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Endometrial cancer (EC) is a frequently diagnosed gynecologic cancer. Identifying reliable prognostic genes for predicting EC onset is crucial for reducing patient morbidity and mortality. Here, a comprehensive strategy with transcriptomic and proteomic data was performed to measure EC's characteristics. Based on the publicly available RNA-seq data, death-associated protein kinase 3, recombination signal-binding protein for the immunoglobulin kappa J region, and myosin light chain 9 were screened out as potential biomarkers that affect the EC patients' prognosis. A linear model was further constructed by multivariate Cox regression for the prediction of the risk of being malignant. From further integrative analysis, exosomes were found to have a highly enriched role that might participate in EC occurrence. The findings were validated by qRT-polymerase chain reaction (PCR) and western blotting. Collectively, we constructed a prognostic-gene-based model for EC prediction and found that exosomes participate in EC incidents, revealing significantly promising support for the diagnosis of EC.
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Kidney stone disease (KSD, also named renal calculi, nephrolithiasis, or urolithiasis) is a common urological disease entailing the formation of minerals and salts that form inside the urinary tract, frequently caused by diabetes, high blood pressure, hypertension, and monogenetic components in most patients. 10% of adults worldwide are affected by KSD, which continues to be highly prevalent and with increasing incidence. For the identification of novel therapeutic targets in KSD, we adopted high-throughput sequencing and mass spectrometry (MS) techniques in this study and carried out an integrative analysis of exosome proteomic data and DNA methylation data from blood samples of normal and KSD individuals. Our research delineated the profiling of exosomal proteins and DNA methylation in both healthy individuals and those afflicted with KSD, finding that the overexpressed proteins and the demethylated genes in KSD samples are associated with immune responses. The consistency of the results in proteomics and epigenetics supports the feasibility of the comprehensive strategy. Our insights into the molecular landscape of KSD pave the way for a deeper understanding of its pathogenic mechanism, providing an opportunity for more precise diagnosis and targeted treatment strategies for KSD.
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Metilación de ADN , Cálculos Renales , Proteómica , Humanos , Cálculos Renales/genética , Cálculos Renales/metabolismo , Proteómica/métodos , Metilación de ADN/genética , Exosomas/metabolismo , Exosomas/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Masculino , Femenino , Adulto , Epigénesis Genética , Persona de Mediana Edad , MultiómicaRESUMEN
Chemical labeling methods for proteins are highly researched. Herein, we introduced ß-carbonyl sulfonium compounds for selective cysteine modification in proteins within biological systems. Structural tuning led to sulfonium-based probes with high reactivity and selectivity. These probes show excellent biocompatibility, cell uptake, and specificity towards cysteine profiling in live cells.
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Cisteína , Compuestos de Sulfonio , Cisteína/química , Proteínas/química , Compuestos de Sulfonio/químicaRESUMEN
The structure of organic ligand scaffolds of copper complexes critically affects their electrocatalytic properties toward water oxidation, which is widely regarded as the bottleneck of overall water splitting. Herein, two novel mononuclear Cu complexes, [Cu(dmabpy)](ClO4)2 (1, dmabpy = 6,6'-bis(dimethylaminomethyl)-2,2'-bipyridine) and [Cu(mabpy)](ClO4)2 (2, mabpy = 6,6'-bis(methylaminomethyl)-2,2'-bipyridine), with four-coordinated distorted planar quadrilateral geometry were synthesized and explored as efficient catalysts for electrochemical oxygen evolution in phosphate buffer solution. Interestingly, complex 1 with a tertiary amine group catalyzes water oxidation with lower onset overpotential and better catalytic performance, while complex 2 containing a secondary amine fragment displays much lower catalytic activity under identical conditions. The water oxidation catalytic mechanism of the two complexes is proposed based on the electrochemical test results. Experimental methods indicate that phosphate coordinated on the Cu center of the two complexes inhibits their reaction with substrate water molecules, resulting in lower activity toward water oxidation. Electrochemical tests reveal that the structure of the coordinated nitrogen atom improves the catalytic performance of the Cu complexes by modulating the coordination of phosphate on the Cu center, indicating that a minor alteration of the coordinating nitrogen atom of the ligand has a detrimental effect on the catalytic performance of electrochemical WOCs based on transition metal complexes.
