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TH1L (also known as NELF-C/D) is a member of the Negative Elongation Factor (NELF) complex, which is a metazoan-specific factor that regulates RNA Polymerase II (RNAPII) pausing and transcription elongation. However, the function and molecular mechanisms of TH1L in cancer progression are still largely unknown. In this study, we found that TH1L was highly expressed in colorectal cancer (CRC) tissues and the faeces of CRC patients. Overexpression of TH1L significantly enhanced the proliferation and migration of CRC cells, while its knockdown markedly suppressed these processes. In mechanism, RNA sequencing revealed that CCL20 was upregulated in TH1L-overexpressed CRC cells, leading to activation of the NF-κB signalling pathway. Rescue assays showed that knockdown of CCL20 could impair the tumour-promoting effects of THIL in CRC cells. Taken together, these results suggest that TH1L may play a vital role via the CCL20/NF-κB signalling pathway in CRC proliferation and migration and may serve as a potential target for diagnosis and therapy of CRC.
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Movimiento Celular , Proliferación Celular , Quimiocina CCL20 , Neoplasias Colorrectales , Regulación Neoplásica de la Expresión Génica , FN-kappa B , Transducción de Señal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Línea Celular Tumoral , Movimiento Celular/genética , Quimiocina CCL20/metabolismo , Quimiocina CCL20/genética , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , FN-kappa B/metabolismoRESUMEN
A CuH-catalyzed reductive coupling of nitroarenes with phosphine oxides is developed, which produces a series of phosphamides in moderate to excellent yields with good functional group tolerance. Gram-scale synthesis and late-stage modification of nitro-aromatic functional molecule niclosamide are also successfully conducted. The mechanism study shows that the nitro group is transformed after being reduced to nitroso and a nucleophilic addition procedure is involved during the reaction.
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An efficient method for the construction of C-P(V) and C-P(III) bonds via the iron-catalyzed phosphorylation of alcohols under ligand-free conditions is disclosed. This strategy represents a straightforward process to prepare a series of phosphine oxides and phosphine compounds in good to excellent yields from the readily available alcohols and P-H compounds. A plausible mechanism is also proposed. We anticipate that this mode of transforming simple alcohols would apply in chemical synthesis widely.
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A palladium-catalyzed decarbonylative annulation of 2-arylbenzoic acids with internal alkynes via C(sp2)-H activation has been developed. A series of phenanthrenes were produced in moderate to good yield with good functional group tolerance. The mechanism study indicated that the C(sp2)-H activation should be the rate-determining step during the reaction.
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The C-H amination and C-O alkenylation of aryl triflates was achieved through Pd/norbornene (NBE) cooperative catalysis. By this strategy, various ortho-alkenyl tertiary anilines including those bearing functional groups were produced in good to excellent yields. This reaction represents a new conversion model for phenoxides. It expands the scope of Catellani-type reactions and the application of phenoxides in organic synthesis.
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Autophagy is a cellular self-degrading process that plays a key role in cellular health and functioning. Since autophagy disorder is related to many diseases, it is highly important to detect autophagy. This study aimed to establish a dual-sensing mechanism-based ratiometric viscosity-sensitive lysosome-targeted two-photon fluorescent probe Vis-sun to track the autophagy process (the increase in lysosome viscosity during autophagy) by combining through bond energy transfer (TBET) and aggregation-induced emission (AIE). The introduction of TBET not only overcame the interference of background signals but also achieved the baseline separation of two emission peaks, thus reducing the crosstalk between emissions, as well as the noninvasive bio-sensing of biological targets and long-term real-time tracer imaging by introducing AIE. In vitro experiments showed that the fluorescence intensity at 485 nm decreased gradually on increasing the volume ratio of water to tetrahydrofuran (Vwater/VTHF), while the fluorescence intensity at 605 nm increased significantly. Also, the fluorescence signal was maximized when the water content reached 100%. At the same time, the probe exhibited a significant dependence on the ambient viscosity. Therefore, the dynamic monitoring of lysosome viscosity during autophagy and the in situ imaging of autophagy fluctuations during stroke-induced neuroinflammation were successfully achieved by implementing Vis-sun lysosome anchoring with morpholine.
