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BACKGROUND: Colorectal cancer is a common malignancy and various methods have been introduced to decrease the possibility of recurrence. Early recurrence (ER) is related to worse prognosis. To date, few observational studies have reported on the analysis of rectal cancer. Hence, we reported on the timing and risk factors for the ER of resectable rectal cancer at our institute. AIM: To analyze a cohort of patients with local and/or distant recurrence following the radical resection of the primary tumor. METHODS: Data were retrospectively collected from the institutional database from March 2011 to January 2021. Clinicopathological data at diagnosis, perioperative and postoperative data, and first recurrence were collected and analyzed. ER was defined via receiver operating characteristic curve. Prognostic factors were evaluated using the Kaplan-Meier method and Cox proportional hazards modeling. RESULTS: We included 131 patients. The optimal cut off value of recurrence-free survival (RFS) to differentiate between ER (n = 55, 41.9%) and late recurrence (LR) (n = 76, 58.1%) was 8 mo. The median post-recurrence survival (PRS) of ER and LR was 1.4 mo and 2.9 mo, respectively (P = 0.008) but PRS was not strongly associated with RFS (R² = 0.04). Risk factors included age ≥ 70 years [hazard ratio (HR) = 1.752, P = 0.047], preoperative concurrent chemoradiotherapy (HR = 3.683, P < 0.001), colostomy creation (HR = 2.221, P = 0.036), and length of stay > 9 d (HR = 0.441, P = 0.006). CONCLUSION: RFS of 8 mo was the optimal cut-off value. Although ER was not associated with PRS, it was still related to prognosis; thus, intense surveillance is recommended.
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Background: It is unclear how perioperative hemoglobin decrease (ΔHb) influences the balance between risks and benefits of red blood cell transfusion after cardiac surgery. Methods: We retrospectively analyzed data on 8186 adults who underwent valve surgery and/or coronary artery bypass grafting under cardiopulmonary bypass at two large cardiology centers. We explored the potential association of ΔHb, defined relative to the preoperative level and postoperative nadir, with a composite outcome of in-hospital mortality, myocardial infarction, stroke, and acute kidney injury using multivariable logistic regression, restricted cubic spline, and piecewise-linear models. Results: Among 6316 patients without preoperative anemia, ΔHb ≥ 50 % was associated with an elevated risk of the composite outcome [adjusted odds ratio (aOR) 1.95, 95 % confidence interval (CI) 1.81-2.35]. Among 869 patients without preoperative anemia and with ΔHb ≥ 50 %, postoperative transfusion of no more than four units of red blood cell appeared to decrease the risk of the composite outcome, whereas transfusion of more than six units increased risk. Among 5447 patients without preoperative anemia and with ΔHb < 50 %, postoperative transfusion appeared not to decrease the risk of the composite outcome. Among 1870 patients with preoperative anemia, ΔHb ≥ 30 % significantly increased the risk of the composite outcome (aOR 1.61, 95 % CI 1.23-2.10), and this risk might be moderated by postoperative transfusion of no more than four units of red blood cell, but increased by transfusion of more than six units. Conclusions: ΔHb may influence the balance between risks and benefits of red blood cell transfusion after cardiac surgery.
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PURPOSE: To analyze the situation and influencing factors of patients returning to work after spinal surgery, and to provide reference for clinical intervention measures of patients returning to work after spinal surgery. METHODS: A computer search was conducted in Chinese and English database on the situation and influencing factors of patients returning to work after spinal surgery from the establishment of the database to February 2023. Meta-analysis was performed using RevMan 5.3 and StataMP 17.0 software. RESULTS: A total of 10 literatures were included, involving 11,548 subjects. Meta-analysis results showed that 58% of patients returned to work after spinal surgery [95%CI (0.47-0.69)]. Gender [OR = 2.41, 95%CI (1.58-3.37)], age [OR = 1.32, 95%CI (1.03-1.51)], job nature [OR = 5.94, 95%CI (3.54-9.62)], education level [OR = 0.23, 95%CI (0.06-0.48)], fear of disease progression [OR = 0.82, 95%CI (0.84-0.95)], and social support [OR = 1.21, 95%CI (1.12-1.37)] were the influencing factors for patients returning to work after spinal surgery. CONCLUSION: The rate of patients returning to work after spinal surgery is low, and is affected by many factors. Medical personnel should pay comprehensive attention to the above high-risk groups and give timely intervention and support.
