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Ultrasound imaging stands as the predominant modality for neonatal health assessment, with recent advancements in ultrafast Doppler (µDoppler) technology offering significant promise in fields such as neonatal brain imaging. Combining µDoppler with high-frequency ultrasound (HF-µDoppler) presents a potential efficient avenue to enhance in vivo microvascular imaging in small animals, notably newborn rats, a crucial preclinical animal model for neonatal disease and development research. It is necessary to verify the imaging performance of HF-µDoppler in preclinical trials. This study investigates the microvascular imaging capabilities of HF-µDoppler using a 30 MHz high-frequency linear array probe in newborn rats. Results demonstrate the clarity of cerebral microvascular imaging in rats aged 1 to 7 postnatal days, extending to whole-body microvascular imaging, encompassing the central nervous system, including the brain and spinal cord. In conclusion, HF-µDoppler technology emerges as a reliable imaging tool, offering a new perspective for preclinical investigations into neonatal diseases and development.
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Animais Recém-Nascidos , Encéfalo , Microvasos , Animais , Ratos , Microvasos/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Encéfalo/irrigação sanguínea , Ratos Sprague-Dawley , Ultrassonografia Doppler/métodosRESUMO
Klebsiella pneumoniae (K. pneumoniae) is a gram-negative conditionally pathogenic bacterium that causes disease primarily in immunocompromised individuals. Recently, highly virulent K. pneumoniae strains have caused severe disease in healthy individuals, posing significant challenges to global infection control. Capsular polysaccharide (CPS), a major virulence determinant of K. pneumoniae, protects the bacteria from being killed by the host immune system, suggesting an urgent need for the development of drugs to prevent or treat K. pneumoniae infections. In this study, BY3 compounded traditional Chinese medicine residue (TCMR) was carried out using Lactobacillus rhamnosus as a fermentation strain, and BY3 compounded TCMR fermentation broth (BY3 fermentation broth) was obtained. The transcription of K. pneumoniae CPS-related biosynthesis genes after treatment with BY3 fermentation broth was detected using quantitative real-time polymerase chain reaction. The effects of BY3 fermentation broth on K. pneumoniae serum killing, macrophage phagocytosis, complement deposition and human ß-defensin transcription were investigated. The therapeutic effect of BY3 fermentation broth on K. pneumoniae-infected mice was also observed, and the major active components of BY3 fermentation broth were analysed via LCâMS analysis, network pharmacology, and molecular docking. The results showed that BY3 fermentation broth inhibited K. pneumoniae CPS production and downregulated transcription of CPS-related biosynthesis genes, which weakened bacterial resistance to serum killing and phagocytosis, while promoting bacterial surface complement C3 deposition and human ß-defensin expression. BY3 fermentation broth demonstrated safety and therapeutic effects in vivo and in vitro, restoring body weight and visceral indices, significantly reducing the organ bacterial load and serum cytokine levels, and alleviating pathological organ damage in mice. In addition, three natural compounds-oleanolic acid, quercetin, and palmitoleic acid-were identified as the major active components in the BY3 fermentation broth. Therefore, BY3 fermentation broth may be a promising strategy for the prevention or treatment of K. pneumoniae infections.
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The first aerobic protocol of direct transformation of p-methoxybenzyl (PMB) ethers to carboxylic acids efficiently with Fe(NO3)3â¢9H2O and TEMPO as catalysts at room temperature has been developed. The reaction accommodates C-Br bond, terminal/non-terminal C-C triple bond, amide, cyano, nitro, ester, and trifluoromethyl groups, etc. Even highly selective oxidative deprotection of different benzylic PMB ethers has been realized. The reaction has been successfully applied to the total synthesis of natural product, (R)-6-hydroxy-7,9-octadecadiynoic acid, demonstrating the practicality of the method. Based on experimental studies, a possible mechanism involving oxygen-stabilized benzylic cation has been proposed.
