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Enzymes are indispensable in many biological processes, and with biomedical literature growing exponentially, effective literature review becomes increasingly challenging. Natural language processing methods offer solutions to streamline this process. This study aims to develop an annotated enzyme corpus for training and evaluating enzyme named entity recognition (NER) models. A novel pipeline, combining dictionary matching and rule-based keyword searching, automatically annotated enzyme entities in >4800 full-text publications. Four deep learning NER models were created with different vocabularies (BioBERT/SciBERT) and architectures (BiLSTM/transformer) and evaluated on 526 manually annotated full-text publications. The annotation pipeline achieved an F1-score of 0.86 (precision = 1.00, recall = 0.76), surpassed by fine-tuned transformers for F1-score (BioBERT: 0.89, SciBERT: 0.88) and recall (0.86) with BiLSTM models having higher precision (0.94) than transformers (0.92). The annotation pipeline runs in seconds on standard laptops with almost perfect precision, but was outperformed by fine-tuned transformers in terms of F1-score and recall, demonstrating generalizability beyond the training data. In comparison, SciBERT-based models exhibited higher precision, and BioBERT-based models exhibited higher recall, highlighting the importance of vocabulary and architecture. These models, representing the first enzyme NER algorithms, enable more effective enzyme text mining and information extraction. Codes for automated annotation and model generation are available from https://github.com/omicsNLP/enzymeNER and https://zenodo.org/doi/10.5281/zenodo.10581586.
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Algoritmos , Aprendizaje Profundo , Enzimas , Procesamiento de Lenguaje Natural , Anotación de Secuencia Molecular/métodos , Humanos , Minería de Datos/métodosRESUMEN
BACKGROUND: There is a dearth of research combining geographical big data on medical resource allocation and growth with various statistical data. Given the recent achievements of China in economic development and healthcare, this study takes China as an example to investigate the dynamic geographical distribution patterns of medical resources, utilizing data on healthcare resources from 290 cities in China, as well as economic and population-related data. The study aims to examine the correlation between economic growth and spatial distribution of medical resources, with the ultimate goal of providing evidence for promoting global health equity. METHODS: The data used in this study was sourced from the China City Statistical Yearbook from 2001 to 2020. Two indicators were employed to measure medical resources: the number of doctors per million population and the number of hospital and clinic beds per million population. We employed dynamic convergence model and fixed-effects model to examine the correlation between economic growth and the spatial distribution of medical resources. Ordinary least squares (OLS) were used to estimate the ß values of the samples. RESULTS: The average GDP for all city samples across all years was 36,019.31 ± 32,029.36, with an average of 2016.31 ± 1104.16 doctors per million people, and an average of 5986.2 ± 6801.67 hospital beds per million people. In the eastern cities, the average GDP for all city samples was 47,672.71 ± 37,850.77, with an average of 2264.58 ± 1288.89 doctors per million people, and an average of 3998.92 ± 1896.49 hospital beds per million people. Cities with initially low medical resources experienced faster growth (all ß < 0, P < 0.001). The long-term convergence rate of the geographic distribution of medical resources in China was higher than the short-term convergence rate (|ßi + 1| > |ßi|, i = 1, 2, 3, , 9, all ß < 0, P < 0.001), and the convergence speed of doctor density exceeded that of bed density (bed: |ßi| >doc: |ßi|, i = 3, 4, 5, , 10, P < 0.001). Economic growth significantly affected the convergence speed of medical resources, and this effect was nonlinear (doc: ßi < 0, i = 1, 2, 3, , 9, P < 0.05; bed: ßi < 0, i = 1, 2, 3, , 10, P < 0.01). The heterogeneity between provinces had a notable impact on the convergence of medical resources. CONCLUSIONS: The experiences of China have provided significant insights for nations worldwide. Governments and institutions in all countries worldwide, should actively undertake measures to actively reduce health inequalities. This includes enhancing healthcare standards in impoverished regions, addressing issues of unequal distribution, and emphasizing the examination of social determinants of health within the domain of public health research.
