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The synthesis of stable polynitrogen compounds with high-energy density has long been a major challenge. The cyclo-pentazolate anion (cyclo-N5 -) is successfully converted into aromatic and structurally symmetric bipentazole (N10) via electrochemical synthesis using highly conductive multi-walled carbon nanotubes (MWCNTs) as the substrate and sodium pentazolate hydrate ([Na(H2O)(N5)]·2H2O) as the raw material. Attenuated total refraction Fourier transform infrared spectroscopy, Raman spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, transmission electron microscopy, and density functional theory calculations confirmed the structure and homogeneous distribution of N10 in the sidewalls of the MWCNTs (named MWCNT-N10-n m). The MWCNT-N10-2.0 m is further used as a catalyst for electrochemical oxygen reduction to synthesize hydrogen peroxide from oxygen with a two-electron selectivity of up to 95%.
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Single-atom catalysts show good oxygen reduction reaction (ORR) performance in metal-air battery. However, the symmetric electron distribution results in discontented adsorption energy of ORR intermediates and a lower ORR activity. Herein, Fe-Co dual-atom catalyst with FeN3-CoN3 configuration was prepared by encapsulating nitrogen-rich ion (triethylenediamine cobalt complex, [Co(en)3]3+) in Fe based MOF cage to greatly enhance ORR performance. Due to the confinement effect of the MOF cage, the encapsulated [Co(en)3]3+ is closer to Fe of MOF, thus easily generating FeN3-CoN3 sites. The FeN3-CoN3 sites can break the symmetric electron distribution of single-atom sites, optimizing adsorption energy of oxygen intermediate. Thus, FeCo-NC exhibits extraordinary ORR activity with a high half-wave potential of 0.915 V and 0.789 V in alkaline and acidic electrolyte, respectively, while it was 0.874 V and 0.79 V for Pt/C. The liquid and solid Zn-air batteries with FeCo-NC as cathode show higher peak power density and specific capacity. DFT results indicate that FeN3-CoN3 site can reduce the reaction energy barrier of the rate-determining step resulting in an excellent ORR performance.
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As a remote and non-contact stimulus, light offers the potential for manipulating the polarization of ferroelectric materials without physical contact. However, in current research, the non-contact write-read (erase) process lacks direct observation through the stable current as output signal. To address this limitation, we investigated the photoinduced polarization switching capabilities of the cyanide-bridged compound [Fe2Co] using visible light, leading to the achievement of rewritable polarization. By subjecting [Fe2Co] crystals to alternating irradiation with 785 nm and 532 nm light, the polarization changes exhibited a distinct square wave pattern, confirming the reliability of the writing and erasing processes. Initialization involved exposing specific crystal units to 532 nm light for storing "1" or "0" information, while reading was accomplished by scanning the units with 785 nm light, resulting in brief current pulses for "1" states and no current signal for "0" states. This research unveils new possibilities for optical storage systems, paving the way for efficient and rewritable data storage and retrieval technologies, such as the next-generation memories.
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PURPOSE: The purpose of this study is to investigate whether gene mutations can lead to the growth of malignant pulmonary nodules. METHODS: Retrospective analysis was conducted on patients with pulmonary nodules at Hebei Provincial People's Hospital, collecting basic clinical information such as gender, age, BMI, and hematological indicators. According to the inclusion and exclusion criteria, 85 patients with malignant pulmonary nodules were selected for screening, and gene mutation testing was performed on all patient tissues to explore the relationship between gene mutations and the growth of malignant pulmonary nodules. RESULTS: There is a correlation between KRAS and TP53 gene mutations and the growth of pulmonary nodules (P < 0.05), while there is a correlation between KRAS and TP53 gene mutations and the growth of pulmonary nodules in the subgroup of invasive malignant pulmonary nodules (P < 0.05). CONCLUSION: Mutations in the TP53 gene can lead to the growth of malignant pulmonary nodules and are correlated with the degree of invasion of malignant pulmonary nodules.
