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AIMS: We aim to integrate the parameters of two-dimensional (2D) echocardiography and identify the high-risk population for all-cause mortality in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). METHODS: The study involved a retrospective cohort population with STEMI who were admitted to Yongchuan Hospital of Chongqing Medical University between January 2016 and January 2019. Baseline data were collected, including 2D echocardiography parameters and left ventricular ejection fraction (LVEF). The parameters of 2D echocardiography were subjected to cluster analysis. Logistic regression models were employed to assess univariate and multivariate adjusted odds ratios (ORs) of cluster information in relation to all-cause mortality. Four logistic regression models were generated, utilizing cluster information, clinical variables, clinical variables in conjunction with LVEF, and clinical variables in conjunction with LVEF and cluster information as predictive variables, respectively. The area under the curve (AUC) were utilized to evaluate the incremental risk stratification value of cluster information. RESULTS: The study included 633 participants with 28.8% female, a mean age of 65.68 ± 11.98 years. Over the course of a 3-year follow-up period, 108 (17.1%) patients experienced all-cause mortality. Utilizing cluster analysis of 2D echocardiography parameters, the patients were categorized into two distinct clusters, with statistically significant differences observed in most clinical variables, echocardiography, and survival outcomes between the clusters. Multivariate regression analysis revealed that cluster information was independently associated with the risk of all-cause mortality with adjusted OR 7.33 (95% confidence interval [CI] 3.99-14.06, P < 0.001). The inclusion of LVEF enhanced the predictive capacity of the model utilized with clinical variables with AUC 0.848 (95% CI 0.809-0.888) versus AUC 0.872 (95% CI 0.836-0.908) (P < 0.001), and the addition of cluster information further improved its predictive performance with AUC 0.906 (95% CI 0.878-0.934, P < 0.001). This cluster analysis was translated into a free available online calculator (https://app-for-mortality-prediction-cluster.streamlit.app/). CONCLUSIONS: The 2D echocardiographic diagnostic information based on cluster analysis had good prognostic value for STEMI population, which was helpful for risk stratification and individualized intervention.
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Drug resistance represents a significant obstacle in cancer treatment, underscoring the need for the discovery of novel therapeutic targets. Ubiquitin-specific proteases (USPs), a subclass of deubiquitinating enzymes, play a pivotal role in protein deubiquitination. As scientific research advances, USPs have been recognized as key regulators of drug resistance across a spectrum of treatment modalities, including chemotherapy, targeted therapy, immunotherapy, and radiotherapy. This comprehensive review examines the complex relationship between USPs and drug resistance mechanisms, focusing on specific treatment strategies and highlighting the influence of USPs on DNA damage repair, apoptosis, characteristics of cancer stem cells, immune evasion, and other crucial biological functions. Additionally, the review highlights the potential clinical significance of USP inhibitors as a means to counter drug resistance in cancer treatment. By inhibiting particular USP, cancer cells can become more susceptible to a variety of anti-cancer drugs. The integration of USP inhibitors with current anti-cancer therapies offers a promising strategy to circumvent drug resistance. Therefore, this review emphasizes the importance of USPs as viable therapeutic targets and offers insight into fruitful directions for future research and drug development. Targeting USPs presents an effective method to combat drug resistance across various cancer types, leading to enhanced treatment strategies and better patient outcomes.
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Antineoplásicos , Resistencia a Antineoplásicos , Neoplasias , Proteasas Ubiquitina-Específicas , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/genética , Neoplasias/patología , Neoplasias/metabolismo , Proteasas Ubiquitina-Específicas/antagonistas & inhibidores , Proteasas Ubiquitina-Específicas/metabolismo , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Animales , Terapia Molecular Dirigida , Reparación del ADN , Apoptosis/efectos de los fármacosRESUMEN
Perovskite solar cells have made significant strides in recent years. However, there are still challenges in terms of photoelectric conversion efficiency and long-term stability associated with perovskite solar cells. The presence of defects in perovskite materials is one of the important influencing factors leading to subpar film quality. Adopting additives to passivate defects within perovskite materials is an effective approach. Therefore, we first discuss the types of defects that occur in perovskite materials and the mechanisms of their effect on performance. Then, several types of additives used in perovskite solar cells are discussed, including ionic compounds, organic molecules, polymers, etc. This review provides guidance for the future development of more sustainable and effective additives to improve the performance of solar cells.
