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Construction of mesoporous frameworks by noncovalent bonding still remains a great challenge. Here, we report a micelle-directed nanocluster modular self-assembly approach to synthesize a novel type of two-dimensional (2-D) hydrogen-bonded mesoporous frameworks (HMFs) for the first time based on nanoscale cluster units (1.0-3.0 nm in size). In this 2-D structure, a mesoporous cluster plate with â¼100 nm in thickness and several micrometers in size can be stably formed into uniform hexagonal arrays. Meanwhile, such a porous plate consists of several (3-4) dozens of layers of ultrathin mesoporous cluster nanosheets. The size of the mesopores can be precisely controlled from 11.6 to 18.5 nm by utilizing the amphiphilic diblock copolymer micelles with tunable block lengths. Additionally, the pore configuration of the HMFs can be changed from spherical to cylindrical by manipulating the concentration of the micelles. As a general approach, various new HMFs have been achieved successfully via a modular self-assembly of nanoclusters with switchable configurations (nanoring, Keggin-type, and cubane-like) and components (titanium-oxo, polyoxometalate, and organometallic clusters). As a demonstration, the titanium-oxo cluster-based HMFs show efficient photocatalytic activity for hydrogen evolution (3.6 mmol g-1h-1), with a conversion rate about 2 times higher than that of the unassembled titanium-oxo clusters (1.5 mmol g-1h-1). This demonstrates that HMFs exhibited enhanced photocatalytic activity compared with unassembled titanium-oxo clusters units.
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OBJECTIVES: To compare the clinical efficacy and safety of single-use and reusable digital flexible ureteroscopy for the treatment of lower pole stones. METHODS: We enrolled 135 patients underwent reusable flexible ureteroscopy (FURS) and 78 patients underwent single-use digital FURS. Demographic, clinical variables, anatomical parameters of the lower calyx and perioperative indicators were compared in the two groups. RESULTS: Thirty-six patients in the infundibuloureter angle (IPA) < 45° subgroup had a mini-percutaneous nephrolithotomy (mini-PCNL), including 25 patients in the reusable FURS group and 11 patients in the single-use FURS group. The demographic and clinical variables in the two FURS groups were comparable. There was no statistical difference in the success rate of stone searching (P > 0.05). In terms of the success rate of lithotripsy, there was also no statistical difference in the IPA ≥ 45° subgroup (P > 0.05), whereas single-use FURS was superior in the IPA < 45° subgroup (χ2 = 6.513, P = 0.011). The length of the working fiber in the reusable FURS and single-use FURS groups was 3.20 ± 0.68 mm and 1.75 ± 0.47 mm, respectively (t = 18.297, P < 0.05). The use of a stone basket in the reusable FURS (31/135, 23.0%) was significantly higher than that in the single-use FURS (8/78, 10.3%) (χ2 = 5.336, P = 0.021). Compared with the reusable FURS group, the single-use FURS group had shorter operation times (P < 0.05) and higher stone-free rate (SFR) (χ2 = 4.230, P = 0.040). There was no statistical difference in the intraoperative transfer of mini-PCNL and postoperative complications between the two groups (P > 0.05). CONCLUSIONS: Single-use and reusable FURS are alternative methods for removal of lower pole stones (i.e., 2 cm or less). Single-use FURS has a high success rate of lithotripsy, shorter operation time, and high stone-free rate.
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Equipo Reutilizado , Cálculos Renales , Ureteroscopios , Ureteroscopía , Humanos , Ureteroscopía/métodos , Ureteroscopía/instrumentación , Masculino , Femenino , Estudios Retrospectivos , Cálculos Renales/cirugía , Persona de Mediana Edad , Adulto , Estudios de Casos y Controles , Resultado del Tratamiento , Diseño de Equipo , Equipos Desechables , AncianoRESUMEN
Pt-based supported materials, a widely used electrocatalyst for hydrogen evolution reaction (HER), often experience unavoidable electron loss, resulting in a mismatching of electronic structure and HER behavior. Here, a Pt/WO3 catalyst consisting of Pt species strongly coupled with defective WO3 polycrystalline nanorods is rationally designed. The electronic structure engineering of Pt sites on WO3 can be systematically regulated, and so that the optimal electron-rich Pt sites on Pt/WO3 -600 present an excellent HER activity with only 8 mV overpotential at 10 mA cm-2 . Particularly, the mass activity reaches 7015 mA mg-1 at the overpotential of 50 mV, up to 26-fold higher than that of the commercial Pt/C. The combination of experimental and theoretical results demonstrates that the O vacancies of WO3 effectively mitigate the tendency of electron transfer from Pt sites to WO3 , so that the d-band center could reach an appropriate level relative to Fermi level, endowing it with a suitable Δ G H ∗ $\Delta {G_{{{\rm{H}}^ * }}}$ . This work identifies the influence of the electronic structure on catalytic activity.
