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Chiroptical activities arising in nanoclusters (NCs) are emerging as one of the most dynamic areas of modern science. However, devising an overarching strategy that is capable of concurrently enhancing the photoluminescence (PL) and circularly polarized luminescence (CPL) of metal NCs remains a formidable challenge. Herein, gold and silver nanoclusters (AuNCs, AgNCs) are endowed with CPL, for the first time, through a universal host-guest approachâcentered around perturbing a chiral microenvironment within chiral hosts, simultaneously enhancing emissions. Remarkably, the photoluminescence quantum yield (PLQY) of AuNCs has undergone an increase of over 200 times upon confinement, escalating from 0.05% to 12%, and demonstrates a CPL response. Moreover, a three-dimensional (3D) model termed "NCs@CMOF" featuring CPL activity is created using metal cluster-based assembly inks through the process of 3D printing. This work introduces a potentially straightforward and versatile approach for achieving both PL enhancement and CPL activities in metal clusters.
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Atom-precise metal nanoclusters (NCs) with large bulk (nuclearity >60) are important species for insight into the embryonic phase of metal nanoparticles and their top-down etching synthesis. Herein, we report a metastable rod-shaped 70-nuclei copper-hydride NC, [Cl@Cu70H22(PhC≡C)29(CF3COO)16]2+ (Cu70), with Cl- as the template, in which the Cl@Cu59 kernel adopts a distinctive metal packing mode along the bipolar direction, and the protective ligand shell exhibits corresponding site differentiation. In terms of metal nuclearity, Cu70 is the largest alkynyl-stabilized Cu-hydride cluster to date. As a typical highly active intermediate, Cu70 could undergo a transformation into a series of robust modularly assembled Cu clusters (B-type Cu8, A-A-type Cu22, A-B-type Cu23, and A-B-A-type Cu38) upon etching by p-tert-butylthiacalix[4]arene (H4TC4A), which could not be achieved by "one-pot" synthetic methods. Notably, the patterns of A and B blocks in the Cu NCs could be effectively modulated by employing appropriate counterions and blockers, and the modular assembly mechanism was illustrated through comprehensive solution chemistry analysis using HR-ESI-MS. Furthermore, catalytic investigations reveal that Cu38 could serve as a highly efficient catalyst for the cycloaddition of propargylic amines with CO2 under mild conditions. This work not only enriched the family of high-nuclear copper-hydride NCs but also provided new insights into the growth mechanism of metal NCs.
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BACKGROUND: Acute aortic syndrome (AAS) is a life-threatening condition. Inflammation plays a key role in the pathogenesis, development and progression of AAS, and is associated with significant mortality and morbidity. Understanding the inflammatory responses and inflammation resolutions is essential for an appropriate management of AAS. METHOD: Thirty Chinese cardiovascular centers have collaborated to create a multicenter observational registry (named Chinese Additive Anti-inflammatory Action for Aortopathy & Arteriopathy [5A] registry), with consecutive enrollment of adult patients who underwent surgery for AAS that was started on Jan 1, 2016 and will be ended on December 31, 2040. Specially, the impact of inflammation and anti-inflammatory strategies on the early and late adverse events are investigated. Primary outcomes are severe systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), Sequential Organ Failure Assessment (SOFA) scores at 7 days following this current surgery. Secondary outcomes are SISR, 30-day mortality, operative mortality, hospital mortality, new-onset stroke, acute kidney injury, surgical site infection, reoperation for bleeding, blood transfusion and length of stay in the intensive care unit. DISCUSSION: The analysis of this multicenter registry will allow our better knowledge of the prognostic importance of preoperative inflammation and different anti-inflammatory strategies in adverse events after surgery for AAS. This registry is expected to provide insights into novel different inflammatory resolutions in management of AAS beyond conventional surgical repair. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04398992 (Initial Release: 05/19/2020).
