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Developing high-efficiency durable electrocatalysts in wide pH range for water splitting is significant for environmentally-friendly synthesis of renewable hydrogen energy. Herein, a facile method by dealloying designable multicomponent metallic glass precursors is reported to synthesize amorphous-crystalline heterostructured nanoporous high-entropy alloys (AC-HEAs) of CuAgAuPtPd, CuAgAuIrRu, and CuAgAuPtPdIrRu, heaped up by nanocrystalline particles with an average size of 2-3 nm and the amorphous glued phase. The synthesized AC-HEA-CuAgAuPtPd owns highly catalytic performances for hydrogen evolution reaction (HER), with 9.5 and 20 mV to reach 10 mA·cm-2 in 0.5 m H2SO4 and 1.0 m KOH, and AC-HEA-CuAgAuIrRu delivers 208 and 200 mV for oxygen evolution reaction (OER). Moreover, a two-electrode electrolyzer made of the AC-HEA-CuAgAuIrRu bifunctional electrodes exhibit a low cell voltage of 1.48 and 1.49 V in the acidic and alkaline conditions at 10 mA·cm-2 for overall water splitting. Combining the enhanced catalytic activities from nanoscale amorphous structure and atom-level synergistic catalyst in AC-HEAs provides an effective pathway for pH-universal electrocatalysts of water splitting.
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Background: The impact of dominant ventricular morphology on Fontan patient outcomes remain controversial. This study evaluates long-term results of right ventricle (RV) dominance versus left ventricle (LV) dominance in Fontan circulation without hypoplastic left heart syndrome (HLHS). Methods: We retrospectively examined 323 Fontan operations from our center. To minimize pre- and intra-Fontan heterogeneity, 42 dominant RV patients were matched with 42 dominant LV patients using propensity score matching, allowing for a comparative analysis of outcomes between groups. Results: The mean follow-up was 8.0 ± 4.6 years for matched RV dominant and 6.5 ± 4.7 years for matched LV dominant group (p > 0.05), showing no significant difference. The cumulative incidence of moderate or greater atrioventricular valve regurgitation was also comparable between the two groups (p > 0.05). Similarly, 10-year freedom from death or transplantation following the Fontan operation was 84% ± 7% in the matched dominant RV group, similar to 81% ± 7% in the matched dominant LV group (p > 0.05). The 10-year freedom from Fontan failure was 78% ± 8% in the matched dominant RV group, also similar to 75% ± 8% in the matched dominant LV group (p > 0.05). Multivariate analysis did not identify RV dominance as a risk factor for Fontan failure (p > 0.05). Conclusions: In the pre- and intra-Fontan context, RV dominance demonstrated similar and comparable long-term outcomes compared to LV dominance in non-HLHS Fontan circulation.
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The increasing atmospheric CO2 concentration (e[CO2]) has mixed effects on soybean most varieties' yield. This study elucidated the effect of e[CO2] on soybean yield and the underlying mechanisms related to photosynthetic capacity, non-structural carbohydrate (NSC) accumulation, and remobilisation. Four soybean cultivars were cultivated in open-top chambers at two CO2 levels. Photosynthesis rates were determined from R2 to R6. Plants were sampled at R5 and R8 to determine carbohydrate concentrations. There were significant variations in yield responses among the soybean cultivars under e[CO2], from no change in DS1 to a 22% increase in SN14. DS1 and SN14 had the smallest and largest increase, respectively, in daily carbon assimilation capacity. Under e[CO2], DS1, MF5, and XHJ had an increase in Ci, at which point the transition from Rubisco-limited to ribulose-1,5-bisphosphate regeneration-limited photosynthesis occurred, in contrast with SN14. Thus, the cultivars might have distinct mechanisms that enhance photosynthesis under e[CO2] conditions. A positive correlation was between daily carbon assimilation response to e[CO2] and soybean yield, emphasising the importance of enhanced photosynthate accumulation before the R5 stage in determining yield response to e[CO2]. E[CO2] significantly influenced NSC accumulation in vegetative organs at R5, with variation among cultivars. There was enhanced NSC remobilisation during seed filling, indicating cultivar-specific responses to the remobilisation of sucrose and soluble sugars, excluding sucrose and starch. A positive correlation was between leaf and stem NSC remobilisation and yield response to e[CO2], emphasising the role of genetic differences in carbohydrate remobilisation mechanisms in determining soybean yield variation under elevated CO2 levels.