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The deposition time was controlled to prepare Mn nanowires of different lengths and diameters on templates of anodic aluminum oxide (AAO) with different pore sizes. The surface of as-prepared Mn nanowires was modified with SiO2 using the sol-gel method to improve their dispersion in aqueous solution. The effects of the diameter and length of the as-prepared Mn nanowires coated with SiO2 on the relaxivity were investigated. It was found that the Mn@SiO2 nanowires have smaller diameters and a higher longitudinal relaxivity (r1) with an increased length. Mn3@SiO2 nanowires had the highest r1 value of 5.8 mM-1 s-1 among the Mn@SiO2 nanowires (Mn3 nanowires have a diameter of about 30 nm and a length of about 0.5 µm length). Additionally, the biocompatibility and in vivo imaging ability of the Mn3@SiO2 nanowires were evaluated. The Mn3@SiO2 nanowires had good cytotoxicity and biocompatibility, and the kidney of SD rats showed a positive enhancement effect during small animal imaging at 1.5 T. This study showed that the Mn3@SiO2 nanowires could potentially become contrast agents (CAs) of longitudinal relaxation time (T1).
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OBJECTIVE: Alterations in DNA methylation are early events in endometrial cancer (EC) development and may have utility in EC detection via tampon-collected vaginal fluid. METHODS: For discovery, DNA from frozen EC, benign endometrium (BE), and benign cervicovaginal (BCV) tissues underwent reduced representation bisulfite sequencing (RRBS) to identify differentially methylated regions (DMRs). Candidate DMRs were selected based on receiver operating characteristic (ROC) discrimination, methylation level fold-change between cancers and controls, and absence of background CpG methylation. Methylated DNA marker (MDM) validation was performed using qMSP on DNA from independent EC and BE FFPE tissue sets. Women ≥45 years of age with abnormal uterine bleeding (AUB) or postmenopausal bleeding (PMB) or any age with biopsy-proven EC self-collected vaginal fluid using a tampon prior to clinically indicated endometrial sampling or hysterectomy. Vaginal fluid DNA was assayed by qMSP for EC-associated MDMs. Random forest modeling analysis was performed to generate predictive probability of underlying disease; results were 500-fold in-silico cross-validated. RESULTS: Thirty-three candidate MDMs met performance criteria in tissue. For the tampon pilot, 100 EC cases were frequency matched by menopausal status and tampon collection date to 92 BE controls. A 28-MDM panel highly discriminated between EC and BE (96% (95%CI 89-99%) specificity; 76% (66-84%) sensitivity (AUC 0.88). In PBS/EDTA tampon buffer, the panel yielded 96% (95% CI 87-99%) specificity and 82% (70-91%) sensitivity (AUC 0.91). CONCLUSION: Next generation methylome sequencing, stringent filtering criteria, and independent validation yielded excellent candidate MDMs for EC. EC-associated MDMs performed with promisingly high sensitivity and specificity in tampon-collected vaginal fluid; PBS-based tampon buffer with added EDTA improved sensitivity. Larger tampon-based EC MDM testing studies are warranted.
