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Acute lung injury (ALI) is a major pathophysiological problem characterized by severe inflammation, resulting in high morbidity and mortality. Plumbagin (PL), a major bioactive constituent extracted from the traditional Chinese herb Plumbago zeylanica, has been shown to possess anti-inflammatory and antioxidant pharmacological activities. However, its protective effect on ALI has not been extensively studied. The objective of this study was to investigate the protective effect of PL against ALI induced by LPS and to elucidate its possible mechanisms both in vivo and in vitro. PL treatment significantly inhibited pathological injury, MPO activity, and the wet/dry ratio in lung tissues, and decreased the levels of inflammatory cells and inflammatory cytokines TNF-α, IL-1ß, IL-6 in BALF induced by LPS. In addition, PL inhibited the activation of the PI3K/AKT/mTOR signalling pathway, increased the activity of antioxidant enzymes CAT, SOD, GSH and activated the Keap1/Nrf2/HO-1 signalling pathway during ALI induced by LPS. To further assess the association between the inhibitory effects of PL on ALI and the PI3K/AKT/mTOR and Keap1/Nrf2/HO-1 signalling, we pretreated RAW264.7 cells with 740Y-P and ML385. The results showed that the activation of PI3K/AKT/mTOR signalling reversed the protective effect of PL on inflammatory response induced by LPS. Moreover, the inhibitory effects of PL on the production of inflammatory cytokines induced by LPS also inhibited by downregulating Keap1/Nrf2/HO-1 signalling. In conclusion, the results indicate that the PL ameliorate LPS-induced ALI by regulating the PI3K/AKT/mTOR and Keap1-Nrf2/HO-1 signalling, which may provide a novel therapeutic perspective for PL in inhibiting ALI.
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Lesión Pulmonar Aguda , Proteína 1 Asociada A ECH Tipo Kelch , Lipopolisacáridos , Factor 2 Relacionado con NF-E2 , Naftoquinonas , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Serina-Treonina Quinasas TOR , Animales , Lesión Pulmonar Aguda/metabolismo , Lesión Pulmonar Aguda/tratamiento farmacológico , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/patología , Factor 2 Relacionado con NF-E2/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Proteína 1 Asociada A ECH Tipo Kelch/metabolismo , Lipopolisacáridos/efectos adversos , Lipopolisacáridos/toxicidad , Naftoquinonas/farmacología , Transducción de Señal/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones , Masculino , Citocinas/metabolismo , Hemo-Oxigenasa 1/metabolismo , Células RAW 264.7 , Antiinflamatorios/farmacología , Hemo Oxigenasa (Desciclizante)/metabolismo , Proteínas de la Membrana/metabolismoRESUMEN
P2Y12 receptor inhibitors are commonly used in clinical antiplatelet therapy, typically alongside other medications. Vicagrel, a promising P2Y12 receptor inhibitor, has submitted a new drug marketing application to the United States Food and Drug Administration. Its primary metabolites and some metabolic pathways are identical to those of clopidogrel. The aim of this study was to investigate the effects of the thiol methyltransferase inhibitor (±)-2,3-dichloro-α-methylbenzylamine (DCMB) on the metabolism and pharmacokinetics of vicagrel. In vitro incubation with human and rat liver microsomes revealed that DCMB significantly inhibited the methylation of vicagrel's thiol metabolite M15-1. Rats were orally administered 6 mg/kg [14C]vicagrel (100 µCi/kg) 1 hour after peritoneal injection with or without DCMB (80 mg/kg). Compared with the control group, the plasma of DCMB-pretreated rats exhibited maximum plasma concentration (C max) decrease and time to reach C max (T max) delay for all vicagrel-related substances, the methylation product of the thiol metabolite (M9-2), and the derivatization product of the active thiol metabolite (MP-M15-2). However, no significant changes in area under the curve (AUC) or half-life (t 1/2) were observed. DCMB had negligible effect on the total radiological recovery of vicagrel within 72 hours, although the rate of vicagrel excretion slowed down within 48 hours. DCMB had a negligible impact on the metabolic pathway of vicagrel. Overall, the present study found that DCMB did not significantly affect the total exposure, metabolic pathways, metabolite profiles, or total excretion rates of vicagrel-related metabolites in rats, but led to C max decrease, T max delay, and slower excretion rate within 48 hours. SIGNIFICANCE STATEMENT: This study used liquid chromatography-tandem mass spectrometry combined with radiolabeling technology to investigate the effects of the thiol methyltransferase inhibitor (±)-2,3-dichloro-α-methylbenzylamine on the absorption, metabolism, and excretion of vicagrel in rats. This work helps to better understand the in vivo metabolism of active thiol metabolites of P2Y12 inhibitors such as clopidogrel, vicagrel, etc.
