Identification of drug responsive enhancers by predicting chromatin accessibility change from perturbed gene expression profiles.

Individual may response to drug treatment differently due to their genetic variants located in enhancers. These variants can alter transcription factor's (TF) binding strength, affect enhancer's chromatin activity or interaction, and eventually change expression level of downstream gene. Here, we propose a computational framework, PERD, to Predict the Enhancers Responsive to Drug. A machine learning model was trained to predict the genome-wide chromatin accessibility from transcriptome data using the paired expression and chromatin accessibility data collected from ENCODE and ROADMAP. Then the model was applied to the perturbed gene expression data from Connectivity Map (CMAP) and Cancer Drug-induced gene expression Signature DataBase (CDS-DB) and identify drug responsive enhancers with significantly altered chromatin accessibility. Furthermore, the drug responsive enhancers were related to the pharmacogenomics genome-wide association studies (PGx GWAS). Stepping on the traditional drug-associated gene signatures, PERD holds the promise to enhance the causality of drug perturbation by providing candidate regulatory element of those drug associated genes.

Artemyriantholides A-K, guaiane-type sesquiterpenoid dimers from Artemisia myriantha var. pleiocephala and their antihepatoma activity.

Artemyriantholides A-K (1-11) as well as 14 known compounds (12-25) were isolated from Artemisia myriantha var. pleiocephala (Asteraceae). The structures and absolute configuration of compounds 2 and 8-9 were confirmed by the single crystal X-ray diffraction analyses, and the others were elucidated by MS, NMR spectral data and electronic circular dichroism calculations. All compounds were chemically characterized as guaiane-type sesquiterpenoid dimers (GSDs). Compound 1 was the first example of the GSD fused via C-3/C-11' and C-5/C-13' linkages, and compounds 2 and 5 were rare GSDs containing chlorine atoms. Eleven compounds showed obvious inhibitory activity in HepG2, Huh7 and SK-Hep-1 cell lines by antihepatoma assay to provide the IC50 values ranging from 7.9 to 67.1 µM. Importantly, compounds 5 and 8 exhibited the best inhibitory activity with IC50 values of 14.2 and 18.8 (HepG2), 9.0 and 11.5 (Huh7), and 8.8 and 11.3 µM (SK-Hep-1), respectively. The target of compound 5 was predicted to be MAP2K2 by a computational prediction model. The interaction between compound 5 and MAP2K2 was conducted to give docking score of -9.0 kcal/mol by molecular docking and provide KD value of 43.7 µM by Surface Plasmon Resonance assay.

Artificial Vegetation for Sand Stabilization May Impact Sand Lake Dynamics in Dune Regions.

Vegetation on dunes regulates the water supply from the dunes to the inter-dune lowland, which is a crucial factor affecting lake water dynamics in the inter-dune lowland. Previous researchers have paid insufficient attention to the water regulation function of dunes on a landscape- and regional scale. To fill this gap, both remote sensing technology and field observations were used to analyze the variations in the lake area and their influence factors, such as vegetation coverage and precipitation in the lake watershed, on a multi-year scale (2000-2020) and one-year scale (2021), respectively. The results showed that precipitation is the main factor influencing the changes in lake water, and artificial sand vegetation can regulate the changes in lake water. On the multi-year scale, with the coverage of artificial sand-fixing vegetation increasing on sand dunes in the lake watershed, the areas of the lakes were gradually decreasing. On the one-year scale, with dune vegetation coverage increased, the water supply from dunes to lakes showed a decreasing trend. This model can provide a possibility for estimating and predicting the influence of water supply from dunes to lakes that is affected by sand-fixing vegetation. The findings have significant theoretical and practical utility for the rational utilization of water resources in sandy land, as well as for assisting in the selection of an optimized construction mode for desert control projects.

Design, synthesis, and biological evaluation of artemyrianolide H derivatives as potential antihepatoma agents.

