Oregano Essential Oil as a Natural Plant Additive Affects Growth Performance and Serum Antibody Levels by Regulating the Rumen Microbiota of Calves.

This experiment aimed to investigate whether supplementation of calves with different doses of oregano essential oil (OEO) could promote the development of the gastrointestinal tract and enhance the immune ability of calves by regulating the rumen microbiota. Twenty-four 70-day-old healthy and disease-free Holstein male calves were randomly divided into four groups, with the control group fed a basal diet, and the treatment group provided 4 g, 6 g, and 8 g of oregano essential oil per day in addition to the basal diet. After the 14-day pre-test, a 56-day formal test was conducted. At days 0 and 56 of the standard test period, calves were weighed, the average daily weight gain of calves during the test period was calculated, and serum samples were collected to measure the concentration of immunoglobulins (IgA, IgG, and IgM) in the serum; at day 56 of the formal test period, rumen fluid was collected from the calves, and 16SrRNA was sequenced to analyze changes in the rumen microbiota of the calves. The changes in the rumen microbiota of calves were analyzed by 16SrRNA sequencing. The results of the study showed that (1) OEO supplementation in calves significantly increased end weight and average daily gain (p < 0.05); (2) OEO supplementation in calves significantly increased serum concentrations of immunoglobulins IgA and IgM (p < 0.05); (3) OEO supplementation in calves significantly increased the abundance and diversity of rumen microbial organisms (p < 0.05); (4) OEO supplementation in calves significantly regulates the relative abundance of some species, and biomarkers with significant differences were screened by LEfSe analysis: g_Turicibacter, g_Romboutsia, f_Peptostreptococcaceae, f_Clostridiaceae, g_Clostridium_sensu_stricto_1, o_Clostridiales, g_unclassified_f_Synergistaceae, c_Coriobacteriia, o_Coriobacteriales, f_Atopobiaceae, g_Olsenella, p_Actinobacteriota, g_Defluviitaleaceae_UCG-011, f_Defluviitaleaceae, o_Corynebacteriales, g_Corynebacterium, f_Corynebacteriaceae, g_Shuttleworthia, f_Hungateiclostridiaceae, o_norank_c_Clostridia, g_Saccharofermentans, g_Streptococcus, f_Streptococcaceae, g_unclassified_o_Oscillospirales, and f_unclassified_o_Oscillospirales (p < 0.05, LDA ≥ 3); and (5) OEO supplementation in calves significantly enriched the metabolism of cofactors and vitamins pathway (p < 0.05). (6) Using Superman's correlation analysis, we screened unclassified_c_Clostridia, Shuttleworthia, and Christensenellaceae_R-7_group, three beneficial strains for calves. (7) Daily supplementation with 8g of OEO significantly affected rumen microbiota regulation in calves.

Effects of Essential Oil and/or Encapsulated Butyrate on Fecal Microflora in Neonatal Holstein Calves.

This study was conducted to investigate the effects of feeding oregano essential oil, butyrate, and its mixture on the intestinal microbial diversity of calves. A completely randomized experimental design was used. Sixty-four healthy neonatal Holstein female calves with birth weight ≥ 35 kg were randomly divided into one control and three treatments (16 calves per group). The control group was fed normally, and the treatment group was fed oregano essential oil, butyrate, and their mixture, respectively. The experiment lasted for 70 days, and the lactation period lasted for 56 days. On days 55 and 70, rectal fecal samples from five calves were collected from each group for 16S rRNA amplification and sequencing. The results showed as follows: (1) the three treatments had no significant effects on the intestinal microbial community diversity, community uniformity, and community pedigree diversity of calves (p > 0.05). (2) At the phylum level, Firmicutes, Bacteroidota, Spriochatetota, Actinobacteriota, Firmicutes, and Bacteroidota gates of the main bacteria were detected in feces. (3) At the genus level, the top ten species with relative abundance detected are: norank_ F_Muribaaculaceae, Ruminococcus, unclassified_ F_ Lachnospiraceae, UCG-005, Prevotelaceae_NK3B31_Group, Prevotella, Bacteroides, Rikenellaceae_RC9_Gut_Group, and Faecalibacterium, Alloprevotella. (4) LEfSe analysis results show that the species with significant differences in the control group were f__Lachnospiraceae, o__Lachnospirales, o__Coriobacteriales, and c__Coriobacteriia, g__Megasphaera; in the essential oil group were g__Lachnospiraceae_AC2044_group, o__Izemoplasmatales, g__norank_f__norank_o__Izemoplasmatales, and f__norank_o__Izemoplasmatales; in the sodium butyrate group were g__Lachnospiraceae_NK4A136_group, and g__Sharpea, g__Fournierella; in the mixed group were g__Flavonifractor, and g__UBA1819. (5) The functional prediction analysis of calf gut microbes, found on the KEGG pathway2, shows that essential oil significantly improved membrane transport, Sodium butyrate inhibits lipid metabolism and improves the body's resistance to disease. (p < 0.05). (6) The effects of each treatment on the intestinal microbial structure of calves did not last for 14 days after the treatment was stopped. In conclusion, the addition of oregano essential oil, butyrate, and its mixtures to milk fed to calves can modulate the microbial structure, and it is recommended that oregano essential oil and butyrate be used separately, as a mixture of the two can increase the rate of diarrhea in calves.