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Protein ubiquitination, one of the most significant post-translational modifications, plays an important role in controlling the proteins activity in diverse cellular processes. The reversible process of protein ubiquitination, known as deubiquitination, has emerged as a critical mechanism for maintaining cellular homeostasis. The deubiquitinases (DUBs), which participate in deubiquitination process are increasingly recognized as potential candidates for drug discovery. Among these DUBs, ubiquitin-specific protease 9× (USP9X), a highly conserved member of the USP family, exhibits versatile functions in various cellular processes, including the regulation of cell cycle, protein endocytosis, apoptosis, cell polarity, immunological microenvironment, and stem cell characteristics. The dysregulation and abnormal activities of USP9X are influenced by intricate cellular signaling pathway crosstalk and upstream non-coding RNAs. The complex expression patterns and controversial clinical significance of USP9X in cancers suggest its potential as a prognostic biomarker. Furthermore, USP9X inhibitors has shown promising antitumor activity and holds the potential to overcome therapeutic resistance in preclinical models. However, a comprehensive summary of the role and molecular functions of USP9X in cancer progression is currently lacking. In this review, we provide a comprehensive delineation of USP9X participation in numerous critical cellular processes, complicated signaling pathways within the tumor microenvironment, and its potential translational applications to combat therapeutic resistance. By systematically summarizing the updated molecular mechanisms of USP9X in cancer biology, this review aims to contribute to the advancement of cancer therapeutics and provide essential insights for specialists and clinicians in the development of improved cancer treatment strategies.
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Neoplasias , Transducción de Señal , Ubiquitina Tiolesterasa , Ubiquitinación , Humanos , Ubiquitina Tiolesterasa/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/genética , Animales , Terapia Molecular Dirigida , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Microambiente TumoralRESUMEN
Electrides have attracted significant attention in the fields of physics, materials science, and chemistry due to their distinctive electron properties characterized by weak nuclear binding. In this study, based on first-principles calculations and symmetry analysis, we report that the pure zirconium with alpha-phase (α-Zr) is expected to be the electrically neutral electride with topological nodal loop. Furthermore, the nodal loop located at thekz= 0 plane exhibits a clear drumhead-like surface state. The energy levels of the topological nodal loop can be regulated by applying uniaxial strain, resulting in the topological nodal loop being closer to the Fermi level. Remarkably, the work function of the electride Zr shows a significant anisotropy along the (001), (100), and (110) directions, particularly with a low work function of 3.14 eV along the (110) surface. Therefore, we predict thatα-Zr provides a promising platform for future research on topological electrides.
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Background: The occurrence of necrotizing enterocolitis (NEC) is a common and severe disease of the digestive system in neonates. This study aims to assess the value of the intestinal tissue oxygen saturation (rintSO2) combined with the levels of procalcitonin (PCT) and mean platelet volume (MPV) in predicting the severity of NEC in preterm infants. Methods: This experiment was a retrospective cohort study conducted in the Department of Pediatrics, Hongqi Hospital Affiliated to Mudanjiang Medical University between January 2017 and July 2022. Premature neonates with NEC were enrolled and divided into mild-moderate NEC group and severe NEC group according to Bell's stage. The general information data, rintSO2 and blood parameters such as the white blood cell (WBC) count, platelet count (PLT), PCT, MPV, red blood cell distribution width (RDW), hemoglobin (Hb), C-reactive protein (CRP) were compared between the two groups. Results: A total of 122 patients were enrolled, including 79 mild-moderate NEC and 43 severe NEC. The rintSO2 was lower in severe group than in mild-moderate group (P = 0.042), the PCT and MPV were both higher in severe group than in mild-moderate group (P = 0.048, P = 0.049). The results of logistic regression suggested that the rintSO2 (OR = 1.491, P = 0.003), PCT (OR = 3.071, P = 0.001) and MPV (OR = 4.027, P = 0.015) were independent predictive factors for severity of NEC. The area under the curve (AUC) of the rintSO2 combined with PCT and MPV showed good diagnostic ability in the severity of NEC. Conclusion: The rintSO2 combined with PCT and MPV may be considered as the early biomarkers in the severity of NEC and could help us to diagnose the case early with early treatment with better prognosis.
