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Benzophenone-type UV filters (BPs) are ubiquitous contaminants in aquatic environments, possibly posing ecological risks to aquatic populations. So far, little is known about the potential adverse effects of BPs on amphibians. Given their potential estrogenic property, we investigated the detrimental effects of the commonly used BPs, BP-3, BP-2, and BP-1, on testis development in amphibians using Xenopus laevis as a model species. Following exposure to 10, 100, 1000 nM BP-3, BP-2, or BP-1 from stages 45/46 to 52, tadpoles presented morphological abnormal testes, characterized by reduced gonomere size and testis area, coupled with suppressed cell proliferation. Meanwhile, the downregulation of testis-biased gene expression and the upregulation of ovary-biased gene expression were observed in BPs-treated testes. Moreover, the estrogen receptor (ER) antagonist ICI 182780 significantly antagonized ovary-biased gene upregulation caused by BPs, suggesting that the effects of BPs on testis differentiation could be mediated by ER, at least partially. Of note, the effects of BPs were not concentration-dependent, but the lowest concentration generally exerted significant effects. Altogether, these observations indicate that the three BPs inhibited testis differentiation and exerted feminizing effects. Importantly, when BP-2 exposure was extended to two months post-metamorphosis, testes of froglets were generally less-developed, with relatively fewer spermatocytes, more spermatogonia, and poorly formed seminiferous tubules. Considering the fact that the lowest concentration (10 nM) of BPs in this study are detectable in aquatic environments, we conclude that BP-3, BP-2, and BP-1, even at environmentally relevant concentrations, can retard testis differentiation at pre-metamorphic stages and cause testis dysgenesis after metamorphosis in the amphibian X. laevis. Our findings suggest that ubiquitous BPs in aquatic environments could pose a potential risk to amphibians.

Identifying relatives across cohorts makes one of the basic routines for genomic data. As conventional such practice often requires explicit genomic data sharing, it is easily hampered by privacy or ethical constraints. In this study, using our proposed scheme for genomic encryption we developedencG-reg, a regression approach that is able to detect relatives of various degrees based on encrypted genomic data. The encryption properties ofencG-regis built on random matrix theory, which masks the original genotypic matrix but still provides controllable precision to that of direct individual-level genotype data. After having found tractable eighth-order moments for encrypted genotype, we established connection between the dimension of a random matrix and the required precision of a study.encG-regconsequently led to balanced i) false positive and false negative rates and ii) the computational cost and the degree of relatives to be searched. We validatedencG-regin 485,158 UKBiobank multi-ethnical samples, and the resolution ofencG-regwas comparable with the conventional method such as KING. In a more complex application, we launched a fine-devised multi-center collaboration across 6 research institutes in China, covering 11 cohorts of 64,091 GWAS samples. In both examples,encG-regrobustly identified and validated relatives existing across the cohorts even under various ethnical background and different genotypic qualities.

Protein kinases are a crucial component of signaling pathways involved in a wide range of cellular responses, including growth, proliferation, differentiation, and migration. Systematic investigation of protein kinases is critical to better understand phosphorylation-mediated signaling pathways and may provide insights into the development of potential therapeutic drug targets. Here we perform a systems-level analysis of the mouse kinome by analyzing multi-omics data. We used bulk and single-cell transcriptomic data from the C57BL/6J mouse strain to define tissue- and cell-type-specific expression of protein kinases, followed by investigating variations in sequence and expression between C57BL/6J and DBA/2J strains. We then profiled a deep brain phosphoproteome from C57BL/6J and DBA/2J strains as well as their reciprocal hybrids to infer the activity of the mouse kinome. Finally, we performed phenome-wide association analysis using the BXD recombinant inbred (RI) mice (a cross between C57BL/6J and DBA/2J strains) to identify any associations between variants in protein kinases and phenotypes. Collectively, our study provides a comprehensive analysis of the mouse kinome by investigating genetic sequence variation, tissue-specific expression patterns, and associations with downstream phenotypes.