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Unidades de Cuidados Intensivos , Enfermedades Vasculares , Adulto , Humanos , Antiinflamatorios , China , Inflamación , Estudios Multicéntricos como Asunto , Sistema de Registros , Estudios Observacionales como AsuntoRESUMEN
The dual emission (DE) characteristics of atomically precise copper nanoclusters (Cu NCs) are of significant theoretical and practical interest. Despite this, the underlying mechanism driving DE in Cu NCs remains elusive, primarily due to the complexities of excited state processes. Herein, a novel [Cu4(PPh3)4(C≡C-p-NH2C6H4)3]PF6 (Cu4) NC, shielded by alkynyl and exhibiting DE, was synthesized. Hydrostatic pressure was applied to Cu4, for the first time, to investigate the mechanism of DE. With increasing pressure, the higher-energy emission peak of Cu4 gradually disappeared, leaving the lower-energy emission peak as the dominant emission. Additionally, the Cu4 crystal exhibited notable piezochromism transitioning from cyan to orange. Angle-dispersive synchrotron X-ray diffraction results revealed that the reduced inter-cluster distances under pressure brought the peripheral ligands closer, leading to the formation of new C-Hâ â â N and N-Hâ â â N hydrogen bonds in Cu4. It is proposed that these strengthened hydrogen bond interactions limit the ligands' vibration, resulting in the vanishing of the higher-energy peak. In situ high-pressure Raman and vibrationally resolved emission spectra demonstrated that the benzene ring C=C stretching vibration is the structural source of the DE in Cu4.
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Objective To explore the preliminary application of single-cell RNA sequencing (scRNA-seq) in the renal arterial lesions in Takayasu arteritis (TA) patients. Methods This study included 2 TA patients with renal artery stenosis treated by bypass surgery in the Department of Vascular Surgery,Beijing Hospital.The obtained 2 renal artery samples were digested with two different protocols (GEXSCOPE kit and self-made digestion liquid) before scRNA-seq and bioinformatics analysis. Results A total of 2920 cells were obtained for further analysis.After unbiased cluster analysis,2 endothelial cell subsets,2 smooth muscle cell subsets,1 fibroblast subset,2 mononuclear macrophage subsets,1 T cell subset,and 1 undefined cell subset were identified.Among them,the two subsets of smooth muscle cells were contractile and secretory,respectively.The results of scRNA-seq indicated that enzymatic hydrolysis with GEXSCOPE kit produced a large number of endothelial cells (57.46%) and a small number of immune cells (13.21%).However,immune cells (34.64%) were dominant in the cells obtained by enzymatic hydrolysis with self-made digestive liquid. Conclusion scRNA-seq can be employed to explore the cellular heterogeneity of diseased vessels in TA patients.Different enzymatic digestion protocols may impact the proportion of different cells.
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Arteritis de Takayasu , Humanos , Células Endoteliales , Transcriptoma , Biología Computacional , FibroblastosRESUMEN
Stimuli-responsive circularly polarized luminescence (CPL) materials are ideal for information anti-countering applications, but the best-performing materials have not yet been identified. This work presents enantiomorphic hybrid antimony halides R-(C5 H12 NO)2 SbCl5 (1) and S-(C5 H12 NO)2 SbCl5 (2) showing mirror-imaged CPL activity with a dissymmetry factor of 1.2×10-3 . Interestingly, the DMF-induced structural transformation is realized to obtain non-emissive R-(C5 H12 NO)2 SbCl5 â DMF (3) and S-(C5 H12 NO)2 SbCl5 â DMF (4) upon exposure to DMF vapor. The transformation process is reversed upon heating. DFT calculations showed that the DMF-induced-quenched-luminescence is attributed to the intersection of the ground and excited state curves on the configuration coordinates. Unexpectedly, the nanocrystals of the chiral antimony halides 1 and 2 were prepared and indicate the excellent solution process performance. The reversible PL and CPL switching gives the system applications in information technology, anti-counterfeiting, encryption-decryption, and logic gates.
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Stable stimulus-responsive materials are highly desirable due to their widespread potential applications and growing demand in recent decades. Despite the fact that viologen derivatives have long been known as excellent photochromic and electrochromic materials, the development of stable viologen-based multifunctional smart materials with short coloration times remains an exciting topic. To obtain photochromic and electrochromic dual responsive materials, embedding the viologen ligand into a robust metal oxide cluster to increase its stability and sensitivity is an effective strategy. Herein, a viologen-based metal-organic polyhedron (MOP) {[Zr6L3(µ3-O)2(µ2-OH)6Cp6]·8Cl·CH3OH·DMF} [Zr-MOP-1; H2L·2Cl = 1,1'-bis(4-carboxyphenyl)-4,4'-bipyridinium dichloride, and Cp = η5-C5H5] was successfully prepared and characterized. It consists of trinuclear Zr-oxygen secondary building units and exhibits reversible photochromic and electrochromic dual responsive behaviors. As expected, the designed robust viologen-based nanocage with a V2E3 (V = vertex, and E = edge) topology can maintain its stability and rapid photo/electrochromic behaviors with an obvious reversible change in color from purple (brown) to green, mainly due to the enclosed cluster structure and the abundant free viologen radicals that originate from the effective Cl â N and O â N electron transfers. Spectroelectrochemistry and theoretical calculations of this Zr-MOP were also performed to verify the chromic mechanism.