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Metiltransferasas , Microsomas Hepáticos , Ratas Sprague-Dawley , Animales , Ratas , Masculino , Microsomas Hepáticos/metabolismo , Microsomas Hepáticos/efectos de los fármacos , Humanos , Metiltransferasas/antagonistas & inhibidores , Metiltransferasas/metabolismo , Bencilaminas/farmacocinética , Bencilaminas/farmacología , Metilación , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/farmacocinética , Tiofenos/farmacocinética , Tiofenos/farmacología , Interacciones Farmacológicas , FenilacetatosRESUMEN
A metal-free and thiol-free organophosphorus-catalyzed method for forming thioethers was disclosed, driven by PIII/PVâO redox cycling. In this work, one-step dehydroxylative thioetherification of alcohols was fulfilled with various hypervalent organosulfur compounds. This established strategy features an excellent functional group tolerance and broad substrate scope, especially inactivated alcohols. The scale-up reaction and further transformation of the product were also successful. Additionally, this method offers a protecting-group-free and step-efficient approach for synthesizing peroxisome proliferator-activated receptor agonists which exhibited promising potential for treating osteoporosis in mammals.
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BACKGROUND: The mortality rate and prognosis of short-term and long-term acute kidney injury (AKI) patients who undergo continuous renal replacement therapy (CRRT) are different. Setting up risk stratification tools for both short-term and long-term deaths is highly important for clinicians. METHOD: A total of 1535 AKI patients receiving CRRT were included in this study, with 1144 from the training set (the Dryad database) and 391 from the validation set (MIMIC IV database). A model for predicting mortality within 10 and 90 days was built using nine different machine learning (ML) algorithms. AUROC, F1-score, accuracy, sensitivity, specificity, precision, and calibration curves were used to assess the predictive performance of various ML models. RESULTS: A total of 420 (31.1%) deaths occurred within 10 days, and 1080 (68.8%) deaths occurred within 90 days. The random forest (RF) model performed best in both predicting 10-day (AUROC: 0.80, 95% CI: 0.74-0.84; accuracy: 0.72, 95% CI: 0.67-0.76; F1-score: 0.59) and 90-day mortality (AUROC: 0.78, 95% CI: 0.73-0.83; accuracy: 0.73, 95% CI: 0.69-0.78; F1-score: 0.80). The importance of the feature shows that SOFA scores are rated as the most important risk factor for both 10-day and 90-day mortality. CONCLUSION: Our study, utilizing multiple machine learning models, estimates the risk of short-term and long-term mortality among AKI patients who commence CRRT. The results demonstrated that the prognostic factors for short-term and long-term mortality are different. The RF model has the best prediction performance and has valuable potential for clinical application.
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Lesión Renal Aguda , Terapia de Reemplazo Renal Continuo , Aprendizaje Automático , Humanos , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/terapia , Masculino , Femenino , Persona de Mediana Edad , Anciano , Medición de Riesgo/métodos , Pronóstico , Factores de TiempoRESUMEN
Cytosolic DNA activates cGAS (cytosolic DNA sensor cyclic AMP-GMP synthase)-STING (stimulator of interferon genes) signaling, which triggers interferon and inflammatory responses that help defend against microbial infection and cancer. However, aberrant cytosolic self-DNA in Aicardi-Goutière's syndrome and constituently active gain-of-function mutations in STING in STING-associated vasculopathy with onset in infancy (SAVI) patients lead to excessive type I interferons and proinflammatory cytokines, which cause difficult-to-treat and sometimes fatal autoimmune disease. Here, in silico docking identified a potent STING antagonist SN-011 that binds with higher affinity to the cyclic dinucleotide (CDN)-binding pocket of STING than endogenous 2'3'-cGAMP. SN-011 locks STING in an open inactive conformation, which inhibits interferon and inflammatory cytokine induction activated by 2'3'-cGAMP, herpes simplex virus type 1 infection, Trex1 deficiency, overexpression of cGAS-STING, or SAVI STING mutants. In Trex1-/- mice, SN-011 was well tolerated, strongly inhibited hallmarks of inflammation and autoimmunity disease, and prevented death. Thus, a specific STING inhibitor that binds to the STING CDN-binding pocket is a promising lead compound for STING-driven disease.
