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Cypermethrin, one kind of pyrethroid pesticides, has been shown to act as endocrine-disrupting chemicals (EDCs). The purpose of this study was to explore the roles of Sertoli cell apoptosis through mitochondrial pathway associated with calcium (Ca2+) in cypermethrin-induced male reproductive toxicology. The mouse Sertoli cells TM4 were cultured with 0 μM, 10 μM, 20 μM, 40 μM and 80 μM of cypermethrin. We used flow cytometry, Fluo-4 AM, western blot and JC-1 Assay Kit to examine apoptosis, intracellular Ca2+, expressions of mitochondrial apoptotic pathway-related proteins and mitochondrial membrane potential. We found cypermethrin increased apoptosis rate of TM4 cells significantly and with a significant increase in intracellular Ca2+ concentration. Cypermethrin significantly decreased the protein expressions of cytosolic B-cell lymphoma-2 (Bcl-2) and mitochondrial cytochrome c (Cyt-c). The protein expressions of cytosolic Bcl-2-associated x (Bax), Cyt-c, cleaved caspase-3, calmodulin (CaM), Ca2+/CaM-dependent protein kinases II (CaMKII) and phosphorylated CaMKII were increased significantly in cypermethrin-exposed TM4 cells. Cypermethrin decreased mitochondrial membrane potential significantly. Then, Bcl-2 family and Ca2+/CaM/CaMKII pathway participate in cypermethrin-induced homeostasis. Ca2+ overload activates mitochondrial pathway by increasing permeability of mitochondrial membrane and decreasing mitochondrial membrane potential. We suggest cypermethrin induces Sertoli cell apoptosis involving mitochondrial pathway associated with Ca2+ regulated by Bcl-2 family and Ca2+/CaM/CaMKII pathway. The study provides a new insight into mechanisms involved in cypermethrin-induced male reproductive toxicology.

Objective In the previous study, we identified bone morphogenetic protein 4 (BMP4) responsible for non-syndromic cleft lip with or without cleft palate (NSCL/P). We aimed to elucidate the effects and mechanisms of BMP4 on epithelial–mesenchymal transition (EMT) through Smad1 signaling pathway to be involved in NSCL/P. Methods The human oral epidermoid carcinoma cells (KBs) were transfected with plasmids or small interfering RNA (siRNA) to build the models. The migration of the cells was evaluated by transwell assay. Western blotting and quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) were used to detect the expressions of BMP4, E-cadherin, N-cadherin, EMT-related transcription factors snal1 and snal2, matrix metalloproteinase 2 (MMP2), MMP9, Smad1, and phosphorylated Smad1. Results In the overexpression group, the migration number of cells was increased significantly. The protein expression of E-cadherin was decreased significantly, while the protein expression level of the N-cadherin was increased significantly. The protein and mRNA expressions of MMP2, MMP9, snal1, and snal2 were significantly higher. The expression level of Smad1 was not significantly changed, while the phosphorylation of Smad1 was significantly increased. In the BMP4-siRNA group, the migrating number cells was significantly decreased. The protein expression of E-cadherin was increased significantly, while the expression of N-cadherin was significantly decreased. The protein and mRNA expressions of MMP2, MMP9, snal1, and snal2 were significantly lower than that of the control group. The expressions of Smad1 and phosphorylation of Smad1 were not significantly changed. Conclusions BMP4 enhances cell migration and promotes cell EMT through Smad1 signaling pathway. Abnormal BMP4 mediates migration and EMT through other relevant signaling pathways resulting in NSCL/P. The study provides new insight into the mechanisms of NSCL/P associated with BMP4.n

Abscisic acid (ABA) receptors are considered as the targeted manipulation of ABA sensitivity and water productivity in plants. Regulation of their stability or activity will directly affect ABA signalling. Mitogen-activated protein kinase (MAPK) cascades link multiple environmental and plant developmental cues. However, the molecular mechanism of ABA signalling and MAPK cascade interaction remains largely elusive. TaMPK3 overexpression decreases drought tolerance and wheat sensitivity to ABA, significantly weakening ABA's inhibitory effects on growth. Under drought stress, overexpression lines show lower survival rates, shoot fresh weight and proline content, but higher malondialdehyde levels at seedling stage, as well as decreased grain width and 1000 grain weight in both glasshouse and field conditions at the adult stage. TaMPK3-RNAi increases drought tolerance. TaMPK3 interaction with TaPYL4 leads to decreased TaPYL4 levels by promoting its ubiquitin-mediated degradation, whereas ABA treatment diminishes TaMPK3-TaPYL interactions. In addition, the expression of ABA signalling proteins is impaired in TaMPK3-overexpressing wheat plants under ABA treatment. The MPK3-PYL interaction module was found to be conserved across monocots and dicots. Our results suggest that the MPK3-PYL module could serve as a negative regulatory mechanism for balancing appropriate drought stress response with normal plant growth signalling in wheat.