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Neoplasias Endometriales , Humanos , Femenino , Marcadores Genéticos , Ácido Edético/metabolismo , Neoplasias Endometriales/diagnóstico , Neoplasias Endometriales/genética , Neoplasias Endometriales/metabolismo , Endometrio/metabolismo , ADN , Metilación de ADNRESUMEN
BACKGROUND: Dealing with the giant pheochromocytomas (maximum diameter ≥ 6 cm) has long been a tough challenge for urologists. We introduced a new retroperitoneoscopic adrenalectomy method modified with renal-rotation techniques to treat giant pheochromocytomas. METHODS: 28 diagnosed patients were prospectively recruited as the intervention group. Meanwhile, by referring to the historical records in our database, matched patients who had undergone routine retroperitoneoscopic adrenalectomy (RA), transperitoneal laparoscopic adrenalectomy (TA), or open adrenalectomy (OA) for giant pheochromocytomas were selected as controls. Perioperative and follow-up data were collected for comparative assessment. RESULTS: Among all the groups, the intervention group had the minimal bleeding volume (28.93 ± 25.94 ml, p < 0.05), the least intraoperative blood pressure variation (59.11 ± 25.68 mmHg, p < 0.05), the shortest operation time (115.32 ± 30.69 min, p < 0.05), the lowest postoperative ICU admission rates (7.14%, p < 0.05), and shortest drainage time length (2.57 ± 0.50 days, p < 0.05). Besides, compared with TA and OA groups, intervention group was also characterized by lower pain scores (3.21 ± 0.63, p < 0.05), less postoperative complications (p < 0.05), earlier diet initiation time (1.32 ± 0.48 postoperative days, p < 0.05) and ambulation time (2.68 ± 0.48 postoperative days, p < 0.05). Follow-up blood pressure and metanephrine and normetanephrine levels in all intervention group patients remained normal. CONCLUSION: Compared with RA, TA, and OA, retroperitoneoscopic adrenalectomy with renal-rotation techniques is a more feasible, efficient, and secure surgical treatment for giant pheochromocytomas. TRIAL REGISTRATION: This study has been prospectively registered on the Chinese Clinical Trial Registry website (ChiCTR2200059953, date of first registration: 14/05/2022).
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Neoplasias de las Glándulas Suprarrenales , Laparoscopía , Feocromocitoma , Humanos , Neoplasias de las Glándulas Suprarrenales/cirugía , Adrenalectomía/métodos , Laparoscopía/métodos , Feocromocitoma/cirugía , Complicaciones Posoperatorias/cirugía , Estudios RetrospectivosRESUMEN
BACKGROUND: The risk factors for osteoporosis and its prognostic value in patients with bronchiectasis is not well characterized. We explored the risk factors for osteoporosis and its prognostic impact in hospitalized non-cystic fibrosis bronchiectasis (NCFB) patients in Southeast China. METHODS: This observational cohort study consecutively enrolled 179 hospitalized patients with NCFB bronchiectasis between 2017 and 2021. The risk factors and the impact of osteoporosis on all-cause mortality were assessed. RESULTS: 21.2% (38/179) of hospitalized NCFB patients were diagnosed with osteoporosis. Patients with osteoporosis had more severe symptoms (assessed by chronic airway assessment test, CAT, median 22 vs. 17, P = 0.017), poorer quality of life (assessed by St. George Respiratory Questionnaires, SQRC, median 42 vs. 27, P = 0.007), more severe disease stage (assessed by bronchiectasis severity index, BSI, median 14 vs. 11, P = 0.02), more comorbidities (assessed by Bronchiectasis Aetiology Comorbidity Index, BACI, median 5 vs. 4, P = 0.021) than patients without. Age, female sex, anemia, post-infection, and history of regular inhaled corticosteroid treatment were independent risk factors for osteoporosis in those patients. 21 patients (11.7%) died over a median follow-up period of 32 months. The all-cause mortality in NCFB patients with osteoporosis [28.94% (11/38)] was significantly higher than those without osteoporosis [7.09% (10/141)] [hazard ratio (HR) 5.34, 95% confidence interval (CI) 2.26-12.67, P < 0.001]. After adjusting for BSI and other confounding factors, osteoporosis was still independently associated with all-cause mortality in hospitalized NCFB patients (HR 4.29, 95% CI 1.75-10.49, P < 0.001). CONCLUSIONS: Osteoporosis had an independent effect on all-cause mortality in hospitalized NCFB patients. Management of comorbidities, including bone health, is a critical aspect of treating NCFB patients.