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Proteínas de la Membrana/antagonistas & inhibidores , Nucleótidos Cíclicos/metabolismo , Animales , Sitios de Unión , Biotinilación , Muerte Celular , Exodesoxirribonucleasas/deficiencia , Humanos , Inflamación/patología , Proteínas de la Membrana/química , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Ratones , Simulación del Acoplamiento Molecular , Mutación/genética , Fosfoproteínas/deficiencia , Dominios Proteicos , Transducción de SeñalRESUMEN
Seeking organic cathode materials with low cost and long cycle life that can be employed for large-scale energy storage remains a significant challenge. This work has synthesized an organic compound, triphenazino[2,3-b](1,4,5,8,9,12-hexaazatriphenylene) (TPHATP), with as high as 87.16% yield. This compound has a highly π-conjugated and rigid molecular structure, which is synthesized by capping hexaketocyclohexane with three molecules of 2,3-diaminophenazine derived from low-cost o-phenylenediamine, and is used as a cathode material for assembling aqueous rechargeable zinc ion batteries. Both experiments and DFT calculations demonstrate that the redox mechanism of TPHATP is predominantly governed by H+ storage. The Zn-intercalation product of nitride-type compound, is too unstable to form in water. Moreover, the TPHATP cathode exhibits a capacity of as high as 318.3 mAh g-1 at 0.1 A g-1 , and maintained a stable capacity of 111.9 mAh g-1 at a large current density of 10 A g-1 for 5000 cycles with only a decay of 0.000512% per cycle. This study provides new insights into understanding pyrazine as an active redox group and offers a potential affordable aqueous battery system for grid-scale energy storage.
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Endocytic recycling of internalized transmembrane proteins is essential for many important physiological processes. Recent studies have revealed that retromer-related Sorting Nexin family (SNX)-Bin/Amphiphysin/Rvs (BAR) proteins can directly recognize cargoes like cation-independent mannose 6-phosphate receptor (CI-MPR) and Insulin-like growth factor 1 receptor (IGF1R); however, it remains poorly understood how SNX-BARs select specific cargo proteins and whether they recognize additional ligands. Here, we discovered that the binding between SNX-BARs and CI-MPR or IGF1R is mediated by the phox-homology (PX) domain of SNX5 or SNX6 and a bipartite motif, termed SNX-BAR-binding motif (SBM), in the cargoes. Using this motif, we identified over 70 putative SNX-BAR ligands, many of which play critical roles in apoptosis, cell adhesion, signal transduction, or metabolite homeostasis. Remarkably, SNX-BARs could cooperate with both SNX27 and retromer in the recycling of ligands encompassing the SBM, PDZ-binding motif, or both motifs. Overall, our studies establish that SNX-BARs function as a direct cargo-selecting module for a large set of transmembrane proteins transiting the endosome, in addition to their roles in phospholipid recognition and biogenesis of tubular structures.
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Proteoma/metabolismo , Receptor IGF Tipo 2/metabolismo , Nexinas de Clasificación/química , Nexinas de Clasificación/metabolismo , Secuencias de Aminoácidos , Sitios de Unión , Transporte Biológico , Simulación por Computador , Técnicas de Inactivación de Genes , Células HeLa , Humanos , Dominios Proteicos , Proteoma/química , Receptor IGF Tipo 2/química , Semaforinas/metabolismo , Nexinas de Clasificación/genéticaRESUMEN
A green method to construct C-S bonds using sulfonyl chlorides and alcohols/acids via a PIII/PVâO catalytic system is reported. The organophosphorus-catalyzed umpolung reaction promotes us to propose the "dual-substrate deoxygenation" strategy. Herein, we adopt the "dual-substrate deoxygenation" strategy, which achieves the deoxygenation of sulfonyl chlorides and alcohols/acids to synthesize thioethers/thioesters driven by PIII/PVâO redox cycling. The catalytic method represents an operationally simple approach using stable phosphine oxide as a precatalyst and shows broad functional group tolerance. The potential application of this protocol is demonstrated by the late-stage diversification of drug analogues.
