Molecular mapping and characterization of QBp.caas-3BL for black point resistance in wheat (Triticum aestivum L.).

KEY MESSAGE: We fine-mapped QBp.caas-3BL for black point resistance in an interval of 1.7 Mb containing five high-confidence annotated genes and developed a KASP marker suitable for selection of QBp.caas-3BL. Wheat black point, which occurs in most wheat-growing regions of the world, is detrimental to grain appearance, processing and nutrient quality. Mining and characterization of genetic loci for black point resistance are helpful for breeding resistant wheat cultivars. We previously identified a major QTL QBp.caas-3BL in a recombinant inbred line (RIL) population of Linmai 2/Zhong 892 across five environments. Here we confirmed the QTL in two additional environments. The genetic region of QBp.caas-3BL was enriched with newly developed markers. Using four sets of near isogenic lines, QBp.caas-3BL was narrowed down to a physical interval of approximately 1.7 Mb, including five annotated genes according to IWGSC reference genome. TraesCS3B02G404300, TraesCS3B02G404600 and TraesCS3B02G404700 were predicted as candidate genes based on the analyses of sequence polymorphisms and differential expression. We also converted a SNP of TraesCS3B02G404700 into a breeding-applicable KASP marker and verified its efficacy for marker-assisted breeding in a panel of germplasm. The findings not only lay a foundation for map-based cloning of QBp.caas-3BL but also provide a useful marker for selection of resistant cultivars genotypes in wheat breeding.

miR-671-5p Attenuates Neuroinflammation via Suppressing NF-κB Expression in an Acute Ischemic Stroke Model.

This study was designed to investigate the role of miR-671-5p in in vitro and in vivo models of ischemic stroke (IS). Middle cerebral artery occlusion and reperfusion (MCAO/R) in C57BL/6 mice as well as oxygen-glucose deprivation and reoxygenation (OGD/R) in a mouse hippocampal HT22 neuron line were used as in vivo and in vitro models of IS injury, respectively. miR-671-5p agomir, miR-671-5p antagomir, pcDNA3.1-NF-κB, and negative controls were transfected into cells using riboFECT CP reagent. miR-671-5p agomir, pcDNA3.1-NF-κB, and negative vectors were administered into MCAO/R mice via intracerebroventricular injection. The results showed that miR-671-5p was significantly downregulated and that miR-671-5p agomir alleviated injury and neuroinflammation induced by ischemic reperfusion. A dual-luciferase reporter assay confirmed that NF-κB is a direct target of miR-671-5p. Reverse experiments showed that miR-671-5p agomir reduced neuroinflammation via suppression of NF-κB expression in both in vitro and in vivo models of IS. Our data suggest that miR-671-5p may be a viable therapeutic target for diminishing neuroinflammation in patients with IS.

Reevaluation of lymphovascular invasion in gastric cancer using endothelial markers D2-40 and EVG: Enhanced detection, better predictor of lymph node metastasis and biological aggressiveness.

BACKGROUND AND OBJECTIVES: The diagnosis of lymphovascular invasion (LVI) is often inaccurate with routine histology. This study aimed to evaluate the use of immunohistochemistry (IHC) in detecting LVI and reevaluate the clinical implications of LVI in gastric cancer. METHODS: This prospective unrandomized cohort study analyzed the rates of LVI positivity and its relevance with other clinicopathologic features. RESULTS: Between November 2017 and April 2018, 558 patients undergoing curative gastrectomy were enrolled and assigned to the IHC group (n = 285) and hematoxylin-eosin group (n = 273). The use of IHC increased the rates of LVI positivity (60.8% vs. 43.3%, p < .001) and decreased the rates of undetermined LVI subtype (7.7% vs. 27.1%, p < .001). The LVI-negative patients identified by IHC had fewer lymph node metastases (16.8% vs. 34.6%, p = .002) and earlier pathological stage (p = .004) than those identified by routine histology. The LVI-positive patients identified by IHC had a higher percentage of perineural invasion (p = .019). CONCLUSIONS: The use of endothelial markers significantly enhanced the detection of LVI. The LVI detected by IHC could be a better predictor of lymph node metastasis and biological aggressiveness in gastric cancer.

Triglyceride glucose-body mass index and the risk of diabetes: a general population-based cohort study.