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Neoplasias Pulmonares , Mutación , Proteínas Proto-Oncogénicas p21(ras) , Proteína p53 Supresora de Tumor , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Proteínas Proto-Oncogénicas p21(ras)/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Proteína p53 Supresora de Tumor/genética , Anciano , Nódulos Pulmonares Múltiples/genética , Nódulos Pulmonares Múltiples/diagnóstico por imagen , Nódulos Pulmonares Múltiples/patología , Adulto , Análisis Mutacional de ADN , Genes p53/genéticaRESUMEN
BACKGROUND: Age-related hearing loss (ARHL) - also termed presbycusis - is prevalent among older adults, leading to a range of issues. Although considerable progress in the understanding of ARHL over the decades, available reports lack data from recent years and do not comprehensively reflect the latest advancements and trends. Therefore, our study sought to assess research hotspots and trends in ARHL over the past 5 years to provide the basis for future research. MATERIALS AND METHODS: The Web of Science Core Collection database was searched and screened from January 1, 2019 to October 21, 2023, according to the inclusion criteria. CiteSpace (5.8.R3), VOSviewer (1.6.19), and Microsoft Excel 2019 were employed for bibliometric analysis and visualization. RESULTS: 3084 articles from 92 countries led by the United States and China were included. There has been a steady upward trend in the number of publications from 2019 to 2023. The most productive institutions, authors, and journals are Johns Hopkins University (n = 113), Lin FR (n = 66), and Ear and Hearing (n = 135), respectively. Trend topic analyses revealed that "cochlear synaptopathy" and "dementia" were the predominant foci. Keywords, including "individuals" and "national health", began to appear. CONCLUSION: Over the past 5 years, the annual number of publications has increased significantly and will continue to do so. Research on the mechanism of ARHL, represented by "oxidative stress", is a continuing focus. Emerging topics such as "individual differences" and "national health" may be potential future hotspots in this field.
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Bibliometría , Presbiacusia , Humanos , Presbiacusia/epidemiología , Investigación Biomédica/tendencias , AncianoRESUMEN
Therapeutic HPV vaccines that induce potent HPV-specific cellular immunity and eliminate pre-existing infections remain elusive. Among various candidates under development, those based on DNA constructs are considered promising because of their safety profile, stability, and efficacy. However, the use of electroporation (EP) as a main delivery method for such vaccines is notorious for adverse effects like pain and potentially irreversible muscle damage. Moreover, the requirement for specialized equipment adds to the complexity and cost of clinical applications. As an alternative to EP, lipid nanoparticles (LNPs) that are already commercially available for delivering mRNA and siRNA vaccines are likely to be feasible. Here, we have compared three intramuscular delivery systems in a preclinical setting. In terms of HPV-specific cellular immune responses, mice receiving therapeutic HPV DNA vaccines encapsulated with LNP demonstrated superior outcomes when compared to EP administration, while the naked plasmid vaccine showed negligible responses, as expected. In addition, SM-102 LNP M exhibited the most promising results in delivering candidate DNA vaccines. Thus, LNP proves to be a feasible delivery method in vivo, offering improved immunogenicity over traditional approaches.
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(+)-Ambrein is the primary component of ambergris, a rare product found in sperm whales (Physeter microcephalus). Microbial production using sustainable resources is a promising way to replace animal extraction and chemical synthesis. We constructed an engineered yeast strain to produce (+)-ambrein de novo. Squalene is a substrate for the biosynthesis of (+)-ambrein. Firstly, strain LQ2, with a squalene yield of 384.4 mg/L was obtained by optimizing the mevalonate pathway. Then we engineered a method for the de novo production of (+)-ambrein using glucose as a carbon source by overexpressing codon-optimized tetraprenyl-ß-curcumene cyclase (BmeTC) and its double mutant enzyme (BmeTCY167A/D373C), evaluating different promoters, knocking out GAL80, and fusing the protein with BmeTC and squalene synthase (AtSQS2). Nevertheless, the synthesis of (+)-ambrein is still limited, causing low catalytic activity in BmeTC. We carried out a protein surface amino acid modification of BmeTC. The dominant mutant BmeTCK6A/Q9E/N454A for the first step was obtained to improve its catalytic activity. The yield of (+)-ambrein increased from 35.2 to 59.0 mg/L in the shake flask and finally reached 457.4 mg/L in the 2 L fermenter, the highest titer currently available for yeast. Efficiently engineered strains and inexpensive fermentation conditions for the industrial production of (+)-ambrein. The metabolic engineering tools provide directions for optimizing the biosynthesis of other high-value triterpenes.