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A dysprosium(III) metal-organic framework constructed using dysprosium(III) cubanes as secondary building units has been reported to exhibit field-induced slow magnetic relaxation behavior and an unprecedented ecu topology, which is the first example of an 8-connected Ln-cubane-based framework material and a rare Dy4-MOF showing slow magnetic relaxation.
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Proteolysis Targeting Chimera (PROTAC) technology represents a promising new approach for target protein degradation using a cellular ubiquitin-proteasome system. Recently, we developed a split-and-mix nanoplatform based on peptide self-assembly, which could serve as a self-adjustable platform for multifunctional applications. However, the lower drug efficacy limits further biomedical applications of peptide-based SM-PROTAC. In this study, we develop a novel split-and-mix PROTAC system based on liposome self-assembly (LipoSM-PROTAC), concurrent with modification of FA (folate) to enhance its tumor-targeting capabilities. Estrogen receptors (ERα) were chosen as the protein of interest (POI) to validate the efficacy of Lipo degraders. Results demonstrate that this PROTAC can be efficiently and selectively taken up into the cells by FA receptor-positive cells (FR+) and degrade the POI with significantly reduced concentration. Compared to the peptide-based SM-PROTACs, our designed LipoSM-PROTAC system could achieve therapeutic efficacy with a lower concentration and provide opportunities for clinical translational potential. Overall, the LipoSM-based platform shows a higher drug efficacy, which offers promising potential applications for PROTAC and other biomolecule regulations.
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Water oxidation is the bottleneck of water splitting, which is a promising strategy for hydrogen production. Therefore, it is significant to develop efficient water oxidation catalysts. Herein, electrochemical water oxidation catalyzed by three nickel complexes, namely [Ni(bptn)(H2O)](ClO4)2 (1), [Ni(mbptn)(CH3CN)](ClO4)2 (2), and [Ni(tmbptn)(H2O)](ClO4)2 (3) (bptn = 1,9-bis(2-pyridyl)-2,5,8-triazanonane, mbptn = 5-methyl-1,9-bis(2-pyridyl)-2,5,8-triazanonane, and tmbptn = 1,9-bis(2-pyridyl)-2,5,8-triazanonane), is studied under near-neutral condition (pH 9.0). Meanwhile, the homogeneous catalytic behaviors of the three mononuclear nickel complexes were investigated and confirmed by scanning electron microscopy, energy dispersive spectrometry, X-ray photoelectron spectroscopy and electrochemical method. Complex 1 stabilized by a pentadentate ligand with three N-H fragments homogeneously catalyzes water oxidation to oxygen with the lowest onset overpotential. Complex 2 stabilized by a similar ligand with two N-H groups and one N-CH3 group exhibits relatively higher onset overpotential but higher catalytic current and turnover frequency. However, complex 3 with three N-CH3 coordination environment shows the highest onset overpotential and the highest catalytic current at higher potential. Comparison of catalytic behaviors and ligand structure of the three complexes reveals that the methyl group on the polypyridine amine ligand affects the water oxidation activity of the complexes obviously. The electronic effect of N-CH3 coordination environment leads to higher redox potential of the metal center and potential demand for water oxidation, while it leads to higher reaction activity of high-valent intermediates, which account for higher catalytic current and efficiency of water oxidation. This work reveals that electrocatalytic water oxidation performance of nickel complexes can be finely modulated by constructing suitable N-CH3 coordination.
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Spin crossover (SCO) complexes have been extensively explored as bistable materials and recently used as molecular modules for the development of new multifunctional molecular magnetic materials. Herein, we present the synthesis, crystal structure, magnetic, and electrical properties of a mononuclear cobalt complex constructed by a halogen-functionalized terpyridine derivative and organosulfonate. A complete and gradual spin transition with the T1/2 =200â K was observed for the Co2+ ions through both the magnetic measurement and dynamic crystallographic experiments. Interestingly, considerable room temperature proton conductivity of 6.9×10-5 â S cm-1 under 98% relative humidity was evidenced because of the presence of sulfonate-assisted hydrogen-bonded proton hopping pathways. The forgoing results not only provide an unprecedented proton-conducting cobalt(II) SCO complex but also a promising way for the design and construction of bifunctional SCO molecular conductors via the incorporation of SCO transition and proton conduction.