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Bronquiectasia , Fibrosis Quística , Osteoporosis , Femenino , Humanos , Pronóstico , Calidad de Vida , Bronquiectasia/complicaciones , Bronquiectasia/epidemiología , Bronquiectasia/diagnóstico , Osteoporosis/complicaciones , Osteoporosis/epidemiología , Factores de RiesgoRESUMEN
PURPOSE: The study aimed to construct a predictive model for clinically significant prostate cancer (csPCa) and investigate its clinical efficacy to reduce unnecessary prostate biopsies. METHODS: A total of 847 patients from institute 1 were included in cohort 1 for model development. Cohort 2 included a total of 208 patients from institute 2 for external validation of the model. The data obtained were used for retrospective analysis. The results of magnetic resonance imaging were obtained using Prostate Imaging Reporting and Data System version 2.1 (PI-RADS v2.1). Univariate and multivariate analyses were performed to determine significant predictors of csPCa. The diagnostic performances were compared using the receiver operating characteristic (ROC) curve and decision curve analyses. RESULTS: Age, prostate-specific antigen density (PSAD), and PI-RADS v2.1 scores were used as predictors of the model. In the development cohort, the areas under the ROC curve (AUC) for csPCa about age, PSAD, PI-RADS v2.1 scores, and the model were 0.675, 0.823, 0.875, and 0.938, respectively. In the external validation cohort, the AUC values predicted by the four were 0.619, 0.811, 0.863, and 0.914, respectively. Decision curve analysis revealed that the clear net benefit of the model was higher than PI-RADS v2.1 scores and PSAD. The model significantly reduced unnecessary prostate biopsies within the risk threshold of > 10%. CONCLUSIONS: In both internal and external validation, the model constructed by combining age, PSAD, and PI-RADS v2.1 scores exhibited excellent clinical efficacy and can be utilized to reduce unnecessary prostate biopsies.
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Imágenes de Resonancia Magnética Multiparamétrica , Neoplasias de la Próstata , Masculino , Humanos , Neoplasias de la Próstata/diagnóstico por imagen , Imagen por Resonancia Magnética , Antígeno Prostático Específico , Estudios RetrospectivosRESUMEN
The metal surfaces tend to be oxidized in air through dissociation of the O-O bond of oxygen to reduce the performances in various fields. Although several ligand modification routes have alleviated the oxidation of bulky metal surfaces, it is still a challenge for the oxidation resistance of small-size metal nanoparticles. Herein, we fixed the small-size Pd nanoparticles in tin-contained MFI zeolite crystals, where the tin acts as an electron donor to efficiently hinder the oxidation of Pd by weakening the adsorption of molecular oxygen and suppressing the O-O cleavage. This oxidation-resistant Pd catalyst exhibited superior performance in directly synthesizing hydrogen peroxide from hydrogen and oxygen, with the productivity of hydrogen peroxide at ≈10,170â mmol gPd -1 h-1 , steadily outperforming the catalysts tested previously. This work leads to the hypothesis that tin is an electron donor to realize oxidation-resistant Pd within zeolite crystals for efficient catalysis to overcome the limitation of generally supported Pd catalysts and further motivates the use of oxidation-resistant metal nanoparticles in various fields.
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High-risk individuals (HRIs) with familial and genetic predisposition to pancreatic ductal adenocarcinoma (PDAC) are eligible for screening. There is no accurate biomarker for detecting early-stage PDAC. We previously demonstrated that a panel of methylated DNA markers (MDMs) accurately detect sporadic PDAC. In this study we compared the distribution of MDMs in DNA extracted from tissue of PDAC cases who carry germline mutations and non-carriers with family history, with control tissue and demonstrate high discrimination like that seen in sporadic PDAC. These results provide scientific rationale for examining plasma MDMs in HRIs with the goal of developing a minimally-invasive early detection test.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patología , Marcadores Genéticos , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patología , Neoplasias PancreáticasRESUMEN
OBJECTIVE: Aberrant DNA methylation is an early event in carcinogenesis which could be leveraged to detect ovarian cancer (OC) in plasma. METHODS: DNA from frozen OC tissues, benign fallopian tube epithelium (FTE), and buffy coats from cancer-free women underwent reduced representation bisulfite sequencing (RRBS) to identify OC MDMs. Candidate MDM selection was based on receiver operating characteristic (ROC) discrimination, methylation fold change, and low background methylation among controls. Blinded biological validation was performed using methylated specific PCR on DNA extracted from independent OC and FTE FFPE tissues. MDMs were tested using Target Enrichment Long-probe Quantitative Amplified Signal (TELQAS) assays in pre-treatment plasma from women newly diagnosed with OC and population-sampled healthy women. A random forest modeling analysis was performed to generate predictive probability of disease; results were 500-fold in silico cross-validated. RESULTS: Thirty-three MDMs showed marked methylation fold changes (10 to >1000) across all OC subtypes vs FTE. Eleven MDMs (GPRIN1, CDO1, SRC, SIM2, AGRN, FAIM2, CELF2, RIPPLY3, GYPC, CAPN2, BCAT1) were tested on plasma from 91 women with OC (73 (80%) high-grade serous (HGS)) and 91 without OC; the cross-validated 11-MDM panel highly discriminated OC from controls (96% (95% CI, 89-99%) specificity; 79% (69-87%) sensitivity, and AUC 0.91 (0.86-0.96)). Among the 5 stage I/II HGS OCs included, all were correctly identified. CONCLUSIONS: Whole methylome sequencing, stringent filtering criteria, and biological validation yielded candidate MDMs for OC that performed with high sensitivity and specificity in plasma. Larger plasma-based OC MDM studies, including testing of pre-diagnostic specimens, are warranted.
