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The discovery of efficient and stable electrocatalysts for oxygen evolution reaction (OER) in acid is vital for the commercialization of the proton-exchange membrane water electrolyzer. In this work, we demonstrate that short-range Ru atom arrays with near-ideal Ru-Ru interatomic distances and a unique Ru-O hybridization state can trigger direct O*-O* radical coupling to form an intermediate O*-O*-Ru configuration during acidic OER without generating OOH* species. Further, the Ru atom arrays suppress the participation of lattice oxygen in the OER and the dissolution of active Ru. Benefiting from these advantages, the as-designed Ru array-Co3O4 electrocatalyst breaks the activity/stability trade-off that plagues RuO2-based electrocatalysts, delivering an excellent OER overpotential of only 160 mV at 10 mA cm-2 in 0.5 M H2SO4 and outstanding durability during 1500 h operation, representing one of the best acid-stable OER electrocatalysts reported to date. 18O-labeled operando spectroscopic measurements together with theoretical investigations revealed that the short-range Ru atom arrays switched on an oxide path mechanism (OPM) during the OER. Our work not only guides the design of improved acidic OER catalysts but also encourages the pursuit of short-range metal atom array-based electrocatalysts for other electrocatalytic reactions.
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Effectively targeting transcription factors in therapeutic interventions remains challenging, especially in core-binding factor-acute myeloid leukaemia (CBF-AML) characterized by RUNX1::ETO and CBFß::MYH11 fusions. However, recent studies have drawn attention towards aberrant amino acid metabolisms as actionable therapeutic targets. Here, by integrating the expression profile and genetic makeup in AML cohort, we found higher BCAT1 expression in CBF-AML patients compared with other subtypes. Metabolic profiling revealed that high BCAT1 expression led to reprogrammed branch amino acid metabolism in CBF-AML and was associated with sphingolipid pathway relating to the fitness of leukaemia cells, supported by transcriptomic profiling. Mechanistically, we demonstrated in cell lines and primary patient samples that BCAT1 was directly activated by RUNX1::ETO and CBFß::MYH11 fusion proteins similarly in a RUNX1-dependent manner through rewiring chromatin conformation at the BCAT1 gene locus. Furthermore, BCAT1 inhibition resulted in blunted cell cycle, enhanced apoptosis and myeloid differentiation of CBF-AML cells in vitro, and alleviated leukaemia burden and prolonged survival in vivo. Importantly, pharmacological inhibition of BCAT1 using the specific inhibitor Gabapentin demonstrated therapeutic effects, as evidenced by delayed leukaemia progression and improved survival in vivo. In conclusion, our study uncovers BCAT1 as a genetic vulnerability and a promising targeted therapeutic opportunity for CBF-AML.
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Subunidade alfa 2 de Fator de Ligação ao Core , Leucemia Mieloide Aguda , Proteínas de Fusão Oncogênica , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/patologia , Subunidade alfa 2 de Fator de Ligação ao Core/genética , Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo , Proteínas de Fusão Oncogênica/genética , Proteínas de Fusão Oncogênica/metabolismo , Animais , Subunidade beta de Fator de Ligação ao Core/genética , Subunidade beta de Fator de Ligação ao Core/metabolismo , Camundongos , Regulação Leucêmica da Expressão Gênica , Linhagem Celular TumoralRESUMO
BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC
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Quimiorradioterapia , Quimioterapia de Indução , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Pontuação de Propensão , Humanos , Masculino , Feminino , Carcinoma Nasofaríngeo/terapia , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/tratamento farmacológico , Pessoa de Meia-Idade , Quimiorradioterapia/métodos , Adulto , Neoplasias Nasofaríngeas/terapia , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/tratamento farmacológico , Quimioterapia de Indução/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Inibidores de Checkpoint Imunológico/uso terapêutico , Idoso , Cisplatino/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Estudos Retrospectivos , GencitabinaRESUMO
Mesenchymal stem cells (MSCs) exert beneficial therapeutic effects in acute kidney injury (AKI), while the detailed repair mechanism remains unclear. Herein, we probed the underlying mechanisms of MSC therapy in AKI by performing unbiased single-cell RNA sequencing in IRI model with/without MSC treatment. Our analyses uncovered the tubular epithelial cells (TECs) and immune cells transcriptomic diversity and highlighted a repair trajectory involving renal stem/progenitor cell differentiation. Our findings also suggested that profibrotic TECs expressing pro-fibrotic factors such as Zeb2 and Pdgfb promoted the recruitment of inflammatory monocytes and Th17 cells to injured kidney tissue, inducing TGF-ß1 secretion and renal fibrosis. Finally, in addition to activating the repair properties of renal progenitor/stem cells, we uncovered a role for MSC-derived miR-26a-5p in mediating the therapeutic effects of MSCs by inhibiting Zeb2 expression and suppressing pro-fibrotic TECs and its subsequent recruitment of immune cell subpopulations. These findings may help to optimize future AKI treatment strategies.