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Metabolismo dos Carboidratos , Dióxido de Carbono , Glycine max , Fotossíntese , Sementes , Glycine max/metabolismo , Glycine max/crescimento & desenvolvimento , Glycine max/efeitos dos fármacos , Glycine max/fisiologia , Dióxido de Carbono/metabolismo , Dióxido de Carbono/farmacologia , Fotossíntese/efeitos dos fármacos , Sementes/metabolismo , Sementes/crescimento & desenvolvimento , Sementes/efeitos dos fármacosRESUMO
To address the measurement accuracy challenges posed by the internal flow complexity in atypical circular bend pipes with short turning sections and without extended straight pipe segments, this study designed an experimental circular "S"-shaped bent pipe with a diameter of 0.4 m and a bending angle of 135°. Numerical analysis was used to determine the stable region for velocity distribution within the experimental segment. Furthermore, a novel evaluation method based on the coefficient of variation was proposed to accurately locate the optimal position for installing thermal mass flow meters on the test cross section. Additionally, a formula for calculating the pipeline flow rate based on velocity differences was derived. This formula considers pipeline flow as the dependent variable and uses the velocity at two points in the test cross section as the independent variable. Experimental validation on a primary standard test bench demonstrated that the flow rate calculated by this method had an error controlled within 0.625% compared to the standard flow rate, thus effectively verifying the method's high accuracy and engineering applicability. This research provides a new testing methodology and practical basis for flow measurement in complex pipeline systems, offering significant guidance for research and applications in related fields.
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A magnetic MXene aerogel (Fe3O4@MXene@PEI) was prepared by crosslinking amino modified MXene with polyethyleneimine using epichlorohydrin as a cross-linker. Adsorption properties of Fe3O4@MXene@PEI aerogel for phenolic acids were evaluated by adsorption kinetics and isotherms experiments, showing that the high adsorption affinity was governed by multilayer chemisorption process. An efficient MSPE/HPLC method was developed for the determination of phenolic acids with excellent selectivity, good linearity (0.025-5.0 µg mL-1), low LODs (0.007-0.017 µg mL-1), and satisfactory recoveries (80.0-120.0 %). Moreover, the antioxidant activity of the Fe3O4@MXene@PEI purified compounds was superior to that of the conventional method as demonstrated by the results of scavenging experiments on 2,2 -diphenyl-1-picrylhydrazyl radical scavenging assay. Finally, 65 organic acids were identified in the Fe3O4@MXene@PEI treated honeysuckle extracts by UHPLC-Q-Exactive Orbitrap MS/MS analysis. The proposed sorbent exhibits remarkable promise for the selective separation and purification of organic acids from herbal products.
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Hidroxibenzoatos , Polietilenoimina , Hidroxibenzoatos/química , Hidroxibenzoatos/análise , Hidroxibenzoatos/isolamento & purificação , Polietilenoimina/química , Adsorção , Cromatografia Líquida de Alta Pressão/métodos , Géis/química , Plantas Medicinais/química , Extração em Fase Sólida/métodos , Antioxidantes/química , Antioxidantes/análise , Antioxidantes/isolamento & purificação , Espectrometria de Massas em Tandem/métodosRESUMO
Towards realizing the future quantum internet1,2, a pivotal milestone entails the transition from two-node proof-of-principle experiments conducted in laboratories to comprehensive multi-node set-ups on large scales. Here we report the creation of memory-memory entanglement in a multi-node quantum network over a metropolitan area. We use three independent memory nodes, each of which is equipped with an atomic ensemble quantum memory3 that has telecom conversion, together with a photonic server where detection of a single photon heralds the success of entanglement generation. The memory nodes are maximally separated apart for 12.5 kilometres. We actively stabilize the phase variance owing to fibre links and control lasers. We demonstrate concurrent entanglement generation between any two memory nodes. The memory lifetime is longer than the round-trip communication time. Our work provides a metropolitan-scale testbed for the evaluation and exploration of multi-node quantum network protocols and starts a stage of quantum internet research.