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Axillary osmidrosis (AO) and primary hyperhidrosis (PH) are common diseases, but there are still difficulties in treatment. Microwave therapy may become a new method. In order to evaluate long-time efficacy of patients with AO or PH treated by microwave and to discuss possible mechanism of microwave therapy by combining results of clinical and pathological, the study was carried out. Ten AO or PH patients with moderate or severe level were selected as subjects, and each subject received microwave treatment of bilateral armpits. The follow-up period lasted 2 years, and the changes of perspiration and odor were evaluated in subjective and objective ways. Each subject took skin biopsy in the treatment area before and after treatment or each follow-up. Hematoxylin-eosin and immunohistochemical staining were performed. Both subjective and objective index reflected the significant improvement of AO and PH after treatment (p < 0.05). Dermatology life quality index score decreased by 10.4 ± 4.6 (p < 0.05). The number of apocrine glands decreased significantly after treatment, and most of them changed from secretory phase to quiescent phase. In conclusion, microwave therapy can destroy apocrine sweat glands, reduce number of functional glands, so as to improve symptoms of AO and PH and elevate quality of life, which is safe, effective, and stable.
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Hiperhidrosis , Microondas , Axila/patología , Humanos , Hiperhidrosis/diagnóstico , Hiperhidrosis/radioterapia , Microondas/efectos adversos , Calidad de Vida , Resultado del TratamientoRESUMEN
OBJECTIVES: To investigate the necessity of cone-beam computed tomography (CBCT) in adrenal venous sampling (AVS). METHODS: This retrospective study included 120 consecutive patients with primary hyperaldosteronism who underwent AVS. Based on the learning curve of the interventional radiologists, the patients were divided into the learning (n = 36) and proficiency (n = 84) groups chronologically. Based on the imaging pattern of the right adrenal vein (RAV), the patients were divided into the typical (n = 36) and atypical (n = 84) groups. The success rate, radiation dose, and sampling time were compared among the entire study population and each subgroup. RESULTS: A total of 69 patients underwent CBCT, whereas 51 patients did not. The overall success rate was 85.8%, and no difference was noted between patients with and without CBCT (P = 0.347). However, radiation dose (P = 0.018) and sampling time (P = 0.001) were significantly higher in patients who underwent CBCT than in patients who did not. In learning group, CBCT improved success rate from 62.5 to 96.4% (P = 0.028), whereas it was not found in the proficiency group (P = 0.693). Additionally, success rate in patients with an atypical RAV imaging pattern was significantly higher when CBCT was used than when it was not used (P = 0.041), whereas no difference was noted in patients with typical RAV imaging pattern (P = 0.511). CONCLUSION: For physicians not very experienced doing AVS, there is a clear significant improvement in success rate when CBCT is used. However, CBCT only has minimal benefit for experienced operators, meanwhile CBCT may take an extra time and increase the radiation dose during AVS.
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Hiperaldosteronismo , Humanos , Hiperaldosteronismo/diagnóstico por imagen , Estudios Retrospectivos , Cateterismo/métodos , Glándulas Suprarrenales/diagnóstico por imagen , Glándulas Suprarrenales/irrigación sanguínea , Tomografía Computarizada de Haz CónicoRESUMEN
BACKGROUND: The renal artery is often involved in aortic dissection, leading to kidney ischaemia and renal dysfunction. However, some patients with aortic dissection with combined renal artery involvement do not show clinical renal dysfunction. This study aimed to analyse the relationship between renal artery involvement and renal function. METHODS: Data and images were collected from 79 patients (Group A), in Beijing Anzhen hospital between January 2015 and December 2017, who had type A aortic dissection, in order to analyse the relationship between renal artery involvement and serum creatinine. In order to further analyse the relationship between renal artery involvement and single kidney function, data from 27 patients (Group B) with aortic dissection from August 2018 to October 2018 were collected. Renal dynamic imaging was conducted, and clinical and image data were recorded. RESULTS: Results showed that patients with one partially occluded renal artery had higher variance of serum creatinine after surgery compared with patients with one false-lumen renal artery (5.8±22.7 µmol/L vs -18.7±22.7 µmol/L; p=0.003). The glomerular filtration rate of a single kidney that had a partially occluded renal artery was lower than that of a single kidney with a normal renal artery (37.77±9.57 vs 42.73±10.54; p=0.04). CONCLUSIONS: A partially occluded renal artery in aortic dissection was associated with impaired renal function after surgery, even though patients did not present high serum creatinine. More attention should be paid to those experiencing aortic dissection.