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The monitoring of the lifetime of cutting tools often faces problems such as life data loss, drift, and distortion. The prediction of the lifetime in this situation is greatly compromised with respect to the accuracy. The recent rise of deep learning, such as Gated Recurrent Unit Units (GRUs), Hidden Markov Models (HMMs), Convolutional Neural Networks (CNNs), Recurrent Neural Networks (RNNs), Attention networks, and Transformers, has dramatically improved the data problems in tool lifetime prediction, substantially enhancing the accuracy of tool wear prediction. In this paper, we introduce a novel approach known as PCHIP-Enhanced ConvGRU (PECG), which leverages multiple-feature fusion for tool wear prediction. When compared to traditional models such as CNNs, the CNN Block, and GRUs, our method consistently outperformed them across all key performance metrics, with a primary focus on the accuracy. PECG addresses the challenge of missing tool wear measurement data in relation to sensor data. By employing PCHIP interpolation to fill in the gaps in the wear values, we have developed a model that combines the strengths of both CNNs and GRUs with data augmentation. The experimental results demonstrate that our proposed method achieved an exceptional relative accuracy of 0.8522, while also exhibiting a Pearson's Correlation Coefficient (PCC) exceeding 0.95. This innovative approach not only predicts tool wear with remarkable precision, but also offers enhanced stability.
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BACKGROUND: Oxidative stress and inflammatory cytokines in the hypothalamus paraventricular nucleus (PVN) have been implicated in sympathetic nerve activity and the development of hypertension, but the specific mechanisms underlying their production in the PVN remains to be elucidated. Previous studies have demonstrated that activation of nuclear transcription related factor-2 (Nrf2) in the PVN reduced the production of reactive oxygen species (ROS) and inflammatory mediators. Moreover, AMP-activated protein kinase (AMPK), has been observed to decrease ROS and inflammatory cytokine production when activated in the periphery. 5-amino-1-ß-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) is an AMPK agonist. However, little research has been conducted on the role of AMPK in the PVN during hypertension. Therefore, we hypothesized that AICAR in the PVN is involved in regulating AMPK/Nrf2 pathway, affecting ROS and inflammatory cytokine expression, influencing sympathetic nerve activity. METHODS: Adult male Sprague-Dawley rats were utilized to induce two-kidney, one-clip (2K1C) hypertension via constriction of the right renal artery. Bilateral PVN was microinjected with either artificial cerebrospinal fluid or AICAR once a day for 4 weeks. RESULTS: Compared to the SHAM group, the PVN of 2K1C hypertensive rats decreased p-AMPK and p-Nrf2 expression, increased Fra-Like, NAD(P)H oxidase (NOX)2, NOX4, tumor necrosis factor-α and interleukin (IL)-1ß expression, elevated ROS levels, decreased superoxide dismutase 1 and IL-10 expression, and elevated plasma norepinephrine levels. Bilateral PVN microinjection of AICAR significantly ameliorated these changes. CONCLUSION: These findings suggest that repeated injection of AICAR in the PVN suppresses ROS and inflammatory cytokine production through the AMPK/Nrf2 pathway, reducing sympathetic nerve activity and improving hypertension.