Indefinite kernel support vector machine (IKSVM) has recently attracted increasing attentions in machine learning. Since IKSVM essentially is a non-convex problem, existing algorithms either change the spectrum of indefinite kernel directly but risking losing some valuable information or solve the dual form of IKSVM whereas suffering from a dual gap problem. In this paper, we propose a primal perspective for solving the problem. That is, we directly focus on the primal form of IKSVM and present a novel algorithm termed as IKSVM-DC for binary and multi-class classification. Concretely, according to the characteristics of the spectrum for the indefinite kernel matrix, IKSVM-DC decomposes the primal function into the subtraction of two convex functions as a difference of convex functions (DC) programming. To accelerate convergence rate, IKSVM-DC combines the classical DC algorithm with a line search step along the descent direction at each iteration. Furthermore, we construct a multi-class IKSVM model which can classify multiple classes in a unified form. A theoretical analysis is then presented to validate that IKSVM-DC can converge to a local minimum. Finally, we conduct experiments on both binary and multi-class datasets and the experimental results show that IKSVM-DC is superior to other state-of-the-art IKSVM algorithms.

The amphibian metamorphosis assay (AMA) was proposed by the Organization for Economic Cooperation and Development (OECD) to screen thyroid disruptors of vertebrate species. The general experimental...

Dechlorane 602 (Dec 602), a chlorinated flame retardant, has been widely detected in different environmental matrices and biota. However, toxicity data for Dec 602 seldom have been reported. A metabolomics study based on ultra-high performance liquid chromatography coupled with ion trap time-of-flight mass spectrometry was employed to study the urine and sera metabolic profiles of mice administered with Dec 602 (0, 0.001, 0.1, and 10 mg/kg body weight per day) for 7 days. A significant difference in metabolic profiling was observed between the Dec 602 treated group and the control group by multivariate analysis, which directly reflected the metabolic perturbations caused by Dec 602. The metabolomics analyses of urine from Dec 602-exposed animals exhibited an increase in the levels of thymidine and tryptophan as well as a decrease in the levels of tyrosine, 12,13-dihydroxy-9Z-octadecenoic acid, 2-hydroxyhexadecanoic acid and cuminaldehyde. The metabolomics analyses of sera showed a decrease in the levels of kynurenic acid, daidzein, adenosine, xanthurenic acid and hypoxanthine from Dec 602-exposed animals. These findings indicated Dec 602 induced disturbance in phenylalanine, tyrosine and tryptophan biosynthesis, tryptophan metabolism, tyrosine metabolism, pyrimidine metabolism, purine metabolism, ubiquinone and other terpenoid-quinone biosynthesis; phenylalanine metabolism and aminoacyl-tRNA biosynthesis. Significant alterations of immune and neurotransmitter-related metabolites (tyrosine, tryptophan, kynurenic acid, and xanthurenic acid) suggest that the toxic effects of Dec 602 may contribute to its interactions with the immune and neuronal systems. This study demonstrated that the UHPLC-ESI-IT-TOF-MS-based metabolomic approach can obtain more specific insights into the potential toxic effects of Dec 602 at molecular level.

Brassica oleracea comprises various economically important vegetables and presents extremely diverse morphological variations. They provide a rich source of nutrition for human health and have been used as a model system for studying polyploidization. Transposable elements (TEs) account for nearly 40% of the B. oleracea genome and contribute greatly to genetic diversity and genome evolution. Although the proliferation of TEs has led to a large expansion of the B. oleracea genome, little is known about the population dynamics and evolutionary activity of TEs. A comprehensive mobilome profile of 45,737 TE loci was obtained from resequencing data from 121 diverse accessions across nine B. oleracea morphotypes. Approximately 70% (32,195) of the loci showed insertion polymorphisms between or within morphotypes. In particular, up to 1221 loci were differentially fixed among morphotypes. Further analysis revealed that the distribution of the population frequency of TE loci was highly variable across different TE superfamilies and families, implying a diverse expansion history during host genome evolution. These findings provide better insight into the evolutionary dynamics and genetic diversity of B. oleracea genomes and will potentially serve as a valuable resource for molecular markers and association studies between TE-based genomic variations and morphotype-specific phenotypic differentiation.