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Disección Aórtica , Enfermedades Renales , Enfermedad Arterial Periférica , Riñón Único , Disección Aórtica/complicaciones , Disección Aórtica/diagnóstico , Creatinina , Femenino , Humanos , Riñón , Masculino , Arteria Renal/diagnóstico por imagen , Estudios Retrospectivos , Riñón Único/complicaciones , Resultado del TratamientoRESUMEN
In this study, 280 batches of Zingiberis Rhizoma samples from nine producing areas were analyzed to obtain infrared spectral information based on near-infrared spectroscopy(NIRS). Pluralistic chemometrics such as principal component analysis(PCA), partial least squares-discriminant analysis(PLS-DA), orthogonal partial least squares-discriminant analysis(OPLS-DA), K-nearest neighbors(KNN), support vector machine(SVM), random forest(RF), artificial neural network(ANN), and gradient boosting(GB) were applied for tracing of origins. The results showed that the discriminative accuracy of the spectral preprocessing by standard normal variate transformation coupled with the first derivative was 93.9%, which could be used for the construction of the discrimination model. PCA and PLS-DA score plots showed that samples from Shandong, Sichuan, Yunnan, and Guizhou could be effectively distinguished, but the remaining samples were partially overlapped. As revealed by the analysis results by machine learning algorithms, the AUC values of KNN, SVM, RF, ANN, and GB algorithms were 0.96, 0.99, 0.99, 0.99, and 0.98, respectively, with overall prediction accuracies of 83.3%, 89.3%, 90.5%, 91.7%, and 89.3%. It indicated that the developed model was reliable and the machine learning algorithm combined with NIRS for origin identification was sufficiently feasible. OPLS-DA showed that Zingiberis Rhizoma from Sichuan(genuine producing areas) could be significantly distinguished from other regions, with good discriminative accuracy, suggesting that the NIRS established in this study combined with chemometrics can be used for the identification of Zingiberis Rhizoma from Sichuan. This study established a rapid and nondestructive identification and reliable data analysis method for origin identification of Zingiberis Rhizoma, which is expected to provide a new idea for the origin tracing of Chinese medicinal materials.
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Quimiometría , Máquina de Vectores de Soporte , Algoritmos , China , Zingiber officinale , Análisis de los Mínimos Cuadrados , Extractos Vegetales , Análisis de Componente PrincipalRESUMEN
In order to evaluate the composition and distribution characteristics of inorganic elements in Laminaria japonica, this study employed inductively coupled plasma mass spectrometry(ICP-MS) to detect the inorganic elements and used high performance liquid chromatography tandem ICP-MS(HPLC-ICP-MS) to determine the content of different arsenic species in L. japonica from diffe-rent origins. Micro X-ray fluorescence(Micro-XRF) was used to determine micro-area distribution of inorganic elements in L. japonica. The results showed that the average content of Mn, Fe, Sr, and Al was high, and that of As and Cr exceeded the limits of the national food safety standard. According to the results of HPLC-ICP-MS, arsenobetaine(AsB) was the main species of As contained in L. japonica. The more toxic inorganic arsenic accounts for a small proportion, whereas its content was 1-4 times of the limit in the national food safety standard. The results of Micro-XRF showed that As, Pb, Fe, Cu, Mn, and Ni were mainly distributed on the surface of L. japonica. Among them, As and Pb had a clear tendency to diffuse from the surface to the inside. The results of the study can provide a basis for the processing as well as the medicinal and edible safety evaluation of L. japonica.