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Metilación de ADN , Neoplasias Ováricas , Biomarcadores de Tumor/genética , Proteínas CELF/genética , Carcinoma Epitelial de Ovario/diagnóstico , Carcinoma Epitelial de Ovario/genética , Estudios de Factibilidad , Femenino , Marcadores Genéticos , Humanos , Proteínas del Tejido Nervioso/genética , Neoplasias Ováricas/diagnóstico , Neoplasias Ováricas/genética , Transaminasas/genéticaRESUMEN
NEW FINDINGS: What is the central question of this study? How does miR-302a-3p play a role in hypoxia-reoxygenation-induced pyroptosis of renal tubular epithelial cells? What is the main finding and its importance? Hypoxia-reoxygenation treatment upregulated the expression of miR-302a-3p in HK-2 cells, and then inhibited the transcription of FMRP translational regulator 1 (FMR1), so as to promote the activation of the NLRP3 inflammasome and aggravate the pyroptosis of HK-2 cells. miR-302a-3p was used as a molecular target in this study, which provides a new theoretical basis for the treatment of renal failure. ABSTRACT: Hypoxia-reoxygenation (H/R) induction can affect miRNA expression and then control NLR family pyrin domain containing 3 (NLRP3) inflammasome-mediated pyroptosis. This study investigated the mechanism of miR-302a-3p in H/R-induced renal tubular epithelial cell (RTEC) pyroptosis. Human HK-2 RTECs were induced by H/R. Lactate dehydrogenase content, cell activity and pyroptosis, and levels of NLRP3, GSDMD-N, caspase-1, interleukin (IL)-1ß, IL-18, superoxide dismutase, and malondialdehyde were detected to verify the effect of H/R on HK-2 cells. The NLRP3 inflammasome action was evaluated after H/R-induced HK-2 cells were treated with BAY11-7082, an inflammasome inhibitor. After inhibiting miR-302a-3p expression, the changes of pyroptosis were observed. The binding relation between miR-302a-3p and FMRP translational regulator 1 (FMR1) was verified. A function-rescue experiment verified the role of FMR1 in the regulation of pyroptosis. H/R-induced HK-2 cells showed significant pyroptosis injury, and the NLRP3 inflammasome was activated. After inhibiting the NLRP3 inflammasome, H/R-induced apoptosis was inhibited. After H/R treatment, miR-302a-3p in HK-2 cells was increased, and miR-302a-3p downregulation limited H/R-induced NLRP3 inflammasome-mediated pyroptosis. FMR1 is the target of miR-302a-3p. Inhibition of FMR1 alleviated the inhibition of H/R-induced HK-2 cell pyroptosis by miR-302a-3p inhibitor. Collectively, inhibiting miR-302a-3p can weaken its targeted inhibition on FMR1, thereby inhibiting the activation of NLRP3 inflammasomes and reducing caspase-1-dependent pyroptosis in HK-2 cells.
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MicroARNs , Piroptosis , Células Epiteliales/metabolismo , Proteína de la Discapacidad Intelectual del Síndrome del Cromosoma X Frágil/farmacología , Humanos , Hipoxia , Inflamasomas , MicroARNs/genética , MicroARNs/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis/genéticaRESUMEN
Heterogeneous catalysis plays a significant role in the modern chemical industry. Towards the rational design of novel catalysts, understanding reactions over surfaces is the most essential aspect. Typical industrial catalytic processes such as syngas conversion and methane utilisation can generate a large reaction network comprising thousands of intermediates and reaction pairs. This complexity not only arises from the permutation of transformations between species but also from the extra reaction channels offered by distinct surface sites. Despite the success in investigating surface reactions at the atomic scale, the huge computational expense of ab initio methods hinders the exploration of such complicated reaction networks. With the proliferation of catalysis studies, machine learning as an emerging tool can take advantage of the accumulated reaction data to emulate the output of ab initio methods towards swift reaction prediction. Here, we briefly summarise the conventional workflow of reaction prediction, including reaction network generation, ab initio thermodynamics and microkinetic modelling. An overview of the frequently used regression models in machine learning is presented. As a promising alternative to full ab initio calculations, machine learning interatomic potentials are highlighted. Furthermore, we survey applications assisted by these methods for accelerating reaction prediction, exploring reaction networks, and computational catalyst design. Finally, we envisage future directions in computationally investigating reactions and implementing machine learning algorithms in heterogeneous catalysis.