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Desarrollo Económico , Instituciones de Salud , Humanos , Hospitales , China , CiudadesRESUMEN
BACKGROUND: Chickenpox is an old but easily neglected infectious disease. Although chickenpox is preventable by vaccines, vaccine breakthroughs often occur, and the chickenpox epidemic is on the rise. Chickenpox is not included in the list of regulated communicable diseases that must be reported and controlled by public and health departments; therefore, it is crucial to rapidly identify and report varicella outbreaks during the early stages. The Baidu index (BDI) can supplement the traditional surveillance system for infectious diseases, such as brucellosis and dengue, in China. The number of reported chickenpox cases and internet search data also showed a similar trend. BDI can be a useful tool to display the outbreak of infectious diseases. OBJECTIVE: This study aimed to develop an efficient disease surveillance method that uses BDI to assist in traditional surveillance. METHODS: Chickenpox incidence data (weekly from January 2017 to June 2021) reported by the Yunnan Province Center for Disease Control and Prevention were obtained to evaluate the relationship between the incidence of chickenpox and BDI. We applied a support vector machine regression (SVR) model and a multiple regression prediction model with BDI to predict the incidence of chickenpox. In addition, we used the SVR model to predict the number of chickenpox cases from June 2021 to the first week of April 2022. RESULTS: The analysis showed that there was a close correlation between the weekly number of newly diagnosed cases and the BDI. In the search terms we collected, the highest Spearman correlation coefficient was 0.747. Most BDI search terms, such as "chickenpox," "chickenpox treatment," "treatment of chickenpox," "chickenpox symptoms," and "chickenpox virus," trend consistently. Some BDI search terms, such as "chickenpox pictures," "symptoms of chickenpox," "chickenpox vaccine," and "is chickenpox vaccine necessary," appeared earlier than the trend of "chickenpox virus." The 2 models were compared, the SVR model performed better in all the applied measurements: fitting effect, R2=0.9108, root mean square error (RMSE)=96.2995, and mean absolute error (MAE)=73.3988; and prediction effect, R2=0.548, RMSE=189.1807, and MAE=147.5412. In addition, we applied the SVR model to predict the number of reported cases weekly in Yunnan from June 2021 to April 2022 using the same period of the BDI. The results showed that the fluctuation of the time series from July 2021 to April 2022 was similar to that of the last year and a half with no change in the level of prevention and control. CONCLUSIONS: These findings indicated that the BDI in Yunnan Province can predict the incidence of chickenpox in the same period. Thus, the BDI is a useful tool for monitoring the chickenpox epidemic and for complementing traditional monitoring systems.
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Varicela , Humanos , Varicela/epidemiología , Varicela/prevención & control , Vacuna contra la Varicela , China/epidemiología , Brotes de Enfermedades/prevención & control , Incidencia , Infodemiología , Máquina de Vectores de Soporte , Vigilancia de GuardiaRESUMEN
The correlation of bile acid (BA) metabolism disorder with the pathogenesis of ulcerative colitis (UC) is realized nowadays. Farnesoid X receptor (FXR), a controller for BA homeostasis and inflammation, is a promising target for UC therapy. Nigakinone has potential therapeutic effects on colitis. Herein, we investigated the anti-UC effects and mechanism of nigakinone in colitic animals induced by dextran sulfate sodium (DSS). The related targets involved in the nucleotide-binding oligomerization domain, leucine-rich repeat, and pyrin domain-containing 3 (NLRP3) signaling pathway were measured. BA-targeted metabolomics was employed to reveal the regulatory effects of nigakinone on BA profile in colitis, while expressions of FXR and its mediated targets referring to BA enterohepatic circulation were determined. The critical role of FXR in the treatment of nigakinone for colitis was studied via molecule-docking, dual-luciferase reporter® (DLR™) assays, FXR silencing cells, and FXR knockout mice. Results showed nigakinone attenuated DSS-induced colitis symptoms, including excessive inflammatory response by NLRP3 activation, and injury of the intestinal mucosal barrier. Nigakinone regulated BA disorders by controlling cholesterol hydroxylase and transporters mediated by FXR, then decreased BA accumulation in colon. Molecular-docking and DLR™ assays indicated FXR might be a target of nigakinone. In vitro, nigakinone restrained BA-induced inflammation and cell damage via FXR activation and inhibition of inflammatory cytokines. However, ameliorating effects of nigakinone on colitis were suppressed by FXR knockout or silencing in vivo or in vitro. Taken together, nigakinone ameliorated experimental colitis via regulating BA profile and FXR/NLRP3 signaling pathway.
