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The development of monolithic integrated energy-efficient complementary circuits is crucial for the large-scale application of wide bandgap semiconductor-based high-frequency and high-power field-effect transistors (FETs). However, the inferior performance of p-channel FETs attributed to low hole density and mobility presents a substantial challenge. Diamond is a promising candidate due to its excellent comprehensive electrical properties and high thermal conductivity. Here, we report the fabrication of normally off diamond FETs based on a low work function metal gate and (110) hydrogen-terminated diamond with high hole density. The use of high-quality SiO2 layer ensures the complete depletion of the channel by the gate and offers high gating efficiency. Therefore, the developed devices demonstrate exceptional reproducibility of normally off characteristics with centrally distributed threshold voltages (-0.37 ± 0.3 V) and realize large current and voltage handling capabilities and low static standby power consumption in a synergic manner with record-high on/off ratio exceeding 1010, high current density (â¼200 µA·µm-1), ultralow off-state current (â¼fA·µm-1), and high breakdown voltage (-676 V). Additionally, the thermal desorption of negatively charged acceptors has been proven to significantly reduce carrier scattering. This work offers superior performance p-channel FETs for implementing energy-efficient complementary circuits, laying the groundwork for accelerated development in wide bandgap semiconductor power electronics.
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KEY MESSAGE: One hundred and fifty-five QTL for trace element concentrations in foxtail millet were identified using a genome-wide association study, and a candidate gene associated with Ni-Co-Cr concentrations was detected. Foxtail millet (Setaria italica) is an important regional crop known for its rich mineral nutrient content, which has beneficial effects on human health. We assessed the concentrations of ten trace elements (Ba, Co, Cr, Cu, Fe, Mn, Ni, Pb, Sr, and Zn) in the grain of 408 foxtail millet accessions. Significant differences in the concentrations of five elements (Ba, Co, Ni, Sr, and Zn) were observed between two subpopulations of spring- and summer-sown foxtail millet varieties. Moreover, 84.4% of the element pairs exhibited significant correlations. To identify the genetic factors influencing trace element accumulation, a comprehensive genome-wide association study was conducted, identifying 155 quantitative trait locus (QTL) for the ten trace elements across three different environments. Among them, ten QTL were consistently detected in multiple environments, including qZn2.1, qZn4.4, qCr4.1, qFe6.3, qFe6.5, qCo6.1, qPb7.3, qPb7.5, qBa9.1, and qNi9.1. Thirteen QTL clusters were detected for multiple elements, which partially explained the correlations between elements. Additionally, the different concentrations of five elements between foxtail millet subpopulations were caused by the different frequencies of high-concentration alleles associated with important marker-trait associations. Haplotype analysis identified a candidate gene SETIT_036676mg associated with Ni accumulation, with the GG haplotype significantly increasing Ni-Co-Cr concentrations in foxtail millet. A cleaved amplified polymorphic sequence marker (cNi6676) based on the two haplotypes of SETIT_036676mg was developed and validated. Results of this study provide valuable reference information for the genetic research and improvement of trace element content in foxtail millet.
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Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Setaria (Planta) , Oligoelementos , Setaria (Planta)/genética , Oligoelementos/análisis , Mapeo Cromosómico , Fenotipo , Polimorfismo de Nucleótido Simple , GenotipoRESUMEN
KEY MESSAGE: Eleven QTLs for agronomic traits were identified by RTM- and MLM-GWAS, putative candidate genes were predicted and two markers for grain weight were developed and validated. Foxtail millet (Setaria italica), the second most cultivated millet crop after pearl millet, is an important grain crop in arid regions. Seven agronomic traits of 408 diverse foxtail millet accessions from 15 provinces in China were evaluated in three environments. They were clustered into two divergent groups based on genotypic data using ADMIXTURE, which was highly consistent with their geographical distribution. Two models for genome-wide association studies (GWAS), namely restricted two-stage multi-locus multi-allele (RTM)-GWAS and mixed linear model (MLM)-GWAS, were used to dissect the genetic architecture of the agronomic traits based on 13,723 SNPs. Eleven quantitative trait loci (QTLs) for seven traits were identified using two models (RTM- and MLM-GWAS). Among them, five were considered stable QTLs that were identified in at least two environments using MLM-GWAS. One putative candidate gene (SETIT_006045mg, Chr4: 744,701-746,852) that can enhance grain weight per panicle was identified based on homologous gene comparison and gene expression analysis and was validated by haplotype analysis of 330 accessions with high-depth (10×) resequencing data (unpublished). In addition, homologous gene comparison and haplotype analysis identified one putative foxtail millet ortholog (SETIT_032906mg, Chr2: 5,020,600-5,029,771) with rice affecting the target traits. Two markers (cGWP6045 and kTGW2906) were developed and validated and can be used for marker-assisted selection of foxtail millet with high grain weight. The results provide a fundamental resource for foxtail millet genetic research and breeding and demonstrate the power of integrating RTM- and MLM-GWAS approaches as a complementary strategy for investigating complex traits in foxtail millet.