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We studied the origin of the vibrational signatures in the sum-frequency generation (SFG) spectrum of fibrillar collagen type I in the carbon-hydrogen stretching regime. For this purpose, we developed an all-reflective, laser-scanning SFG microscope with minimum chromatic aberrations and excellent retention of the polarization state of the incident beams. We performed detailed SFG measurements of aligned collagen fibers obtained from rat tail tendon, enabling the characterization of the magnitude and polarization-orientation dependence of individual tensor elements Xijk2 of collagen's nonlinear susceptibility. Using the three-dimensional atomic positions derived from published crystallographic data of collagen type I, we simulated its Xijk2 elements for the methylene stretching vibration and compared the predicted response with the experimental results. Our analysis revealed that the carbon-hydrogen stretching range of the SFG spectrum is dominated by symmetric stretching modes of methylene bridge groups on the pyrrolidine rings of the proline and hydroxyproline residues, giving rise to a dominant peak near 2942 cm-1 and a shoulder at 2917 cm-1. Weak asymmetric stretches of the methylene bridge group of glycine are observed in the region near 2870 cm-1, whereas asymmetric CH2-stretching modes on the pyrrolidine rings are found in the 2980 to 3030 cm-1 range. These findings help predict the protein's nonlinear optical properties from its crystal structure, thus establishing a connection between the protein structure and SFG spectroscopic measurements.
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Carbono , Colágeno Tipo I , Hidrogênio , Hidrogênio/química , Carbono/química , Colágeno Tipo I/química , Ratos , Animais , Análise Espectral/métodosRESUMO
Acute kidney injury (AKI) is a clinically common kidney disease. Age is an important factor that contributes to the susceptibility to AKI. Mesenchymal stem cells (MSCs) are a promising therapy for AKI, and miRNAs in exosomes (Exos) derived from MSCs are an important aspect of MSC treatment. However, the therapeutic effect of miRNA from MSC-derived Exos on AKI and the related mechanism have not been fully clarified. Whether there is a relationship between the mechanisms of senescence for AKI susceptibility and the therapeutic effect of MSCs has not been studied. We compared the degree of cisplatin-induced AKI injury in young and elderly mice and investigated changes in the expression of p53 and markers of DNA damage and apoptosis, which are important in both senescence and AKI. Ageing mice exhibited increased expression of p53 and pro-apoptosis markers. Upregulation of the senescence-associated DNA damage/p53 pathway may be an important susceptibility factor for cisplatin-induced AKI. Treatment with MSCs can reduce the degree of DNA damage and suppress p53 expression and apoptosis. Upon screening for differentially expressed miRNAs, let-7b-5p levels were found to be lower in aged mice than in young mice, and MSC treatment increased let-7b-5p levels. The presence of let-7b-5p in MSC-derived Exos alleviates tubular epithelial cell apoptosis by inhibiting p53, which reduces DNA damage and apoptosis pathway activity. Let-7b-5p downregulation may lead to increased renal AKI susceptibility, thus indicating that this miRNA is a potential driver of the MSC treatment response in AKI.