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Colorantes Fluorescentes , Fotones , Humanos , Viscosidad , Colorantes Fluorescentes/química , Autofagia , Agua , Células HeLaRESUMEN
The low photon energy and deep penetrating ability of near-infrared (NIR) light make it an ideal light source for a photoelectrochemical (PEC) immunosensing system. Absorption wavelengths of the metal-organic frameworks (MOFs) can be regulated by adjusting the metal ions and the conjugation degree of the ligands. Herein, an ionic liquid with a large conjugated structure was synthesized and was used as a ligand to coordinate with Nd ions to prepare Nd-MOF nanorods with a band gap of 1.26 eV. The Nd-MOF rods show a good photoabsorption property from 200 to 980 nm. A PEC platform was constructed by using Nd-MOF nanorods as the photoelectroactive element. A detachable double-stranded DNA labeled with alkaline phosphatase (ALP), which is specific to VEGF165, was immobilized onto the PEC sensing interface. After blocking unspecific active sites with bovine albumin, an NIR PEC aptasensing system was developed for VEGF165 detection. After being incubated in a mixture of VEGF165, l-ascorbic acid 2-phosphate (magnesium salt hydrate) (AAP), and chloroauric acid, the aptamers for VEGF165 were detached from the PEC aptasensing interface, thus resulting in the decrease of the charge-transfer resistance and the increase of the photocurrent response. The shedding of the aptamers also makes the ALP approach the electrode surface, thus catalyzing the reduction of AAP to produce ascorbic acid (AA). Subsequently, AA reduces in situ chloroauric acid to produce AuNPs on the Nd-MOF-based sensing interface. With the excellent conductivity and localized surface plasmon resonance effect, the AuNPs can accelerate the separation of electron-hole pairs generated from Nd-MOF nanorods, thus promoting the photoelectric conversion efficiency and achieving signal amplification. Under optimized conditions, the PEC responses were linearly related to the VEGF165 concentrations in the range of 0.01-100 ng mL-1 and exhibit a low detection limit of 3.51 pg mL-1 (S/N = 3). VEGF165 in human serum samples was detected by the NIR PEC aptasensor. Their concentrations were found to be well consistent with that obtained from ELISA. Furthermore, the PEC aptasensor demonstrated recoveries from 96.07 to 103.8%. The relative standard deviations were within 5%, indicating good accuracy and precision. The results further verify its practicability for clinical diagnosis.
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Técnicas Biosensibles , Líquidos Iónicos , Nanopartículas del Metal , Nanotubos , Animales , Bovinos , Humanos , Oro/química , Nanopartículas del Metal/química , Técnicas Biosensibles/métodos , Nanotubos/química , Técnicas Electroquímicas/métodos , Límite de DetecciónRESUMEN
Fluorescence imaging using probes with two-photon excitation and near-infrared emission is currently the most popular in situ method for monitoring biological species or events, with a large imaging depth, low background fluorescence, low optical damage, and high spatial and temporal resolution. Nevertheless, current fluorescent dyes with near-infrared emission still have some disadvantages such as poor water solubility, low fluorescence quantum yield, and small two-photon absorption cross sections. These drawbacks are mainly caused by the structural characteristics of dyes with large conjugation surfaces but lacking strong and rigid structures. Herein, a lysosome-targeted and viscosity-sensitive probe (NCIC-VIS) is designed and synthesized. The protonation of morpholine not only helps anchor NCIC-VIS to the lysosome but also significantly enhances its water solubility. More importantly, its viscosity can increase the rigid structure of NCIC-VIS, which will improve the fluorescence quantum yield and the two-photon absorption cross section due to the imposed restrictions on molecular torsion. Based on the abovementioned characteristics, the real-time imaging of cellular autophagy (could increase the viscosity of lysosomes) was realized using NCIC-VIS. The results demonstrated that the level of autophagy was significantly enhanced in mice during stroke, while the inhibition of oxidative stress significantly reduced the degree of autophagy. The study corroborates that oxidative stress induced by stroke can lead to the development of autophagy.
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Lisosomas , Accidente Cerebrovascular , Animales , Autofagia , Colorantes Fluorescentes/química , Células HeLa , Humanos , Lisosomas/química , Ratones , Imagen Óptica , Viscosidad , Agua/análisisRESUMEN
The direct decarbonylative cyanation of benzoic acids with TMSCN was achieved through palladium catalysis. By this strategy, a wide range of nitriles including those with functional groups was synthesized in good to high yields. Moreover, this reaction applied to modifying bioactive molecules such as adapalene, probenecid, telmisartan, and 3-methylflavone-8-carboxylic acid. These results demonstrate that this new reaction has potential synthetic value in organic synthesis.
