Model and Data Dual-Driven Double-Point Observation Network for Ultra-Short MI EEG Classification.

Although deep networks have succeeded in various signal classification tasks, the time sequence samples used to train the deep models are usually required to reach a certain length. Especially, in brain computer interface (BCI) research, around 3.5s-long motor imagery (MI) Electroencephalography (EEG) samples are needed to obtain satisfactory classification performance. This time-span requirement of the training samples makes real-time MI BCI systems impossible to implement based on deep networks, which restricts the related researches within laboratory and makes practical application hard to accomplish. To address this issue, a double-point observation deep network (DoNet) is developed to classify ultra-short samples buried in noise. First, an analytical solution is developed theoretically to perform ultra-short signal classification based on double-point couples. Then, a signal-noise model is constructed to study the interference of noise on classification based on double-point couples. Based on which, an independent identical distribution condition is utilized to improve the classification accuracy in a data-driven manner. Combining the theoretical model and data-driven mechanism, DoNet can construct a steady data-distribution for the double-point couples of the samples with the same label. Therefore, the conditional probability of each double-point couple of a test sample can be obtained. With a voting strategy, the samples can be accurately classified by fusing these conditional probabilities. Meanwhile, the noise interference can be suppressed. DoNet has been evaluated on two public EEG datasets. Compared to most state-of-the-art methods, the 1s-long EEG signal classification accuracy has been improved by more than 3%.

Tests and classification methods in adaptive designs with applications.

Statistical tests for biomarker identification and classification methods for patient grouping are two important topics in adaptive designs of clinical trials related to genomic studies. In this article, we evaluate four test methods for biomarker identification in the first stage of an adaptive design: a model-based identification method, the popular two-sided t-test, the nonparametric Wilcoxon Rank-Sum test (two-sided), and the Regularized Generalized Linear Models. For patients grouping in the second stage, we examine classification methods such as Random Forest, Elastic-net Regularized Generalized Linear Models, Support Vector Machine (SVM), Gradient Boosting Machine (GBM), and Extreme Gradient Boosting (XGBoost). Simulation studies are carried out to assess the performance of the different methods. The best identification methods are chosen based on the well-known F 1 score, while the best classification techniques are selected based on the area under a receiver operating characteristic curve (AUC). The chosen methods are then applied to the Adaptive Signature Design (ASD) with a real data set from breast cancer patients for the purpose of evaluating the performance of ASD in different situations.

Topological Hall effect in SrRuO3thin films and heterostructures.

Transition metal oxides hold a wide spectrum of fascinating properties endowed by the strong electron correlations. In 4dand 5doxides, exotic phases can be realized with the involvement of strong spin-orbit coupling (SOC), such as unconventional magnetism and topological superconductivity. Recently, topological Hall effects (THEs) and magnetic skyrmions have been uncovered in SrRuO3thin films and heterostructures, where the presence of SOC and inversion symmetry breaking at the interface are believed to play a key role. Realization of magnetic skyrmions in oxides not only offers a platform to study topological physics with correlated electrons, but also opens up new possibilities for magnetic oxides using in the low-power spintronic devices. In this review, we discuss recent observations of THE and skyrmions in the SRO film interfaced with various materials, with a focus on the electric tuning of THE. We conclude with a discussion on the directions of future research in this field.

Gene cloning of a highly active phytase from Lactobacillus plantarum and further improving its catalytic activity and thermostability through protein engineering.

Phytase belongs to orthophosphate monoester hydrolase, which can catalyze the gradual hydrolysis of phytic acid to inositol phosphate. It can be added to animal feed to reduce the anti-nutritional factor of phytic acid in feed. The thermostability and specific activity of phytases are two key factors determining their potential applications. In this study, a highly active 233-aa phytase gene (LpPHY233) from Lactobacillus plantarum was cloned and expressed in Escherichia coli (E. coli), achieving 800 times higher activity than that expressed in L. plantarum. Next, the temperature characteristic and catalytic performance of LpPHY233 was improved by disulfide bond engineering and C-terminal truncation, respectively. Surprisingly, the specific activity of the C-terminal truncated mutant LpPHY200 was about 5.6 times higher than that of LpPHY233, and the optimal temperature for the mutant LpPHY233S58C/K61C introduced disulfide bond was 15 °C higher than that of LpPHY233. Moreover, these phytase mutants displayed excellent pH property and kinetic parameters, and have great application prospect in feed additives field. The molecular basis for its catalytic performance was preliminarily explained by in silico design methods. Our results provided a solid theoretical foundation for further molecular modification and industrial application of phytases.