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Iron ion is widely present in the environment and in biological systems, and are indispensable trace elements in living organisms, so development of an efficient and simple sensor for sensing Fe(III) ions has attracted much attention. Here, six heterometallic AE-Ln coordination polymers (CPs) [Ln2 (pda)4(Hnda)2Ca2(H2O)2]·MeOH (Ln = Eu (1), Tb (2); H2pda = 2,6-pyridinedicarboxylic acid, H2nda = 2,3-naphthalenedicarboxylic acid), [Ln (pda)2 (nda)AE2(HCOO)(H2O)] (AE = Sr, Ln = Eu (3), Tb (4); AE = Ba, Ln = Eu (5), Tb (6)) with two-dimensional (2D) layer structures were synthesized by hydrothermal method. All of them were characterized by elemental analysis, XRD, IR, TG, as well as single crystal X-ray diffraction. They all show infinite 2D network structure, where complexes 1 and 2 are triclinic with space group of P 1 ¯ , while 3-6 belong to the monoclinic system, space group P21/n . The solid-state fluorescence lifetimes of complexes 1, 3 and 5 are τobs1 = 1930.94, 2049.48 and 2,413.04 µs, respectively, and the quantum yields Ф total are 63.01, 60.61, 87.39%, respectively, which are higher than those of complexes 2, 4 and 6. Complexes 1-6 all exhibited efficient fluorescence quenching response to Fe3+ ions in water, and were not interfered by the following metal ions: Cu2+, Cd2+, Mg2+, Ni2+, Co2+, Ca2+, Ba2+, Sr2+, Li+, Na+, K+, Al3+, Fe2+, Pb2+, Cr3+, Mn2+ and Zn2+. The quenching coefficient K SV for complexes 1-6 is 1.41 × 105 M-1, 7.10 × 104 M-1, 1.70 × 105 M-1, 1.57 × 105 M-1, 9.37 × 104 M-1, 1.27 × 105 M-1, respectively. The fluorescence quenching mechanism of these complexes towards Fe3+ ions was also investigated. It is possible that the weak interaction formed between the complexes and the Fe3+ ions reduce the energy transfer from the ligand to the Ln3+ ion, producing the emission burst effect. This suggests that complexes 1-6 can be candidate for efficient luminescent sensor of Fe3+.
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The abuse of antibiotics has caused serious threat to human health, so it is of great significance to develop a simple and sensitive method for the detection of trace residues of antibiotics in the environment and food. Herein, a novel label-free fluorescent biosensing platform based on the fluorescence change of aptamers-capped zeolitic imidazolate framework-8 (ZIF-8) @ 2,2',2â³,2â´-((ethene-1,1,2,2-tetrayltetrakis (benzene-4,1-diyl)) tetrakis (oxy)) tetraacetic acid (TPE) through ATP-assisted competitive coordination reaction was designed for such an end. ZIF-8@TPE/Aptamer (Apt) emits strong fluorescence at 425 nm in HEPES buffer due to the aggregation induced luminescence properties of TPE molecules in confined state. Once kanamycin was added, the conformation of aptamer capped on the surface of ZIF-8@TPE changes because of the specific recognition of kanamycin with aptamer, leading to the collapse of ZIF-8 and release of TPE, accompanied with a dramatic decrease of fluorescence intensity. Under the optimal conditions, a good correlation was obtained between the fluorescence intensity of ZIF-8@TPE/Apt and the concentration of kanamycin ranging from 10 to 103 ng/mL with a detection limit of 7.3 ng/mL. The satisfactory analytical performance of the assay for kanamycin detection suggests good prospect for its application in food safety analysis.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Estructuras Metalorgánicas , Aptámeros de Nucleótidos/química , Humanos , Kanamicina/análisis , Kanamicina/química , Límite de DetecciónRESUMEN