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Injúria Renal Aguda , Células-Tronco Mesenquimais , MicroRNAs , Camundongos , Animais , Cisplatino/efeitos adversos , Proteína Supressora de Tumor p53/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Apoptose , Células-Tronco Mesenquimais/metabolismoRESUMO
Regime shifts between nitrogen (N) and phosphorus (P) limitation, which trigger cyanobacterial succession, occur in shallow eutrophic lakes seasonally. However, the underlying mechanism is not yet fully illustrated. We provide a novel insight to address this from interactions between sediment P and nitrification through monthly field investigations including 204 samples and microcosm experiments in Lake Chaohu. Total N to P mass ratios (TN/TP) varied significantly across seasons especially during algal bloom in summer, with the average value being 26.1 in June and descending to 7.8 in September gradually, triggering dominant cyanobacterial succession from Microcystis to Dolichospermum. The regulation effect of sediment N/P on water column TN/TP was stronger in summer than in other seasons. Iron-bound P and alkaline phosphatase activity in sediment, rather than ammonium, contributed to the higher part of nitrification. Furthermore, our microcosm experiments confirmed that soluble active P and enzymatic hydrolysis of organic P, accumulating during algal bloom, fueled nitrifiers and nitrification in sediments. These processes promoted lake N removal and led to relative N deficiency in turn. Our results highlight that N and P cycles do not exist independently but rather interact with each other during lake eutrophication, supporting the dual N and P reduction program to mitigate eutrophication in shallow eutrophic lakes.
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Cianobactérias , Lagos , Nitrificação , Fósforo/análise , Nitrogênio/análise , Eutrofização , ChinaRESUMO
BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly developing and sometimes lethal pulmonary disease. Accurately predicting COVID-19 mortality will facilitate optimal patient treatment and medical resource deployment, but the clinical practice still needs to address it. Both complete blood counts and cytokine levels were observed to be modified by COVID-19 infection. This study aimed to use inexpensive and easily accessible complete blood counts to build an accurate COVID-19 mortality prediction model. The cytokine fluctuations reflect the inflammatory storm induced by COVID-19, but their levels are not as commonly accessible as complete blood counts. Therefore, this study explored the possibility of predicting cytokine levels based on complete blood counts. METHODS: We used complete blood counts to predict cytokine levels. The predictive model includes an autoencoder, principal component analysis, and linear regression models. We used classifiers such as support vector machine and feature selection models such as adaptive boost to predict the mortality of COVID-19 patients. RESULTS: Complete blood counts and original cytokine levels reached the COVID-19 mortality classification area under the curve (AUC) values of 0.9678 and 0.9111, respectively, and the cytokine levels predicted by the feature set alone reached the classification AUC value of 0.9844. The predicted cytokine levels were more significantly associated with COVID-19 mortality than the original values. CONCLUSIONS: Integrating the predicted cytokine levels and complete blood counts improved a COVID-19 mortality prediction model using complete blood counts only. Both the cytokine level prediction models and the COVID-19 mortality prediction models are publicly available at http://www.healthinformaticslab.org/supp/resources.php .