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Arsénico , Laminaria , Oligoelementos , Arsénico/análisis , Cromatografía Líquida de Alta Presión/métodos , Espectrometría de Masas/métodos , Análisis Espectral , Oligoelementos/análisisRESUMEN
Developing efficient sensor materials with superior performance for selective, fast and sensitive detection of gases and volatile organic compounds (VOCs) is essential for human health and environmental protection, through monitoring indoor and outdoor air pollutions, managing industrial processes, controlling food quality and assisting early diagnosis of diseases. Metal-organic frameworks (MOFs) are a unique type of crystalline and porous solid material constructed from metal nodes (metal ions or clusters) and functional organic ligands. They have been investigated extensively for possible use as high performance sensors for the detection of many different gases and VOCs in recent years, due to their large surface area, tunable pore size, functionalizable sites and intriguing properties, such as electrical conductivity, magnetism, ferroelectricity, luminescence and chromism. The high porosity of MOFs allows them to interact strongly with various analytes, including gases and VOCs, thus resulting in easily measurable responses to different physicochemical parameters. Although much of the recent work on MOF-based luminescent sensors have been summarized in several excellent reviews (up to 2018), a comprehensive overview of these materials for sensing gases and VOCs based on chemiresistive, magnetic, ferroelectric, and colorimertic mechanisms is missing. In this review, we highlight the most recent progress in developing MOF sensing and switching materials with an emphasis on sensing mechanisms based on electricity, magnetism, ferroelectricity and chromism. We provide a comprehensive analysis on the MOF-analyte interactions in these processes, which play a key role in the sensing performance of the MOF-based sensors and switches. We discuss in detail possible applications of MOF-based sensing and switching materials in detecting oxygen, water vapor, toxic industrial gases (such as hydrogen sulfide, ammonia, sulfur dioxide, nitrous oxide, carbon oxides and carbon disulfide) and VOCs (such as aromatic and aliphatic hydrocarbons, ketones, alcohols, aldehydes, chlorinated hydrocarbons and N,N'-dimethylformamide). Overall, this review serves as a timely source of information and provides insight for the future development of advanced MOF materials as next-generation gas and VOC sensors.
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Atomically precise enantiomeric metal clusters are scarce, and copper(I) alkynyl clusters with intense circularly polarized luminescence (CPL) responses have not been reported. A pair of chiral alkynyl ligands, (R/S)-2-diphenyl-2-hydroxylmethylpyrrolidine-1-propyne (abbreviated as R/S-DPM) we successfully prepared and single crystals were characterized of optically pure enantiomeric pair of atomically-precise copper(I) clusters, [Cu14 (R/S-DPM)8 ](PF6 )6 (denoted as R/S-Cu14 ), which feature bright red luminescence and CPL with a high luminescence anisotropy factor (glum ). A dilute solution containing R/S-Cu14 was nonluminescent and CPL inactive at room temperature. Crystallization- and aggregation-induced emission (CIE and AIE, respectively) contribute to the triggering of the CPL of R/S-Cu14 in the crystalline and aggregated states. Their AIE behavior and good biocompatibility indicated applications of these copper(I) clusters in cell imaging in HeLa and NG108-15 cells.
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The pine wood nematode (PWN) Bursaphelenchus xylophilus has caused serious damage to pine forests in China. Effectors secreted by phytonematodes play a role in host infection. We identified and characterized an effector, BxSapB1, based on the B. xylophilus transcriptome at the early stages of infection and the transient expression of proteins in Nicotiana benthamiana. BxSapB1 triggered cell death in N. benthamiana when secreted into the apoplast, and this effect was independent of N. benthamiana brassinosteroid-insensitive 1-associated kinase 1 (NbBAK1) and suppressor of BIR1-1 (NbSOBIR1). The signal peptide of BxSapB1 was proven to be functional in yeast using the yeast signal sequence trap system and BxSapB1 was strongly expressed in the subventral gland cells of B. xylophilus, as revealed by in-situ hybridization. In addition, based on local BLAST analysis, the BxSapB1 showed 100% identity to BUX.s00139.62, which was identified from the B. xylophilus secretome during Pinus thunbergii infection. BxSapB1 was upregulated in a highly virulent strain and downregulated in a weakly virulent strain of PWN at the early stages of infection. RNA interference assays showed that silencing BxSapB1 resulted in decreased expression of pathogenesis-related genes (PtPR-1b, PtPR-3, and PtPR-5) as well as delayed onset of symptoms in P. thunbergii infected by B. xylophilus. The combined data suggest that BxSapB1 can trigger cell death in N. benthamiana and that it contributes to the virulence in B. xylophilus during parasitic interaction.
