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Background: The p21-activated kinases 4 (PAK4) refer to a promising target for cancer treatment. Currently, a wide range of PAK4 inhibitors has been reported. Objective: The objective of this study is to study the structural requirements of quinoline derivatives as PAK4 inhibitors and to design novel PAK4 inhibitors. Methods: In the present study, a set of quinazoline PAK4 inhibitors underwent CoMFA, CoMSIA, molecular docking, as well as molecular dynamics simulations. Results: The built CoMFA (q2=0.595, r2=0.986, r2 pred =0.689) and CoMSIA (q2=0.762, r2=0.984, r2 pred=0.822) models exhibited high robustness and prominent predicting ability. As revealed from the results of molecular docking and molecular dynamics simulations, hydrogen bond and hydrophobic interactions primarily impact the affinity of PAK4 inhibitors, and Leu398 acts as an amino acid that leads to significant stabilization of the mentioned inhibitors. Moreover, the present study developed five novel molecules exhibiting high biological activity predicted and satisfactory ADME properties. Conclusion: The structural basis of PAK4 with respect to the activities of its inhibitors was revealed, which may be conducive to designing novel PAK4 inhibitors.

The circadian clock is an endogenous regulation mechanism that coordinates biological processes with daily changes, which are regulated by circadian clock genes. Bmal1 and Period are key circadian clock genes and their roles in reproductive development have been widely studied. The spawning time of Sinonovacula constricta is limited to the night even under external artificial stimulation, and it might be regulated by the internal circadian clock. In this study, the heart rate of S. constricta was higher between 20:00-04:00 at night and lower between 12:00-16:00 during the day, and the sex hormone contents were the highest at 00:00 and the lowest at 18:00 (P < 0.01). Therefore, these obvious changes in the circadian rhythm indicate that S. constricta is a nocturnal animal. The open reading frame (ORF) of Bmal1 comprises 1944 bp encoding 647 aa, while the ORF of Period comprises 3111 bp encoding 1036 aa. Bmal1 and Period were both expressed in four tissues, but they had opposite rhythmic expression patterns. Bmal1 expression was higher at 00:00-06:00 and lower at 12:00-18:00, and Period expression was opposite, thereby suggesting that Bmal1 and Period are involved in positive and negative pathways regulated by the circadian clock, respectively. Strong protein fluorescence signals of Bmal1 and Period proteins were observed in mature oocytes, spermatids, hepatocytes, and epithelial cells of siphons. After siRNA interference, the expression of both Bmal1 and Period significantly decreased (P < 0.01), and the sex hormone contents decreased significantly from 3 to 7 days in the siRNA treatment groups (P < 0.01). Therefore Bmal1 and Period may regulate nocturnal spawning by controlling sex hormone secretion. These findings provide a theoretical basis for understanding the molecular mechanism related to spawning, and may facilitate the artificial propagation of mollusks.

Additional file 1. Appendices

Additional file 4: Table S3. Sequences of Cu/Zn-SOD motifs.

Additional file 2: Fig. S1. synteny of SOD family members in Crassostrea gigas, Crassostrea virginica, Crassostrea hongkongensis, and Saccostrea glomerata. CV represented Crassostrea virginica; CG, Crassostrea gigas; CH, Crassostrea hongkongensis; Sgl, Saccostrea glomerata. The line represented the genome collinear relationship between four species. The red triangle and colored lines showed the SODs in Crassostrea gigas and the collinear relationship with other three species.

黑麂是中国特有的濒危鹿科动物，分布于浙闽赣皖四省的部分山地丘陵。为明确黑麂的活动节律及适宜环境温度，探讨四省区域的潜在分布区情况，2018年1月至2019年1月，在遂昌牛头山林场内布设57台Ltlacorn红外相机，对黑麂及其同域物种进行研究。监测期间红外相机共有效监测到黑麂26次，相对多度指数为1.79。根据监测到黑麂位点与文献记录，共确定黑麂出现位点16个。根据黑麂栖息地特征选择6个生境因子为预测背景，利用MaxEnt模型预测黑麂在浙闽赣皖四省的潜在适生区。模型预测结果准确性较高(AUC=0.976)。结果表明：(1)黑麂年活动高峰季节为夏季，日活动高峰为7：00-9：00和16：00-18：00；(2)温度是影响黑麂活动的重要因素，其活动最适宜温度范围为18-28℃；(3)黑麂潜在适生区总面积约为25980.62 km2，占四省总面积的4.87%；(4)黑麂潜在适生区分为浙赣皖潜在分布区、浙赣潜在分布区、洞宫山潜在分布区和括苍山潜在分布区4个区域。建议(1)加强潜在分布区内种群资源的调查；(2)识别并建立各适宜生境之间的生态廊道；(3)建立黑麂保护网络。