The evolution of temperature field of the continual motion induction cladding and the depth of heat affected zone are studied in this study. A three-dimensional finite element model for the point type continual induction cladding is established to investigate temperature distributions of fixed and motion induction cladding modes. The novel inductor is designed for cladding of curved surfaces. The modeling reliability is verified by the temperature measurements. The influence of process parameters on the maximum temperature and the generation and transfer of heat are studied. Quantitative calculation is performed to its melting rate to verify the temperature distribution and microstructures. The results show that a good metallurgical bond can be formed between the cladding layer and substrate. The melting rate gradually falls from the top of the cladding layer to the substrate, and the grain size in the substrate gradually rises. The heat affected zone is relatively small compared to integral heating.

Aiming at the problems existing in the Chinese-Khmer parallel corpus, such as single field, small scale, and poor timeliness, a method of Chinese-Khmer parallel fragment extraction from comparable corpus based on Dirichlet process is proposed. The method firstly obtains the topic distribution of bilingual comparable corpus through bilingual topic model, then uses Poisson distribution to randomly divide the bilingual texts, sets up a threshold to initially filter parallel fragment of comparable corpus, and then obtains the matching probability between parallel fragments by Dirichlet process. Obtaining the final parallel fragments by Gibbs sampling. From the comparison experiments, the method of parallel fragment extraction from bilingual comparable corpus based on Dirichlet process can obtain higher quality parallel fragments without providing any parallel data, which is more suitable for languages where bilingual resources are low.

Ocean waves are complex systems with the contributions of wind waves and swells. The study on interaction mechanism between electromagnetic wave and actual sea surface is of significant importance in ocean remote sensing and engineering application, which is also helpful in the prediction and inversion of wave information. In this paper, an efficient model for estimating backscattering coefficient is built, considering the characteristics of the wind-wave regime based on the inverse wave age. The backscattering coefficient results have been verified by comparing with the data collected in Lingshan Island during the period of October and November 2014 at low grazing angles and the Ku-band measurements at moderate grazing angles. The results indicate perfect agreement (within about 2 dB) with field data. Deep learning is an excellent method that can be used not only for classification but also for inversion and fitting of non-linear functions. In order to simulate the application of actual radar detection and inversion technology, the inversion of significant wave height from actual sea surface backscattering coefficients train data sets has been performed by using deep learning technology. The accuracy of 99.01% has been achieved under the condition of three hidden layers and iterating 100 times. The root mean square errors of the test data sets are less than 0.10, which indicates that deep learning is available in the inversion of significant wave height.

A base-promoted (2+4) annulation of benzofuran-derived azadienes with para-quinone methide derivatives has been established, which afforded spiro-benzofuran derivatives in generally high yields (57–97%) and with good diastereoselectivities (85:15 to >95:5 dr). This reaction not only represents the first application of benzofuran-derived azadienes as two-carbon building blocks in annulations, but also provides an efficient protocol for the construction of spiro-benzofuran scaffolds with chemoselectivity and high diastereoselectivity. This approach will enrich the chemistry of benzofuran-derived azadiene-involved reactions.

