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Hydroformylation is an industrial process for the production of aldehydes from alkenes1,2. Regioselective hydroformylation of propene to high-value n-butanal is particularly important, owing to a wide range of bulk applications of n-butanal in the manufacture of various necessities in human daily life3. Supported rhodium (Rh) hydroformylation catalysts, which often excel in catalyst recyclability, ease of separation and adaptability for continuous-flow processes, have been greatly exploited4. Nonetheless, they usually consist of rotationally flexible and sterically unconstrained Rh hydride dicarbonyl centres, only affording limited regioselectivity to n-butanal5-8. Here we show that proper encapsulation of Rh species comprising Rh(I)-gem-dicarbonyl centres within a MEL zeolite framework allows the breaking of the above model. The optimized catalyst exhibits more than 99% regioselectivity to n-butanal and more than 99% selectivity to aldehydes at a product formation turnover frequency (TOF) of 6,500 h-1, surpassing the performance of all heterogeneous and most homogeneous catalysts developed so far. Our comprehensive studies show that the zeolite framework can act as a scaffold to steer the reaction pathway of the intermediates confined in the space between the zeolite framework and Rh centres towards the exclusive formation of n-butanal.
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Patients with type 2 diabetes (T2D) are at a higher risk of developing renal cell carcinoma (RCC) than the general population. In vitro and in vivo investigations of the effects of sodium glucose cotransporter-2 inhibitors (SGLT2I) have shown a significantly reduced risk of RCC. However, the impact of these drugs on the incidence of RCC in the human population is unclear. This study aimed to examine the association between SGLT2I use and RCC risk in patients with T2D. We undertook a nationwide retrospective cohort study using the Health and Welfare Data Science Center database (2016-2020). The primary outcome was the risk of incident RCC by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Multiple Cox regression modeling was applied to analyze the association between SGLT2I use and RCC risk in patients with T2D. In a cohort of 241,772 patients with T2D who were using SGLT2Is and 483,544 participants who were not, 220 and 609 RCC cases, respectively, were recorded. The mean follow-up period of the study subjects was 2 years. There was a decreased risk of RCC for SGLT2I users after adjusting for the index year, sex, age, comorbidities, and concurrent medication (adjusted HR 0.68; 95% CI, 0.58-0.81). The sensitivity test for the propensity score 1:1-matched analyses showed similar results (adjusted HR 0.67; 95% CI, 0.55-0.81). The subgroup analysis revealed consistent results for sex, age (<70 years), and comorbidity with chronic kidney disease. The present study indicates that SGLT2I therapy significantly decreases RCC risk in patients with T2D. This finding was also consistent among the sensitivity test and subgroup analysis for those with or without chronic kidney disease/hypertension.
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Carcinoma de Células Renais , Diabetes Mellitus Tipo 2 , Neoplasias Renais , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/epidemiologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Renais/tratamento farmacológico , Estudos Retrospectivos , Idoso , Incidência , Adulto , Modelos de Riscos Proporcionais , Fatores de RiscoRESUMO
Parkinson's disease (PD), being the second largest neurodegenerative disease, poses challenges in early detection, resulting in a lack of timely treatment options to effectively manage the disease. By the time clinical diagnosis becomes possible, more than 60% of dopamine neurons in the substantia nigra (SN) of patients have already degenerated. Therefore, early diagnosis or identification of warning signs is crucial for the prompt and timely beginning of the treatment. However, conducting invasive or complex diagnostic procedures on asymptomatic patients can be challenging, making routine blood tests a more feasible approach in such cases. Numerous studies have been conducted over an extended period to search for effective diagnostic biomarkers in blood samples. However, thus far, no highly effective biomarkers have been confirmed. Besides classical proteins like α-synuclein (α-syn), phosphorylated α-syn and oligomeric α-syn, other molecules involved in disease progression should also be given equal attention. In this review, we will not only discuss proposed biomarkers that are currently under investigation but also delve into the mechanisms underlying the disease, focusing on processes such as α-syn misfolding, intercellular transmission and the crossing of the blood-brain barrier (BBB). Our aim is to provide an updated overview of molecules based on these processes that may potentially serve as blood biomarkers.