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Glucosa , Ingeniería Metabólica , Saccharomyces cerevisiae , Ingeniería Metabólica/métodos , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Glucosa/metabolismo , Escualeno/metabolismoRESUMEN
Alzheimer's disease (AD) is one of the most prevalent chronic neurodegenerative disorders globally, with a rapidly growing population of AD patients and currently no effective therapeutic interventions available. Consequently, the development of therapeutic anti-AD drugs and the identification of AD targets represent one of the most urgent tasks. In this study, in addition to considering known drugs and targets, we explore compound-protein interactions (CPIs) between compounds and proteins relevant to AD. We propose a deep learning model called CKG-IMC to predict Alzheimer's disease compound-protein interaction relationships. CKG-IMC comprises three modules: a collaborative knowledge graph (CKG), a principal neighborhood aggregation graph neural network (PNA), and an inductive matrix completion (IMC). The collaborative knowledge graph is used to learn semantic associations between entities, PNA is employed to extract structural features of the relationship network, and IMC is utilized for CPIs prediction. Compared with a total of 16 baseline models based on similarities, knowledge graphs, and graph neural networks, our model achieves state-of-the-art performance in experiments of 10-fold cross-validation and independent test. Furthermore, we use CKG-IMC to predict compounds interacting with two confirmed AD targets, 42-amino-acid ß-amyloid (Aß42) protein and microtubule-associated protein tau (tau protein), as well as proteins interacting with five FDA-approved anti-AD drugs. The results indicate that the majority of predictions are supported by literature, and molecular docking experiments demonstrate a strong affinity between the predicted compounds and targets.
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Enfermedad de Alzheimer , Aprendizaje Profundo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Humanos , Redes Neurales de la Computación , Mapas de Interacción de Proteínas , Biología Computacional/métodosRESUMEN
Accurate skin lesion segmentation from dermoscopic images is of great importance for skin cancer diagnosis. However, automatic segmentation of melanoma remains a challenging task because it is difficult to incorporate useful texture representations into the learning process. Texture representations are not only related to the local structural information learned by CNN, but also include the global statistical texture information of the input image. In this paper, we propose a transFormer network (SkinFormer) that efficiently extracts and fuses statistical texture representation for Skin lesion segmentation. Specifically, to quantify the statistical texture of input features, a Kurtosis-guided Statistical Counting Operator is designed. We propose Statistical Texture Fusion Transformer and Statistical Texture Enhance Transformer with the help of Kurtosis-guided Statistical Counting Operator by utilizing the transformer's global attention mechanism. The former fuses structural texture information and statistical texture information, and the latter enhances the statistical texture of multi-scale features. Extensive experiments on three publicly available skin lesion datasets validate that our SkinFormer outperforms other SOAT methods, and our method achieves 93.2% Dice score on ISIC 2018. It can be easy to extend SkinFormer to segment 3D images in the future. Our code is available at https://github.com/Rongtao-Xu/SkinFormer.
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Current clinical guidelines limit surgical intervention to patients with cT1-2N0M0 small cell lung cancer (SCLC). Our objective was to reassess the role of surgery in SCLC management, and explore novel prognostic indicators for surgically resected SCLC. We reviewed all patients diagnosed with SCLC from January 2011 to April 2021 in our institution. Survival analysis was conducted using the Kaplan-Meier method, and independent prognostic factors were assessed through the Cox proportional hazard model. In addition, immunohistochemistry (IHC) staining was performed to evaluate the predictive value of selected indicators in the prognosis of surgically resected SCLC patients. In the study, 177 SCLC patients undergoing surgical resection were ultimately included. Both univariate and multivariate Cox analysis revealed that incomplete postoperative adjuvant therapy emerged as an independent risk factor for adverse prognosis (p < 0.001, HR 2.96). Survival analysis revealed significantly superior survival among pN0-1 patients compared to pN2 patients (p < 0.0001). No significant difference in postoperative survival was observed between pN1 and pN0 patients (p = 0.062). Patients with postoperative stable disease (SD) exhibited lower levels of tumor inflammatory cells (TIC) (p = 0.0047) and IFN-γ expression in both area and intensity (p < 0.0001 and 0.0091, respectively) compared to those with postoperative progressive disease (PD). Conversely, patients with postoperative SD showed elevated levels of stromal inflammatory cells (SIC) (p = 0.0453) and increased counts of CD3+ and CD8+ cells (p = 0.0262 and 0.0330, respectively). Survival analysis indicated that high levels of SIC, along with low levels of IFN-γ+ cell area within tumor tissue, may correlate positively with improved prognosis in surgically resected SCLC (p = 0.017 and 0.012, respectively). In conclusion, the present study revealed that the patients with pT1-2N1M0 staging were a potential subgroup of SCLC patients who may benefit from surgery. Complete postoperative adjuvant therapy remains an independent factor promoting a better prognosis for SCLC patients undergoing surgical resection. Moreover, CD3, CD8, IFN-γ, TIC, and SIC may serve as potential indicators for predicting the prognosis of surgically resected SCLC.