Background Non-syndrome cleft lip with or without cleft palate (NSCL/P) is the most common congenital defect with a complex etiology involving both genetic and environmental factors. Our previous research has identified susceptibility genes of NSCL/P using whole-exome sequencing. The study was to determine the effects of small interfering RNA (siRNA)-mediated silencing of genes on cell proliferation and migration to confirm the roles of the genes in NSCL/P. Methods We silenced the genes by RNA interference (RNAi) with siRNA in human oral keratinocyte (HOK). We used the Cell Counting Kit-8 (CCK8) assay to determine cell proliferation and the wound healing assay to determine cell migration. Results Migration of HOK was inhibited by RNAi-induced silencing of adenosine triphosphate binding cassette transporter A4 (ABCA4), erythropoietin produces hepatocyte A receptor 3 (EPHA3), alpha-parvin (PARVA), and platelet-derived growth factor C (PDGFC). The change of proliferation was not found. Treated with siRNA-mediated silencing of type IV collagen (COL4A2), eukaryotic translation initiation factor 2B subunit (EIF2B3), fibroblast growth factor receptor 2 (FGFR2), kinesin family member 20B (KIF20B), β-lactamase serine-like protein (LACTB), SEC16 homolog A (SEC16A) and thyroid adenoma target gene (THADA) had no effects on cell proliferation and migration of HOK. Conclusions We suggest mutations of the four susceptibility genes ABCA4, EPHA3, PARVA and PDGFC are involved in NSCL/P through inhibiting cell migration. The study provides new candidates for future study of NSCL/P.

In the field of sea clutter research, the key of sea targets recognition and detection is that accuracy estimated parameters of the Doppler Spectrum modeling through the optimal solution search algorithm. Our work provides two ways to improve heuristic search algorithm. One is CGA(Continuesmutation Genetic Algorithm) that cloud prevent Hamming Cliff, which is considered as GA’s inherent issue. The other is that the PSO-GA (Particle Swarm Optimization and Genetic Algorithm) and PSO-CGA (Particle Swarm Optimization and Continuesmutation Genetic Algorithm) obtained by combining algorithms, which can take advantages of the original methods and increase the individuals utilization rate. Both these method can reduce the error of the obtained results without increase solving time. In addition, we also proposes a new evaluation method of the heuristic search algorithm to efficiency measure algorithms.

Background Cleft lip with or without cleft palate (CL/P) is one of the most common congenital defects, which etiology involves both genetic and environmental factors. Previous studies have shown that miR-199a-5p may mediate the occurrence of CL/P. However, the key target genes regulated by miR-199a-5p are not clear. In this study, we employed a systematic bioinformatics analysis of target genes regulated by miR-199a-5p which may be involved in CL/P. Methods The miRBase, Human miRNA tissue atlas, miRecords, miRpathDB, miRWalk, miRTarBase, DIANA-TarBase (v7.0), Literature search, DAVID software, Cytoscape plugin ClueGO + Cluepedia app, MalaCards, TargetScanhuman7.1, Venny 2.1, STRING and GEO databases were comprehensive employed to identify the key genes regulated by miR-199a-5p associated with CL/P. Results Total 429 experimentally validated target genes were obtained from five miRNAs related databases. Expressions of miR-199a-5p and its experimentally validated target genes were elevated in bone, brain and skin. KEGG pathway analysis revealed that the target genes were enriched in focal adhesion, microRNAs in cancer and hippo signaling pathway. Biological process categorization revealed that significant portions of the target genes were grouped as transcription, DNA-templated. Total eight intersection genes were identified by using MalaCards and TargetScanhuman7.1. The target gene transforming growth factor alpha (TGFA) of miR-199a-5p involved in CL/P is screened and verified. Conclusion MiR-199a-5p may mediate CL/P by regulating key target gene TGFA. The study may contribute to a better understanding of the etiology of CL/P.