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Reinserción al Trabajo , Humanos , Factores de Edad , Progresión de la Enfermedad , Escolaridad , Miedo/psicología , Factores Sexuales , Apoyo Social , Columna Vertebral/cirugíaRESUMEN
Oxygenated volatile organic compounds (OVOCs), emitted in large quantities by the chemical industry, are a major contributor to the formation of ozone and subsequent particulate matter. For the efficient catalytic oxidation of OVOCs, the challenges of molecular activation and intermediate inhibition remain. The construction of bifunctional active sites with specific structures offers a promising way to overcome these problems. Here, the Pd@Layered-CoOx/MFI bifunctional catalyst with core-shell active sites was rationally fabricated though a two-step ligand pyrolysis method, which exhibits a superb oxidation efficiency toward ethyl acetate (EA). Over this, 13.4% of EA (1000 ppm) can be oxidized at just 140 °C with a reaction rate of 13.85 mmol·gPd-1·s-1, around 176.7 times higher than that of the conventional Pd-CoOx/MFI catalyst. The electronic coupling of the Pd-Co pair promotes the electron back-donation from Pd nanoparticles to the layered CoOx shell and facilitates the formation of Pd2+ species, which greatly enhances the adsorption and activation of the electron-rich CâO bond of the EA molecules. In addition, the synergy of these core-shell Pd@Layered-CoOx sites accelerates the activation and transformation of *O species, which inhibit the formation of acetaldehyde and ethanol byproducts, ensuring the rapid total oxidation of EA molecules via the Mars-van Krevelen mechanism. This work established a solid foundation for exploring robust bifunctional catalysts for deep OVOC purification.
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Oxidación-Reducción , Catálisis , Paladio/química , Compuestos Orgánicos Volátiles/química , Acetatos/químicaRESUMEN
The widespread presence of formaldehyde (HCHO) pollutant has aroused significant environmental and health concerns. The catalytic oxidation of HCHO into CO2 and H2O at ambient temperature is regarded as one of the most efficacious and environmentally friendly approaches; to achieve this, however, accelerating the intermediate formate species formation and decomposition remains an ongoing obstacle. Herein, a unique tandem catalytic system with outstanding performance in low-temperature HCHO oxidation is proposed on well-structured Pd/Mn3O4-MnO catalysts possessing bifunctional catalytic centers. Notably, the optimized tandem catalyst achieves complete oxidation of 100 ppm of HCHO at just 18 °C, much better than the Pd/Mn3O4 (30%) and Pd/MnO (27%) counterparts as well as other physical tandem catalysts. The operando analyses and physical tandem investigations reveal that HCHO is primarily activated to gaseous HCOOH on the surface of Pd/Mn3O4 and subsequently converted to H2CO3 on the Pd/MnO component for deep decomposition. Theoretical studies disclose that Pd/Mn3O4 exhibits a favorable reaction energy barrier for the HCHO â HCOOH step compared to Pd/MnO; while conversely, the HCOOH â H2CO3 step is more facilely accomplished over Pd/MnO. Furthermore, the nanoscale intimacy between two components enhances the mobility of lattice oxygen, thereby facilitating interfacial reconstruction and promoting interaction between active sites of Pd/Mn3O4 and Pd/MnO in local vicinity, which further benefits sustained HCHO tandem catalytic oxidation. The tandem catalysis demonstrated in this work provides a generalizable platform for the future design of well-defined functional catalysts for oxidation reactions.
