Doubly elastic net regularized online portfolio optimization with transaction costs.

Online portfolio optimization with transaction costs is a big challenge in large-scale intelligent computing community, since its undersample from rapidly-changing market and complexity from varying transaction costs. In this paper, we focus on this problem and solve it by machine learning system. Specifically, we reformulate the optimization problem with the minimization over simplex containing three items, which are negative expected return, the elastic net regularization of transaction costs controlled term and portfolio variable, respectively. We propose to apply linearized augmented Lagrangian method (LALM) and the alternating direction method of multipliers (ADMM) to solve the optimization model in a higher efficiency, meanwhile theoretically guarantee their convergence and deduce closed-form solutions of their subproblems in each iteration. Furthermore, we conduct extensive experiments on five benchmark datasets from real market to demonstrate that the proposed algorithms outperform compared state-of-the-art strategies in most cases in six dimensions.

Dual analysis of wild-type and attenuated Orf virus and host cell transcriptomes revealed novel virus-host cell interactions.

IMPORTANCE: Currently, the only available commercial vaccines for Orf virus (ORFV) are live attenuated vaccines, which present a potential risk of reversion to virulence. Therefore, understanding the pathogenic mechanisms of different virulent strains of ORFV and host immune responses triggered by these viruses is crucial for developing new vaccines and interventions. In this study, we found that the attenuated strain downregulates the host innate immune response and antiviral activity. In addition, we noted that the wild-type strain can induce the immune response pattern centered on interferon-stimulated genes and interferon regulatory factor gene family. We predicted that STAT1 and STAT2 are the main transcription factors upstream of target gene promoters through gene regulatory networks and exert significant regulatory effects on co-expressed genes. Our study elucidated the complex interaction between ORFV strains and host cell immune responses, providing new insights into vaccine research for ORFV.

Genetic Analysis of Orf Virus (ORFV) Strains Isolated from Goats in China: Insights into Epidemiological Characteristics and Evolutionary Patterns.

Contagious ecthyma (CE) is an acute infectious zoonosis caused by orf virus (ORFV) that mainly infects sheep and goats and causes obvious lesions and low market value of livestock, resulting in huge economic losses for farmers. In this study, two strains of ORFV were isolated from Shaanxi Province and Yunnan Province in China, named FX and LX. The two ORFVs were located in the major clades of domestic strains respectively, and exhibited distinct sequence homology. We analyzed the genetic data of core genes (B2L, F1L, VIR, ORF109) and variable genes (GIF, ORF125 and vIL-10) of ORFV to investigate its epidemiological and evolutionary characteristics. The sequences from 2007 to 2018 constituted the majority of the viral population, predominantly concentrated in India and China. Most genes were clustered into SA00-like type and IA82-like type, and the hotspots in East and South Asia were identified in the ORFV transmission trajectories. For these genes, VIR had the highest substitution rate of 4.85 × 10-4, both VIR and vIL-10 suffered the positive selection pressure during ORFV evolution. Many motifs associated with viral survival were distributed among ORFVs. In addition, some possible viral epitopes have been predicted, which still require validation in vivo and in vitro. This work gives more insight into the prevalence and phylogenetic relationships of existing orf viruses and facilitate better vaccine design.

Intestinal Microbial Diversity of Free-Range and Captive Yak in Qinghai Province.

