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Flavonoids are a kind of secondary metabolite which widely exist in plants. They contain a lot of active hydroxyls, which can react with toxic chemicals to produce potential exposure biomarkers. In this article, the model plant Arabidopsis thaliana (L.) was exposed to the nerve agent O-Ethyl N,N-dimethyl phosphoramidocyanidate (Tabun). By comparing with the plant not exposed to Tabun, some characteristic ions were identified by quadrupole-time of flight mass spectrometry in the acetonitrile extract of the exposed leaves. These characteristic ions were selected as parent ions to produce product ion mass spectra (PIMS). Some interesting fragmentation pathways were revealed, including neutral loss of glucoside, rhamnose and ethylene. O-Ethyl N,N-dimethyl phosphoryl modified flavonoids were deduced from assignment of the PIMS. The element components and the accurate mass of the product ions from each parent ion matched well with those of the proposed fragmentation pathways. Through comparison with the PIMS of structurally closely related chemical of Isobutyl methylphosphonyl modified flavonoids, the structures and the fragmentation pathways of the O-Ethyl N,N-dimethyl phosphoryl modified flavonoids were finally confirmed. Successfully finding and identifying these three specific exposure biomarkers in plants provided a new strategy for the retrospective analysis of organophosphorus exposure and forensic analysis.
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Arabidopsis , Agentes Neurotóxicos , Flavonoides/química , Espectrometria de Massas em Tandem/métodos , Estudos Retrospectivos , Cromatografia Líquida de Alta Pressão/métodos , PlantasRESUMO
Meiosis is one of the most finely orchestrated events during gametogenesis with distinct developmental patterns in males and females. However, the molecular mechanisms involved in this process remain not well known. Here, we report detailed transcriptome analyses of cell populations present in the mouse female gonadal ridges (E11.5) and the embryonic ovaries from E12.5 to E14.5 using single-cell RNA sequencing (scRNA seq). These periods correspond with the initiation and progression of meiosis throughout the first stage of prophase I. We identified 13 transcriptionally distinct cell populations and 7 transcriptionally distinct germ cell subclusters that correspond to mitotic (3 clusters) and meiotic (4 clusters) germ cells. By analysing cluster-specific gene expression profiles, we found four cell clusters correspond to different cell stages en route to meiosis and characterized their detailed transcriptome dynamics. Our scRNA seq analysis here represents a new important resource for deciphering the molecular pathways driving female meiosis initiation.
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Perfilação da Expressão Gênica/métodos , Meiose , Ovário/citologia , Análise de Célula Única/métodos , Transcriptoma , Animais , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Camundongos , Camundongos Endogâmicos C57BL , Ovário/embriologiaRESUMO
Ovarian cancer is the deadliest gynecological cancer, leading to over 152,000 deaths each year. A late diagnosis is the primary factor causing a poor prognosis of ovarian cancer and often occurs due to a lack of specific symptoms and effective biomarkers for an early detection. Currently, cancer antigen 125 (CA125) is the most widely used biomarker for ovarian cancer detection, but this approach is limited by a low specificity. In recent years, multimarker panels have been developed by combining molecular biomarkers such as human epididymis secretory protein 4 (HE4), ultrasound results, or menopausal status to improve the diagnostic efficacy. The risk of ovarian malignancy algorithm (ROMA), the risk of malignancy index (RMI), and OVA1 assays have also been clinically used with improved sensitivity and specificity. Ongoing investigations into novel biomarkers such as autoantibodies, ctDNAs, miRNAs, and DNA methylation signatures continue to aim to provide earlier detection methods for ovarian cancer. This paper reviews recent advancements in molecular biomarkers for the early detection of ovarian cancer.