Hemorrhagic fever with renal syndrome (HFRS) occurs widely throughout Eurasia. Unfortunately, there is no effective treatment, and prophylaxis remains the best option against the major pathogenic agent, hantaan virus (HTNV), which is an Old World hantavirus. However, the absence of cellular immune responses and immunological memory hampers acceptance of the current inactivated HFRS vaccine. Previous studies revealed that a lysosome-associated membrane protein 1 (LAMP1)-targeting strategy involving a DNA vaccine based on the HTNV glycoprotein Gn successfully conferred long-term immunity, and indicated that further research on Gc, another HTNV antigen, was warranted. Plasmids encoding Gc and lysosome-targeted Gc, designated pVAX-Gc and pVAX-LAMP/Gc, respectively, were constructed. Proteins of interest were identified by fluorescence microscopy following cell line transfection. Five groups of 20 female BALB/c mice were subjected to the following inoculations: inactivated HTNV vaccine, pVAX-LAMP/Gc, pVAX-Gc, and, as the negative controls, pVAX-LAMP or the blank vector pVAX1. Humoral and cellular immunity were assessed by enzyme-linked immunosorbent assays (ELISAs) and 15-mer peptide enzyme-linked immunospot (ELISpot) epitope mapping assays. Repeated immunization with pVAX-LAMP/Gc enhanced adaptive immune responses, as demonstrated by the specific and neutralizing antibody titers and increased IFN-γ production. The inactivated vaccine induced a comparable humoral reaction, but the negative controls only elicited insignificant responses. Using a mouse model of HTNV challenge, the in vivo protection conferred by the inactivated vaccine and Gc-based constructs (with/without LAMP recombination) was confirmed. Evidence of pan-epitope reactions highlighted the long-term cellular response to the LAMP-targeting strategy, and histological observations indicated the safety of the LAMP-targeting vaccines. The long-term protective immune responses induced by pVAX-LAMP/Gc may be due to the advantage afforded by lysosomal targeting after exogenous antigen processing initiation and major histocompatibility complex (MHC) class II antigen presentation trafficking. MHC II-restricted antigen recognition effectively primes HTNV-specific CD4+ T-cells, leading to the promotion of significant immune responses and immunological memory. An epitope-spreading phenomenon was observed, which mirrors the previous result from the Gn study, in which the dominant IFN-γ-responsive hot-spot epitopes were shared between HLA-II and H2d. Importantly, the pan-epitope reaction to Gc indicated that Gc should be with potential for use in further hantavirus DNA vaccine investigations.

The overall supporting capacity of ordinary concrete-filled steel tube support (CFSTS) can be decreased due to the self-shrinkage of concrete and the cracks of hardened concrete. The micro-expansive CFSTS is put forward in this paper. Firstly, the optimum proportion of micro-expansion concrete was determined by concrete strength testing. Then, the deformation of micro-expansion CFSTS and ordinary CFSTS under the same load w studied by numerical simulation. Finally, the micro-expansion CFSTS and ordinary CFSTS were applied to the roadway respectively. The results show: The expansive agent content and water reducer content is 11 and 0.5% in the optimum proportion of micro-expansive concrete, respectively. Under the same load, the deformation of the ordinary CFSTS was much larger than that of the micro-expansion CFSTS. The deformations of roof–floor and two sides of roadway supported by the micro-expansion CFSTS were obviously smaller than that of roadway supported by the ordinary CFSTS. The micro-expansion CFSTS has stronger supporting capacity than ordinary CFSTS.

Purpose This study aims to present that the chemo-responsive shape recovery of thermoplastic polyurethane (TPU) is tunable by solvents with different solubility parameters, and it is generic for chemo-responsive shape-memory polymer and its composites. Design/methodology/approach Two kinds of commercial TPU samples with different thicknesses were prepared by panel vulcanizer and injection molding (an industrial manner) to investigate their chemo-responsive shape memory properties in acetic ether and acetone. Findings Results showed that all of TPU films with different thicknesses can fully recover their original shapes weather they recover in acetic ether or acetone. But the recovery time of TPU films in acetone is greatly reduced, especially for the twisting samples. The residual strains of recovery TPU samples after extension reduce obviously. Research limitations/implications The great decrement of recovery time is related to two factors. One is due to the bigger solubility parameter of acetone with higher dipole moment compared with those of acetic ether, and the other is the remained internal stress of TPU films after preparation. The internal stress is identified to have an effect on the shape-memory properties by comparing the recovery process of samples with/without annealing. The reduced residual strains of recovery TPU samples after extension is due to the increasing mobility of polymer segments after molecules of acetic ether penetrates into the polymeric chains. Originality/value This is a universal strategy to control the recovery process of shape-memory materials or composites. The underlying mechanism is generic and should be applicable to chemo-responsive shape-memory polymers or their composites.