The immobilization of lipase on solid supports provides a significant improvement to the stability and reusability of lipase. During immobilization, the restricted surface area and inferior separation capacity of matrix materials are crucial for obtaining high-quality immobilized lipase. Carbon nitride nanosheets (C3N4-NS) as a type of two-dimensional nanomaterial have attracted various attentions for their prominent 2D planar nanostructure, characteristic surface area, thermostability and biocompatibility. Herein, we report a rational design and fabrication of immobilized Candida rugosa lipase based on carbon nitride nanosheets (C3N4-NS) as the matrix. The synthetic C3N4-NS are characterized by transmission electron microscopy, Brunauer-Emmett-Teller gas sorptometry measurement, X-ray powder diffraction, Fourier transform infrared spectroscopy and thermogravimetric analysis. These results show that C3N4-NS possess an as-expected two-dimensional nanostructure with a large surface area of 74.374 m2 g-1. In addition, we chose glutaraldehyde-assisted covalent attachment to combine C3N4-NS and Candida rugosa lipase (CRL) via amino groups at the margins of C3N4-NS. The as-constructed immobilized lipase (C3N4-NS@CRL) exhibits satisfactory enzyme-loading (44.76 mg g-1), pH-flexibility, thermostability (after 180 min at 50 °C, 67% of the initial activity remained) and recyclability (after 10 runs, 72% of the initial activity remained). When compared with the free CRL, all experimental data indicate that C3N4-NS@CRL exhibited improved stability and enhanced practicability. To our knowledge, this is the first report of the application of carbon nitride nanosheets to enzyme immobilization.
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Silole derivatives, the first reported and famous AIEgens, are a series of Si-containing conjugated rings with the σ*-π* conjugation, and this unique electronic structure imparts them high electron affinity and fast electron mobility, but not ideal blue luminogens due to their relatively long conjugation length. By replacing the Si atom with the C one, six new AIEgens without the σ*-π* conjugation effect are successfully synthesized based on a tetraphenylcyclopentadiene core. In addition to the sky-blue emission (λEL = 492 nm) with Lmax , ηC,max , and ηP,max up to 24 096 cd m-2 , 6.80 cd A-1 , and 4.07 lm W-1 , respectively, the careful control of the conjugation degree by changing the linkage mode, results in the blue one (λEL = 440 nm) with relatively good performance (Lmax : 8721 cd m-2 and ηC,max : 3.40 cd A-1 ), indicating that the replacement of the Si atom by C one is an alternative design strategy to yield blue even deep-blue AIEgens with good device performance. Meanwhile, their reversible mechanochromic properties are realized with apparent fluorescence changes between deep-blue and green emissive colors, offering them additional promising applications in optoelectronic devices.
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By adding just a small amount of commercially available oxygen-containing molecules (OCMs), organometallic precursors could be easily converted to CNTs with high yield and high quality through the solid-state pyrolysis (SSP) process, although only nanospheres were obtained under the same conditions without the presence of OCMs, providing a convenient approach for the preparation of CNTs.
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A relay strategy has been proposed to design a new Hg(2+) chemodosimeter (TPE-S), by coupling Hg(2+)-promoted deprotection reaction with ketone-enol isomerization, realizing the multistage amplifying effect. Changes in both of color and fluorescence could occur immediately, and TPE-S displayed high selectivity for Hg(2+), other metal ions (Ag(+), Fe(3+), Cu(2+), Pb(2+), Co(2+), Cr(3+), Al(3+), Cd(2+), Mg(2+), Mn(2+), Ba(2+), Fe(2+), Ca(2+), Ni(2+), Zn(2+), Li(+), K(+) and Na(+)) gave nearly no disturbance to the sensing process. When fabricated as test strips similar to pH-indicator papers, immediate color change from colorless to purple could be visually observed by naked-eyes without the aid of any additional equipment, with the detection limit as low as 1 × 10(-7) M (Hg(2+) in aqueous solution). Due to its easy synthesis, high selectivity and sensitivity, combined with the portable test strips, TPE-S could be developed as a convenient and cost-effective tool for the detection of Hg(2+) in on-site inspections.