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1.
Nat Commun ; 14(1): 4663, 2023 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-37537164

RESUMO

Molecular interplay between host epigenetic factors and viral proteins constitutes an intriguing mechanism for sustaining hepatitis B virus (HBV) life cycle and its chronic infection. HBV encodes a regulatory protein, HBx, which activates transcription and replication of HBV genome organized as covalently closed circular (ccc) DNA minichromosome. Here we illustrate how HBx accomplishes its task by hijacking Spindlin1, an epigenetic reader comprising three consecutive Tudor domains. Our biochemical and structural studies have revealed that the highly conserved N-terminal 2-21 segment of HBx (HBx2-21) associates intimately with Tudor 3 of Spindlin1, enhancing histone H3 "K4me3-K9me3" readout by Tudors 2 and 1. Functionally, Spindlin1-HBx engagement promotes gene expression from the chromatinized cccDNA, accompanied by an epigenetic switch from an H3K9me3-enriched repressive state to an H3K4me3-marked active state, as well as a conformational switch of HBx that may occur in coordination with other HBx-binding factors, such as DDB1. Despite a proposed transrepression activity of HBx2-21, our study reveals a key role of Spindlin1 in derepressing this conserved motif, thereby promoting HBV transcription from its chromatinized genome.


Assuntos
Vírus da Hepatite B , Transativadores , Proteínas Virais Reguladoras e Acessórias , DNA Circular/metabolismo , DNA Viral/genética , Vírus da Hepatite B/fisiologia , Transativadores/genética , Transativadores/metabolismo , Proteínas Virais Reguladoras e Acessórias/genética , Proteínas Virais Reguladoras e Acessórias/metabolismo , Replicação Viral/genética
2.
Sci Adv ; 9(30): eadh1789, 2023 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-37506201

RESUMO

Fast and high-resolution x-ray imaging demands scintillator films with negligible afterglow, high scintillation yield, and minimized cross-talk. However, grain boundaries (GBs) are abundant in polycrystalline scintillator film, and, for current inorganic scintillators, detrimental dangling bonds at GBs inevitably extend radioluminescence lifetime and increase nonradiative recombination loss, deteriorating afterglow and scintillation yield. Here, we demonstrate that scintillators with one-dimensional (1D) crystal structure, Cs5Cu3Cl6I2 explored here, possess benign GBs without dangling bonds, yielding nearly identical afterglow and scintillation yield for single crystals and polycrystalline films. Because of its 1D crystal structure, Cs5Cu3Cl6I2 films with desired columnar morphology are easily obtained via close space sublimation, exhibit negligible afterglow (0.1% at 10 ms) and high scintillation yield (1.2 times of CsI:Tl). We have also demonstrated fast x-ray imaging with 27 line pairs mm-1 resolution and frame rate up to 33 fps, surpassing most existing scintillators. We believe that the 1D scintillators can greatly boost x-ray imaging performance.

3.
Research (Wash D C) ; 6: 0125, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37223485

RESUMO

Lead halide perovskite nanocrystals have recently demonstrated great potential as x-ray scintillators, yet they still suffer toxicity issues, inferior light yield (LY) caused by severe self-absorption. Nontoxic bivalent europium ions (Eu2+) with intrinsically efficient and self-absorption-free d-f transition are a prospective replacement for the toxic Pb2+. Here, we demonstrated solution-processed organic-inorganic hybrid halide BA10EuI12 (BA denotes C4H9NH4+) single crystals for the first time. BA10EuI12 was crystallized in a monoclinic space group of P21/c, with photoactive sites of [EuI6]4- octahedra isolated by BA+ cations, which exhibited high photoluminescence quantum yield of 72.5% and large Stokes shift of 97 nm. These properties enable an appreciable LY value of 79.6% of LYSO (equivalent to ~27,000 photons per MeV) for BA10EuI12. Moreover, BA10EuI12 shows a short excited-state lifetime (151 ns) due to the parity-allowed d-f transition, which boosts the potential of BA10EuI12 for use in real-time dynamic imaging and computer tomography applications. In addition, BA10EuI12 demonstrates a decent linear scintillation response ranging from 9.21 µGyair s-1 to 145 µGyair s-1 and a detection limit as low as 5.83 nGyair s-1. The x-ray imaging measurement was performed using BA10EuI12 polystyrene (PS) composite film as a scintillation screen, which exhibited clear images of objects under x-ray irradiation. The spatial resolution was determined to be 8.95 lp mm-1 at modulation transfer function = 0.2 for BA10EuI12/PS composite scintillation screen. We anticipate that this work will stimulate the exploration of d-f transition lanthanide metal halides for sensitive x-ray scintillators.

