Search

In this study, deep eutectic solvent (DES), as a new green solvent, was used to extract bioactive alkaloids from Ephedrae Herba using supersonic extraction. In a variety of tested hydrophilic and hydrophobic DESs, DES composed of choline chloride and xylitol was proved to be the most efficient solvent. Factors affecting extraction efficiency, including the mole ratio of hydrogen bond acceptor/hydrogen bond donor, water contention, and solid/liquid ratio, were optimized individually. Under optimal conditions, the yield of ephedrine (EP) and pseudoephedrine obtained using this new method was 14.24 and 4.32 mg/g, respectively, which was higher than that using the traditional solvent (acidified water and methanol). Furthermore, the extraction mechanism of DES and EP was investigated using molecular dynamics simulation study. Structural properties such as radial distribution functions and average number of hydrogen bonds were then computed. The results showed that hydrogen bonds and van der Waals forces are important driving forces of extraction; in addition, the hydrogen bonds between the Cl atom of choline chloride and N atom of EP played a dominant part in the extraction process. Based on the extraction principle, the extraction method using choline chloride as extraction solvent was also discussed.

BACKGROUND: Sternal fracture can result from multiple types of severe chest trauma and carries significant risk. Surgical fixation is an effective method for sternal fracture. METHODS: The clinical data of patients with sternal fractures who presented to our hospital between August 2016 and July 2019 were collected. The 42 patients were divided into three groups, with 15 patients treated by internal fixation with NI-TI memory alloy embracing fixator, 10 patients receiving steel wire fixation, and 17 who received non-surgical treatment and who was designated as a control (conservative) group. Differences in clinical indices included the duration of surgery, blood loss, hospitalization, wound healing, hospitalization expenses, VAS scores, and patient satisfaction scores between the three groups was compared. The analysis of variance and t-test were used for quantitative variables, which were approximately normally distributed. Dichotomous data were compared used Pearson χ(2) or Fisher’s exact test, and a P value less than 0.05 was considered as statistically significant. RESULTS: All patients were cured, and there were no significant differences in general clinical features between the three groups (P>0.05). Thoracic deformity in the surgical groups was corrected anatomically and received better pain scores, while patients in the NI-TI memory alloy embracing fixator group showed advantages of bleeding and patient satisfaction (P

Outbreaks of COVID-19 caused by the novel coronavirus SARS-CoV-2 is still a threat to global human health. In order to understand the biology of SARS-CoV-2 and developing drug against COVID-19, a vast amount of genomic, proteomic, interatomic, and clinical data is being generated, and the bioinformatics researchers produced databases, webservers and tools to gather those publicly available data and provide an opportunity of analyzing such data. However, these bioinformatics resources are scattered and researchers need to find them from different resources discretely. To facilitate researchers in finding the resources in one frame, we have developed an integrated web portal called OverCOVID (http://bis.zju.edu.cn/overcovid/). The publicly available webservers, databases and tools associated with SARS-CoV-2 have been incorporated in the resource page. In addition, a network view of the resources is provided to display the scope of the research. Other information like SARS-CoV-2 strains is visualized and various layers of interaction resources is listed in distinct pages of the web portal. As an integrative web portal, the OverCOVID will help the scientist to search the resources and accelerate the clinical research of SARS-CoV-2.

The recent discovery of circular RNAs (circRNAs) and characterization of their functional roles have opened a new avenue for understanding the biology of genomes. circRNAs have been implicated to play important roles in a variety of biological processes, but their precise functions remain largely elusive. Currently, a few approaches are available for novel circRNA prediction, but almost all these methods are intended for animal genomes. Considering that the major differences between the organization of plant and mammal genomes cannot be neglected, a plant-specific method is needed to enhance the validity of plant circRNA identification. In this study, we present CircPlant, an integrated tool for the exploration of plant circRNAs, potentially acting as competing endogenous RNAs (ceRNAs), and their potential functions. With the incorporation of several unique plant-specific criteria, CircPlant can accurately detect plant circRNAs from high-throughput RNA-seq data. Based on comparison tests on simulated and real RNA-seq datasets from Arabidopsis thaliana and Oryza sativa, we show that CircPlant outperforms all evaluated competing tools in both accuracy and efficiency. CircPlant is freely available at http://bis.zju.edu.cn/circplant.