BACKGROUND: The gut microbiome is a large and complex organic assemblage with subtle and close relationships with the host. This symbiotic mechanism is important for the health and adaptability of the host to the environment. Compared with other ruminants, there are few studies on yak intestinal microbes. The study of the gut microbiota of the yak will help us better understand the correlation between the microbiota and the environmental adaptability of the host. In this study, we adapted 16S rDNA sequencing technology to investigate the diversity and composition of the intestinal microbial community in free-range yaks and captive yaks living on the Qinghai-Tibet Plateau (QTP). RESULTS: Sequencing results showed that the intestinal microbial community diversity was significantly different between free-range yaks and captive yaks. Firmicutes and Bacteroidetes were the dominant bacteria in both free-range and captive yaks. However, there were differences between the microbes of the two analyzed feeding styles in different classification levels. Compared with the captive type, free-range yaks had a higher abundance of Ruminococcaceae, Eubacteriaceae, Desulfovibrionaceae, Elusimicrobium, and Oscillibacter, while the abundance of Succinivibrionaceae, Clostridiales, Lachnospiraceae, Prevotellaceae, Roseburia, and Barnesiella was relatively low. The feeding method may be the key factor for the formation of intestinal flora differences in yaks, while altitude did not significantly affect Qinghai yak. CONCLUSIONS: In this study, we used 16S rDNA sequencing technology to investigate the composition of intestinal flora in free-range and captive yaks living on the QTP. The exploration of dietary factors can provide a theoretical basis for scientifically and rationally breeding yaks and provides a new direction for the development of prebiotics and microecological agents.

Molecular Characterization and Elucidation of Pathways to Identify Novel Therapeutic Targets in Pulmonary Arterial Hypertension.

Background: Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disease. However, there are limited studies reflecting the available biomarkers from separate gene expression profiles in PAH. This study explored two microarray datasets by an integrative analysis to estimate the molecular signatures in PAH. Methods: Two microarray datasets (GSE53408 and GSE113439) were exploited to compare lung tissue transcriptomes of patients and controls with PAH and to estimate differentially expressed genes (DEGs). According to common DEGs of datasets, gene and protein overrepresentation analyses, protein-protein interactions (PPIs), DEG-transcription factor (TF) interactions, DEG-microRNA (miRNA) interactions, drug-target protein interactions, and protein subcellular localizations were conducted in this study. Results: We obtained 38 common DEGs for these two datasets. Integration of the genome transcriptome datasets with biomolecular interactions revealed hub genes (HSP90AA1, ANGPT2, HSPD1, HSPH1, TTN, SPP1, SMC4, EEA1, and DKC1), TFs (FOXC1, FOXL1, GATA2, YY1, and SRF), and miRNAs (hsa-mir-17-5p, hsa-mir-26b-5p, hsa-mir-122-5p, hsa-mir-20a-5p, and hsa-mir-106b-5p). Protein-drug interactions indicated that two compounds, namely, nedocromil and SNX-5422, affect the identification of PAH candidate biomolecules. Moreover, the molecular signatures were mostly localized in the extracellular and nuclear areas. Conclusions: In conclusion, several lung tissue-derived molecular signatures, highlighted in this study, might serve as novel evidence for elucidating the essential mechanisms of PAH. The potential drugs associated with these molecules could thus contribute to the development of diagnostic and therapeutic strategies to ameliorate PAH.

Edging on Mutational Bias, Induced Natural Selection From Host and Natural Reservoirs Predominates Codon Usage Evolution in Hantaan Virus.

The molecular evolutionary dynamics that shape hantaviruses' evolution are poorly understood even now, besides the contribution of virus-host interaction to their evolution remains an open question. Our study aimed to investigate these two aspects in Hantaan virus (HTNV)-the prototype of hantaviruses and an emerging zoonotic pathogen that infects humans, causing hemorrhagic fever with renal syndrome (HFRS): endemic in Far East Russia, China, and South Korea-via a comprehensive, phylogenetic-dependent codon usage analysis. We found that host- and natural reservoir-induced natural selection is the primary determinant of its biased codon choices, exceeding the mutational bias effect. The phylogenetic analysis of HTNV strains resulted in three distinct clades: South Korean, Russian, and Chinese. An effective number of codon (ENC) analysis showed a slightly biased codon usage in HTNV genomes. Nucleotide composition and RSCU analyses revealed a significant bias toward A/U nucleotides and A/U-ended codons, indicating the potential influence of mutational bias on the codon usage patterns of HTNV. Via ENC-plot, Parity Rule 2 (PR2), and neutrality plot analyses, we would conclude the presence of both mutation pressure and natural selection effect in shaping the codon usage patterns of HTNV; however, natural selection is the dominant factor influencing its codon usage bias. Codon adaptation index (CAI), Relative codon deoptimization index (RCDI), and Similarity Index (SiD) analyses uncovered the intense selection pressure from the host (Human) and natural reservoirs (Striped field mouse and Chinese white-bellied rat) in shaping HTNV biased codon choices. Our study clearly revealed the evolutionary processes in HTNV and the role of virus-host interaction in its evolution. Moreover, it opens the door for a more comprehensive codon usage analysis for all hantaviruses species to determine their molecular evolutionary dynamics and adaptability to several hosts and environments. We believe that our research will help in a better and deep understanding of HTNV evolution that will serve its future basic research and aid live attenuated vaccines design.