4.
Adv Mater ; 34(17): e2110252, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35165950

RESUMO

Controlling the carrier polarity and concentration underlies most electronic and optoelectronic devices. However, for the intensively studied lead halide perovskites, the doping tunability is inefficient. In this work, taking CsPbBr3 as an example, it is revealed that the coexistence of metallic Pb or CsBr3 /Br2 , rather than the precursor ratio, can provide Pb-rich/Br-poor or Br-rich/Pb-poor chemical conditions, enabling the tunability of electrical properties from weak n-type, intrinsic, to moderate p-type. Experimentally, under Br2 -exposure treatment, a shift of the Fermi level as large as 1.00 eV is achieved, which is one of the highest value among all kinds of doping methods. The X-ray detector based on the intrinsic CsPbBr3 exhibits excellent performance, with a negligible dark-current drift of 7.1 × 10-4 nA cm-1 s-1 V-1 , a low detection limit of 103.6 nGyair s-1 , and a high sensitivity of 9085 µC Gyair -1 cm-2 . This work provides a critical understanding and guidance for tuning the electrical properties of lead halide perovskites, which establishes good foundations for achieving intrinsic perovskite semiconductors and also constructing potential homojunction devices.

6.
ACS Appl Mater Interfaces ; 13(36): 43787-43794, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34467752

RESUMO

In ferroelectric-based integrated devices, there are usually buffer layers between ferroelectric films and semiconductor substrates. Here, Bix%FeO3-δ (x = 95, 100, and 105) (BFOx) films are prepared directly on n-Si substrates by the sol-gel method, and the variation of the hysteresis loops with Bi content and heat treatment is investigated. With the help of the dielectric measurement and the composition analysis, a PN heterojunction is believed to exist at the BFOx/Si interface. The Bi/Fe ratio determines not only the type and concentration of charged defects in the films but also the height of the interface barrier and its binding effect on mobile charges. Furthermore, the distribution and the migration of charges can be regulated reversibly by heat treatment. This work reveals the interaction between ferroelectric films and semiconductor substrates, providing an important reference for the design and application of ferroelectric/semiconductor heterostructures.

7.
J Phys Chem Lett ; 12(29): 6919-6926, 2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34282920

RESUMO

The present work reports highly efficient flexible and reabsorption-free scintillators based on two zero-dimensional (0D) organic copper halides (TBA)CuX2 (TBA = tetrabutylammonium cation; X = Cl, Br). The (TBA)CuX2 exhibit highly luminescent green and sky-blue emissions peaked at 510 and 498 nm, with large Stokes shifts of 224 and 209 nm and high photoluminescence quantum yields (PLQYs) of 92.8% and 80.5% at room temperature for (TBA)CuCl2 and (TBA)CuBr2 single crystals (SCs), respectively. Interestingly, above room temperature, their PLQYs increase with temperature and reach near unity at 320 and 345 K for (TBA)CuCl2 and (TBA)CuBr2, respectively. The excellent properties originate from self-trapped excitons (STEs) in individual [CuX2]- quantum rods, which is demonstrated by the temperature-dependent PL, ultrafast transient absorption (TA) combined with density functional theory (DFT) calculations. The (TBA)CuX2 scintillators show bright radioluminescence (RL), impressive linear response to dose rate in a broad range, and high light yields. Their potential application in X-ray imaging is demonstrated by using (TBA)CuX2 composite scintillation screens. Importantly, flexible scintillators are demonstrated to be superior than flat ones for imaging nonplanar objects by conformally coating, which produce accurate images with negligible distortion.

8.
Nano Lett ; 21(3): 1392-1399, 2021 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-33480701

RESUMO

An all-inorganic lead-free halides Cs-Cu-I system, represented by Cs3Cu2I5 and CsCu2I3, has attracted attention for their good photophysical characteristics recently. Successive works had reported their application potential in light-emitting devices. However, there is no report for CsCu2I3 in X-ray scintillation detectors so far. We notice that CsCu2I3 may be advantageous in such an application due to the one-dimensional crystal structure, the congruent-melting feature, and the high spectral matching to some photosensors. In this work, we explore the scintillation properties and imaging application of CsCu2I3 in X-ray scintillator detector. The oriented structure is designed to enhance the imaging performance of a CsCu2I3 detector. Close-space sublimation process and nanoscale seed screening strategy are employed to realize this design by producing a large-area (25 cm2) CsCu2I3 thick film layer with the oriented nanorod structure. This CsCu2I3 detector eventually achieves a high spatial resolution of 7.5 lp mm-1 in X-ray imaging.