Dexmedetomidine relieves inflammatory pain by enhancing GABAergic synaptic activity in pyramidal neurons of the anterior cingulate cortex.

Pyramidal neuron (Pyn) hyperactivity in the anterior cingulate cortex (ACC) is involved in the modulation of pain. Previous studies indicate that the activation of α2 adrenoceptors (α2-ARs) by dexmedetomidine (DEX) is a safe and effective means of alleviating multiple types of pain. Here, we showed that systemically administered DEX can ameliorate the inflammatory pain induced by hindpaw injection of formalin (FA) and further examined the molecular and synaptic mechanisms of this DEX-elicited antinociceptive effect. We found that FA caused an increase in c-Fos expression in contralateral layer 2/3 (L2/3) ACC, and that intra-ACC infusion of DEX could also relieve phase 2 inflammatory pain behavior. DEX elicited an increase in the amplitude and frequency of miniature inhibitory post-synaptic currents (mIPSCs) and evoked IPSC amplitude, as well as a reduction in the hyperexcitability and both paired-pulse and excitation/inhibition ratios in contralateral L2/3 ACC Pyns of FA mice. These electrophysiological effects were associated with the upregulation of GABA A receptor (GABAAR) subunits. The interaction of phosphorylated Akt (p-Akt) with GABAAR subunits increased in the ACC following administration of DEX. These results suggest that DEX treatment reduces hyperactivity and enhances GABAergic inhibitory synaptic transmission in ACC Pyns, which produces analgesic effects by increasing GABAAR levels and activating the Akt signaling pathway.

Multi-task banded regression model: A novel individual survival analysis model for breast cancer.

PURPOSE: To reveal the hazard probability of individual breast cancer patients, a multi-task banded regression model is proposed for individual survival analysis of breast cancer. METHODS: A banded verification matrix is designed to construct the response transform function of the proposed multi-task banded regression model, which can solve the repeated switching of survival rate. A martingale process is introduced to construct different nonlinear regressions for different survival subintervals. The concordance index (C-index) is used to compare the proposed model with Cox proportional hazards (CoxPH) models and previous multi-task regression models. RESULTS: Two commonly-used breast cancer datasets are employed to validate the proposed model. Specifically, the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) includes 1981 breast cancer patients, of which 57.7% died of breast cancer. The Rotterdam & German Breast Cancer Study Group (GBSG) includes 1546 patients with lymph node-positive breast cancer in a randomized clinical trial, of which 44.4% died. Experimental results indicate that the proposed model is superior to some existing models for overall and individual survival analysis of breast cancer, with the C-index of 0.6786 for the GBSG and 0.6701 for the METABRIC. CONCLUSION: The superiority of the proposed model can be contributed to three novel ideas. One is that a banded verification matrix can band the response of the survival process. Second, the martingale process can construct different nonlinear regressions for different survival subintervals. Third, the novel loss can adapt the model to making the multi-task regression similar to the real survival process.

High-Speed Path Probing Method for Large-Scale Network.