Artemyrianolide H (AH) is a germacrene-type sesquiterpenolid isolated from Artemisia myriantha, and showed potent cytotoxicity against three human hepatocellular carcinoma cell lines HepG2, Huh7, and SK-Hep-1 with IC50 values of 10.9, 7.2, and 11.9 µM, respectively. To reveal structure-activity relationship, 51 artemyrianolide H derivatives including 19 dimeric analogs were designed, synthesized, and assayed for their cytotoxicity against three human hepatoma cell lines. Among them, 34 compounds were more active than artemyrianolide H and sorafenib on the three cell lines. Especially, compound 25 exhibited the most promising activity with IC50 values of 0.7 (HepG2), 0.6 (Huh7), and 1.3 µM (SK-Hep-1), which were 15.5, 12.0, and 9.2-fold higher than that of AH and 16.4, 16.3 and 17.5-fold higher than that of sorafenib. Cytotoxicity evaluation on normal human liver cell lines (THLE-2) demonstrated good safety profile of compound 25 with SI of 1.9 (HepG2), 2.2 (Huh 7) and 1.0 (SK-Hep1). Further studies revealed that compound 25 dose-dependently arrested cells at G2/M phase which was correlated with the up-regulation of both cyclin B1 and p-CDK1, and induced apoptosis through the activation of mitochondrial pathways in HepG2 cells. In addition, the migratory and invasive abilities in HepG2 cells after treatment with 1.5 µM of compound 25 were decreased by 89% and 86% with the increase of E-cadherin expression accompanied by the decrease of N-cadherin, vimentin expression. Bioinformatics analysis based on machine learning predicted that PDGFRA and MAP2K2 might be acting targets of compound 25, and SPR assays demonstrated compound 25 were bound with PDGFRA and MAP2K2 with KD value of 0.168 nM, and 8.49 µM, respectively. This investigation proposed that compound 25 might be considered as a promising lead compound for the development of antihepatoma candidate.

The genetic diversity, replication, and transmission of 2009 pandemic H1N1 viruses in China.

Background: The 2009 pandemic H1N1 influenza A virus (pdm09) continue to evolve, and few studies have systemically analyzed the evolution, replication, and transmission of pmd09 viruses in China. Methods: To better understand the evolution and pathogenicity of pdm09 viruses, we systematically analyzed viruses that were confirmed in 2009-2020 in China and characterized their replication and transmission ability. We extensively analyzed the evolution characteristics of pdm/09 in China over the past decades. The replication ability of 6B.1 and 6B.2 lineages on Madin-Darby canine kidney (MDCK) and human lung adenocarcinoma epithelial (A549) cells and their pathogenicity and transmission in guinea pigs were also compared. Results: In total, 3,038 pdm09 viruses belonged to clade 6B.1 (62% of all pdm09 viruses) and clade 6B.2 (4%). Clade 6B.1 pdm09 viruses are the predominant clade, with proportions of 54.1%, 78.9%, 57.2%, 58.6%, 61.7%, 76.3%, and 66.6% in the North, Northeast, East, Central, South, Southwest, and Northeast regions in China, respectively. The isolation proportion of clade 6B.1 pdm/09 viruses was 57.1%, 74.3%, 96.1%, 98.2%, 86.7%, and 78.5% in 2015-2020, respectively. A clear differentiation time point appeared in 2015 before which the evolution trend of pdm09 viruses in China was similar to that in North America but then showed a different trend after that point. To characterize pdm09 viruses in China after 2015, we further analyzed 33 pdm09 viruses isolated in Guangdong in 2016-2017, among which A/ Guangdong/33/2016 and A/Guangdong/184/2016 (184/2016) belonged to clade 6B.2, and the other 31 strains belonged to clade 6B.1. A/Guangdong/887/2017 (887/2017) and A/Guangdong/752/2017 (752/2017) (clade 6B.1), 184/2016 (clade 6B.2) and A/California/04/2009 (CA04) replicated efficiently in MDCK cells and A549 cells, as well as the turbinates of guinea pigs. 184/2016 and CA04 could transmit among guinea pigs through physical contact. Conclusion: Our findings provide novel insights into the evolution, pathogenicity, and transmission of pdm09 virus. The results show that enhancing surveillance of pdm09 viruses and timely evaluation of their virulence are essential.