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Proteínas Quinasas Activadas por AMP , Aminoimidazol Carboxamida , Hipertensión , Factor 2 Relacionado con NF-E2 , Núcleo Hipotalámico Paraventricular , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno , Ribonucleótidos , Transducción de Señal , Animales , Núcleo Hipotalámico Paraventricular/efectos de los fármacos , Núcleo Hipotalámico Paraventricular/metabolismo , Masculino , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/farmacología , Aminoimidazol Carboxamida/administración & dosificación , Ribonucleótidos/farmacología , Ribonucleótidos/administración & dosificación , Proteínas Quinasas Activadas por AMP/metabolismo , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Ratas , Transducción de Señal/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Presión Sanguínea/efectos de los fármacos , Sistema Nervioso Simpático/efectos de los fármacos , Sistema Nervioso Simpático/metabolismo , Estrés Oxidativo/efectos de los fármacos , Citocinas/metabolismoRESUMEN
BACKGROUND: The Bai people in Yunlong County, northwest Yunnan, China, have used medicinal plants and traditional remedies for ethnoveterinary practices. The Bai have mastered ethnoveterinary therapeutic methods in livestock breeding since ancient times. The Bai's traditional ethnoveterinary knowledge is now facing extinction, and their unique ethnoveterinary practices have rarely been recorded. This study documented animal diseases, EMPs, and related traditional knowledge in Yunlong County, China. METHODS: Ethnobotanical fieldwork was conducted in six villages and townships of Yunlong County between 2021 and 2022. Data were obtained through semi-structured interviews, participatory observations, and keyperson interviews. A total of 68 informants were interviewed, and the informant consensus factor and use reports (URs) were used to evaluate the current ethnoveterinary practices among the local communities. Information on livestock diseases, medicinal plants, and traditional ethnoveterinary medicine knowledge were also obtained. RESULTS: A total of 90 plant species belong to 51 families, 84 genera were recorded as being used as EMPs by the Bai people, and Asteraceae plants are most frequently used. A total of 68 informants were interviewed, including 58 men (85.3%) and 10 women (14.7%). The most commonly used EMPs parts included the roots, whole plants, leaves, and stems, and the common livestock diseases identified in this field investigation included trauma and fracture, gastrointestinal disorders, respiratory disorders, parasitic diseases, miscellaneous, venomous snake bites, reproductive diseases, infectious diseases, skin disease, and urinary diseases. Most of the EMPs are herbs (77.78%). Courtyard is one of the habitats of medicinal plants in Yunlong County. CONCLUSION: Traditional knowledge of ethnoveterinary medicine is related to the local sociocultural characteristics of the Bai. Plants are used in cultural traditions, which, in turn, nourish the plant culture. Cultural diversity and biodiversity are interdependent. This traditional knowledge is at risk of disappearance because of the increasing extension of Western veterinary medicine, lifestyle changes, and mainstream cultural influences. Therefore, it is important to continue research on ethnoveterinary practices.
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Plantas Medicinales , Pueblos del Sudeste Asiático , Masculino , Animales , Humanos , Femenino , Fitoterapia/métodos , China , Fitomejoramiento , Etnobotánica/métodos , GanadoRESUMEN
Objective: This retrospective analysis aims to assess the efficacy of transesophageal ultrasound-guided patent foramen ovale (PFO) closure in treating migraine in adolescents and compare the therapeutic outcomes of PFO closure for migraine with and without aura. Methods: We conducted a retrospective analysis of 86 cases of adolescents (12-20 years old) who underwent PFO closure for migraine at our institution over the past 3 years. The efficacy was evaluated using the visual analogue scale (VAS), headache impact test (HIT)-6, and pediatric migraine disability assessment (PedMIDAS) scores, as well as by assessing the monthly frequency of migraine attacks, duration of each attack, and overall migraine burden. The patients were divided into two groups: an aura group (55 cases) and a non-aura group (31 cases) to investigate difference in therapeutic efficacy between the groups. The effect of residual shunt on migraine burden was assessed. Results: Among the 86 patients, 46 (54%) experienced complete remission of migraine, while 71 (83%) achieved a >50% reduction in migraine burden during the one-year follow-up period. Patients in the aura group showed more significant improvements in VAS, HIT-6, and PedMIDAS scores, as well as in monthly migraine attack frequency, duration of each attack, and overall migraine burden, than patients in the non-aura group. Moreover, patients with residual shunt did not exhibit statistically significant differences in therapeutic efficacy compared to patients with complete closure. Conclusion: PFO closure can effectively alleviate migraine symptoms in adolescents with migraine with concomitant PFO. The therapeutic efficacy is particularly pronounced for migraine with aura. Furthermore, minor levels of residual shunt have no effect on the improvement in migraine symptoms.