Analysis of codon usage patterns and influencing factors in rice tungro bacilliform virus.

Rice tungro bacilliform virus (RTBV) belongs to genus Tungrovirus within the family Caulimoviridae harbors circular double-stranded DNA (dsDNA). Rice tungro disease (RTD) caused by RTBV, responsible for severe rice yield losses in South and Southeast Asia. Here, we performed a systematic evolutionary and codon usage bias (CUB) analysis of RTBV genome sequences. We analysed different bioinformatics techniques to calculate the nucleotide compositions, the relative synonymous codon usage (RSCU), and other indices. The results indicated slightly or low codon usage bias in RTBV isolates. Mutation and natural selection pressures have equally contributed to this low codon usage bias. Additionally, multiple factors such as host, geographical distribution also affect codon usage patterns in RTBV genomes. RSCU analysis revealed that RTBV shows mutation bias and prefers A and U ended codons to code amino acids. Codon usage patterns of RTBV were also found to be influenced by its host. This indicates that RTBV have evolved codon usage patterns that are specific to its host. The findings from this study are expected to increase our understanding of factors leading to viral evolution and fitness with respect to hosts and the environment.

Genomic Features and Evolution of the Parapoxvirus during the Past Two Decades.

Parapoxvirus (PPV) has been identified in some mammals and poses a great threat to both the livestock production and public health. However, the prevalence and evolution of this virus are still not fully understood. Here, we performed an in silico analysis to investigate the genomic features and evolution of PPVs. We noticed that although there were significant differences of GC contents between orf virus (ORFV) and other three species of PPVs, all PPVs showed almost identical nucleotide bias, that is GC richness. The structural analysis of PPV genomes showed the divergence of different PPV species, which may be due to the specific adaptation to their natural hosts. Additionally, we estimated the phylogenetic diversity of seven different genes of PPV. According to all available sequences, our results suggested that during 2010-2018, ORFV was the dominant virus species under the selective pressure of the optimal gene patterns. Furthermore, we found the substitution rates ranged from 3.56 × 10-5 to 4.21 × 10-4 in different PPV segments, and the PPV VIR gene evolved at the highest substitution rate. In these seven protein-coding regions, purifying selection was the major evolutionary pressure, while the GIF and VIR genes suffered the greatest positive selection pressure. These results may provide useful knowledge on the virus genetic evolution from a new perspective which could help to create prevention and control strategies.

Compositional and Functional Comparisons of the Microbiota in the Colostrum and Mature Milk of Dairy Goats.