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The dispersion stability of carbonyl iron particle (CIP)-based magnetorheological fluid (MRF) is improved by CIP, which particle is etched with hydrochloric acid (HCl) to form porous structure with many hydroxyl groups and subsequently coated with silane coupling agents that have varying chain lengths. The microstructures, coating effect and magnetism of the CIPs were examined using the Scanning Electron Microscopy, Automatic Surface and Porosity Analyzer (BET), Fourier-Transform Infrared Spectroscopy, Thermogravimetric Analysis and Vibrating Sample Magnetometer. Furthermore, the rheological properties and dispersion stability of the MRFs were assessed using a Rotating Rheometer and Turbiscan-lab. The results revealed that the nanoporous structure appeared on the CIPs and the specific surface area increased remarkably after being etched by hydrochloric acid. Additionally, as the chain length of the silane coupling agent increases, the coated mass on the particles increases, the the density and the saturation magnetization of particles decreased, and the coated particles with different shell thicknesses were obtained; without a magnetic field, the viscosity of MRF prepared by coated particles increase slightly, due to the enhancement of special three-dimensional network structure; under a magnetic field, the viscosity of the MRF decreased distinctly; the sedimentation rate of MRF decreased from 58 to 3.5% after 100 days of sedimentation, and the migration distances of the MRFs were 22.4, 3.7, 2.4, and 0 mm, with particle sedimentation rates of 0.149, 0.019, 0.017, and 0 mm/h, respectively. The MRF with high dispersion stability was obtained, and the etching of CIP by HCl and the proper chain length of the coating of silane coupling agent were proved effective manners to improve the dispersion stability of MRF.
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Objective: This study aimed to determine the associated risk factors for proximal deep vein thrombosis (DVT) in patients with lower extremity and pelvic-acetabular fractures. Methods: The medical records of 4,056 patients with lower extremity and pelvic-acetabular fractures were retrospectively reviewed. The patients were classified into proximal or non-proximal DVT groups. Logistic regression models were used to determine the independent risk variables for proximal DVT. The predictive value of the related risk factors was further analyzed using receiver operating characteristic curves. Results: The prevalence of proximal DVT was 3.16%. Sex, body mass index (BMI), fracture site, injury mechanism, diabetes, coronary heart disease (CHD), injury-to-admission interval, hematocrit, platelet counts, and D-dimer levels differed significantly between the two groups. BMI ≥ 24.0â kg/m2, femoral shaft fractures, high-energy injury, diabetes, injury-to-admission interval >24â h were independent risk factors for proximal DVT. CHD decreased the risk of proximal DVT. The platelet and D-dimer had high negative predictive value for predicting proximal DVT formation, with cut-off values of 174 × 109/L and 2.18â mg/L, respectively. Conclusion: BMI ≥ 24.0â kg/m2, femoral shaft fractures, high-energy injury, diabetes, injury-to-admission interval >24â h were independent risk factors for proximal DVT in patients with lower extremity and pelvic-acetabular fractures. Platelet count and D-dimer level were effective indicators for excluding proximal DVT occurrence. CHD decreased the risk of proximal DVT.