Triple-negative breast cancer (TNBC) is a heterogeneous disease with diverse, often poor prognoses and treatment responses. In order to identify targetable biomarkers and guide personalized care, scientists have developed multiple molecular classification systems for TNBC based on transcriptomic profiling. However, there is no consensus on the molecular subtypes of TNBC, likely due to discrepancies in technical and computational methods used by different research groups. Here, we reassessed the major steps for TNBC subtyping, validated the reproducibility of established TNBC subtypes, and identified two more subtypes with a larger sample size. By comparing results from different workflows, we demonstrated the limitations of formalin-fixed, paraffin-embedded samples, as well as batch effect removal across microarray platforms. We also refined the usage of computational tools for TNBC subtyping. Furthermore, we integrated high-quality multi-institutional TNBC datasets (discovery set: n = 457; validation set: n = 165). Performing unsupervised clustering on the discovery and validation sets independently, we validated four previously discovered subtypes: luminal androgen receptor, mesenchymal, immunomodulatory, and basal-like immunosuppressed. Additionally, we identified two potential intermediate states of TNBC tumors based on their resemblance with more than one well-characterized subtype. In summary, we addressed the issues and limitations of previous TNBC subtyping through comprehensive analyses. Our results promote the rational design of future subtyping studies and provide new insights into TNBC patient stratification.

A tumor is a complex tissue comprised of heterogeneous cell subpopulations which exhibit substantial diversity at morphological, genetic and epigenetic levels. Under the selective pressure of cancer therapies, a minor treatment-resistant subpopulation could survive and repopulate. Therefore, the intra-tumor heterogeneity is recognized as a major obstacle to effective treatment. In this paper, we propose a stochastic clonal expansion model to simulate the dynamic evolution of tumor subpopulations and the therapeutic effect at different times during tumor progression. The model is incorporated in the CES webserver, for the convenience of simulation according to initial user input. Based on this model, we investigate the influence of various factors on tumor progression and treatment consequences and present conclusions drawn from observations, highlighting the importance of treatment timing. The model provides an intuitive illustration to deepen the understanding of temporal intra-tumor heterogeneity dynamics and treatment responses, thus helping the improvement of personalized diagnostic and therapeutic strategies.

Deep eutectic solvents (DESs) were applied as eco-friendly solvents in this study for the extraction of alkaloids from lotus leaf, including O-nornuciferine, N-nornuciferine, nuciferine and roemerine. A series of hydrophilic and hydrophobic DESs with different hydrogen bond donors and a acceptors were synthesized and screened for a suitable DESs for extraction of alkaloids from lotus leaf. The study results showed that the hydrophilic DES with choline chloride and propanediol had the highest extraction yield. The main factors affecting the extraction efficiency-choline chloride-propanediol ratio, water content in deep eutectic solvents, solid-liquid ratio and extraction time-were investigated via a single-factor experiment. The optimized extraction conditions were 30% of water in choline chloride-propanediol (1:4) for heated extraction for 30 min and solid-liquid ratio 1:100 g/ml. Under optimum conditions, the extraction yields of O-nornuciferine, N-nornuciferine, nuciferine and roemerine were 0.069, 0.152, 0.334 and 0.041 g/100 g respectively, which were higher than those of methanol in acidified aqueous solution. This study suggests considerable potential for DESs as promising materials for the green and efficient extraction solvents for bioactive alkaloids from natural sources.

Global climate change influences not only vascular plants, but also biological soil crusts (biocrusts), which play important roles in dryland vegetation dynamics by redistributing rainfall in soils. Different types of biocrusts, spanning a spectrum from cyanobacteria-dominated and moss-dominated, have distinct roles in rainfall redistribution patterns, but the ecohydrological effects of different biocrust types on dryland ecosystem dynamics remain largely unclear. This study developed an ecohydrological model with biocrust as a system state variable to explicitly explore the effects of different biocrust types on dryland vegetation dynamics in Shapotou region in northern China, particularly after restoration. The results indicated that both cyanobacteria- and moss-dominated biocrusts could support high grass cover (approximately 40%) after restoration. Cyanobacterial, but not moss biocrusts, could also maintain a high level of shrub cover (13 and 3%, respectively). Shifting from cyanobacteria to mosses gradually increased the biocrust cover from approximately 40% to 80%. The biocrust's water-holding capacity (the volume of water it can intercept per unit area) is likely be able to explain the dynamics of biocrust and shrub cover (with correlation efficiency of R2 = 0.972 and 0.987, respectively), but not grass cover (R2 = 0.224). The findings suggest that biocrust type may significantly affect coverage of biocrusts and shrubs, but not grass coverage, and global climate change may influence dryland restoration by altering biocrust types.