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COVID-19 , Humanos , Área Sob a Curva , Citocinas , Modelos Lineares , Análise de Componente PrincipalRESUMO
BACKGROUND: The diagnosis of primary membranous nephropathy (PMN) often depends on invasive renal biopsy, and the diagnosis based on clinical manifestations and target antigens may not be completely reliable as it could be affected by uncertain factors. Moreover, different experts could even have different diagnosis results due to their different experiences, which could further impact the reliability of the diagnosis. Therefore, how to properly integrate the knowledge of different experts to provide more reliable and comprehensive PMN diagnosis has become an urgent issue. METHODS: This paper develops a belief rule-based system for PMN diagnosis. The belief rule base is constructed based on the knowledge of the experts, with 9 biochemical indicators selected as the input variables. The belief rule-based system is developed of three layers: (1) input layer; (2) belief rule base layer; and (3) output layer, where 9 biochemical indicators are selected as the input variables and the diagnosis result is provided as the conclusion. The belief rule base layer is constructed based on the knowledge of the experts. The final validation was held with gold pattern clinical cases, i.e., with known and clinically confirmed diagnoses. RESULTS: 134 patients are used in this study, and the proposed method is defined by its sensitivity, specificity, accuracy and area under curve (AUC), which are 98.0%, 96.9%, 97.8% and 0.93, respectively. The results of this study present a novel and effective way for PMN diagnosis without the requirement of renal biopsy. CONCLUSIONS: Through analysis of the diagnosis results and comparisons with other methods, it can be concluded that the developed system could help diagnose PMN based on biochemical indicators with relatively high accuracy.
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Glomerulonefrite Membranosa , Humanos , Glomerulonefrite Membranosa/diagnóstico , Sistemas Inteligentes , Reprodutibilidade dos Testes , Receptores da Fosfolipase A2 , ComputadoresRESUMO
Importance: There are currently no therapies approved by the US Food and Drug Administration for nasopharyngeal carcinoma (NPC). Gemcitabine-cisplatin is the current standard of care for the first-line treatment of recurrent or metastatic NPC (RM-NPC). Objective: To determine whether toripalimab in combination with gemcitabine-cisplatin will significantly improve progression-free survival and overall survival as first-line treatment for RM-NPC, compared with gemcitabine-cisplatin alone. Design, Setting, and Participants: JUPITER-02 is an international, multicenter, randomized, double-blind phase 3 study conducted in NPC-endemic regions, including mainland China, Taiwan, and Singapore. From November 10, 2018, to October 20, 2019, 289 patients with RM-NPC with no prior systemic chemotherapy in the RM setting were enrolled from 35 participating centers. Interventions: Patients were randomized (1:1) to receive toripalimab (240 mg [n = 146]) or placebo (n = 143) in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. Main Outcome: Progression-free survival as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival, progression-free survival assessed by investigator, duration of response, and safety. Results: Among the 289 patients enrolled (median age, 46 [IQR, 38-53 years; 17% female), at the final progression-free survival analysis, toripalimab treatment had a significantly longer progression-free survival than placebo (median, 21.4 vs 8.2 months; HR, 0.52 [95% CI, 0.37-0.73]). With a median survival follow-up of 36.0 months, a significant improvement in overall survival was identified with toripalimab over placebo (hazard ratio [HR], 0.63 [95% CI, 0.45-0.89]; 2-sided P = .008). The median overall survival was not reached in the toripalimab group, while it was 33.7 months in the placebo group. A consistent effect on overall survival, favoring toripalimab, was found in subgroups with high and low PD-L1 (programmed death-ligand 1) expression. The incidence of all adverse events, grade 3 or greater adverse events, and fatal adverse events were similar between the 2 groups. However, adverse events leading to discontinuation of toripalimab or placebo (11.6% vs 4.9%), immune-related adverse events (54.1% vs 21.7%), and grade 3 or greater immune-related adverse events (9.6% vs 1.4%) were more frequent in the toripalimab group. Conclusions and Relevance: The addition of toripalimab to chemotherapy as first-line treatment for RM-NPC provided statistically significant and clinically meaningful progression-free survival and overall survival benefits compared with chemotherapy alone, with a manageable safety profile. These findings support the use of toripalimab plus gemcitabine-cisplatin as the new standard of care for this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT03581786.