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OBJECTIVE: To investigate the blood cadmium concentrations and the related change in Chinese urban children derived from the China Nutrition and Health Survey 2002 and 2012(CNHS 2002 and CNHS 2012). METHODS: The Chinese urban children aged 6-11 years were selected according to gender, age and regional distribution using the multi-stage stratified cluster random sampling method, as well as the corresponding whole blood samples. The blood cadmium concentration was carefully determined by the quadrupole inductively coupled plasma mass spectrometry(ICP-MS) and the percentage of blood cadmium over 2 µg/L was subsequently estimated. In addition, the upper limit values of the 95%CI of the 95th percentiles of available blood cadmium data was assessed as the threshold of cadmium exposure. RESULTS: Totally, 2182 Chinese urban children were included, and of these, 1036 children were from the CNHS 2002 and 1146 children were from the CNHS 2012. From the CNHS 2002 to the CNHS 2012, the median blood cadmium concentration was increased from 0.28 µg/L to 0.95 µg/L, and the percentage of blood cadmium with over 2 µg/L was elevated from 1.45% to 10.47%. In addition, the new estimated threshold of blood cadmium was ascended from 1.24 µg/L up to 2.89 µg/L. CONCLUSION: The risk of cadmium exposure in Chinese urban children aged 6-11 years was increasingly aggravated from the CHNS 2002 to the CNHS 2012.
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Cádmio , Exposição Ambiental , Criança , Humanos , Cádmio/sangue , China , População do Leste AsiáticoRESUMO
Using Euryale ferox husk as raw material, pristine biochar (EBC), Bi2MoO6-modified biochar (BM-EBC), and BiFeO3-modified biochar (BF-EBC) were prepared and employed for decontaminating Congo red (CR) from wastewater. Compared with EBC (217.59 mg/g) and BF-EBC (359.49 mg/g), a superior adsorption capacity of 460.77 mg/g was achieved by BM-EBC. Based on the evaluation results of the Freundlich and pseudo-second-order models, multilayer chemisorption was suggested as the adsorption mechanism. The adsorption process of BM-EBC was spontaneous and endothermic, and the rate-limiting step pertained to liquid film diffusion and intraparticle diffusion. The underlying removal mechanism was explored via SEM, BET, FTIR, XPS, Raman spectra, and Zeta potential analyses. The introduction of bismuth oxymetallates with their high number of M-O (M: Bi, Mo, Fe) structural elements provided the adsorbent with enlarged surface areas and reinforced oxygen functional groups, thereby promoting pore filling, π-π interactions, hydrogen bonding, and complexation, leading to enhanced adsorption capacity. These results demonstrate that Euryale ferox husk biochar modified by bismuth oxymetallates has high prospects for valorizing biomass waste and removing CR from wastewater.
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Bismuto , Carvão Vegetal , Vermelho Congo , Águas Residuárias , Poluentes Químicos da Água , Adsorção , Carvão Vegetal/química , Águas Residuárias/química , Bismuto/química , Vermelho Congo/química , Poluentes Químicos da Água/química , Purificação da Água/métodosRESUMO
Unlike graphene derived from graphite, borophenes represent a distinct class of synthetic two-dimensional materials devoid of analogous bulk-layered allotropes, leading to covalent bonding within borophenes instead of van der Waals (vdW) stacking. Our investigation focuses on 665 vdW-stacking boron bilayers to uncover potential bulk-layered boron allotropes through vdW stacking. Systematic high-throughput screening and stability analysis reveal a prevailing inclination toward covalently bonded layers in the majority of boron bilayers. However, an intriguing outlier emerges in δ5 borophene, demonstrating potential as a vdW-stacking candidate. We delve into electronic and topological structural similarities between δ5 borophene and graphene, shedding light on the structural integrity and stability of vdW-stacked boron structures across bilayers, multilayers, and bulk-layered allotropes. The δ5 borophene analogues exhibit metallic properties and characteristics of phonon-mediated superconductors, boasting a critical temperature near 22 K. This study paves the way for the concept of "borophite", a long-awaited boron analogue of graphite.