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Compuestos Organofosforados , Catálisis , Oxígeno/química , Alcoholes/química , Ácidos/química , Compuestos Organofosforados/químicaRESUMEN
The stimulator of interferon genes (STING) is a critical protein in the activation of the immune system in response to DNA. It can participate the inflammatory response process by modulating the inflammation-preferred translation program through the STING-PKR-like endoplasmic reticulum kinase (PERK)-eIF2α pathway or by inducing the secretion of type I interferons (IFNs) and a variety of proinflammatory factors through the recruitment of TANK-binding kinase 1 (TBK1) and interferon regulatory factor 3 (IRF3) or the regulation of the nuclear factor kappa-B (NF-κB) pathway. Based on the structure, location, function, genotype, and regulatory mechanism of STING, this review summarizes the potential value of STING inhibitors in the prevention and treatment of infectious diseases, psoriasis, systemic lupus erythematosus, non-alcoholic fatty liver disease, and other inflammatory and autoimmune diseases.
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Proteínas de la Membrana , Transducción de Señal , Humanos , Proteínas de la Membrana/metabolismo , FN-kappa B/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , ADN , Factor 3 Regulador del Interferón/metabolismo , Inmunidad InnataRESUMEN
Antimony is more than an emerging pollutant in water but a scare resource. In this study, we report an adsorbent with the record capacity so far from the balanced view of Sb(III) and Sb(V). The composite adsorbent was fabricated by encapsulating hollow Fe3O4 nanosphere with the EDTA grafted chitosan, and it has superhigh adsorption capacity of for 657.1 mg/g for Sb(III) and 467.3 mg/g for Sb(V), respectively. The mechanism study reveals that the adsorption of Sb initializes from the Fe3O4, propagates along the chitosan with hydrogen bond, and terminates at the inner sphere complex with the EDTA moiety in the adsorbent. In view of the ultra-high adsorption capacity of the adsorbent, the recovered adsorbent that contains abundant (>36.4%) highly dispersed antimony nanoparticles (600-FCSE-Sb) is applied to Li-ion battery anode after reduction. This article provides a new idea for connecting water treatment and electric energy storage.
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Quitosano , Nanosferas , Antimonio , Ácido Edético , ElectrodosRESUMEN
BDNF and its expressing neurons in the brain critically control feeding and energy expenditure (EE) in both rodents and humans. However, whether BDNF neurons would function in thermoregulation during temperature challenges is unclear. Here, we show that BDNF neurons in the dorsomedial hypothalamus (DMHBDNF ) of mice are activated by afferent cooling signals. These cooling-activated BDNF neurons are mainly GABAergic. Activation of DMHBDNF neurons or the GABAergic subpopulations is sufficient to increase body temperature, EE, and physical activity. Conversely, blocking DMHBDNF neurons substantially impairs cold defense and reduces energy expenditure, physical activity, and UCP1 expression in BAT, which eventually results in bodyweight gain and glucose/insulin intolerance. Therefore, we identify a subset of DMHBDNF neurons as a novel type of cooling-activated neurons to promote cold defense. Thus, we reveal a critical role of BDNF circuitry in thermoregulation, which deepens our understanding of BDNF in controlling energy homeostasis and obesity.