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Anticorpos Monoclonais Humanizados , Antineoplásicos , Cisplatino , Gencitabina , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Cisplatino/uso terapêutico , Método Duplo-Cego , Gencitabina/administração & dosagem , Gencitabina/efeitos adversos , Gencitabina/uso terapêutico , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Carcinoma Nasofaríngeo/secundário , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Neoplasias Nasofaríngeas/secundário , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Estados Unidos , InternacionalidadeRESUMO
With the intensification of human disturbance in urban lakes, the loss of eukaryotic biodiversity (macroinvertebrates, etc.) reduces the accuracy of the index of biotic integrity (IBI) assessment. Therefore, how to accurately evaluate the ecological status of urban lakes based on IBI has become an important issue. In this study, 17 sampling sites from four lakes in Wuhan City, China were selected to analyze the composition and diversity characteristics of benthic and microbial communities and their relationship with environmental factors based on eDNA high-throughput sequencing, and compare the application effects of the benthic index of biotic integrity (B-IBI) and the microbial index of biotic integrity (M-IBI). Canonical correspondence analysis showed that the key environmental factors affecting benthic family/genus composition were temperature, conductivity, total phosphorus (TP), and total nitrogen (TN). Redundancy analysis showed that pH, TP, conductivity, and ammonia nitrogen had the greatest impact on microbial phyla/genera. After screening, four and six core metrics were determined from candidate parameters to establish B-IBI and M-IBI. The B-IBI evaluation results showed that healthy, sub-heathy, and poor accounted for 58.8%, 35.3%, and 5.9%, respectively, in the sites. The results of the M-IBI evaluation showed that 29.4% of the sites were healthy, 47.1% were sub-healthy, and 23.5% were common. M-IBI was positively correlated with water quality (r = 0.74, P < 0.001), whereas B-IBI was not. Further results showed that M-IBI was negatively correlated with the relative abundance of bloom-forming cyanobacteria Planktothrix (r = -0.54, P < 0.05). Therefore, M-IBI is more sensitive than B-IBI and can better reflect the actual water pollution status. This study can provide a new perspective for ecological assessment and management of urban lakes strongly disturbed by human activities.
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DNA Ambiental , Microbiota , Humanos , Monitoramento Ambiental/métodos , Ecossistema , Lagos , Rios , China , Nitrogênio/análiseRESUMO
BACKGROUND: Platinum-based concurrent chemoradiotherapy is the standard of care for patients with locoregionally advanced nasopharyngeal carcinoma. Additional gemcitabine and cisplatin induction chemotherapy has shown promising efficacy in phase 2 trials. METHODS: In a parallel-group, multicenter, randomized, controlled, phase 3 trial, we compared gemcitabine and cisplatin as induction chemotherapy plus concurrent chemoradiotherapy with concurrent chemoradiotherapy alone. Patients with locoregionally advanced nasopharyngeal carcinoma were randomly assigned in a 1:1 ratio to receive gemcitabine (at a dose of 1 g per square meter of body-surface area on days 1 and 8) plus cisplatin (80 mg per square meter on day 1), administered every 3 weeks for three cycles, plus chemoradiotherapy (concurrent cisplatin at a dose of 100 mg per square meter every 3 weeks for three cycles plus intensity-modulated radiotherapy) or chemoradiotherapy alone. The primary end point was recurrence-free survival (i.e., freedom from disease recurrence [distant metastasis or locoregional recurrence] or death from any cause) in the intention-to-treat population. Secondary end points included overall survival, treatment adherence, and safety. RESULTS: A total of 480 patients were included in the trial (242 patients in the induction chemotherapy group and 238 in the standard-therapy group). At a median follow-up of 42.7 months, the 3-year recurrence-free survival was 85.3% in the induction chemotherapy group and 76.5% in the standard-therapy group (stratified hazard ratio for recurrence or death, 0.51; 95% confidence interval [CI], 0.34 to 0.77; P = 0.001). Overall survival at 3 years was 94.6% and 90.3%, respectively (stratified hazard ratio for death, 0.43; 95% CI, 0.24 to 0.77). A total of 96.7% of the patients completed three cycles of induction chemotherapy. The incidence of acute adverse events of grade 3 or 4 was 75.7% in the induction chemotherapy group and 55.7% in the standard-therapy group, with a higher incidence of neutropenia, thrombocytopenia, anemia, nausea, and vomiting in the induction chemotherapy group. The incidence of grade 3 or 4 late toxic effects was 9.2% in the induction chemotherapy group and 11.4% in the standard-therapy group. CONCLUSIONS: Induction chemotherapy added to chemoradiotherapy significantly improved recurrence-free survival and overall survival, as compared with chemoradiotherapy alone, among patients with locoregionally advanced nasopharyngeal carcinoma. (Funded by the Innovation Team Development Plan of the Ministry of Education and others; ClinicalTrials.gov number, NCT01872962.).