9.
Eur J Immunol ; 51(4): 978-988, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33354776

RESUMO

Icaritin, a small molecule currently being investigated in phase III clinical trials in China (NCT03236636 and NCT03236649) for treatment of advanced hepatocellular carcinoma (HCC), is a prenylflavonoid derivative obtained from the Epimedium genus. Previously, it was found that Icaritin decreased the expression of PD-L1, but its direct molecular targets and the underlying mechanisms have not been identified. In this study, we report the identification of IKK-α as the protein target of Icaritin by biotin-based affinity binding assay. The further mutagenesis assay has provided evidence that C46 and C178 in IKK-α were essential amino acids for Icaritin binding to IKK-α, revealing the binding sites of Icaritin to IKK-α for the first time. Functionally, Icaritin inhibited the NF-κB signalling pathway by blocking IKK complex formation, which led to decreased nuclear translocation of NF-κB p65, and subsequent downregulation of PD-L1 expression in a dose-dependent manner. More importantly, PD-L1-positive patients exhibited longer overall survival upon Icaritin therapy. Finally, Icaritin in combination with checkpoints antibodies, such as α-PD-1, has demonstrated much better efficacy than any single therapy in animal models. This is the first report that anticancer effects of Icaritin are mediated, at least in part, by impairing functions of IKK-α.


Assuntos
Antígeno B7-H1/genética , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Quinase I-kappa B/antagonistas & inibidores , Animais , Antígeno B7-H1/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Epimedium/química , Feminino , Flavonoides/química , Células HEK293 , Humanos , Quinase I-kappa B/genética , Quinase I-kappa B/metabolismo , Células Jurkat , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos Endogâmicos C57BL , Estrutura Molecular , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Células THP-1 , Carga Tumoral/efeitos dos fármacos
10.
Zhonghua Nan Ke Xue ; 26(9): 793-797, 2020 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-33377701

RESUMO

OBJECTIVE: To evaluate the clinical effect and safety of transurethral 180 W front-firing GreenLight laser vaporization of the prostate (PVP) in the treatment of benign prostatic hyperplasia (BPH). METHODS: A total of 61 BPH patients underwent 180W front-firing GreenLight laser PVP (n = 30, the PVP group) or transurethral plasmakinetic resection of the prostate (n = 31, the control group) from March to December 2019. We collected the pre-, intra- and post-operative clinical data and compared them between the two groups of patients. RESULTS: Operations were successfully completed in all the cases with no blood transfusion or serious complications. Compared with the controls, the patients of the PVP group showed remarkably less intra-operative blood loss (ï¼»62.3 ± 15.9ï¼½ vs ï¼»48.8 ± 9.6ï¼½ ml, P < 0.05), shorter operation time (ï¼»75.0 ± 9.9ï¼½ vs ï¼»57.5 ± 19.0ï¼½ min, P < 0.05), postoperative bladder lavage time (ï¼»64.4 ± 10.5ï¼½ vs ï¼»25.2 ± 11.5ï¼½ h, P < 0.05), catheter-indwelling time (ï¼»5.1 ± 0.5ï¼½ vs ï¼»2.5 ± 0.5ï¼½ d, P < 0.05) and hospitalization time (ï¼»7.3 ± 1.7ï¼½ vs ï¼»4.1 ± 0.6ï¼½ d, P < 0.05), and a lower incidence of postoperative hematuria (12.9% ï¼»4/31ï¼½ vs 0% ï¼»0/30ï¼½, P < 0.05). No statistically significant differences, however, were found between the two groups in the incidence rates of capsular perforation, transurethral resection syndrome (TURS), urinary incontinence, urethral stricture and post-extubation urinary retention. Significant improvement was observed in IPSS, QOL, Qmax and PVR in both groups post-operatively (P < 0.05). CONCLUSIONS: Compared with transurethral plasmakinetic resection of the prostate, 180W front-firing GreenLight laser PVP, with the advantages of less bleeding, shorter catheter-indwelling time and faster recovery, is safer and more effective for the treatment of BPH, with no need for drug withdrawal for those taking anticoagulants, and especially applicable to the elderly and high-risk patients.