BACKGROUND: Triglyceride glucose-body mass index (TyG-BMI) has been proven to be a reliable substitute for insulin resistance. However, whether a causal association exists between TyG-BMI and new-onset diabetes remains uncertain. The purpose of this study was to investigate the causal association and predictive performance between TyG-BMI and diabetes. METHODS: A total of 116,661 subjects who underwent a physical examination were included in this study. The subjects were divided into five equal points according to the quintile of TyG-BMI, and the outcome of interest was the occurrence of diabetic events. TyG-BMI = ln [fasting plasma glucose (mg/dL) × fasting triglycerides (mg/dL)/2] × BMI. RESULTS: During the average follow-up period of 3.1 (0.95) years, 1888 men (1.61 %) and 793 women (0.68 %) were newly diagnosed with diabetes. Multivariate Cox regression analysis showed that TyG-BMI was an independent predictor of new-onset diabetes (HR 1.50 per SD increase, 95 %CI: 1.40 to 1.60, P-trend < 0.00001), and the best TyG-BMI cutoff value for predicting new-onset diabetes was 213.2966 (area under the curve 0.7741, sensitivity 72.51 %, specificity 69.54 %). Additionally, the results of subgroup analysis suggested that the risk of TyG-BMI-related diabetes in young and middle-aged people was significantly higher than that in middle-aged and elderly people, and the risk of TyG-BMI-related diabetes in non-obese people was significantly higher than that in overweight and obese people (P for interaction < 0.05). CONCLUSIONS: This cohort study of the Chinese population shows that after excluding other confounding factors, there is a causal association of TyG-BMI with diabetes, and this independent association is more obvious in young, middle-aged and non-obese people.

The therapeutic effect of bone marrow-derived mesenchymal stem cells on osteoarthritis is improved by the activation of the KDM6A/SOX9 signaling pathway caused by exposure to hypoxia.

Abnormal expression of KDM6A and SOX9 is a key factor in the pathogenesis of osteoarthritis (OA). Cellular treatments of OA with articular cartilage chondrocytes (ACCs) and bone marrow mesenchymal stem cells (BMSCs) are promising, but their underlying mechanisms remain to be explored. The pellet size, weight and sulfated glycosaminoglycan/DNA content of ACCs were measured to evaluate the effect of BMSCs on the chondrogenic differentiation of SCCs. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to analyze the proliferation of ACCs cultured along or cocultured with BMSCs. Quantitative polymerase chain reaction (qPCR) was performed to evaluate the messenger RNA expression of KDM6A, SOX9, type2 collagen, and Aggrecan in ACCs and OA rats. Western blot and immunohistochemistry were performed to analyze the expression of KDM6A and SOX9 proteins. Bisulfite sequencing PCR was performed to assess the DNA methylation level of the SOX9 promoter. Flow cytometry was used to evaluate the apoptotic status of ACCs. The chondrogenic differentiation of ACCs was significantly enhanced by coculturing with BMSCs, especially under a hypoxic condition. The expression of KDM6A, SOX9, type2 collagen, and Aggrecan was remarkably elevated in ACCs cocultured with BMSCs. Also, the DNA methylation of SOX9 promoter was decreased in ACCs cocultured with BMSCs, along with notably reduced apoptosis. Moreover, ACCs cocultured with BMSCs could repair cartilage lesions and prevent the abnormal expression of KDM6A, SOX9, type2 collagen, and Aggrecan in OA rats. In this study, we cocultured ACCs with BMSCs and used them to treat OA rats. Our findings presented a mechanistic basis for explaining the therapeutic effect of BMSCs on OA treatment.

Chinese version of the international positive and negative affect schedule short form: factor structure and measurement invariance.