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Biomarcadores , Doença de Parkinson , Humanos , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Biomarcadores/sangue , alfa-Sinucleína/sangue , Barreira Hematoencefálica/metabolismoRESUMO
OBJECTIVES: The recent emergence of carbapenem-resistant Enterobacterales poses a major and escalating threat to global public health. This study aimed to analyse the global distribution and antimicrobial resistance of Enterobacterales harbouring variant OXA-48-like carbapenemase-related genes. METHODS: Enterobacterales isolates were collected from the Antimicrobial Testing Leadership and Surveillance (ATLAS) programme during 2018-2021. Comprehensive antimicrobial susceptibility testing and ß-lactamase gene detection were also conducted, along with statistical analysis of the collected data. RESULTS: Among the 72â244 isolates, 1934 Enterobacterales isolates were identified to harbour blaOXA-48-like genes, predominantly Klebsiella spp. (86.9%). High rates of multidrug resistance were observed, with only ceftazidime/avibactam and tigecycline showing favourable susceptibility. A discrepancy between the genotype and phenotype of carbapenem resistance was evident: 16.8% (233 out of 1384) of the Enterobacterales isolates with blaOXA-48-like genes exhibited susceptibility to meropenem. Specifically, 37.4% (64/95) of Escherichia coli strains with blaOXA-48-like genes displayed meropenem susceptibility, while the corresponding percentages for Klebsiella pneumoniae and Enterobacter cloacae complex were 25.2% (160/1184) and 0% (0/36), respectively (Pâ<â0.05). Geographical analysis revealed that the highest prevalence of blaOXA-48-like genes occurred in Asia, the Middle East and Eastern Europe. The proportion of K. pneumoniae isolates harbouring blaOXA-232 increased from 23.9% in 2018 to 56.0% in 2021. By contrast, the proportion of blaOXA-48 decreased among K. pneumoniae isolates during 2018-2021. CONCLUSIONS: This study underscores the widespread and increasing prevalence of blaOXA-48-like genes in Enterobacterales and emphasizes the need for enhanced surveillance, improved diagnostic methods and tailored antibiotic stewardship to combat the spread of these resistant pathogens.
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Antibacterianos , Proteínas de Bactérias , Infecções por Enterobacteriaceae , Testes de Sensibilidade Microbiana , beta-Lactamases , beta-Lactamases/genética , Humanos , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/epidemiologia , Antibacterianos/farmacologia , Proteínas de Bactérias/genética , Enterobacteriaceae/genética , Enterobacteriaceae/efeitos dos fármacos , Enterobacteriaceae/enzimologia , Saúde Global , Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Enterobacteriáceas Resistentes a Carbapenêmicos/isolamento & purificação , Monitoramento Epidemiológico , Farmacorresistência Bacteriana Múltipla/genéticaRESUMO
BACKGROUND: Elizabethkingia spp. are emerging as nosocomial pathogens causing various infections. These pathogens express resistance to a broad range of antibiotics, thus requiring antimicrobial combinations for coverage. However, possible antagonistic interactions between antibiotics have not been thoroughly explored. This study aimed to evaluate the effectiveness of antimicrobial combinations against Elizabethkingia infections, focusing on their impact on pathogenicity, including biofilm production and cell adhesion. METHODS: Double-disc diffusion, time-kill, and chequerboard assays were used for evaluating the combination effects of antibiotics against Elizabethkingia spp. We further examined the antagonistic effects of antibiotic combinations on biofilm formation and adherence to A549 human respiratory epithelial cells. Further validation of the antibiotic interactions and their implications was performed using ex vivo hamster precision-cut lung sections (PCLSs) to mimic in vivo conditions. RESULTS: Antagonistic effects were observed between cefoxitin, imipenem and amoxicillin/clavulanic acid in combination with vancomycin. The antagonism of imipenem toward vancomycin was specific to its effects on the genus Elizabethkingia. Imipenem further hampered the bactericidal effect of vancomycin and impaired its inhibition of biofilm formation and the adhesion of Elizabethkingia meningoseptica ATCC 13253 to human cells. In the ex vivo PCLS model, vancomycin exhibited dose-dependent bactericidal effects; however, the addition of imipenem also reduced the effect of vancomycin. CONCLUSIONS: Imipenem reduced the bactericidal efficacy of vancomycin against Elizabethkingia spp. and compromised its capacity to inhibit biofilm formation, thereby enhancing bacterial adhesion. Clinicians should be aware of the potential issues with the use of these antibiotic combinations when treating Elizabethkingia infections.