Comparison of Modified Above-Knee and Conventional Surgery with the Stripping of the Great Saphenous Vein of Varicose Veins of the Lower Extremities: A Retrospective Study.

OBJECTIVE: To compare the clinical effects of modified above-knee and conventional surgery with the stripping of the great saphenous vein of varicose veins of the lower extremities. METHODS: Clinical data of patients with a varicose vein of the lower extremity from May 2016 to May 2018 were collected. A retrospective study was conducted on the patients receiving modified above-knee and conventional surgery with the great saphenous vein stripping. The baseline characteristics and long-term follow-up data were compared between the groups. RESULTS: There were no significant differences in baseline characteristics between the two groups (P > 0.05). The surgeries were successfully performed by the same group of surgeons under local anesthesia and neuraxial anesthesia. The hospital stay, operation time, intraoperative blood loss, total length, and number of incisions in the above-knee group were comparable to those in the conventional surgery group (P > 0.05). The incidence of saphenous nerve injury and subcutaneous hematoma in the above-knee group was lower than that in the conventional surgery group (P < 0.05). There were no significant differences in recurrent varicose vein incidences (P > 0.05). After surgery, the venous clinical severity score (VCSS) and chronic venous insufficiency questionnaire (CIVIQ-14) scores of both groups were higher than those before operation (P < 0.05). There was no significant difference in VCSS score or CIVIQ-14 scores between the two groups postoperation (P > 0.05). At 24 months after surgery, the above-knee group (71.8%) and conventional surgery group (73.2%) resulted in changes of at least two CEAP-C clinical classes lower than baseline, respectively. CONCLUSION: The modified above-knee technique can ensure clinical outcomes, reduce intraoperative blood loss and complication incidences, and shorten the operative time. This gives evidence that the modified above-knee technique is worthy of clinical application.

Knowledge-driven feature component interpretable network for motor imagery classification.

Objective. The end-to-end convolutional neural network (CNN) has achieved great success in motor imagery (MI) classification without a manual feature design. However, all the existing deep network solutions are purely datadriven and lack interpretability, which makes it impossible to discover insightful knowledge from the learned features, not to mention to design specific network structures. The heavy computational cost of CNN also makes it challenging for real-time application along with high classification performance.Approach. To address these problems, a novel knowledge-driven feature component interpretable network (KFCNet) is proposed, which combines spatial and temporal convolution in analogy to independent component analysis and a power spectrum pipeline. Prior frequency band knowledge of sensory-motor rhythms has been formulated as band-pass linear-phase digital finite impulse response filters to initialize the temporal convolution kernels to enable the knowledge-driven mechanism. To avoid signal distortion and achieve a linear phase and unimodality of filters, a symmetry loss is proposed, which is used in combination with the cross-entropy classification loss for training. Besides the general prior knowledge, subject-specific time-frequency property of event-related desynchronization and synchronization has been employed to construct and initialize the network with significantly fewer parameters.Main results.Comparison of experiments on two public datasets has been performed. Interpretable feature components could be observed in the trained model. The physically meaningful observation could efficiently assist the design of the network structure. Excellent classification performance on MI has been obtained.Significance. The performance of KFCNet is comparable to the state-of-the-art methods but with much fewer parameters and makes real-time applications possible.

Research on Interlayer Bonding Quality Control Method of Dam Concrete Based on Equivalent Age.

Interlayer bonding quality is the key to the stability and durability of dam concrete. In this study, interlayer splitting tensile strength, relative permeability coefficient, and electric flux of dam concrete at different temperatures were tested. The relationships between equivalent age and strength coefficient, relative permeability coefficient ratio, and electric flux ratio were established. Meanwhile, a comprehensive early-warning and control system of dam interlayer bonding quality based on the above relationships was proposed. The results showed that the interlayer mechanical properties, impermeability, and anti-chloride ion permeability of dam concrete decreased with the increase of temperature. Moreover, the equivalent age was linearly correlated with strength coefficient, relative permeability coefficient ratio, and electric flux ratio of concrete. The correlation coefficients were 0.986, 0.973, and 0.924, respectively. In addition, the interlayer bonding quality of dam concrete can be effectively controlled by the early-warning system established according to the relationship between equivalent age and interlayer properties parameters.