Chloroplast phylogenomics and the taxonomy of Saxifraga section Ciliatae (Saxifragaceae).

Comprising ca. 200 species, Saxifraga sect. Ciliatae is the most species-rich section of Saxifraga s.str., whose center of diversity is in the Tibeto-Himalayan region. The infra-sectional classification of sect. Ciliatae is still in debate due to the high level of species richness, as well as remarkable variations of habitat, morphology, physiology and life cycles. Subdivisions of this section proposed in various taxonomic systems have not been adequately tested in previous phylogenetic studies, partly due to low taxonomic sampling density, but also to the use of few DNA markers. In order to achieve a more robust infra-sectional classification of sect. Ciliatae, complete chloroplast genomes of 94 taxa from this section were analyzed, of which 93 were newly sequenced, assembled and annotated. The length of the 94 plastomes of sect. Ciliatae taxa range from 143,479 to 159,938 bp, encoding 75 to 79 unique protein-coding genes (PCGs). Analyses of the 94 plastomes revealed high conservation in structural organization, gene arrangement, and gene content. Gene loss and changes of IR boundaries were detected but in extremely low frequency. The molecular phylogenetic tree from concatenated PCGs and complete chloroplast genome sequences exhibited high resolution and support values and confirms that sect. Ciliatae is monophyletic. Three well-supported clades were revealed within the section that agree relatively well with the subsectional taxonomy of Gornall (1987), but some minor modifications should be made. Firstly, the monotypic subsection Cinerascentes should be abandoned and its constituent species, S. cinerascens, assigned to subsect. Gemmiparae. Secondly, subsections Rosulares and Serpyllifoliae should be merged and become subsect. Rosulares. Section Ciliatae thus comprises: subsect. Hirculoideae Engl. & Irmsch.; subsect. Rosulares Gornall; subsect. Gemmiparae Engl. & Irmsch.; subsect. Flagellares (C. B. Clarke) Engl. & Irmsch. and subsect. Hemisphaericae (Engl. & Irmsch.) Gornall.

A glutathione S-transferase GhTT19 determines flower petal pigmentation via regulating anthocyanin accumulation in cotton.

Anthocyanin accumulations in the flowers can improve seed production of hybrid lines, and produce higher commodity value in cotton fibre. However, the genetic mechanism underlying the anthocyanin pigmentation in cotton petals is poorly understood. Here, we showed that the red petal phenotype was introgressed from Gossypium bickii through recombination with the segment containing the R3 bic region in the A07 chromosome of Gossypium hirsutum variety LR compared with the near-isogenic line of LW with white flower petals. The cyanidin-3-O-glucoside (Cy3G) was the major anthocyanin in red petals of cotton. A GhTT19 encoding a TT19-like GST was mapped to the R3 bic site associated with red petals via map-based cloning, but GhTT19 homologue gene from the D genome was not expressed in G. hirsutum. Intriguingly, allelic variations in the promoters between GhTT19LW and GhTT19LR , rather than genic regions, were found as genetic causal of petal colour variations. GhTT19-GFP was found localized in both the endoplasmic reticulum and tonoplast for facilitating anthocyanin transport. An additional MYB binding element found only in the promoter of GhTT19LR , but not in that of GhTT19LW , enhanced its transactivation by the MYB activator GhPAP1. The transgenic analysis confirmed the function of GhTT19 in regulating the red flower phenotype in cotton. The essential light signalling component GhHY5 bonded to and activated the promoter of GhPAP1, and the GhHY5-GhPAP1 module together regulated GhTT19 expression to mediate the light-activation of petal anthocyanin pigmentation in cotton. This study provides new insights into the molecular mechanisms for anthocyanin accumulation and may lay a foundation for faster genetic improvement of cotton.