Goat milk is essential for the initial development of kids by providing a great source of commensal bacteria. In this study, we analyzed the microbiota of the milk of 30 healthy Saanen dairy goats. The 30 samples comprised 15 colostrum and 15 mature milk samples, collected from three different farms of Shaanxi Province. Colostrum samples were collected daily for five days post-delivery and mature milk was collected on the 7th, 10th, 20th, 30th, and 40th days. The result showed that microbial alpha diversity was higher in the mature milk compared with that in the colostrum. Linear discriminant analysis effect size (LEfSe) was performed to detect differentially abundant taxa in colostrum and goat milk. According to taxonomy results, Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes were the predominant bacteria phyla in both colostrum and mature milk. In addition, lactation stage noticeably influenced the composition of milk microbiota. Specifically, Novosphingobium, Brachybacterium, Psychrobacter, Lactobacillus, Yersinia, Roseateles, Rothia, Sanguibacter, Cloacibacterium, Variovorax, Sphingobacterium, and Coxiella were enriched in the colostrum, while Georgenia, Peptostreptococcus, Bacteroidales, Yaniella, Planomicrobium, Cloacibacterium, Azospirillum, Turicibacter, Cupriavidus, Herbaspirillum, Rhodobacteraceae, and Aeromonadales were the dominant genera in the mature milk. The enriched metabolic functions of the goat milk microbiota were predicted by PICRUSt and classified by KEGG pathway. Moreover, the abundances of environmental information processing, cellular processes pathway, genetic information processing pathway, organismal systems pathway, and metabolism pathway were significantly different between microbiota of colostrum and mature milk. Altogether, our study disclosed the significant difference between the microbial communities of colostrum and mature milk and provided grounds for further research in dairy microbiology.

The gut bacterial diversity of sheep associated with different breeds in Qinghai province.

BACKGROUND: Gut microbiota play important roles in their co-evolution with mammals. However, little is understood about gut bacterial community of Tibetan sheep compared with other sheep breeds. In this study, we investigated the gut bacterial community in 4 different sheep breeds living in the Qinghai-Tibetan Plateau (QTP) of China using high-throughput sequencing (HTS) technique. RESULTS: The results suggested that bacterial community abundance and breeds diversity of Tibetan sheep (TS) were significantly lower than that of the other three breeds of sheep [Dorset sheep (DrS), Dorper sheep (DrS) and Small Tail Han sheep (STHS)] (p < 0.05). Principal coordinates analysis (PCoA) and nonmetric multidimensional scaling (NMDS) analysis indicated that microbiome composition of TS was significantly different from that of other three sheep breeds (p < 0.01). Firmicutes was the most predominant microbial phylum in the gut, followed by Bacteroidetes. The gut bacterial community of TS showed higher proportions of phylum Spirochaetes, Proteobacteria and Verrucomicrobia, compared to the other three sheep breeds, but the Deferribacteres was absent in TS. At the genus level, Treponema, Succinivibrio, 5-7 N15 and Prevotella showed significantly higher abundance in TS than in the other three sheep breeds (p < 0.05). CONCLUSIONS: In this study, we first employed HTS to understand the gut microbiomes among different sheep breeds in QTP of China.

Codon Usage Bias Analysis of Bluetongue Virus Causing Livestock Infection.

Bluetongue virus (BTV) is a double-stranded RNA virus with multiple segments and belongs to the genus Orbivirus within the family Reoviridae. BTV is spread to livestock through its dominant vector, biting midges of genus Culicoides. Although great progress has been made in genomic analyses, it is not fully understood how BTVs adapt to their hosts and evade the host's immune systems. In this study, we retrieved BTV genome sequences from the National Center for Biotechnology Information (NCBI) database and performed a comprehensive research to explore the codon usage patterns in 50 BTV strains. We used bioinformatic approaches to calculate the relative synonymous codon usage (RSCU), codon adaptation index (CAI), effective number of codons (ENC), and other indices. The results indicated that most of the overpreferred codons had A-endings, which revealed that mutational pressure was the major force shaping codon usage patterns in BTV. However, the influence of natural selection and geographical factors cannot be ignored on viral codon usage bias. Based on the RSCU values, we performed a comparative analysis between BTVs and their hosts, suggesting that BTVs were inclined to evolve their codon usage patterns that were comparable to those of their hosts. Such findings will be conducive to understanding the elements that contribute to viral evolution and adaptation to hosts.

The protective and pathogenic roles of IL-17 in viral infections: friend or foe?