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Pinus , Tylenchida , Virulencia , Animales , Muerte Celular , China , Pinus/parasitología , Tylenchida/genética , Tylenchida/patogenicidad , Virulencia/genéticaRESUMEN
Plant pathogens employ diverse secreted effector proteins to manipulate host physiology and defense in order to foster diseases. The destructive Phytophthora pathogens encode hundreds of cytoplasmic effectors, which are believed to function inside the plant cells. Many of these cytoplasmic effectors contain the conserved N-terminal RXLR motif. Understanding the virulence function of RXLR effectors will provide important knowledge of Phytophthora pathogenesis. Here, we report the characterization of RXLR effector PcAvh1 from the broad-host range pathogen Phytophthora capsici. Only expressed during infection, PcAvh1 is quickly induced at the early infection stages. CRISPR/Cas9-knockout of PcAvh1 in P. capsici severely impairs virulence while overexpression enhances disease development in Nicotiana benthamiana and bell pepper, demonstrating that PcAvh1 is an essential virulence factor. Ectopic expression of PcAvh1 induces cell death in N. benthamiana, tomato, and bell pepper. Using yeast two-hybrid screening, we found that PcAvh1 interacts with the scaffolding subunit of the protein phosphatase 2A (PP2Aa) in plant cells. Virus-induced gene silencing of PP2Aa in N. benthamiana attenuates resistance to P. capsici and results in dwarfism, suggesting that PP2Aa regulates plant immunity and growth. Collectively, these results suggest that PcAvh1 contributes to P. capsici infection, probably through its interaction with host PP2Aa.
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Phytophthora , Enfermedades de las Plantas , Proteínas Protozoarias , Virulencia , Secuencias de Aminoácidos , Capsicum/parasitología , Phytophthora/genética , Phytophthora/patogenicidad , Enfermedades de las Plantas/parasitología , Inmunidad de la Planta , Proteínas Protozoarias/genética , Proteínas Protozoarias/metabolismo , Nicotiana/parasitología , Virulencia/genéticaRESUMEN
Chiral assembly and asymmetric synthesis are critically important for the generation of chiral metal clusters with chiroptical activities. Here, a racemic mixture of [K(CH3 OH)2 (18-crown-6)]+ [Cu5 (St Bu)6 ]- (1â CH3 OH) in the chiral space group was prepared, in which the chiral red-emissive anionic [Cu5 (St Bu)6 ]- cluster was arranged along a twofold screw axis. Interestingly, the release of the coordinated CH3 OH of the cationic units turned the chiral 1â CH3 OH crystal into a mesomeric crystal [K(18-crown-6)]+ [Cu5 (St Bu)6 ]- (1), which has a centrosymmetric space group, by adding symmetry elements of glide and mirror planes through both disordered [Cu5 (St Bu)6 ]- units. The switchable chiral/achiral rearrangement of [Cu5 (St Bu)6 ]- clusters along with the capture/release of CH3 OH were concomitant with an intense increase/decrease in luminescence. We also used cationic chiral amino alcohols to induce the chiral assembly of a pair of enantiomers, [d/l-valinol(18-crown-6)]+ [Cu5 (St Bu)6 ]- (d/l-Cu5V ), which display impressive circularly polarized luminescence (CPL) in contrast to the CPL-silent racemic mixture of 1â CH3 OH and mesomeric 1.
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BACKGROUND This study aimed to identify the relationship between miR-125a polymorphism rs12976445 and the post-ablation recurrence of atrial fibrillation (AF), as well as to explore the underlying mechanism of miR-125a in AF recurrence. MATERIAL AND METHODS Microarray analysis was performed to search for miRNAs potentially involved in the regulation of AF recurrence, while real-time PCR (polymerase chain reaction) and Western blot analyses were carried out to study the expression of miR-125a (microRNA-125a), IL-6R (interleukin-6 receptor), and IL-16 (interleukin-16) in different experimental groups, so as to understand the regulatory relationships among miR-125a, IL-6R, and IL-16. Subsequently, a logistic regression analysis was utilized to investigate the survival status of recurrent AF in subjects harboring different genotypes of rs12976445. RESULTS The subjects in the GG and GC/CC groups of miR-125a polymorphism rs12976445 showed no obvious difference regarding all demographic characteristics that were collected in this study. In addition, 19 miRNAs were identified as potentially involved in the regulation of AF recurrence. Among these miRNAs, 6 were upregulated and 13 were downregulated in the group with early recurrence. According to real-time PCR results, the expression of miR-125a was dramatically upregulated in LRAF (late recurrence of atrial fibrillation) as well as in subjects harboring the GG genotype. On the contrary, the level of IL-6R mRNA was dramatically downregulated in LRAF and subjects harboring the GG genotype. Furthermore, IL-6R was confirmed as a candidate target of miR-125a by a luciferase reporter assay. CONCLUSIONS MicroRNA-125a polymorphism rs12976445 plays a role in AF recurrence via the regulation of IL-6R.