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Colitis Ulcerosa , Colitis , Animales , Ratones , Ácidos y Sales Biliares , Colitis/inducido químicamente , Colitis/tratamiento farmacológico , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Colon , Modelos Animales de Enfermedad , Inflamación/metabolismo , Ratones Endogámicos C57BL , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Transducción de Señal/fisiologíaRESUMEN
BACKGROUND: Child maltreatment is a prevalent and notable problem in rural China, and the prevalence and severity of depression in rural areas are higher than the national norm. Several studies have found that loneliness and coping skills respectively mediated the relationship between child maltreatment and depression. However, few studies have examined the roles of loneliness and coping skills in child maltreatment and depression based on gender differences. METHODS: All participants were from rural communities aged more than 18 years in Shandong province, and 879 valid samples (female:63.4%) ranging in age from 18 to 91 years old were analyzed. The Childhood Trauma Questionnaire-Short Form (CTQ-SF), the Center for Epidemiologic Studies-Depression (CES-D), the Simple Coping Style Questionnaire (SCSQ), and the Emotional and Social Loneliness Scale (ESLS) were used to evaluate child maltreatment, depression, coping skills and loneliness. RESULTS: Child maltreatment was more common and severe in males than females (F = 3.99; p < 0.05). Loneliness and coping skills partially mediated the relationship between child maltreatment and depression in males, but loneliness fully mediated the relationship between child maltreatment and depression in females. CONCLUSION: In this study, males were more likely to experience child maltreatment. Child maltreatment and depression were correlated. We also found a mediating role of loneliness and coping skills for males and a mediating role of loneliness in females.
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Maltrato a los Niños , Soledad , Adaptación Psicológica , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Niño , Maltrato a los Niños/psicología , Depresión/psicología , Femenino , Humanos , Soledad/psicología , Masculino , Persona de Mediana Edad , Población Rural , Adulto JovenRESUMEN
Carotenoids are important photosynthetic pigments with many physiological functions, nutritional properties and high commercial value. ß-carotene hydroxylase is one of the key enzymes in the carotenoid synthesis pathway of Chlamydomonas reinhardtii for the conversion of ß-carotene to astaxanthin. The vector p64DZ containing the ß-carotene hydroxylase gene crtZ from Haematococcus pluvialis was transformed into C. reinhardtii CC-503. The transformants were selected by alternate culture in solid-liquid medium containing spectinomycin (100 µg mL-1). PCR results indicated that the gene crtZ and aadA were integrated into the genome of C. reinhardtii. RT-PCR analysis showed that the gene crtZ was transcribed in Chlamydomonas transformants. HPLC analysis showed that the content of astaxanthin and ß-carotene in cells of C. reinhardtii were simultaneously increased. Under medium light intensity cultivation (60 µmol m-2 s-1), transgenic C. reinhardtii had an 85.8% increase in ß-carotene content compared with the wild type. The content of astaxanthin and ß-carotene reached 1.97 ± 0.13 mg g-1 fresh cell weight (FCW) and 105.94 ± 5.84 µg g-1 FCW, which were increased 18% and 42.4% than the wild type after 6 h of high light treatment (200 µmol m-2 s-1), respectively. Our results indicate the regulatory effect on pigments in C. reinhardtii by ß-carotene hydroxylase gene of H. pluvialis, and demonstrate the positive effect of high light stress on pigment accumulation in transgenic C. reinhardtii.
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Chlamydomonas reinhardtii , beta Caroteno , Chlamydomonas reinhardtii/genética , Chlamydomonas reinhardtii/metabolismo , Oxigenasas de Función Mixta , XantófilasRESUMEN
Acute pancreatitis (AP) is a severe inflammatory disorder hampered by a lack of effective drugs in its clinical practice. Empagliflozin (EMP) exhibits potential effects against AP but is limited by poor water-solubility and low bioavailability. Herein, a novel self-nanomicellizing formulation of EMP with phytochemical rebaudioside A (RA) as the nanocarrier (RA-EMP) was fabricated to address these issues. RA-EMP powder could be simply prepared and exhibited excellent storage stability, dramatically improved EMP's apparent solubility, and instantly self-assembled into micelles with high EMP encapsulation efficiency in water. In vivo experimental studies showed that RA-EMP exhibited significantly enhanced oral bioavailability of EMP and dramatically improved therapeutic efficacy against AP. The mechanisms through suppressing the effects of oxidative stress and proinflammatory cytokines were involved in this therapeutic effect. The results demonstrated that RA-EMP could serve as a promising way to enhance the oral bioavailability and strengthen the potential therapeutic efficacy of EMP against AP.