Effects of hydroxyethyl starch and gelatin on the risk of acute kidney injury following orthotopic liver transplantation: A multicenter retrospective comparative clinical study.

OBJECTIVES: This multicenter retrospective study aimed to compare the effects of HES and gelatin (GEL) on the risk of post-OLT AKI. METHOD: A total of 1,672 patients undergoing OLT were enrolled from major transplant centers in China between 2005 and 2013. These patients were divided into three groups: GEL, hydroxyethyl starch (HES), and GEL + HES group. RESULTS: There was no significant difference in the incidence of post-OLT AKI among the GEL, HES, and GEL + HES groups. The GEL + HES group had a lower incidence of stage II post-OLT AKI than the other two groups. Compared with patients receiving GEL, patients receiving HES did not harbor an increased risk of AKI. Our results showed that MELD score (adjusted odds ratio [OR], 1.579; 95% confidence interval [CI], 1.123-2.219; P = 0.009) and preoperative anemia (adjusted OR, 1.533; 95% CI, 1.212-1.939; P < 0.001) were independent risk factors for post-OLT AKI, and normal preoperative Scr level (vs abnormal; adjusted OR, 0.402; 95% CI, 0.222-0.729; P = 0.003) was independent protective factors for post-OLT AKI. CONCLUSION: This large-scale multicenter retrospective study found that the intraoperative use of HES did not increase the overall incidence of post-OLT AKI in patients when compared with GEL, and whether to increase the risk of post-OLT AKI needs to be further explored.

Prediction Model of Concrete Initial Setting Time Based on Stepwise Regression Analysis.

Mass concrete is usually poured in layers. To ensure the interlayer bonding quality of concrete, the lower layer should be kept in a plastic state before the upper layer is added. Ultimately, it will lead to the prediction of concrete setting time as a critical task in concrete pouring. In this experiment, the setting time of concrete in laboratory and field environments was investigated. The equivalent age of concrete at the initial setting was also analyzed based on the maturity theory. Meanwhile, factors affecting the setting time in the field environment were studied by means of multiple stepwise regression analysis. Besides, the interlayer splitting tensile strength of concrete subjected to different temperatures and wind speeds was determined. The results of laboratory tests show that both setting time and interlayer splitting tensile strength of concrete decrease significantly with the increase of air temperature and wind speed. In addition, the equivalent age of concrete at initial setting remains the same when subjected to different temperatures, while it decreases obviously with the increase of wind speed. In the field environment, the equivalent age of concrete at initial setting is greatly different, which is related to the variability of relative humidity and wind speed. The average air temperature and maximum wind speed are the main factors affecting the initial setting time of concrete. Furthermore, a prediction model is established based on the stepwise regression analysis results, which can predict the actual setting state in real-time, and hence controlling the interlayer bonding quality of dam concrete.

Supplementation with beta-1,3-glucan improves productivity, immunity and antioxidative status in transition Holstein cows.

Dairy cows undergo dramatic physiological changes during the transition from late pregnancy to early lactation, which make them vulnerable to metabolic stress and immune dysfunction. The objective of this study was to evaluate the effects of a commercial beta-1,3-glucan product (Aleta™, containing 50% beta-1,3-glucan) on productivity, immunity and antioxidative status in transition cows. Fifty-four multiparous Holstein cows received a control diet or a diet supplemented with 5 or 10 g of beta-1,3-glucan per cow per day from 21 days before expected calving to 21 days after parturition. Blood samples were collected at day -21, 1, and 21 relative to calving. Colostrum and milk were collected at day 1 and 21 after calving, respectively. Data showed that supplementation with beta-1,3-glucan had no effect on milk composition, but increased milk production. Beta-1,3-glucan treatment also improved the milk quality, as shown by reduced milk somatic cell count and increased immunoglobulin levels in colostrum. Notably, beta-1,3-glucan markedly reduced serum levels of pro-inflammatory cytokines and C-reactive protein, while elevated serum immunoglobulin levels, indicating its immunity enhancement in transition cows. Moreover, beta-1,3-glucan addition reduced the serum malondialdehyde level and enhanced the activities of serum superoxide dismutase and catalase, which enhanced the antioxidative capacity in transition cows. In summary, supplementation with beta-1,3-glucan improves productivity, immunity and antioxidative status in transition dairy cows.

miR-10b-5p Suppresses the Proliferation and Invasion of Primary Hepatic Carcinoma Cells by Downregulating EphA2.