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BACKGROUND: The complex physical structure and abundant repeat sequences make it difficult to assemble the mitogenomes of seed plants, especially gymnosperms. Only approximately 33 mitogenomes of gymnosperms have been reported. However, as the most widely distributed and the second largest family among gymnosperms, Cupressaceae has only six assembled mitogenomes, including five draft mitogenomes and one complete mitogenome, which has greatly hindered the understanding of mitogenome evolution within this large family, even gymnosperms. RESULTS: In this study, we assembled and validated the complete mitogenome of Thuja sutchuenensis, with a size of 2.4 Mb. Multiple sequence units constituted its complex structure, which can be reduced to three linear contigs and one small circular contig. The analysis of repeat sequences indicated that the numbers of simple sequence repeats increased during the evolutionary history of gymnosperms, and the mitogenome of Thuja sutchuenensis harboured abundant extra-long repeats (more than 5 kb). Additionally, the longest repeat sequence identified in these seven gymnosperms also came from the mitogenome of Thuja sutchuenensis, with a length of up to 47 kb. The analysis of colinear blocks and gene clusters both revealed that the orders of mitochondrial genes within gymnosperms was not conserved. The comparative analysis showed that only four tRNAs were shared by seven gymnosperms, namely, trnD-GUC, trnE-UUC, trnI-CAU and trnY-GUA. Furthermore, four genes have undergone potential positive selection in most gymnosperm species, namely, atp8, ccmB, mttB and sdh4. CONCLUSION: We successfully assembled the second complete mitogenome within Cupressaceae and verified that it consisted of multiple sequence units. Our study also indicated that abundant long repeats may contribute to the generation of the complex conformation of the mitogenome of Thuja sutchuenensis. The investigation of Thuja sutchuenensis's mitogenome in our study provides new insight into further understanding the complex mitogenome architecture within gymnosperms.
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Cupressaceae , Genoma Mitocondrial , Thuja , Cupressaceae/genética , Sequências Repetitivas de Ácido Nucleico , Cycadopsida/genética , FilogeniaRESUMO
The application of drug-loaded nanodroplets is still limited by their insufficient accumulation owing to the enhanced permeability and retention (EPR) effect failure in cancer therapy. To overcome these limitations, we propose an alternative magnetic particle-encapsulated nanodroplet (MPE-ND) with outstanding biosafety and magnetic targeting by encapsulating fluorinated Fe3O4-SiO2 nanoparticles inside the liquid core of the nanodroplets. Meanwhile, doxorubicin (DOX) can be stably loaded into the shell through both electrostatic and hydrophobic interactions to obtain drug-loaded MPE-NDs. Both in vitro and in vivo experiments have consistently demonstrated that drug-loaded MPE-NDs can significantly increase the local drug concentration and enhance the damage of tumor tissues through acoustic droplet vaporization under a static magnetic field (eADV therapy). Histological examination reveals that eADV therapy efficiently suppresses tumor proliferation by inducing apoptosis, destroying supply vessels, and inhibiting neovascularization. Drug-loaded MPE-NDs can be expected to open a new gateway for ultrasound-triggered drug delivery and cancer treatment.
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Nanopartículas , Neoplasias , Volatilização , Preparações Farmacêuticas , Dióxido de Silício , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Doxorrubicina/química , Nanopartículas/uso terapêutico , Nanopartículas/química , Acústica , Fenômenos Magnéticos , Neoplasias/tratamento farmacológicoRESUMO
Following the progress on mono-heteroaryl azo switches (Het-N=N-Ph), a few bis-heteroaryl azo switches (Het-N=N-Het) have been studied recently, whereas the nonsymmetric bis-heteroaryl ones (Het1 -N=N-Het2 ) that can combine the respective merits of each heterocycle, have received little attention. Here we report thiazolylazopyrazoles as nonsymmetric bis-heteroaryl azo switches that combine the visible-light switching character of the thiazole ring and the ease of o-substitution of the pyrazole ring. Thiazolylazopyrazoles can achieve (near-)quantitative visible-light isomerization in both directions and long Z-isomer thermal half-lives of several days. In contrast to the drastically destabilizing effect of o-methylation, o-carbonylation of the pyrazole ring can remarkably stabilize Z isomers by inducing attractive intramolecular interactions (dispersion, C-Hâ â â N bond, and lone-pairâ â â π interaction). Our work highlights the importance of the rational combination of two heterocycles and suitable structural substitution in developing bis-heteroaryl azo switches.