BACKGROUND: This study translated the International Positive and Negative Affect Schedule Short Form (I-PANAS-SF) into Chinese and examined its factor structure and measurement invariance in Chinese adolescents in Hong Kong. METHODS: A sample of 4136 Chinese adolescents in Hong Kong was invited to complete a set of questionnaires. The factor structure of the I-PANA-SF was examined using confirmatory factor analysis (CFA) and exploratory structural equational modeling (ESEM). Internal consistency reliability was evaluated using Cronbach's alpha coefficients, and nomological validity was assessed using bivariate correlations between positive affect (PA) and negative affect (NA) subscales with effort, worry and lack of concentration. Finally, measurement invariance across genders and grades was examined to evaluate the invariance of the I-PANAS-SF. RESULTS: Factor structure analysis suggested that the ESEM model outperformed the CFA model. The results of ESEM analysis indicated that one item ("alert") was problematic and a 9-item two-factor measurement model with that item removed was a better fit for the data. The Cronbach's alpha values were above 0.70 (0.81 and 0.83), revealing excellent internal consistency reliability. The PA subscale was positively associated with effort and negatively associated with worry and lack of concentration. The NA subscale was negatively associated effort and positively associated with lack of concentration and worry, indicating nomological validity. Finally, measurement invariance analysis revealed strict invariance across genders and grades. CONCLUSIONS: The results of the study provide preliminary support for validity and reliability of the 9-item Chinese version of the I-PANAS-SF and suggest that it is suitable for use among Chinese adolescents in Hong Kong.

Insights into transcriptional characteristics and homoeolog expression bias of embryo and de-embryonated kernels in developing grain through RNA-Seq and Iso-Seq.

Bread wheat (Triticum aestivum L.) is an allohexaploid, and the transcriptional characteristics of the wheat embryo and endosperm during grain development remain unclear. To analyze the transcriptome, we performed isoform sequencing (Iso-Seq) for wheat grain and RNA sequencing (RNA-Seq) for the embryo and de-embryonated kernels. The differential regulation between the embryo and de-embryonated kernels was found to be greater than the difference between the two time points for each tissue. Exactly 2264 and 4790 tissue-specific genes were found at 14 days post-anthesis (DPA), while 5166 and 3784 genes were found at 25 DPA in the embryo and de-embryonated kernels, respectively. Genes expressed in the embryo were more likely to be related to nucleic acid and enzyme regulation. In de-embryonated kernels, genes were rich in substance metabolism and enzyme activity functions. Moreover, 4351, 4641, 4516, and 4453 genes with the A, B, and D homoeoloci were detected for each of the four tissues. Expression characteristics suggested that the D genome may be the largest contributor to the transcriptome in developing grain. Among these, 48, 66, and 38 silenced genes emerged in the A, B, and D genomes, respectively. Gene ontology analysis showed that silenced genes could be inclined to different functions in different genomes. Our study provided specific gene pools of the embryo and de-embryonated kernels and a homoeolog expression bias model on a large scale. This is helpful for providing new insights into the molecular physiology of wheat.

Factor structure and measurement invariance of the Subjective Vitality Scale: evidence from Chinese adolescents in Hong Kong.

PURPOSE: This study translates the Subjective Vitality Scale (SVS) into Chinese and examines its factor structure and measurement invariance in a sample of Chinese adolescents in Hong Kong. METHODS: Chinese adolescents in Hong Kong were invited to participate in the study. Four models of the SVS (a 7-item model, two 6-item models and a 5-item model) were compared using confirmatory factor analysis (CFA). The internal consistency reliability was evaluated using Cronbach's alpha coefficients, and the criterion validity was assessed using bivariate correlations between subjective vitality and positive and negative affect. Finally, measurement invariance across genders and time points was examined to evaluate the invariance of the SVS model. RESULTS: The results of the CFA analysis indicated that the 5-item measurement model fit the data better than the other three models. The Cronbach's alpha was above 0.70 (0.92), revealing excellent internal consistency reliability, and the SVS was significantly associated with positive affect and negatively associated with negative affect, indicating criterion validity. Finally, the measurement invariance analysis of the 5-item model displayed strict invariance across genders and time points. CONCLUSIONS: The results support the 5-item measurement model of the Chinese version of the SVS. This model has excellent internal consistency reliability, supports the criterion validity of the instrument and demonstrates strict invariance across genders and time points. In summary, the findings suggest that the 5-item Chinese version of the SVS is a reliable and valid instrument for assessing the subjective vitality of Chinese adolescents in Hong Kong.

PPIM: A Protein-Protein Interaction Database for Maize.