OBJECTIVE: To analyze the function of miR-10b-5p in suppressing the invasion and proliferation of primary hepatic carcinoma cells by downregulating erythropoietin-producing hepatocellular receptor A2 (EphA2). Material and Methods. Eighty-six hepatic carcinoma (HCC) tissue specimens and 86 corresponding adjacent tissue specimens were collected, and the mRNA expression of miR-10b-5p and Ephrin type-A receptor 2 (EphA2) in the specimens was determined using a reverse transcription-polymerase chain reaction (RT-PCR) assay. Western blot was employed to quantify EphA2, B-cell chronic lymphocytic leukemia/lymphoma-2 (Bcl-2), Bcl-2-associated X protein (Bax), and Caspase-3 in the cells, and CCK8, Transwell assay, and flow cytometry were applied to evaluate the proliferation, invasion, and apoptosis of cells, respectively. Moreover, the dual luciferase reporter assay was utilized for correlation analysis between miR-10b-5p and EphA2. RESULTS: miR-10b-5p was lowly expressed in HCC, while EphA2 was highly expressed. Cell experiments revealed that miR-10b-5p overexpression or EphA2 knockdown could reduce cell proliferation, accelerate apoptosis, strongly upregulate Bax and Caspase-3, and downregulate Bcl-2. In contrast, miR-10b-5p knockdown or EphA2 overexpression gave rise to reverse biological phenotypes. Furthermore, dual luciferase reporter assay verified that miR-10b-5p was a target of EphA2, and the rescue experiment implied that transfection of pCMV-EphA2 or Si-EphA2 could reverse EphA2 expression and cell biological functions caused by miR-10b-5p overexpression or knockdown. CONCLUSIONS: miR-10b-5p reduced HCC cell proliferation but accelerate apoptosis by regulating EphA2, suggesting it has the potential to be a clinical target for HCC.

Short-term efficacy of precise hepatectomy and traditional hepatectomy for primary liver cancer: a systematic review and meta-analysis.

BACKGROUND: As the base of hepatitis B patients has been increasing annually, it has developed into a high incidence source of primary liver cancer worldwide. The fatality rate of liver cancer is still relatively high. Among the many treatment methods, liver resection is the first-line treatment of primary liver cancer. Although precision hepatectomy has achieved rapid development in recent years, the understanding of its efficacy is still not completely clear. This study aimed to analyze and compare the safety and effectiveness of precision hepatectomy and traditional hepatectomy in the treatment of primary liver cancer. METHODS: We performed a literature search of the CNKI, Wanfang, Weipu.com, PubMed, Cochrane Library, Web of Science databases for studies on precision liver resection (precision group) and traditional liver resection (traditional group) for the treatment of primary liver cancer. Data including the operation time, intraoperative blood loss, hospital stay, postoperative complications, liver function, and survival rate were analyzed using RevMan 5.3 software to compare the differences in the effects of the two surgical procedures. RESULTS: Ten articles were included in the study, involving a total of 1,969 patients, including 1,045 cases in the precision group and 924 cases in the traditional group. Meta-analysis results showed that compared with the traditional group, the precision group had a longer operation time [mean difference (MD) =8.01, P=0.004], and total bilirubin (TBiL; MD =-2.78, P=0.055) was similar. Meanwhile, the precision group exhibited advantages in terms of intraoperative blood loss (MD =-149.37, P=0.000), hospital stay (MD =-5.59, P=0.000), postoperative liver function indexes [aspartate aminotransferase (AST; MD =-11.61, P=0.000) and alanine aminotransferase (ALT; MD =-18.53, P=0.000)], postoperative complication rate [relative risk (RR) =0.51, P=0.000], and 1-year survival rate (RR =1.11, P=0.000). DISCUSSION: The application of precision surgery in the treatment of primary liver cancer can be a safe and effective method. It can minimize intraoperative blood loss, mitigate surgical risk, reduce postoperative complications, improve patient prognosis and quality of life, and provide better short-term curative effect and patient benefits.

Effects of beta-1,3-glucan supplementation on concentrations of serum metabolites in transition Holstein cows.

