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OBJECTIVE: To analyze the clinical features and gene mutations in four families with hereditary protein C (PC) deficiency and explore their association with vascular thromboembolism. METHODS: The clinical data of four patients with PC deficiency were retrospectively analyzed. Venous blood samples were collected from the four affected patients and their family members, and relevant coagulation indexes and thrombin production and inhibition tests were performed. PCR was used to amplify and directly sequence the PROC gene of the probands. Software analysis was conducted to assess the conservativeness and pathogenicity of the mutated loci. Protein models were constructed to analyze the spatial structure before and after the mutation. RESULTS: Thrombin generation and inhibition assays demonstrated impaired anticoagulation in all four probands. Proband 1 and 4 presented clinically with pulmonary embolism and lower extremity deep vein thrombosis (DVT), Proband 2 with cerebral infarction, and Proband 3 with DVT. Genetic analysis revealed the presence of the following mutations: c.541T > G heterozygous missense mutation, c.577-579delAAG heterozygous deletion mutation, c.247-248insCT heterozygous insertion mutation, c.659G > A heterozygous missense mutation, and a new variant locus c.1146_1146delT heterozygous deletion mutation in the four probands, respectively. In particular, c.1146_1146delT heterozygous deletion mutations not reported previously. Conservativeness and pathogenicity analyses confirmed that most of these amino acid residues were conserved, and all the mutations were found to be pathogenic. Analysis of protein modeling revealed that these mutations induced structural alterations in the protein or led to the formation of truncated proteins. According to the American College of Medical Genetics and Genomics (ACMG) classification criteria and guidelines for genetic variants, c.1146_1146delT was rated as pathogenic (PVS1 + M2 + PM4 + PP1 + PP3 + PP4). CONCLUSION: The identified mutations are likely associated with decreased PC levels in each of the four families. The clinical manifestations of hereditary PC deficiency exhibit considerable diversity.
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Linhagem , Deficiência de Proteína C , Proteína C , Humanos , Deficiência de Proteína C/genética , Deficiência de Proteína C/complicações , Feminino , Masculino , Adulto , Proteína C/genética , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombose Venosa/genética , Trombose Venosa/sangue , Mutação de Sentido Incorreto , Embolia Pulmonar/genética , MutaçãoRESUMO
With the rapid development of 3D reconstruction, especially the emergence of algorithms such as NeRF and 3DGS, 3D reconstruction has become a popular research topic in recent years. 3D reconstruction technology provides crucial support for training extensive computer vision models and advancing the development of general artificial intelligence. With the development of deep learning and GPU technology, the demand for high-precision and high-efficiency 3D reconstruction information is increasing, especially in the fields of unmanned systems, human-computer interaction, virtual reality, and medicine. The rapid development of 3D reconstruction is becoming inevitable. This survey categorizes the various methods and technologies used in 3D reconstruction. It explores and classifies them based on three aspects: traditional static, dynamic, and machine learning. Furthermore, it compares and discusses these methods. At the end of the survey, which includes a detailed analysis of the trends and challenges in 3D reconstruction development, we aim to provide a comprehensive introduction for individuals who are currently engaged in or planning to conduct research on 3D reconstruction. Our goal is to help them gain a comprehensive understanding of the relevant knowledge related to 3D reconstruction.