Maize (Zea mays) is one of the most important crops worldwide. To understand the biological processes underlying various traits of the crop (e.g. yield and response to stress), a detailed protein-protein interaction (PPI) network is highly demanded. Unfortunately, there are very few such PPIs available in the literature. Therefore, in this work, we present the Protein-Protein Interaction Database for Maize (PPIM), which covers 2,762,560 interactions among 14,000 proteins. The PPIM contains not only accurately predicted PPIs but also those molecular interactions collected from the literature. The database is freely available at http://comp-sysbio.org/ppim with a user-friendly powerful interface. We believe that the PPIM resource can help biologists better understand the maize crop.

The process by which perceived autonomy support predicts motivation, intention, and behavior for seasonal influenza prevention in Hong Kong older adults.

BACKGROUND: This study examined the effectiveness of a theoretical framework that integrates self-determination theory (SDT) and the theory of planned behavior (TPB) in explaining the use of facemasks to prevent seasonal influenza among Hong Kong older adults. METHODS: Data were collected at two time points in the winter in Hong Kong, during which influenza is most prevalent. At Time 1, older adults (N = 141) completed self-report measures of SDT (perceived autonomy support from senior center staff, autonomous motivation for influenza prevention) and TPB (attitude, subjective norm, perceived behavioral control, and intention for influenza prevention) constructs with respect to facemask used to prevent infection. Two weeks later, at Time 2, participants' acceptance of a facemask to prevent influenza in the presence of an experimenter with flu-like symptoms was recorded. RESULTS: Path analysis found that perceived autonomy support of senior center staff was positively and significantly linked to autonomous motivation for facemask use, which, in turn, was positively related to intentions to wear facemasks through the mediation of attitude, subjective norm, and perceived behavioral control. However, the effect of intention on facemask use was not significant. CONCLUSIONS: Results generally support the proposed framework and the findings of previous studies with respect to intention, but the non-significant intention-behavior relationship may warrant future research to examine the reasons for older adults not to wear facemasks to prevent seasonal influenza despite having positive intentions to do so.

[Efficacy and safety of alogliptin in treatment of type 2 diabetes mellitus: a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial in mainland China].

OBJECTIVE: To evaluate the efficacy and safety of alogliptin in Chinese patients with type 2 diabetes (T2DM). METHODS: This was a multicenter, randomized, double-blind, placebo-controlled phase III trial. A total of 491 subjects with T2DM were randomized in a 1:1 ratio to receive alogliptin (25 mg once daily) or placebo for 16 weeks. Among them, 181 were in the monotherapy group (group A), 186 were in the add-on to metformin group (group B), and 124 were in the add-on to pioglitazone group (group C). RESULTS: After 16 weeks of therapy, glycosylated hemoglobin A1c (HbA1c) levels decreased in both alogliptin and placebo groups. The mean changes in HbA1c for alogliptin and placebo were 1.00% and 0.43% (P<0.001), 0.91% and 0.23% (P<0.001), and 0.76% and 0.25% (P<0.001) in group A, B and C, respectively. Compared with placebo, alogliptin treatment led to a greater decrease in fasting plasma glucose (FPG) and a higher percentage of subjects who achieved HbA1c targets of ≤ 6.5% and ≤ 7.0%. The percentage of subjects who experienced all adverse events including hypoglycemia with alogliptin were comparable to those with placebo. CONCLUSIONS: Alogliptin 25 mg once daily reduced HbA1c and FPG, and increased a greater proportion of subjects achieving HbA1c goals of ≤6.5% and ≤7.0% compared with placebo when used as a monotherapy, add-on to metformin, or add-on to pioglitazone. The hypoglycemia rates and safety profiles with alogliptin were similar to those with placebo.

A BRIEF NOTE ON THE VALIDITY AND RELIABILITY OF THE RATING OF PERCEIVED EXERTION SCALE IN MONITORING EXERCISE INTENSITY AMONG CHINESE OLDER ADULTS IN HONG KONG.

This study examined the validity and reliability of the Cantonese Borg 6-20 Rating of Perceived Exertion (RPE) scale in monitoring exercise intensity among Chinese older adults. A total of 40 apparently healthy older adults (16 men, 24 women; M age=69.8 yr., SD=4.56) performed two trials of three intermittent exercise tests administered in random order using the cycle ergometer. Results revealed significant differences of RPE, HR, and VO2 between different workloads, and there were moderate to high correlations between RPE and HR and VO2, respectively. Results also found moderate consistency of RPE between Trial 1 and Trial 2. These indicated that the Cantonese 6-20 RPE scale can be used as a valid and reliable tool for monitoring exercise intensity among the Chinese older adults.

