Physico-chemical assessment of on-farm bioconversion of organic waste in dairy farms in context to sustainability and circular bioeconomy.

On a milk-producing dairy farm, milk production is correlated with manure production and the number of cattle, and manure is widely used as a soil fertilizer. However, excessive dairy manure production is linked with greenhouse gas emissions and water quality issues. On-farm planning of manure storage and application to enhance soil nutrients are essential in a circular economy to reduce environmental impact, where manure is not landfilled and incinerated. Instead, it creates a nutrient resource for crops and soil. Dairy manure, which is rich in nutrients, is a valuable fertilizer that contains many nutrients such as nitrogen (N), organic matter (OM), phosphorous (P), Potassium (K) and micronutrients. In this work, a pilot field research was conducted between 2016 and 2018 in various parts of California, USA (San Joaquin Valley, Sacramento Valley, Shasta Cascade, and the North Coast of California) to assess physio-chemical characteristics of solid fractions of dairy manure among various dairy farms. A total of 156 samples were collected from the gut (n = 107) and toe (n = 49) of the manure piles across California for determining total solid (TS), volatile solid (VS), temperature, moisture content and carbon-nitrogen ratio (C: N). Here, using the observations of field study and analysis, we show that C: N, OM and MC of solid fractions of dairy manure vary significantly among dairy farms. The average C: N ratio of manure (26-32) among various regions was close to an ideal C: N value of 24:1 for soil microbes to stimulate nutrient release to crops. Manure pH ranged between 7.0 and 8.0, which was close to an optimal pH range for common crops (6.0-8.0). Moreover, considering less cost and surplus availability, manure will likely continue providing a cost-effective organic fertilizer resource compared to commercial chemical fertilizers.

High-Matching and Low-Cost Realization of the FHN Neuron Model on Reconfigurable FPGA Board.

The main objectives of neuromorphic engineering are the research, modeling, and implementation of neural functioning in the human brain. We provide a hardware solution that can replicate such a nature-inspired system by merging multiple scientific domains and is based on neural cell processes. This work provides a modified version of the original Fitz-Hugh Nagumo (FHN) neuron using a simple 2V term called Hybrid Piece-Wised Base-2 Model (HPWBM), which accurately reproduces numerous patterns of the original neuron model. With reduced terms, we suggest modifying the original nonlinear term to achieve high matching accuracy and little computing error. Time domain and phase portraits are used to validate the proposed model, which shows that it can reproduce all of the FHN model's properties with high accuracy and little mistake. We provide an effective digital hardware approach for large-scale neuron implementations based on resource-sharing and pipelining strategies. The Hardware Description Language (HDL) is used to construct the hardware on an FPGA as a proof of concept. The recommended model hardly uses 0.48 percent of the resources on a Virtex 4 FPGA board, according to the results of the hardware implementation. The circuit can run at a maximum frequency of 448.236 MHz, according to the static timing study.

Identification of Key Genes Related to Immune Cells in Patients with COVID-19 Via Integrated Bioinformatics-Based Analysis.

COVID-19 has spread all over the world which poses a serious threat to social economic development and public health. Despite enormous progress has been made in the prevention and treatment of COVID-19, the specific mechanism and biomarker related to disease severity or prognosis have not been clarified yet. Our study intended to further explore the diagnostic markers of COVID-19 and their relationship with serum immunology by bioinformatics analysis. The datasets about COVID-19 were downloaded from the Gene Expression Omnibus (GEO) dataset. The differentially expressed genes (DEGs) were selected via the limma package. Then, weighted gene co-expression network analysis (WGCNA) was conducted to identify the critical module associated with the clinic status. The intersection DEGs were processed for further enrichment analysis. The final diagnostic genes for COVID-19 were selected and verified through special bioinformatics algorithms. There were significant DEGs between the normal and COVID-19 patients. These genes were mainly enriched in cell cycle, complement and coagulation cascade, extracellular matrix (ECM) receptor interaction, and the P53 signaling pathway. As much as 357 common intersected DEGs were selected in the end. These DEGs were enriched in organelle fission, mitotic cell cycle phase transition, DNA helicase activity, cell cycle, cellular senescence, and P53 signaling pathway. Our study also identified CDC25A, PDCD6, and YWAHE were potential diagnostic markers of COVID-19 with the AUC (area under curve), 0.958 (95% CI 0.920-0.988), 0.941(95% CI 0.892-0.980), and 0.929 (95% CI 0.880-0.971). Moreover, CDC25A, PDCD6, and YWAHE were correlated with plasma cells, macrophages M0, T cells CD4 memory resting, T cells CD8, dendritic cells, and NK cells. Our study discovered that CDC25A, PDCD6, and YWAHE can be used as diagnostic markers for COVID-19. Moreover, these biomarkers were also closely associated with immune cell infiltration, which plays a pivotal role in the diagnosis and progression of COVID-19.