In this study, a simple and effective method was developed for the enantiomeric analysis of five β-agonists (terbutaline, clorprenaline, tulobuterol, clenbuterol, and salbutamol) in water samples using deep eutectic solvent (DES) based dispersive liquid-liquid microextraction and chiral LC-MS. In such a framework, different kinds of hydrophobic DESs were tailored to examine their extraction ability for five β-agonists from aqueous sample. After an initial screening, the primary factors affecting the extraction recovery of DES based dispersive liquid-liquid microextraction, such as hydrogen-bond acceptor/hydrogen-bond donor ratio, DES volume, type and volume of disperser solvent and so on, were investigated and optimized. Finally, the established method was validated and found to be linear, precise, and accurate. The method was successfully applied to analyze the five β-agonists in water samples, which will help better understand the behavior of individual enantiomer and make accurate risk assessment on the ecosystem.

This work studied the response of tree growth to the increased drought and carbon dioxide in semi-arid areas of northwestern China. Forests ecosystems play a key role in the global carbon cycle. However, effects of increased drought and rising atmospheric carbon dioxide (Ca) on it are complex and there are many uncertainties. In this study, we evaluated this issue through dendroecology in semi-arid regions of northwest China. Results found the basal area increment of trees decreased by 28% (from 7.59 to 5.43 cm2 year−1) as the intrinsic water use efficiency increased 32% (from 98.61 to 130.28 µmol mol−1). Despite both Ca and drought positively affected intrinsic water use efficiency, they did not promote tree growth. Meanwhile, values of intercellular [CO2] increased 14% (from 158.83 to 180.89 ppm) while the ratio of intercellular [CO2] to Ca decreased 7% (from 0.50 to 0.46). Our study advances understanding of the variability of the global carbon cycle under climate change.

Introduction In the present study, a green and efficient extraction method using deep eutectic solvents as extraction solvent was developed for extracting the four major active compounds narirutin, naringin, hesperidin and neohesperidin from Aurantii Fructus. Methodology A series of tunable deep eutectic solvents were prepared and investigated by mixing choline chloride or betaine to different hydrogen-bond donors, and betaine/ethanediol was found to be the most suitable extraction solvent. To achieve the best extraction yield, the primary factors affecting the extraction efficiency, such as hydrogen-bond acceptor/hydrogen-bond donor ratio, water content in deep eutectic solvents, extraction temperature, solid/liquid ratio and extraction time, were investigated. Results The optimal extraction conditions were 40% of water in betaine/ethanediol (1:4) at 60°C for heated extraction of 30 min and solid/liquid ratio 1:100 g/mL. Under the optimum extraction condition, the extraction yields of narirutin, naringin, hesperidin, and neohesperidin were 8.39 ± 0.61, 83.98 ± 1.92, 3.03 ± 0.35 and 35.94 ± 0.63 mg/g, respectively, which were much higher than those of methanol as extraction solvent (5.5 ± 0.48, 64.23 ± 1.51, 2.16 ± 0.15 and 30.14 ± 0.62 mg/g). Conclusion The present results showed that deep eutectic solvents could be promising green and efficient solvents for extraction of the bioactive ingredients from traditional Chinese medicine.