The insecticide cypermethrin has been considered as an endocrine-disrupting chemicals (EDCs) with anti-androgenic activity by interfering with interleukin-6 (IL-6) – induced ligand-independent AR signaling. The purpose of this study was to clarify whether the signal transducer and activator of transcription 3 (STAT3) was involved in the antagonism effect of cypermethrin. In this study, the Western blot was to test the level of STAT3 phosphorylation and the mammalian two-hybrid assay was developed to assess the AR–STAT3 interaction. The date showed that IL-6 increased the phosphorylation level of STAT3 and enhanced the AR–STAT3 interaction. Cypermethrin did not affect the phosphorylation level of STAT3 induced by IL-6, while suppressed the AR-STAT3 interaction induced by IL-6 significantly at the concentration of 10−5 M (p

Background Prophylaxis is widely adopted the best choice against Hemorrhagic fever with renal syndrome (HFRS) caused by Hantavirus. However, loss of memory immune response maintenance remains as major shortcoming in current HFRS vaccine. A recombinant DNA vaccine, pVAX-LAMP/Gn was previously proved efficient, requiring long-term evaluations. Methods & results Immune responses of Balb/c mice were assessed by specific and neutralizing antibodies, interferon-γ ELISpot assay, and cytotoxic T-lymphocyte cytotoxicity assay. HTNV-challenge assay identified long-term protection. Safety was confirmed by histological and behavioral analysis. Epitope-spreading phenomenon was noted, revealing two sets of dominant T-cell epitopes cross-species. Conclusion pVAX-LAMP/Gn established memory responses within a long-term protection. Lysosome-targeted strategy showed promise on Gn-based DNA vaccine and further investigations are warranted in other immunogenic Hantaviral antigens.

It is hypothesized that the pesticide cypermethrin may induce androgen receptor (AR) antagonism via ligand-independent mechanisms. The Real-Time Cell Analysis (RTCA) iCELLigence system was used to investigate the inhibitory effect of cypermethrin on interleukin-6 (IL-6)-induced ligand-independent LNCaP cell growth. Then, the mammalian two-hybrid assays were applied to clarify whether the mechanism of IL-6-induced AR antagonism of cypermethrin was associated with the interactions of the AR and co-activator steroid receptor co-activator-1 (SRC-1) and co-repressor silencing mediator for retinoid and thyroid hormone receptors (SMRT). Cypermethrin inhibited the LNCaP cell growth induced by IL-6. The interactions of AR-SRC-1 and AR-SMRT mediated by IL-6 were suppressed by cypermethrin. The results indicate that the IL-6-mediated AR antagonism induced by cypermethrin is related to repress the recruitment of co-regulators SRC-1 and SMRT to the AR in a ligand-independent manner. Inhibition of the interactions of AR-SRC-1 and AR-SMRT mediated by IL-6 contributes to the AR antagonism induced by cypermethrin.

The purpose of this study was to investigate the anti-androgenic mechanism of cypermethrin involving coactivators.Mammalian two-hybrid assays were performed to study the effects of cypermethrin on interactions of the androgen receptor (AR) with the coactivators androgen receptor-associated protein 70 (ARA70) and androgen receptor-associated protein 55 (ARA55).The results showed that AR-ARA70 and AR-ARA55 interactions were remarkably enhanced by dihydrotestosterone (DHT,The study indicates that cypermethrin exhibits inhibitory effects on AR transcription associated with repression of AR-ARA70 and AR-ARA55 interactions in a ligand-dependent manner. The data show novel anti-androgenic mechanisms of cypermethrin that contribute to male reproductive toxicology.

Previous studies have demonstrated that the anti-androgenic effects of cypermethrin (CYP) are associated with testosterone (T) - related signaling pathway. This study was to investigate the effects of CYP on mouse Sertoli cells (TM4) and clarify whether the mechanisms were mediated by non-classical T signaling pathway activating mitogen-activated protein kinase (MAPK) cascade. The Cell Counting Kit 8 (CCK8) and Real-Time Cell Analysis iCELLigence (RTCA-iCELLigence) system were performed to detect the effects of 10 μM, 20 μM, 40 μM and 80 μM CYP on the viability and proliferation of TM4. The mammalian two hybrid assay, quantitative Real-Time PCR (qRT-PCR) and western blot were conducted to analyze the key genes and proteins involved in T-mediated MAPK signaling pathway. CYP was found to inhibit the viability and proliferation of TM4. Additionally, CYP disturbed the functions of Sertoli cells by inhibiting inhibin B (INH B) expression and facilitating androgen binding protein (ABP) and transferrin (TF) expression. Moreover, CYP suppressed the interaction of AR and Src kinase and inhibited androgen-mediated phosphorylation of Src, epidermal growth factor receptor (EGFR), extracellular-regulated kinase1/2 (ERK1/2) and transcription factor cAMP response element binding protein (CREB). Furthermore, the androgen-induced mRNA and protein expression of CREB-regulated gene early growth response factor (Egr1) decreased after treated with CYP. It is indicated that CYP inhibits the viability and proliferation of Sertoli cells and non-classical T signaling pathway activation of MAPK cascade is involved in anti-androgenic effect of CYP. This study provides a novel insight into the CYP-induced reproductive toxicity.