Endoplasmic Reticulum Stress: A Key Regulator of Cardiovascular Disease.

The problems associated with economic development and social progress have led to an increase in the occurrence of cardiovascular diseases (CVDs), which affect the health of an increasing number of people and are a leading cause of disease and population mortality worldwide. Endoplasmic reticulum stress (ERS), a hot topic of interest for scholars in recent years, has been confirmed in numerous studies to be an important pathogenetic basis for many metabolic diseases and play an important role in maintaining physiological processes. The endoplasmic reticulum (ER) is a major organelle that is involved in protein folding and modification synthesis, and ERS occurs when several physiological and pathological factors allow excessive amounts of unfolded/misfolded proteins to accumulate. ERS often leads to initiation of the unfolded protein response (UPR) in a bid to re-establish tissue homeostasis; however, UPR has been documented to induce vascular remodeling and cardiomyocyte damage under various pathological conditions, leading to or accelerating the development of CVDs such as hypertension, atherosclerosis, and heart failure. In this review, we summarize the latest knowledge gained concerning ERS in terms of cardiovascular system pathophysiology, and discuss the feasibility of targeting ERS as a novel therapeutic target for the treatment of CVDs. Investigation of ERS has immense potential as a new direction for future research involving lifestyle intervention, the use of existing drugs, and the development of novel drugs that target and inhibit ERS.

Plasma cell-free DNA promise monitoring and tissue injury assessment of COVID-19.

Coronavirus 2019 (COVID-19) is a complex disease that affects billions of people worldwide. Currently, effective etiological treatment of COVID-19 is still lacking; COVID-19 also causes damages to various organs that affects therapeutics and mortality of the patients. Surveillance of the treatment responses and organ injury assessment of COVID-19 patients are of high clinical value. In this study, we investigated the characteristic fragmentation patterns and explored the potential in tissue injury assessment of plasma cell-free DNA in COVID-19 patients. Through recruitment of 37 COVID-19 patients, 32 controls and analysis of 208 blood samples upon diagnosis and during treatment, we report gross abnormalities in cfDNA of COVID-19 patients, including elevated GC content, altered molecule size and end motif patterns. More importantly, such cfDNA fragmentation characteristics reflect patient-specific physiological changes during treatment. Further analysis on cfDNA tissue-of-origin tracing reveals frequent tissue injuries in COVID-19 patients, which is supported by clinical diagnoses. Hence, our work demonstrates and extends the translational merit of cfDNA fragmentation pattern as valuable analyte for effective treatment monitoring, as well as tissue injury assessment in COVID-19.

Race-Ethnic Differences in the Effects of COVID-19 on the Work, Stress, and Financial Outcomes of Older Adults.

OBJECTIVES: This study investigates race-ethnic differences among older non-Hispanic Black, non-Hispanic White, and Hispanic adults' financial, employment, and stress consequences of COVID-19. METHODS: We use data from the Health and Retirement Study, including the 2020 COVID-panel, to evaluate a sample of 2,929 adults using a combination of bivariate tests, OLS regression analysis, and moderation tests. RESULTS: Hispanic and non-Hispanic Black older adults experienced more financial hardships, higher levels of COVID-19 stress, and higher rates of job loss associated with COVID-19 relative to their Non-Hispanic White counterparts. Non-Hispanic Black and Hispanic adults reported significantly higher levels of COVID-19 resilience resources, yet, these resources were not protective of the consequences of COVID-19. DISCUSSION: Understanding how the experiences of managing and coping with COVID-19 stressors differ by race-ethnicity can better inform intervention design and support services.

Environmental Adaptation in the Process of Human-Land Relationship in Southeast China's Ethnic Minority Areas and Its Significance on Sustainable Development.