Tobacco (Nicotiana tabacum) is one of the most widely cultivated commercial non-food crops with significant social and economic impacts. Here we profiled transcriptome and metabolome from 54 tobacco samples (2–3 replicates; n = 151 in total) collected from three varieties (i.e. genetic factor), three locations (i.e. environmental factor), and six developmental stages (i.e. developmental process). We identified 3,405 differentially expressed (DE) genes (DEGs) and 371 DE metabolites, respectively. We used quantitative real-time PCR to validate 20 DEGs, and confirmed 18/20 (90%) DEGs between three locations and 16/20 (80%) with the same trend across developmental stages. We then constructed nine co-expression gene modules and four co-expression metabolite modules , and defined seven de novo regulatory networks, including nicotine- and carotenoid-related regulatory networks. A novel two-way Pearson correlation approach was further proposed to integrate co-expression gene and metabolite modules to identify joint gene–metabolite relations. Finally, we further integrated DE and network results to prioritize genes by its functional importance and identified a top-ranked novel gene, LOC107773232, as a potential regulator involved in the carotenoid metabolism pathway. Thus, the results and systems-biology approaches provide a new avenue to understand the molecular mechanisms underlying complex genetic and environmental perturbations in tobacco.

Two–dimensional (2 D) ZnO nanosheets and one–dimensional (1 D) bud−like, grenade−like, prism−like, bamboo−like, brush−like, arrow−like, pencil−like, drip pipe−like, baseball bat−like, gear−like, walking stick−like, taper−like, shuttle−like, and/or hollow tower−like ZnO nanorods (nanotubes) with various tips were synthesized by a simple hydrothermal route from the system of CO(NH2)2 N2H4. All the samples exhibit the wurtzite structure of ZnO. With the increase of the amount of N2H4 or decrease of CO(NH2)2, the interplanar spacing of different planes of ZnO increases or decreases simultaneously. FTIR shows that except the nanosheets of S1, all other samples are pure. The average reflectance of S8 reaches about 85% in the wavelengths ranging from 450 to 550 nm, and the reflectance of S3 is about 75%. The Eg values of ZnO from S1–S8 are 3.234, 3.215, 3.223, 3.215, 3.230, 3.243, 3.230 and 3.234 eV respectively. Raman spectra of S1 and S2 are obviously different from those of S3–S8. PL spectra of the ZnO samples exhibit a dominant UV luminescence peak of S1–S7, especially that of S1, S2 and S4. The addition of N2H4 can suppress the defects on the ZnO surface. However, the decrease of CO(NH2)2 introduces the defect. The BET surface area shows that except S1 (55.3 m2/g), S5 is a center of symmetric distribution of surface areas of S2–S8. From above discussion, the density, PL intensity of UV emission, and BET surface area of the ZnO nanorods can be easily tuned by controlling the concentrations of N2H4 and CO(NH2)2. The average values of photocurrent density of S1−S8 are 0.059, 0.170, 0.137, 0.184, 0.215, 0.091, 0.465 and 0.152 μA/cm2, respectively. S4, S2 and S7 possess the rapid photocatalytic activities and decompose 65%, 55% and 50% of MB within 50 min respectively. The order of the average diameters of S3, S4, S5, S6, and S7 agrees with that of photocatalytic efficiency, indicating that the polar (002) plane and/or the nanorod tips affect the photocatalytic activity. The decrease of the amount of CO(NH2)2 introduces the defects, which affects the photocatalytic activity of S8.

Multihole ZnO hierarchical architectures were prepared by tartaric acid assisted hydrothermal synthesis, TA acts as a capping agent and structure-directing agent during the synthesis. Hydrazine acts as alkali source. XRD confirmed that that all ZnO possess the hexagonal wurtzite structure, and the crystalline of the sample turns better after annealed. The PL spectra can be tuned by changing TA concentration. The FTIR spectra of ZnO nanostructures shows the main absorbance peaks of all samples are located at about 547 cm−1, which are attributed to the vibrations of elongation of ZnO without any other bonds.