Background Large-scale afforestation can significantly change the ground cover and soil physicochemical properties, especially the soil fertility maintenance and water conservation functions of artificial forests, which are very important in semi-arid mountain ecosystems. However, how different tree species affect soil nutrients and soil physicochemical properties after afforestation, and which is the best plantation species for improving soil fertility and water conservation functions remain largely unknown. Methods This study investigated the soil nutrient contents of three different plantations (Larix principis-rupprechtii, Picea crassifolia, Pinus tabuliformis), soils and plant-soil feedbacks, as well as the interactions between soil physicochemical properties. Results The results revealed that the leaves and litter layers strongly influenced soil nutrient availability through biogeochemical processes: P. tabuliformis had higher organic carbon, ratio of organic carbon to total nitrogen (C:N) and organic carbon to total phosphorus (C:P) in the leaves and litter layers than L. principis-rupprechtii or P. crassifolia, suggesting that higher C:N and C:P hindered litter decomposition. As a result, the L. principis-rupprechtii and P. crassifolia plantation forests significantly improved soil nutrients and clay components, compared with the P. tabuliformis plantation forest. Furthermore, the L. principis-rupprechtii and P. crassifolia plantation forests significantly improved the soil capacity, soil total porosity, and capillary porosity, decreased soil bulk density, and enhanced water storage capacity, compared with the P. tabuliformis plantation forest. The results of this study showed that, the strong link between plants and soil was tightly coupled to C:N and C:P, and there was a close correlation between soil particle size distribution and soil physicochemical properties. Conclusions Therefore, our results recommend planting the L. principis-rupprechtii and P. crassifolia as the preferred tree species to enhance the soil fertility and water conservation functions, especially in semi-arid regions mountain forest ecosystems.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has created an unprecedented threat to public health. The pandemic has been sweeping the globe, impacting more than 200 countries, with more outbreaks still lurking on the horizon. At the time of the writing, no approved drugs or vaccines are available to treat COVID-19 patients, prompting an urgent need to decipher mechanisms underlying the pathogenesis and develop curative treatments. To fight COVID-19, researchers around the world have provided specific tools and molecular information for SARS-CoV-2. These pieces of information can be integrated to aid computational investigations and facilitate clinical research. This paper reviews current knowledge, the current status of drug development and various resources for key steps toward effective treatment of COVID-19, including the phylogenetic characteristics, genomic conservation and interaction data. The final goal of this paper is to provide information that may be utilized in bioinformatics approaches and aid target prioritization and drug repurposing. Several SARS-CoV-2-related tools/databases were reviewed, and a web-portal named OverCOVID (http://bis.zju.edu.cn/overcovid/) is constructed to provide a detailed interpretation of SARS-CoV-2 basics and share a collection of resources that may contribute to therapeutic advances. These information could improve researchers’ understanding of SARS-CoV-2 and help to accelerate the development of new antiviral treatments.

Background: Large-scale afforestation can significantly change the ground cover and soil physicochemical properties, especially the soil fertility maintenance and water conservation functions of artificial forests are very important in semi-arid mountain ecosystems. However, how different tree growth affect soil nutrient and soil physicochemical properties following afforestation and which is the best plantation tree species for improving soil fertility and water conservation functions remain largely unknown. Methods: This study investigated the soil nutrient contents of three plantations with different tree species (Larix principis-rupprechtii, Picea crassifolia, Pinus tabuliformis), soils and plant-soil feedbacks, as well as the interaction between soil physicochemical properties. Results: The results revealed that the leaf and litter layer strongly influence soil nutrient availability through biogeochemical processes: P. tabuliformis has higher organic carbon, ratio of organic carbon to total nitrogen (C:N) and organic carbon to total phosphorus (C:P) in the leaves and litter layer than L. principis-rupprechtii or P. crassifolia, suggesting that higher C:N and C:P hinder litter decomposition. As a result, the L. principis-rupprechtii and P. crassifolia plantation forests significantly improve soil nutrients and clay components than the P. tabuliformis plantation forest. Furthermore, the L. principis-rupprechtii and P. crassifolia plantation forests significantly improved the soil capacity, soil total porosity, and capillary porosity, decreased soil bulk density, and enhanced water storage capacity than the P. tabuliformis plantation forest. In conclusion, the results of this study showed that the strong link between plants and soil is tightly coupled to C:N and C:P, and there had a close correlation between soil particle size distribution and soil physicochemical properties. Conclusions: Therefore, our results recommend planting the L. principis-rupprechtii and P. crassifolia as the preferred tree species to enhance the soil fertility and water conservation functions, especially in semi-arid regions mountain forest ecosystems.