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Formaldehído , Paladio , Temperatura , Dominio Catalítico , Oxidación-Reducción , Catálisis , Paladio/químicaRESUMEN
Spacious M4 L6 tetrahedra can act as catalytic inhibitors for base-mediated reactions. Upon adding only 5 % of a self-assembled Fe4 L6 cage complex, the conversion of the conjugate addition between ethylcyanoacetate and ß-nitrostyrene catalyzed by proton sponge can be reduced from 83 % after 75 mins at ambient temperature to <1 % under identical conditions. The mechanism of the catalytic inhibition is unusual: the octacationic Fe4 L6 cage increases the acidity of exogenous water in the acetonitrile reaction solvent by favorably binding the conjugate acid of the basic catalyst. The inhibition only occurs for Fe4 L6 hosts with spacious internal cavities: minimal inhibition is seen with smaller tetrahedra or Fe2 L3 helicates. The surprising tendency of the cationic cage to preferentially bind protonated, cationic ammonium guests is quantified via the comprehensive modeling of spectrophotometric titration datasets.
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BACKGROUND: Glioblastomas (GBMs) are the most lethal brain cancer with a median survival rate of fewer than 15 months. Both clinical and biological features of GBMs are largely different from those of low-grade gliomas (LGs), but the reasons for this intratumoral heterogeneity are not entirely clear. Transfer RNA (tRNA)-derived small RNAs (tsRNAs) were derived from tRNA precursors and mature tRNA, referring to the specific cleavage of tRNAs by dicer and angiogenin (ANG) in particular cells or tissues or under certain conditions such as stress and hypoxia. With the characteristics of wide expression and high stability, tsRNAs could be used as favorable biomarkers for diagnosis, treatment, and prognosis prediction of the tumor, viral infection, neurological as well as other systemic diseases. In this study, we have compared the differential expressed tsRNAs between GBMs and LGs, so as to investigate the possible pathogenic molecules and provide references for discovering novel nucleic acid drugs in future studies. METHODS: Fresh tumor tissues of patients that were diagnosed as GBMs (4 cases) and LGs (5 cases) at the First Affiliated Hospital of Wenzhou Medical University from 2019.05 to 2021.01 were collected. The tsRNAs' levels were analyzed and compared through high-throughput sequencing, candidate tsRNAs were chosen according to the expression level, and the expression of the candidate tsRNAs was validated through qPCR. Finally, the potential targets were imputed using the Miranda and TargetScan databases, and possible biological functions of the differentially expressed (DE) tsRNAs' targets were enriched based on GO and KEGG databases. RESULTS: A total of 4 GBMs and 5 LGs patients were enrolled in the current study. High-throughput sequencing showed that 186 tsRNAs were expressed in two groups, over them, 43 tsRNAs were unique to GBMs, and 24 tsRNAs were unique to LGs. A total of 9 tsRNAs were selected as candidate tsRNAs according to the tsRNA expression level, among which 6 tsRNAs were highly expressed in GBMs and 3 tsRNAs were low expressed in GBMs. qPCR verification further demonstrated that 5 tsRNAs were significantly up-regulated and 1 tsRNA was significantly down-regulated in GBMs: tRF-1-32-chrM.Lys-TTT (p=0.00118), tiRNA-1-33-Gly-GCC-1 (p=0.00203), tiRNA-1-33-Gly-CCC-1 (p=0.00460), tRF-1-31-His-GTG-1 (p=0.00819), tiRNA-1-33-Gly-GCC-2-M3 (p=0.01032), and tiRNA-1-34-Lys-CTT-1-M2 (p=0.03569). Enrichment analysis of the qPCR verified DE tsRNAs showed that the 5 up-regulated tsRNAs seemed to be associated with axon guidance, pluripotent stem cells regulation, nucleotide excision repair, Hippo signaling pathway, and cancer-related pathways, while the down-regulated tsRNA (tRF-1-32-chrM.Lys-TTT) was associated with oocyte meiosis and renin secretion. CONCLUSION: The tsRNAs were differentially expressed in tumor tissues between GBMs and LGs, especially tRF-1-32-chrM.Lys-TTT, tiRNA-1-33-Gly-GCC-1, tiRNA-1-33-Gly-CCC-1, tRF-1-31-His-GTG-1, tiRNA-1-33-Gly-GCC-2-M3, and tiRNA-1-34-Lys-CTT-1-M2. These tsRNAs seemed to be associated with nucleotide excision repair, Hippo signaling, and cancer-related pathways. This may be the main reason for the differences in clinical characteristics between GBMs and LGs, which may provide a certain theoretical basis for further functional research and development of related nucleic acid drugs. CONCLUSION: The tsRNAs were differentially expressed in tumor tissues between GBMs and LGs, especially tRF-1-32-chrM.Lys-TTT, tiRNA-1-33-Gly-GCC-1, tiRNA-1-33-Gly-CCC-1, tRF-1-31-His-GTG-1, tiRNA-1-33-Gly-GCC-2-M3, and tiRNA-1-34-Lys-CTT-1-M2. These tsRNAs seemed to be associated with nucleotide excision repair, Hippo signaling, and cancer-related pathways. This may be the main reason for the differences in clinical characteristics between GBMs and LGs, which may provide a certain theoretical basis for further functional research and development of related nucleic acid drugs.