Neuroprotective effects of electro acupuncture on hypoxic-ischemic encephalopathy in newborn rats Ass.

Hypoxic-ischemic encephalopathy (HIE) is a common and potentially devastating condition in the neonate, associated with high mortality and morbidity. Effective treatment options are limited and therefore alternative therapies such as acupuncture are increasingly used. Previous studies have shown that electro acupuncture promoted proliferation of neural progenitor cell and increased expression of neurotrophic factor in HIE. However, effects of electro acupuncture on downstream signaling pathways have been rarely researched. So, in the present study, we aimed to evaluate the neuroprotective effects of electro acupuncture on HIE and to further investigate the role of GDNF family receptor member RET and its key downstream PI3-K/Akt pathway in the process. A rat HIE model was constructed by the left common carotid artery (LCCA) ligation method in combination with hypoxic treatment. Considering that Baihui (GV20), Dazhui (GV14), Quchi (LI11) and Yongquan (KI1) are commonly used in clinics for stroke treatment and are easy to locate, we chose the above four acupoints as the combination for electro acupuncture treatment which was performed once a day for different time periods. Hematoxylin-eosin (HE) staining and transmission electron microscopy results showed that electro acupuncture could ameliorate neurologic damage and alleviate the degenerative changes of ultra structure of cortical neurons in rats subjected to HIE. And the longer acupuncture treatment lasted, the better its therapeutic effect would be. This was accompanied by gradually increased expression of GDNF family receptor RET at the mRNA level and its downstream signaling Akt at the protein level in the ischemic cortex. These findings suggest that electro acupuncture shows neuroprotective effects in HIE, which at least in part is attributed to activation of PI3-K/Akt signaling pathway.

The Divergent Effects of Resilience Qualities and Resilience Support in Predicting Pre-Competition Anxiety and Championship Performance.

Purpose: Psychological resilience is vital to the development of sport talents. Qualitative research has consistently demonstrated that sport resilience encapsulates a mixed package of resilience qualities (reflecting positive traits and characteristics) and resilience support (reflecting perceived support and related resources). Ironically, sport resilience research adopting quantitative methods has been assessing resilience as a unidimensional construct, with little attention to the multi-facet nature of resilience and its effects on performance. In the present research, we tested a novel proposition that resilience qualities predict reduced pre-competition cognitive anxiety and contribute to performance more than resilience support. Methods & Results: Across two samples of competitive table tennis players (Study 1: N = 196 competing at province level; Study 2: N = 106 competing at national level), we consistently found resilience qualities, rather than resilience support, predicted lower levels of pre-competition cognitive anxiety and superior performance at a national championship. Results also suggest that pre-competition cognitive anxiety mediated the relationship between resilience qualities and performance. Conclusion: The findings provide the first evidence supporting the divergent effects of resilience qualities and resilience support in predicting pre- competition anxiety and championship performance and call for the consideration of such a distinction when designing and delivering resilience programs.

Axial Crushing Theory and Optimization of Lattice-Filled Multicellular Square Tubes.

A lattice-filled multicellular square tube features a regular cross-sectional shape, good energy consumption, and good crashworthiness, which is suitable for the design of energy absorbers in various protection fields such as automobiles, aerospace, bridges, etc. Based on the super folding theory, two reference planes are set to refine the energy consumption zone of the super folding element in this study. The energy consumption calculation of convex panel stretching is involved, and the critical crushing force formula is introduced in this study. Meanwhile, the calculation method from a single-cell square tube to a multicellular thin-walled square tube is extended and the structural optimization is investigated, in which the NSGAII algorithm is used to obtain the Pareto front (PF) of the crashworthiness performance index of the square multicellular tubes, the Normal Boundary Intersection (NBI) method is adopted to select knee points, and the influence of different cross-sectional widths on the number, as well as the thickness, of cells are discussed. This study's results indicate that the theoretical value is consistent with that obtained from the numerical simulation, meaning that the improved theoretical model can be applied to predict the crashworthiness of multicellular square cross-sectional tubes. Also, the optimization method and study results proposed in this study can provide a reference for the design of square lattice multicellular tubes.

Mental health literacy, mental health experiences and help-seeking behaviours of Chinese elite athletes: a qualitative study.