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Ácidos Carboxílicos , Paladio , Catálisis , Cianuros , Compuestos de TrimetilsililoRESUMEN
A nickel-catalyzed decarbonylative thioetherification of carboxylic acids with thiols was developed. Under the reaction conditions, benzoic acids, cinnamic acids, and benzyl carboxylic acids coupled with various thiols including both aromatic and aliphatic ones produce the corresponding thioethers in up to 99% yields. Moreover, this reaction was applicable to the modification of bioactive molecules such as 3-methylflavone-8-carboxylic acid, probenecid, and flufenamic acid, and the synthesis of acaricide chlorbenside. These results well demonstrated the potential synthetic value of this new reaction in organic synthesis.
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Ácidos Carboxílicos , Níquel , Catálisis , Compuestos de Sulfhidrilo , SulfurosRESUMEN
A base-promoted direct deaminative olefination of organoammonium salts was developed. Only mediated by KOtBu, a series of benzyl and cinnamyl ammonium salts reacted smoothly with sulfones, producing the valuable stilbenes and related 1,3-diene derivatives in good to high yields with good functional group tolerance and excellent E-selectivity. With this developed method, biologically active resveratrol and DMU-212 were also successfully prepared, which further demonstrates the practicality of this reaction.
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Estilbenos , Sulfonas , Polienos , Sales (Química)RESUMEN
A palladium-catalyzed difunctionalization of bicyclic alkenes with organoammonium salts and organoboronic compounds was reported. A wide range of functionalized cyclic products, including those bearing functional groups, were produced stereoselectively in good to excellent yields. The gram-scale experiment, one-pot operation, and synthetic application of ß-borylated products further demonstrated the synthetic value of this new reaction in organic synthesis.
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A transition-metal-free and base promoted C-C bond forming reaction of benzyl C(sp3)-H bond with organoammonium salts via C-N bond cleavage has been reported. Benzyl ammonium salts as well as cinnamyl ammonium salt could couple readily with various benzyl C(sp3)-H species, producing the corresponding products in moderate to excellent yields with good functional group tolerance. Late stage chemical manipulation enabled the specific 1,2-diarylethane structure of products transformed into useful olefin compounds via dehydrogenation, which further demonstrated the utility of this reaction.
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A "wet" process and two "dry" processes for converting phosphonate esters to phosphonic acids catalyzed by a Brønsted acid have been developed. Thus, in the presence of water, a range of alkyl-, alkenyl-, and aryl-substituted phosphonates can be generally hydrolyzed to the corresponding phosphonic acids in good yields catalyzed by trifluoromethyl sulfonic acid (TfOH) at 140 °C (the wet process). On the other hand, with specific substituents of the phosphonate esters, the conversion to the corresponding phosphonic acids can be achieved under milder conditions in the absence of water (the dry process). Thus, the conversion of dibenzyl phosphonates to the corresponding phosphonic acids took place smoothly at 80 °C in toluene or benzene in high yields. Moreover, selective conversion of benzyl phosphonates RP(O)(OR')(OBn) to the corresponding mono phosphonic acids RP(O)(OR')(OH) can also be achieved under the reaction conditions. The dealkylation via the generation of isobutene of di-tert-butyl phosphonate, and the related catalysis by TfOH took place even at room temperature to give the corresponding phosphonic acids in good to high yields. Nafion also shows high catalytic activity for these reactions. By using Nafion as the catalyst, phosphonic acids could be easily prepared on a large scale via a simple process.
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Lamellar MoS2 nanosheets were successfully prepared by hydrothermal synthesis using 1-(3-mercaptopropyl)-3-methyl-imidazolium bromine (MIMBr) ionic liquid as a sulfur source and a morphology control agent, and sodium molybdate as a molybdenum source. Gold nanoparticles were assembled on the surface of MoS2 nanosheets by the in situ reduction of chloroauric acid at low temperatures to successfully fabricate AuNP/2D-MoS2 nanocomposites, thus improving photoelectrochemical response. AuNP/2D-MoS2 nanocomposites were used as photoelectrically active materials modified onto a glassy carbon electrode surface to construct a photoelectrochemical (PEC) sensor. Then, using 1-(N-pyrrolpropyl)-3-methyl-imidazolium bromine (PMIMBr) ionic liquid as a functional monomer and pro-gastrin-releasing peptide (Pro-GRP) as a template, a molecularly imprinted polymerized ionic liquid film was electrochemically deposited on an AuNP/2D-MoS2/GCE surface. Upon removing the templates, a molecularly imprinted photoelectrochemical sensor was constructed for the sensing of a tumor marker, pro-gastrin-releasing peptide. Experimental conditions including ascorbic acid concentration, polymerization conditions, incubation time, and pH value of the incubation solution have been optimized. Under the optimized conditions, the molecularly imprinted photoelectrochemical sensor can specifically detect the target protein Pro-GRP in the range of 0.02 ng mL-1-5 ng mL-1 with a detection limit of 0.0032 ng mL-1 (S/N = 3). The practicability of this photoelectrochemical sensor was demonstrated by accurately determining Pro-GRP in human serum samples.