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Sugar nucleotides are essential glycosylation donors in the carbohydrate metabolism. Naturally, most sugar nucleotides are derived from a limited number of common sugar nucleotides by de novo biosynthetic pathways, undergoing single or multiple reactions such as dehydration, epimerization, isomerization, oxidation, reduction, amination, and acetylation reactions. However, it is widely believed that such complex bioconversions are not practical for synthetic use due to the high preparation cost and great difficulties in product isolation. Therefore, most of the discovered sugar nucleotides are not readily available. Here, based on de novo biosynthesis mainly, 13 difficult-to-access sugar nucleotides were successfully prepared from two common sugars D-Man and sucrose in high yields, at a multigram scale, and without the need for tedious purification manipulations. This work demonstrated that de novo biosynthesis, although undergoing complex reactions, is also practical and cost-effective for synthetic use by employing a cascade conversion strategy.
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Nucleotídeos , Açúcares , Glicosilação , Humanos , Nucleotídeos/metabolismo , Açúcares/metabolismoRESUMO
Biomedical imaging technology (like digital subtraction angiography (DSA)) based on contrast agents has been widely employed in the diagnosis of vascular-related diseases. While the DSA achieves the high-resolution observation of specified vessels and their downstream perfusion at the cost of invasive, radioactive operation and hepatorenal toxicity. To address those problems, this study develops arterial labeling ultrasound (US) subtraction angiography (ALUSA) based on a new perfluorobutane (PFB) nanodroplets with a lower vaporization threshold through spontaneous nucleation. The nanodroplets can be selectively vaporized to microbubbles, indicating a highly echogenic signal at B-mode images only using a diagnostic transducer. By labeling a single blood vessel for nanodroplets vaporization and tracking its downstream blood perfusion in segmental renal arteries at a frame rate of 500 Hz. The results demonstrate the color-coded super-resolution ALUSA image, exhibiting the downstream arcuate and interlobular arteries of each segmental renal artery with a resolution of 36 µm in a rabbit kidney. Furthermore, ALUSA could offer the vascular structures, blood flow velocity, and direction of their primary supply vessels in the mouse breast tumor. ALUSA fills the gap of noninvasive labeling angiography in US and opens a broad vista in the diagnosis and treatment of tumor and vascular-related diseases.
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Acústica , Microbolhas , Angiografia Digital , Animais , Artérias , Camundongos , Coelhos , Ultrassonografia/métodosRESUMO
Proteolysis-targeting chimeras (PROTACs) are a class of bifunctional molecules that can induce the ubiquitin degradation of its target protein by hijacking the E3 ligase to form a target protein-PROTAC-E3 ligase ternary complex. Its underlying principle has inspired the development of a wide range of protein degraders that are similar to or beyond PROTACs in recent years. The formation of the ternary complexes is the key to the success of PROTAC-induced protein degradation. Nevertheless, the lack of effective ternary complex modeling techniques has limited the application of computer-aided drug discovery tools to this emerging and fast developing new land in drug industry. Thus, in this study, we explored the application of the more physically sound molecular dynamics simulation and the molecular mechanics combined with the generalized Born and surface area continuum solvation (MM/GBSA) method to solve the underlying three-body problem in PROTAC modeling. We first verified the accuracy of our approach using a series of known Brd4 BD2 degraders. The calculated binding energy showed a good correlation with the experimental Kd values. The modeling of a unique property, namely, the α value, for PROTACs was also first and accurately performed to our best knowledge. The results also demonstrated the importance of PROTAC-induced protein-protein interactions in its modeling, either qualitatively or quantitatively. Finally, by standing on the success of earlier docking-based approaches, our protocol was also applied as a rescoring function in pose prediction. The results showed a notable improvement in reranking the initial poses generated from a modified Rosetta method, which was reportedly one of the best among a handful of PROTAC modeling approaches available in this field. We hope this work could provide a practical protocol and more insights to study the binding and the design of PROTACs and other protein degraders.