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Factor Neurotrófico Derivado del Encéfalo , Frío , Hipotálamo , Animales , Humanos , Ratones , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Metabolismo Energético , Hipotálamo/metabolismo , Neuronas/metabolismoRESUMEN
The intercrystalline interfaces have been proven vital in heterostructure catalysts. However, it is still challenging to generate specified heterointerfaces and to make clear the mechanism of a reaction on the interface. Herein, this work proposes a strategy of Fe-catalyzed cascade formation of heterointerfaces for comprehending the hydrogen evolution reaction (HER). In the pure solid-phase reaction system, Fe catalyzes the in situ conversion of MoO2 to MoC and then Mo2 C, and the consecutive formation leaves lavish intercrystalline interfaces of MoO2 -MoC (in Fe-MoO2 /MoC@NC) or MoC-Mo2 C (in Fe-MoC/ß-Mo2 C@NC), which contribute to HER activity. The improved HER activity on the interface leads to further checking of the mechanism with density functional theory calculation. The computation results reveal that the electroreduction (Volmer step) produced H* prefers to be adsorbed on Mo2 C; then two pathways are proposed for the HER on the interface of MoC-Mo2 C, including the single-molecular adsorption pathway (Rideal mechanism) and the bimolecular adsorption pathway (Langmuir-Hinshelwood mechanism). The calculation results further show that the former is favorable, and the reaction on the MoC-Mo2 C heterointerface significantly lowers the energy barriers of the rate-determining steps.
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Hidrógeno , Hierro , Catálisis , Hidrógeno/química , Molibdeno/químicaRESUMEN
ATP citrate lyase (ACLY) is an important metabolic enzyme involved in the synthesis of fatty acid and cholesterol. The inhibition of ACLY is considered as a promising therapeutic strategy for various metabolic diseases and numerous malignancies. In this study, a novel macrocyclic compound 2 has been identified as a potent ACLY inhibitor with the "ring closing" strategy for conformational restriction based on NDI-091143. It showed potent ACLY inhibitory activity and binding affinity comparable to the positive control. Furthermore, compared with the positive control (T1/2 = 3.36 min), the metabolic stability of 2 in HLMs (T1/2 = 531.22 min) was significantly improved. All of these results characterized 2 as a promising lead compound worthy of further study.
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ATP Citrato (pro-S)-Liasa , Neoplasias , ATP Citrato (pro-S)-Liasa/química , ATP Citrato (pro-S)-Liasa/metabolismo , Inhibidores Enzimáticos/farmacología , Humanos , Neoplasias/metabolismoRESUMEN
Carbon materials derived from metal-organic frameworks have attracted increasing attention as anodes for energy storage. In this study, Fe, Ni-doped ZIF-8 is carbonized at high temperature to obtain bimetallic Fe and Ni modified tension -relaxed carbon (FeNi@trC). Fe and Ni have opposite structural modification effects when the metal ions are doped into the ZIF-8 dodecahedron. The obtained carbon material maintains the regular dodecahedron morphology, which means the relaxation of tension and strong thermal stability during annealing. Moreover, the presence of nickel enhances the carbonization degree and electrochemical stability of FeNi@trC, while the calcination of the tensive ZIF-8 precursor offers more defect sites. The discharge capacities of FeNi@trC materials are stable at 182.9 mAh·g-1and 567.9 mAh·g-1for sodium-ion batterie (SIB) and lithium-ion batterie (LIB) at 0.05 A·g-1. Compared with the current density of 0.05 A·g-1, the discharge capacity of SIB and LIB attenuates by 29.4% and 55.9% at 1 A·g-1, respectively, and the FeNi@trC shows good performance stability in the following cycles.
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Actuated by the non-ionic heavy metal of antimony (Sb) contaminants with undesired toxicity to the environment and human health, capturing Sb is urgent to remedy contaminated water. Herein, the lamellar MnCo hydrotalcite was grown on catkin-derived biochar through the in situ etching of ZIF-L to construct a hierarchical microtube@nanosheet hybrid (CLMH) for Sb immobilization. The adsorption behaviour and mechanism of trivalent antimony (Sb (III)) on the CLMH were investigated. The CLMH shows good pH applicability for capturing Sb(III) at pH from 2 to 9. The excellent adsorption capacity of CLMH for Sb(III) is 247.62 mg g-1at 303 K, and the endothermic process is proved by the positive value of ΔH0(10.54 kJ mol-1). The adsorption process is fitted with the intra-particle diffusion model, which can be described with external mass transfer, intraparticle diffusion in pores, and equilibrium stage. The adsorption mechanism is proved, which includes the bind of Metal-O-Sb bonds by inner-sphere complex, the embedding of Sb in the intercalation of hydrotalcite, redox between Mn and Sb, and functional groups dependent anchoring effect. The work benefits the understanding of the antimony removal behaviour over the hierarchical microtube@nanosheet hybrids.