The relationship between regional human development and geographic environment is the basis for dynamic social change, and studying the evolution of human-land relations in typical regions can provide background knowledge for global change studies. This study is based on GIS and spatio-temporal statistical techniques, combined with the analysis of toponymic cultural landscapes, to study ethnic minority regions of southeastern China. The results show that: (1) The geographical environment of the region will affect the naming of villages, and the orientation and family name are the most common; the frequency of plants, pit (keng), animals, and flat (ping) is also very high. (2) Han settlements and She settlements have obvious spatial differentiation, and in general the Han distribution area is lower than that of the She. Han settlements are mainly distributed in plain areas along rivers with elevations less than 200 m; She settlements are mainly distributed in hilly areas (200~500 m) and low mountain areas (500~800 m). (3) The results of quadrat analysis and nearest neighbor index analysis show that both Han and She settlements are clustered in the spatial distribution pattern, and the distribution of She settlements is more clustered than that of Han, with more dense settlements at a certain spatial scale. The regional cultural landscape is the result of the development and evolution of human-land relationship, and the comprehensive analysis of cultural landscape can understand the process of human-land relationship in a small region. The settlements in the region are indicative of the geographic environment in terms of village naming, spatial pattern, elevation differentiation and relationship with rivers, which can reflect the environmental adaptation process of human activities.

Critical Assessment of Short-Read Assemblers for the Metagenomic Identification of Foodborne and Waterborne Pathogens Using Simulated Bacterial Communities.

Metagenomics offers the highest level of strain discrimination of bacterial pathogens from complex food and water microbiota. With the rapid evolvement of assembly algorithms, defining an optimal assembler based on the performance in the metagenomic identification of foodborne and waterborne pathogens is warranted. We aimed to benchmark short-read assemblers for the metagenomic identification of foodborne and waterborne pathogens using simulated bacterial communities. Bacterial communities on fresh spinach and in surface water were simulated by generating paired-end short reads of Illumina HiSeq, MiSeq, and NovaSeq at different sequencing depths. Multidrug-resistant Salmonella Indiana SI43 and Pseudomonas aeruginosa PAO1 were included in the simulated communities on fresh spinach and in surface water, respectively. ABySS, IDBA-UD, MaSuRCA, MEGAHIT, metaSPAdes, and Ray Meta were benchmarked in terms of assembly quality, identifications of plasmids, virulence genes, Salmonella pathogenicity island, antimicrobial resistance genes, chromosomal point mutations, serotyping, multilocus sequence typing, and whole-genome phylogeny. Overall, MEGHIT, metaSPAdes, and Ray Meta were more effective for metagenomic identification. We did not obtain an optimal assembler when using the extracted reads classified as Salmonella or P. aeruginosa for downstream genomic analyses, but the extracted reads showed consistent phylogenetic topology with the reference genome when they were aligned with Salmonella or P. aeruginosa strains. In most cases, HiSeq, MiSeq, and NovaSeq were comparable at the same sequencing depth, while higher sequencing depths generally led to more accurate results. As assembly algorithms advance and mature, the evaluation of assemblers should be a continuous process.

Green Financial Reform and Corporate ESG Performance in China: Empirical Evidence from the Green Financial Reform and Innovation Pilot Zone.

Does the establishment of pilot zones for green finance reform and innovations in 2017 have an impact on the Environment, Social and Governance (ESG) scores of enterprises? This paper selects data from Chinese A-share listed companies from 2014-2020 and uses the differences-in-differences (DID) model to analyze the impact of green financial reform on the ESG scores of enterprises. The study shows that the establishment of the Green Financial Reform and Innovation Pilot Zone (GFPZ) policy helps enterprises to obtain higher ESG scores through environmental, social and governance mechanisms. When ESG is measured using environmental, social and governance data, our results suggest that the contribution of green finance reforms to ESG scores is primarily driven by social responsibility scores. The adjustment effect analysis shows that for large enterprises in the GFPZ, the above effects have stronger influence, but there is no significant difference between heavily polluting and non-heavily polluting firms in the GFPZ. Expansive analysis shows that the improvement in ESG scores of enterprises in the GFPZ not only contributes to the green performance of enterprises, but also to their financial performance.