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Simulação de Dinâmica Molecular , Proteínas Nucleares/metabolismo , Proteólise , Fatores de Transcrição/metabolismo , Mapeamento de Interação de ProteínasRESUMO
Industrial production, ore smelting and sewage disposal plant can discharge large amounts of heavy metals every year, which may contaminate soil, water and air, posing a great threat to ecological environment and animal production. Hexavalent chromium [Cr (VI)], a recognized metallic contaminant, has been shown to impair kidney, liver and gastrointestinal tract of many species, but little is known about the gut microbial characteristics of chickens exposed to Cr (VI). Herein, this study characterized the gut microbial alternations of chickens exposed to Cr (VI). Results indicated that the gut microbial alpha-diversity in chickens exposed to Cr (VI) decreased significantly, accompanied by a distinct shifts in taxonomic composition. Microbial taxonomic analysis demonstrated that the preponderant phyla (Firmicutes, Bacteroidetes, Proteobacteria and Epsilonbacteraeota) were the same in both groups, but different in types and relative abundances of dominant genera. Moreover, some bacterial taxa including 2 phyla and 47 genera significantly decreased, whereas 3 phyla and 17 genera significantly increased during Cr (VI) exposure. Among decreased taxa, 9 genera (Coprobacter, Ruminococcus_1, Faecalicoccus, Eubacterium_nodatum_group, Parasutterella, Slackia, Barnesiella, Family_XIII_UCG-001 and Collinsella) even cannot be detected. In conclusion, this study revealed that Cr (VI) exposure dramatically decrased the gut microbial diversity and altered microbial composition of chickens. Additionally, this study also provided a theoretical basis for relieving Cr (VI) poisoning from the perspective of gut microbiota.
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Galinhas , Microbioma Gastrointestinal , Animais , Bacteroidetes , Cromo/toxicidade , Firmicutes , HomeostaseRESUMO
Glycosylation is catalyzed by glycosyltransferases using sugar nucleotides or occasionally lipid-linked phosphosugars as donors. However, only very few common sugar nucleotides that occur in humans can be obtained readily, while the majority of sugar nucleotides that exist in bacteria, plants, archaea, or viruses cannot be synthesized in sufficient quantities by either enzymatic or chemical synthesis. The limited availability of such rare sugar nucleotides is one of the major obstacles that has greatly hampered progress in glycoscience. Herein we describe a general cofactor-driven cascade conversion strategy for the efficient synthesis of sugar nucleotides. The described strategy allows the large-scale preparation of rare sugar nucleotides from common sugars in high yields and without the need for tedious purification processes.
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Glicosiltransferases , Nucleotídeos , Glicosilação , Glicosiltransferases/metabolismo , Humanos , Nucleotídeos/metabolismo , AçúcaresRESUMO
Optimizing the alkali treatment process alone without tracking the changes of algae and agar quality with each pretreatment process will not achieve the optimal agar yield and final quality. In this study, we monitored the changes of the morphology and weight of algae with each treatment process, and comprehensively analyzed the effects of each pretreatment process on the quality of agar by combining the changes of the physicochemical properties of agar. In conventional alkali-extraction technology, alkali treatment (7%, w/v) alone significantly reduced the weight of algae (52%), but hindered the dissolution of algae, resulting in a lower yield (4%). Acidification could solve the problem of algal hardening after alkali treatment to improve the yield (12%). In enzymatic extraction technology, agar with high purity cannot be obtained by enzyme treatment alone, but low gel strength (405 g/cm2) and high sulfate content (3.4%) can be obtained by subsequent acidification and bleaching. In enzyme-assisted extraction technology, enzyme damage to the surface fiber of algae promoted the penetration of low-concentration alkali (3%, w/v), which ensured a high desulfurization efficiency and a low gel degradation rate, thus improving yield (24.7%) and gel strength (706 g/cm2), which has the potential to replace the traditional alkali-extraction technology.
