in human non-small-cell lung cancer H1299 and A549 cells. It was found that cepharanthine inhibited the growth of H1299 and A549 cells in a dose-dependent manner which was associated with the generation of reactive oxygen species(ROS) and the dissipation of mitochondrial membrane potential (Δψm). These effects were markedly abrogated when cells were pretreated with N-acetylcysteine (NAC), a specific ROS inhibitor, indicating that the apoptosis-inducing effect of cepharanthine in lung cancer cells was mediated by ROS. In addition, cepharanthine triggered apoptosis in non-small lung cancer cells via the upregulation of Bax, downregulation of Bcl-2 and significant activation of caspase-3 and PARP. These results provide the rationale for further research and preclinical investigation of cepharanthine's anti-tumor effect against human non-small-cell lung cancer.