Viral infections cause substantial human morbidity and mortality, and are a significant health burden worldwide. Following a viral infection, the host may initiate complex antiviral immune responses to antagonize viral invasion and replication. However, proinflammatory antiviral immune responses pose a great threat to the host if not properly held in check. Interleukin (IL)-17 is a pleiotropic cytokine participating in a variety of physiological and pathophysiological conditions, including tissue integrity maintenance, cancer progression, autoimmune disease development and, more intriguingly, infectious diseases. Abundant evidence suggests that while IL-17 plays a crucial role in enhancing effective antiviral immune responses, it may also promote and exacerbate virus-induced illnesses. Accumulated experimental and clinical evidence has broadened our understanding of the seemingly paradoxical role of IL-17 in viral infections and suggests that IL-17-targeted immunotherapy may be a promising therapeutic option. Herein, we summarize current knowledge regarding the protective and pathogenic roles of IL-17 in viral infections, with emphasis on underlying mechanisms. The various and critical roles of IL-17 in viral infections necessitate the development of therapeutic strategies that are uniquely tailored to both the infectious agent and the infection environment.

Fully-automated magnetic stirring-assisted lab-in-syringe dispersive liquid-liquid microextraction for the determination of arsenic species in rice samples.

Fully-automated magnetic stirring-assisted lab-in-syringe dispersive liquid-liquid microextraction (MAS-LIS-DLLME), combined with graphite furnace atomic absorption spectrometry (GFAAS) was developed for the fast and efficient separation and preconcentration of trace levels of inorganic arsenic species in rice samples. This totally automated analytical procedure combines the advantages of lab-in-syringe flow system and dispersive liquid-liquid microextraction (DLLME) aiming at separation of trace arsenite and arsenate species from natural matrix for the first time. With a single syringe pump that is coupled with a multiposition valve, the whole lab-in-syringe microextraction process including cleaning, mixing, microextraction, phase separation, and target analyte collection was implemented in a fully-automated way. Significant factors of the MAS-LIS-DLLME method were sample acidity, concentration of the chelating agent, amounts of ionic liquids (ILs), aspiration speed and matrix interference. Using the present method, the limits of detection (LODs) for As(v) was 0.005 µg L-1. The relative standard deviation (RSDs) for seven replicate measurements of 2.0 µg L-1 of As(v) was 3.7%. The linear dynamic range (LDR) was 0.04-5.0 µg L-1 and the determination coefficients was 0.9990. Under the optimum conditions, the developed totally automated analytical procedure was successfully applied for the trace arsenite and arsenate species studies in natural rice samples and standard reference materials with satisfactory results.

Analysis of codon usage bias of Crimean-Congo hemorrhagic fever virus and its adaptation to hosts.

Crimean-Congo hemorrhagic fever virus (CCHFV) is a negative-sense, single stranded RNA virus with a three-segmented genome that belongs to the genus Nairovirus within the family Bunyaviridae. CCHFV uses Hyalomma ticks as a vector to infect humans with a wide range of clinical signs, from asymptomatic to Zika-like syndrome. Despite significant progress in genomic analyses, the influences of viral relationships with different hosts on overall viral fitness, survival, and evading the host's immune systems remain unknown. To better understand the evolutionary characteristics of CCHFV, we performed a comprehensive analysis of the codon usage pattern in 179 CCHFV strains by calculating the relative synonymous codon usage (RSCU), effective number of codons (ENC), codon adaptation index (CAI), and other indicators. The results indicate that the codon usage bias of CCHFV is relatively low. Several lines of evidence support the hypothesis that a translation selection factor is shaping codon usage pattern in this virus. A correspondence analysis (CA) showed that other factors, such as base composition, aromaticity, and hydrophobicity may also be involved in shaping the codon usage pattern of CCHFV. Additionally, the results from a comparative analysis of RSCU between CCHFV and its hosts suggest that CCHFV tends to evolve codon usage patterns that are comparable to those of its hosts. Furthermore, the selection pressures from Homo sapiens, Bos taurus, and Ovis aries on the CCHFV RSCU patterns were dominant when compared with selection pressure from Hyalomma spp. vectors. Taken together, both natural selection and mutation pressure are important for shaping the codon usage pattern of CCHFV. We believe that such findings will assist researchers in understanding the evolution of CCHFV and its adaptation to its hosts.