The Doppler spectrum of the electromagnetic (EM) scattering field from the two-dimensional dynamic sea surface is calculated based on the composite scattering model. The two-dimensional dynamic sea surfaces are generally simulated as a superposition of large-scale gravity waves and small-scale capillary ripples. On this basis, the Doppler spectrum of the EM scattering field from the two-dimensional dynamic sea surface can be calculated based on the composite scattering model, which takes both the quasi-specular scattering and Bragg scattering mechanism into account. However, due to the high resolution and real-time dynamic complexity of the dynamic sea surfaces, the calculation of the Doppler spectrum will be computationally expensive and very time-consuming. In this paper, a GPU-based algorithm of Doppler spectrum was proposed by utilizing the Tesla K80 GPUs with diverse CUDA optimization techniques. The GPU-based Doppler spectrum implementation includes five optimization strategies: first, the temporary arrays are utilized to reduce the repeat float-points operations in the loop; then the device memory was effectively exploited to reduce the data transfer time between the CPU and GPU; the fast math compiler option was also utilized to further improve the computation performance of the Doppler spectrum calculation; finally the data transfer time between the device and host memories can be effectively hide by using the asynchronous data transfer (ADT). Compared to the CPU serial program executed on Intel(R) Core(TM) i5-3450 CPU, the GPU-based Doppler spectrum implementation can achieve a significant speedup of1200× .

A chemiluminescent immunoassay for the staphylococcal enterotoxin C1 (SEC1) based on the use of dye-encapsulated mesoporous silica nanoparticles (m-SiNPs) as a label is described. The dyes are retained in the m-SiNPs via strong hydrophobic interactions. The assay comprises the following steps: (a) Microplates coated with antibody against SEC1 are filled with sample upon which the SEC antigen will be bound to the surface; (b) following a washing step, secondary antibody linked to m-SiNPs (that were covalently labeled with rhodamine 6G and fluorescein) were added to form the sandwich complex; (c) after another washing step, bis(2,4,6-trichlorophenyl) oxalate, H2O2 and imidazole are added to generate chemiluminescence whose intensity is proportional to the number of m-SiNPs and thus to the number of antigen (SEC) molecules. It is found that the use of functionalized m-SiNPs strongly amplifies the signal. Enterotoxin SEC1 can be detected by this method in the 0.025 to 2 ng⋅mL‾1 concentration range, the detection limit is 19 pg⋅mL‾1 (at 3σ), and the relative standard deviation (for 11 parallel measurements at a 1 ng⋅mL‾1 level) is 4.6 %. The use of an automated chemiluminescence analyzer further improves detection.

Synthetic pyrethroids are used as insecticides in agriculture and a variety of household applications worldwide. Pyrethroids are widely distributed in all environmental compartments and the general populations are exposed to pyrethroids through various routes. Pyrethroids have been identified as endocrine-disrupting chemicals (EDCs) which are responsible for the male reproductive impairments. The data confirm pyrethroids cause male reproductive damages. The insecticides exert the toxic effects on male reproductive system through various complex mechanisms including antagonizing androgen receptor (AR), inhibiting steroid synthesis, affecting the hypothalamic-pituitary-gonadal (HPG) axis, acting as estrogen receptor (ER) modulators and inducing oxidative stress. The mechanisms of male reproductive toxicity of pyrethroids involve multiple targets and pathways. The review will provide further insight into pyrethroid-induced male reproductive toxicity and mechanisms, which is crucial to preserve male reproductive health.

Objective To observe the clinical efficacy of electroacupuncture (EA) combined with iontophoresis of Chinese medicine for lumbar intervertebral disc herniation (LIDH).