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OBJECTIVE: Benign nerve sheath tumors (BNSTs) present diagnostic challenges due to their heterogeneous nature. This study aimed to determine the significance of NRG1 as a novel diagnostic biomarker in BNST, emphasizing its involvement in the PI3K-Akt pathway and tumor immune regulation. METHODS: Differential genes related to BNST were identified from the GEO database. Gene co-expression networks, protein-protein interaction networks, and LASSO regression were utilized to pinpoint key genes. The CIBERSORT algorithm assessed immune cell infiltration differences, and functional enrichment analyses explored BNST signaling pathways. Clinical samples helped establish PDX models, and in vitro cell lines to validate NRG1's role via the PI3K-Akt pathway. RESULTS: Nine hundred eighty-two genes were upregulated, and 375 downregulated in BNST samples. WGCNA revealed the brown module with the most significant difference. Top hub genes included NRG1, which was also determined as a pivotal gene in disease characterization. Immune infiltration showed significant variances in neutrophils and M2 macrophages, with NRG1 playing a central role. Functional analyses confirmed NRG1's involvement in key pathways. Validation experiments using PDX models and cell lines further solidified NRG1's role in BNST. CONCLUSION: NRG1 emerges as a potential diagnostic biomarker for BNST, influencing the PI3K-Akt pathway, and shaping the tumor immune microenvironment.
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Neoplasias de Bainha Neural , Fosfatidilinositol 3-Quinases , Humanos , Proteínas Proto-Oncogênicas c-akt , Algoritmos , Biomarcadores , Microambiente Tumoral , Neuregulina-1/genéticaRESUMO
Soil biogeochemical cycles are essential for regulating ecosystem functions and services. However, little knowledge has been revealed on microbe-driven biogeochemical processes and their coupling mechanisms in soil profiles. This study investigated the vertical distribution of soil functional composition and their contribution to carbon (C), nitrogen (N) and phosphorus (P) cycling in the humus horizons (A-horizons) and parent material horizons (C-horizons) in Udic and Ustic Isohumosols using shotgun sequencing. Results showed that the diversity and relative abundance of microbial functional genes was influenced by soil horizons and soil types. In A-horizons, the relative abundances of N mineralization and liable C decomposition genes were significantly greater, but the P cycle-related genes, recalcitrant C decomposition and denitrification genes were lower compared to C-horizons. While, Ustic Isohumosols had lower relative abundances of C decomposition genes but higher relative abundances of N mineralization and P cycling-related pathways compared to Udic Isohumosols. The network analysis revealed that C-horizons had more interactions and stronger stability of functional gene networks than in A-horizons. Importantly, our results provide new insights into the potential mechanisms for the coupling processes of soil biogeochemical cycles among C, N and P, which is mediated by specific microbial taxa. Soil pH and carbon quality index (CQI) were two sensitive indicators for regulating the relative abundances and the relationships of functional genes in biogeochemical cycles. This study contributes to a deeper understanding of the ecological functions of soil microorganisms, thus providing a theoretical basis for the exploration and utilization of soil microbial resources and the development of soil ecological control strategies.