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Disulfuros/química , Electroquímica/instrumentación , Oro/química , Nanopartículas del Metal/química , Impresión Molecular , Molibdeno/química , Procesos Fotoquímicos , Precursores de Proteínas/análisis , Células HeLa , Humanos , Concentración de Iones de Hidrógeno , Líquidos Iónicos/química , Límite de Detección , Nanocompuestos/química , Propiedades de SuperficieRESUMEN
MoS2 nanosheets were prepared by exfoliating MoS2 bulk crystals with ultrasonication in N-methylpyrrolidone and were integrated with gold nanostars (AuNS) to fabricate an AuNS/MoS2 nanocomposite. All nanomaterials were characterized by transmission electron microscope, scanning electron microscope, ultraviolet-visible spectroscopy, X-ray diffraction, and X-ray photoelectron spectroscopy. AuNS/MoS2 nanocomposites were coated onto a glassy carbon electrode (GCE) surface to construct a nanointerface for immobilizing neuron-specific enolase antibody (anti-NSE) thus forming a photoelectrochemical immunoassay system. AuNS can significantly promote the photoelectric conversion of MoS2 nanosheets improving the performance for a photoelectrochemical assay. Being illuminated with white light LED and controlling the potential at 0.05 V (vs. SCE), the photocurrent generated from anti-NSE(BSA)/AuNS/MoS2/GCE using 0.15 mol L-1 ascorbic acid as electron donor can be recorded with amperometry and used as an output signal for NSE quantitative assay. Under optimized experimental conditions, the photocurrent variation for the affinity-binding NSE is proportional to the logarithm of NSE concentration in the range 5.0 pg mL-1 to 1.5 ng mL-1 with a detection limit of 3.5 pg mL-1 (S/N = 3). The practicability of the PEC immunoassay system was evaluated by determining NSE in clinical serum samples. The recoveries ranged from 93.0 to 103% for the determination of NSE in serum samples with a standard addition method. The PEC immunoassay system possesses good accuracy for determining NSE in real samples. Graphical abstract.
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Disulfuros/química , Técnicas Electroquímicas/métodos , Inmunoensayo/métodos , Nanopartículas del Metal/química , Molibdeno/química , Fosfopiruvato Hidratasa/sangre , Anticuerpos Inmovilizados/inmunología , Disulfuros/efectos de la radiación , Oro/química , Humanos , Luz , Nanopartículas del Metal/efectos de la radiación , Molibdeno/efectos de la radiación , Fosfopiruvato Hidratasa/inmunología , Procesos FotoquímicosRESUMEN
Four CeO2 nanomaterials with the morphologies of a nanoplate (CeO2-p), a nanocube (CeO2-c), a porous triangular microplate (CeO2-t), and of a porous hierarchical rod-stacked nanobundle (CeO2-b) were synthesized using a hydrothermal method. They were characterized by scanning and transmission electron microscopies, X-ray diffraction and X-ray photoelectron spectroscopy. Electrochemical characterizations reveal the tuning of their morphology and the presence of exposed crystal planes of CeO2 that can be realized by changing the alkali sources. Among these materials, the CeO2-b features the largest specific surface and lowest electron transfer resistance towards the redox probe Fe(CN)63-/4-. The best voltammetric response to dopamine and epinephrine is thus achieved by using the Nafion-CeO2-b coated electrode. A sensitive and selective method was developed that can voltammetrically detect dopamine (with a peak near 0.13 V vs. SCE), and epinephrine (with a peak near 0.25 V vs. SCE). The detection limits are 2.9 and 0.67 nM, respectively. Graphical abstractSchematic representation of morphology tailoring of CeO2 and electrochemical sensing of dopamine and epinephrine on these CeO2 samples with different morphologies.