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Antibacterianos , Biofilmes , Infecções por Flavobacteriaceae , Imipenem , Testes de Sensibilidade Microbiana , Vancomicina , Animais , Imipenem/farmacologia , Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Humanos , Vancomicina/farmacologia , Infecções por Flavobacteriaceae/microbiologia , Infecções por Flavobacteriaceae/tratamento farmacológico , Flavobacteriaceae/efeitos dos fármacos , Aderência Bacteriana/efeitos dos fármacos , Células A549 , Cricetinae , Interações Medicamentosas , Pulmão/microbiologiaRESUMO
OBJECTIVES: We aimed to investigate the value of deep learning (DL) models based on multimodal ultrasonographic (US) images to quantify RA activity. METHODS: Static greyscale (SGS), dynamic greyscale (DGS), static power Doppler (SPD) and dynamic power Doppler (DPD) US images were collected and evaluated by two expert radiologists according to the EULAR-OMERACT Synovitis Scoring system. Four DL models were developed based on the ResNet-type structure, evaluated on two separate test cohorts, and finally compared with the performance of 12 radiologists with different levels of experience. RESULTS: In total, 1244 images were used for the model training, and 152 and 354 for testing (cohort 1 and 2, respectively). The best-performing models for the scores of 0/1/2/3 were the DPD, SGS, DGS and SPD models, respectively (Area Under the receiver operating characteristic Curve [AUC] = 0.87/0.95/0.74/0.95; no significant differences). All the DL models provided results comparable to the experienced radiologists on a per-image basis (intraclass correlation coefficient: 0.239-0.756, P < 0.05). The SPD model performed better than the SGS one on test cohort 1 (score of 0/2/3: AUC = 0.82/0.67/0.95 vs 0.66/0.66/0.75, respectively) and test cohort 2 (score of 0: AUC = 0.89 vs 0.81). The dynamic DL models performed better than the static ones in most of the scoring processes and were more accurate than the most of senior radiologists, especially the DPD model. CONCLUSION: DL models based on multimodal US images allow a quantitative and objective assessment of RA activity. Dynamic DL models in particular have potential value in assisting radiologists to improve the accuracy of RA US-based grading.
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Artrite Reumatoide , Aprendizado Profundo , Humanos , Ultrassonografia , Artrite Reumatoide/diagnóstico por imagem , Curva ROC , RadiologistasRESUMO
Cysteine and glycine-rich protein 2 (CSRP2) is expressed differently in numerous cancers and plays a key role in carcinogenesis. However, the role of CSRP2 in glioma is unknown. This study sought to determine the expression profile and clinical significance of CSRP2 in glioma and explore its biological functions and mechanisms via lentivirus-mediated CSRP2 silencing experiments. Increased CSRP2 was frequently observed in gliomas, which was associated with clinicopathological characteristics and an unfavourable prognosis. Decreasing CSRP2 led to the suppression of malignant proliferation, metastasis and stemness in glioma cells while causing hypersensitivity to chemotherapeutic drugs. Mechanistic investigations revealed that CSRP2 plays a role in mediating the Notch signalling cascade. Silencing CSRP2 decreased the levels of Notch1, cleaved Notch1, HES1 and HEY1, suppressing the Notch signalling cascade. Reactivation of Notch markedly diminished the tumour-inhibiting effects of CSRP2 silencing on the malignant phenotypes of glioma cells. Notably, CSRP2-silencing glioma cells exhibited reduced potential in the formation of xenografts in nude mice in vivo, which was associated with an impaired Notch signalling cascade. These results showed that CSRP2 is overexpressed in glioma and has a crucial role in sustaining the malignant phenotypes of glioma, suggesting that targeting CSRP2 could be a promising strategy for glioma treatment.
