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The stem and leaves of fresh corn plants can be used as green silage or can be converted to biofuels, and the stalk sugar content and yield directly determine the application value of fresh corn. To identify the genetic variations and candidate genes responsible for the related traits in fresh corn, the genome-wide scan and genome-wide association analysis (GWAS) were performed. A total of 32 selective regions containing 172 genes were detected between sweet and waxy corns. Using the stalk sugar content and seven other agronomic traits measured in four seasons over two years, the GWAS identified ninety-two significant single nucleotide polymorphisms (SNPs). Most importantly, seven SNPs associated with the stalk sugar content were detected across multiple environments, which could explain 13.68-17.82% of the phenotypic variation. Accessions differing in genotype for certain significant SNPs showed significant variation in the stalk sugar content and other agronomic traits, and the expression levels of six important candidate genes were significantly different between two materials with different stalk sugar content. The genetic variations and candidate genes provide valuable resources for future studies of the molecular mechanism of the stalk sugar content and establish the foundation for molecular marker-assisted breeding of fresh corn.

The sulfonylurea herbicide nicosulfuron is efficient, harmless and selective at low doses and has been widely used in maize cultivation. In this study, a pair of corn sister lines, HK301 (nicosulfuron-tolerence, NT) and HK320 (nicosulfuron-sensitive, NS), was chosen to study the effect of nicosulfuron on plant growth and sugar metabolism in sweet maize (Zea mays L.) seedlings. All the experimental samples were subjected to treatment with water or 80 mg kg-1 of nicosulfuron when the sweet maize seedlings grew to the four-leaf stage. Nicosulfuron significantly inhibited the growth of NS line. The content of sucrose and the activities of sucrose phosphate synthase and sucrose synthase in the two inbred lines increased differentially under nicosulfuron stress compared with the respective control treatment. After nicosulfuron treatment, the activities of hexokinase and 6-phosphofructokinase and the contents of pyruvic acid and citric acid in NS line decreased significantly compared with those of NT line, while the content of sucrose and activities of sucrose phosphate synthase and sucrose synthase increased significantly. The disruption of sugar metabolism in NS line led to a lower supply of energy for growth. This study showed that the glycolysis pathway and the tricarboxylic acid cycle were enhanced in nicosulfuron-tolerant line under nicosulfuron stress in enhancing the adaptability of sweet maize., Competing Interests: The authors have declared that no competing interests exist.

Many deep learning (DL)-based molecular generative models have been proposed to design novel molecules. These models may perform well on benchmarks, but they usually do not take real-world constraints into account, such as available training data set, synthetic accessibility, and scaffold diversity in drug discovery. In this study, a new algorithm, ChemistGA, was proposed by combining the traditional heuristic algorithm with DL, in which the crossover of the traditional genetic algorithm (GA) was redefined by DL in conjunction with GA, and an innovative backcrossing operation was implemented to generate desired molecules. Our results clearly show that ChemistGA not only retains the strength of the traditional GA but also greatly enhances the synthetic accessibility and success rate of the generated molecules with desired properties. Calculations on the two benchmarks illustrate that ChemistGA achieves impressive performance among the state-of-the-art baselines, and it opens a new avenue for the application of generative models to real-world drug discovery scenarios.

The U-box E3 ( PUB ) family genes encode the E3 ubiquitin ligase enzyme, which determines substrate specific recognition during protein ubiquitination. They are widespread in plants and are critical for plant growth, development, and response to external stresses. However, there are few studies on the functional characteristic of PUB gene family in the important staple crop, maize ( Zea mays L.). In this study, the PUB gene in maize was aimed to identify and classify through whole-genome screening. Phylogenetic tree, gene structure, conserved motif, chromosome location, gene duplication (GD), synteny, and cis-acting regulatory element of PUB member were analyzed. The expression profiles of ZmPUB gene family in maize during development and under abiotic stress and hormones treatment were analyzed by the RNA-seq data. A total of 79 PUB genes were identified in maize genome, and they were stratified into seven categories. There were 25 pairs of segmental duplications (SD) and 1 pair of tandem duplication (TD) identified in the maize PUB gene family. A close relationship was observed between the monocot plant maize and rice in PUB gene family. There were 94 kinds of cis-acting elements identified in the maize PUB gene family, which included 46 biotic- and abiotic-responsive elements, 19 hormone-responsive elements, 13 metabolic and growth-related elements. The expression profiles of maize PUB gene family showed characteristics of tissue specificity and response to abiotic stress and hormones treatment. These results provided an extensive overview of the maize PUB gene family.