In existing deep learning methods, almost all loss functions assume that sample data values used to be predicted are the only correct ones. This assumption does not hold for laboratory test data. Test results are often within tolerable or imprecision ranges, with all values in the ranges acceptable. By considering imprecision samples, we propose an imprecision range loss (IR loss) method and incorporate it into Long Short Term Memory (LSTM) model for disease progress prediction. In this method, each sample in imprecision range space has a certain probability to be the real value, participating in the loss calculation. The loss is defined as the integral of the error of each point in the impression range space. A sampling method for imprecision space is formulated. The continuous imprecision space is discretized, and a sequence of imprecise data sets are obtained, which is convenient for gradient descent learning. A heuristic learning algorithm is developed to learn the model parameters based on the imprecise data sets. Experimental results on real data show that the prediction method based on IR loss can provide more stable and consistent prediction result when test samples are generated from imprecision range.

The tiger frog Hoplobatrachus rugulosus (Wiegmann 1834) is a large robust dicroglossid frog widely distributed in southern China, Malaysia, Myanmar, Vietnam and Thailand. The escaped bred tiger frog introduced from Thailand hybridized with Chinese native population may have affected the genetic diversity of local Chinese tiger frogs. However, previous microsatellite loci of this species do not offer enough information to construct the genetic map. Here, we reported 33 new microsatellite loci from transcriptome sequencing for H. rugulosus. Alleles ranged between 1 and 10 per locus and only one locus (HRT001) was monomorphic. The polymorphic information content, observed and expected heterozygosity were 0–0.794, 0–0.969 and 0–0.831, respectively. None of the loci was observed in linkage disequilibrium and two loci (HRT023 and HRT068) deviated from Hardy–Weinberg equilibrium after Bonferroni correction for multiple tests. These transcriptome-derived microsatellite markers will be used to study the genetic divergence and construct the genetic map in H. rugulosus.

Body temperature is the most important physiological variable affecting the performance of ectothermic animals.In June and October of 2011,we collected female and male subadults(gonads have not yet matured),juveniles(tails have just been completely absorbed),and tadpoles(stages 28—38) of the tiger frog Hoplobatrachus chinensis,which is a national secondary grade protection animal,from the herpetological laboratory of Lishui University,Zhejiang,East China.The objectives of this study were to examine ontogenetic shifts in the selected body temperature(Tsel),critical thermal maximum(CTmax),and critical thermal minimum(CTmin) of the tiger frog.Tsel of tadpoles was measured by recording the water temperature of their selected location in a thermal gradient ranging from 10—42℃,while Tsel of juveniles and subadults was measured by recording cloacal temperature in a thermal gradient ranging from 20—45℃.We cooled(for CTmin determination) or heated(for CTmax determination) experimental animals from 25℃.Body temperatures associated with a transient loss of the righting response at lower and upper limits of thermal tolerance were considered to be the endpoints for CTmin and CTmax,respectively.Statistical analysis by ANOVA showed that there were significant differences in Tsel,CTmin,CTmax,and viable temperature range among the three age groups.The Tsel of juveniles(24.10℃) was significantly lower than that of female subadults(28.06℃),male subadults(29.17℃),and tadpoles(28.23℃),while there was no significant difference in Tsel among the latter three groups.The CTmin of juveniles(13.85℃) was significantly higher than that of female subadults(11.27℃),male subadults(10.84℃),and tadpoles(10.74℃),while there was no significant difference in CTmin among the latter three.Tadpoles had the highest CTmax,which was 43.31℃,followed by subadults(female: 39.55℃;male: 39.02℃) and juveniles in decreasing order.Similarly,tadpoles had the widest viable temperature range(32.58℃),followed by subadults(female: 28.28℃;male: 28.18℃),and juveniles(21.62℃) in decreasing order.There were no significant differences in Tsel,CTmin,CTmax,and viable temperature range between female and male subadults.Body temperature of juveniles and subadults of H.chinensis was significantly correlated with water temperature in both decreasing and increasing rates.After removing the effects of water temperature,changes in rates of body temperature variation were removed by using residuals from the regression.Two-way ANOVA(cooling and heating rate were measured repeatedly) indicated that the rates of change in the body temperature of juveniles were significantly greater than rates of change of subadults.Types of thermal changes(i.e.rates of cooling and heating) and the interaction of these factors had no effect on changes in the body temperature of H.chinensis.In conclusion,we suggest that in the tiger frog H.chinensis,fundamental thermal niche separation and development restrictions are the most probable explanations for our findings.