Objectives of this study were to evaluate the alleviating effects of a commercial beta-1,3-glucan product (Aleta, containing 50% beta-1,3-glucan, Kemin Industries) on metabolic stress in transition Holstein cows as reflected by circulating metabolites and enzymes. Fifty-four multiparous Holstein cows were randomly allocated to three groups with 18 cows each. Cows in each group received a commercial basal diet or the basal diet supplemented with Aleta calculated to supply 5 or 10 g of Aleta per cow per day. Blood samples were collected at day -21, 1, and 21 relative to calving for determination of serum triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDLC), very low density lipoprotein (VLDL), glucose, insulin, ß-hydroxybutyric acid (BHBA), aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamyl transpeptidase (GGT), and non-esterified fatty acid (NEFA). Supplementation with Aleta markedly elevated serum concentrations of TG, TC, HDLC, LDL-C and VLDL, implying its positive effect on lipid metabolism in transition dairy cows. Aleta treatment significantly decreased the serum concentrations of NEFA and BHBA, but markedly elevated the serum concentrations of glucose and insulin. Also, Aleta treatment significantly elevated the dry matter intake and milk production in postpartum cows, indicating the alleviating effect of Aleta on negative energy balance in transition cows. Moreover, Aleta treatment significantly reduced the serum activities of AST, ALT and GGT, indicating its hepatoprotective effect on transition cows. These results suggest that Aleta supplementation may help to improve fat metabolism disorder initiated by negative energy balance in transition dairy cows.

[Gene editing technology and its recent progress in disease therapy].

Gene editing is a genetic manipulation technology which utilizes bacterial nucleases to accurately and efficiently modify DNA or RNA. Gene editing has broad applications in basic research, breeding, and drug screening, and it is gaining validity and applicability to the therapy of many diseases especially genetic-based disease. In this review, we summarize the development of gene editing technology, its different strategies and applications in the treatment of disease, and the research of gene editing therapy for genetic diseases (including base editor and epigenetic regulation) in the treatment of disorders and diseases of the blood system, liver, muscle and nervous system. Finally, we discuss the future development prospects of gene editing therapy.

[Screening of pyrene degradation bacteria strain from the Kochia scoparia roots and its potential for promoting growth]. / ç„¦åŒ–åŽ‚åœ°è‚¤æ ¹å† è§£èŠ˜ç»†èŒçš„ç­›é€‰åŠä¿ƒç”Ÿæ½œåŠ›.

The endophytic bacteria were isolated from the roots of polycyclic aromatic hydrocarbon (PAHs)-tolerant plant. We investigated their ability of PAHs degradation and plant growth promo-ting, with the aim to provide theoretical support for bacterial-plant cooperative soil remediation. Kochia scoparia living in coking plant area were selected for strains isolation. Eight endophytic bacteria strains, which used pyrene and 1-aminocyclopropane-1-carboxylic acid (ACC) as sole carbon and nitrogen source, were isolated from the roots of K. scoparia. Three endophytic bacteria, KSE4, KSE7 and KSE8, displayed high degradation efficiency in pyrene degradation experiment. They were identified as Bacillus sp., Pseudomonas sp., and Sphingobacterium sp., respectively. The abili-ties of those three strains to produce ACC deaminase and their effects on seed germination of K. scoparia were examined under pyrene stress through liquid culture tests. The results showed that the activity of ACC deaminase decreased with increasing pyrene concentration (0-15 mg·L-1). KSE7 had the strongest promotion effect. When pyrene concentration reached to 15 mg·L-1, the germination rate and bud length of K. scoparia increased by 44.8% and 61.1%, respectively. Our results indicated that KSE7 is a promising bacterial strain for soil remediation in coking plant area.

Widespread positive selection on cetacean TLR extracellular domain.