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Pancreatitis , Enfermedad Aguda , Administración Oral , Compuestos de Bencidrilo , Disponibilidad Biológica , Glucósidos , Humanos , Micelas , Pancreatitis/tratamiento farmacológico , Solubilidad , AguaRESUMEN
CCCH-type zinc finger proteins (ZFP) are a large family of proteins that play various important roles in plant growth and development; however, the functions of most proteins in this family are uncharacterized. In this study, a CCCH-type ZFP, AaZFP3, was identified in the floral organ of Adonis amurensis. Quantitative real-time PCR (qPCR) analysis revealed that AaZFP3 was widely expressed in the flowers of A.amurensis. Subcellular localization analysis showed that the AaZFP3 protein was mainly localized to the cytoplasm in tobacco and Arabidopsis. Furthermore, the overexpression of AaZFP3 promoted early flowering in Arabidopsis under both normal and relatively low-temperature conditions. RNA-sequencing and qPCR analyses revealed that the expression of multiple key flowering-time genes was altered in transgenic Arabidopsis overexpressing AaZFP3 compared to wild-type. Of these genes, FLOWERING LOCUS T (AtFT) expression was most significantly up-regulated, whereas FLOWERING LOCUS C (AtFLC) was significantly down-regulated. These results suggest that the overexpression of AaZFP3 promotes early flowering in Arabidopsis by affecting the expression of flowering-time genes. Overall, our study indicates that AaZFP3 may be involved in flowering regulation in A.amurensis and may represent an important genetic resource for improving flowering-time control in other ornamental plants or crops.
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Adonis , Proteínas de Arabidopsis , Arabidopsis , Adonis/genética , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Flores , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/genética , Dedos de Zinc/genéticaRESUMEN
This research aimed to excavate compounds with activity reducing hepatocytes lipid accumulation from Delphinium brunonianum. Four novel diterpenoid alkaloids, brunodelphinine B-E, were isolated from D. brunonianum together with eleven known diterpenoid alkaloids through a phytochemical investigation. Their structures were elucidated by comprehensive spectroscopy methods including HR-ESI-MS, NMR, IR, UV, CD, and single-crystal X-ray diffraction analysis. The inhibitory effects of a total of 15 diterpenoid alkaloids on hepatocytes lipid accumulation were evaluated using 0.5 mM FFA (oleate/palmitate 2:1 ratio) to induce buffalo rat liver (BRL) cells by measuring the levels of triglyceride (TG), total cholesterol (TC), alanine transaminase (ALT), aspartate transaminase (AST), and the staining of oil red O. The results show that five diterpenoid alkaloids-brunodelphinine E (4), delbruline (5), lycoctonine (7), delbrunine (8), and sharwuphinine A (12)-exhibited significant inhibitory effects on lipid accumulation in a dose-dependent manner and without cytotoxicity. Among them, sharwuphinine A (12) displayed the strongest inhibition of hepatocytes lipid accumulation in vitro. Our research increased the understanding on the chemical composition of D. brunonianum and provided experimental and theoretical evidence for the active ingredients screened from this herbal medicine in the treatment of the diseases related to lipid accumulation, such as non-alcoholic fatty liver disease and hyperlipidemia.