Ecologists are increasingly focusing on the effects of biological invasions on soil biodiversity and ecosystem functioning. We compared soil nematodes under plant communities dominated by invasive Solidago canadensis and native plant Phragmites australis at 6 sites (Zhenhai, Fengxian, Pinghu, Haiyan, Cixi and Hangzhou) in Hangzhou Bay to assess the effects of S. canadensis invasions on soil nematode communities. The total number of genera and diversity of soil nematode did not differ between S. canadensis and P. australis communities. Trophic diversity, most of the proportions of trophic groups and nematode community structure varied between the two plant communities. These results suggested that the invasion of S. canadensis changed soil community structure and functioning in Hangzhou Bay. Compared to P. australis communities, the proportion of fungivores tended to increase in soil under S. canadensis communities, suggesting that the invasion might modify soil nutrient cycling. The proportion of herbivores decreased in soil dominated by S. canadensis, suggesting that the exotic S. canadensis is less vulnerable to parasitic nematodes than the native P. australis. Interactions between plant community type and site were significant for nematode diversity and community structure, which indicated that site was an important factor in determining the impact of the invasive plant on soil fauna. Soil grain composition, soil carbon and soil nitrogen were identified as the most important factors in shaping nematode communities.

Matings and crosses within and among two different geographic stocks from Shandong and Jiangsu populations in Meretrix meretrix were produced in order to breed new strains for farming. Two populations,designated S♀×S♂ and J♀×J♂,were from matings of wild populations of Shangdong and Jiangsu. Two populations,that was S♀×J♂ and J♀×S♂,were from crosses between Shangdong and Jiangsu respectively. The traits of fertilizing rate,hatching rate,growth of D-larvae and growth of juveniles (1-12 months age) were analyzed by ANOVA. The results showed that the fertilizing rate and hatching rate of matings and crosses were not significantly different at the end of second month. There were great changes of growth of juveniles in early-term (3-12 months). Growth of S♀×J♂,S♀×S♂ and J♀×S♂ had no significant difference from each other,but all had significant difference with J♀×J♂ at the early-term (3-12 months). The results indicated that there was different extent heterosis (6%-68%) for growth in F1 crosses. The uptrend among traits was wet weight being greater than other three traits of shell length,shell width and shell height respectively. There were obviously higher growth rate and lower variation coefficicent in S♀×J♂,which indicated the Shandong population would be a good parental stock as maternal for genetic breeding. Water temperature could affect growth of Meretrix meretrix significantly,and the growth rate reached a peak in October and November,but reached a nadir after December. Four populations gained were considered as the basic populations to breed new strains. Increased variation parameters in first filial generation(F1) of cross could be a very good potential for selection of new strains.

The interaction between recombinant Fab57P and the coat protein of tobacco mosaic virus was studied using quantitative structure–activity relationship (QSAR) method. The development of quantitative multivariate model has shown to be a promising approach for unraveling protein–protein interactions by designed mutations in peptide sequence. This approach makes it possible to stereo-chemically determine which residue properties contribute most to the interaction. A set of side-chain descriptors was proposed and applied in structural characterization of three positions (positions 142, 145 and 146) in the peptide antigen. Quantitative sequence–kinetics relationship (QSKR) models describing the dissociation rates (log kd) were developed successfully using orthogonal signal correction–partial least squares method. The results showed that peptides will have high log kd values when the amino acids in position 142 and 145 have high net charge index, and when residue 145 has high hydrophobicity and residue 146 has low hydrophobicity.

A set of 70 peptides with affinity for the class I MHC HLA-A*0201 molecule was subjected to quantitative analyses of structure-affinity relationship based on the SCORE function with good results (r(2)=0.6982, q(2)=0.6188, RMS=0.280). Then the 'leave-one-out' cross-validation (LOO-CV) and an outer test set including 18 outer samples were used to validate the QSAR model, and the results show that the QSAR model has good predictability for outside samples. Statistical analysis showed that the hydrophobic and hydrogen bond interaction played a significant role in peptide-MHC molecule binding. The study also provided useful information for structure modification of CTL epitope, and laid theoretical base for molecular design of therapeutic vaccine.