Toll like receptors (TLRs), key members of innate immune system, can recognize a wide diversity of pathogens and initiate both innate and adaptive immune responses in vertebrate. Cetaceans must have faced new challenges of pathogens when their terrestrial relatives transitioned from the terrestrial to aquatic environment. Here, we sequenced the extracellular domain (ECD) of 10 TLRs in cetacean lineages because this region involved in the recognition of pathogens. A total of 148 sites ranging between 5-26 codons (0.01%-4.83%) were identified to be robust candidates of positive selection at the ECD of 10 TLRs. In addition, the majority (90.54%) of these positively selected codons were found to have radical amino acid changes, which strengthen the evidence of positive selection. Importantly, more radical amino acid changes in selected sites were enriched in the period of early evolutionary transition from land to semi-aquatic and from semi-aquatic to full-aquatic habitat, which might endow cetaceans with a faster adaptation to new pathogens as they transitioned into novel habitat. Interestingly, similar selective intensity was detected in both viral and non-viral TLRs in cetaceans, which was not in line with previous studies on primates and birds that reported stronger positive selection in non-viral TLRs than in viral TLRs. This result may be explained by the fact that cetaceans might have faced diversity of bacteria and viruses during its transitions from terrestrial to aquatic environment whereas both primates and birds probably being affected by only a restricted number of related viruses due to their homogeneous habitat.

Biocompatibility and Immunotoxicology of the Preclinical Implantation of a Collagen-based Artificial Dermal Regeneration Matrix.

OBJECTIVE: Graft rejection, with the possibility of a violent immune response, may be severe and life threatening. Our aim was to thoroughly investigate the biocompatibility and immunotoxicology of collagen-based dermal matrix (DM) before assessment in clinical trials. METHODS: DM was subcutaneously implanted in BALB/c mice in two doses to induce a potential immune response. The spleen and lymph nodes were assessed for shape, cell number, cell phenotype via flow cytometry, cell activation via CCK8 kit, Annexin V kit, and Ki67 immunostaining. Serum samples were used to measure antibody concentration by enzyme-linked immunosorbent assay. Local inflammation was analyzed by histology and immunohistochemistry staining. Data analysis was performed by one-way ANOVA and non-parametric tests. RESULTS: Our data illustrate that the spleen and lymph node sizes were similar between the negative control mice and mice implanted with DM. However, in the high-dose DM (DM-H) group, the total cell populations in the spleen and lymph nodes, T cells and B cells in the spleen had slight increases in prophase, and the low-dose DM (DM-L) group did not display gross abnormities. Moreover, DM-H initiated moderate cell activation and proliferation in the early phase post-immunization, whereas DM-L did not. Neither DM-H nor DM-L implantation noticeably increased IgM and IgG serum concentrations. Examination of the local cellular response revealed only benign cell infiltration and TNF-α expression in slides of DM in the early phase. CONCLUSION: Overall, DM-H may have induced a benign temporary acute immune response post-implantation, whereas DM-L had quite low immunogenicity. Thus, this DM can be regarded as a safe product.

Genetic basis of brain size evolution in cetaceans: insights from adaptive evolution of seven primary microcephaly (MCPH) genes.

BACKGROUND: Cetacean brain size expansion is an enigmatic event in mammalian evolution, yet its genetic basis remains poorly explored. Here, all exons of the seven primary microcephaly (MCPH) genes that play key roles in size regulation during brain development were investigated in representative cetacean lineages. RESULTS: Sequences of MCPH2-7 genes were intact in cetaceans but frameshift mutations and stop codons was identified in MCPH1. Extensive positive selection was identified in four of six intact MCPH genes: WDR62, CDK5RAP2, CEP152, and ASPM. Specially, positive selection at CDK5RAP2 and ASPM were examined along lineages of odontocetes with increased encephalization quotients (EQ) and mysticetes with reduced EQ but at WDR62 only found along odontocete lineages. Interestingly, a positive association between evolutionary rate (ω) and EQ was identified for CDK5RAP2 and ASPM. Furthermore, we tested the binding affinities between Calmodulin (CaM) and ASPM IQ motif in cetaceans because only CaM combined with IQ, can ASPM perform the function in determining brain size. Preliminary function assay showed binding affinities between CaM and IQ motif of the odontocetes with increased EQ was stronger than for the mysticetes with decreased EQ. In addition, evolution rate of ASPM and CDK5RAP2 were significantly related to mean group size (as one measure of social complexity). CONCLUSIONS: Our study investigated the genetic basis of cetacean brain size evolution. Significant positive selection was examined along lineages with both increased and decreased EQ at CDK5RAP2 and ASPM, which is well matched with cetacean complex brain size evolution. Evolutionary rate of CDK5RAP2 and ASPM were significantly related to EQ, suggesting that these two genes may have contributed to EQ expansion in cetaceans. This suggestion was further indicated by our preliminary function test that ASPM might be mainly linked to evolutionary increases in EQ. Most strikingly, our results suggested that cetaceans evolved large brains to manage complex social systems, consisting with the 'social brain hypothesis', as evolutionary rate of ASPM and CDK5RAP2 were significantly related to mean group size.