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Glioblastoma , Glioma , Humanos , Glioblastoma/genética , ARN de Transferencia/genética , Glioma/genética , Secuenciación de Nucleótidos de Alto Rendimiento , Precursores del ARNRESUMEN
To predict 3-Level version of European Quality of Life-5 Dimensions (EQ-5D-3L) questionnaire utility from the chronic obstructive pulmonary disease (COPD) assessment test (CAT), the study attempts to collect EQ-5D-3L and CAT data from COPD patients. Response mapping under a backward elimination procedure was used for EQ-5D score predictions from CAT. A multinomial logistic regression (MLR) model was used to identify the association between the score and the covariates. Afterwards, the predicted scores were transformed into the utility. The developed formula was compared with ordinary least squares (OLS) regression models and models using Mean Rank Method (MRM). The MLR models performed as well as other models according to mean absolute error (MAE) and root mean squared error (RMSE) evaluations. Besides, the overestimation for low utility patients (utility ≤ 0.6) and underestimation for near health (utility > 0.9) in the OLS method was improved through the means of the MLR model based on bubble chart analysis. In conclusion, response mapping with the MLR model led to performance comparable to the OLS and MRM models for predicting EQ-5D utility from CAT data. Additionally, the bubble charts analysis revealed that the model constructed in this study and MRM could be a better predictive model.
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Enfermedad Pulmonar Obstructiva Crónica , Calidad de Vida , Humanos , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Investigación , Modelos Logísticos , AlgoritmosRESUMEN
Volatile organic amines are a category of typical volatile organic compounds (VOCs) extensively presented in industrial exhausts causing serious harm to the atmospheric environment and human health. Monometallic Pd and Cu-based catalysts are commonly adopted for catalytic destruction of hazardous organic amines, but their applications are greatly limited by the inevitable production of toxic amide and NOx byproducts and inferior low-temperature activity. Here, a CuO/Pd@SiO2 core-shell-structured catalyst with diverse functionalized active sites was creatively developed, which realized the total decomposition of n-butylamine at 260 °C with a CO2 yield and N2 selectivity reaching up to 100% and 98.3%, respectively (obviously better than those of Pd@SiO2 and CuO/SiO2), owing to the synergy of isolated Pd and Cu sites in independent mineralization of n-butylamine and generation of N2, respectively. The formation of amide and short-chain aliphatic hydrocarbon intermediates via C-C bond cleavage tended to occur over Pd sites, while the C-N bond was prone to breakage over Cu sites, generating NH2· species and long free-N chain intermediates at low temperatures, avoiding the production of hazardous amide and NOx. The SiO2 channel collapse and H+ site production resulted in the formation of N2O via suppressing NH2· diffusion. This work provides critical guidance for a rational fabrication of catalysts with high activity and N2 selectivity for environmentally friendly destruction of nitrogen-containing VOCs.
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Butilaminas , Dióxido de Silicio , Humanos , Dióxido de Silicio/química , Dominio Catalítico , AmidasRESUMEN
The androgen receptor (AR) antagonists are efficient therapeutics for the treatment of prostate cancer (PCa). All the approved AR antagonists to date are targeted to the ligand-binding pocket (LBP) of AR and have suffered from various drug resistances, whereas AR antagonist targeting non-LBP site of AR is conceived as a promising strategy. Through the scaffold hopping of AR LBP antagonists, the 2-chloro-4-(1H-pyrazol-1-yl)benzonitrile was designed as a new core structure for AR antagonists. A total of 46 compounds were synthesized and biologically evaluated to disclose compounds 2f, 2k, and 4c, exhibiting potent AR antagonistic activities (IC50 up to 69 nM), force against antiandrogen resistance, and untraditional targeting site of probably AR binding function 3. Therein, 4c exhibited effective tumor growth inhibition in LNCaP xenograft study upon oral administration. This work provides a novel chemical scaffold for AR antagonists and offers new perspective for the development of PCa therapy.