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As an efficient way to integrate multiple distributed energy resources (DERs) and the user side, a microgrid is mainly faced with the problems of small-scale volatility, uncertainty, intermittency and demand-side uncertainty of DERs. The traditional microgrid has a single form and cannot meet the flexible energy dispatch between the complex demand side and the microgrid. In response to this problem, the overall environment of wind power, thermostatically controlled loads (TCLs), energy storage systems (ESSs), price-responsive loads and the main grid is proposed. Secondly, the centralized control of the microgrid operation is convenient for the control of the reactive power and voltage of the distributed power supply and the adjustment of the grid frequency. However, there is a problem in that the flexible loads aggregate and generate peaks during the electricity price valley. The existing research takes into account the power constraints of the microgrid and fails to ensure a sufficient supply of electric energy for a single flexible load. This paper considers the response priority of each unit component of TCLs and ESSs on the basis of the overall environment operation of the microgrid so as to ensure the power supply of the flexible load of the microgrid and save the power input cost to the greatest extent. Finally, the simulation optimization of the environment can be expressed as a Markov decision process (MDP) process. It combines two stages of offline and online operations in the training process. The addition of multiple threads with the lack of historical data learning leads to low learning efficiency. The asynchronous advantage actor-critic (Memory A3C, M-A3C) with the experience replay pool memory library is added to solve the data correlation and nonstatic distribution problems during training. The multithreaded working feature of M-A3C can efficiently learn the resource priority allocation on the demand side of the microgrid and improve the flexible scheduling of the demand side of the microgrid, which greatly reduces the input cost. Comparison of the researched cost optimization results with the results obtained with the proximal policy optimization (PPO) algorithm reveals that the proposed algorithm has better performance in terms of convergence and optimization economics.
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Algoritmos , Suministros de Energía Eléctrica , Simulación por Computador , Electricidad , VientoRESUMEN
PURPOSE: 68Ga-prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is valuable for detecting primary and recurrent prostatic lesions. This study aimed to evaluate the efficacy of 68Ga-PSMA-11 PET/CT as a triage tool for prostate biopsy (PSMA-TB) and compare with transrectal ultrasound-guided biopsy (TRUS-GB) for the diagnosis of clinically significant prostate cancer (csPCa). METHODS: This single-centre study randomly allocated 120 patients with elevated serum prostate-specific antigen (PSA) levels (> 4 ng/ml) to PSMA-PET or TRUS group. Patients with PSMA-avid lesions (SUVmax ≥ 8.0) underwent PSMA-TB via a single-puncture percutaneous transgluteal approach (n = 25), whilst patients with negative PSMA-PET underwent systematic TRUS-GB (n = 35). All patients in the TRUS group underwent TRUS-GB directly (n = 60). RESULTS: PCa and csPCa were detected in 26/60 (43.3%) and 24/60 (40.0%) patients in the PSMA-PET group and 19/60 (31.6%) and 15/60 (25.0%) in the TRUS group, respectively. In the PSMA-PET group, the detection rate of PCa and csPCa were significantly higher in PSMA-PET-positive than negative patients (PCa, 23/25 (92.0%) vs 3/35 (8.6%), P < 0.01; csPCa, 22/25 (88.0%) vs 2/35 (5.7%), P < 0.01). PSMA-TB detected significantly more PCa and csPCa than TRUS-GB in the TRUS controls (PCa, 21/25 (84.0%) vs 19/60 (31.6%), P < 0.01; csPCa, 20/25 (80.0%) vs 15/60 (25.0%), P < 0.01). PSMA-PET detected significantly more cases of csPCa amongst patients with PSA 4.0-20.0 ng/ml than TRUS (27.02% vs 8.82%, P < 0.05). No haematuria, urinary retention or pelvic infection was observed after PSMA-TB compare with TRUS-GB. CONCLUSIONS: 68Ga-PSMA-11 PET/CT is a feasible imaging technique that may serve as a triage tool for prostate biopsy, and may improve the detection rate of csPCa compared with TRUS-GB, especially in patients with serum PSA 4.0-20.0 ng/ml.