The amphibian metamorphosis assay (AMA) was proposed by the Organization for Economic Cooperation and Development (OECD) to screen thyroid disruptors of vertebrate species. The general experimental design of the AMA exposes Nieuwkoop and Faber (NF) stage 51

Epidemiological and animal studies indicate that increased exposure to bisphenol A (BPA) induces various human cardiovascular diseases (CVDs), including myocardial infarction, arrhythmias, dilated cardiomyopathy, atherosclerosis, and hypertension. Bisphenol S (BPS), an alternative to BPA, is increasingly present in various consumer products and human bodies worldwide. Recently, emerging evidence has shown that BPS might be related to cardiovascular disorders. In this review, we present striking evidence of the correlation between BPA exposure and various CVDs, and show that a nonmonotonic dose-response curve (NMDRC) was common in studies of the CV effects of BPA in vivo. The CV impairment induced by low doses of BPA should be highlighted, especially during developmental exposure or during coexposure with other risk factors. Furthermore, we explored the possible underlying mechanisms of these effects-particularly nuclear receptor signaling, ion channels, and epigenetic mechanisms-and the possible participation of lipid metabolism, oxidative stress and cell signaling. As the potential risks of BPA exposure in humans are still noteworthy, studies of BPA in CVDs should be strengthened, especially with respect to the mechanisms, prevention and treatment. Moreover, the potential CV risk of BPS reported by in vivo studies calls for immediate epidemiological investigations and animal studies to reveal the relationships of BPS and other BPA alternatives with human CVDs.

Acetylcholinesterase (AChE, EC 3.1.1.7) is a classical biomarker for monitoring contamination and intoxication of organophosphate (OP) and carbamate pesticides. In addition to these classical environmental AChE inhibitors, other organic toxic substances have been found to alter AChE activity in various species. These emerging organic AChE disruptors include certain persistent organic pollutants (POPs), polycyclic aromatic hydrocarbons (PAHs), and wildly used chemicals, most of which have received considerable public health concern in recent years. It is necessary to re-evaluate the environmental significances of AChE in terms of these toxic substances. Therefore, the present review is aiming to summarize correlations of AChE activity of certain organisms with the level of the contaminants in particular habitats, disruptions of AChE activity upon treatment with the emerging disruptors in vivo and in vitro, and action mechanisms underlying the effects on AChE. Over 40 chemicals belonging to six main categories were reviewed, including 12 POPs listed in the Stockholm Convention. AChE activity in certain organisms has been found to be well correlated with the contamination level of certain persistent pesticides and PAHs in particular habitats. Moreover, it has been documented that most of the listed toxic chemicals could inhibit AChE activity in diverse species ranging from invertebrates to mammals. Besides directly inactivating AChE, the mechanisms in terms of interference with the biosynthesis have been recognized for some emerging AChE disruptors, particularly for dioxins. The collected evidence suggests that AChE could serve as a potential biomarker for a diverse spectrum of organic environmental pollutants.

A guttering plough with two adjusting stages was designed in this paper, which can adjust its configure and position in two stages. With these two adjusting movements, the ploughshare of this guttering plough can be put in soil at a deep position, to dig out a deeper channel than normal ones. The boundary conditions including loading and constraint were obtained, when it work normally. Combined with it, and the transformed configure and position in two stages, and the structure and loading characteristics of the guttering plough, a mechanical model was established with finite element analysis method. Then its analysis and solution were carried out by using ANSYS software. Under normal working condition, the stress and strain distributions of each part of this guttering plough were obtained. The calculation results showed that the structure of this guttering plough can meet the requirement of strength, but the positions of the joints were slightly poor, so it should be properly enlarged. Finite element software can be used to analyze the spatial static of this guttering plough, which can be certified as a feasible method for the design and improvement of the plow frame structure.