Assuntos
Terapia a Laser , Hiperplasia Prostática , Idoso , Humanos , Masculino , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Ressecção Transuretral da Próstata , Resultado do Tratamento
11.
Sensors (Basel) ; 20(24)2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33302513

RESUMO

An improved Near-Field Computer Vision (NFCV) system for intelligent fire robot was proposed that was based on our previous works in this paper, whose aims are to realize falling position prediction of jet trajectory in fire extinguishing. Firstly, previous studies respecting the NFCV system were briefly reviewed and several issues during application testing were analyzed and summarized. The improved work mainly focuses on the segmentation and discrimination of jet trajectory adapted to complex lighting environment and interference scenes. It mainly includes parameters adjustment on the variance threshold and background update rate of the mixed Gaussian background method, jet trajectory discrimination based on length and area proportion parameters, parameterization, and feature extraction of jet trajectory based on superimposed radial centroid method. When compared with previous works, the proposed method reduces the average error of prediction results from 1.36 m to 0.1 m, and the error variance from 1.58 m to 0.13 m. The experimental results suggest that every part plays an important role in improving the functionality and reliability of the NFCV system, especially the background subtraction and radial centroid methods. In general, the improved NFCV system for jet trajectory falling position prediction has great potential for intelligent fire extinguishing by fire-fighting robots.

12.
Cancer Manag Res ; 12: 10151-10161, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33116870

RESUMO

BACKGROUND: Hypoxic environment and exosomes (exos)-mediated intercellular communication are crucial for cancer invasion and metastasis, but the mechanisms are not yet fully understood. In this study, we investigated the regulatory effect of hypoxic tumor cell-secreted exosomal miR-582-3p on non-small-cell lung cancer (NSCLC) cell malignant phenotypes. METHODS: The concentration and diameters of exos were evaluated by nanosight particle tracking analysis. microRNA-582-3p (miR-582-3p) expression was detected by quantitative real-time PCR. The fluorescent dye PKH26 was used to label exos. The direct interaction between miR-582-3p and secreted frizzled-related protein 1 (SFRP1) was determined by dual-luciferase activity assay. NSCLC cell proliferation, migration, and invasion abilities were assessed by cell count kit-8 assay, wound healing assay, and transwell migration and invasion assay. Western blot analysis was performed to detect the protein expression level. RESULTS: Hypoxic NSCLC cell-derived exos promoted the proliferation, migration, and invasion of normoxic NSCLC cells. miR-582-3p expression was upregulated in hypoxic NSCLC cells and hypoxic NSCLC cell-secreted exos. Hypoxic NSCLC cell-derived exos transmitted miR-582-3p to normoxic NSCLC cells. Hypoxic NSCLC cell-secreted exosomal miR-582-3p promoted the proliferation, migration, and invasion of normoxic NSCLC cells. miR-582-3p inhibited the expression of SFRP1 protein by binding to its 3'-UTR. In addition, enforced expression of SFRP1 restrained malignant phenotypes of normoxic NSCLC cells, which was abrogated by hypoxic NSCLC cell-secreted exosomal miR-582-3p. CONCLUSION: Hypoxic NSCLC cell-secreted exosomal miR-582-3p drives cancer cell malignant phenotypes by targeting SFRP1, which provides a better understanding of cancer metastasis and may facilitate the development of therapeutics against human NSCLC.

13.
FASEB J ; 34(12): 16536-16551, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33078445

RESUMO

MicroRNAs are important coordinators of circadian regulation that mediate the fine-tuning of gene expression. Although many studies have shown the effects of individual miRNAs on the circadian clock, the global functional miRNA-mRNA interaction network involved in the circadian system remains poorly understood. Here, we used CLEAR (Covalent Ligation of Endogenous Argonaute-bound RNAs)-CLIP (Cross-Linking and Immuno-Precipitation) to explore the regulatory functions of miRNAs in the circadian system by comparing the miRNA-mRNA interactions between Drosophila wild-type strain W1118 and a mutant of the key circadian transcriptional regulator Clock (Clkjrk ). This experimental approach unambiguously identified tens of thousands of miRNA-mRNA interactions in both the head and body. The miRNA-mRNA interactome showed dramatic changes in the Clkjrk flies. Particularly, among ~300 miRNA-mRNA circadian relevant interactions, multiple interactions involving core clock genes pdp1, tim, and vri displayed distinct changes as a result of the Clk mutation. Based on the CLEAR-CLIP analysis, we found a novel regulation of the circadian rhythm and sleep by the miR-375-timeless interaction. The results indicated that Clk disruption abolished normal rhythmic expression of miR-375 and the functional regulation occurred in the l-LNv neurons, where miR-375 modulated the circadian rhythm and sleep via targeting timeless. This work provides the first global view of miRNA regulation in the circadian rhythm.