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Fibrilación Atrial/genética , MicroARNs/genética , Receptores de Interleucina-6/genética , Anciano , Fibrilación Atrial/metabolismo , Fibrilación Atrial/patología , Femenino , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Masculino , MicroARNs/biosíntesis , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , ARN Mensajero/genética , Receptores de Interleucina-6/biosíntesis , Receptores de Interleucina-6/metabolismo , RecurrenciaRESUMEN
Neuroblastoma, featured by a high rate of spontaneous remissions, is the most common extra-cranial solid tumor in infants and children. Numerous reports have demonstrated that MicroRNAs (miRNAs) play essential roles in cancer progression, including cell proliferation, apoptosis, invasion, metastasis and angiogenesis. miR-421 functions as an onco-miR in some malignancies. However, its role in neuroblastoma remains poorly understood. In the present study, we found that miR-421 was increased in neuroblastoma tissues compared with matched adjacent normal tissues. Forced overexpression of miR-421 substantially enhanced cell proliferation, cell-cycle progression, migration, and invasion of neuroblastoma cells. At the molecular level, tumor suppressor menin was found to be a target of miR-421. Furthermore, downregulation of menin by small interfering RNA oligos exhibited similar effects with overexpression of miR-421. On the other hand, overexpression of menin partially reversed the proliferative effects of miR-421 in neuroblastoma cells. Collectively, miR-421 may promote neuroblastoma cell growth and motility partially by targeting menin.
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Regulación Neoplásica de la Expresión Génica/fisiología , MicroARNs/metabolismo , Neuroblastoma/patología , Proteínas Proto-Oncogénicas/biosíntesis , Western Blotting , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Regulación hacia Abajo , Humanos , MicroARNs/genética , Invasividad Neoplásica/genética , Neuroblastoma/genética , ARN Interferente Pequeño , Reacción en Cadena en Tiempo Real de la Polimerasa , TransfecciónRESUMEN
Background: Numerous observational studies have presented an association between Vitamin D (VD) and Alcoholic Liver Disease (ALD). However, sufficient evidence from Randomized Controlled Trials (RCTs) substantiating this correlation is scarce, thus leaving the causality of this relationship ambiguous. To overcome the shortcomings of traditional observational studies, we performed a two-sample bidirectional Mendelian randomization (MR) analysis to ascertain the causal relationship between VD and ALD. Methods: We utilized summary statistics datasets from Genome-Wide Association Studies (GWAS) for VD and ALD. We selected genetic instruments that measure circulating VD levels (n = 64,979), and retrieved ALD statistics from GWASs, inclusive of 1,416 cases and 217,376 healthy controls, while excluding chronic liver diseases such as nonalcoholic fatty liver disease, toxic liver disease, and viral hepatitis. Subsequent, MR analyses were performed to obtain effect estimates using inverse variance weighted (IVW) random effect models. Cochran's Q statistic and MR-Egger regression intercept analyses were used to assess pleiotropy. Sensitivity analyses using the MR Egger, weighted median, simple mode, and weighted mode methods were also performed. Leave-one-out analysis was used to identify SNPs with potential effect. Reverse MR analysis was also performed. Results: In IVW, our MR analysis incorporated 21 independent SNPs, circulating VD levels had no causal effect on ALD [OR = 0.624 (0.336-1.160), p = 0.136] and ALD had no causal effect on circulating VD [OR = 0.997 (0.986-1.008), p = 0.555]. No heterogeneity or pleiotropy was observed (p > 0.05). Other MR methods also agreed with IVW results. Conclusion: This study provides the causal relationship between genetically predicted circulating Vitamin D levels and ALD and provides new insights into the genetics of ALD.