Introduction: Elite athletes' help-seeking on mental health might be influenced by their mental health literacy (MHL) and mental health experiences. The current study aimed to explore the MHL, experiences and help-seeking behaviours among elite athletes using a qualitative approach. Methods: Face-to-face semi-structured interviews were conducted among 20 Chinese elite athletes, 12 coaches, and 5 team officials. Interview data was analyzed using content analysis. Results: Seven main themes emerged from the analysis. The current study revealed that Chinese elite athletes suffered from various mental health issues and athletes' MHL levels, help-seeking attitudes and intentions, Chinese sports environments, and Chinese cultural background could impact their help-seeking behaviours. Conclusion: Support for Chinese elite athletes' mental health and help-seeking requires improvement.

Factor structure and measurement invariance of the University Demand-Resource Questionnaire: further evidence from Hungarian university students.

Purpose: The present study aimed to further examine the factor structure and measurement invariance of the UDRQ among a sample of Hungarian university students. Methods: Firstly, the factor structure of the UDRQ was examined among 837 Hungarian university students. Specifically, two measurement models (first-order model and second-order model) were constructed and compared. Secondly, the internal consistency reliability of the UDRQ was examined. Thirdly, measurement invariance of the UDRQ was evaluated across genders. Finally, measurement invariance of the UDRQ was evaluated across two different samples. Results: It was found that the first-order model outperformed the second-order model and better represented the factor structure of the UDRQ subscales. Results of Cronbach's alpha and Composite Reliability suggested that the internal consistency reliabilities of the two UDRQ subscales were satisfactory. Measurement invariance analysis revealed that the UDRQ measurement model was strict invariant across genders and samples. Conclusion: The findings of the present study indicated that the UDRQ displayed satisfactory reliability and validity and could be used to assess demands and resources of Hungarian university students.

Development and initial validation of the Engagement in Athletic Training Scale.

The current study presents the development process and initial validation of the Engagement in Athletic Training Scale (EATS), which was designed to evaluate athletes' engagement in athletic training. In study 1, item generation and initial content validity of the EATS were achieved. In study 2, the factor structure of the EATS was examined using exploratory factor analysis (EFA) and exploratory structural equation modeling (ESEM). Internal consistency reliabilities of the subscales were examined (N = 460). In study 3, factor structure, discriminant validity, internal consistency reliability, and nomological validity of the EATS were further examined in an independent sample (N = 513). Meanwhile, measurement invariance of the EATS across samples (study 2 and study 3) and genders was evaluated. Overall, results from the 3 rigorous studies provided initial psychometric evidence for the 19-item EATS and suggested that the EATS could be used as a valid and reliable measure to evaluate athletes' engagement in athletic training.

Inferring gene regulatory networks from gene expression data by path consistency algorithm based on conditional mutual information.

MOTIVATION: Reconstruction of gene regulatory networks (GRNs), which explicitly represent the causality of developmental or regulatory process, is of utmost interest and has become a challenging computational problem for understanding the complex regulatory mechanisms in cellular systems. However, all existing methods of inferring GRNs from gene expression profiles have their strengths and weaknesses. In particular, many properties of GRNs, such as topology sparseness and non-linear dependence, are generally in regulation mechanism but seldom are taken into account simultaneously in one computational method. RESULTS: In this work, we present a novel method for inferring GRNs from gene expression data considering the non-linear dependence and topological structure of GRNs by employing path consistency algorithm (PCA) based on conditional mutual information (CMI). In this algorithm, the conditional dependence between a pair of genes is represented by the CMI between them. With the general hypothesis of Gaussian distribution underlying gene expression data, CMI between a pair of genes is computed by a concise formula involving the covariance matrices of the related gene expression profiles. The method is validated on the benchmark GRNs from the DREAM challenge and the widely used SOS DNA repair network in Escherichia coli. The cross-validation results confirmed the effectiveness of our method (PCA-CMI), which outperforms significantly other previous methods. Besides its high accuracy, our method is able to distinguish direct (or causal) interactions from indirect associations. AVAILABILITY: All the source data and code are available at: http://csb.shu.edu.cn/subweb/grn.htm. CONTACT: lnchen@sibs.ac.cn; zpliu@sibs.ac.cn SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.