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimiorradioterapia , Cisplatino/administração & dosagem , Desoxicitidina/análogos & derivados , Quimioterapia de Indução , Carcinoma Nasofaríngeo/tratamento farmacológico , Adolescente , Adulto , Cisplatino/efeitos adversos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Feminino , Humanos , Quimioterapia de Indução/efeitos adversos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/terapia , Análise de Sobrevida , Adulto Jovem , GencitabinaRESUMO
Electrically accelerated self-healable poly(ionic liquids) copolymers that exhibit resistor-capacitor (RC) circuit properties are developed. At low alternating current (AC) frequencies these materials behave as a resistor (R), whereas at higher frequencies as a capacitor (C). These properties are attributed to a combination of dipolar and electrostatic interactions in (1-[(2-methacryloyloxy)ethyl]-3-butylimidazolium bis(trifluoromethyl-sulfonyl)imide) copolymerized with methyl methacrylate (MMA) monomers to form p(MEBIm-TSFI/MMA)] copolymers. When the monomer molar ratio (MEBIm-TSFI:MMA) is 40/60, these copolymers are capable of undergoing multiple damage-repair cycles and self-healing is accelerated by the application of alternating 1.0-4.0 V electric field (EF). Self-healing in the absence of EFs is facilitated by van der Waals (vdW) interactions, but the application of AC EF induces back and forth movement of charges against the opposing force that result in dithering of electrostatic dipoles giving rise to interchain physical crosslinks. Electrostatic inter- and intrachain interactions facilitated by copolymerization of ionic liquid monomers with typically dielectric acrylic-based monomers result in enhanced cohesive energy densities that accelerate the recovery of vdW forces facilitating self-healing. Incorporating ionic liquids into commodity polymers offers promising uses as green conducting solid polyelectrolytes in self-healable energy storage, energy-harvesting devices, and many other applications.
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Líquidos Iônicos , Íons , Polimerização , Polímeros , Eletricidade EstáticaRESUMO
We present a generalized perturbative analytical formalism for evaluation and optimization of the chromatic dispersion of complex ultrafast optical systems. Notably, we identify polynomial and recursive relations associated with the chromatic dispersion orders that are identical to the Lah and Laguerre transforms. We explicitly outline the first ten dispersion terms and dispersion slope parameters and visualize the significance of the chromatic dispersion orders for several advanced ultrafast optical and photonic systems consisting of various optical materials and nanostructures, grating and prism-pair compressors, and hollow-core photonic anti-resonant fibers. The derived simple hypergeometric transforms are applicable for evaluation of infinitely high orders for any type of frequency-dependent phase and can facilitate the optimization of complex optical systems with controlled dispersion balance at the single-cycle waveform extreme.