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OBJECTIVE: To evaluate the diagnostic value of prostate cancer antigen 3 and the Prostate Health Index for the detection of overall and clinically significant prostate cancer at initial biopsy. METHODS: A search was conducted in the online databases PubMed, Embase and the Cochrane database, and relevant articles published up to 23 February 2020 were extracted. RESULTS: Twenty studies including 10 376 patients were included in the meta-analysis. The pooled sensitivity and specificity were 0.55 (95% confidence interval 0.53-0.57) and 0.74 (95% confidence interval 0.72-0.75) for prostate cancer antigen 3 and 0.88 (95% confidence interval 0.86-0.90) and 0.36 (95% confidence interval 0.34-0.38) for the Prostate Health Index. The area under the curve was 0.72 for prostate cancer antigen 3 and 0.76 for the Prostate Health Index. The combination of prostate cancer antigen 3 and the Prostate Health Index had a higher area under the curve (0.79) and diagnostic odds ratio (5.83) than the use of Prostate Health Index (area under the curve 0.75, diagnostic odds ratio 4.69) or prostate cancer antigen 3 (area under the curve 0.77, diagnostic odds ratio 4.84) alone. For clinically significant prostate cancer detection, the pooled sensitivity and specificity were 0.80 (95% confidence interval 0.76-0.84) and 0.53 (95% confidence interval 0.50-0.55), respectively, for prostate cancer antigen 3, and 0.77 (95% confidence interval 0.71-0.82) and 0.64 (95% confidence interval 0.61-0.67), respectively, for the Prostate Health Index. The area under the curve was 0.71 for prostate cancer antigen 3 and 0.77 for the Prostate Health Index. CONCLUSION: Both the Prostate Health Index and prostate cancer antigen 3 showed acceptable and similar results for the detection of overall and clinically significant prostate cancer at first biopsy. A combination of these two diagnostic tests may be more helpful than the use of either test alone in prostate cancer management.
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Neoplasias de la Próstata , Biopsia , Humanos , Masculino , Oportunidad Relativa , Neoplasias de la Próstata/diagnóstico , Sensibilidad y EspecificidadRESUMEN
BACKGROUND & AIMS: Precursors of pancreatic cancer arise in the ductal epithelium; markers exfoliated into pancreatic juice might be used to detect high-grade dysplasia (HGD) and cancer. Specific methylated DNA sequences in pancreatic tissue have been associated with adenocarcinoma. We analyzed these methylated DNA markers (MDMs) in pancreatic juice samples from patients with pancreatic ductal adenocarcinomas (PDACs) or intraductal papillary mucinous neoplasms (IPMNs) with HGD (cases), and assessed their ability to discriminate these patients from individuals without dysplasia or with IPMNs with low-grade dysplasia (controls). METHODS: We obtained pancreatic juice samples from 38 patients (35 with biopsy-proven PDAC or pancreatic cystic lesions with invasive cancer and 3 with HGD) and 73 controls (32 with normal pancreas and 41 with benign disease), collected endoscopically from the duodenum after secretin administration from February 2015 through November 2016 at 3 medical centers. Samples were analyzed for the presence of 14 MDMs (in the genes NDRG4, BMP3, TBX15, C13orf18, PRKCB, CLEC11A, CD1D, ELMO1, IGF2BP1, RYR2, ADCY1, FER1L4, EMX1, and LRRC4), by quantitative allele-specific real-time target and signal amplification. We performed area under the receiver operating characteristic curve analyses to determine the ability of each marker, and panels of markers, to distinguish patients with HGD and cancer from controls. MDMs were combined to form a panel for detection using recursive partition trees. RESULTS: We identified a group of 3 MDMs (at C13orf18, FER1L4, and BMP3) in pancreatic juice that distinguished cases from controls with an area under the receiver operating characteristic value of 0.90 (95% CI, 0.83-0.97). Using a specificity cut-off value of 86%, this group of MDMs distinguished patients with any stage of pancreatic cancer from controls with 83% sensitivity (95% CI, 66%-93%) and identified patients with stage I or II PDAC or IPMN with HGD with 80% sensitivity (95% CI, 56%-95%). CONCLUSIONS: We identified a group of 3 MDMs in pancreatic juice that identify patients with pancreatic cancer with an area under the receiver operating characteristic value of 0.90, including patients with early stage disease or advanced precancer. These DNA methylation patterns might be included in algorithms for early detection of pancreatic cancer, especially in high-risk cohorts. Further optimization and clinical studies are needed.