In the past few decades, industrialization has caused a large number of pollutants to be released into the atmosphere. Forest ecosystems play an important function in regulating the biogeochemistry and the circulation of metal ions pollutants. Forest ecosystems affect the absorption of pollutants and dissolution of nutrients from the atmosphere and vegetation canopy, thereby influencing the content and composition of forest floor leachate and soil solution. This study examined changes in acid anions (NO3−, SO42−, Cl−) and metal cations (K+, Ca2+, Na2+, Mg2+, Fe3+, Pb2+, Cu2+, Cd2+) in rainfall, throughfall, stemflow, and forest floor leachate for five different forests (Larix principis-rupprechtii, Picea wilsonii, Picea crassifolia, Betula platyphylla and Rhododendron communities). The results showed that the enrichment capacity of acid anions and metal cations in the vegetation canopy of the coniferous forests (L. principis-rupprechtii, P. wilsonii, P. crassifolia) was stronger than that of the broad-leaved forests (B. platyphylla and Rhododendron communities). The content of acid anions and metal cations in stemflow of coniferous forests were 3.7–5.6 times and 0–9.3 times higher than those of broad-leaved forests, respectively. Corresponding values in throughfall were 1–1.4 times and 0.3–2.4 times, respectively. The contents of NO3−, Cl−, K+, Mg2+, Fe3+, Pb2+, Cu2+, and Cd2+ in leachate filtered from the soil layers that are deepening gradually showed consistent decreasing trend for all the forest stands. In addition, NO3−, Cl−, K+, Mg2+, Fe3+, and Pb2+ were also concentrated in the topsoil, except for Cu2+ and Cd2+. Nevertheless, SO42− and Na+ were concentrated in the subsoil, whereas Ca2+ was concentrated in the upper soil layers. Soil organic carbon (SOC) and total nitrogen (TN) contents in coniferous forest stands were 20–37% and 34–63% higher than those in broad-leaved forest stands, respectively. This results also shown that the contents of OC and TN has a strong correlation with the content of partial metal cations in soil and litter, indicating that coniferous forest stands had stronger ion scavenging and adsorption capacity in soil layer and litter layer than broad-leaved forest stands. Therefore, L. principis-rupprechtii, P. wilsonii, P. crassifolia had higher air pollutant adsorption and soil pollution remediation capacities than the other two forests. Thus, we recommend planting coniferous tree species (L. principis-rupprechtii, P. wilsonii and P. crassifolia) for eco-rehabilitation and water purification to improve the ecological service function of forest ecosystems.

Background Genetic regulation is known to contribute to the divergent expression of duplicate genes; however, little is known about how epigenetic modifications regulate the expression of duplicate genes in plants. Methods The histone modification (HM) profile patterns of different modes of gene duplication, including the whole genome duplication, proximal duplication, tandem duplication and transposed duplication were characterized based on ChIP-chip or ChIP-seq datasets. In this study, 10 distinct HM marks including H2Bub, H3K4me1, H3K4me2, H3K4me3, H3K9ac, H3K9me2, H3K27me1, H3K27me3, H3K36me3 and H3K14ac were analyzed. Moreover, the features of gene duplication with different HM patterns were characterized based on 88 RNA-seq datasets of Arabidopsis thaliana. Results This study showed that duplicate genes in Arabidopsis have a more similar HM pattern than single-copy genes in both their promoters and protein-coding regions. The evolution of HM marks is found to be coupled with coding sequence divergence and expression divergence after gene duplication. We found that functionally selective constraints may impose on epigenetic evolution after gene duplication. Furthermore, duplicate genes with distinct functions have more divergence in histone modification compared with the ones with the same function, while higher expression divergence is found with mutations of chromatin modifiers. This study shows the role of epigenetic marks in regulating gene expression and functional divergence after gene duplication in plants based on sequencing data.

DNA repeats are abundant in eukaryotic genomes and have been proved to play a vital role in genome evolution and regulation. A large number of approaches have been proposed to identify various repeats in the genome. Some de novo repeat identification tools can efficiently generate sequence repetitive scores based on k-mer counting for repeat detection. However, we noticed that these tools can still be improved in terms of repetitive score calculation, sensitivity to segmental duplications and detection specificity. Therefore, here, we present a new computational approach named Repeat Locator (RepLoc), which is based on weighted k-mer coverage to quantify the genome sequence repetitiveness and locate the repetitive sequences. According to the repetitiveness map of the human genome generated by RepLoc, we found that there may be relationships between sequence repetitiveness and genome structures. A comprehensive benchmark shows that RepLoc is a more efficient k-mer counting based tool for de novo repeat detection. The RepLoc software is freely available at http://bis.zju.edu.cn/reploc.