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MicroRNAs , Neoplasias Ovarianas , Algoritmos , Autoanticorpos , Biomarcadores Tumorais , Antígeno Ca-125 , Carcinoma Epitelial do Ovário , Feminino , Humanos , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/patologia , Proteínas/metabolismoRESUMO
Based on the theory of Q-marker, the hairy root of Salvia miltiorrhiza and S. miltiorrhiza in many provinces were studied. The relative expressions of SmCPS, SmKSL and CYP76AH1 genes in hairy roots were detected by real-time fluorescence quantitative PCR and the contents of tanshinoneâ ¡_A, cryptotanshinone, tanshinoneâ , 1,2-dihydrotanshinone, ferruginol and miltiradiene were detected by UPLC and GC-MS, respectively. Statistical analysis shows as fllows: in the hairy root of S. miltiorrhiza, the content of miltiradiene and ferruginol is positively correlated with the content of tanshinone compounds in the downstream, and the relative expression of important genes in the biosynthetic pathway of tanshinone can reflect the content of tanshinone compounds to a certain extent; in many provinces of S. miltiorrhiza, the content of ferruginol and tanshinone compounds can also be found that there is a positive correlation between the contents. Based on the biosynthetic pathway of tanshinone compounds, which is a special index component in S. miltiorrhiza, this study focused on the important relationship between the upstream gene, the middle intermediate compound and the downstream tanshinone compound content of the biosynthetic pathway, and explored the possible research ideas of improving the quality marker system of S. miltiorrhiza, and then provided the possible research ideas for understanding and studying the quality marker of traditional Chinese medicine from the biosynthetic pathway.
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Salvia miltiorrhiza , Abietanos , Vias Biossintéticas , Raízes de PlantasRESUMO
From the previous research, it has been supported that activin A (ActA) is conducive to ovarian development in vitro. In the present paper, with the aim to identify the molecular pathways through which ActA can influence processes of the fetal and early postnatal oogenesis, we analyzed the transcriptome of embryonic ovaries (12.5 days postcoitum) in vitro cultured with or without ActA for 6 days, as well as the produced oocytes for 28 days, and further compared the gene expression profile with their in vivo counterparts. With the confirmation of designed test, we found that the addition of ActA to the ovary culture tended, generally, to align oocyte gene expression to the in vivo condition, in particular of a number of genes involved in meiosis and epigenetic modifications of histones. In particular, we identified DNA recombination during the oocyte meiotic prophase I and lysine trimethylation of the histone H3K27 during the oocyte growth phase as molecular pathways modulated by ActA.
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Ativinas/genética , Meiose/genética , Oogênese/genética , Transcriptoma/genética , Animais , Apoptose/genética , Feto , Código das Histonas/genética , Histona Desmetilases com o Domínio Jumonji/genética , Camundongos , Oócitos/crescimento & desenvolvimento , Oócitos/metabolismoRESUMO
Osteochondroma is a benign autosomal dominant hereditary disease characterized by abnormal proliferation of cartilage in the long bone. It is divided into solitary osteochondroma and hereditary multiple exostoses (HMEs). The exostosin-1 (EXT-1) and exostosin-2 (EXT-2) gene mutations are well-defined molecular mechanisms in the pathogenesis of HME. EXT-1 and EXT-2 encode glycosyltransferases that are necessary for the synthesis of heparin sulfate. Accumulating evidence suggests that mutations in the EXT family induce changes in isolated hypogonadotropic hypogonadism-parathyroid hormone-related protein, bone morphogenetic protein, and fibroblast growth factor signaling pathways. Studies have also found that a large number of microRNAs (miRNAs) are abnormally expressed in osteochondroma tissues, and some of them also participate in several major signaling pathways. The regulation of miRNA expression could be another breakthrough in the treatment of osteochondroma. Although the pathogenesis of osteochondroma is very complicated, significant progress has been made in recent years. It is hoped that the pathogenesis of osteochondroma will be clearly understood and the most effective methods for the prevention and treatment of osteochondroma will be determined. This review provides an update on the recent progress in the interpretation of the underlying molecular mechanisms of osteochondroma.