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Alcaloides , Delphinium , Diterpenos , Alcaloides/química , Alcaloides/farmacología , Delphinium/química , Diterpenos/química , Diterpenos/farmacología , Hepatocitos , Lípidos , Espectroscopía de Resonancia Magnética , Estructura MolecularRESUMEN
Background: In recent years, carbapenem-resistant Klebsiella pneumoniae (CRKP) has emerged rapidly in China with the abuse and overuse of antibiotics, and infections caused by CRKP pose a serious threat to global public health safety. The present study aimed to explore the epidemiological characteristics of CRKP isolates in Northern China and to elucidate their drug resistance mechanisms. Methods: 45 CRKP strains were consecutively collected at a teaching hospital from March 1st, 2018 to June 30th, 2018. Antimicrobial susceptibility was determined by the VITEK2 compact system and microbroth dilution method. Polymerase chain reaction (PCR) and sequencing were used to analyze multilocus sequence typing (MLST), drug resistance determinants, and plasmid types. The transfer of resistance genes was determined by conjugation. All statistical analysis was performed using SPSS 22.0 software. Results: All 45 isolates showed multidrug resistance (MDR). MLST analysis showed ST11 (48.9%, 22/45) was the most frequent type. All of the 45 CRKP isolates contained carbapenemase genes, extended-spectrum ß-lactamase (ESBL) genes, and plasmid-mediated quinolone resistance (PMQR) genes. For carbapenemase genes, KPC-2 (93.3%, 42/45) was the main genotype, and followed by GES (37.8%, 17/45) and NDM-1 (11.1%, 5/45). Plasmid typing analysis showed that IncFII and IncFIB were the most prevalent plasmids. The carbapenem resistance rate of K.pneumoniae was 11.4% and ICU was the main CRKP infection source. Conclusions: ST11 is the most frequent sequence type and KPC-2 is the predominant carbapenemase of CRKP strains in Northern China. KPC-2-ST11 are representative clonal lineages.
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Endovascular treatment (EVT) has been widely used for treating acute ischemic stroke (AIS). However, the safety and efficacy of treating AIS with tirofiban combined with EVT remain controversial. Therefore, we conducted a meta-analysis to evaluate this treatment. Randomized controlled trials and cohort studies that compared treatment with tirofiban combined with EVT and EVT alone were included in our meta-analysis. Those published from inception to March 31, 2020, were searched using the PubMed, Web of Science, Embase, and Cochrane Library databases. Safety was assessed based on symptomatic intracranial hemorrhage (sICH) incidence and 3-month mortality. Efficacy was assessed based on modified Rankin Scale (mRS) scores at 3 months post-EVT and recanalization rates. Data were analyzed using either the random-effects or fixed-effects model based on the heterogeneity of studies. In total, one RCT, six prospective studies, and four retrospective studies (2387 AIS cases) were assessed. Our meta-analysis showed that tirofiban combined with EVT did not increase sICH risk (RR, 1.06; 95%CI, 0.79 to 1.42; P = 0.72) and 3-month mortality (RR, 0.87; 95%CI, 0.74 to 1.04; P = 0.12). Recanalization rates were not significantly different between patients treated with tirofiban combined with EVT and those treated with EVT alone (RR, 1.04; 95%CI, 1.00 to 1.08; P = 0.07), but tirofiban combined with EVT was significantly associated with favorable functional outcomes (mRS score, 0-2) in AIS patients (RR, 1.13; 95%CI, 1.02 to 1.25; P = 0.02). Tirofiban combined with EVT appears to be safe and potentially effective in treating AIS.
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Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Isquemia Encefálica/terapia , Humanos , Estudios Prospectivos , Estudios Retrospectivos , Accidente Cerebrovascular/tratamiento farmacológico , Tirofibán , Resultado del TratamientoRESUMEN
Bacteremia caused by Eggerthia catenaformis is a rarely reported pathogen in cancer patients. Herein, we report a case of bacteremia caused by E.catenaformis in a patient with gastric cancer in China. The patient was a 55-year-old man, diagnosed with gastric cancer more than one month ago, with intermittent fever at a maximum of 39.5⯰C for more than half a month. He received symptomatic and supportive treatment after admission to our hospital; a rare anaerobic microorganism, E. catenaformis was isolated from an anaerobic blood culture sample taken from the patient. The antimicrobial susceptibility testing was performed after the isolates were successfully identified by MALDI-TOF MS and 16S rRNA sequencing. The patient was then successfully treated for the bacteremia with metronidazole. To the best of our knowledge, this is the first report of E. catenaformis bacteremia in a patient with cancer.