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BACKGROUND: Publication of registered clinical trials is a critical step in the timely dissemination of trial findings. However, a significant proportion of completed clinical trials are never published, motivating the need to analyze the factors behind success or failure to publish. This could inform study design, help regulatory decision-making, and improve resource allocation. It could also enhance our understanding of bias in the publication of trials and publication trends based on the research direction or strength of the findings. Although the publication of clinical trials has been addressed in several descriptive studies at an aggregate level, there is a lack of research on the predictive analysis of a trial's publishability given an individual (planned) clinical trial description. OBJECTIVE: We aimed to conduct a study that combined structured and unstructured features relevant to publication status in a single predictive approach. Established natural language processing techniques as well as recent pretrained language models enabled us to incorporate information from the textual descriptions of clinical trials into a machine learning approach. We were particularly interested in whether and which textual features could improve the classification accuracy for publication outcomes. METHODS: In this study, we used metadata from ClinicalTrials.gov (a registry of clinical trials) and MEDLINE (a database of academic journal articles) to build a data set of clinical trials (N=76,950) that contained the description of a registered trial and its publication outcome (27,702/76,950, 36% published and 49,248/76,950, 64% unpublished). This is the largest data set of its kind, which we released as part of this work. The publication outcome in the data set was identified from MEDLINE based on clinical trial identifiers. We carried out a descriptive analysis and predicted the publication outcome using 2 approaches: a neural network with a large domain-specific language model and a random forest classifier using a weighted bag-of-words representation of text. RESULTS: First, our analysis of the newly created data set corroborates several findings from the existing literature regarding attributes associated with a higher publication rate. Second, a crucial observation from our predictive modeling was that the addition of textual features (eg, eligibility criteria) offers consistent improvements over using only structured data (F1-score=0.62-0.64 vs F1-score=0.61 without textual features). Both pretrained language models and more basic word-based representations provide high-utility text representations, with no significant empirical difference between the two. CONCLUSIONS: Different factors affect the publication of a registered clinical trial. Our approach to predictive modeling combines heterogeneous features, both structured and unstructured. We show that methods from natural language processing can provide effective textual features to enable more accurate prediction of publication success, which has not been explored for this task previously.
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Idioma , Projetos de Pesquisa , HumanosRESUMO
BACKGROUND: Slow-release fertilizer is widely used in cereal crop production because it is ecofriendly and laborsaving. Effects of different application stages (zero-, three-, and six-leaf stages, denoted as SN0, SN3, and SN6, respectively) of slow-release (N/P2 O5 /K2 O = 225/75/75 kg ha-1 ) fertilizer on physicochemical properties of starch from spring-sown waxy maize were investigated in 2018 and 2019. Application of traditional fertilizer (NCK, compound fertilizer; N/P2 O5 /K2 O = 75/75/75 kg ha-1 ) at sowing time and urea (N = 150 kg ha-1 ) at six-leaf stage was designated as the control. RESULTS: In comparison to the NCK, SN0 reduced grain starch content by 4.9%. Meanwhile, SN3 and SN6 did not affect this parameter. Nevertheless, all treatments, particularly SN6, increased average starch granule size. The slow-release fertilizer reduced proportion of chains with degree of polymerization (DP) > 24. Relative to NCK, SN6 increased starch crystallinity in both years, whereas SN0 and SN3 increased it in 2018 but reduced it in 2019. SN0 reduced peak, trough, and final viscosities, whereas SN3 and SN6 produced similar starch viscosities to those produced by NCK. No fertilizer mode affected gelatinization parameters, but SN6 produced a low retrogradation percentage. In comparison to data for 2018, starch produced in 2019 showed a small granule size, and a high proportion of short amylopectin chains. These properties endowed starch with high viscosity and low retrogradation percentage. CONCLUSION: In spring-sown waxy maize production, applying slow-release fertilizer at the six-leaf stage produced starch with high viscosity and low retrogradation tendency by enlarging granule size, increasing crystallinity, and reducing the proportion of long chains. © 2021 Society of Chemical Industry.
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Produção Agrícola/métodos , Preparações de Ação Retardada/química , Fertilizantes/análise , Amido/química , Zea mays/efeitos dos fármacos , Zea mays/metabolismo , Preparações de Ação Retardada/farmacologia , Estações do Ano , Sementes/química , Sementes/efeitos dos fármacos , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Amido/metabolismo , Viscosidade , Zea mays/química , Zea mays/crescimento & desenvolvimentoRESUMO
A visible-light-induced decarboxylation reaction was developed for the synthesis of alkylated benzimidazo[2,1-a]isoquinoline-6(5H)-ones and indolo[2,1-a]isoquinolin-6(5H)-ones under metal-free conditions. Impressively, metal catalysts and traditionally volatile organic solvents could be effectively avoided.