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BACKGROUND: Persistent left superior vena cava (PLSVC), a relatively rare thoracic vascular malformation, can inconvenience perfusionists and operators when encountered during deep hypothermic circulatory arrest (DHCA). CASE SUMMARY: Herein, we describe the case of a patient with concurrent giant aortic arch aneurysm, aortic stenosis, and PLSVC. To treat these conditions, we performed right hemiarch and aortic valve replacements under DHCA. Notably, we applied "bilateral superior vena cava retrograde cerebral perfusion (RCP)" for cerebral protection, which significantly optimized the surgical procedure and reduced the risk of postoperative complications. The patient was discharged 14 d after surgery with no complications. CONCLUSION: Surgical intervention for PLSVC under DHCA can be performed using the bilateral superior vena cava RCP approach.
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Sensitive detection of ochratoxin A (OTA) is significant and essential because OTA may pose risks to human and animal health. Here, we developed an electrochemical aptasensor for OTA analysis using polyamidoamine (PAMAM) dendrimers as a signal amplifier. As a carrier, PAMAM has numerous primary amino groups that can be coupled with thiolated complementary strand DNA (cDNA), allowing it to recognize aptamers bound to the surface of horseradish peroxidase (HRP)-modified gold nanoparticles (AuNPs), thereby improving the sensitivity of the aptasensor. When monitoring the positive samples, OTA was captured by the aptamer fixed on the HRP-conjugated AuNP surface by specific recognition, after which the formed OTA-aptamer conjugates were detached from the electrode surface, ultimately decreasing the electrochemical signal monitored by differential pulse voltammetry. The novel aptasensor achieved a broad linear detection range from 5 to 105 ng L-1 with a low detection limit of 0.31 ng L-1. The proposed aptasensor was successfully applied for OTA analysis in red wine, with recovery rates ranging from 94.15 to 106%. Furthermore, the aptasensor also exhibited good specificity and storage stability. Therefore, the devised aptasensor represents a sensitive, practical and reliable tool for monitoring OTA in agricultural products, which can also be adapted to other mycotoxins.
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Aptámeros de Nucleótidos , Técnicas Biosensibles , Nanopartículas del Metal , Ocratoxinas , Humanos , Oro , Técnicas Electroquímicas , Ocratoxinas/análisis , ADN Complementario , Límite de DetecciónRESUMEN
BACKGROUND: RNA modifications, especially N6-methyladenosine, N1-methyladenosine and 5-methylcytosine, play an important role in the progression of cardiovascular disease. However, its regulatory function in dilated cardiomyopathy (DCM) remains to be undefined. METHODS: In the study, key RNA modification regulators (RMRs) were screened by three machine learning models. Subsequently, a risk prediction model for DCM was developed and validated based on these important genes, and the diagnostic efficiency of these genes was assessed. Meanwhile, the relevance of these genes to clinical traits was explored. In both animal models and human subjects, the gene with the strongest connection was confirmed. The expression patterns of important genes were investigated using single-cell analysis. RESULTS: A total of 4 key RMRs were identified. The risk prediction models were constructed basing on these genes which showed a good accuracy and sensitivity in both the training and test set. Correlation analysis showed that insulin-like growth factor binding protein 2 (IGFBP2) had the highest correlation with left ventricular ejection fraction (LVEF) (R = -0.49, P = 0.00039). Further validation expression level of IGFBP2 indicated that this gene was significantly upregulated in DCM animal models and patients, and correlation analysis validation showed a significant negative correlation between IGFBP2 and LVEF (R = -0.87; P = 6*10-5). Single-cell analysis revealed that this gene was mainly expressed in endothelial cells. CONCLUSION: In conclusion, IGFBP2 is an important biomarker of left ventricular dysfunction in DCM. Future clinical applications could possibly use it as a possible therapeutic target.