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Glioma , Camundongos Nus , Transdução de Sinais , Humanos , Glioma/patologia , Glioma/metabolismo , Glioma/genética , Animais , Linhagem Celular Tumoral , Camundongos , Masculino , Proliferação de Células , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/genética , Feminino , Fenótipo , Receptores Notch/metabolismo , Receptores Notch/genética , Receptor Notch1/metabolismo , Receptor Notch1/genética , Camundongos Endogâmicos BALB C , Pessoa de Meia-Idade , Regulação Neoplásica da Expressão Gênica , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
INTRODUCTION/AIMS: The current diagnosis of ulnar neuropathy at the elbow (UNE) relies mainly on the clinical presentation and nerve electrodiagnostic (EDX) testing, which can be uncomfortable and yield false negatives. The aim of this study was to investigate the diagnostic value of conventional ultrasound, shear wave elastography (SWE), and superb microvascular imaging (SMI) in diagnosing UNE. METHODS: We enrolled 40 patients (48 elbows) with UNE and 48 healthy volunteers (48 elbows). The patients were categorized as having mild, moderate or severe UNE based on the findings of EDX testing. The cross-sectional area (CSA) was measured using conventional ultrasound. Ulnar nerve (UN) shear wave velocity (SWV) and SMI were performed in a longitudinal plane. RESULTS: Based on the EDX findings, UNE severity was graded as mild in 4, moderate in 10, and severe in 34. The patient group showed increased ulnar nerve CSA and stiffness at the site of maximal enlargement (CSA mean at the site of max enlargement [CSAmax] and SWV mean at the site of max enlargement [SWVmax]), ulnar nerve CSA ratio, and stiffness ratio (elbow-to-upper arm), compared with the control group (p < .001). Furthermore, the severe UNE group showed higher ulnar nerve CSAmax and SWVmax compared with the mild and moderate UNE groups (p < .001). The cutoff values for diagnosis of UNE were 9.5 mm2 for CSAmax, 3.06 m/s for SWVmax, 2.00 for CSA ratio, 1.36 for stiffness ratio, and grade 1 for SMI. DISCUSSION: Our findings suggest that SWE and SMI are valuable diagnostic tools for the diagnosis and assessment of severity of UNE.
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Técnicas de Imagem por Elasticidade , Cotovelo , Nervo Ulnar , Neuropatias Ulnares , Ultrassonografia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Técnicas de Imagem por Elasticidade/métodos , Neuropatias Ulnares/diagnóstico por imagem , Neuropatias Ulnares/fisiopatologia , Cotovelo/diagnóstico por imagem , Ultrassonografia/métodos , Idoso , Nervo Ulnar/diagnóstico por imagem , Nervo Ulnar/fisiopatologia , Microvasos/diagnóstico por imagem , Eletrodiagnóstico/métodosRESUMO
BACKGROUND: During the COVID-19 pandemic, medical workers were concerned about the care of their children or family members and the impact of being separated from them. This increased stress could harm the relationship between nurses and patients. This study assessed how medical workers' parental role may affect burnout during such a high-stress period. METHODS: This cross-sectional observational study was carried out in 2021 during the COVID-19 pandemic. The client burnout (CB) scale of the Copenhagen Burnout Inventory, the Nordic Musculoskeletal Questionnaire, and a demographic questionnaire were used. Statistical methods such as the t-test, one-way ANOVA, and univariable/multiple linear regression were applied. RESULTS: A total of 612 nurses were included in this study. The likely risk factors of CB were identified and the parenthood effect was found to be associated with reduced CB. The parental role and leisure activity with family and friends on CB were found to have an impact. Engaging in leisure activity with family and playing the role of a parent diligently will help relieve nurses' burnout from frequent contact with patients and their families, thus lowering the risk of clinical burnout. CONCLUSION: The parental role, family/friends relationships, and a complex work environment associated with nurses' burnout during the COVID-19 pandemic. This finding allows us to re-examine the importance of family life and parent-child relationships in high-stress work environments.