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Neoplasias de la Próstata , Receptores Androgénicos , Acetamidas/farmacología , Antagonistas de Andrógenos/farmacología , Antagonistas de Receptores Androgénicos/química , Línea Celular Tumoral , Proliferación Celular , Humanos , Ligandos , Masculino , Neoplasias de la Próstata/patología , Pirazoles , Receptores Androgénicos/metabolismoRESUMEN
Pulmonary ischemia and reperfusion (I/R) injury occurs in many clinical conditions and causes severe damage to the lungs. Diabetes mellitus (DM) predisposes to pulmonary I/R injury. We previously found that remote liver ischemia preconditioning protected lungs against pulmonary I/R injury. The aim of the present study was to investigate whether remote liver ischemic postconditioning (RLIPost) attenuates pulmonary damage induced by I/R injury in non-diabetic or diabetic rats. Male Sprague-Dawley rats were assigned into non-diabetic and diabetic groups. All rats except for the sham were exposed to 45 min of left hilum occlusion followed by 2 h of reperfusion. RLIPost was conducted at the onset of pulmonary reperfusion by four cycles of 5 min of liver ischemia and reperfusion. Lung injury was assessed by the wet/dry weight ratio, pulmonary oxygenation, histopathological changes, apoptosis and the expression of inflammatory cytokines. Reperfusion-associated protein phosphorylation states were determined. RLIPost offered strong pulmonary-protection in both non-diabetic and diabetic rats, as reflected in reduced water content and pulmonary structural damage, recovery of lung function, inhibition of apoptosis and inflammation after ischemia-reperfusion. RLIPost induced the activation of pulmonary STAT-3, a key component in the SAFE pathway, but not activation of the proteins in the RISK pathway, in non-diabetic rats. In contrast, RLIPost-induced pulmonary protection in diabetic lungs was independent of SAFE or RISK pathway activation. These results demonstrate that RLIPost exerts pulmonary protection against I/R-induced lung injury in non-diabetic and diabetic rats. The underlying mechanism for protection may be different in non-diabetic (STAT-3 dependent) versus diabetic (STAT-3 independent) rats.
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Diabetes Mellitus Experimental , Poscondicionamiento Isquémico , Precondicionamiento Isquémico , Lesión Pulmonar , Daño por Reperfusión , Animales , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/patología , Poscondicionamiento Isquémico/métodos , Precondicionamiento Isquémico/métodos , Hígado/metabolismo , Pulmón/patología , Lesión Pulmonar/etiología , Lesión Pulmonar/patología , Lesión Pulmonar/prevención & control , Masculino , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/complicaciones , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & controlRESUMEN
Glucocorticoids (GCs) are the most commonly used anti-inflammatory drugs. However, their excellent therapeutic effects are often accompanied by undesirable side effects. To discover selective glucocorticoid receptor modulators (SGRMs) that preferentially induce transrepression with little or no transactivation activity, a structure-based virtual screening by combining molecular docking and InteractionGraphNet (IGN) rescoring was performed, and compound HP210 was identified. HP210 did not induce the transactivation functions of GR while still acted on the NF-κB mediated tethered transrepression function (IC50 = 2.32 µM), and suppressed the secretion of pro-inflammation cytokines IL-1ß and IL-6. Compared with dexamethasone, HP210 showed no cross activities with phylogenetically related mineralcorticoid receptor and progesterone receptor and no significant effect on osteoprotegerin, exhibiting a reduced side-effect profile. Then, guided by the molecular dynamics simulations and binding free energy calculations, compound HP210_b4 with over two-fold higher transrepression activity (IC50 = 0.99 µM) was discovered. This study reported a group of non-steroidal new-scaffold SGRMs, providing valuable clues for the development of novel anti-inflammatory drugs.