Assuntos
Relógios Circadianos/fisiologia , Ritmo Circadiano/fisiologia , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , MicroRNAs/metabolismo , Sono/fisiologia , Animais , Proteínas CLOCK/metabolismo , Expressão Gênica/fisiologia , Regulação da Expressão Gênica/fisiologia , Masculino , Atividade Motora/fisiologia , Neurônios/metabolismo , RNA Mensageiro/metabolismo
14.
Anal Methods ; 12(23): 3038-3044, 2020 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-32930164

RESUMO

Based on the surface plasmon resonance imaging (SPRi) technique, a new detection method for morphine in urine samples was developed. Sample labelling was not required, and qualitative and quantitative analysis could be completed in 20 minutes. According to an indirect competitive immunoassay, the mixture of morphine at different concentrations and morphine antibody at a certain concentration as the mobile phase was reacted with morphine BSA fixed on a chip surface in a competitive way. A calibration curve was obtained by correlating the signals generated from SPRi with the concentrations of morphine. By the addition of morphine to a blank urine sample, this method was confirmed to be feasible for the detection of morphine in actual urine. The limit of detection was as low as 9.59 ng mL-1. This method is fast and sensitive and can be applied in many fields.


Assuntos
Morfina , Ressonância de Plasmônio de Superfície , Anticorpos , Imunoensaio , Testes Imunológicos
15.
PLoS Negl Trop Dis ; 14(8): e0008669, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32866146

RESUMO

Exposure of adult mosquitoes to pyriproxyfen (PPF), an analog of insect juvenile hormone (JH), has shown promise to effectively sterilize female mosquitoes. However, the underlying mechanisms of the PPF-induced decrease in mosquito fecundity are largely unknown. We performed a comprehensive study to dissect the mode of PPF action in Aedes aegypti mosquitoes. Exposure to PPF prompted the overgrowth of primary follicles in sugar-fed Ae. aegypti females but blocked the development of primary follicles at Christopher's Stage III after blood feeding. Secondary follicles were precociously activated in PPF-treated mosquitoes. Moreover, PPF substantially altered the expression of many genes that are essential for mosquito physiology and oocyte development in the fat body and ovary. In particular, many metabolic genes were differentially expressed in response to PPF treatment, thereby affecting the mobilization and utilization of energy reserves. Furthermore, PPF treatment on the previtellogenic female adults considerably modified mosquito responses to JH and 20-hydroxyecdysone (20E), two major hormones that govern mosquito reproduction. Krüppel homolog 1, a JH-inducible transcriptional regulator, showed consistently elevated expression after PPF exposure. Conversely, PPF upregulated the expression of several key players of the 20E regulatory cascades, including HR3 and E75A, in the previtellogenic stage. After blood-feeding, the expression of these 20E response genes was significantly weaker in PPF-treated mosquitoes than the solvent-treated control groups. RNAi-mediated knockdown of the Methoprene-tolerant (Met) protein, the JH receptor, partially rescued the impaired follicular development after PPF exposure and substantially increased the hatching of the eggs produced by PPF-treated female mosquitoes. Thus, the results suggested that PPF relied on Met to exert its sterilizing effects on female mosquitoes. In summary, this study finds that PPF exposure disturbs normal hormonal responses and metabolism in Ae. aegypti, shedding light on the molecular targets and the downstream signaling pathways activated by PPF.