Evolutionary Genetics of Hypoxia Tolerance in Cetaceans during Diving.

Hypoxia was a major challenge faced by cetaceans during the course of secondary aquatic adaptation. Although physiological traits of hypoxia tolerance in cetaceans have been well characterized, the underlying molecular mechanisms remain unknown. We investigated the sequences of 17 hypoxia-tolerance-related genes in representative cetaceans to provide a comprehensive insight into the genetic basis of hypoxia tolerance in these animals. Genes involved in carrying and transporting oxygen in the blood and muscle (hemoglobin-α and ß, myoglobin), and genes involved in the regulation of vasoconstriction (endothelin-1, -2, and -3; endothelin receptor type A and B; adrenergic receptor α-1D; and arginine vasopressin) appear to have undergone adaptive evolution, evidence for positive selection on their particular sites, and radical physiochemical property changes of selected condons. Interestingly, "long-diving" cetaceans had relatively higher ω (dN/dS) values than "short-diving" cetaceans for the hemoglobin ß gene, indicating divergent selective pressure presented in cetacean lineages with different diving abilities. Additionally, parallel positive selection or amino acid changes (ADRA1D: P50A, A53G,AVPR1B: I/V270T) among animals exposed to different hypoxia habitats reflect functional convergence or similar genetic mechanisms of hypoxia tolerance. In summary, positive selection, divergent selective pressures, and parallel evolution at the molecular level provided some new insights into the genetic adaptation of hypoxia tolerance.

Molecular network-based analysis of guizhi-shaoyao-zhimu decoction, a TCM herbal formula, for treatment of diabetic peripheral neuropathy.

AIM: Guizhi-shaoyao-zhimu decoction (GSZ), a traditional Chinese medicine (TCM) herbal formula, has been shown effective in the treatment of diabetic peripheral neuropathy (DPN). In this study, network analysis was performed to decipher the molecular mechanisms of GSZ in the treatment of DPN. METHODS: The chemical components of the 3 herbs forming GSZ, ie, Ramulus Cinnamomi (Guizhi), Paeonia lactiflora (Shaoyao) and Rhizoma Anemarrhenae (Zhimu), were searched in Chinese medicine dictionaries, and their target proteins were identified in PubChem. DPN genes were searched in PubMed gene databases. Ingenuity Pathway Analysis (IPA) was used to build the GSZ pharmacological network and DPN molecular network. The canonical pathways between the two networks were compared to decipher the molecular mechanisms of GSZ in the treatment of DPN. RESULTS: Sixty-one protein targets for Guizhi, 31 targets for Shaoyao, 47 targets for Zhimu, as well as 23 genes related to DPN were identified and uploaded to IPA. The primary functions of the DPN molecular network were inflammatory response, metabolic disease, cellular assembly and organization. As far as the pharmacological network functions were concerned, Guizhi target proteins were involved in neurological disease, inflammatory disease, cellular growth and proliferation, cell signaling, molecular transport, and nucleic acid metabolism, Shaoyao target proteins were related to neurological disease, inflammatory disease, and Zhimu target proteins focused on cell death and survival, cellular movement, immune cell trafficking, DNA replication, recombination and repair, and cell cycle. In the three-herb combination GSZ, several new network functions were revealed, including the inflammatory response, gene expression, connective tissue development and function, endocrine system disorders, and metabolic disease. The canonical pathway comparison showed that Shaoyao focused on IL-12 signaling and production in macrophages, and Zhimu focused on TNFR2 signaling, death receptor signaling, ILK signaling, IL-17A in gastric cells, IL-6 signaling, IL-8 signaling, the role of JAK1, JAK2, and TYK2 in interferon signaling, IL-9 signaling, HMGB1 signaling, NO production and ROS production in macrophages, whereas GSZ focused aryl hydrocarbon receptor signaling and apoptosis signaling in addition to those pathways induced by Guizhi, Shaoyao and Zhimu. CONCLUSION: Although each single herb can affect some DPN-related functions and pathways, GSZ exerts more effects on DPN-related functions and pathways. The effects of GSZ on aryl hydrocarbon receptor signaling and apoptosis signaling pathways may be the key components of its total molecular mechanisms.