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MicroRNAs/biossíntese , N-Acetilglucosaminiltransferases/metabolismo , Proteínas de Neoplasias/metabolismo , Osteocondroma/metabolismo , RNA Neoplásico/biossíntese , Transdução de Sinais , Regulação Neoplásica da Expressão Gênica , Humanos , Osteocondroma/patologiaRESUMO
As one of the most prevalent contaminants in animal and human food, the deleterious effects of trichothecene mycotoxin deoxynivalenol (DON) warrant extensive investigation. Here, to assess the effects of DON exposure to the populations of gut microbiota, four-weeks-old mice were exposed to different doses (1.0 and 5.0â¯mg/kg) of DON every two days for 14â¯days. The contents of the cecum were then collected for DNA extraction and metagenomic shotgun sequencing, in order to detect alterations of the gut microbiota. We found that the average body weight and daily gain in the high dose DON treated group decreased. Metagenomic analysis demonstrated that the relative abundance of Firmicutes in the low and Bacteroidetes in the high dose groups increased compared to that in the untreated control group. Moreover, using gene calling and functional annotation, we found that large numbers of biosynthesis and degradation dependent populations were altered. As a result, metabolism pathways including sphingolipid, protein digestion/absorption, and lipoic acid pathways in the high dose DON exposed group dramatically fluctuated in comparison to the control and low dose groups. In addition, metagenomic binning identified ten microbiota genome drafts, with high levels of completeness, that further explain the DON-induced intestinal toxicity. Our findings suggested that DON exposure significantly impacted the microbiota community in the mouse, causing biosynthesis and degradation damage and metabolism pathway disorders.
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Bactérias/efeitos dos fármacos , Ceco/efeitos dos fármacos , DNA Bacteriano/genética , Microbiologia de Alimentos , Microbioma Gastrointestinal/efeitos dos fármacos , Genoma Bacteriano , Metagenômica/métodos , Tricotecenos/toxicidade , Animais , Bactérias/genética , Bactérias/metabolismo , Ceco/microbiologia , Disbiose , Fezes/microbiologia , CamundongosRESUMO
Novel nanocomposites consisting of polystyrene-block-polybutadienyl polyhexamethylene dicarbamate-block-polystyrene (PS-b-HTPB5-b-PS) and multiwalled carbon nanotubes (MWCNTs) were designed and prepared via noncovalent interactions. Scanning electron microscopy and transmission electron microscopy observations showed that segregated networks of MWCNTs were formed due to the cladding of PS-b-HTPB5-b-PS, presenting a parallel-arranged topology of the MWCNTs in a continuous PS-b-HTPB5-b-PS phase, which improved the dispersibility of the MWCNTs. The nanocomposites were fabricated into vapor sensing elements to detect CH2Cl2 vapor in the environment, exhibiting excellent responsive sensitivity, reproducibility and a low limit of detection (LOD) of 1 ppm when exposed to CH2Cl2 vapor. The chain extension of HTPB overcame the fragility and improved the tenacity of the thin films, and the responsivity was optimized by adjusting the content of the MWCNTs and the length of the PS chains. The newly developed conductive composites can be applied as a promising vapor sensor to accurately monitor CH2Cl2 vapor in the environment.
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Zearalenone (ZEA) is one of mycotoxins which are from corn, sorghum and wheat. As an estrogenic compound, ZEA mainly affects animal growth and reproduction with causing abnormal reproduction capability. Previous studies have shown that ZEA poses adverse effects on follicular development, but the mechanism of genetic toxicity of ZEA is not understood. The purpose of this study was to explore the effects of ZEA exposure on granulosa cells which play vital roles during follicular development. Mouse granulosa cells were exposed to 10⯵M or 30⯵M ZEA for 72â¯h in vitro, and the differences in gene expression patterns between control and ZEA exposures were analyzed by RNA-seq. The data demonstrated that 30⯵M ZEA had a significant effect on the gene expression, especially ZEA exposure increased the expression of many genes related to different kinds of cancers and cancer related pathways like Hippo signaling pathway and the related genes, such as Ccnd1, Smad3, Tead3, Yap1 and Wwtr1. Furthermore, immunohistochemistry confirmed the increase in the protein levels of YAP1, WWTR1 and CCND1 in 30⯵M ZEA exposure group. Collectively, this investigation indicated that ZEA exposure promoted the expression of tumorigenesis genes in mouse granulosa cells to.