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Ágar/química , Gracilaria , Animais , Organismos Aquáticos , Química VerdeRESUMO
Di-(2-ethylhexyl) phthalate (DEHP) is a common plasticizer which is mainly used as a kind of plastic additive to increase the flexibility of plastic products. Given the widespread use of plastic products, DEHP, as a ubiquitous artificial pollutant, are widely present in the environment. In addition, DEHP could cause biological damage in various organs through oxidative stress. Nano-Selenium, a novel form of selenium, has a wide variety of biomedical applications as an antioxidant, anticancer and anti-inflammatory agent. Nevertheless, researches on the toxicity of DEHP in chicken hepatocyte lines is insufficient. In particular, researches on the interaction between DEHP and nano-selenium is insufficient in chicken cell. Therefore, the innovation of this study is to explore the theoretical mechanism of DEHP toxicity in hepatocytes and the antagonistic effect of nano-selenium on a series of damage in chicken hepatocytes caused by DEHP. Our results showed that, after DEHP exposure, oxidative stress levels in hepatocytes increased, and the mRNA and protein levels of apoptosis-related genes p53, Capsase9, Caspase3 and Bax increased significantly except Bcl-2. The protein levels of apoptosis markers cleaved-Caspase9 and cleaved-Caspase3 also increased significantly. Moreover, the result of TUNEL assay also showed that the level of apoptotic cells increased after DEHP exposure. Meanwhile, the mRNA and protein levels of PI3K, AKT and p-AKT decreased. Therefore, DEHP is able to enhance the degree of oxidative damage and apoptosis of chicken liver cells. Nevertheless, the addition of nano-selenium can reverse the above changes. Experimental results revealed that nano-selenium antagonizes the toxic effects of DEHP via the PI3K/AKT pathway.
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Hexavalent chromium [Cr (VI)] is a hazardous heavy metal that pollutes soil, water and crops. Moreover, its prolonged exposure can harm the gastrointestinal system, liver and respiratory tract in different species, but knowledge regarding Cr (VI) influence on gut microbiota in chickens remains scarce. Therefore, this study was performed to investigate the impact of Cr (VI) on gut microbiota in chickens. Results revealed that the gut microbiota in Cr (VI)-induced chickens exhibited a distinct reduction in alpha diversity, accompanied by significant shifts in microbial composition. Specifically, Firmicutes and Bacteroidetes were the most dominant phyla in the control chickens, whereas Firmicutes and Actinobacteria were observed to be predominant in the Cr (VI)-induced populations. Moreover, the types and relative abundances of predominant bacterial genus in control and Cr (VI)-induced chickens were also different. Bacterial taxonomic analysis revealed that the relative abundances of 3 phyla and 7 genera obviously increased, whereas 8 phyla and 30 genera dramatically decreased during Cr (VI) induction. Among them, 1 phylum (Deferribacteres) and 5 genera (Butyricicoccus, Butyricimonas, Intestinimonas, Lachnospiraceae_FCS020_group and Ruminococcaceae_V9D2013_group) even could not be found in the gut microbial community of Cr (VI)-induced chickens. Taken together, our study indicated that the long-term exposure to Cr (VI) dramatically alter the gut microbial diversity and composition in chickens. Notably, it represents a breakthrough in understanding the impact of Cr (VI) on the intestinal microbiota of chickens.
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Microbioma Gastrointestinal , Animais , Galinhas , Cromo/toxicidade , DisbioseRESUMO
Oligosaccharides together with oligonucleotides and oligopeptides comprise the three major classes of natural biopolymers. Automated systems for oligonucleotide and oligopeptide synthesis have significantly advanced developments in biological science by allowing nonspecialists to rapidly and easily access these biopolymers. Researchers have endeavored for decades to develop a comparable general automated system to synthesize oligosaccharides. Such a system would have a revolutionary impact on the understanding of the roles of glycans in biological systems. The main challenge to achieving automated synthesis is the lack of general synthetic methods for routine synthesis of glycans. Currently, the two main methods to access homogeneous glycans and glycoconjugates are chemical synthesis and enzymatic synthesis. Enzymatic glycosylation can proceed stereo- and regiospecifically without protecting group manipulations. Moreover, the reaction conditions of enzyme-catalyzed glycosylations are extremely mild when compared to chemical glycosylations. Over the past few years methodology toward the automated chemical synthesis of oligosaccharides has been developed. Conversely, while automated enzymatic synthesis is conceptually possible, it is not as well developed. The goal of this survey is to provide a foundation on which continued technological advancements can be made to promote the automated enzymatic synthesis of oligosaccharides.