Assuntos
Aedes/efeitos dos fármacos , Culicidae/efeitos dos fármacos , Inseticidas/farmacologia , Metoprene/metabolismo , Esterilização , Animais , Ecdisterona/farmacologia , Corpo Adiposo/crescimento & desenvolvimento , Feminino , Glicogênio/metabolismo , Proteínas de Insetos/genética , Hormônios Juvenis/farmacologia , Ovário/crescimento & desenvolvimento , Piridinas , Interferência de RNA , Triglicerídeos/metabolismo
16.
Medicine (Baltimore) ; 99(29): e21282, 2020 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-32702919

RESUMO

INTRODUCTION: Intensive care unit-acquired weakness (ICU-AW) occurs in 25% to 100% of critically ill patients, and is associated with prolonged mechanical ventilation, extended ICU stay, and total hospital stay, increased hospital costs, higher risk of death, impaired physical function, and decreased quality of life. However, there are not any current guidelines that mention management of ICU-AW. The present study will evaluate the effects of a combination of early nutrition and early exercise compared to those of either early exercise alone or the standard care for patients in ICUs. METHODS: This is a 3-arm, parallel, randomized controlled trial including an estimated 147 critically ill patients aged ≥18 years recruited from the ICUs of 2 hospitals in Heilongjiang, China. Patients will be prospectively randomized 1:1:1 to receive early mobilization, early nutrition combined with early mobilization, or standard care (minimal exercises, experience-based initiation and enrollment of nutrition support). Outcomes are assessed at ICU discharge after baseline. The primary outcome is occurrence of ICU-AW according to the Medical Research Council scale at the end of treatment. Muscle strength, organ failure, functional independence, self-care ability, time of ICU stay, duration of mechanical ventilation, and ICU mortality are secondary outcome measures. DISCUSSION: This trial has the potential to identify a novel strategy for preventing or managing ICU-AW. The findings may increase the clinical knowledge about nutrition and mobilization interventions for people with ICU-AW, and contribute to the formation of practice guidelines for managing this condition. TRIAL REGISTRATION NUMBER: ChiCTR2000033482.


Assuntos
Deambulação Precoce , Unidades de Terapia Intensiva , Debilidade Muscular/etiologia , Terapia Nutricional , Adulto , Deambulação Precoce/métodos , Terapia por Exercício/métodos , Feminino , Humanos , Masculino , Debilidade Muscular/prevenção & controle , Terapia Nutricional/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Método Simples-Cego
17.
PLoS Genet ; 16(4): e1008765, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32339167

RESUMO

microRNAs (miRNAs) are increasingly recognized as important regulators of many biological processes in mosquitoes, vectors of numerous devastating infectious diseases. Identification of bona fide targets remains the bottleneck for functional studies of miRNAs. In this study, we used CLEAR-CLIP assays to systematically analyze miRNA-mRNA interactions in adult female Anopheles gambiae mosquitoes. Thousands of miRNA-target pairs were captured after direct ligation of the miRNA and its cognate target transcript in endogenous Argonaute-miRNA-mRNA complexes. Using two interactions detected in this manner, miR-309-SIX4 and let-7-kr-h1, we demonstrated the reliability of this experimental approach in identifying in vivo gene regulation by miRNAs. The miRNA-mRNA interaction dataset provided an invaluable opportunity to decipher targeting rules of mosquito miRNAs. Enriched motifs in the diverse targets of each miRNA indicated that the majority of mosquito miRNAs rely on seed-based canonical target recognition, while noncanonical miRNA binding sites are widespread and often contain motifs complementary to the central or 3' ends of miRNAs. The time-lapse study of miRNA-target interactomes in adult female mosquitoes revealed dynamic miRNA regulation of gene expression in response to varying nutritional sources and physiological demands. Interestingly, some miRNAs exhibited flexibility to use distinct sequences at different stages for target recognition. Furthermore, many miRNA-mRNA interactions displayed stage-specific patterns, especially for those genes involved in metabolism, suggesting that miRNAs play critical roles in precise control of gene expression to cope with enormous physiological demands associated with egg production. The global mapping of miRNA-target interactions contributes to our understanding of miRNA targeting specificity in non-model organisms. It also provides a roadmap for additional studies focused on regulatory functions of miRNAs in Anopheles gambiae.