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Carcinógenos/toxicidade , Genes Neoplásicos/efeitos dos fármacos , Células da Granulosa/efeitos dos fármacos , Micotoxinas/toxicidade , Neoplasias Ovarianas/induzido quimicamente , Neoplasias Ovarianas/genética , Ovário/citologia , Zearalenona/toxicidade , Animais , Carcinogênese , Transformação Celular Neoplásica/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Ovário/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacosRESUMO
Zearalenone (ZEA), a natural contaminant found in feed, has been shown to have a negative impact on domestic animal reproduction, particularly in pigs. There are species-specific differences in the ZEA-induced toxicity pattern. Here, we investigated the different biological effects of ZEA exposure on porcine and mouse granulosa cells, using RNA-seq analysis. We treated murine and porcine granulosa cells with 10⯵M and 30⯵M ZEA during 72â¯h of culturing, in vitro. The results showed that 10⯵M ZEA exposure significantly altered mitosis associated genes in porcine granulosa cells, while the same treatment significantly altered the steroidogenesis associated genes in mouse granulosa cells. Exposure to 30⯵M ZEA resulted in significantly up-regulated expression of inflammatory related genes in porcine granulosa cells as well as the cancer related genes in mouse granulosa cells. Similarly, 30⯵M ZEA exposure significantly decreased the expression of tumor suppressor factors in the mouse granulosa cells. Furthermore, immunofluorescence, RT-qPCR as well as western-blot analysis verified the different expression of related genes in ZEA exposed porcine and mouse granulosa cells. Collectively, these results illustrate the presence of species differences with regards to ZEA effects between porcine and mouse ovarian granulosa cells, in vitro.
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Estrogênios não Esteroides/toxicidade , Células da Granulosa/efeitos dos fármacos , Células da Granulosa/fisiologia , Análise de Sequência de RNA/métodos , Zearalenona/toxicidade , Animais , Bovinos , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Expressão Gênica , Camundongos , Especificidade da Espécie , SuínosRESUMO
With the implementation of garbage classification, perishable waste has become increasingly concentrated. This has led to a significant change in the VOC release characteristics at residential garbage collection points, posing a potential risk with unknown characteristics. This study investigated the release characteristics, odor pollution, and health risks of VOCs at garbage collection points under different classification effectiveness, seasons, garbage drop-off periods, and garbage collection point types. The results showed that the average concentration of VOCs released from the garbage sorting collection points (SPs) was 341.43 ± 261.16 µg/m3, and oxygenated compounds (e.g., ethyl acetate and acetone) were the main VOC components. The VOC concentration increased as the community classification effectiveness improved, and it was higher in summer (followed by spring, autumn, and winter). Moreover, the VOC concentrations were higher in the evenings than in the mornings and at centralized garbage collection points (CPs) than at SPs. Further, odor activity value (OAV) assessments indicated that acrolein, styrene, and ethyl acetate were the critical odorous components, with an average OAV of 0.87 ± 0.85, implying marginal odor pollution in some communities. Health risk assessments further revealed that trichloroethylene, benzene, and chlorotoluene were the critical health risk substances, with an average carcinogenic risk (CR) value of 10-6-10-4, and a non-carcinogenic risk (HI) value < 1. These results indicated that HIs were acceptable, but potential CRs existed in the communities. Therefore, VOC pollution prevention and control measures should be urgently strengthened at the garbage collection points in high pollution risk scenarios.
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Acetatos , Poluentes Atmosféricos , Compostos Orgânicos Voláteis , Monitoramento Ambiental/métodos , Poluentes Atmosféricos/análise , Compostos Orgânicos Voláteis/análise , ChinaRESUMO
Plants are widely existing in the environments and have been considered as potential sentinel species of toxic chemicals' exposure. In this study, the deadly toxic chemicals of three nitrogen mustards (NMs, including NH1, NH2 and NH3) were selected as the investigated targets. First, the reactivities of common endogenous plant components with NMs were examined in vitro. Then, the model plant Nicotiana benthamiana Domin was exposed to NMs. Three γ-aminobutyric acid-nitrogen mustard adducts (GABA-NMs) were identified in the living plant by high resolution mass spectrometry and comparison with the synthesized references. A sensitive detection method with the limits of quantification of 0.0500 ng mL-1 was developed using ultrahigh performance liquid chromatography-triple quadrupole mass spectrometry. The GABA-NMs could be detected after 120 days of the exposure and even in the dead leaves without obvious decrease. Furthermore, 20 different plant species grown in diverse climate zones were exposed to HN1, and the adduct of GABA-HN1 was identified in all the leaves. The results showed the good universality and specificity of GABA-NMs as plant biomarkers for NMs exposure. This work provides a new approach for the pollution investigation of toxic chemicals through analysing biomarkers in plant materials.