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Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Carcinoma Ductal Pancreático/diagnóstico , ADN , Detección Precoz del Cáncer , Humanos , Jugo Pancreático , Neoplasias Pancreáticas/diagnósticoRESUMEN
Magnetic nanostructures and nanomaterials play essential roles in modern bio medicine and technology. Proper surface functionalization of nanoparticles (NPs) allows the selective bonding thus application of magnetic forces to a vast range of cellular structures and biomolecules. However, the spherical geometry of NPs poises a series of limitations in various potential applications. Mostly, typical spherical core shell structure consists of magnetic and non-magnetic layers have little tunability in terms of magnetic responses, and their single surface functionality also limits chemical activity and selectivity. In comparison to spherical NPs, nanowires (NWs) possess more degrees of freedom in achieving magnetic and surface chemical tenability. In addition to adjustment of magnetic anisotropy and inter-layer interactions, another important feature of NWs is their ability to combine diï¬erent components along their length, which can result in diverse bio-magnetic applications. Magnetic NWs have become the candidate material for biomedical applications owing to their high magnetization, cheapness and cost effective synthesis. With large magnetic moment, anisotropy, biocompatibility and low toxicity, magnetic NWs have been recently used in living cell manipulation, magnetic cell separation and magnetic hyperthermia. In this review, the basic concepts of magnetic characteristics of nanoscale objects and the influences of aspect ratio, composition and diameter on magnetic properties of NWs are addressed. Some underpinning physical principles of magnetic hyperthermia (MH), magnetic resonance imaging (MRI) and magnetic separation (MS) have been discussed. Finally, recent studies on magnetic NWs for the applications in MH, MRI and MS were discussed in detail.
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Hipertermia Inducida/métodos , Imagen por Resonancia Magnética/métodos , Imanes/análisis , Nanotecnología/métodos , Nanocables/análisis , Animales , Medios de Contraste/análisis , Diseño de Equipo , Humanos , Hipertermia Inducida/instrumentación , Imagen por Resonancia Magnética/instrumentación , Magnetismo/instrumentación , Magnetismo/métodos , Nanotecnología/instrumentación , Nanocables/ultraestructuraRESUMEN
The first-principles kinetic Monte Carlo (kMC) simulation has been demonstrated as a reliable multiscale modeling approach in silico to disclose the interplay among all the elementary steps in a complex reaction network for heterogeneous catalysis. Heterogeneous catalytic systems frequently contain fast surface diffusion processes of some adsorbates while the elementary steps in it would be much slower than those in fast diffusion. Consequently, the kMC simulation for these systems is easily trapped in the sub-basins of a super basin on a potential energy surface due to the continuous and repeated sampling of these fast processes, which would significantly increase the total accessible simulation time and even make it impossible to get the reasonable simulation results using the kMC simulation. In this work, we present an improved fast species redistribution (FSR) method for the kMC simulation to overcome the stiffness problem resulting from the low-barrier surface diffusion to accelerate the heterogeneous catalytic kMC simulation. Taking CO oxidations on Pt(111) and Pt(100) as examples, we demonstrate that the FSR approach can properly reproduce the results of an equivalent first-principles microkinetic model simulation with more reasonable reaction rates. The improved kMC simulation based on the FSR method can accurately incorporate the effect of the fast diffusion of species on the surface and provide several orders of magnitude of acceleration compared to the standard kMC simulation.