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Complejo CD3 , Inmunohistoquímica , Interferón gamma , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Pronóstico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/mortalidad , Interferón gamma/metabolismo , Anciano , Carcinoma Pulmonar de Células Pequeñas/cirugía , Carcinoma Pulmonar de Células Pequeñas/patología , Carcinoma Pulmonar de Células Pequeñas/mortalidad , Carcinoma Pulmonar de Células Pequeñas/metabolismo , Complejo CD3/metabolismo , Antígenos CD8/metabolismo , Antígenos CD8/análisis , Adulto , Biomarcadores de Tumor/análisis , Análisis de Supervivencia , Anciano de 80 o más Años , Estimación de Kaplan-Meier , Células del Estroma/patología , Células del Estroma/metabolismoRESUMEN
INTRODUCTION: Crohn's Disease (CD) is a chronic inflammatory condition characterized by intestinal fibrosis, severely impacting patient quality of life. The molecular mechanisms driving this fibrosis remain inadequately understood. Recent evidence implicates mesenteric adipose tissue (MAT) in CD pathogenesis, particularly through its exosome secretion, which may influence fibrogenic pathways. Understanding the role of MAT-derived exosomes is crucial for unraveling these molecular processes. OBJECTIVES: This study aims to elucidate the role of MAT-derived exosomes in CD-related intestinal fibrosis. We focus on investigating their molecular composition and the potential impact on fibrosis progression, with an emphasis on identifying novel therapeutic targets. METHODS: We induced chronic intestinal inflammation in mice using dinitrobenzene sulfonic acid (DNBS), simulating CD-like fibrosis. Exosomes were isolated from DNBS-treated mice (MG) and normal controls (NG) for characterization using electron microscopy and proteomic analysis. Additionally, human colonic fibroblasts were exposed to exosomes from CD patients and healthy individuals, with subsequent assessment of fibrogenesis through proteomic and RNA sequencing analyses. RESULTS: Proteomic analyses revealed a significant activation of the TGF-ß signaling pathway in MG-treated mice compared to controls, correlating with enhanced intestinal fibrosis. In vitro experiments demonstrated that colonic fibroblasts exposed to CD patient-derived exosomes exhibited increased fibrogenic activity. Protein docking and co-immunoprecipitation studies suggested a critical interaction between TINAGL1 and SMAD4, enhancing fibrosis. Importantly, in vivo experiments corroborated that recombinant TINAGL1 protein exacerbated DNBS-induced intestinal fibrosis. CONCLUSION: Our findings highlight the pivotal role of MAT-derived exosomes, particularly those carrying TINAGL1, in the progression of intestinal fibrosis in CD. The involvement of the TGF-ß signaling pathway, especially the SMAD4 protein, offers new insights into the molecular mechanisms of CD-related fibrosis and presents potential targets for therapeutic intervention.