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Glucocorticoides , Receptores de Glucocorticoides , Antiinflamatorios/farmacología , Glucocorticoides/farmacología , Simulación del Acoplamiento Molecular , FN-kappa B/metabolismo , Receptores de Glucocorticoides/químicaRESUMEN
Objective: Systematic analysis of the incidence of percutaneous spinal endoscopic technique and traditional open surgery for lumbar disc herniation. Methods: A randomized controlled trial (RCT) and cohort study on complications related to traditional open surgery was searched on the MEDLINE, Cochrane Library, PubMed, Web of Science, Chinese journal full-text database (CNKI), Wanfang, and Embase database. Language is not limited. The quality of each study was evaluated, various complications were compiled into electronic baseline tables, and the data from these studies were available. Meta-analysis and synthesis were performed with the RevMan 5.3 software to evaluate the statistical significance of both surgical techniques in terms of various complications. Results: 12 studies were eventually included, and a total of 2,797 patients were included in the analysis. Meta-analysis results showed that there was no statistical difference in postoperative paresthesia between percutaneous spinal endoscopy and traditional open surgery (OR = 1.17, 95% CI (0.82, 1.66), P = 0.38, I 2 = 0%, Z = 0.88), direct nerve root damage (OR = 0.79, 95% CI (0.58, 1.07), P = 0.13, I 2 = 73%, Z = 1.52), and intraoperative hemorrhage and hematoma formation (OR = 1.00, 95% CI (0.67, 1.48), P = 0.99, I 2 = 0%, Z = 0.02), but there was a statistical difference in disc recurrence (OR = 2.24, 95% CI (1.56, 3.21), P < 0.0001, I 2 = 81%, Z = 4.39). Conclusion: Compared with the traditional open surgical treatment of lumbar disc herniation, percutaneous spinal endoscopic technology has obvious advantages in reducing nerve root injury, dural injury, and surgical area wound complications, but it is limited to preventing the technical characteristics of the surgical site, which is worse than that of open surgery.
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Discectomía Percutánea , Desplazamiento del Disco Intervertebral , Discectomía Percutánea/métodos , Endoscopía/efectos adversos , Endoscopía/métodos , Humanos , Desplazamiento del Disco Intervertebral/cirugía , Vértebras Lumbares/cirugía , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
The development of highly active single-atom catalysts (SACs) and identifying their intrinsic active sites in oxidizing industrial hazardous hydrocarbons are challenging prospects. Tuning the electronic metal-support interactions (EMSIs) is valid for modulating the catalytic performance of SACs. We propose that the modulation of the EMSIs in a Pt1 -CuO SAC significantly promotes the activity of the catalyst in acetone oxidation. The EMSIs promote charge redistribution through the unified Pt-O-Cu moieties, which modulates the d-band structure of atomic Pt sites, and strengthens the adsorption and activation of reactants. The positively charged Pt atoms are superior for activating acetone at low temperatures, and the stretched Cu-O bonds facilitate the activation of lattice oxygen atoms to participate in subsequent oxidation. We believe that this work will guide researchers to engineer efficient SACs for application in hydrocarbon oxidation reactions.
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Androgen receptor (AR) antagonists have been widely used for the treatment of prostate cancer (PCa). As a link between the AR and its transcriptional function, the activation function 2 (AF2) region has recently been revealed as a novel targeting site for developing AR antagonists. Here, we reported a series of N-(4-(benzyloxy)-phenyl)-sulfonamide derivatives as new-scaffold AR antagonists targeting the AR AF2. Therein, compound T1-12 showed excellent AR antagonistic activity (IC50 = 0.47 µM) and peptide displacement activity (IC50 = 18.05 µM). Furthermore, the in vivo LNCaP xenograft study confirmed that T1-12 offered effective inhibition on tumor growth when administered intratumorally. The study represents the first successful attempt to identify a small molecule targeting the AR AF2 with submicromolar AR antagonistic activity by structure-based virtual screening and provides important clues for the development of novel therapeutics for PCa treatment.