Assuntos
Biomarcadores , Espectrometria de Massas em Tandem , Ácido gama-Aminobutírico , Ácido gama-Aminobutírico/análise , Ácido gama-Aminobutírico/metabolismo , Biomarcadores/análise , Cromatografia Líquida de Alta Pressão , Folhas de Planta/química , Folhas de Planta/metabolismo , Mecloretamina/análise , Mecloretamina/toxicidade , Mecloretamina/química , Nicotiana/química , Plantas/química , Plantas/metabolismo , Limite de Detecção , Espectrometria de Massa com Cromatografia LíquidaRESUMO
This study aimed to study the effects of different catalyst introduction methods on the distribution of SiC nanowires (SiCNWs) and the mechanical properties of SiCf/SiC composites. Two different catalyst-introduction methods (electroplating (EP) vs. atomic deposition (AD)) have been used to catalyze the growth of SiC nanowires in SiCf preforms. The morphology, structure and phase composition were systematically investigated using scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD). The SiCNWs-reinforced SiCf/SiC composited was densified by CVI. The compressive strength of the SiCNWs-reinforced SiCf/SiC composites was evaluated by radial crushing test. Compared with EP, atomic Ni catalysts fabricated by AD have higher diffusivity for better diffusion into the SiCf preform. The yield of SiCNWs is effectively increased in the internal pores of the SiCf preform, and a denser network forms. Therefore, the mechanical properties of SiCNW-containing SiCf/SiC composites are significantly improved. Compared with the EP-composites and SiCf/SiC composites, the compressive strength of AD-composites is increased by 51.1% and 56.0%, respectively. The results demonstrate that the use of AD method to grow SiCNWs is promising for enhancing the mechanical properties of SiCf/SiC composites.
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Cr-coated Zr alloys are widely considered the most promising accident-tolerant fuel (ATF) cladding materials for engineering applications in the near term. In this work, Cr coatings were prepared on the surfaces of 1400 mm long N36 cladding tubes using an industrial multiple arc source system. Orthogonal analyses were conducted to demonstrate the significance level of various process parameters influencing the characteristics of coatings (surface roughness, defects, crystal orientation, grain structure, etc.). The results show that the arc current mainly affects the coating deposition rate and the droplet particles on the surface or inside the coatings; however, the crystal preferred orientation and grain structure are more significantly influenced by the gas pressure and negative bias voltage, respectively. Then, the underlying mechanisms are carefully discussed. At last, a set of systemic methods to control the quality and microstructures of Cr coatings are summarized.
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As vegetation is part of our lives, plants are good candidates as indicators of toxic chemicals. Numerous components in plants may react with toxic chemicals to produce exposure biomarkers. Plant biomarkers formed by the modification of endogenous plant components by chemical warfare agents have not been reported. In this article, the model plant Arabidopsis thaliana (L.) was exposed to the nerve agent isobutyl S-2-diethylaminoethyl methylphosphonothiolate (iBuVX). Some characteristic ions were identified by liquid chromatography-high resolution mass spectrometry and their product ion mass spectra were recorded and interpreted. Some interesting fragmentation pathways were revealed including neutral loss of glucoside, rhamnose and isobutylene. Isobutyl methylphosphonyl modified flavonoids were deduced from assignment of product ions. The element components and the accurate mass of the product ions matched well with those of the proposed fragmentation pathways. The binding site of the nerve agent on flavonoids was proved to be the hydroxyl group on the benzene ring of the flavonoids by density functional theory computation and by the synthesis of the reference chemical, which was confirmed by 1H-31P HMBC NMR. The phosphonyl-modified flavonoids were evaluated for specificity in different plants. Four new flavonoid adducts as potential biomarkers were identified in the leaves of the iBuVX-exposed plant, which provided a novel strategy for the retrospective analysis of organophosphorus exposure for chemical weapon verification and forensic analysis.