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Setaria (Planta) , Setaria (Planta)/genética , Estudio de Asociación del Genoma Completo , Sitios de Carácter Cuantitativo , Fitomejoramiento , Fenotipo , Grano ComestibleRESUMEN
PURPOSE: To explore the relationship between brain function changes and clinical serological indicators and behavioral cognitive assessment in patients with neuropsychiatric systemic lupus erythematosus (NPSLE), and understand the pathogenesis of NPSLE from the perspective of imaging. METHODS: The resting-state functional imaging data, clinical serological, and behavioral cognitive assessment scores of 28 patients with NPSLE and 22 healthy controls (HC) were prospectively collected. The resting-state amplitude of low-frequency fluctuation (ALFF) values obtained from the analysis and processing were correlated with the serological data and behavioral cognitive assessment scores to determine the relationship between these data. RESULTS: The average age of the patients of the NPSLE group was older than that of the HC group; significant differences in education level, Auditory Verbal Learning Test Hua Shan Version (AVLT-H), and Trail Making Test scores were observed between the two groups. The NPSLE group demonstrated increased brain activity in the insula, precentral gyrus, and superior temporal gyrus, and decreased brain activity in the superior parietal gyrus. The ALFF value of the insula positively correlated with the Anti-ß2gp1 antibody and negatively correlated with the anti-nucleosome antibody and the AVL-recall (RC) score. The ALFF of the precentral gyrus negatively correlated with the AVL-immediate recall (I). The ALFF value of the superior temporal gyrus negatively correlated with the AVL-RC score. The left superior parietal gyrus positively correlated with the c-reactive protein. The right superior parietal gyrus positively correlated with the System Lupus Erythematosus Disease Activity Index and negatively correlated with the AVL-I score. CONCLUSION: Patients with NPSLE show different brain activity changes in different brain regions, and the abnormal brain regions are correlated with certain lupus antibodies, inflammatory factors, and cognitive assessment, thereby suggesting that the correlation between the three could provide novel insights into the pathogenesis of NPSLE.
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Disfunción Cognitiva , Lupus Eritematoso Sistémico , Vasculitis por Lupus del Sistema Nervioso Central , Humanos , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Encéfalo/patología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiologíaRESUMEN
Purpose: Observational studies have revealed that serum minerals and vitamins are associated with cancer. However, the causal relationships between serum minerals and vitamins and renal malignancies remain unclear. Methods: Mendelian randomization (MR) was used for causal estimation. Single nucleotide polymorphisms (SNPs) for serum minerals and vitamins were obtained from published genome-wide association studies (GWAS). GWAS for malignant kidney neoplasm was obtained from the FinnGen consortium. Methods of inverse variance weighted (IVW), MR-Egger, and weighted median were carried out for causal inference. F-statistic was calculated to ensure a robust instrumental variable. Cochran's Q statistics was applied to calculate heterogeneity. MR-Egger regression, MR-pleiotropy residual sum and outlier methods (MR-PRESSO) methods were used to perform pleiotropy analysis. Meanwhile, confounding factors were considered to determine whether causal inference would be biased. Results: Eight different micronutrients were included (zinc, iron, magnesium, calcium, copper, selenium, phosphate, and vitamin B12). After MR analysis, we found a protective effect of serum zinc against malignant kidney neoplasm (IVW: odds ratios (ORs), 0.86; 95% confidence interval (95% CI), 0.78-0.94; p, 0.0016; MR-Egger: OR, 0.80; 95% CI, 0.64-0.97; p, 0.052; weighted median: OR, 0.85; 95% CI, 0.75-0.96; p, 0.011). Causal relationships between other micronutrients and malignant kidney neoplasm were not obtained. No heterogeneity and pleiotropy were detected, while causality was not biased by confounding factors. Conclusion: We considered that serum zinc exerted a protective effect against malignant kidney neoplasm. In clinical practice, for people with high malignant kidney neoplasm risk, an oral zinc supplementation might play a role in a potential therapeutic target.