Cross-Resistance and Fitness Costs of the cis-Nitromethylene Neonicotinoid Cycloxaprid Resistance in Melon Aphid, Aphis gossypii (Hemiptera: Aphididae).

The melon aphid, Aphis gossypii Glover, is an important pest on various vegetables around the world and has developed resistance to neonicotinoids in fields. Cycloxaprid is a novel cis-nitromethylene configuration neonicotinoid insecticide that is different from trans-configuration neonicotinoids like imidacloprid and thiamethoxam. Herein, the cross-resistance to the other seven insecticides and fitness costs were investigated in the cycloxaprid-resistant A. gossypii strain (Cpd-R), which has developed 69.5-fold resistance to cycloxaprid. The results showed that the Cpd-R strain had very low levels of cross-resistance to imidacloprid (4.3-fold), acetamiprid (2.9-fold), thiamethoxam (3.7-fold), nitenpyram (6.1-fold), flupyradifurone (2.2-fold), and sulfoxaflor (4.5-fold), while it exhibited a cross-resistance to dinotefuran (10.6-fold). The fitness of the Cpd-R strain by life table analysis was only 0.799 compared to the susceptible strain (Cpd-S). This Cpd-R strain exhibited significantly reduction in fecundity, oviposition days, and developmental time of nymph stage compared to the Cpd-S strain. Moreover, the expression levels of some genes related to the development and reproduction, including EcR, USP, JHAMT, and JHEH were significantly up-regulated, while Vg was down-regulated in the Cpd-R strain. This study indicates that the Cpd-R strain possessed a certain fitness cost. The above research results are useful for rational application of cycloxaprid and implementing the appropriate resistance management strategy for A. gossypii.

Validating Accuracy of a Mobile Application against Food Frequency Questionnaire on Key Nutrients with Modern Diets for mHealth Era.

In preparation for personalized nutrition, an accurate assessment of dietary intakes on key essential nutrients using smartphones can help promote health and reduce health risks across vulnerable populations. We, therefore, validated the accuracy of a mobile application (app) against Food Frequency Questionnaire (FFQ) using artificial intelligence (AI) machine-learning-based analytics, assessing key macro- and micro-nutrients across various modern diets. We first used Bland and Altman analysis to identify and visualize the differences between the two measures. We then applied AI-based analytics to enhance prediction accuracy, including generalized regression to identify factors that contributed to the differences between the two measures. The mobile app underestimated most macro- and micro-nutrients compared to FFQ (ranges: -5% for total calories, -19% for cobalamin, -33% for vitamin E). The average correlations between the two measures were 0.87 for macro-nutrients and 0.84 for micro-nutrients. Factors that contributed to the differences between the two measures using total calories as an example, included caloric range (1000-2000 versus others), carbohydrate, and protein; for cobalamin, included caloric range, protein, and Chinese diet. Future studies are needed to validate actual intakes and reporting of various diets, and to examine the accuracy of mobile App. Thus, a mobile app can be used to support personalized nutrition in the mHealth era, considering adjustments with sources that could contribute to the inaccurate estimates of nutrients.

Assessment of gaseous ozone treatment on Salmonella Typhimurium and Escherichia coli O157:H7 reductions in poultry litter.

Poultry litter is used as soil amendment or organic fertilizer. While poultry litter is enriched with organic matter suitable for land, the presence of pathogens such as Salmonella in poultry litter is a concern. To investigate the effect of gaseous ozone on pathogen reductions in poultry litter, this study conducted a series of experiments that involved understanding of Salmonella Typhimurium and Escherichia coli O157:H7 inactivation at various doses of Ozone (O3) in wet and dry poultry litter conditions. Previously, ozone treatment has been shown to disinfect the surface of foods and plant materials including fruits, juices, and wastewater, however, additional research are needed to better understand the impacts of ozone on treatment of soil amendments. Sanitizing methods capable of eliminating pathogens of soil amendments are crucial to mitigate disease outbreaks related with litter/manure-based fertilizers. In this study, a bench scale continuous ozone treatment system was designed to produce O3 gas, with a range O3 concentrations (7.15-132.46 mg·L-1), monitor ozone concentrations continuously, and control the ozone exposure time (15 to 90 mins) to understand the effectiveness of O3 in eliminating S. Typhimurium and E. coli O157:H7 in poultry litter. Results showed that 7.15 mg·L-1 did not reduce the counts of S. Typhimurium until exposure to O3 for 90 min. The O3 concentrations of 43.26 ~ 132.46 mg·L-1 exposure reduced the bacterial counts. Furthermore, the moisture content of poultry litter was found to be an influencing factor for pathogen reduction. The pathogen reduction rates were reduced when the moisture content was increased. At higher moisture content, high concentrations of O3 (132.46 mg·L-1) were needed for pathogen reductions. The moisture content of 30% or lower was found to be more effective for controlling pathogen levels in poultry litter. Our study demonstrates that gaseous O3 treatment could be used as an additional decontamination technique to ensure the certain degree of microbiological safety of poultry litter based soil amendment.