Geometric distribution is a very important distribution in reliability area. The aim of this paper is to study the estimation problem of reliability of Geometric distribution. Hierarchical Bayesian method is more robust than ordinary Bayesian method. A new Hierarchical Bayesian and E-Bayesian estimation methods are put forward under scaled squared error loss function. First, we develop a new hierarchical prior distribution of reliability of Geometric distribution on the basis of negative logarithm gamma distribution, which can fit all kinds of density functions on the interval (0, 1) when changing values of it’s parameters. Then we derive hierarchical Bayesian and E-Bayesian estimators under scaled squared error loss function. Finally, Monte Carlo simulations prove that the hierarchical Bayesian estimation is more robust than E-Bayeisan estimation.

In the present work, four β-cyclodextrin derivatives including neutral (methyl- and hydroxypropyl-) and anionic (carboxymethyl- and sulfated-) β-cyclodextrin derivatives have been tested for the enantioseparation of higenamine by capillary electrophoretic method. To our knowledge, there is no literature about using capillary electrophoresis for the chiral separation of higenamine. To achieve the best resolution in the presence of each β-cyclodextrin derivative, the primary factors affecting separation efficiency, such as buffer pH and concentration of β-cyclodextrin derivatives, were investigated. All enantiomeric separation was performed by 30 mmol/L phosphate buffer with an applied voltage of 20 kV or − 20 kV. Under the optimum conditions, four β-cyclodextrin derivatives (methyl-β-cyclodextrin, hydroxypropyl-β-cyclodextrin, carboxymethyl-β-cyclodextrin and sulfated-β-cyclodextrin) exhibited good separation performances for higenamine with the Rs value of 2.3, 5.8, 9.4 and 11.7 respectively. As well as the chiral separation abilities of different β-cyclodextrin derivatives were compared. Moreover, the method for determining R-(+)-higenamine in Nelumbins plumula was proposed employing carboxymethyl-β-cyclodextrin as the chiral selector.

lung adenocarcinoma (LUAD) is the highest incidence of malignant tumors in China, because its early symptoms are not easily ignored by most people, so screening reliable markers is the focus of research. In order to screen stable, cross-platform prognostic lncRNA of LUAD, we combined gene expression profiles and RNAseq data to screen stable lncRNA pairs shared by both platforms and significantly reversed lncRNA pairs in LUAD samples, and then screened the prognostic-related lncRNA from the reversed lncRNA pairs. The stability of the gene pairs obtained from the normal samples was 98.72%. Twenty pairs of survival-related significantly reversed lncRNA gene pairs with 33 lncRNA were found. The results of functional enrichment showed that the functions of these lncRNA pairs were consistent with the known results. Because of its cross-platform and easy detection of independent samples, this result can be better applied to clinical diagnosis and can detect the risk and prognosis of possible LUAD in advance.

Background Genetic regulation is known to contribute to the divergent expression of duplicate genes; however, little is known about how epigenetic modifications regulate the expression of duplicate genes in plants. Methods The histone modification (HM) profile patterns of different modes of gene duplication, including the whole genome duplication, proximal duplication, tandem duplication and transposed duplication were characterized based on ChIP-chip or ChIP-seq datasets. In this study, 10 distinct HM marks including H2Bub, H3K4me1, H3K4me2, H3K4me3, H3K9ac, H3K9me2, H3K27me1, H3K27me3, H3K36me3 and H3K14ac were analyzed. Moreover, the features of gene duplication with different HM patterns were characterized based on 88 RNA-seq datasets of Arabidopsis thaliana. Results This study showed that duplicate genes in Arabidopsis have a more similar HM pattern than single-copy genes in both their promoters and protein-coding regions. The evolution of HM marks is found to be coupled with coding sequence divergence and expression divergence after gene duplication. We found that functionally selective constraints may impose on epigenetic evolution after gene duplication. Furthermore, duplicate genes with distinct functions have more divergence in histone modification compared with the ones with the same function, while higher expression divergence is found with mutations of chromatin modifiers. This study shows the role of epigenetic marks in regulating gene expression and functional divergence after gene duplication in plants based on sequencing data.