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Bacteriemia/diagnóstico , Bacteriemia/microbiología , Firmicutes/clasificación , Firmicutes/efectos de los fármacos , Neoplasias Gástricas/complicaciones , Bacteriemia/complicaciones , Técnicas de Tipificación Bacteriana , China , ADN Bacteriano/genética , Firmicutes/aislamiento & purificación , Humanos , Masculino , Persona de Mediana Edad , ARN Ribosómico 16S/genética , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
BACKGROUND: Drug resistance of paclitaxel (TAX), the first-line chemotherapy drug for breast cancer, was reported to develop in 90% of patients with breast cancer, especially metastatic breast cancer. Investigating the mechanism of TAX resistance of breast cancer cells and developing the strategy improving its therapeutic efficiency are crucial to breast cancer cure. METHODS AND RESULTS: We here report an elegant nanoparticle (NP)-based technique that realizes efficient breast cancer treatment of TAX. Using lentiviral vector-mediated gene knockdown, we first demonstrated that TAX therapeutic efficiency was closely correlated with metadherin (MTDH) gene expression in breast cancer cell lines. This finding was also supported by efficacy of TAX treatment in breast cancer patients from our clinical studies. Specifically, TAX treatment became more effective when MTDH expression was decreased in MCF-7 cancer cells by the blocking nuclear factor-kappa B (NF-κB) pathway. Based on these findings, we subsequently synthesized a polymeric NP that could co-deliver MTDH-small interfering RNA (MTDH-siRNA) and TAX into the breast cancer tumors in tumor-bearing mice. The NPs were composed of a cationic copolymer, which wrapped TAX in the inside and adsorbed the negatively charged siRNA on their surface with high drug-loading efficiency and good stability. CONCLUSIONS: NP-based co-delivery approach can effectively knock down the MTDH gene both in vitro and in vivo, which dramatically inhibits breast tumor growth, achieving effective TAX chemotherapy treatment without overt side effects. This study provides a potential therapeutic strategy for the treatment of a wide range of solid tumors highly expressing MTDH.
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Neoplasias de la Mama/tratamiento farmacológico , Moléculas de Adhesión Celular/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Paclitaxel/farmacología , Interferencia de ARN , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Antineoplásicos Fitogénicos/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Moléculas de Adhesión Celular/metabolismo , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Resistencia a Antineoplásicos/genética , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Proteínas de la Membrana , Ratones Desnudos , Nanopartículas/administración & dosificación , Nanopartículas/química , Proteínas de Unión al ARN , Estudios Retrospectivos , Carga Tumoral/efectos de los fármacos , Carga Tumoral/genéticaRESUMEN
The metabolic and pharmacokinetic studies on complanatuside, a quality marker of a Chinese materia medicatonic, Semen Astragali Complanati, were carried out. The UHPLC-Q-TOF/MS (ultra-high performance liquid chromatography coupled with electrospray ionization tandem quadrupole-time-of-flight mass spectrometry) method was applied to identify the metabolites of complanatuside in rat plasma, bile, stool, and urine after oral administration at the dosage of 72 mg/kg. Up to 34 metabolites (parent, 2 metabolites of the parent drug, and 31 metabolites of the degradation products) were observed, including processes of demethylation, hydroxylation, glucuronidation, sulfonation, and dehydration. The results indicated glucuronidation and sulfonation as major metabolic pathways of complanatuside in vivo. Meanwhile, a HPLC-MS method to quantify complanatuside and its two major metabolites-rhamnocitrin 3-O-ß-glc and rhamnocitrin-in rat plasma for the pharmacokinetic analysis was developed and validated. The Tmax (time to reach the maximum drug concentration) of the above three compounds were 1 h, 3 h, and 5.3 h, respectively, while the Cmax (maximum plasma concentrations)were 119.15 ng/mL, 111.64 ng/mL, and 1122.18 ng/mL, and AUC(0-t) (area under the plasma concentration-time curve) was 143.52 µg/L·h, 381.73 µg/L·h, and 6540.14 µg/L·h, accordingly. The pharmacokinetic characteristics of complanatuside and its two metabolites suggested that complanatuside rapidly metabolized in vivo, while its metabolites-rhamnocitrin-was the main existent form in rat plasma after oral administration. The results of intracorporal processes, existing forms, and pharmacokinetic characteristics of complanatuside in rats supported its low bioavailability.