Assessment of the impact of geogenic and climatic factors on global risk of urinary stone disease.

Urinary Stone Disease (USD) or urolithiasis has plagued humans for centuries, and its prevalence has increased over the past few decades. Although USD pathology could vary significantly among individuals, previous qualitative assessments using limited survey data demonstrated that the prevalence of USD might exhibit a distinctive geographical distribution (the so-called "stone belt"), without any knowledge about the characteristics and contribution factors of the belt. Here, we argue that the spatial distribution of USD can at least partly be explained by geogenic and climatic factors, as it correlates with the ambient geo-environmental conditions modulated by lithology/mineralogy, water quality and climate. Using a Bayesian risk model, we assessed the global risk of USD based on updated big data of four key geogenic factors: phosphorite mines (inventory >1600 points), carbonate rocks (at the scale of 1:40 million), Ca2+/Mg2+ molar ratio of river water (1.27 million samples distributed over 17,000 sampling locations), and mean air temperature (0.5o × 0.5° resolution) representing the climate. We quantitatively identified possible contributions of the factors to USD and delineated the regions with the high USD risk which stretched from southern North America, via the Mediterranean region, northeastern Africa, southern China to Australia, and roughly coincide with the world's major areas of carbonate outcropping. Under current climate conditions, the areas with the probabilities for the USD prevalence of ≥50% and ≥30% covered 3.7% and 20% of the Earth's land surface, respectively. By the end of the 21st century, such total areas could rise to 4.4% and 25% as a result of global warming. Since the USD data used in this study were quite heterogeneous, the prediction results needed further calibration with additional high-quality prevalence data in the future.

Using Bayesian spatio-temporal model to determine the socio-economic and meteorological factors influencing ambient PM2.5 levels in 109 Chinese cities.

OBJECTIVE: Ambient particulate pollution, especially PM2.5, has adverse impacts on health and welfare. To manage and control PM2.5 pollution, it is of great importance to determine the factors that affect PM2.5 levels. Previous studies commonly focused on a single or several cities. This study aims to analyze the impacts of meteorological and socio-economic factors on daily concentrations of PM2.5 in 109 Chinese cities from January 1, 2015 to December 31, 2015. METHODS: To evaluate potential risk factors associated with the spatial and temporal variations in PM2.5 levels, we developed a Bayesian spatio-temporal model in which the potential temporal autocorrelation and spatial autocorrelation of PM2.5 levels were taken into account to ensure the independence of the error term of the model and hence the robustness of the estimated parameters. RESULTS: Daily concentrations of PM2.5 peaked in winter and troughed in summer. The annual average concentration reached its highest value (79 µg/m3) in the Beijing-Tianjin-Hebei area. The city-level PM2.5 was positively associated with the proportion of the secondary industry, the total consumption of liquefied petroleum gas and the total emissions of industrial sulfur dioxide (SO2), but negatively associated with the proportion of the primary industry. A reverse U-shaped relationship between population density and PM2.5 was found. The city-level and daily-level of weather conditions within a city were both associated with PM2.5. CONCLUSION: PM2.5 levels had significant spatio-temporal variations which were associated with socioeconomic and meteorological factors. Particularly, economic structure was a determinant factor of PM2.5 pollution rather than per capita GDP. This finding will be helpful for the intervention planning of particulate pollution control when considering the environmental and social-economic factors as part of the strategies.

A causation-based method developed for an integrated risk assessment of heavy metals in soil.