Esophageal squamous cell carcinoma (ESCC) is a deadly disease that requires extensive research. In this review, we update recent progress in the research area of targeted therapy for ESCC. SOX2 and its associated proteins (e.g., ΔNP63α), which regulate lineage survival of ESCC cells, are proposed as therapeutic targets. It is believed that targeting the lineage-survival mechanism may be more effective than targeting other mechanisms. With the advent of a new era of personalized targeted therapy, there is a need to move from the tumor-centric model into an organismic model.

A novel single-isomer cyclodextrin derivative, heptakis {2,6-di-O-[3-(1,3-dicarboxyl propylamino)-2-hydroxypropyl]}-β-cyclodextrin (glutamic acid-β-cyclodextrin) was synthesized and used as a chiral selector in capillary electrophoresis for the enantioseparation of 12 basic drugs, including terbutaline, clorprenaline, tulobuterol, clenbuterol, procaterol, carvedilol, econazole, miconazole, homatropine methyl bromide, brompheniramine, chlorpheniramine and pheniramine. The primary factors affecting separation efficiency, which include the background electrolyte pH, the concentration of glutamic acid-β-cyclodextrin and phosphate buffer concentration, were investigated. Satisfactory enantioseparations were obtained using an uncoated fused-silica capillary of 50 cm (effective length 40 cm) × 50 μm id with 120 mM phosphate buffer (pH 2.5-4.0) containing 0.5-4.5 mM glutamic acid-β-cyclodextrin as background electrolyte. A voltage of 20 kV was applied and the capillary temperature was kept at 20°C. The results proved that glutamic acid-β-cyclodextrin was an effective chiral selector for studied 12 basic drugs. Moreover, the possible chiral recognition mechanism of brompheniramine, chlorpheniramine and pheniramine on glutamic acid-β-cyclodextrin was investigated using the semi-empirical Parametric Method 3.

The transpiration of trees plays a decisive role in the water balance of forest stands and in water yields from forested catchments, especially an artificial forest planted for the purpose of soil and water conservation in semiarid mountain ecosystem regions. For proper management of watershed ecosystems, quantification of water use, sensitivity and adaptation for artificial forest is needed. This study were monitored the sap flow for Larix principis-rupprechtii plantation by thermal dissipation probes (TDP), analyzed the correlation between the sap flow and the meteorological factors on daily and seasonal scale, and upscaled stand transpiration from individual sap flow measurements. Within a daily timescale, the net radiation (Ra), air temperature (AT), air humidity (AH), vapor pressure deficit (VPD) and wind speed (WS) showed a significantly positive correlation with sap flow velocity in day-time, but in the night-time sap flow had no significant correlation. Within a monthly timescale, the Ra, AT, WS, and VPD showed a significantly positive correlation with stand water use, whereas precipitation (Pr) showed a significantly negative correlation with stand water use. Our results also showed that the daily transpiration of L. principis-rupprechtii continued to increase with the increase of net radiation (Ra), until the late stages of growth season (except rainy and cloudy days), and the sap flow velocity showed an obvious hysteresis response to meteorological factors to alleviate plant water stress from June to October, while there was no significant correlation between day-time and night-time water use during the stage of germination and rapid growth in May. Besides, due to the relatively low temperature, the water consumption of forest stands was only about 151.05 mm during the whole growing season, and there was no obvious ‘noon break’ phenomenon in the whole growing season. These results indicated that L. principis-rupprechtii could manage the water consumption conservatively, and were appropriate for afforestation in the mountains ecosystem with high altitude and low temperature.

Deoxyribonuclease I (DNase I)-hypersensitive site sequencing (DNase-seq) has been widely used to determine chromatin accessibility and its underlying regulatory lexicon. However, exploring DNase-seq data requires sophisticated downstream bioinformatics analyses. In this study, we first review computational methods for all of the major steps in DNase-seq data analysis, including experimental design, quality control, read alignment, peak calling, annotation of cis-regulatory elements, genomic footprinting and visualization. The challenges associated with each step are highlighted. Next, we provide a practical guideline and a computational pipeline for DNase-seq data analysis by integrating some of these tools. We also discuss the competing techniques and the potential applications of this pipeline for the analysis of analogous experimental data. Finally, we discuss the integration of DNase-seq with other functional genomics techniques.