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Ecossistema , Solo , Solo/química , Microbiologia do Solo , Nitrogênio/análise , Carbono/metabolismo , Fósforo/metabolismo , Concentração de Íons de HidrogênioRESUMO
Selecting an appropriate intensity of epidemic prevention and control measures is of vital significance to promoting the two-way dynamic coordination of epidemic prevention and control and economic development. In order to balance epidemic control and economic development and suggest scientific and reasonable traffic control measures, this paper proposes a SEIQR model considering population migration and the propagation characteristics of the exposed and the asymptomatic, based on the data of COVID-19 cases, Baidu Migration, and the tourist economy. Further, the factor traffic control intensity is included in the model. After determining the functional relationship between the control intensity and the number of tourists and the cumulative number of confirmed cases, the NSGA-II algorithm is employed to perform multi-objective optimization with consideration of the requirements for epidemic prevention and control and for economic development to get an appropriate traffic control intensity and suggest scientific traffic control measures. With Xi'an City as an example. The results show that the Pearson correlation coefficient between the predicted data of this improved model and the actual data is 0.996, the R-square in the regression analysis is 0.993, with a significance level of below 0.001, suggesting that the predicted data of the model are more accurate. With the continuous rise of traffic control intensity in different simulation scenarios, the cumulative number of cases decreases by a significant amplitude. While balancing the requirements for epidemic prevention and control and for tourist economy development, the model works out the control intensity to be 0.68, under which some traffic control measures are suggested. The model presented in this paper can be used to analyze the impacts of different traffic control intensities on epidemic transmission. The research results in this paper reveal the traffic control measures balancing the requirements for epidemic prevention and control and for economic development.
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COVID-19 , Epidemias , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Cidades/epidemiologia , Desenvolvimento Econômico , China/epidemiologiaRESUMO
Hole-transport-layer-free perovskite solar cells have attracted strong interest due to their simple structure and low cost, but charge recombination is serious. Built-in electric field engineering is an intrinsic driver to facilitate charge separation transport and improve the efficiency of photovoltaic devices. However, the enhancement of the built-in electric field strength is often accompanied by the narrowing of the space charge region, which becomes a key constraint to the performance improvement of the device. Here, we propose an effective regulation method, the component engineering of quantum dots, to enhance the strength of the built-in electric field and broaden the range of space charge. By using all inorganic CsPbBrxI3-x (x = 0, 1, 2, 3) quantum dot interface modification to passivate the defects of MAPbI3 perovskite films, the regulation law of quantum dot components on the work function of perovskite films was revealed, and the mechanism of their influence on the internal electric field intensity and space charge region distribution was further clarified, thereby fundamentally solving the serious problem of charge recombination. As directly observed by electron-beam-induced current (EBIC), the introduction of CsPbBr2I quantum dots can effectively enhance the interfacial electric field intensity, widening the space charge region from 160 to 430 nm. Moreover, the efficiency of the hole-free transport layer perovskite solar cells modified by CsPbBr2I quantum dots was also significantly enhanced by 1.5 times. This is an important guideline for electric field modulation and efficiency improvement within photovoltaic devices with other simplified structures.
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The skin is intrinsically a cell-membrane-compartmentalized hydrogel with high mechanical strength, potent antimicrobial ability, and robust immunological competence, which provide multiple protective effects to the body. Methods capable of preparing hydrogels that can simultaneously mimic the structure and function of the skin are highly desirable but have been proven to be a challenge. Here, dual structurally and functionally skin-mimicking hydrogels are generated by crosslinking cell-membrane compartments. The crosslinked network is formed via free radical polymerization using olefinic double bond-functionalized extracellular vesicles as a crosslinker. Due to the dissipation of stretching energy mediated by vesicular deformation, the obtained compartment-crosslinked network shows enhanced mechanical strength compared to hydrogels crosslinked by regular divinyl monomers. Biomimetic hydrogels also exhibit specific antibacterial activity and adequate ability to promote the maturation and activation of dendritic cells given the existence of numerous extracellular vesicle-associated bioactive substances. In addition, the versatility of this approach to tune both the structure and function of the resulting hydrogels is demonstrated through introducing a second network by catalyst-free click reaction-mediated crosslinking between alkyne-double-ended polymers and azido-decorated extracellular vesicles. This study provides a platform to develop dual structure- and function-controllable skin-inspired biomaterials.