Background Non-syndromic cleft lip with or without cleft palate (NSCL/P) is among the most common congenital malformations. The etiology of NSCL/P remains poorly characterized owing to its complex genetic heterogeneity. The objective of this study was to identify genetic variants that increase susceptibility to NSCL/P. Material and Methods Whole-exome sequencing (WES) was performed in 8 fetuses with NSCL/P in China. Bioinformatics analysis was performed using commercially available software. Variants detected by WES were validated by Sanger sequencing. Results By filtering out synonymous variants in exons, we identified average 8575 nonsynonymous single nucleotide variants (SNVs). We subsequently compared the SNVs against public databases including NCBI dbSNP build 135 and 1000 Genomes Project and obtained an average of 203 SNVs. Total 12 reported candidate genes were verified by Sanger sequencing. Sanger sequencing also confirmed 16 novel SNVs shared by two or more samples. Conclusions We have found and confirmed 16 susceptibility genes responsible for NSCL/P, which may play important role in the etiology of NSCL/P. The susceptibility genes identified in this study will not only be useful in revealing the etiology of NSCL/P but also in diagnosis and treatment of the patients with NSCL/P. Key words:Non-syndromic cleft lip with or without cleft palate, whole-exome sequencing, sanger sequencing, susceptibility gene, single nucleotide variants (SNVs).

Peanut shell generated from peanut harvesting has a great potential to be converted into an energy resource in developing countries such as China, Vietnam, and Indonesia. The main objective of this study is to investigate the combustion characteristics of peanut shell in a pilot-scale vortexing fluidized-bed combustor with flue gas recirculation. Crushed and pelletized peanut shells are used as the feeding materials. The effects of in-bed stoichiometric oxygen ratio (Sb), particle sizes, and particle shapes on the combustion characteristics as well as pollutant emissions are investigated. Results show that similar temperature profiles are observed in all cases. CO emissions from the combustion of both fuels are all less than 70 ppm. CO emission decreases, while NOx emissions increase with particle sizes. CO and NOx emissions of pellet combustion show an inverse trend from that of crushed shell combustion at different in-bed stoichiometric oxygen ratios.

We have shown Bisphenol A (BPA) acts as an androgen receptor (AR) antagonist in the previous study. However, the mechanisms underlying anti-androgenic effects of BPA remain unclear. The objective of this study was to explore whether the AR signaling was involved in AR antagonism of BPA. The Cell Counting Kit-8 (CCK-8) assay and Real-Time Cell Analysis (RTCA) iCELLigence system were applied to analyze the mouse Sertoli cell TM4 proliferation. The mammalian two-hybrid assays were performed to investigate the effects of BPA on the AR amino- and carboxyl-terminal regions (N/C) interaction and the interactions of the AR with steroid receptor coactivator-1 (SRC-1), co-repressors including silencing mediator for thyroid hormone receptors (SMRT) and nuclear receptor co-repressor (NCoR). BPA exposure resulted in decreased TM4 cell proliferation. BPA inhibited the AR N/C interaction significantly. Furthermore, BPA enhanced the interactions of AR-SMRT and AR-NCoR significantly. In conclusion, these data suggest BPA inhibits Sertoli cell proliferation due to its anti-androgenic actions. The mechanisms responsible for AR antagonism of BPA involve inhibiting the AR N/C interaction and enhancing the interactions of AR-SMRT and AR-NCoR. The data uncover novel anti-androgenic mechanisms by which BPA antagonizes AR signaling, contributing to Sertoli cell proliferation suppression and male reproductive toxicology.

The androgen receptor (AR) can be stimulated by interleukin-6 (IL-6) in the absence of androgens to induce prostate cancer progression. The purpose of this study was to investigate whether the co-activator steroid receptor coactivator-1 (SRC-1) and co-repressor silencing mediator for retinoid and thyroid hormone receptors (SMRT) are involved in IL-6-induced AR activation. The effects of IL-6 on LNCaP cell proliferation were monitored using real-time cell analysis (RTCA) iCELLigence system. The impacts of IL-6 on the association of the AR with SRC-1 and SMRT were investigated using the mammalian two-hybrid assay. IL-6 increased the proliferation of LNCaP cells with maximal induction at 50 ng/mL. The AR-SRC-1interaction was enhanced by IL-6, with maximal induction at the concentration of 50 ng/mL (P

Using self-designed 30cm×30cm gas explosion experiment pipe and data acquisition system, we found Fe-Ni foam metal suppresses better gas explosion. We analyzed mechanism of suppressing gas explosion from material characteristics,. The three-dimensional holing-through structure of foam metal can quench exploding flame and decline exploding shock wave. Foam metal material has dual advantages of material and structure which can suppress transmission of fire and shock wave. Effect on different parameters of Fe-Ni foam metal materials was contrasted from declining overpressure and flame temperature, and suitable Fe-Ni form metal was optimized for engineering application.