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Flavonoles/metabolismo , Flavonoles/farmacocinética , Glucósidos/metabolismo , Glucósidos/farmacocinética , Administración Oral , Animales , Cromatografía Líquida de Alta Presión , Flavonoles/administración & dosificación , Glucósidos/administración & dosificación , Masculino , Metabolómica , Ratas , Ratas Sprague-Dawley , Espectrometría de Masa por Ionización de Electrospray , Espectrometría de Masas en TándemRESUMEN
PURPOSE: We undertook a meta-analysis of randomized trials to evaluate the efficacy of multitargeted antiangiogenic tyrosine kinase inhibitors (MATKIs) in addition to chemotherapy in metastatic breast cancer. METHODS: PubMed, Web of Knowledge databases and the ASCO meeting abstracts were searched for eligible literature published up to August 30, 2013. The endpoints included progression-free survival (PFS), overall survival (OS), overall response rate (ORR) and toxicities. Pooled hazard ratios (HRs) for survival outcomes and odds ratio (ORs) for dichotomous data with 95 % confidence intervals (CIs) were derived. RESULTS: Eight studies including 2,077 participants were analyzed. Compared to chemotherapy alone, adding MATKIs to chemotherapy resulted in a 14 % risk reduction of PFS events. However, the benefit did not reach statistical significance (HR 0.86; 95 % CI 0.70-1.04, P=0.126). Also, no OS benefit was observed (HR 1.03; 95 % CI 0.89-1.18, P=0.724). The addition of MATKIs significantly increased the ORR (OR 1.57; 95 % CI 1.30-1.91, P=0.000). Subgroup analysis revealed that sorafinib showed a significantly greater effect on PFS in patients with HER2 negative metastatic breast cancer (HR 0.67; 95 % CI 0.55-0.82, P=0.000) in comparison to chemotherapy alone. Additionally, sunitinib seemed to have no substantial efficacy for metastatic breast cancer. Toxicities were more frequent in patients receiving MATKIs. CONCLUSION: Overall, regimens consisting of MATKIs seemed not to be superior to chemotherapy alone in terms of PFS and OS, although significant improvement in ORR was observed. However, the addition of sorafenib significantly improved PFS. Further studies are needed to corroborate this finding.
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Inhibidores de la Angiogénesis/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias de la Mama/irrigación sanguínea , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/patología , Supervivencia sin Enfermedad , Femenino , Humanos , Terapia Molecular Dirigida , Metástasis de la Neoplasia , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
Superatoms are crucial in the assembly of functional and optoelectronic materials. This study investigates the endohedral metallo-boron nitride [boron nitride (BN)] fullerenes U@B12N12, Cm@B12N12, and U@B16N16 in theory. Our findings confirm that U@B12N12, Cm@B12N12, and U@B16N16 are superatoms and their electronic configurations are 1P61S21D101F142P62S22D102F123P6, 1P61S21D101F141G161H162S22P62D102F12, and 1P61S21D101F142P62S22D102F14, respectively. Notably, the orbital energy levels in these superatoms exhibit a flipping phenomenon, deviating from those of previous superatom studies. Further, the orbital composition analyses reveal that superatomic orbitals 1S, 1P, 1D, and 1F mainly originate from BN cages, whereas the 2S, 2P, 2D, 2F, and 3P superatomic orbitals arise from hybridizations between BN cage orbitals and the 7s, 7p, 6d, and 5f orbitals of actinide atoms. And the energy gap of endohedral metallo-BN fullerene superatoms is reduced by introducing actinide atoms. Additionally, the analyses of ionization potentials and electron affinities show that U@B12N12, Cm@B12N12, and U@B16N16 have lower ionization potentials and higher electron affinities, suggesting decreased stability compared to that of pure BN cages. This instability may be linked to the observed flipping of the superatomic orbital energy levels. These insights introduce new members to the superatom family and offer new building blocks for the design of nanoscale materials with tailored properties.