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Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Ácido Edético/análogos & derivados , Isótopos de Galio , Radioisótopos de Galio , Humanos , Masculino , Oligopéptidos , Estudios Prospectivos , Antígeno Prostático Específico , Neoplasias de la Próstata/diagnóstico por imagen , Ultrasonografía IntervencionalRESUMEN
A novel armor-type composite of metal-organic framework (MOF)-encapsulated CoCu nanoparticles with a Fe3 O4 core (Fe3 O4 @SiO2 -NH2 -CoCu@UiO-66) has been designed and synthesized by the half-way injection method, which successfully serves as an efficient and recyclable catalyst for the selective transfer hydrogenation. In this half-way injection approach, the pre-synthetic Fe3 O4 @SiO2 -NH2 -CoCu was injected into the UiO-66 precursor solution halfway through the MOF budding period. The formed MOF armor could play a role of providing significant additional catalytic sites besides CoCu nanoparticles, protecting CoCu nanoparticles, and improving the catalyst stability, thus facilitating the selective transfer hydrogenation of nitrobenzaldehydes into corresponding nitrobenzyl alcohols in high selectivity (99 %) and conversion (99 %) rather than nitro group reduction products. Notably, this method achieves the precise assembly of a MOF-encapsulated composite, and the ingenious combination of MOF and nanoparticles exhibits excellent catalytic performance in the selective hydrogen transfer reaction, implementing a "1+1>2" strategy in catalysis.
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BACKGROUND: The single nucleotide polymorphism (SNP) of dopamine D4 receptor (DRD4) promoter (-616; rs747302) is associated with abnormalities of the thalamus in children suffering from primary nocturnal enuresis (PNE). PURPOSE: To investigate the effect of DRD4 -616 C/G SNP on thalamic gamma-aminobutyric acid (GABA) levels in PNE children. STUDY TYPE: Prospective, observational. SUBJECTS: One hundred and seventy-six children with PNE and 161 healthy control children. FIELD STRENGTH/SEQUENCE: 3 T, three-dimensional T1-weighted turbo field echo sequence and MEscher-Garwood Point RESolved Spectroscopy (MEGA-PRESS) MRS sequence. ASSESSMENT: The MEGA-PRESS MRS sequence was used to measure thalamic GABA spectra. The thalamic GABA+ level was calculated using the Gannet 3.0 software package for each participant. A questionnaire was used to determine arousal from sleep (AS) scores. STATISTICAL TESTS: Comparisons of the AS scores and thalamic GABA+ levels were performed using the Mann-Whitney U test between C-allele carriers and GG homozygotes in the PNE and control groups. Spearman correlation analysis was performed to determine the association between AS scores and thalamic GABA levels in PNE children. RESULTS: Thalamic GABA levels in the PNE group were significantly higher than those in the healthy control group (0.178 (0.169-0.186) vs. 0.154 (0.146-0.164), Z = 8.526, Pcorrected < 0.001). The GABA levels in C-allele carriers were significantly higher than those in GG homozygotes in both the PNE and control groups (0.184 (0.181-0.193) vs. 0.170 (0.165-0.177), Z = 8.683, Pcorrected < 0.001; 0.166 (0.156-0.170) vs. 0.147 (0.141-0.152), Z = 9.445, Pcorrected < 0.001). GABA levels in the thalamus were also significantly and positively correlated with AS scores in C-allele carriers in the PNE group (r = 0.747, P < 0.05). DATA CONCLUSION: DRD4 -616 C allele may be associated with increased thalamic GABA+ levels, especially in C-allele carrying PNE children. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 3.
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Enuresis Nocturna , Receptores de Dopamina D4 , Ácido gamma-Aminobutírico/análisis , Niño , Humanos , Enuresis Nocturna/genética , Estudios Prospectivos , Receptores de Dopamina D4/genética , Tálamo/diagnóstico por imagenRESUMEN
A copper-mediated cyclization and dimerization of indole derived oxime acetate was developed to generate a series of biimidazo[1,2-a]indole scaffolds with two contiguous stereogenic quaternary carbons in one step.