A comprehensive and fact-based risk assessment of heavy metals in soils is paramount for defining strategies for environmental management. However, the risk assessment approaches of heavy metals in soils are often incomplete, in particular, causation-based pollution source apportionment is absent at present. Here, we developed a causation-based method framework of an integrated risk assessment of soil heavy metals. This method framework involves risk identification, causation-based source apportionment and an environmental sensitivity assessment. Dongtang Township in Guangdong Province, China was used as a case study. We found that air Cd, the background value and metallurgical industries (Danxia and Fankou plants) were identified as the major causes of soil Cd, and air and soil Cd as well as water Cd interacted causally. Danxia and Fankou plants, the mining area and background value were the major causes of soil Pb. The risk level and environmental sensitivity of the Danxia and Fankou plants were assessed. This is the first study to establish a causation-based method framework of an integrated risk assessment of soil heavy metals. This framework promotes systematic integration of risk assessment of soil heavy metals and expands traditional research on pollution source apportionment from a correlation-based approach to crucial insights into causation.

Six-Year Nitrogen-Water Interaction Shifts the Frequency Distribution and Size Inequality of the First-Order Roots of Fraxinus mandschurica in a Mixed Mature Pinus koraiensis Forest.

The variation in fine root traits in terms of size inequality at the individual root level can be identified as a strategy for adapting to the drastic changes in soil water and nutrient availabilities. The Gini and Lorenz asymmetry coefficients have been applied to describe the overall degree of size inequality, which, however, are neglected when conventional statistical means are calculated. Here, we used the Gini coefficient, Lorenz asymmetry coefficient and statistical mean in an investigation of Fraxinus mandschurica roots in a mixed mature Pinus koraiensis forest on Changbai Mountain, China. We analyzed 967 individual roots to determine the responses of length, diameter and area of the first-order roots and of branching intensity to 6 years of nitrogen addition (N), rainfall reduction (W) and their combination (NW). We found that first-order roots had a significantly greater average length and area but had smaller Gini coefficients in NW plots compared to in control plots (CK). Furthermore, the relationship between first-order root length and branching intensity was negative in CK, N, and W plots but positive in NW plots. The Lorenz asymmetry coefficient was >1 for the first-order root diameter in NW and W plots as well as for branching intensity in N plots. The bimodal frequency distribution of the first-order root length in NW plots differed clearly from the unimodal one in CK, N, and W plots. These results demonstrate that not only the mean but also the variation and the distribution mode of the first-order roots of F. mandschurica respond to soil nitrogen and water availability. The changes in size inequality of the first-order root traits suggest that Gini and Lorenz asymmetry coefficients can serve as informative parameters in ecological investigations of roots to improve our ability to predict how trees will respond to a changing climate at the individual root level.

The Lattice Kinetic Monte Carlo Simulation of Atomic Diffusion and Structural Transition for Gold.

For the kinetic simulation of metal nanoparticles, we developed a self-consistent coordination-averaged energies for Au atoms based on energy properties of gold bulk phases. The energy barrier of the atom pairing change is proposed and holds for the microscopic reversibility principle. By applying the lattice kinetic Monte Carlo simulation on gold films, we found that the atomic diffusion of Au on the Au(111) surface undergoes a late transition state with an energy barrier of about 0.2 eV and a prefactor between 40~50 Å(2)/ps. This study also investigates the structural transition from spherical to faceted gold nanoparticles upon heating. The temperatures of structural transition are in agreement with the experimental melting temperatures of gold nanoparticles with diameters ranging from 2 nm to 8 nm.

Assessment of epidermal growth factor receptor mutation/copy number and K-ras mutation in esophageal cancer.