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Cerio/química , Dopamina/análisis , Técnicas Electroquímicas/métodos , Epinefrina/análisis , Electrodos , Humanos , Límite de Detección , Nanoestructuras/química , Oxidación-ReducciónRESUMEN
A hexafluorophosphate ionic liquid is used as a functional monomer to prepare a metal-organic framework (Zn-MOF). Zn-MOF is used as a template for MoS2 nanosheets synthesis and further carbonized to yield light-responsive ZnS/C/MoS2 nanocomposites. Zn-MOF, carbonized-Zn-MOF, and ZnS/C/MoS2 nanocomposites are characterized by Fourier transform infrared spectroscopy, transmission electron microscopy, X-ray diffraction pattern, scanning electron microscopy (SEM), element mapping, Raman spectroscopy, X-ray photoelectron spectroscopy, fluorescence, and nitrogen-adsorption analysis. Carcinoembryonic antigen (CEA) is selected as a model to construct an immunosensing platform to evaluate the photo-electrochemical (PEC) performances of ZnS/C/MoS2 nanocomposites. A sandwich-type PEC immunosensor is fabricated by immobilizing CEA antibody (Ab1 ) onto the ZnS/C/MoS2 /GCE surface, subsequently binding CEA and the alkaline phosphatase-gold nanoparticle labeled CEA antibody (ALP-Au-Ab2 ). The catalytic conversion of vitamin C magnesium phosphate produces ascorbic acid (AA). Upon being illuminated, AA can react with photogenerated holes from ZnS/C/MoS2 nanocomposites to generate a photocurrent for quantitative assay. Under optimized experimental conditions, the PEC immunosensor exhibits excellent analytical characteristics with a linear range from 2.0 pg mL-1 to 10.0 ng mL-1 and a detection limit of 1.30 pg mL-1 (S/N = 3). The outstanding practicability of this PEC immunosensor is demonstrated by accurate assaying of CEA in clinical serum samples.
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Técnicas Biosensibles , Antígeno Carcinoembrionario/análisis , Disulfuros/química , Técnicas Electroquímicas , Inmunoensayo , Estructuras Metalorgánicas/química , Molibdeno/química , Nanocompuestos/química , Sulfuros/química , Compuestos de Zinc/química , Adsorción , Luz , Nanocompuestos/ultraestructura , Nitrógeno/química , Espectroscopía de FotoelectronesRESUMEN
The applications of graphene-based adsorbents were limited because of their complicated manufacturing technology and hi cost, thus it is very important to prepare new inexpensive and easily manufactured graphene-based adsorbents. Herein, novel GCP hydrogels with different graphene oxide (GO), chitosan (CS), and poly(vinyl alcohol) (PVA) ratios were facilely prepared through a method of freeze-thaw physical cross-linking, which was green and low-cost, and the structural characterization and adsorptive property of the optimum GCP1:2:4 hydrogel toward Cd2+ and Ni2+ in wastewater was evaluated. It was found that the GCP1:2:4 hydrogel had good mechanical strength and a special 3D interconnection porous structure. The isotherms of adsorption used the Langmuir model, and the kinetics of adsorption following the pseudo-second-order model were confirmed. Moreover, the adsorption property with respect to Cd2+ and Ni2+ in wastewater has been largely effected by the pH and was less influenced by the ionic strength and humic acid, and the GCP1:2:4 hydrogel possessed excellent adsorptive and recyclable properties. These results demonstrated that the GCP1:2:4 hydrogel could serve as a desirable adsorbent to get rid of heavy metal ions in sewage.
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A capillary monolith consisting of poly[N-(4-vinyl)-benzyl iminodiacetic acid-co-divinylbenzene-co-N,N'-methylene bisacrylamide), referred to as poly(VBIDA-DVB-Bis), has been prepared. It is shown to be an efficient sorbent for the enrichment of Co(II) and Cd(II). The two ions are completely retained by the monolith in the pH range from 4.0 to 9.0. The breakthrough curve tests were adopted to evaluate the adsorption performance of the monolith towards Co(II) and Cd(II). A dose-response model was used to describe the breakthrough curves of the two ions at different initial concentrations. The adsorption capacities for Co(II) and Cd(II) are 1.54 and 1.73 mg·m-1 at a concentration level of 2.5 mg·L-1, respectively. The enrichment factor is 100, and the required sample volume is 5 mL. Following elution of the two ions with 0.5 M HNO3, they were quantified by ICP-MS. The limits of detection in a 1 mL sample are 0.35 ng·L-1 for Co(II) and 0.44 ng·L-1 for Cd(II). The method was applied to the determination of Co(II) and Cd(II) in spiked rice, human urine and seawater samples. Graphical abstract Schematic representation of a monolithic copolymer prepared from N-(4-vinyl)-benzyl iminodiacetic acid (VBIDA), divinylbenzene (DVB) and N,N'-methylene bisacrylamide (Bis) and its application for selective capturing of cadmium(II) and cobalt(II) from complex sample matrices prior to their determination by ICP-MS.