Belowground bud banks and land use change: roles of vegetation and soil properties in mediating the composition of bud banks in different ecosystems.

Introduction: Belowground bud banks play integral roles in vegetation regeneration and ecological succession of plant communities; however, human-caused changes in land use severely threaten their resilience and regrowth. Although vegetation attributes and soil properties mediate such anthropogenic effects, their influence on bud bank size and composition and its regulatory mechanisms under land use change have not been explored. Methods: We conducted a field investigation to examine impacts of land use change on bud bank size and composition, vegetation attributes, and soil properties in wetlands (WL), farmlands (FL), and alpine meadow (AM) ecosystems in Zhejiang Province, China. Results: Overall, 63 soil samples in close proximity to the vegetation quadrats were excavated using a shovel, and samples of the excavated soil were placed in plastic bags for onward laboratory soil analysis. The total bud density (1514.727 ± 296.666) and tiller bud density (1229.090 ± 279.002) in wetland ecosystems were significantly higher than in farmland and alpine meadow ecosystems [i.e., total (149.333 ± 21.490 and 573.647 ± 91.518) and tiller bud density (24.666 ± 8.504 and 204.235 ± 50.550), respectively]. While vegetation attributes critically affected bud banks in WL ecosystems, soil properties strongly influenced bud banks in farmland and alpine meadow ecosystems. In wetland ecosystems, total and tiller buds were predominantly dependent on soil properties, but vegetation density played a significant role in farmlands and alpine meadow ecosystems. Root sprouting and rhizome buds significantly correlated with total C in the top 0 - 10 cm layer of farmland and alpine meadow ecosystems, respectively, and depended mainly on soil properties. Discussion: Our results demonstrate that land use change alters bud bank size and composition; however, such responses differed among bud types in wetland, farmland, and alpine meadow ecosystems.

Grassland coverage change and its humanity effect factors quantitative assessment in Zhejiang province, China, 1980-2018.

This study aims to make clear of grassland coverage change and quantitative assessment its effect factors. We collected the data from the National Bureau of Statistics ( http://www.stats.gov.cn ) and "China 20th Century Land Use/Cover Change (LUCC) Spatio-temporal Platform". Grassland coverage area showed an upward trend from 1980 to 1990, and the grassland coverage area is gradually decreasing from 1990 to 2000, and the grassland coverage area has not changed much from 2000 to 2018. The medium-coverage grassland area has the highest correlation with the total population, and the high-coverage grassland area has the lowest correlation with the total population. Land use types and the composite of gross agricultural output have influence on grassland coverage area. It is hoped that relevant policies should consider land use types and ecological benefits while balancing economic development and urban development.

The molecular characteristics of gastric cancer patients living in Qinghai-Tibetan Plateau.

Gastric cancer, or stomach cancer, that originates in the inner lining of the stomach, was the fifth most common cancer and the fourth mortality globally, with over one million new cases in 2020 and an estimated 769,000 deaths. The molecular characteristics of gastric cancer has been complicated by histological and intratumor heterogeneity. The incidence of gastric cancer shows wide geographical variation. As the largest and highest region in China, Qinghai-Tibetan Plateau is one of the important global biodiversity hotspots. Here, we collect tumour and paired normal bio-samples from 31 primary gastric cancer patients from Qinghai Provincial People's Hospital, and discuss the molecular characteristics for gastric cancer patients living in plateau. They have more single nucleotide polymorphisms (SNP) located in chromosome 7 with C → T and G → A as the most common alteration types, barely share the cancer driver genes with western patients, and have no significant differences in various Chinese nation. These characteristics offers a great opportunity to further understanding the divergent mechanism of gastric cancer, increase the efficacy for diagnosis and prognosis, finally lead the optimal targeted therapeutics.

Effects of multiple antibiotics residues in broiler manure on composting process.