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Esgotamento Profissional , COVID-19 , Humanos , COVID-19/psicologia , COVID-19/epidemiologia , Esgotamento Profissional/epidemiologia , Esgotamento Profissional/psicologia , Taiwan/epidemiologia , Estudos Transversais , Feminino , Adulto , Masculino , Inquéritos e Questionários , Pandemias , Pais/psicologia , SARS-CoV-2 , Pessoa de Meia-Idade , Recursos Humanos de Enfermagem Hospitalar/psicologia , Fatores de RiscoRESUMO
Mixed-matrix membranes (MMMs) have the potential for energy-efficient gas separation by matching the superior mass transfer and anti-plasticization properties of the fillers with processability and scaling up features of the polymers. However, construction of high-performance MMMs has been prohibited due to low filler-loading and the existence of interfacial defects. Here, high MOF-loaded, i.e., 55â wt %, MMMs are developed by a 'dormancy and double-activation' (DDA) strategy. High MOF precursor concentration suppresses crystallization in the membrane casting solution, realizing molecular level mixing of all components. Then, the polymeric matrix was formed with uniform encapsulation of MOF nutrients. Subsequently, double-activation was employed to induce MOF crystallization: the alkali promotes MOFs nucleation to harvest small porous nanocrystals while excessive ligands activate the metal ions to enhance the MOFs conversion. As such, quasi-semi-continuous mass transfer channels can be formed in the MMMs by the connected MOFs nanocrystals to boost the gas permeability. The optimized MMM shows significantly ameliorated CO2 permeability, i.e., 2841 Barrer, five-fold enhancement compared with pristine polymer membrane, with a good CO2 /N2 selectivity of 36. Besides, the nanosized MOFs intensify their interaction with polymer chains, endowing the MMMs with good anti-plasticization behaviour and stability, which advances practical application of MMMs in carbon capture.
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The coupling of electron spin and nuclear spin through spin-exchange collisions compensates for external magnetic field interference in the spin-exchange relaxation-free (SERF) comagnetometer. However, the compensation ability for magnetic field interference along the detection axis is limited due to the presence of nuclear spin relaxation. This paper aims to enhance the self-compensation capability of the system by optimizing the pressure of the noble gas during cell filling. Models are established to describe the relationships between the nuclear spin polarization, the polarizing magnetic field of nuclei, the magnetic field suppression factors, and the pressure of the noble gas in the K-Rb-21Ne atomic ensemble. Experiments are conducted using five cells with different pressure. The results indicate that in the positive pressure area, the nuclear spin polarization decreases while the equivalent magnetic field experienced by the noble gas increases with increasing pressure. The magnetic field suppression factor for transverse fields increases as the pressure increases, leading to a decrease in the ability to suppress low-frequency magnetic field interference. Moreover, at the cell temperature of 180°C and a transverse residual field gradient of 4.012 nT/cm, the system exhibits its strongest capability to suppress transverse magnetic field interference when the pressure of 21Ne is around 0.7 atm.