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Hidrogéis , Pele , Hidrogéis/química , Materiais Biocompatíveis/química , Polímeros , Membrana CelularRESUMO
All-inorganic cesium lead bromide quantum dots (CsPbBr3 -QD) compounds are potential candidates for optoelectronic devices, because of their excellent fluorescence luminescence and thermal stability. However, the many heterojunction interfaces and large band gap induce the low power conversion efficiency in the CsPbBr3 -QD heterojunction, limiting its practical applications. Hereby, in combination with the pressure regulation and TiO2 /CsPbBr3 -QD heterojunction, the interface interaction within the heterojunction can be enhanced and the band gap can be narrowed. The pressure-induced OâTiâO bond softening and PbBr6 octahedron stiffening at the interface region significantly enhance the interface interactions that are favorable to the carrier transport. Compared with CsPbBr3 -QD, the atomic interaction between Pb and Br of TiO2 /CsPbBr3 -QD heterojunction can be dramatically enhanced at high pressures, leading to increased band gap narrowing rate by two times, which is useful to widen the absorption spectrum. The fluorescence intensity increases by two times. Compression increases the photocurrent and maintains it after the pressure is released, which is due to the enhanced interface interaction induced by the high pressure. The findings provide new opportunities to adjust the physical properties of perovskite heterogeneous structures, and have important applications in the field of new-generation photovoltaic devices.
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Herein, a magnetic borate-functionalized MXene composite with multiple boronic affinity sites was fabricated by embedding Fe3 O4 nanoparticles with 4-formylphenylboronic acid functionalized Ti3 C2 Tx nanosheets and served as sorbent for the simultaneous extraction of catecholamines (CAs) in urine samples. The morphology and structure of the magnetic materials were investigated using scanning microscopy, vibrating sample magnetometer, X-ray photoelectron spectrometer, and X-ray diffraction. The introduction of polyethyleneimine can amplify the bonded boronic acid groups, thereby effectively improving the adsorption capacities for CAs based on the multiple interactions of boronic affinity, hydrogen bonding, and metal coordination. The adsorption performance was investigated using the kinetics and isotherms models, and the main parameters that influence the extraction efficiency were optimized. Under the most favorable magnetic solid-phase extraction condition, a sensitive method for the analysis of CAs in urine samples was developed by combining magnetic solid-phase extraction conditions with high-performance liquid chromatography detection. The findings illustrated that the proposed approach possessed a wide linearity range of 0.05-250 ng/mL with an acceptable correlation coefficient (R2 ≥ 0.9984) and detection limits of 0.010-0.015 ng/mL for the target CAs. The research not only provides a notable composite with multiple boronic affinity sites but also offers an effective and feasible measure for the detection of CAs in biological samples.
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Catecolaminas , Nanopartículas de Magnetita , Nitritos , Elementos de Transição , Polietilenoimina/química , Adsorção , Ácidos Borônicos/química , Cromatografia Líquida de Alta Pressão , Extração em Fase Sólida , Nanopartículas de Magnetita/química , Fenômenos MagnéticosRESUMO
INTRODUCTION: Bladder cancer (BLCA) affects millions of people worldwide, with high rates of incidence and mortality. Ferroptosis proves to be a novel form of cell death process that is triggered by oxidative stress. METHODS: We procured a total of 25 single nuclear RNA-seq (snRNA-seq) samples from GSE169379 in GEO database. We obtained different cohorts of BLCA patients from the TCGA and GEO databases for model training and validation. A total of 369 ferroptosis-related genes (FRGs) were selected from the FerrDb database. AUCell analysis was performed to assign ferroptosis scores to all the cell types. Weighted Gene Co-Expression Network Analysis (WGCNA), COX, and LASSO regression analysis were conducted to retain and finalize the genes of prognostic values. Various bioinformatic approaches were utilized to depict immune infiltration profile. We conducted a series of colony formation analysis, flow cytometry and western blot (WB) analysis to determine the role of SKAP1 in BLCA. RESULTS: We divided the cells into