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Automação , Técnicas de Química Sintética/métodos , Glicoconjugados/síntese química , Glicosiltransferases/química , Oligossacarídeos/síntese química , Sequência de Carboidratos , Catálise , Glicoconjugados/química , Glicosilação , Oligossacarídeos/química , EstereoisomerismoRESUMO
OBJECTIVES: Super-resolution ultrasound (SRUS) has become a tool for in vivo microvascular imaging. Most of the SRUS methods are based on microbubble localization: namely, ultrasound localization microscopy (ULM). The aim of this study was to develop a nonlocalization SRUS method and verify its feasibility in microvascular imaging. METHODS: We introduce a new super-resolution strategy based on the postprocessing of contrast-enhanced ultrasound. The proposed method, which is termed ultrasound diffraction attenuation microscopy (UDAM), uses super-resolution radial fluctuations instead of microbubble localization to overcome acoustic diffraction limits. Biceps of Japanese long-ear white rabbits were adopted to validate its feasibility on muscle vascular imaging, using a clinical accessible ultrasound system at a frame rate of 30 Hz under a single bolus injection of SonoVue (Bracco SpA, Milan, Italy). The super-resolution image was compared with the maximum-intensity projection and ULM. RESULTS: The animal study illustrates that the proposed UDAM can obtain super-resolution microvascular images of rabbits' muscles under a single bolus injection of SonoVue with a 150-second contrast-enhanced ultrasound video. Both ULM and UDAM can achieve a very similar vascular structure with the maximum-intensity projection but much higher spatial resolution. The measurement of 1-dimensional signals shows that UDAM can distinguish the subwavelength structures and substantial reduce the full width at half-maximum of microvessels. CONCLUSIONS: We conclude UDAM provides a noninvasive tool for in vivo super-resolution microvascular imaging.
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Microbolhas , Microvasos , Animais , Meios de Contraste , Itália , Microvasos/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Coelhos , UltrassonografiaRESUMO
Historically, researchers have put considerable effort into developing automation systems to prepare natural biopolymers such as peptides and oligonucleotides. The availability of such mature systems has significantly advanced the development of natural science. Over the past twenty years, breakthroughs in automated synthesis of oligosaccharides have also been achieved. A machine-driven platform for glycopeptide synthesis by a reconstructed peptide synthesizer is described. The designed platform is based on the use of an amine-functionalized silica resin to facilitate the chemical synthesis of peptides in organic solvent as well as the enzymatic synthesis of glycan epitopes in the aqueous phase in a single reaction vessel. Both syntheses were performed by a peptide synthesizer in a semiautomated manner.
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Enzimas/química , Glicopeptídeos/síntese química , Automação , Técnicas de Química SintéticaRESUMO
Circular RNA (circRNA) play important roles in the pathological processes of many diseases. By analyzing the results of the GSE100186 chip, we found that the expression of circRNA ZNF609 (circ-ZNF609) was significantly increased in renal cell carcinoma. Recently, there are studies showing that circ-ZNF609 can regulate cell proliferation and invasion ability of various cells. In this study, we investigated whether circ-ZNF609 may affect cell invasion and proliferation in renal carcinoma. Quantitative reverse transcription polymerase chain reaction was performed to detect the expression of circ-ZNF609 in renal carcinoma cell lines and renal epithelial cells. The direct interaction between microRNA-138-5p (miR-138-5p) and forkhead box P4 (FOXP4) or circ-ZNF609 was confirmed by luciferase reporter assay and RNA immunoprecipitation assay. We use Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, and Matrigel assays to assess the effect of miR-138-5p or circ-ZNF609 on cell proliferation or invasion ability. And we found that circ-ZNF609 is significantly increased in renal carcinoma cell lines. In addition, the high expression of circ-ZNF609 promotes cell proliferation and invasion ability. In short, our current study reveals the role of the circ-ZNF609/miR-138-5p/FOXP4 regulatory network in renal carcinoma and provides a new perspective for the pathogenesis of renal carcinoma.