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Enterohemorrhagic Escherichia coli (EHEC) is a highly adaptive pathogen and has acquired diverse genetic elements, such as genomic islands and prophages, via horizontal gene transfer to promote fitness in vivo. Two-component signaling systems (TCSs) allow bacteria to sense, respond to, and adapt to various environments. This study identified a putative two-component signaling system composed of the histidine kinase EDL5436 (renamed LmvK) and the response regulator EDL5428 (renamed LmvR) in EHEC. lmvK and lmvR along with EDL5429 to EDL5434 (EDL5429-5434) between them constitute the OI167 genomic island and are highly associated with the EHEC pathotype. EDL5429-5434 encode transporters and metabolic enzymes that contribute to growth on mannose and are directly upregulated by LmvK/LmvR in the presence of mannose, as revealed by quantitative PCR (qPCR) and DNase I footprint assays. Moreover, LmvR directly activates the expression of the type III secretion system in response to mannose and promotes the formation of attaching and effacing lesions on HeLa cells. Using human colonoid and mouse infection models, we show that lmvK and lmvR contributed greatly to adherence and microcolony (MC) formation ex vivo and colonization in vivo. Finally, RNA sequencing and chromatin immunoprecipitation coupled with sequencing analyses identified additional direct targets of LmvR, most of which are involved in metabolism. Given that mannose is a mucus-derived sugar that induces virulence and is preferentially used by EHEC during infection, our data revealed a previously unknown mechanism by which EHEC recognizes the host metabolic landscape and regulates virulence expression accordingly. Our findings provide insights into how pathogenic bacteria evolve by acquiring genetic elements horizontally to adapt to host environments. IMPORTANCE The gastrointestinal tract represents a complex and challenging environment for enterohemorrhagic Escherichia coli (EHEC). However, EHEC is a highly adaptable pathogen, requiring only 10 to 100 CFUs to cause infection. This ability was achieved partially by acquiring mobile genetic elements, such as genomic islands, that promote overall fitness. Mannose is an intestinal mucus-derived sugar that stimulates virulence and is preferentially used by EHEC during infection. Here, we characterize the OI167 genomic island of EHEC, which encodes a novel two-component signaling system (TCS) and transporters and metabolic enzymes (EDL5429-5434) involved in mannose utilization. The TCS directly upregulates EDL5429-5434 and genes encoding the type III secretion system in the presence of mannose. Moreover, the TCS contributes greatly to EHEC virulence ex vivo and in vivo. Our data demonstrate an elegant example in which EHEC strains evolve by acquiring genetic elements horizontally to recognize the host metabolic landscape and regulate virulence expression accordingly, leading to successful infections.