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Antagonistas de Receptores Androgénicos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Próstata/tratamiento farmacológico , Receptores Androgénicos/metabolismo , Sulfonamidas/uso terapéutico , Antagonistas de Receptores Androgénicos/síntesis química , Antagonistas de Receptores Androgénicos/metabolismo , Animales , Antineoplásicos/síntesis química , Antineoplásicos/metabolismo , Sitios de Unión , Proliferación Celular/efectos de los fármacos , Expresión Génica/efectos de los fármacos , Humanos , Masculino , Ratones SCID , Simulación del Acoplamiento Molecular , Estructura Molecular , Transporte de Proteínas/efectos de los fármacos , Receptores Androgénicos/química , Relación Estructura-Actividad , Sulfonamidas/síntesis química , Sulfonamidas/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Though the highest CO2 capture capacity belongs to liquid amine-solutions, solid matters capable of CO2 capture are also highly sought, providing that, they offer at least analogous CO2 adsorption capacity and CO2/N2 selectivity. Herein, a surprisingly high-performance Ni-based metal-organic framework for CO2 adsorption, namely MOF-74(Ni), was synthesized by a facile condensation reflux approach. It was found that the structure and CO2 adsorption isosteric heat of MOF-74(Ni) could tune upon varying the synthesis duration under various temperatures. The optimized MOF-74(Ni)-24-140 (synthesized at 140 °C for 24 h) displays outstanding CO2 adsorption capacity of 8.29/6.61 mmol/g at 273/298 K under normal pressure of 1.0 bar, several times higher than previously reported MOF-74-Ni (2.0/2.1 times), UTSA-16 (1.5/1.6 times), and DA-CMP-1 (3.6/4.9 times) under similar conditions. The excellent CO2 capture capacity is associated to the abundant adsorption sites (mainly arising from the cationic Ni2+ ions) and narrow micropore channels (mainly arising from the cage structure of Ni2+ ions coordinated with organic linkers). Offering a high CO2 selectivity (CO2/N2 = 49) and a well-tuned isosteric heat of CO2 adsorption (27-52 kJ/mol) besides its decent CO2 capture capacity, MOF-74(Ni) strongly stands out as an efficient and strong CO2 capturing material with industrial scale applicability.
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Achieving excellent efficiency to mineralize volatile organic compounds (VOCs) under nonthermal plasma catalysis (NTP-catalysis) systems tremendously relies on the catalyst design. Herein, we report a dual-template strategy for synthesizing a core-shell structured nitrogen-enriched hollow hybrid carbon (N-HHC) by a facile pyrolysis of a Mn-ZIF-8@polydopamine core-shell precursor. N-HHC exhibits a remarkable plasma synergy effect and superior degradation efficiency for toluene (up to 90% with a specific input energy of 281 J/L), excellent CO2 selectivity (>45%), and byproduct-inhibiting capability. Such outstanding functionality of the developed N-HHC is uniquely attributed to its hollow multistage and channeling structure, high concentration of O3-decomposing species (pyrrolic and oxide pyridinic-N), and abundant ZnO active sites. Shedding light on an efficient synthetic strategy for designing an advanced nanocatalyst with enhanced VOC destruction in the NTP-catalysis system, the present results could be extended to design other N-doped metal/metal oxide-decorated hollow porous carbons for environment-related applications.
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OBJECTIVE: To evaluate the effects of administering tranexamic acid (TXA) after cardiopulmonary bypass, instead of after anesthesia induction, on postoperative seizures and blood transfusion requirements. METHODS: Adult patients who underwent valve surgery and/or coronary artery bypass grafting at West China Hospital between July 1, 2011 and December 31, 2016 were retrospectively analyzed. Patients either received TXA after bypass (n = 2062) or not (n = 4236). Logistic regression and propensity score matching analysis were performed to assess effects of TXA on postoperative seizures and blood product requirements in hospital. RESULTS: Among 6298 patients, seizures occurred in 2.4% (102/4236) in the no-TXA group and 2.7% (56/2062) in the TXA group (P = 0.46). The number of patients receiving any blood products was greater in the no-TXA group (57.3%, 2428/4236) than in the TXA group (53.1%, 1095/2062) (P < 0.01), and the volume of blood products was also greater in the no-TXA group (1.5 vs. 1.0 units, P < 0.01). TXA was not associated with increased incidence of postoperative seizures (adjusted OR 1.16, 95% CI 0.83-1.62) but was associated with lower incidence of a requirement for blood products (adjusted OR 0.82, 95% CI 0.73-0.92). Similar results were obtained after patients from the two groups were matched based on propensity scoring. TXA was associated with reduced requirements for fresh frozen plasma, platelets and cryoprecipitate, but not red blood cells. CONCLUSIONS: Administering TXA after bypass may reduce requirements for blood products without increasing risk of seizures following cardiac surgery.