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Acquired thrombotic thrombocytopenic purpura (aTTP) is a fatal hematologic disease. Despite the currently high standards of care, some patients who develop refractory or recurrent disease still have a poor prognosis. Although N-acetylcysteine (NAC) is recommended for the treatment of aTTP, its use in aTTP treatment is still controversial. We aimed to evaluate the association of NAC with mortality in patients with aTTP. This was a retrospective cohort study of patients with aTTP with in-hospital mortality as the primary outcome and time to platelet recovery and neurological recovery as secondary outcomes. We used multifactorial COX regression analysis to check for an association of NAC with mortality. Moreover, we performed a sensitivity analysis check the stability of our results. Finally, 89 patients with aTTP were enrolled. After adjusting for potential confounders, we found NAC to be associated with 75% lower in-hospital mortality (HR = 0.25, 95% CI = 0.1-0.64). The results of sensitivity analyses performed remained stable as the risk of in-hospital mortality in patients reduced in patients with comorbid neurological symptoms (HR = 0.23, 95% CI = 0.06-0.89). However, NAC use did not affect the time to platelet recovery (HR = 1.19, 95% CI = 0.57-2.5) or neurological recovery (HR = 0.32, 95% CI = 0.08-1.25) in patients with aTTP. NAC treatment reduces in-hospital mortality in patients with aTTP but does not shorten the time to platelet recovery or neurological recovery.
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Púrpura Trombocitopênica Trombótica , Humanos , Adulto , Púrpura Trombocitopênica Trombótica/diagnóstico , Acetilcisteína/uso terapêutico , Estudos Retrospectivos , Estudos de Coortes , Mortalidade Hospitalar , Troca PlasmáticaRESUMO
BACKGROUND: Helicobacter pylori bacteremia is rare and difficult to make a definite diagnosis. CASE PRESENTATION: This is a 40-year-old woman represented as fever and unconsciousness accompanied by tics. She was diagnosed as Helicobacter pylori bacteremia and received emergency endotracheal intubation and antibiotics. Her symptoms resolved and she was discharged from ICU at the sixth day. CONCLUSIONS: Helicobacter pylori bacteremia is rare and hard to identify. Varied clinical manifestations leading to more difficult to make a definite diagnosis.
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Bacteriemia , Infecções por Helicobacter , Helicobacter pylori , Helicobacter , Humanos , Feminino , Adulto , Infecções por Helicobacter/complicações , Infecções por Helicobacter/diagnóstico , Bacteriemia/diagnóstico , Convulsões/complicações , Inconsciência/complicaçõesRESUMO
Ruthenium oxide (RuO2), due to its comparable binding energy with *H and cost-effectiveness against Pt, has emerged as a pivotal electrocatalyst for oxygen evolution reaction (OER). In the present study, RuO2 nanocrystals (NCs) and nanowires (NWs) were obtained by a molten salt process and the morphology, crystal structure, and local bonding features were examined by using electron microscopy and X-ray absorption spectroscopy. From the electrochemical measurement, both RuO2 NCs and NWs exhibit favorable stability and activity toward oxygen evolution reaction in an alkali medium, althought NCs exhibit higher activity, which is likely attributed to the larger surface area and the high local structural disorder. The theoretical calculation reveals that RuO2 NWs with a primary (110) orientation show a higher overpotential due to its d-band center's proximity to the Fermi level versus (101). The present work suggests that the molten salt process could be an efficient method for producing metal oxide catalysts with tailorable geometry and performances.
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Protein-ligand docking is an essential tool in structure-based drug design with applications ranging from virtual high-throughput screening to pose prediction for lead optimization. Most docking programs for pose prediction are optimized for redocking to an existing cocrystallized protein structure, ignoring protein flexibility. In real-world drug design applications, however, protein flexibility is an essential feature of the ligand-binding process. Flexible protein-ligand docking still remains a significant challenge to computational drug design. To target this challenge, we present a deep learning (DL) model for flexible protein-ligand docking based on the prediction of an intermolecular Euclidean distance matrix (EDM), making the typical use of iterative search algorithms obsolete. The model was trained on a large-scale data set of protein-ligand complexes and evaluated on independent test sets. Our model generates high quality poses for a diverse set of protein and ligand structures and outperforms comparable docking methods.