Peroxisome proliferator-activated receptors (PPARs) play vital roles in cardiovascular pathophysiology, such as energy balance, cell proliferation/apoptosis, inflammatory response, and adipocyte differentiation. These vital roles make PPARs potential targets for therapeutic prevention of cardiovascular diseases (CVDs). Emerging evidence indicates that the crosstalk of microRNAs (miRNAs) and PPARs contributes greatly to CVD pathogenesis. PPARs are inhibited by miRNAs at posttranscriptional mechanisms in the progress of pulmonary hypertension and vascular dysfunction involving cell proliferation/apoptosis, communication, and normal function of endothelial cells and vascular smooth muscle cells. In the development of atherosclerosis and stroke, the activation of PPARs could change the transcripts of target miRNA through miRNA signalling. Furthermore, the mutual regulation of PPARs and miRNAs involves cell proliferation/apoptosis, cardiac remodeling, and dysfunction in heart diseases. In addition, obesity, an important cardiovascular risk, is modulated by the regulatory axis of PPARs/miRNAs, including adipogenesis, adipocyte dysfunction, insulin resistance, and macrophage polarization in adipose tissue. In this review, the crosstalk of PPARs and miRNAs and their emerging regulatory roles are summarized in the context of CVDs and risks. This provides an understanding of the underlying mechanism of the biological process related to CVD pathophysiology involving the interaction of PPARs and miRNAs and will lead to the development of PPARs/miRNAs as effective anti-CVD medications.

Considering some advantages of Rana nigromaculata as an experimental species, we propose that this species, like Xenopus laevis, could be used to assay thyroid hormone (TH) signaling disrupting actions. To validate the utilizability of R. nigromaculata, we investigated the responsiveness of R. nigromaculata to a TH receptor (TR) agonist (T3) and antagonist (amiodarone) by analyzing expression, based on characterizing TR cDNA and developmental expression patterns. With high levels of identity with the corresponding genes in X. laevis, both TRα and TRβ in R. nigromaculata exhibited roughly similar developmental expression patterns to those of X. laevis, in spite of some species-specific differences. Both TRα and TRβ expression had greater changes in the liver and intestine than in the tail and brain during metamorphosis. T3 exposure for 2days induced more dramatic increases of TRβ expression in stage 27 than in stage 34 tadpoles but not in stage 42 tadpoles, showing that the responsiveness of R. nigromaculata to TH decreased with development and disappeared at the onset of metamorphic climax. Corresponding to greater changes of TRβ expression in the liver and intestine than in the tail and brain during metamorphosis, the liver and intestine had higher responsiveness to exogenous T3 than the tail and brain. Amiodarone inhibited T3-induced TRβ expression. Our results show that R. nigromaculata can be used as a model species for assaying TH signaling disrupting actions by analyzing TRβ expression, and intestine tissues at stage 27 are ideal test materials due to high responsiveness and easy accessibility.

AIM: To evaluate the positive effects of blue-violet light filtering lenses in delaying myopia and relieving asthenopia in juveniles. METHODS: Sixty ametropia juveniles (aged range, 11-15y) were randomized into two groups: the test group (30 children, 60 eyes), wearing blue-violet light filtering lenses; and the control group (30 children, 60 eyes), wearing ordinary aspherical lenses. Baseline refractive power of the affected eyes and axial length of the two groups was recorded. After 1-year, the patients underwent contrast sensitivity (glare and non-glare under bright and dark conditions), accommodation-related testing, asthenopia questionnaire assessment, and adverse reaction questionnaire assessment. RESULTS: After 1y of wearing the filtering lenses, changes in refractive power and axial length were not significantly different between the two groups (P>0.05). Under bright conditions, the contrast sensitivities at low and medium-frequency grating (vision angles of 6.3°, 4.0°, and 2.5°) with glare in the test group were significantly higher than in the control group (P0.05). In the test group, the amplitude of accommodation, accommodative lag, and accommodative sensitivity of patients wearing glasses for 6 and 12mo were significantly elevated (P0.05), and the asthenopia grating was not significantly decreased (P>0.05). In addition, after wearing glasses for 6 to 12mo, the asthenopia grating of patients in the test group decreased significantly compared with the control group (P0.05). CONCLUSION: A 1-year follow-up reveal that compare with ordinary glasses, short-wavelength filtering lenses (blue/violet-light filters) increase the low- and medium-frequency contrast sensitivity under bright conditions and improved accommodation. They effectively relieved asthenopia without severe adverse reactions, suggesting potential for clinical application. However, no significant advantages in terms of refractive power or axial length progression were found compared with ordinary aspheric lenses.