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Antifibrinolíticos , Ácido Tranexámico , Adulto , Antifibrinolíticos/efectos adversos , Pérdida de Sangre Quirúrgica/prevención & control , Puente Cardiopulmonar/efectos adversos , Humanos , Estudios Retrospectivos , Convulsiones/inducido químicamente , Convulsiones/epidemiología , Ácido Tranexámico/efectos adversosRESUMEN
The biguanide, metformin, is the first-choice therapeutic agent for type-2 diabetes, although the mechanisms that underpin metformin clinical efficacy remain the subject of much debate, partly due to the considerable variation in patient response to metformin. Identification of poor responders by genotype could avoid unnecessary treatment and provide clues to the underlying mechanism of action. GWAS identified SNPs associated with metformin treatment success at a locus containing the NPAT (nuclear protein, ataxia-telangiectasia locus) and ATM (ataxia-telangiectasia mutated) genes. This implies that gene sequence dictates a subsequent biological function to influence metformin action. Hence, we modified expression of NPAT in immortalized cell lines, primary mouse hepatocytes and mouse tissues, and analysed the outcomes on metformin action using confocal microscopy, immunoblotting and immunocytochemistry. In addition, we characterised the metabolic phenotype of npat heterozygous knockout mice and established the metformin response following development of insulin resistance. NPAT protein was localised in the nucleus at discrete loci in several cell types, but over-expression or depletion of NPAT in immortalised cell models did not change cellular responses to biguanides. In contrast, metformin regulation of respiratory exchange ratio (RER) was completely lost in animals lacking one allele of npat. There was also a reduction in metformin correction of impaired glucose tolerance, however no other metabolic abnormalities, or response to metformin, were found in the npat heterozygous mice. In summary, we provide methodological advancements for the detection of NPAT, demonstrate that minor reductions in NPAT mRNA levels (20-40%) influence metformin regulation of RER, and propose that the association between NPAT SNPs and metformin response observed in GWAS, could be due to loss of metformin modification of cellular fuel usage.
Asunto(s)
Glucemia/análisis , Proteínas de Ciclo Celular/genética , Índice Glucémico/efectos de los fármacos , Hipoglucemiantes/uso terapéutico , Metformina/uso terapéutico , Animales , Proteínas de la Ataxia Telangiectasia Mutada/genética , Línea Celular Tumoral , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estudio de Asociación del Genoma Completo , Índice Glucémico/fisiología , Células HEK293 , Células Hep G2 , Humanos , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Oxygen vacancy plays an important role in adsorption and activation of oxygen species and therefore promotes the catalytic performance of materials in heterogeneous oxidation reactions. Here, a series of K-doped É-MnO2 materials with different K loadings were synthesized by a reproducible post processing process. Results show that the presence of K+ enhances the reducibility and oxygen vacancy concentration of É-MnO2 due to the break of charge balance and the formation of low valence Mn species. 4-K/MnO2 material exhibits the highest toluene oxidation activity and satisfied long-term stability and water resistance owing to its superior reducibility and abundant surface absorbed oxygen (Oads). In situ DRIFTS demonstrate that Oads greatly accelerates toluene dehydrogenation rate and promotes benzoate formation, enhancing the activation and decomposition of toluene molecules. Moreover, the CC cleavage of benzene ring (forming maleic anhydride) is the rate-determining step of toluene oxidation, which can be easily occurred over 4-K/MnO2.