LncRNAs are involved in a wide range of biological processes, such as chromatin remodeling, mRNA splicing, mRNA editing and translation. They can either upregulate or downregulate gene expression, and play key roles in the progression of various human cancers. However, the functional mechanisms of most lncRNAs still remain unknown at present. This paper aims to provide space for the understanding of lncRNAs by proposing a new method to obtain protein-coding genes (PCGs) regulated by lncRNAs, thus identifying candidate cancer-related lncRNAs using bioinformatics approaches. This study presents a method based on sample correlation, which is applied to the expression profiles of lncRNAs and PCGs in prostate cancer in combination with protein interaction data to build a lncRNA-PCG bipartite network. Candidate cancer-related lncRNAs were extracted from the bipartite network by using a random walk. 14 prostate cancer-related lncRNAs were acquired from the LncRNADisease database and MNDR, of which 6 lncRNAs were present in our network. As one of the seed nodes, ENSG00000234741 achieved the highest score among them. The other two cancer-related lncRNAs (ENSG00000225937 and ENSG00000236830) were ranked within the top 30. In addition, the top candidate lncRNA ENSG00000261777 shares an intron with DDX19, and interacts with IGF2 P1, indicating its involvement in prostate cancer. In this paper, we described a new method for predicting candidate lncRNA targets, and obtained candidate therapeutic targets using this method. We hope that this study will bring a new perspective in future lncRNA studies.

A simple and sensitive analytical method for four isomers of glycopyrrolate in rat plasma was developed using cation-selective exhaustive injection-sweeping cyclodextrin-modified electrokinetic chromatography (CSEI-Sweeping-CDEKC) for online enrichment combined with dispersive micro-solid-phase extraction pretreatment. The CSEI-Sweeping-CDEKC was conducted on an uncoated fused silica capillary (40.2 cm × 75 μm) with an applied voltage of -20 kV. The electrophoretic analysis was carried out in 30 mM phosphate solution at pH 2.0 containing 20 mg/mL sulfated-β-cyclodextrin and 5% acetonitrile. Under these optimized conditions, the detection limit for racemic glycopyrrolate was found to be 2.0 ng/mL and this method could increase 495-fold detection sensitivity compared with the traditional injection method. Additionally, the parameters that affected the extraction efficiency of dispersive micro-solid-phase extraction were also examined systematically. The glycopyrrolate isomers in rat plasma samples as low as 0.0625 μg/mL were able to be separated and detected by capillary electrophoresis with the aid of CSEI-sweeping. The findings of this study show that the dispersive micro-solid-phase extraction pretreatment coupled with CSEI-Sweeping-CDEKC is a rapid and convenient method for analyzing glycopyrrolate isomers in rat plasma.

Copy number alteration (CNA) represents an important class of genetic variations that may contribute to tumorigenesis, tumor growth and metastatic spread. CNA can directly affect the expression of genes within the CNA regions; however, genes within the CNA regions exhibit heterogeneity in gene dosage sensitivity. In this study, a computational framework was built to identify 1170 dosage-sensitive genes (DSGs) and 1215 dosage-resistant genes (DRGs) that were related to ovarian serous cystadenocarcinoma (OV) through the association between CNA and gene expression. To analyze the different functions of the genes within the two groups, the functional annotation results indicated that DRGs were involved in cancer-related processes like immune response, cell death and apoptosis, while DSGs were enriched in essential processes like the cell cycle and the DNA metabolic process. Meanwhile, two three-dimensional regulatory networks for differentially expressed miRNAs, differentially expressed transcription factors (TFs) and DSGs or DRGs were constructed based on feed-forward loops. We identified key regulators (such as miR-16-5p, miR-98-5p, MYB and HOXA5) and cancer prognosis-related network motifs (such as miR-98-5p-HOXA5-TP53 and miR-16-5p-MYB-IGF1R) after the analysis of network topological features. Our results lead us to speculate that these genes and associated regulators may be potential mechanistic biomarkers for tumorigenesis and progression of cancer. Research on the network characteristics and the role of feed-forward loops in OV tumorigenesis and development could lead to feasible suggestions for the prevention and early diagnosis of OV, which will shed light on understanding the functional mechanism of CNA in cancer.