Creating a wide range of new compounds that not only have ideal pharmacological properties but also easily pass long-term toxicity evaluation is still a challenging task in current drug discovery. In this study, we developed a conditional generative model by combining a semisupervised variational autoencoder (SSVAE) with an MGA toxicity predictor. Our aim is to generate molecules with low toxicity, good drug-like properties, and structural diversity. For multiobjective optimization, we have developed a method with hierarchical constraints on the toxicity space of small molecules to generate drug-like small molecules, which can also minimize the effect on the diversity of generated results. The evaluation results of the metrics indicate that the developed model has good effectiveness, novelty, and diversity. The generated molecules by this model are mainly distributed in low-toxicity regions, which suggests that our model can efficiently constrain the generation of toxic structures. In contrast to simply filtering toxic ones after generation, the low-toxicity molecular generative model can generate molecules with structural diversity. Our strategy can be used in target-based drug discovery to improve the quality of generated molecules with low-toxicity, drug-like, and highly active properties.

Background: Temporal dynamics may importantly modulate sensory perception, including taste. For example, enhanced perceived taste intensity is often observed when tastant concentration is fluctuating in pulses. The perceived intensity is higher than that of the solutions with a same averaged, but constant concentrations. Meanwhile, taste intensity often decreases with increase of tastant viscosity, despite no changes to the stimuli concentration. The mechanisms to these phenomena are not well understood, in part due to the complicated transport process of tastant through papillae, taste pores, etc. to reach the taste receptors, a cascade of events that are difficult to quantify., Method: We computationally modeled the human tongue surface as a porous micro-fiber medium, extending a previous study and exposed it to pulsatile tastant solution (0.2 and 0.4Hz) with various added viscosity (~0.0011-~0.09 Pa⋅s)., Results: Our simulation revealed that the stimuli concentration within the papillae structure increase with pulsed stimulation, especially those with a longer period (16% increase at 0.4Hz and 23% at 0.2Hz compared to continuous stimuli) and decrease (-6%) with added viscosity. The trend matched well with measured taste perception to sucrose added apple juice in the literature (R 2  > 0.97 for both low and high viscosity stimuli series). Decreased diffusivity due to the increase in viscosity, however, was not a major factor underlying this process., Conclusion: This study re-affirms the validity and accuracy of modeling human tongue surface as a porous medium to investigate taste stimuli transport processes and such peripheral transport dynamics may have significant effects on taste perception., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Circular RNAs (circRNA) have been shown to be involved in the pathogenesis of colorectal cancer (CRC). CircCTNNA1 was found to be one of the upregulated circRNAs in CRC. However, there are few studies on circCTNNA1, so it is necessary to carry out further studies., Methods: The expression of circCTNNA1, microRNA (miR)-363-3p, and chemokine C-X-C motif ligand 5 (CXCL5) was detected by quantitative real-time PCR (qRT-PCR). The protein levels of CXCL5 and metastasis markers were measured using western blot (WB) analysis. Cell proliferation, apoptosis, cell cycle, migration, and invasion were determined by cell counting kit 8 (CCK8) assay, colony formation assay, flow cytometry, and transwell assay. The relationship between miR-363-3p and circCTNNA1 or CXCL5 was evaluated via dual-luciferase reporter assay and RNA immunoprecipitation assay. Animal study was performed to explore the function of circCTNNA1 on CRC tumorigenesis., Results: CircCTNNA1 and CXCL5 were highly expressed in CRC. Knockdown of circCTNNA1 could inhibit the proliferation, cell cycle, metastasis, and promote the apoptosis of CRC cells. MiR-363-3p could be sponged by circCTNNA1, and the inhibition effect of circCTNNA1 silencing on CRC progression could be reversed by miR-363-3p inhibitor. Moreover, miR-363-3p could interact with CXCL5, and CXCL5 overexpression also could reverse the suppressive effect of miR-363-3p on CRC progression. Downregulation of circCTNNA1 also could hinder the tumor growth of CRC in vivo., Conclusion: CircCTNNA1 enhanced CRC progression via regulating the miR-363-3p/CXCL5 axis.