In large-scale network topology discovery, due to the complex network structure and dynamic change characteristics, it is always the focus of network topology measurement to obtain as many network paths as possible in a short time. In this paper, we propose a large-scale network path probing approach in order to solve the problems of low probing efficiency and high probing redundancy commonly found in current research. By improving the packet delivery order and the update strategy of time-to-live field values, we redesigned and implemented an efficient large-scale network path probing tool. The experimental results show that the method-derived tool can complete path probing for a sample of 12 million/24 network address segments worldwide within 1 hour, which greatly improves the efficiency of network path probing. Meanwhile, compared to existing methods, the proposed method can reduce the number of packets sent by about 10% with the same number of network addresses found, which effectively reduces probing redundancy and alleviates the network load.

An Internet-Oriented Multilayer Network Model Characterization and Robustness Analysis Method.

The Internet creates multidimensional and complex relationships in terms of the composition, application and mapping of social users. Most of the previous related research has focused on the single-layer topology of physical device networks but ignored the study of service access relationships and the social structure of users on the Internet. Here, we propose a composite framework to understand how the interaction between the physical devices network, business application network, and user role network affects the robustness of the entire Internet. In this paper, a multilayer network consisting of a physical device layer, business application layer and user role layer is constructed by collecting experimental network data. We characterize the disturbance process of the entire multilayer network when a physical entity device fails by designing nodal disturbance to investigate the interactions that exist between the different network layers. Meanwhile, we analyze the characteristics of the Internet-oriented multilayer network structure and propose a heuristic multilayer network topology generation algorithm based on the initial routing topology and networking pattern, which simulates the evolution process of multilayer network topology. To further analyze the robustness of this multilayer network model, we combined a total of six target node ranking indicators including random strategy, degree centrality, betweenness centrality, closeness centrality, clustering coefficient and network constraint coefficient, performed node deletion simulations in the experimental network, and analyzed the impact of component types and interactions on the robustness of the overall multilayer network based on the maximum component change in the network. These results provide new insights into the operational processes of the Internet from a multi-domain data fusion perspective, reflecting that the coupling relationships that exist between the different interaction layers are closely linked to the robustness of multilayer networks.

Favoring Expression of Yak Alleles in Interspecies F1 Hybrids of Cattle and Yak Under High-Altitude Environments.

Both cis- and trans-regulation could cause differential expression between the parental alleles in diploid species that might have broad biological implications. Due to the relatively distant genetic divergence between cattle and yak, as well as their differential adaptation to high-altitude environments, we investigated genome-wide allelic differential expression (ADE) in their F1 hybrids using Nanopore long-read RNA-seq technology. From adult F1 hybrids raised in high-altitude, ten lung and liver tissues were individually sequenced for producing 31.6 M full-length transcript sequences. Mapping against autosomal homologous regions between cattle and yak, we detected 17,744 and 14,542 protein-encoding genes expressed in lung and liver tissues, respectively. According to the parental assignments of transcript sequences, a total of 3,381 genes were detected to show ADE in at least one sample. There were 186 genes showing ubiquitous ADE in all the studied animals, and among them 135 and 37 genes had consistent higher expression of yak and cattle alleles, respectively. Functional analyses revealed that the genes with favoring expression of yak alleles have been involved in the biological progresses related with hypoxia adaptation and immune response. In contrast, the genes with favoring expression of cattle alleles have been enriched into different biological progresses, such as secretion of endocrine hormones and lipid metabolism. Our results would support unequal contribution of parental genes to environmental adaptation in the F1 hybrids of cattle and yak.

Genotyping-free parentage assignment using RAD-seq reads.

Parentage assignment is defined as the identification of the true parents of one focal offspring among a list of candidates and has been commonly used in zoological, ecological, and agricultural studies. Although likelihood-based parentage assignment is the preferred method in most cases, it requires genotyping a predefined set of DNA markers and providing their population allele frequencies. In the present study, we proposed an alternative method of parentage assignment that does not depend on genotype data and prior information of allele frequencies. Our method employs the restriction site-associated DNA sequencing (RAD-seq) reads for clustering into the overlapped RAD loci among the compared individuals, following which the likelihood ratio of parentage assignment could be directly calculated using two parameters-the genome heterozygosity and error rate of sequencing reads. This method was validated on one simulated and two real data sets with the accurate assignment of true parents to focal offspring. However, our method could not provide a statistical confidence to conclude that the first ranked candidate is a true parent.