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Carcinoma de Células Renais/genética , Fatores de Transcrição Forkhead/genética , MicroRNAs/genética , RNA Circular/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Transdução de Sinais/genéticaRESUMO
PURPOSE: This study aimed to identify the existence of uterine micro-peristalsis (UMP) by dynamic ultrasound features and evaluate the feasibility of UMP as a tool to distinguish pregnant and non-pregnant infertility patients undergoing in vitro fertilization-embryo transfer (IVF-ET), using clinical pregnancy results as a benchmark. METHODS: Fifty-one women, including 29 pregnant and 22 non-pregnant patients were recruited. Also, ultrasound videos were collected before embryo transfer. First of all, undiscoverable uterine micro-peristalsis was magnified by video magnification. Then, the dynamic features of UMP were characterized by a novel index termed histogram entropy based on the micro-peristalsis feature selection by entropy weight (HEMEW), which was generated by combining frame difference and volume local phase quantization. Finally, a comparative experiment of HEMEW between non-pregnant and pregnant patients, logistic regression analysis for HEMEW and other independent clinical characteristics, and receiver operating characteristic (ROC) analysis were performed. RESULTS: The magnified uterine video clearly exhibited UMP, which was invisible in the original ultrasound video. Further, there existed a significant difference in HEMEW between pregnant patients and non-pregnant patients after micro-motion magnification (p = 0.003, n = 51). The logistic regression result showed that HEMEW (p = 0.006) was significantly associated with clinical pregnancy outcome, while other independent variables had no significant effect on it. The ROC performance of HEMEW was 72.6% accuracy (AUC = 0.774, 95% CI: 0.644-0.905). CONCLUSIONS: The proposed micro-motion magnification and characterization strategy identified the existences of uterine micro-peristalsis, and verified that UMP has the feasibility to distinguish the outcomes of IVF-ET.
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Transferência Embrionária , Fertilização in vitro , Ultrassonografia/métodos , Útero/diagnóstico por imagem , Adulto , Transferência Embrionária/métodos , Entropia , Feminino , Fertilização in vitro/métodos , Humanos , Peristaltismo/fisiologia , Gravidez , Útero/fisiologiaRESUMO
Huntington's disease (HD) is a progressive neurological disorder whose non-motor symptoms include sleep disturbances. Whether sleep and activity abnormalities are primary molecular disruptions of mutant Huntingtin (mutHtt) expression or result from neurodegeneration is unclear. Here, we report Drosophila models of HD exhibit sleep and activity disruptions very early in adulthood, as soon as sleep patterns have developed. Pan-neuronal expression of full-length or N-terminally truncated mutHtt recapitulates sleep phenotypes of HD patients: impaired sleep initiation, fragmented and diminished sleep, and nighttime hyperactivity. Sleep deprivation of HD model flies results in exacerbated sleep deficits, indicating that homeostatic regulation of sleep is impaired. Elevated PKA/CREB activity in healthy flies produces patterns of sleep and activity similar to those in our HD models. We were curious whether aberrations in PKA/CREB signaling were responsible for our early-onset sleep/activity phenotypes. Decreasing signaling through the cAMP/PKA pathway suppresses mutHtt-induced developmental lethality. Genetically reducing PKA abolishes sleep/activity deficits in HD model flies, restores the homeostatic response and extends median lifespan. In vivo reporters, however, show dCREB2 activity is unchanged, or decreased when sleep/activity patterns are abnormal, suggesting dissociation of PKA and dCREB2 occurs early in pathogenesis. Collectively, our data suggest that sleep defects may reflect a primary pathological process in HD, and that measurements of sleep and cAMP/PKA could be prodromal indicators of disease, and serve as therapeutic targets for intervention.