The propagation characteristics of Global Positioning System (GPS) signals at very low elevation angles are frequently affected by tropospheric refraction as the satellite rises or sets at the horizon. Previous research indicated that the signal can be used to detect normal and surface-based duct refractive conditions. Using reciprocity, we develop a model to predict ground-based GPS occultation signal propagation in the presence of marine tropospheric ducts. To involve the effects of refraction, sea surface impedance, roughness, and the Earth’s curvature, the parabolic equation (PE) method is adopted in the low atmosphere. In implementing the PE numerically using the split-step discrete mixed Fourier transform algorithm, we propose a new approach of utilizing the relationship between the impedance coefficient and the reflection coefficient to modeling the right-hand circularly polarized GPS signal. The refraction effects from the top of the PE region to the satellite are modeled by ray tracing technique....

The prevalence of low vision has increased in China especially among youth population, which is an important public health issue. The trend on the prevalence of subnormal visual acuity and updated information is essential to quantify health effects and to prompt decision makers to prioritize action and assess the effectiveness of measures. Therefore, the study aimed to analyze the prevalence and geographical distribution of visual acuity level among young men in China based on 3 national cross-sectional surveys from 1974 to 2012.The data on visual acuity of young men were collected from 3 national surveys among military recruit youth conducted in 1974, 2001, and 2012 by using a stratified cluster sampling method in China. The prevalence of visual acuity among military recruit youth during this period was analyzed by region, year, age, and economic level.A total of 139,929, 72,894, and 58,106 young men were included, covering all 31 provinces of mainland of China, from the 3 national surveys respectively. The prevalence of subnormal visual acuity had geographic diversity and increased significantly from 1974 to 2012 (P < .05). The visual acuity level was negatively correlated with the age (17-23 years) in 2012 (P < .05). Furthermore, the prevalence of subnormal visual acuity was positively correlated with the gross domestic product in 31 provinces of China (P ≤ .001).The prevalence of subnormal visual acuity increased with economic development among young men from 1974 to 2012, with distinct variation among geographic areas in China. Furthermore, subnormal visual acuity was increasingly prevalent with age and warrant public health attention.

To clarify whether the mechanism of androgen receptor (AR) antagonism of the pyrethroid pesticide cypermethrin associates with the interactions between the AR and corepressors silencing mediator for thyroid hormone receptors (SMRT) and nuclear receptor corepressor (NCoR), we have developed the mammalian two-hybrid assays. The AR N-terminal domain 1-660 amino acid residues were subcloned into the plasmid pVP16 to construct VP16-ARNTD. The C-terminal receptor interaction domains (RIDs) of SMRT and NCoR were used to construct pM-SMRT and pM-NCoR. The constructed vectors pVP16-ARNTD, pM-SMRT or pM-NCoR, the reporter pG5CAT and the control pCMVβ were cotranfected into the CV-1 cells. The cells were treated with cypermethrin at the indicated concentrations. The AR N terminus interacted with RIDs of SMRT and NCoR. The interactions between the AR and corepressors SMRT and NCoR were enhanced by cypermethrin, and the significant enhancement was detected at the concentration of 10(-5)M. The mammalian two-hybrid assays demonstrate the utility to detect the interactions of the AR with SMRT and NCoR. Cypermethrin functions as an anti-androgen by enhancing the associations of the AR with SMRT and NCoR. We provide a novel mechanism in anti-androgen action of cypermethrin associated with the recruitment of SMRT and NCoR to AR.

Flight control software has higher requirements on reliability, as well as real-time performance. What's more, the fault of flight control software not only contains traditional functional fault, but also contains real-time fault. Thus, fault localization and removing for Flight Control software is a huge challenge for relative engineers. To locate and remove those faults effectively, this paper adopts Sober algorithm as the functional fault-localization algorithm for flight control software. Meanwhile, this paper proposes the module-level and function- level real-time fault-localization algorithms inspired by Sober algorithm. The experimental results indicate that all algorithms have obtained acceptable localization results. For further goals on increasing the automation level and the efficiency of software fault-localization process, we develop a fault-localization and visualization (FL&V) tool for flight control software at last.