Effects of Astragalus injection and Salvia Miltiorrhiza injection on serum inflammatory markers in patients with stable coronary heart disease: a randomized controlled trial protocol.

BACKGROUND: Coronary heart disease (CHD) is a clinical syndrome caused by coronary atherosclerosis (AS) or functional changes in coronary arteries. We have previously reported that astragaloside IV (in astragalus) and tanshinone IIA (in Salvia miltiorrhiza) improve myocardial ischemic injury. METHODS: This study will employ the randomized, blinded, prospective, single-center experiments approach. Briefly, a total of 160 eligible patients will be equally randomized into three treatment groups and placebo control groups. Patients will receive appropriate treatments every 24 h for seven days after enrollment and followed up for 28 days. The main evaluation indicators will be cell count, serum high-sensitivity C-reactive protein (hs-CRP) level, monocyte chemoattractant protein 1 (MCP-1), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), interleukin-8 (IL-8), interleukin-18 (IL-18), interleukin-10 (IL-10), tumor necrosis factor (TNF)-α, oxidized low density lipoprotein (OX-LDL), angina grade, and Traditional Chinese Medicine (TCM) symptom changes scale. Secondary indicators to be evaluated will include B-type natriuretic peptide (BNP) levels, troponin (cTn), muscle enzyme isoenzyme (CK-MB), heart-type fatty acid binding protein (H-FABP), liver and renal functions, as well as blood coagulation. Close monitoring of adverse events during the trial will also be conducted. DISCUSSION: This randomized controlled trial of Chinese herbal extracts for the treatment of coronary heart disease will generate results that are expected to provide valuable clinical evidence to inform future development of therapies towards management of CHD. TRIAL REGISTRATION: China Clinical Trial Registration Center, ChiCTR1900021590. Registered on 28 February 2019.

A Two-Echelon Cooperated Routing Problem for a Ground Vehicle and Its Carried Unmanned Aerial Vehicle.

In this paper, a two-echelon cooperated routing problem for the ground vehicle (GV) and its carried unmanned aerial vehicle (UAV) is investigated, where the GV travels on the road network and its UAV travels in areas beyond the road to visit a number of targets unreached by the GV. In contrast to the classical two-echelon routing problem, the UAV has to launch and land on the GV frequently to change or charge its battery while the GV is moving on the road network. A new 0-1 integer programming model is developed to formulate the problem, where the constraints on the spatial and temporal cooperation of GV and UAV routes are included. Two heuristics are proposed to solve the model: the first heuristic (H1) constructs a complete tour for all targets and splits it by GV routes, while the second heuristic (H2) constructs the GV tour and assigns UAV flights to it. Random instances with six different sizes (25-200 targets, 12-80 rendezvous nodes) are used to test the algorithms. Computational results show that H1 performs slightly better than H2, while H2 uses less time and is more stable.

A Novel Ensemble Method for Imbalanced Data Learning: Bagging of Extrapolation-SMOTE SVM.

Class imbalance ubiquitously exists in real life, which has attracted much interest from various domains. Direct learning from imbalanced dataset may pose unsatisfying results overfocusing on the accuracy of identification and deriving a suboptimal model. Various methodologies have been developed in tackling this problem including sampling, cost-sensitive, and other hybrid ones. However, the samples near the decision boundary which contain more discriminative information should be valued and the skew of the boundary would be corrected by constructing synthetic samples. Inspired by the truth and sense of geometry, we designed a new synthetic minority oversampling technique to incorporate the borderline information. What is more, ensemble model always tends to capture more complicated and robust decision boundary in practice. Taking these factors into considerations, a novel ensemble method, called Bagging of Extrapolation Borderline-SMOTE SVM (BEBS), has been proposed in dealing with imbalanced data learning (IDL) problems. Experiments on open access datasets showed significant superior performance using our model and a persuasive and intuitive explanation behind the method was illustrated. As far as we know, this is the first model combining ensemble of SVMs with borderline information for solving such condition.