high ferroptosis group and low ferroptosis group according to ferroptosis activity score, and then screened 2150 genes most associated with ferroptosis by differential expression analysis, which are related to UV-induced DNA damage, male hormone response, fatty acid metabolism and hypoxia. Subsequently, WGCNA algorithm further screened 741 ferroptosis related genes from the 2150 genes for the construction of prognostic model. Lasso-Cox regression analysis was used to construct the prognostic model, and the prognostic model consisting of 6 genes was obtained, namely JUN, SYT1, MAP3K8, GALNT14, TCIRG1, and SKAP1. Next, we constructed a nomogram model that integrated clinical factors to improving the accuracy. In addition, we performed drug sensitivity analyses in different subgroups and found that Staurosporine, Rapamycin, Gemcitabine, and BI-2536 may be candidates for the drugs treatment in high-risk populations. The ESTIMATE results showed higher stromal scores, immune scores, and ESTIMATE scores in the low-risk group, indicating a higher overall immunity level and immunogenicity of tumor microenvironment (TME) in this group, and tumor immune dysfunction and exclusion (TIDE) analysis confirmed a better response to immunotherapy in the low-risk group. Finally, we selected the oncogene SKAP1 in the prognostic gene for in vitro validation, and found that SKAP1 directly regulated BLCA cell proliferation and apoptosis. CONCLUSION: We identified a set of six genes, JUN, SYT1, MAP3K8, GALNT14, TCIRG1, and SKAP1, that exhibited significant potential in stratification of BLCA patients with varying prognosis. In addition, we uncovered the direct regulatory effect of SKAP1 on BLCA cell proliferation and apoptosis, shedding some light on the role of FRGs in pathogenesis of BLCA.
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Ferroptose , Neoplasias da Bexiga Urinária , ATPases Vacuolares Próton-Translocadoras , Humanos , Masculino , Multiômica , Ferroptose/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/terapia , Oncogenes , Metabolismo dos Lipídeos , Microambiente TumoralRESUMO
Evidence suggests that the DNA of oral pathogens is detectable in the dilated aortic tissue of abdominal aortic aneurysm (AAA), one of the most fatal cardiovascular diseases. However, the association between oral microbial homeostasis and aneurysm formation remains largely unknown. In this study, a cohort of individuals, including 53 AAA patients and 30 control participants (CTL), was recruited for salivary microbiota investigation by 16S rRNA gene sequencing and bioinformatics analysis. Salivary microbial diversity was decreased in AAA compared with CTL, and the microbial structures were significantly separated between the two groups. Additionally, significant taxonomic and functional changes in the salivary microbiota of AAA participants were observed. The genera Streptococcus and Gemella were remarkably enriched, while Selenomonas, Leptotrichia, Lautropia and Corynebacterium were significantly depleted in AAA. Co-occurrence network analysis showed decreased potential interactions among the differentially abundant microbial genera in AAA. A machine-learning model predicted AAA using the combination of 5 genera and 14 differentially enriched functional pathways, which could distinguish AAA from CTL with an area under the receiver-operating curve of 90.3 %. Finally, 16 genera were found to be significantly positively correlated with the morphological parameters of AAA. Our study is the first to show that AAA patients exhibit oral microbial dysbiosis, which has high predictive power for AAA, and the over-representation of specific salivary bacteria may be associated with AAA disease progression. Further studies are needed to better understand the function of putative oral bacteria in the etiopathogenesis of AAA. Importance: Host microbial dysbiosis has recently been linked to AAA as a possible etiology. To our knowledge, studies of the oral microbiota and aneurysms remain scarce, although previous studies have indicated that the DNA of some oral pathogens is detectable in aneurysms by PCR method. We take this field one step further by investigating the oral microbiota composition of AAA patients against control participants via high-throughput sequencing technologies and unveiling the potential microbial biomarker associated with AAA formation. Our study will provide new insights into AAA etiology, treatment and prevention from a microecological perspective and highlight the effects of oral microbiota on vascular health.