BACKGROUND: The molecular status of epidermal growth factor receptor (EGFR) in esophageal cancer has not been well elucidated. The purpose of the study was to investigate the prevalence of EGFR and K-ras mutation, and EGFR gene copy number status as well as its association with clinicopathologic characteristics, and also to identify the prognostic value of EGFR gene copy number in esophageal cancer. METHODS: EGFR mutation in exon 19/exon 21 and K-ras mutation in codon 12/codon 13 were detected by real-time PCR method, while EGFR gene copy number status was analyzed by fluorescent in situ hybridization (FISH). EGFR gene amplification and high polysomy were defined as high EGFR gene copy number status (FISH-positive), and all else were defined as low EGFR gene copy number status (FISH-negative). The relationship between EGFR gene copy number status and clinicpathologic characteristics was analyzed. Kaplan-Meier method and Cox proportional hazards regression model were employed to evaluate the effects of EGFR gene copy number status on the patients' survival. RESULTS: A total of 57 esophageal squamous cell carcinoma (ESCC) patients and 9 esophageal adenocarcinoma (EADC) patients were enrolled in the study. EGFR mutation was identified in one patient who was diagnosed as ESCC with stage IIIC disease. K-ras mutation was identified in one patient who was diagnosed as EADC. In all, 34 of 66 (51.5%) samples were detected as FISH-positive, which includes 30 ESCC and 4 EADC tumor samples. The correlation analysis showed that FISH-positive was significantly associated with the tumor stage (P=0.019) and lymph node metastasis (P=0.005) in esophageal cancer patients, and FISH-positive was also significantly associated with the tumor stage (P=0.007) and lymph node metastasis (P=0.008) in ESCC patients. Cox regression analysis showed that high EGFR gene copy number was not a significant predictor of a poor outcome for esophageal cancer patients (P=0.251) or for ESCC patients (P=0.092), but esophageal cancer patients or ESCC patients with low EGFR gene copy number may have longer survival than those with high EGFR gene copy number according to the survival curve trends. CONCLUSIONS: The results indicated that EGFR or K-ras mutation was rare in esophageal cancer, but high EGFR gene copy number is frequent, and correlated with advanced pathologic stage and more number of the metastatic regional lymph nodes, especially in ESCC. In addition, high EGFR gene copy number is likely to have a deleterious effect on prognosis of esophageal cancer patients or ESCC patients, although no statistical significance was reached in the study.

Assessment of the clinical application of detecting EGFR, KRAS, PIK3CA and BRAF mutations in patients with non-small cell lung cancer using next-generation sequencing.

BACKGROUND: Next-generation sequencing (NGS) has been widely applied in clinical research, while its application in routine clinical molecular testing requires careful validation. The aim of our study was to assess the clinical usefulness of the NextDaySeq Lung panel on Ion Torrent™ PGM in mutation detection of actionable genes in lung cancer. METHODS: The NextDaySeq assay was evaluated by blinded comparisons to Quantitative Real-Time PCR (qPCR) assays with 188 consecutive samples from Chinese patients with non-small cell lung cancer (NSCLC) to detect mutations in EGFR, KRAS, PIK3CA and BRAF. Discordant variants were further validated by Sanger sequencing and independent qPCR and NGS assays. RESULTS: Our results showed 93.3% concordance of reportable variants mutually covered in both NGS and qPCR assays, with a clinical sensitivity of 89.9%, specificity of 97.5%. Through the comparison, the NGS assays demonstrated its advantages in offering more clinical relevant information, such as detecting non-hotspot mutations and providing mutation allele frequencies (MAF) and accurate mutation sequences. The analytical sensitivity of NGS to detect mutations with low MAF needs further improvement. CONCLUSIONS: The NextDaySeq Lung panel exhibited good clinical performance, strongly supporting the implementation of the NGS assay in routine clinical use to facilitate therapeutic decision-making for lung cancer patients.

Where does methanol lose hydrogen to trigger steam reforming? A revisit of methanol dehydrogenation on the PdZn alloy model obtained from kinetic Monte Carlo simulations.

Pd/ZnO is a promising catalyst studied for methanol steam reforming (MSR) and the 1 : 1 PdZn alloy is demonstrated to be the active component. It is believed that MSR starts from methanol dehydrogenation to methoxy. Previous studies of methanol dehydrogenation on the ideal PdZn(111) surface show that methanol adsorbs weakly on the PdZn(111) surface and it is hard for methanol to transform into methoxy because of the high dehydrogenation barrier, indicating that the catalyst model is not appropriate for investigating the first step of MSR. Using the model derived from our recent kinetic Monte Carlo simulations, we examined the process CH3OH → CH3O → CH2O → CHO → CO. Compared with the ideal model, methanol adsorbs much more strongly and the barrier from CH3OH → CH3O is much lower on the kMC model. On the other hand, the C-H bond breaking of CH3O, CH2O and CHO becomes harder. We show that co-adsorbed water is important for refreshing the active sites. The present study shows that the first MSR step most likely takes place on three-fold hollow sites formed by Zn atoms, and the inhomogeneity of the PdZn alloy may exert significant influences on reactions.