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Contralateral tension pneumothorax is a rare but fatal complication of one-lung ventilation. The life-saving decompression of pleural space was frequently delayed by the difficult confirmation of diagnosis because of general anesthesia that masks specific clinical presentations when the patient is alert. We reported a case of tension pneumothorax in a patient who underwent thoracic spine instrumentation. There were no contralateral tension pneumothorax cases on file from the search of the Anesthesia Quality Institute Closed Claims Database from 2001 to 2017. We systematically searched PubMed, Ovid MEDLINE, Embase, and Google Scholar. Over the past 30 years, there were 21 single case reports and two case series were retrieved. It was a consensus that difficult confirmation of the diagnosis of contralateral tension pneumothorax is the culprit of delayed life-saving intervention. Difficulty of oxygenation with increasing inspiratory pressure was usually the first sign suggesting contralateral pneumothorax; however, earlier presentations of cardiovascular system failure than respiratory failure have significantly increased the incidence of cardiac arrest and death. It is paramount to maintain a high suspicion of tension pneumothorax. The application of esophageal stethoscope, lung ultrasound, and simulator training may improve the chance of early diagnosis and patient outcome.
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In this work, we realized the detection of diamino-pentazolium cation (DAPZ+) in the reaction solution experimentally and proved it to be meta-diamino-pentazole based on the transition state theory. Quantum chemical methods were used to predict its spectral properties, charge distribution, stability and aromaticity. Considering that DAPZ+ has excellent detonation properties, it was further explored by assembling it with N5-, N3- and C(NO2)3- anions, respectively. The results show a strong interaction between DAPZ+ and the three anions, which will have a positive effect on its stability. Thanks to the high enthalpy of formation and density, the calculated detonation properties of the three systems are exciting, especially [DAPZ+][N5-] (D: 10,016 m·s-1; P: 37.94 GPa), whose actual detonation velocity may very likely exceed CL-20 (D: 9773 m·s-1). There is no doubt that this work will become the precursor for the theoretical exploration of new polynitrogen ionic compounds.
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PURPOSE: To construct the comfort status scale for patients with lung cancer after thoracoscopic surgery. DESIGN: Delphi method inquiry to 15 clinical and nursing experts. METHODS: On the basis of the comfort status scale and the subjective experience and objective symptoms of patients with lung cancer after thoracoscopic surgery, the relevant literature was consulted, semistructured interviews and group discussions were conducted, the pool of items of the postoperative comfort status scale for patients with lung cancer was initially formed, and the postoperative comfort status scale for patients with lung cancer was finally established. FINDINGS: The positive coefficient of experts was 100%, the coefficient of authority was 0.92 and 0.93, and the Kendal's W was 0.257 and 0.298, the degree of coordination of expert opinions was statistically significant (P < .05). Finally, a total of 28 items in four dimensions were formed to assess the postoperative comfort status of patients with lung cancer after thoracoscopic surgery. CONCLUSIONS: The Delphi method-based comfort status scale for patients with lung cancer after thoracoscopic surgery is scientific and reliable, and can provide a quantitative basis for the evaluation of the comfort status of patients after lung cancer thoracoscopic surgery, to further provide individual comfort care measures.
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In this study, we investigated reversible intermolecular proton shifting (IPS) coupled with spin transition (ST) in a novel FeII complex. The host FeII complex and the guest carboxylic acid anion were connected by intermolecular hydrogen bonds (IHBs). We extended the intramolecular proton transfer coupled ST phenomenon to the intermolecular system. The dynamic phenomenon was confirmed by variable-temperature single-crystal X-ray diffraction, neutron crystallography, and infrared spectroscopy. The mechanism of IPS was further validated using density functional theory calculations. The discovery of IPS-coupled ST in crystalline molecular materials provides good insights into fundamental processes and promotes the design of novel multifunctional materials with tunable properties for various applications, such as optoelectronics, information storage, and molecular devices.
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Extracting osmotic energy from waste organic solutions via reverse electrodialysis represents a promising approach to reuse such industrial wastes and helps to mitigate the ever-growing energy needs. Herein, a molecularly thin membrane of covalent organic frameworks is engineered via interfacial polymerization to investigate its ion transport behavior in organic solutions. Interestingly, a significant deviation from linearity between ion conductance and reciprocal viscosity is observed, attributed to the nanoscale confinement effect on intermolecular interactions. This finding suggests a potential strategy to modulate the influence of apprarent viscosity on transmembrane transport. The osmotic energy harvesting of the ultrathin membrane in organic systems was studied, achieving an unprecedented output power density of over 84.5 W m-2 at a 1000-fold salinity gradient with a benign conversion efficiency and excellent stability. These findings provide a meaningful stepping stone for future studies seeking to fully leverage the potentials of organic systems in energy harvesting applications.