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BACKGROUND: Hepatocellular carcinoma (HCC) is predominant among all types of primary liver cancers characterised by high morbidity and mortality. Genes in the mediator complex (MED) family are engaged in the tumour-immune microenvironment and function as regulatory hubs mediating carcinogenesis and progression across diverse cancer types. Whereas research studies have been conducted to examine the mechanisms in several cancers, studies that systematically focused on the therapeutic and prognostic values of MED in patients with HCC are limited. METHODS: The online databases ONCOMINE, GEPIA, UALCAN, GeneMANIA, cBioPortal, OmicStudio, STING, Metascape, and TIMER were used in this study. RESULTS: The transcriptional levels of all members of the MED family in HCC presented an aberrant high expression pattern. Significant correlations were found between the MED1, MED6, MED8, MED10, MED12, MED15, MED17, MED19, MED20, MED21, MED22, MED23, MED24, MED25, MED26, and MED27 expression levels and the pathological stage in the patients with HCC. The patients with high expression levels of MED6, MED8, MED10, MED17, MED19, MED20, MED21, MED22, MED24, and MED25 were significantly associated with poor prognosis. Functional enrichment analysis revealed that the members of the MED family were mainly enriched in the nucleobase-containing compound catabolic process, regulation of chromosome organisation, and transcriptional regulation by TP53. Significant correlations were found between the MED6, MED8, MED10, MED17, MED19, MED20, MED21, MED22, MED24, and MED25 expression levels and all types of immune cells (B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells). B cells and MED8 were independent predictors of overall survival. We found significant correlations between the somatic copy number alterations of the MED6, MED8, MED10, MED20, MED21, MED22, MED24, and MED25 molecules and the abundance of immune infiltrates. CONCLUSIONS: Our study delineated a thorough landscape to investigate the therapeutic and prognostic potentials of the MED family for HCC cases, which yielded promising results for the development of immunotherapeutic drugs and construction of a prognostic stratification model.
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Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Complexo Mediador/genética , Biomarcadores Tumorais/imunologia , Carcinoma Hepatocelular/imunologia , Biologia Computacional , Bases de Dados Genéticas , Perfilação da Expressão Gênica/estatística & dados numéricos , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/imunologia , Complexo Mediador/imunologia , Família Multigênica , Prognóstico , Mapas de Interação de Proteínas/genética , Mapas de Interação de Proteínas/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologiaRESUMO
Numerous approaches based on training low-high resolution image pairs have been proposed to address the super-resolution (SR) task. Despite their success, low-high resolution image pairs are usually difficult to obtain in certain scenarios, and these methods are limited in the actual scene (unknown or non-ideal image acquisition process). In this paper, we proposed a novel unsupervised learning framework, termed Enhanced Image Prior (EIP), which achieves SR tasks without low/high resolution image pairs. We first feed random noise maps into a designed generative adversarial network (GAN) for satellite image SR reconstruction. Then, we convert the reference image to latent space as the enhanced image prior. Finally, we update the input noise in the latent space with a recurrent updating strategy, and further transfer the texture and structured information from the reference image. Results on extensive experiments on the Draper dataset show that EIP achieves significant improvements over state-of-the-art unsupervised SR methods both quantitatively and qualitatively. Our experiments on satellite (SuperView-1) images reveal the potential of the proposed approach in improving the resolution of remote sensing imagery compared with the supervised algorithms. Source code is available at https://github.com/jiaming-wang/EIP.