At present, the effect of multiple antibiotics on aerobic composting process and its mechanism are not clear. So in this study, broiler manure containing different doses of Doxycycline (DOX) and Gatifloxacin (GAT) were used as raw materials and mixed with rice hull for aerobic composting, and the effects of the combination of multiple antibiotics on the process parameters of broiler manure composting and the succession of bacterial and fungal community structures were systematically analyzed. Our results showed that at the initial period of composting, the combination of multiple antibiotics led to a delayed temperature and pH increase (T1: 57.0 °C, T2: 48.3 °C, T3: 45.5 °C on Day 3 for temperature and T1: 7.44, T2: 7.1, T3: 6.88 on Day 5 for pH), and a slow total nitrogen decrease (T1: 1.56%, T2: 1.82%, T3: 1.74% on Day 5). Although these effects decreased gradually with the degradation of antibiotics, the relative abundance of Actinobacteriota (T1: 13.29%, T2: 10.57%, T3: 8.99%) and Bacteroidota (T1:27.52%, T2:40.03%, T3:39.81%)) were still influenced by multiple antibiotic residuals until the end of composting period. Higher levels of antibiotics had more lasting effects on the bacterial community (T3 > T2). However, the combination of these two antibiotics did not significantly promote or inhibit the succession of the fungal community structure. The heatmaps showed that composting stage had a greater effect on the microbial community structures than antibiotics. The results provided a theoretical reference for composting broiler manure containing DOX and GAT.

Dissipation Dynamics of Doxycycline and Gatifloxacin and Accumulation of Heavy Metals during Broiler Manure Aerobic Composting.

In this study, broilers were fed with heavy-metal-containing diets (Zn, Cu, Pb, Cr, As, Hg) at three rates (T1: 5 kg premix/ton feed, T2: 10 kg premix/ton feed and T3: 15 kg premix/ton feed) and Doxycycline (DOX) and Gatifloxacin (GAT) at low or high doses (T4: 31.2 mg DOX/bird/day and 78 mg GAT/bird/day, T5: 15.6 mg DOX/bird/day and 48 mg GAT/bird/day) to assess the accumulation of various heavy metals and the fate of two antibiotics in broiler manure after 35 days of aerobic composting. The results indicated that the two antibiotics changed quite differently during aerobic composting. About 14.96-15.84% of Doxycycline still remained at the end of composting, while Gatifloxacin was almost completely removed within 10 days of composting. The half-lives of Doxycycline were 13.75 and 15.86 days, while the half-lives of Gatifloxacin were only 1.32 and 1.38 days. Based on the Redundancy analysis (RDA), the concentration of antibiotics was significantly influenced by physico-chemical properties (mainly temperature and pH) throughout the composting process. Throughout the composting process, all heavy metal elements remained concentrated in organic fertilizer. In this study the Cr content reached 160.16 mg/kg, 223.98 mg/kg and 248.02 mg/kg with increasing premix feed rates, similar to Zn, which reached 258.2 mg/kg, 312.21 mg/kg and 333.68 mg/kg. Zn and Cr concentrations well exceeded the United States and the European soil requirements. This experiment showed that antibiotic residues and the accumulation of heavy metals may lead to soil contamination and pose a risk to the soil ecosystem.

Computational Probing the Methylation Sites Related to EGFR Inhibitor-Responsive Genes.