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Escherichia coli Enterohemorrágica , Infecciones por Escherichia coli , Proteínas de Escherichia coli , Animales , Ratones , Humanos , Escherichia coli Enterohemorrágica/metabolismo , Virulencia/genética , Histidina Quinasa/genética , Histidina Quinasa/metabolismo , Islas Genómicas , Manosa , Células HeLa , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Sistemas de Secreción Tipo III/metabolismo , Infecciones por Escherichia coli/microbiología , Regulación Bacteriana de la Expresión GénicaRESUMEN
Therapeutic approaches of advanced colorectal cancer are more complex, here we present a living biobank of patient-derived tumoroids from advanced colorectal cancer patients and show examples of how these tumoroids can be used to to simulate cancer behavior ex vivo and provide more evidence for tumoroids could be utilized as a predictive platform during chemotherapy treatment to identify the chemotherapy response. Morphological, histological and genomic characterization analysis of colorectal cancer tumoroids was conducted. Further, we treated colorectal cancer tumoroids with different drugs to detect cellular activities to evaluate drug sensitivity using CellTiter-Glo 3 D cell viability assay. Then the drug sensitivity of tumoroids was compared with clinical outcomes. Our results implied that tumoroids recapitulated the histological features of the original tumours and genotypic profiling of tumoroids showed a high-level of similarity to the matched primary tumours. Dose-response curves, area under the curve and tumour inhibitory rate of each therapeutic profiling calculations in tumoroids demonstrated a great diversity and we gained 88.24% match ratio between the sensitivity data of tumoroids with their paired patients' clinical outcomes. tumour inhibitory rate of each treatment parameters in tumoroids performed positive correlation with progression-free survival while area under the curve of each treatment parameters performed negative correlation with progression-free survival of the corresponding patients. In summary, We presented a living biobank of tumoroids from advanced colorectal cancer patients and show tumoroids got great potential for predicting clinical responses to chemotherapy treatment of advanced colorectal cancer.
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Neoplasias Colorrectales , Humanos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Bancos de TejidosRESUMEN
Objective: To evaluate the effectiveness of diffusion-weighted imaging in the assessment of idiopathic epilepsy in Mongolian. Methods: One hundred Mongolian idiopathic epilepsy patients were enrolled as the observation group and 100 healthy Mongolian volunteers as the control group. All the subjects underwent routine MRI, diffusion kurtosis imaging (DKI), and intra-voxel incoherent motion (IVIM) examination on a 3.0 T scanner. Mean kurtosis (MK), mean diffusivity (MD), fractional anisotropy (FA), true water molecular diffusion coefficient (D), mean diffusion coefficient (MD), pseudo-diffusion coefficient (D∗), and perfusion fraction (f) of each region of interest in the brain were measured. Count data were expressed as rates, and the chi-square test was performed for comparison between groups. Measurement data were first assessed by a normality test, and the t test for independent samples was performed for comparison between groups if they met the normal distribution; for non-normal distribution, the Mann-Whitney U test was performed for comparison between groups. A ROC curve analysis was performed to test the effectiveness of each parameter. Results: MK values of the hippocampus, thalamus, and white matter of the temporal lobe in the observation group were significantly higher than those in the control group, while D and F values were significantly lower (all P < 0.05). ROC curve analysis showed that MK, D, and F values of the hippocampus, thalamus, and white matter of the temporal lobe had moderate to good diagnostic efficacy for idiopathic epilepsy (AUC = 0.617-0.749, all P < 0.001). Conclusion: DKI and IVIM can more accurately represent the abnormal changes of brain tissue in patients with epilepsy, and it may have important implications for the clinical diagnosis of Mongolian epileptic patients.
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Epilepsia , Humanos , Epilepsia/diagnóstico por imagen , Encéfalo/diagnóstico por imagenRESUMEN
The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed. Dissecting the genetic architecture of natural variation for maize (Zea mays L.) leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we performed an integrated genome- and transcriptome-wide association studies (GWAS and TWAS) to identify candidate genes putatively regulating variation in leaf gc. Of the 22 plausible candidate genes identified, 4 were predicted to be involved in cuticle precursor biosynthesis and export, 2 in cell wall modification, 9 in intracellular membrane trafficking, and 7 in the regulation of cuticle development. A gene encoding an INCREASED SALT TOLERANCE1-LIKE1 (ISTL1) protein putatively involved in intracellular protein and membrane trafficking was identified in GWAS and TWAS as the strongest candidate causal gene. A set of maize nested near-isogenic lines that harbor the ISTL1 genomic region from eight donor parents were evaluated for gc, confirming the association between gc and ISTL1 in a haplotype-based association analysis. The findings of this study provide insights into the role of regulatory variation in the development of the maize leaf cuticle and will ultimately assist breeders to develop drought-tolerant maize for target environments.