Graph neural networks (GNN) has been considered as an attractive modelling method for molecular property prediction, and numerous studies have shown that GNN could yield more promising results than traditional descriptor-based methods. In this study, based on 11 public datasets covering various property endpoints, the predictive capacity and computational efficiency of the prediction models developed by eight machine learning (ML) algorithms, including four descriptor-based models (SVM, XGBoost, RF and DNN) and four graph-based models (GCN, GAT, MPNN and Attentive FP), were extensively tested and compared. The results demonstrate that on average the descriptor-based models outperform the graph-based models in terms of prediction accuracy and computational efficiency. SVM generally achieves the best predictions for the regression tasks. Both RF and XGBoost can achieve reliable predictions for the classification tasks, and some of the graph-based models, such as Attentive FP and GCN, can yield outstanding performance for a fraction of larger or multi-task datasets. In terms of computational cost, XGBoost and RF are the two most efficient algorithms and only need a few seconds to train a model even for a large dataset. The model interpretations by the SHAP method can effectively explore the established domain knowledge for the descriptor-based models. Finally, we explored use of these models for virtual screening (VS) towards HIV and demonstrated that different ML algorithms offer diverse VS profiles. All in all, we believe that the off-the-shelf descriptor-based models still can be directly employed to accurately predict various chemical endpoints with excellent computability and interpretability.

A method was developed for the determination of biomarkers related to toxicity of deltamethrin in rabbit urine by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). The target analytes in this method are as follows:deltamethrin and its two metabolites (1 R - cis )-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropane carboxylic acid (dibromochrysanthemic acid) and 3-phenoxybenzoic acid (3-PBA), and five toxic biomarkers, viz. serotonin hydrochloride (5-HT), 5-hydroxyindole-3-acetic acid (5-HIAA), 3-nitropropionic acid (3-NPA), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and 6-methoxyguanine. Urine samples were cleaned by matrix solid-phase dispersion extraction (MSPD) with diatomite; and protein was precipitated with trichloroacetic acid; and then the sample solutions were purified with hydrophilic-lipophilic balance (HLB) solid-phase extraction cartridges. The biomarkers were analyzed with electrospray ionization (ESI) in a positive and negative switching scan mode, in which the positive scan mode was used for deltamethrin, 5-HT, 5-HIAA, 8-OHdG, and 6-methoxyguanine, and the negative scan mode was used for (1 R - cis )-3-(2,2-dibromoethenyl)-2,2-dimethylcyclopropane, 3-PBA, and 3-NPA. The target compounds were quantified with the external standard using matrix calibration curves. The linear regression curves of the eight target compounds were linear with correlation coefficients no less than 0.9914. The LOD and LOQ of 5-HIAA were 20 μg/L and 50 μg/L, respectively, and the LODs and LOQs of the other analytes were 0.2-5.0 μg/L and 0.5-10 μg/L, respectively. The average recoveries of the analytes spiked in rabbit urine ranged from 74.2% to 98.7% at three levels, with relative standard deviations (RSDs) no more than 12%. The method was simple, fast, accurate, sensitive, and suitable for the detection for the exposure evaluation of deltamethrin.