Multiple kernel learning for feature selection (MKL-FS) utilizes kernels to explore complex properties of features and performs better in embedded methods. However, the kernels in MKL-FS are generally limited to be positive definite. In fact, indefinite kernels often emerge in actual applications and can achieve better empirical performance. But due to the non-convexity of indefinite kernels, existing MKL-FS methods are usually inapplicable and the corresponding research is also relatively little. In this paper, we propose a novel multiple indefinite kernel feature selection method (MIK-FS) based on the primal framework of indefinite kernel support vector machine (IKSVM), which applies an indefinite base kernel for each feature and then exerts an l 1 -norm constraint on kernel combination coefficients to select features automatically. A two-stage algorithm is further presented to optimize the coefficients of IKSVM and kernel combination alternately. In the algorithm, we reformulate the non-convex optimization problem of primal IKSVM as a difference of convex functions (DC) programming and transform the non-convex problem into a convex one with the affine minorization approximation. We further utilize a leverage score sampling method to select landmark points for solving large-scale problems. Moreover, we extend MIK-FS to multi-class feature selection scenarios. Experiments on real-world datasets demonstrate that MIK-FS is superior to some related state-of-the-art methods in both feature selection and classification performance.

Indefinite kernel support vector machine (IKSVM) has recently attracted increasing attentions in machine learning. Different from traditional SVMs, IKSVM essentially is a non-convex optimization problem. Some algorithms directly change the spectrum of the indefinite kernel matrix at the cost of losing some valuable information involved in the kernels so as to transform the non-convex problem into a convex one. Other algorithms aim to solve the dual form of IKSVM, but suffer from the dual gap between the primal and dual problems in the case of indefinite kernels. In this paper, we directly focus on the non-convex primal form of IKSVM and propose a novel algorithm termed as IKSVM-DC. According to the characteristics of the spectrum for the indefinite kernel matrix, IKSVM-DC decomposes the objective function into the subtraction of two convex functions and thus reformulates the primal problem as a difference of convex functions (DC) programming which can be optimized by the DC algorithm (DCA). In order to accelerate convergence rate, IKSVM-DC further combines the classical DCA with a line search step along the descent direction at each iteration. A theoretical analysis is then presented to validate that IKSVM-DC can converge to a local minimum. Systematical experiments on real-world datasets demonstrate the superiority of IKSVM-DC compared to state-of-the-art IKSVM related algorithms.

A new species of the genus Synersaga Gozmany, Synersaga atriptera Xu & Wang sp. nov. (Lepidoptera: Lecithoceridae) is described from China. Adults, wing venation and male genitalia are illustrated. The new species is similar to S. nigriptera, but is distinguished by the wing venation and the male genitalia. The ground color of wings of S. atriptera sp. nov. is darker than that of the wings of S. nigriptera, especially the hind wings; the forewing of S. atriptera sp. nov. has a broad and blackish transverse outer line, which it is not present in S. nigriptera; and the fringe of S. nigriptera has a paler basal line, which it is not obvious in S. atriptera sp. nov. Juxta of S. atriptera sp. nov. has a pair of claviform lateral lobes, which are separated at the base. Juxta of S. nigriptera also has a pair of claviform lateral lobes, but they are connected at the base by a heavily sclerotized band. Type specimens were deposited in the Insect Collection of the Department of Entomology, South China Agricultural University, Guangzhou, China.

The hepatopancreatic cell culture of the kuruma prawn, Litopenaeusvannamei, was conducted to identify the effects of zinc on cell division. The culturesystem consists of medium 199 (M 199) supplemented with 0.060 mol/L NaCl,1.011g/L glucose, 1000 UI/ml penicillin, 1000 μg/ml treptomycin, 20% heatinactivated fetal calf serum (FCS) for primary cells and 10 % for subculture cells. TheRNA/DNA ratio in cultured cells was measured. The results show that the celldivision of cultured hepatopancreas cells in L. vannamei was increased by the optimalconcentration of Zn2+, 80 μg/L.