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OBJECTIVES: Pancreatic cystic lesions (PCLs) may be precancerous. Those likely to harbor high-grade dysplasia (HGD) or pancreatic cancer (PC) are targets for surgical resection. Current algorithms to predict advanced neoplasia (HGD/PC) in PCLs lack diagnostic accuracy. In pancreatic tissue and cyst fluid (CF) from PCLs, we sought to identify and validate novel methylated DNA markers (MDMs) that discriminate HGD/PC from low-grade dysplasia (LGD) or no dysplasia (ND). METHODS: From an unbiased whole-methylome discovery approach using predefined selection criteria followed by multistep validation on case (HGD or PC) and control (ND or LGD) tissues, we identified discriminant MDMs. Top candidate MDMs were then assayed by quantitative methylation-specific polymerase chain reaction on archival CF from surgically resected PCLs. RESULTS: Of 25 discriminant MDMs identified in tissue, 13 were selected for validation in 134 CF samples (21 cases [8 HGD, 13 PC], 113 controls [45 ND, 68 LGD]). A tree-based algorithm using 2 CF-MDMs (TBX15, BMP3) achieved sensitivity and specificity above 90%. Discrimination was significantly better by this CF-MDM panel than by mutant KRAS or carcinoembryonic antigen, with areas under the receiver operating characteristic curve of 0.93 (95% confidence interval: 0.86-0.99), 0.71 (0.57-0.85), and 0.72 (0.60-0.84), respectively. Cutoffs for the MDM panel applied to an independent CF validation set (31 cases, 56 controls) yielded similarly high discrimination, areas under the receiver operating characteristic curve = 0.86 (95% confidence interval: 0.77-0.94, P = 0.2). DISCUSSION: Novel MDMs discovered and validated in tissue accurately identify PCLs harboring HGD/PC. A panel of 2 MDMs assayed in CF yielded results with potential to enhance current risk prediction algorithms. Prospective studies are indicated to optimize and further evaluate CF-MDMs for clinical use.
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Carcinoma Ductal Pancreático/genética , Cistadenoma Seroso/genética , Metilación de ADN/genética , Quiste Pancreático/genética , Neoplasias Intraductales Pancreáticas/genética , Neoplasias Pancreáticas/genética , Lesiones Precancerosas/genética , Anciano , Proteína Morfogenética Ósea 3/genética , Antígeno Carcinoembrionario/metabolismo , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patología , Líquido Quístico/metabolismo , Cistadenoma Seroso/diagnóstico , Cistadenoma Seroso/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Quiste Pancreático/diagnóstico , Quiste Pancreático/patología , Neoplasias Intraductales Pancreáticas/diagnóstico , Neoplasias Intraductales Pancreáticas/patología , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patología , Reacción en Cadena de la Polimerasa , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/patología , Proteínas Proto-Oncogénicas p21(ras)/genética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Proteínas de Dominio T Box/genéticaRESUMEN
Designing artificial molecular machines to execute complex mechanical tasks, like coupling rotation and translation to accomplish transmission of motion, continues to provide important challenges. Herein, we demonstrated a novel molecular machine comprising a second-generation light-driven molecular motor and a bistable [1]rotaxane unit. The molecular motor can rotate successfully even in an interlocked [1]rotaxane system through a photoinduced cis-to -trans isomerization and a thermal helix inversion, resulting in concomitant transitional motion of the [1]rotaxane. The transmission process was elucidated via 1H NMR, 1H-1H COSY, HMQC, HMBC, and 2D ROESY NMR spectroscopies, UV-visible absorption spectrum, and density functional theory calculations. This is the first demonstration of a molecular motor to rotate against the appreciably noncovalent interactions between dibenzo-24-crown-8 and N-methyltriazolium moieties comprising the rotaxane unit, showing operational capabilities of molecular motors to perform more complex tasks.
RESUMEN
The dysregulated expression of the osteoarthritis (OA)-related genes in cartilage, such as matrix metalloproteinase 13 (MMP-13) and type X collagen (Col X), facilitates the onset and progression of OA. Reduced parathyroid hormone-related protein (PTHrP) may also accelerate this progression. Furthermore, miRNAs, endogenous regulators of mRNAs, are thought to play key roles in the pathogenesis of OA. In this study, we found that miR-195 levels were significantly upregulated in OA tissue, while PTHrP mRNA/protein expression was substantially downregulated, and there was a negative correlation between miR-195 and PTHrP. Upregulated miR-195 strongly inhibited Aggrecan, type II collagen (Col II) mRNA/protein expression, while it enhanced the expression of MMP-13 and Col X at mRNA/protein level; conversely, downregulated miR-195 significantly increased Col II mRNA/protein expression, while it decreased the expression of MMP-13 and Col X mRNA/protein. Moreover, our study demonstrated that PTHrP is a novel target of miR-195 using dual luciferase reporter assay. Finally, miR-195-mediated changes of Col II and OA-related genes were substantially attenuated by siRNAPTHrP treatment. These results suggested that miR-195 is involved in the pathogenesis of OA via PTHrP.