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Estudio de Asociación del Genoma Completo , Zea mays , Hojas de la Planta/metabolismo , Transcriptoma , Ceras/metabolismo , Zea mays/metabolismoRESUMEN
Objective: To investigate the effect of Hsp27 and the inhibitory effect of Atractylenolide I (ATL-1) on the proliferation of prostate cancer cell DU145 and PC-3. Methods: MTT assay was used to detect the inhibitory effect of silencing Hsp27 and ATL-1 on DU145 and PC-3 proliferation of prostate cancer cells. TUNEL detected the apoptosis rate of prostate cancer cell DU145 and PC-3 after silencing Hsp27 and ATL-1 treated. qRT-PCR was used to detect the changes of apoptosis related genes caspase-3, PARP, Bax and Bcl-2 in prostate cancer cell DU145 and PC-3 after the effect of silencing Hsp27 and ATL-1 treated. At the same time, the antitumor effect of ATL-1 combined with cabozantinib was analyzed. Results: Hsp27 was highly expressed in human prostate cancer. MTT assay showed that ATL-1 inhibited the proliferation of prostate cancer cells DU145 and PC-3 compared with the control group. TUNEL results showed that silencing Hsp27 and ATL-1 treated could significantly promote the apoptosis of prostate cancer cells DU145 and PC-3 compared with the control group. qRT-PCR results showed that compared with the control group, ATL-1 could promote the expression of caspase-3, PARP and Bax in DU145 and PC-3 prostate cancer cells. Inhibition of Hsp27 by ATL-1 reduced cell viability and induced apoptosis. ATL-1 inhibits the antitumor effect of Hsp27 - enhanced cabozantinib. Hsp27 regulates eIF4E and mediates cell protection. Conclusion: Silencing Hsp27 inhibits EMT. ATL-1 can inhibit the malignant evolution of prostate cancer cells by inhibiting Hsp27/eIF4E. ATL-1 also enhanced chemosensitization of cabozantinib in prostate cancer.
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Long noncoding RNA growth arrest specific 5 (GAS5) exerts inhibitory effects through the modulation of several target microRNAs (miRs) in cancer. However, its potential roles and underlying relationship during colorectal cancer (CRC) progression are unclear. Therefore, we explored the role of the negative feedback loop formed by the GAS5/miR34a axis and mammalian target of rapamycin/sirtuin 1 (mTOR/SIRT1) pathway on macroautophagy and apoptosis in CRC. Expression of GAS5, miR34a, SIRT1 and mTOR in CRC patients and cell lines was detected by quantitative reverse transcription polymerase chain reaction. Online bioinformatic analysis was used to predict the downstream miRs of GAS5. Luciferase assay and western blotting were performed to demonstrate miR34a as a downstream target gene of GAS5 in CRC cells. The effects of the GAS5/miR34a axis on apoptosis, macroautophagy, and the mTOR/SIRT1 pathway were assessed by flow cytometry, transmission electron microscopy and western blotting, respectively. Our results suggested that GAS5 was downregulated and acted as a molecular sponge of miR34a during CRC progression. miR34a participated in regulating GAS5suppressed CRC cell macroautophagy and induced apoptosis through the mTOR/SIRT1 pathway. GAS5mediated macroautophagy was maintained in an equilibrium state that might have a protective effect on CRC cell apoptosis. The mTOR signaling pathway suppressed GAS5 expression and formed a negative regulation feedback loop with miR34a in CRC cells. Our results suggested that the GAS5/miR34a/SIRT1/mTOR negative regulatory feedback loop mediated CRC cell macroautophagy, and maintained the cells in an autonomous equilibrium state, but not excessive activation state, which functions as a strong antiapoptotic phenotype during human CRC progression.