In recent decades, the frequency and intensity of harmful algal blooms (HABs), as well as a profusion of toxic phytoplankton species, have significantly increased in coastal regions of China. Researchers attribute this to environmental changes such as rising atmospheric CO 2 levels. Such addition of carbon into the ocean ecosystem can lead to increased growth, enhanced metabolism, and altered toxicity of toxic phytoplankton communities resulting in serious human health concerns. In this study, the effects of elevated partial pressure of CO 2 (pCO 2 ) on the growth and toxicity of a strain of Alexandrium tamarense (ATDH) widespread in the East and South China Seas were investigated. Results of these studies showed a higher specific growth rate (0.31±0.05day -1 ) when exposed to 1000μatm CO 2 , (experimental), with a corresponding density of (2.02±0.19)×10 7 cellsL -1 , that was significantly larger than cells under 395μatm CO 2( control). These data also revealed that elevated pCO 2 primarily affected the photosynthetic properties of cells in the exponential growth phase. Interestingly, measurement of the total toxin content per cell was reduced by half under elevated CO 2 conditions. The following individual toxins were measured in this study: C1, C2, GTX1, GTX2, GTX3, GTX4, GTX5, STX, dcGTX2, dcGTX3, and dcSTX. Cells grown in 1000μatm CO 2 showed an overall decrease in the cellular concentrations of C1, C2, GTX2, GTX3, GTX5, STX, dcGTX2, dcGTX3, and dcSTX, but an increase in GTX1 and GTX4. Total cellular toxicity per cell was measured revealing an increase of nearly 60% toxicity in the presence of elevated CO 2 compared to controls. This unusual result was attributed to a significant increase in the cellular concentrations of the more toxic derivatives, GTX1 and GTX4.Taken together; these findings indicate that the A. tamarense strain ATDH isolated from the East China Sea significantly increased in growth and cellular toxicity under elevated pCO 2 levels. These data may provide vital information regarding future HABs and the corresponding harmful effects as a result of increasing atmospheric CO 2 ., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Simple and low cost sensor for the determination of bisphenol A (BPA) based on graphene-1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6) modified glassy carbon electrode was developed. It was an irreversible oxidation process of BPA on the modified electrode. Experimental conditions such as modified volume, pH, scan rate and accumulation time have been optimized. The modified electrode provided a considerable enhancement of BPA oxidation. The electrochemical response of BPA on this modified electrode was better than those on the graphene modified electrode and bare electrode. The detection limit of BPA was 8nM (S/N=3), the linear range was from 20nM to 2µM. The modified electrode has been employed for determination of milk and soda spiked BPA successfully., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Bridge carbon (13)C NMR shifts of a wide set of substituted cinnamyl anilines p-XC(6)H(4)CHCHCHNC(6)H(4)Y-p (XNO(2), Cl, H, Me, MeO, or NMe(2); YNO(2), CN, CO(2)Et, Cl, F, H, Me, MeO or NMe(2)) had been used as a probe to study the change of substituent effect in the conjugated system. The goal of this work was to study the difference among the substituent effect on SCS of all bridge carbons, and find the alternating of substituent effect in this model compounds. In this study, it was found that the change of the inductive effect and the conjugative effect on different bridge carbons is related to the bond number (m) from the substituent to the corresponding carbon, and the adjusted parameters σ(F(rel))(∗) and σ(R(ver))(∗) can be suitable to scale the difference of the inductive effect and the conjugative effect on bridge carbons. Moreover, because of the difference of substituent effect on bridge carbons, the substituent cross-interaction item Δσ(2)(Δσ(2) = (σ(F(rel))(∗)(X) + σ(R(ver))(∗)(X) - σ(F(rel))(∗)(Y) - σ(R(ver))(∗)(Y))(2)) was not suitable simply to scale the interaction between substituents X and Y for all bridge carbons, so the Δσ(2) was recommended to be divided into two parts: Δσ(F(rel))(2) (Δσ(F(rel))(2) = σ(F(rel))(∗)(X) - σ(F(rel))(∗)(Y))(2)) and Δσ(R(ver))(2) (Δσ(R(ver))(2) = (σ(R(ver))(∗)(X) - σ(R(ver))(∗)(Y))(2)). With σ(F(rel))(∗), σ(R(ver))(∗), Δσ(F(rel))(2), Δσ(R(ver))(2), and δ(C,parent), the obtained correlation equation can be used to correlate with the 159 sorts of SCS of the different bridge carbon in cinnamyl aniline derivatives. The correlation coefficient is 0.9993, and the standard deviation is only 0.53 ppm. The multi-parameter correlation equation can be recommended to predict well the corresponding bridge carbons SCS of disubstituted cinnamyl anilines., (Copyright © 2012 Elsevier B.V. All rights reserved.)