Assuntos
Anopheles/genética , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Animais , Anopheles/fisiologia , Proteínas Argonautas/genética , Proteínas Argonautas/metabolismo , Feminino , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Estágios do Ciclo de Vida , MicroRNAs/genética , RNA Mensageiro/genética , Reprodução
18.
PLoS Pathog ; 16(4): e1008453, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32330198

RESUMO

Malaria, caused by the protozoan parasite Plasmodium and transmitted by Anopheles mosquitoes, represents a major threat to human health. Plasmodium's infection cycle in the Anopheles vector is critical for transmission of the parasite between humans. The midgut-stage bottleneck of infection is largely imposed by the mosquito's innate immune system. microRNAs (miRNAs, small noncoding RNAs that bind to target RNAs to regulate gene expression) are also involved in regulating immunity and the anti-Plasmodium defense in mosquitoes. Here, we characterized the mosquito's miRNA responses to Plasmodium infection using an improved crosslinking and immunoprecipitation (CLIP) method, termed covalent ligation of endogenous Argonaute-bound RNAs (CLEAR)-CLIP. Three candidate miRNAs' influence on P. falciparum infection and midgut microbiota was studied through transgenically expressed miRNA sponges (miR-SPs) in midgut and fat body tissues. MiR-SPs mediated conditional depletion of aga-miR-14 or aga-miR-305, but not aga-miR-8, increased mosquito resistance to both P. falciparum and P. berghei infection, and enhanced the mosquitoes' antibacterial defenses. Transcriptome analysis revealed that depletion of aga-miR-14 or aga-miR-305 resulted in an increased expression of multiple immunity-related and anti-Plasmodium genes in mosquito midguts. The overall fitness cost of conditionally expressed miR-SPs was low, with only one of eight fitness parameters being adversely affected. Taken together, our results demonstrate that targeting mosquito miRNA by conditional expression of miR-SPs may have potential for the development of malaria control through genetically engineered mosquitoes.


Assuntos
Anopheles/imunologia , Malária Falciparum/parasitologia , MicroRNAs/imunologia , Mosquitos Vetores/imunologia , Plasmodium berghei/fisiologia , Plasmodium falciparum/fisiologia , Animais , Anopheles/genética , Anopheles/parasitologia , Feminino , MicroRNAs/genética , Mosquitos Vetores/genética , Mosquitos Vetores/parasitologia , Plasmodium berghei/genética , Plasmodium berghei/imunologia , Plasmodium falciparum/genética , Plasmodium falciparum/imunologia
19.
J Phys Chem Lett ; 11(5): 1873-1880, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32040318

RESUMO

Lead halide perovskites have recently shown great potential as X-ray scintillators; however, the toxicity of the lead element seriously restricts their applications. Herein we report a new lead-free and self-absorption-free scintillator based on Rb2CuCl3 metal halide. The Rb2CuCl3 exhibits a near-unity photoluminescence quantum yield (99.4%) as well as a long photoluminescence lifetime (11.3 µs). Furthermore, Rb2CuCl3 demonstrates an appreciable light yield of 16 600 photons per megaelectronvolt and a large scintillation response with a linear range from 48.6 nGyair s-1 to 15.7 µGyair s-1. Notably, the detection limit is as low as 88.5 nGyair s-1, enabling a reduced radiation dose to the human body when a medical and security check is conducted. In addition, Rb2CuCl3 exhibits good stability against the atmosphere, continuous ultraviolet light, as well as X-ray irradiation. The combination of the decent scintillation performance, low toxicity and good stability suggests the Rb2CuCl3 could be a possible promising X-ray scintillator.


Assuntos
Cobre/química , Espectroscopia Fotoeletrônica , Teoria Quântica , Rubídio/química , Raios Ultravioleta , Difração de Raios X
20.
Natl Sci Rev ; 7(2): 278-284, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34692043

RESUMO

Ferroelectric domain walls differ from domains not only in their crystalline and discrete symmetry, but also in their electronic, magnetic, and mechanical properties. Although domain walls provide a degree of freedom to regulate the physical properties at the nanoscale, the relatively lower controllability prevents their practical applications in nano-devices. In this work, with the advantages of 3D domain configuration detection based on piezoresponse force microscopy, we find that the mobility of three types of domain walls (tail-to-tail, head-to-tail, head-to-head) in (001) BiFeO3 films varies with the applied electrical field. Under low voltages, head-to-tail domain walls are more mobile than other domain walls, while, under high voltages, tail-to-tail domain walls become rather active and possess relatively long average lengths. This is due to the high nucleation energy and relatively low growth energy for charged domain walls. Finally, we demonstrate the manipulation of domain walls through successive electric writings, resulting in well-aligned conduction paths as designed, paving the way for their application in advanced spintronic, memory and communication nano-devices.

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