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Cardiomiopatía Dilatada , Disfunción Ventricular Izquierda , Humanos , Biomarcadores , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/diagnóstico , Células Endoteliales , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina , ARN , Volumen Sistólico , Disfunción Ventricular Izquierda/genética , Función Ventricular IzquierdaRESUMEN
CMTM6 has been connected to the development of several malignancies. However, it is still unknown what function CMTM6 serves in pancreatic adenocarcinoma (PAAD). We obtained RNA sequencing information of PAAD from public datasets and predicted statistical significance of CMTM6 survival in accordance with Kaplan-Meier curves. Gene set enrichment assessment (GSEA) was employed to analyze changes in pathways. Then, we systematically investigated the association involving CMTM6 and the immunological traits within the tumor microenvironment (TME) of PAAD, including immune pathways, immunomodulators, immune infiltrating cells, inflammatory activities, and immunotherapy response prediction. To demonstrate the biologically malignant properties of CMTM6 expression, the Cell Counting Kit-8, transwell experiments, colony formation, and wound healing were utilized. Upregulated CMTM6 expression was revealed within PAAD tissues, which was associated with more frequent somatic mutations and worse survival outcomes. Specifically, CMTM6 expression represented stronger immune infiltration, inflammatory activity, and better immunotherapeutic response in TME. Functional studies revealed that CMTM6 promoted the ability to proliferate, migrate, and invade. Additionally, CMTM6 and PD-L1 had a positive relationship, and CMTM6 can co-immunocoprecipitate with PD-L1 protein in pancreatic cell lines. CMTM6 overexpression shapes the inflammatory TME with a strong immune response. These findings support that CMTM6 is an immunotherapeutic target with promising effect to treat PAAD.
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Adenocarcinoma , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/genética , Adenocarcinoma/genética , Microambiente Tumoral , Línea Celular , Neoplasias PancreáticasRESUMEN
Tumors have evolved in various mechanisms to evade the immune system, hindering the antitumor immune response and facilitating tumor progression. Immunotherapy has become a potential treatment strategy specific to different cancer types by utilizing multifarious molecular mechanisms to enhance the immune response against tumors. Among these mechanisms, the ubiquitin-proteasome system (UPS) is a significant non-lysosomal pathway specific to protein degradation, regulated by deubiquitinating enzymes (DUBs) that counterbalance ubiquitin signaling. Ubiquitin-specific proteases (USPs), the largest DUB family with the strongest variety, play critical roles in modulating immune cell function, regulating immune response, and participating in antigen processing and presentation during tumor progression. According to recent studies, the expressions of some USP family members in tumor cells are involved in tumor immune escape and immune microenvironment. This review explores the potential of targeting USPs as a new approach for cancer immunotherapy, highlighting recent basic and preclinical studies investigating the applications of USP inhibitors. By providing insights into the structure and function of USPs in cancer immunity, this review aims at assisting in developing new therapeutic approaches for enhancing the immunotherapy efficacy.
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Inmunoterapia , Neoplasias , Humanos , Citoplasma , Complejo de la Endopetidasa Proteasomal , Ubiquitina , Proteasas Ubiquitina-Específicas , Neoplasias/terapiaRESUMEN
Background: Giant coronary artery aneurysms (GCAAs) were relatively rare. Little was known about its characteristics, its etiology and its therapy. GCAAs with multiple abdominal artery aneurysms (AAAs) were more unusual and rarer. Case presentation: A 29-year-old female presented to our hospital with abrupt-onset abdominal pain in the left upper quadrant and then she died in 2018. In 2016, prior to this visit, she came to our department for intermittent retrosternal compression pain during rest or sports activities. Medical history showed she had a coronary artery aneurysm (CAA) in 2004. We found evidence of multiple coronary aneurysms with severe stenosis and multiple AAAs and coronary artery bypass grafting (CABG) was carried out. In combination with laboratory analysis, imaging studies, and pathological examination, CAA may result from the long-term effects of Kawasaki disease (KD). Finally, the patient died of a ruptured abdominal aneurysm. Conclusions: We report a rare case of GCAAs with severe stenosis and multiple AAAs in a young woman with a history of KD-induced coronary aneurysm. Although the understanding of the optimal treatment strategy for GCAAs combined with multiple aneurysms was limited, we found that CABG was effective in the treatment of GCAAs in this patient. In the clinical treatment of patients with GCAAs, attention should be paid to the examination of systemic blood vessels.