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Aprendizado Profundo , Software , Ligantes , Ligação Proteica , Proteínas/química , Algoritmos , Simulação de Acoplamento MolecularRESUMO
Molecules based on benzimidazolone-dioxazine are known as blue/violet pigments and have been commercialized for decades. However, unfavorable solubility limits the application of these structures as building blocks of conjugated polymers despite their low band gaps. Herein, a series of donor-acceptor conjugated polymers containing soluble benzimidazolone-dioxazine structures as the acceptors and oligothiophene as donors are synthesized and investigated. With increasing numbers of thiophene rings, the steric hindrance diminishes and high molecular weight polymers can be achieved, leading to an improved performance in organic field effect transistor devices. The hole mobility of polymers with three to six thiophene units is in the order of 10-1 cm2 V-1 s -1 . Among all the polymers, polymer P3 with three thiophene units between benzimidazolone-dioxazine structures shows the best hole mobility of 0.4 cm2 V-1 s -1 . Grazing-incidence wide-angle X-ray scattering results reveal that the high mobility of organic field-effect transistors (OFETs) can be accredited by matched donor-acceptor packing in the solid thin films.
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Bandagens , Benzimidazóis , Polímeros , TiofenosRESUMO
BACKGROUND: Permanent pacemaker (PPM) implantation is a well-established treatment for symptomatic sinus node dysfunction (SND). The optimal timing of this intervention is unclear, with atrioventricular blocks often prioritized in resource stressed waiting lists due to mortality concerns. METHODS: Mortality data was compared between patients receiving elective outpatient (OP) PPM implantation, and those presenting to hospital for urgent inpatient (IP) management for symptomatic SND. Survival analysis was conducted using Kaplan-Meier plots and compared using the log-rank test. Univariable and multivariable Cox regression, as well as propensity score matching analyses were performed to assess the prognostic effect on 30-day and 1-year all-cause mortality of inpatient implant. RESULTS: Of the 1269 patients identified with isolated SND, 740 (58%) had PPMs implanted on an OP and 529 (42%) on an IP basis. Mortality was significantly worse in patients where management was driven by hospital admission on an urgent basis (Log-Rank χ2 = 21.6, p < 0.001) and remained an independent predictor of 1-year all-cause mortality (HR 3.40, 95% CI 1.97-5.86, p < 0.001) on multivariable analysis. CONCLUSIONS: SND is predominantly a disease associated with ageing and comorbid populations, where avoidance of deconditioning, hospitalization acquired infections, and polypharmacy is advantageous. Admission avoidance is therefore the preferable strategy.