The emergence of drug resistance is one of the main obstacles to the treatment of lung cancer patients with EGFR inhibitors. Here, to further understand the mechanism of EGFR inhibitors in lung cancer and offer novel therapeutic targets for anti-EGFR-inhibitor resistance via the deep mining of pharmacogenomics data, we associated DNA methylation with drug sensitivities for uncovering the methylation sites related to EGFR inhibitor sensitivity genes. Specifically, we first introduced a grouped regularized regression model (Group Least Absolute Shrinkage and Selection Operator, group lasso) to detect the genes that were closely related to EGFR inhibitor effectiveness. Then, we applied the classical regression model (lasso) to identify the methylation sites associated with the above drug sensitivity genes. The new model was validated on the well-known cancer genomics resource: CTRP. GeneHancer and Encyclopedia of DNA Elements (ENCODE) database searches indicated that the predicted methylation sites related to EGFR inhibitor sensitivity genes were related to regulatory elements. Moreover, the correlation analysis on sensitivity genes and predicted methylation sites suggested that the methylation sites located in the promoter region were more correlated with the expression of EGFR inhibitor sensitivity genes than those located in the enhancer region and the TFBS. Meanwhile, we performed differential expression analysis of genes and predicted methylation sites and found that changes in the methylation level of some sites may affect the expression of the corresponding EGFR inhibitor-responsive genes. Therefore, we supposed that the effectiveness of EGFR inhibitors in lung cancer may be improved by methylation modification in their sensitivity genes.

DeepDRK: a deep learning framework for drug repurposing through kernel-based multi-omics integration.

Recent pharmacogenomic studies that generate sequencing data coupled with pharmacological characteristics for patient-derived cancer cell lines led to large amounts of multi-omics data for precision cancer medicine. Among various obstacles hindering clinical translation, lacking effective methods for multimodal and multisource data integration is becoming a bottleneck. Here we proposed DeepDRK, a machine learning framework for deciphering drug response through kernel-based data integration. To transfer information among different drugs and cancer types, we trained deep neural networks on more than 20 000 pan-cancer cell line-anticancer drug pairs. These pairs were characterized by kernel-based similarity matrices integrating multisource and multi-omics data including genomics, transcriptomics, epigenomics, chemical properties of compounds and known drug-target interactions. Applied to benchmark cancer cell line datasets, our model surpassed previous approaches with higher accuracy and better robustness. Then we applied our model on newly established patient-derived cancer cell lines and achieved satisfactory performance with AUC of 0.84 and AUPRC of 0.77. Moreover, DeepDRK was used to predict clinical response of cancer patients. Notably, the prediction of DeepDRK correlated well with clinical outcome of patients and revealed multiple drug repurposing candidates. In sum, DeepDRK provided a computational method to predict drug response of cancer cells from integrating pharmacogenomic datasets, offering an alternative way to prioritize repurposing drugs in precision cancer treatment. The DeepDRK is freely available via https://github.com/wangyc82/DeepDRK.

Geographical distribution of the dispersal ability of alien plant species in China and its socio-climatic control factors.

Dispersal ability is important for the introduction, establishment, and spread of alien plant species. Therefore, determination of the geographical distribution of the dispersal ability of such species, and the relationship between dispersal ability and socio-climatic factors are essential to elucidate the invasion strategies of the alien plant species. Analytic hierarchy process and inventory, risk rank, and dispersal mode data available on Chinese alien plant species were used to determine their dispersal ability, the geographical distribution thereof, and the relationship between socio-climatic factors and dispersal ability. High-risk alien plant species had a higher natural dispersal ability (or several natural dispersal modes) but a lower anthropogenic dispersal ability (or few anthropogenic dispersal modes) than low-risk alien plant species. The geographical distribution of the dispersal ability of the alien plant species showed an inverse relationship with species density. Alien plant species with low dispersal ability (i.e., with fewer dispersal modes and distribution in the southeast) showed a tendency to adapt to environments with mild climates, while those with high dispersal ability (i.e., with more disposal nodes and distribution in the northwest) showed a tendency to adapt to harsh environments. It is essential for land managers and policy makers to understand the geographical distribution of the dispersal ability of alien plant species and their socio-climatic control factors to formulate strategies to control the natural and anthropogenic dispersal of such plants.

Computational Prediction of Drug Responses in Cancer Cell Lines From Cancer Omics and Detection of Drug Effectiveness Related Methylation Sites.