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Retinal vessel segmentation plays a vital role in the clinical diagnosis of ophthalmic diseases. Despite convolutional neural networks (CNNs) excelling in this task, challenges persist, such as restricted receptive fields and information loss from downsampling. To address these issues, we propose a new multi-fusion network with grouped attention (MAG-Net). First, we introduce a hybrid convolutional fusion module instead of the original encoding block to learn more feature information by expanding the receptive field. Additionally, the grouped attention enhancement module uses high-level features to guide low-level features and facilitates detailed information transmission through skip connections. Finally, the multi-scale feature fusion module aggregates features at different scales, effectively reducing information loss during decoder upsampling. To evaluate the performance of the MAG-Net, we conducted experiments on three widely used retinal datasets: DRIVE, CHASE and STARE. The results demonstrate remarkable segmentation accuracy, specificity and Dice coefficients. Specifically, the MAG-Net achieved segmentation accuracy values of 0.9708, 0.9773 and 0.9743, specificity values of 0.9836, 0.9875 and 0.9906 and Dice coefficients of 0.8576, 0.8069 and 0.8228, respectively. The experimental results demonstrate that our method outperforms existing segmentation methods exhibiting superior performance and segmentation outcomes.
Asunto(s)
Aprendizaje , Vasos Retinianos , Vasos Retinianos/diagnóstico por imagen , Redes Neurales de la Computación , Procesamiento de Imagen Asistido por ComputadorRESUMEN
The misuse of aromatic amines like 4-chloroaniline (4-CA) has led to severe environmental and health issues. However, it's difficult to be utilized by microorganisms for degradation. Nano-zero-valent iron (nZVI) is a promising material for the remediation of chloroaniline pollution, however, the synergistic effect and mechanism of nZVI with microorganisms for the degradation of 4-CA are still unclear. This study investigated the potential of 4-CA removal by the synergistic system involving nZVI and 4-CA degrading microbial flora. The results indicate that the addition of nZVI significantly enhanced the bio-degradation rate of 4-CA from 43.13 % to 62.26 %. Under conditions involving 0.1 % nZVI addition at a 24-hour interval, pH maintained at 7, and glucose as an external carbon source, the microbial biomass, antioxidant enzymes, and dehydrogenase were significantly increased, and the optimal 4-CA degradation rate achieved 68.79 %. Additionally, gas chromatography-mass spectrometry (GC-MS) analysis of intermediates indicated that the addition of nZVI reduced compounds containing benzene rings and enhanced the dechlorination efficiency. The microbial community remained stable during the 4-CA degradation process. This study illustrates the potential of nZVI in co-microbial remediation of 4-CA compounds in the environment.
Asunto(s)
Compuestos de Anilina , Biodegradación Ambiental , Hierro , Contaminantes Químicos del Agua , Compuestos de Anilina/química , Compuestos de Anilina/metabolismo , Hierro/química , Hierro/metabolismo , Contaminantes Químicos del Agua/metabolismo , Contaminantes Químicos del Agua/química , Purificación del Agua/métodos , Bacterias/metabolismo , Nanopartículas del Metal/químicaRESUMEN
In the environment, soil colloids are widespread and possess a significant adsorption capacity. This makes them capable of transporting different pollutants, presenting a potential risk to human and ecological well-being. This study aimed to examine the adsorption and co-migration characteristics of benzo(a)pyrene (BaP) and soil colloids in areas contaminated with organic substances, utilizing both static and dynamic batch experiments. In the static adsorption experiments, it was observed that the adsorption of BaP onto soil colloids followed the pseudo-second-order kinetic model (R2 = 0.966), and the adsorption isotherm conformed to the Langmuir model (R2 = 0.995). The BaP and soil colloids primarily formed bonds through π-π interactions and hydrogen bonds. The dynamic experimental outcomes revealed that elevating colloids concentration contributed to increased BaP mobility. Specifically, when the concentration of soil colloids in influent was 500 mg L-1, the mobility of BaP was 23.2 % compared to that without colloids of 13.4 %. Meanwhile, the lowering influent pH value contributed to increased BaP mobility. Specifically, when the influent pH value was 4.0, the mobility of BaP was 30.1 %. The BaP's mobility gradually declined as the initial concentration of BaP in polluted soil increased. Specifically, when the initial concentration of BaP in polluted soil was 5.27 mg kg-1, the mobility of BaP was 39.1 %. This study provides a support for controlling BaP pollution in soil and groundwater.