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Bloqueio Atrioventricular , Marca-Passo Artificial , Humanos , Síndrome do Nó Sinusal/terapia , Marca-Passo Artificial/efeitos adversos , Pacientes Ambulatoriais , HospitalizaçãoRESUMO
Hepatocellular carcinoma (HCC) remains challenging due to the lack of efficient therapy. Promoting degradation of certain cancer drivers has become an innovative therapy. The nuclear transcription factor sine oculis homeobox 1 (SIX1) is a key driver for the progression of HCC. Here, we explored the molecular mechanisms of ubiquitination of SIX1 and whether targeting SIX1 degradation might represent a potential strategy for HCC therapy. Through detecting the ubiquitination level of SIX1 in clinical HCC tissues and analyzing TCGA and GEPIA databases, we found that ubiquitin specific peptidase 1 (USP1), a deubiquitinating enzyme, contributed to the lower ubiquitination and high protein level of SIX1 in HCC tissues. In HepG2 and Hep3B cells, activation of EGFR-AKT signaling pathway promoted the expression of USP1 and the stability of its substrates, including SIX1 and ribosomal protein S16 (RPS16). In contrast, suppression of EGFR with gefitinib or knockdown of USP1 restrained EGF-elevated levels of SIX1 and RPS16. We further revealed that SNS-023 (formerly known as BMS-387032) induced degradation of SIX1 and RPS16, whereas this process was reversed by reactivation of EGFR-AKT pathway or overexpression of USP1. Consequently, inactivation of the EGFR-AKT-USP1 axis with SNS-032 led to cell cycle arrest, apoptosis, and suppression of cell proliferation and migration in HCC. Moreover, we showed that sorafenib combined with SNS-032 or gefitinib synergistically inhibited the growth of Hep3B xenografts in vivo. Overall, we identify that both SIX1 and RPS16 are crucial substrates for the EGFR-AKT-USP1 axis-driven growth of HCC, suggesting a potential anti-HCC strategy from a novel perspective.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico , Neoplasias Hepáticas/patologia , Gefitinibe , Proteínas Proto-Oncogênicas c-akt/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Receptores ErbB , Proteínas Ribossômicas , Proteínas de Homeodomínio/metabolismoRESUMO
The proliferation and myogenic differentiation of muscle stem cells (MuSCs) are important factors affecting muscle development and beef quality. There is increasing evidence that circRNAs can regulate myogenesis. We found a novel circRNA, named circRRAS2 that is significantly upregulated in the differentiation phase of bovine MuSCs. Here, we aimed to determine its roles in the proliferation and myogenic differentiation of these cells. The results showed that circRRAS2 was expressed in several bovine tissues. CircRRAS2 inhibited MuSCs proliferation and promoted myoblast differentiation. In addition, chromatin isolation by using RNA purification and mass spectrometry in differentiated muscle cells identified 52 RNA-binding proteins that could potentially bind to circRRAS2, in order to regulate their differentiation. The results suggest that circRRAS2 could be a specific regulator of myogenesis in bovine muscle.HighlightsCircRRAS2 expression is higher in DM cells than in GM cells.CircRRAS2 could significantly inhibit the proliferation and apoptosis of bovine MuSCs.CircRRAS2 promotes the differentiation of bovine MuSCs into myotubes.CircRRAS2 may exert regulatory effects through multiple RNA binding proteins.
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Células Satélites de Músculo Esquelético , Bovinos , Animais , Diferenciação Celular/genética , Células Cultivadas , Linhagem Celular , Desenvolvimento Muscular/genética , Músculo Esquelético/metabolismo , Proliferação de Células/genéticaRESUMO
PURPOSE: Carotid ultrasound allows noninvasive assessment of vascular anatomy and function with real-time display. Based on the transfer learning method, a series of research results have been obtained on the optimal image recognition and analysis of static images. However, for carotid plaque recognition, there are high requirements for self-developed algorithms in real-time ultrasound detection. This study aims to establish an automatic recognition system, Be Easy to Use (BETU), for the real-time and synchronous diagnosis of carotid plaque from ultrasound videos based on an artificial neural network. MATERIALS AND METHODS: 445 participants (mean age, 54.6±7.8 years; 227 men) were evaluated. Radiologists labeled a total of 3259 segmented ultrasound images from 445 videos with the diagnosis of carotid plaque, 2725 images were collected as a training dataset, and 554 images as a testing dataset. The automatic plaque recognition system BETU was established based on an artificial neural network, and remote application on a 5G environment was performed to test its diagnostic performance. RESULTS: The diagnostic accuracy of BETU (98.5%) was consistent with the radiologist's (Kappa = 0.967, P < 0.001). Remote diagnostic feedback based on BETU-processed ultrasound videos could be obtained in 150ms across a distance of 1023 km between the ultrasound/BETU station and the consultation workstation. CONCLUSION: Based on the good performance of BETU in real-time plaque recognition from ultrasound videos, 5G plus Artificial intelligence (AI)-assisted ultrasound real-time carotid plaque screening was achieved, and the diagnosis was made.