The accuracy, repeatability, and reproducibility characteristics of a method using immunoaffinity column (IAC) cleanup with postcolumn derivatization and LC with a fluorescence detector (FLD) for determination of aflatoxins (AFs; sum of AFs B1, B2, G1, and G2) in olive oil, peanut oil, and sesame oil have been established in a collaborative study involving 15 laboratories from six countries. Blind duplicate samples of blank, spiked at levels ranging from 0.25 to 20.0 microg/kg for AF, were analyzed. A naturally contaminated peanut oil sample was also included. Test samples were extracted with methanol-water (55 + 45, v/v). After shaking and centrifuging, the lower layer was filtered, diluted with water, and filtered through glass microfiber filter paper. The filtrate was then passed through an IAC, and the toxins were eluted with methanol. The toxins were then subjected to RPLC-FLD analysis after postcolumn derivatization. Average recoveries of AFs from olive oil, peanut oil, and sesame oil ranged from 84 to 92% (at spiking levels ranging from 2.0 to 20.0 microg/kg); of AFB1 from 86 to 93% (at spiking levels ranging from 1.0 to 10.0 microg/kg); of AFB2 from 89 to 95% (at spiking levels ranging from 0.25 to 2.5 microg/kg); of AFG1 from 85 to 97% (at spiking levels ranging from 0.5 to 5.0 microg/kg); and of AFG2 from 76 to 85% (at spiking levels ranging from 0.25 to 2.5 microg/kg). RSDs for within-laboratory repeatability (RSD(r)) ranged from 3.4 to 10.2% for AF, from 3.5 to 10.9% for AFB1, from 3.2 to 9.5% for AFB2, from 6.5 to 14.9% for AFG1, and from 4.8 to 14.2% for AFG2. RSDs for between-laboratory reproducibility (RSDR) ranged from 6.1 to 14.5% for AF, from 7.5 to 15.4% for AFB1, from 7.1 to 14.6% for AFB2, from 10.8 to 18.1% for AFG1, and from 7.6 to 23.7% for AFG2. Horwitz ratio values were < or = 2 for the analytes in the three matrixes.

We propose that cell-cycle-dependent timing of FEN1 nuclease activity is essential for cell-cycle progression and the maintenance of genome stability. After DNA replication is complete at the exit point of the S phase, removal of excess FEN1 may be crucial. Here, we report a mechanism that controls the programmed degradation of FEN1 via a sequential cascade of posttranslational modifications. We found that FEN1 phosphorylation stimulated its SUMOylation, which in turn stimulated its ubiquitination and ultimately led to its degradation via the proteasome pathway. Mutations or inhibitors that blocked the modification at any step in this pathway suppressed FEN1 degradation. Critically, the presence of SUMOylation- or ubiquitination-defective, nondegradable FEN1 mutant protein caused accumulation of Cyclin B, delays in the G1 and G2/M phases, and polyploidy. These findings may represent a newly identified regulatory mechanism used by cells to ensure precise cell-cycle progression and to prevent transformation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Flap endonuclease 1 (FEN1), a member of the Rad2 nuclease family, possesses 5' flap endonuclease (FEN), 5' exonuclease (EXO), and gap-endonuclease (GEN) activities. The multiple, structure-specific nuclease activities of FEN1 allow it to process different intermediate DNA structures during DNA replication and repair. We previously identified a group of FEN1 mutations and single nucleotide polymorphisms that impair FEN1's EXO and GEN activities in human cancer patients. We also established a mouse model carrying the E160D FEN1 mutation, which mimics the mutations seen in humans. FEN1 mutant mice developed spontaneous lung cancer at high frequency at their late life stages. An important unanswered question is whether individuals carrying such FEN1 mutation are more susceptible to tobacco smoke and have an earlier onset of lung cancer. Here, we report our study on E160D mutant mice exposed to benzo[α]pyrene (B[α]P), a major DNA damaging compound found in tobacco smoke. We demonstrate that FEN1 employs its GEN activity to cleave DNA bubble substrates with BP-induced lesions, but the E160D FEN1 mutation abolishes such activity. As a consequence, Mouse cells carrying the E160D mutation display defects in the repair of B[α]P adducts and accumulate DNA double-stranded breaks and chromosomal aberrations upon treatments with B[α]P. Furthermore, more E160D mice than WT mice have an early onset of B[α]P-induced lung adenocarcinoma. All together, our current study suggests that individuals carrying the GEN-deficient FEN1 mutations have high risk to develop lung cancer upon exposure to B[α]P-containing agents such as tobacco smoke., (Copyright © 2011 Elsevier B.V. All rights reserved.)