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Neoplasias Colorrectales/genética , Regulación Neoplásica de la Expresión Génica/inmunología , Macroautofagia/genética , MicroARNs/genética , ARN Largo no Codificante/metabolismo , Anciano , Animales , Azoximetano/administración & dosificación , Azoximetano/toxicidad , Línea Celular Tumoral , Colon/inmunología , Colon/patología , Colon/cirugía , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/cirugía , Retroalimentación Fisiológica , Femenino , Humanos , Macroautofagia/efectos de los fármacos , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Neoplasias Experimentales/inducido químicamente , Neoplasias Experimentales/genética , Neoplasias Experimentales/inmunología , Neoplasias Experimentales/patología , ARN Largo no Codificante/genética , Ratas , Transducción de Señal/genética , Sirolimus/farmacología , Sirtuina 1/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
On the demand of single-photon entangled light sources and high-sensitivity probes in the fields of quantum information processing, weak magnetic field detection and biosensing, the nitrogen vacancy (NV) color center is very attractive and has been deeply and intensively studied, due to its convenience of spin initialization, operation, and optical readout combined with long coherence time in the ambient environment. Although the application prospect is promising, there are still some problems to be solved before fully exerting its characteristic performance, including enhancement of emission of NV centers in certain charge state (NV- or NV0 ), obtaining indistinguishable photons, and improving of collecting efficiency for the photons. Herein, the research progress in these issues is reviewed and commented on to help researchers grasp the current trends. In addition, the development of emerging color centers, such as germanium vacancy defects, and rare-earth dopants, with great potential for various applications, are also briefly surveyed.
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Plant epidermal cuticles are composed of hydrophobic lipids that provide a barrier to non-stomatal water loss, and arose in land plants as an adaptation to the dry terrestrial environment. The expanding maize adult leaf displays a dynamic, proximodistal gradient of cuticle development, from the leaf base to the tip. Recently, our gene co-expression network analyses together with reverse genetic analyses suggested a previously undescribed function for PHYTOCHROME-mediated light signaling during cuticular wax deposition. The present work extends these findings by identifying a role for a specific LIPID TRANSFER PROTEIN (LTP) in cuticle development, and validating it via transgenic experiments in Arabidopsis. Given that LTPs and cuticles both evolved in land plants and are absent from aquatic green algae, we propose that during plant evolution, LTPs arose as one of the innovations of land plants that enabled development of the cuticle.
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Proteínas Portadoras/metabolismo , Fitocromo/metabolismo , Zea mays/metabolismo , Arabidopsis/metabolismo , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/metabolismoRESUMEN
Plant cuticles are composed of wax and cutin and evolved in the land plants as a hydrophobic boundary that reduces water loss from the plant epidermis. The expanding maize adult leaf displays a dynamic, proximodistal gradient of cuticle development, from the leaf base to the tip. Laser microdissection RNA Sequencing (LM-RNAseq) was performed along this proximodistal gradient, and complementary network analyses identified potential regulators of cuticle biosynthesis and deposition. A weighted gene coexpression network (WGCN) analysis suggested a previously undescribed function for PHYTOCHROME-mediated light signaling during the regulation of cuticular wax deposition. Genetic analyses reveal that phyB1 phyB2 double mutants of maize exhibit abnormal cuticle composition, supporting the predictions of our coexpression analysis. Reverse genetic analyses also show that phy mutants of the moss Physcomitrella patens exhibit abnormal cuticle composition, suggesting an ancestral role for PHYTOCHROME-mediated, light-stimulated regulation of cuticle development during plant evolution.
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Hojas de la Planta/crecimiento & desarrollo , Transcriptoma , Zea mays/genética , Bryopsida/genética , Bryopsida/metabolismo , Bryopsida/efectos de la radiación , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas/efectos de la radiación , Luz , Hojas de la Planta/genética , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Transcriptoma/efectos de la radiación , Zea mays/crecimiento & desarrollo , Zea mays/metabolismo , Zea mays/efectos de la radiaciónRESUMEN
Colorectal cancer (CRC) is one of the most common digestive tract tumors worldwide. Catalpol exerts inhibitory effects on the progression of several cancer types by regulating microRNAs (miRs). However, the precise role and carcinostatic mechanism of catalpol on CRC cells are poorly understood which limits the application of catalpol treatment. In the present study, miR34a and sirtuin 1 (SIRT1) expression levels were detected in CRC tissues and CRC cell lines by RTqPCR. Computational software analysis, luciferase assays and western blotting were used to demonstrate the downstream target of miR34a in CRC cells. Effects of catalpol on cell viability, apoptosis, autophagic flux and the miR34a/SIRT1 axis in the CRC cells were assessed by CCK8 assay, flow cytometry, electron microscopy and western blotting, respectively. Whether the miR34a/SIRT1 axis participated in catalpolmediated autophagy and apoptosis was investigated. The effects of catalpol on the miR34a/SIRT1 axis and malignant behavior were evaluated in a rat model of azoxymethane (AOM)induced CRC. It was revealed that miR34a expression levels were significantly decreased while SIRT1 was overexpressed in most of the CRC tissues and all the CRC cell lines. Clinically, a low level of miR34a was correlated with poor clinicopathological characteristics in CRC patients. Catalpol reduced cell viability, suppressed autophagy, promoted apoptosis, and regulated the expression of SIRT1 by inducing miR34a in vitro and in vivo. The autophagyinhibiting effect of catalpol may be a mechanism to promote apoptosis of CRC cells. miR34a mimic transfection resulted in autophagysuppressive activity similar to that of catalpol, while the miR34a inhibitor attenuated the antiautophagic effects of catalpol. In conclusion, miR34a is involved in regulating catalpolmediated autophagy and malignant behavior by directly inhibiting SIRT1 in CRC.