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The prediction of drug-drug interactions (DDIs) is essential for the development and repositioning of new drugs. Meanwhile, they play a vital role in the fields of biopharmaceuticals, disease diagnosis and pharmacological treatment. This article proposes a new method called DBGRU-SE for predicting DDIs. Firstly, FP3 fingerprints, MACCS fingerprints, Pubchem fingerprints and 1D and 2D molecular descriptors are used to extract the feature information of the drugs. Secondly, Group Lasso is used to remove redundant features. Then, SMOTE-ENN is applied to balance the data to obtain the best feature vectors. Finally, the best feature vectors are fed into the classifier combining BiGRU and squeeze-and-excitation (SE) attention mechanisms to predict DDIs. After applying five-fold cross-validation, The ACC values of DBGRU-SE model on the two datasets are 97.51 and 94.98%, and the AUC are 99.60 and 98.85%, respectively. The results showed that DBGRU-SE had good predictive performance for drug-drug interactions.
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Biología Computacional , Interacciones Farmacológicas , Biología Computacional/métodosRESUMEN
Phoebe bournei, belonging to the family Lauraceae, is indigenous to China, where it is a protected species. In March 2022, ca. 90% of 20,000 P. bournei saplings suffered from leaf tip blight in a sapling nursery with an area of 200 m2 in Fuzhou, China. Initially, brown discoloration appeared on the tips of young leaves. The symptomatic tissue continued to expand as the leaf grew. To isolate the pathogen, 10 symptomatic leaves were randomly sampled from the nursery, and surface-sterilized in 75% alcohol for 30 s, followed by a 5% NaClO solution for 3 min, and then rinsed 3 times with sterile water. Twenty small pieces (0.3 x 0.3 cm) were excised from the margin of diseased and healthy tissue and transferred to five PDA plates amended with 50 µg/ml ampicillin. The plates were incubated at 25°C for 5 days. Finally, 17 isolates were obtained, and nine isolates with the highest isolation frequency shared the same morphological characteristics. On PDA, these colonies had aerial hyphae, white in the beginning, and became pale brown with the pigment production. Chlamydospores were observed after incubation for 7 days at 25°C, pale brown and nearly spherical, unicellular, or multicellular. Conidia were unicellular or bicellular, hyaline, and ellipsoidal, 5.15 to 9.89× 3.46 to 5.87 µm, n=50. The 9 fungi were identified as Epicoccum sp (Khoo et al. 2022a, b, c). Furthermore, strain MB3-1 was chosen randomly as the representative of the 9 isolates, and ITS, LSU, TUB sequences were amplified using the primers ITS1/ITS4, LR0R/LR5, Bt2a/Bt2b respectively (Raza et al. 2019). The sequences were submitted to NCBI and analyzed using BLAST. Results of BLAST showed that ITS (OP550308), LSU (OP550304), TUB (OP779213) sequences had 99.59% (490bp out of 492bp), 99.89% (870bp out of 871bp), 100% (321bp out of 321bp) identity to Epicoccum sorghinum sequences MH071389, MW800361, MW165323, respectively. ITS, LSU, TUB sequences were concatenated for phylogenetic analysis using the maximum likelihood method with 1000 bootstrap replicates in MEGA 7.0 software. The phylogenetic tree showed that MB3-1 was clustered together with E. sorghinum. Pathogenicity tests were performed on young leaves of healthy P. bournei saplings in vivo by inoculating with fungal conidia suspension. The conidia were eluted from the colony of MB3-1 and adjusted to 1×106 spores/ml. An amount of 20 µl conidia suspension (0.1% tween-80) was evenly sprayed on three leaves of one P. bournei sapling, 20 µl sterile water was sprayed on three other leaves of the same sapling as control, and three saplings were treated. All the treated saplings were kept at 25°C. MB3-1 caused leaf tip blight symptoms similar to those observed in nature at 6 days post inoculation (dpi). The pathogen was reisolated from inoculated leaves and identified as E. sorghinum. The experiment was repeated twice with the same results. Recently, E. sorghinum has been reported in Brazil (Gasparetto et al. 2017), Malaysia (Khoo et al. 2022a, b, c), and the United States (Imran et al. 2022). To our knowledge, this is the first report of E. sorghinum causing leaf tip blight on P. bournei. Wood from P. bournei is used to produce high-quality furniture due to its vertical grain and durability (Chen et al. 2020). And the demand for wood requires numerous saplings for afforestation. But this disease has the risk of causing insufficient saplings, which would affect the development of the P. bournei timber industry.