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Algoritmos , Processamento de Imagem Assistida por ComputadorRESUMO
The microstructure and nanoindentation hardness of unirradiated, irradiated, annealed and corroded SiC coatings were characterized. Irradiation of 400 keV C+ and 200 keV He+ with approximately 10 dpa did not cause obvious amorphous transformation to nanocrystal SiC coatings and induced helium bubbles with 2-3 nm dimension distributed uniformly in the SiC matrix. High temperature annealing resulted in the transformation of SiC nanocrystals into columnar crystals in the irradiated region. Line-shaped bubble bands formed at the columnar crystal boundaries and their stacking fault planes and made the formation of microcracks of hundreds of nanometers in length. Meanwhile, some isolated helium bubbles distributed in SiC grains still maintained a size of 2-3 nm, despite annealing at 1200 °C for 5 h. The SiC coating showed excellent corrosion resistance under high-temperature, high-pressure water. The weight of the sample decreased with the increase of corrosion time. The nanoindentation hardness and the elastic modulus increased significantly with C+ and He+ irradiation, while their values decreased with high-temperature annealing. An increase in the annealing temperature led to an increased reduction in the values. Corrosion caused the decrease of nanoindentation hardness and the elastic modulus in the whole test depth range, whether the samples were irradiated or unirradiated.
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Litter size (LS), an important economic trait in livestock, is so complicate that involves many aspects of reproduction, the underlying mechanism of which particularly in goat has always been scanty. To uncover the genetic basis of LS, the genomic sequence of Jining Gray goat groups (one famous breed for high prolificacy in China) with LS 1, 2, and 3 for firstborn was analyzed, obtaining 563.67 Gb sequence data and a total of 31,864,651 high-quality single nucleotide polymorphisms loci were identified. Particularly, the increased heterozygosity in higher LS groups, and large continuous homozygous segments associated with lower LS group had been uncovered. Through an integrated analysis of three popular methods for detecting selective sweeps (Fst, nucleotide diversity, and Tajima's D statistic), 111 selected regions and 42 genes associated with LS were scanned genome wide. The candidate genes with highest selective signatures included KIT, KCNH7, and KMT2E in LS2 and PAK1, PRKAA1, and SMAD9 in LS3 group, respectively. Meanwhile, functional terms of programmed cell death involved in cell development and regulation of insulin receptor signaling pathway were mostly enriched with 42 candidate genes, which also included reproduction related terms of steroid metabolic process and cellular response to hormone stimulus. In conclusion, our study identified novel candidate genes involving in regulation of LS in goat, which expand our understanding of genetic fundament of reproductive ability, and the novel insights regarding to LS would be potentially applied to improve reproductive performance.
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Previous studies suggest that radiotherapy (RT) can induce immune activation, which not only reduces the progression of tumors, but also causes the release of tumor antigens. The combination of RT and immune checkpoint blockade, such as the inhibition of programmed cell death 1 (PD1) and programmed cell death ligand 1 (PDL1), has been demonstrated to yield impressive response rates. However, a substantial proportion of patients develop resistance such therapies. Previous studies have shown that indoleamine 2,3dioxygenase (IDO) causes T cell exhaustion and increased formation of regulatory T cells (Tregs), upregulating the expression of inhibitory receptors and ligands. Therefore, the application of IDO inhibitors combined with RT may have a synergistic effect by relieving immunosuppression. Lewis lung cancer cellbearing mice were treated with the IDO inhibitor 1methyltryptophan (1MT) and/or 10 Gy RT. Tumor size was measured every day, flow cytometry was performed to measure the expression of dendritic cell (DC) maturation markers, inhibitory receptors, ligands, cytotoxic T cells and Treg phenotypic markers. Reverse transcriptionquantitative PCR was used to evaluate the mRNA expression levels of IDO, PDL1, PD1, T cell immunoglobulin domain and mucin domain 3 (TIM3), B and Tlymphocyte attenuator (BTLA) and galectin9. Compared with the control group, treatment with 1MT or RT reduced tumor growth, however, the combination therapy was more effective than either treatment alone. Flow cytometry showed the upregulation of CD80, CD86 and the major histocompatibility complex II in spleen DCs and the concurrent downregulation of CD4, CD25 and forkhead box protein P3 in lymphocytes in the treatment groups. Compared with the control group, inhibitory receptors and ligands that affect DCs and T cells were observed, expression levels of PDL1, PD1, TIM3, BTLA and galectin9 are decreased in treatment group compared with control. IDO inhibition synergized with RT to downregulate Tregs, inhibitory receptors and ligands to prevent T cell exhaustion. By activating DCs and T cells, this combination therapy may strongly enhance antitumor immunity and inhibit tumor progression.