Northern quahogs (=hard clam; Mercenaria mercenaria) is a commercially important bivalve naturally distributed along the American Atlantic coast. Because the hard clam was first introduced into China as a candidate for aquaculture in 1997, research has been conducted on its ecologic habits, ecological physiology, metabolism, growth, reproduction, artificial propagation, and seed culture. Little information about their chromosomes and karyotype is available. The present study is designed to study the karyotype of the diploids and triploids to provide a reference to genetic research on introduced M. mercenaria. Triploids were produced by inhibiting the release of second polar body (PBII) with a treatment of 450 μmol/mL 6-deimethylaminopurine (6-DMAP), with untreated fertilized eggs developing as normal diploid controls. Chromosome preparations were made from trochophore larvae with drop-splash method. Chromosomes were measured and classified according to Leven criteria. Statistical analysis of rela...

A new set of electrotopological descriptors called Molecular Electronegativity Topological Distance Vector (METDV) which are used to describe the molecular structure of peptide analogues is proposed based on the Pauling electronegativity and topological distance between each non-hydrogen atom. A quantitative structure activity relationship model, based on biological activity of 58 angiotensin converting enzyme (ACE) inhibitors, was constructed by multiple linear regression method. In order to explain the ability of theMETDV to characterize the molecular structure of peptides, a further investigation was performed by modeling quantitative structure activity relationship of bradykinin-potentiating pentapeptides. The results show that the novelMETDV has both excellent structural characterization ability and good activity estimation ability, and reinforce the key role of the joint use of electronic and topological descriptors.

The transporter associated with antigen processing (TAP) is essential for peptide delivery from the cytosol into the lumen of the endoplasmic reticulum (ER), where these peptides are loaded on a major histocompatibility complex (MHC) I molecules and form peptide-MHC complex. The peptide-MHC leaves the ER and displays their antigenic cargo on the cell surface to cytotoxic T cells and recognized by T-cell receptor. In this study, 89 physicochemical properties of amino acid were used to characterize the peptides which were binding to TAP. Then, quantitative structural activity relationship (QSAR) model was constructed by multiple linear regressions (MLR) with the parameters, which had significant contribution for affinity and screened by the stepwise regression (STR). The QSAR model had good reliability (Q2=0.663) and predictive ability (R test 2=0.673). The normalized regression coefficients (NRC) of the QSAR model could demonstrate the contributions of specific position for affinity and discovery the dominant amino acid TAP binding peptide. Therefore, the QSAR model constructed by STR-MLR has many advantages, such as, easier calculation and explanation, good performance, and definite physiochemical indication, which could be used to guide the design and modification of the TAP binding peptide.

It is important to research misfire diagnostics for On-Board Diagnosis system. Misfire detection based on crankshaft speed fluctuation and engine roughness calculation is a common and useful method. This paper studies the current misfire diagnostic method and the optimizing strategy based on Chery 447F engine. Advanced gasoline engine misfire detection method using multiple filtering is presented without Fuel-Cut Self-Learning and Fuel-On Self-Learning.

This paper designs the diagnosis strategy for OBD system oxygen sensor degradation and the relevant test on engine bench is made by oxygen signal generator. The engine emission influence due to oxygen sensor degradation is analysed. Based on the structure and sensing principle of zirconia type oxygen sensor, the mechanism of oxygen sensor deterioration is analysed, and some proposals are put forward to prevent oxygen sensor degradation.

It would be useful for vaccine development to develop a method of rapidly identifying peptide epitopes. In this paper, the empirical three-dimensional quantitative structure-affinity relationship (3D-QSAR) methods were used to study the relationship between the three dimensional structural parameters (the isotropic surface area, ISA, and the electronic charge index, ECI) of the HLA-A*0201 binding peptide and the HLA-A*0201/peptide binding affinities. A set of 102 peptides having affinity with the class I MHC HLA-A*0201 molecule was used as training set. A test set of 40 peptides was used to determine the predictive value of the models. The 3D-QSAR models yielded a q2 = 0.5724 and a high rpred2 = 0.6955. The standard regression coefficients indicated that the hydrophobic interactions played an important role in peptide-MHC molecule binding and predicted the specific amino acid residue essential at a certain position of the peptide. The approach tested in the current paper is highly complementary to many of the methods described in references and possesses good predictability. It is a rapid and convenient method to detect high affinity peptide epitopes.

This paper introduces our CAT system which is set up for testing the optical properties of LC (liquid crystal) cell. In this system, the transmission spectra of the LC cell at different voltages applied on LC film can be tested by computer control automatically. Simultaneously, the CIE1931 and CIE1971 chromaticity are calculated out in the program. >