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Autofagia , Neoplasias del Colon/tratamiento farmacológico , Neoplasias Colorrectales/tratamiento farmacológico , Glucósidos Iridoides/farmacología , MicroARNs/genética , Rehmannia/química , Sirtuina 1/metabolismo , Anciano , Animales , Apoptosis , Azoximetano/química , Carcinógenos/química , Línea Celular Tumoral , Proliferación Celular , Supervivencia Celular , Neoplasias del Colon/genética , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Modelos Animales de Enfermedad , Medicamentos Herbarios Chinos/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Ratas , Ratas Wistar , Regulación hacia ArribaRESUMEN
The cuticle, a hydrophobic layer of cutin and waxes synthesized by plant epidermal cells, is the major barrier to water loss when stomata are closed at night and under water-limited conditions. Elucidating the genetic architecture of natural variation for leaf cuticular conductance (gc) is important for identifying genes relevant to improving crop productivity in drought-prone environments. To this end, we conducted a genome-wide association study of gc of adult leaves in a maize inbred association panel that was evaluated in four environments (Maricopa, AZ, and San Diego, CA, in 2016 and 2017). Five genomic regions significantly associated with gc were resolved to seven plausible candidate genes (ISTL1, two SEC14 homologs, cyclase-associated protein, a CER7 homolog, GDSL lipase, and ß-D-XYLOSIDASE 4). These candidates are potentially involved in cuticle biosynthesis, trafficking and deposition of cuticle lipids, cutin polymerization, and cell wall modification. Laser microdissection RNA sequencing revealed that all these candidate genes, with the exception of the CER7 homolog, were expressed in the zone of the expanding adult maize leaf where cuticle maturation occurs. With direct application to genetic improvement, moderately high average predictive abilities were observed for whole-genome prediction of gc in locations (0.46 and 0.45) and across all environments (0.52). The findings of this study provide novel insights into the genetic control of gc and have the potential to help breeders more effectively develop drought-tolerant maize for target environments.
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Estudio de Asociación del Genoma Completo , Zea mays , Sequías , Regulación de la Expresión Génica de las Plantas , Hojas de la Planta/genética , Ceras , Zea mays/genéticaRESUMEN
Hollow core anti-resonant fiber (HARF) has found a handful applications in optical communications, nonlinear optics and high power delivery. The intrinsic property of the fiber also renders it an ideal candidate for biosensing, which has not been explored intensively. Herein, we demonstrate an optical fiber sensing platform, taking advantages of the state-of-the-art HARF technology and superior physicochemical properties of 2D material black phosphorus, for ultra-sensitive detection of bisphenol A (BPA) in blood and environmental samples. The specially designed HARF can not only achieve broadband transmission of light, but also confine light in the low refractive-index liquid core, ensuring maximum overlap of light and liquid core. Modification of the inner surface of HARF with 2D black phosphorus nanoflakes functionalized with fluorescently labeled BPA-specific aptamer provides a smart sensing interface enabling highly selective detection of BPA via measuring the fluorescence. The limit of detection is 1.69pM, which is more than two orders of magnitude enhancement compared to the conventional plate assay. The proposed assay is not interfered with the BPA analogues BPB and BPS. The long optical path with tight optical confinement greatly enhances the analyte-light interaction and improves the sensitivity of the sensing platform. The proposed sensing platform can be further developed for versatile applications.