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Isoquinolinas , Fotossíntese , CatáliseRESUMO
Known for their adaptability to surroundings, capability of transport control of molecules, or the ability of converting one type of energy to another as a result of external or internal stimuli, responsive polymers play a significant role in advancing scientific discoveries that may lead to an array of diverge applications. This review outlines recent advances in the developments of selected commodity polymers equipped with stimuli-responsiveness to temperature, pH, ionic strength, enzyme or glucose levels, carbon dioxide, water, redox agents, electromagnetic radiation, or electric and magnetic fields. Utilized diverse applications ranging from drug delivery to biosensing, dynamic structural components to color-changing coatings, this review focuses on commodity acrylics, epoxies, esters, carbonates, urethanes, and siloxane-based polymers containing responsive elements built into their architecture. In the context of stimuli-responsive chemistries, current technological advances as well as a critical outline of future opportunities and applications are also tackled.
Assuntos
Polímeros Responsivos a Estímulos , Sistemas de Liberação de Medicamentos , Polímeros , TemperaturaRESUMO
Salinization in estuarine wetlands significantly alters the balance between their nitrogen (N) removal and retention abilities but these processes have not yet been characterized effectively. In the present study, the potential rates of sediment denitrification, anaerobic ammonium oxidation (anammox), and dissimilatory nitrate reduction to ammonium (DNRA) were mapped using N isotope tracing methods along salinity gradients across the Yellow River Delta wetland (YRDW) in China. The contribution of anammox to total dissimilatory N transformations in YRDW was merely 6.8%, whereas denitrification and DNRA contributed 52.3% and 40.9%, respectively. The potential rate of denitrification (5.82 µmol/kg/h) decreased significantly along salinity gradients and markedly exceeded DNRA potential rate (2.7 µmol/kg/h) in fresh wetlands, but was lower than that of DNRA in oligohaline wetlands (3.06 and 3.18 µmol/kg/h, respectively). Moreover, a significantly positive relationship between salinity and DNRA/denitrification was obeserved, indicating that increased salinity may favor DNRA over denitrification. Furthermore, total sulfur (TS) content and ratio of total organic carbon to total nitrogen (C/N) increased with the salinity gradient and showed evident positive relationships with the DNRA/denitrification ratio. In this study, we proved that increased salinization resulted in the dominance of DNRA over denitrification, possible through the addition of S and alteration of the C/N in estuarine wetlands, leading to increased N retention in estuarine wetlands during salinization, which would enhance the eutrophication potential within wetlands and in downstream ecosystems.
Assuntos
Compostos de Amônio , China , Desnitrificação , Ecossistema , Nitratos/análise , Nitrogênio/análise , Oxirredução , Salinidade , Áreas AlagadasRESUMO
Background: During the outbreak period of COVID-19 pneumonia, cancer patients have been neglected and in greater danger. Furthermore, the differential diagnosis between COVID-19 pneumonia and radiation pneumonitis in cancer patients remains a challenge. This study determined their clinical presentations and radiological features in order to early diagnose and separate COVID-19 pneumonia from radiation pneumonitis patients promptly. Methods and Findings: From January 21, 2020 to February 18, 2020, 112 patients diagnosed with suspected COVID-19 were selected consecutively. A retrospective analysis including all patients' presenting was performed. Four patients from 112 suspected individals were selected, including 2 males and 2 females with a median age of 54 years (range 39-64 years). After repeated pharyngeal swab nucleic acid tests, 1 case was confirmed and 3 cases were excluded from COVID-19 pneumonia. Despite the comparable morphologic characteristics of lung CT imaging, the location, extent, and distribution of lung lesions between COVID-19 pneumonia and radiation pneumonitis differed significantly. Conclusions: Lung CT imaging combined with clinical and laboratory findings can facilitate early diagnosis and appropriate management of COVID-19 pneumonia with a history of malignancy and radiation therapy.