Accurately predicting the response of a cancer patient to a therapeutic agent remains an important challenge in precision medicine. With the rise of data science, researchers have applied computational models to study the drug inhibition effects on cancers based on cancer genomics and transcriptomics. Moreover, a common epigenetic modification, DNA methylation, has been related to the occurrence and development of cancer, as well as drug effectiveness. Therefore, it is helpful for improvement of drug response prediction through exploring the relationship between DNA methylation and drug effectiveness. Here, we proposed a computational model to predict drug responses in cancers through integration of cancer genomics, transcriptomics, epigenomics, and compound chemical properties. Meanwhile, we applied a regularized regression model (Least Absolute Shrinkage and Selection Operator, lasso) to detect the methylation sites that were closely related to drug effectiveness. The prediction models were trained on a well-known pharmacogenomics data resource, Genomics of Drug Sensitivity in Cancer (GDSC). The cross-validation indicates that the performance of the prediction model using DNA methylation is comparable to that of using other cancer omics, including oncogene mutation and gene expression data. It indicates the important role of DNA methylation in prediction of drug responses. Encyclopedia of DNA Elements (ENCODE) and Transcriptional Regulatory Relationships Unraveled by Sentence-based Text mining (TRRUST2) database analyses suggest that the methylation sites associated with drug effectiveness are mainly located in the transcription factor (TF) binding region. Therefore, we hypothesized that the sensitivity of cancer cells to drugs could be regulated by changing the methylation modification of TF binding region. In conclusion, we confirmed the important role of DNA methylation in prediction of drug responses, and provided some methylation sites that closely related to the drug effectiveness, which may be a great regulatory target for improvement of drug treatment effects on cancer patients.

Effects of climatic and social factors on dispersal strategies of alien species across China.

Determination of dispersal strategies of alien species and its relationship with social and climatic factors are essential to understand the mechanisms of species invasion and adaption. Based on morphological trait, dispersal mode, and dispersal agent of diaspore of 562 alien species across China, we determined: (i) the proportions of five dispersal strategies (i.e., autochory, anemochory, hydrochory, zoochory, and anthropochory), (ii) the relationships between the dispersal strategies and socio-climatic factors in 34 administrative regions across China, and (iii) the correlations between different dispersal strategies. Anthropochory, zoochory, and anemochory account for nearly 90.0% of all the dispersal strategies of alien species. Mean frost days (MFD), mean annual humidity (MAH), and gross domestic product (GDP) were the main climatic and social factors that were correlated to different dispersal strategies. Zoochory was positively related to MFD, but negatively related to the autochory and anthropochory. MAH negatively influenced the anemochory, while GDP positively influenced the hydrochory. We classified the six dispersal strategies into two groups based on the correlations among dispersal strategies, group I included autochory and anthropochory, and group II included anemochory, hydrochory, and zoochory. Within a group, dispersal strategies were positively correlated, while between groups, dispersal strategies were negatively correlated. Positive correlation between different strategies might be co-owned while negative correlation between different strategies might not be co-owned by one alien species. Understanding the characteristics of the dispersal strategies of alien species is important for policy makers when controlling the dispersal of malignant invasive alien species, predicting the distribution, and decreasing or cutting off the dispersal pathways of invasive alien species.

The Clinical and Molecular Characterization of Gastric Cancer Patients in Qinghai-Tibetan Plateau.

Gastric cancer was the fifth most common malignancy and the third deadliest cancer (738,000 deaths in 2018) in the world. The analysis of its molecular characteristics has been complicated by histological and intratumor heterogeneity. Furthermore, the previous studies indicate that the incidence of gastric cancer shows wide geographical variation. As the largest and highest region in China, Qinghai-Tibetan Plateau (QTP) is one of the important global biodiversity hotspots. Here, to better understand the mechanism of gastric cancer and offer the targeted therapeutic strategies specially designed for patients in QTP, we collect tumor and blood samples from 30 primary gastric adenocarcinoma cancer patients at Qinghai Provincial People's Hospital. We discuss the clinical and molecular characteristics for these patients that have been ascribed to the unique features in this place, including high altitude (the average height above sea level is around 4,000 m), multi-ethnic groups, and the specific ways of life or habits (such as eating too much beef and mutton, have alcohol and cigarette problem, et al.). By comparing with the western gastric cancer patients collected from TCGA data portal, some unique characteristics for patients in QTP are suggested. They include high incidence in younger people, most of tumor are located in body, most of SNP are detected in chromosome 7, and the very different molecular atlas in minor ethnic groups and Han Chinese. These characteristics will provide the unprecedented opportunity to increase the efficacy for diagnosis and prognosis of gastric cancer in QTP. Furthermore, to suggest the targeted therapeutics specially designed for these 30 patients, an adapted kernel-based learning model and a compilation of pharmacogenomics data of 462 patient-derived tumor cells (PDCs) that illustrate the diverse genetic and molecular backgrounds of cancer patients, were introduced. In conclusion, our study offers a big opportunity to better understand the mechanism of gastric cancer in QTP and guide the optimal patient-tailored therapy for them.

Geographical distribution and determining factors of different invasive ranks of alien species across China.

Determination of the geographical distribution and life-form spectra of alien species with different invasive abilities are essential to understand the process of invasion and to develop measures to manage alien species. Based on six classifications of Chinese alien species, environmental and social data, we determined species density, life-form spectrum of alien species, and the relationship between species density of alien species and climatic or social factors. The species density of alien species increased from the northwest to the southeast regions of China for all the six ranks. The boundary line between low and high species density of alien species was consistent with the dividing line of population density (the "Hu Line"). Mean annual precipitation was the most important factor for species density in malignant invaders, serious invaders, local invaders, and species requiring further observation (Ranks I, II, III, and V, respectively). Gross domestic product per square kilometer and annual minimum temperature were the most important factors in mild invaders and cultivated aliens (Ranks IV and VI, respectively). Annual and biennial herbs made up 52.9% to 71.2% of total species in Ranks I to IV; shrubs and trees 3.7% to 14.7%. The annual and biennial herbs were 35.5% and 32.6%, and the shrubs and trees were 25.3% and 31.6% in Ranks IV and VI. Results implied that precipitation was the most important factor on species density for the invasive alien species. However, social factors and temperature were the most important factors for the non-invasive alien species. The invasive alien species had a high proportion of annual and biennial herbs and non-invasive alien had a high proportion of shrubs and trees. It is important to understand the geographical distribution and life-form spectra of various invasive alien species for alien species controls.

Associating divergent lncRNAs with target genes by integrating genome sequence, gene expression and chromatin accessibility data.

Recent RNA knockdown experiments revealed that a dozen divergent long noncoding RNAs (lncRNAs) positively regulate the transcription of genes in cis. Here, to understand the regulatory mechanism of divergent lncRNAs, we proposed a computational model IRDL (Identify the Regulatory Divergent LncRNAs) to associate divergent lncRNAs with target genes. IRDL took advantage of the cross-tissue paired expression and chromatin accessibility data in ENCODE and a dozen experimentally validated divergent lncRNA target genes. IRDL integrated sequence similarity, co-expression and co-accessibility features, battled the scarcity of gold standard datasets with an increasingly learning framework and identified 446 and 977 divergent lncRNA-gene regulatory associations for mouse and human, respectively. We found that the identified divergent lncRNAs and target genes correlated well in expression and chromatin accessibility. The functional and pathway enrichment analysis suggests that divergent lncRNAs are strongly associated with developmental regulatory transcription factors. The predicted loop structure validation and canonical database search indicate a scaffold regulatory model for divergent lncRNAs. Furthermore, we computationally revealed the tissue/cell-specific regulatory associations considering the specificity of lncRNA. In conclusion, IRDL provides a way to understand the regulatory mechanism of divergent lncRNAs and hints at hundreds of tissue/cell-specific regulatory associations worthy for further biological validation.