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BACKGROUND: Tea-garden pest control is crucial to ensure tea quality. In this context, the time-series prediction of insect pests in tea gardens is very important. Deep-learning-based time-series prediction techniques are advancing rapidly but research into their use in tea-garden pest prediction is limited. The current study investigates the time-series prediction of whitefly populations in the Tea Expo Garden, Jurong City, Jiangsu Province, China, employing three deep-learning algorithms, namely Informer, the Long Short-Term Memory (LSTM) network, and LSTM-Attention. RESULTS: The comparative analysis of the three deep-learning algorithms revealed optimal results for LSTM-Attention, with an average root mean square error (RMSE) of 2.84 and average mean absolute error (MAE) of 2.52 for 7 days' prediction length, respectively. For a prediction length of 3 days, LSTM achieved the best performance, with an average RMSE of 2.60 and an average MAE of 2.24. CONCLUSION: These findings suggest that different prediction lengths influence model performance in tea garden pest time series prediction. Deep learning could be applied satisfactorily to predict time series of insect pests in tea gardens based on LSTM-Attention. Thus, this study provides a theoretical basis for the research on the time series of pest and disease infestations in tea plants. © 2024 Society of Chemical Industry.
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Camellia sinensis , Jardins , Hemípteros , Animais , Camellia sinensis/química , Camellia sinensis/parasitologia , China , Aprendizado Profundo , Doenças das Plantas/parasitologia , Insetos , JardinagemRESUMO
Malignant brain tumors rank among the most challenging type of malignancies to manage. The current treatment protocol commonly entails surgery followed by radiotherapy and/or chemotherapy, however, the median patient survival rate is poor. Recent developments in immunotherapy for a variety of tumor types spark optimism that immunological strategies may help patients with brain cancer. Chimeric antigen receptor (CAR) T cells exploit the tumor-targeting specificity of antibodies or receptor ligands to direct the cytolytic capacity of T cells. Several molecules have been discovered as potential targets for immunotherapy-based targeting, including but not limited to EGFRvIII, IL13Rα2, and HER2. The outstanding clinical responses to CAR T cell-based treatments in patients with hematological malignancies have generated interest in using this approach to treat solid tumors. Research results to date support the astounding clinical response rates of CD19-targeted CAR T cells, early clinical experiences in brain tumors demonstrating safety and evidence for disease-modifying activity, and the promise for further advances to ultimately assist patients clinically. However, several variable factors seem to slow down the progress rate regarding treating brain cancers utilizing CAR T cells. The current study offers a thorough analysis of CAR T cells' promise in treating brain cancer, including design and delivery considerations, current strides in clinical and preclinical research, issues encountered, and potential solutions.
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Neoplasias Encefálicas , Imunoterapia Adotiva , Humanos , Proteínas Adaptadoras de Transdução de Sinal , Anticorpos , Antígenos CD19 , Neoplasias Encefálicas/terapia , Morte Celular , Receptores de Antígenos Quiméricos , Linfócitos TRESUMO
BACKGROUND: Hypertensive patients show highly heterogeneous treatment effects (HTEs) and cardiovascular prognosis, and not all benefit from intensive blood pressure treatment.MethodsâandâResults: We used the causal forest model to identify potential HTEs of patients in the Systolic Blood Pressure Intervention Trial (SPRINT). Cox regression was performed to assess hazard ratios (HRs) for cardiovascular disease (CVD) outcomes and to compare the effects of intensive treatment among groups. The model revealed 3 representative covariates and patients were partitioned into 4 subgroups: Group 1 (baseline body mass index [BMI] ≤28.32 kg/m2and estimated glomerular filtration rate [eGFR] ≤69.53 mL/min/1.73 m2); Group 2 (baseline BMI ≤28.32 kg/m2and eGFR >69.53 mL/min/1.73 m2); Group 3 (baseline BMI >28.32 kg/m2and 10-year CVD risk ≤15.8%); Group 4 (baseline BMI >28.32 kg/m2and 10-year CVD risk >15.8%). Intensive treatment was shown to be beneficial only in Group 2 (HR 0.54, 95% confidence interval [CI] 0.35-0.82; P=0.004) and Group 4 (HR 0.69, 95% CI 0.52-0.91; P=0.009). CONCLUSIONS: Intensive treatment was effective for patients with high BMI and 10-year CVD risk, or low BMI and normal eGFR, but not for those with low BMI and eGFR, or high BMI and low 10-year CVD risk. Our study could facilitate the categorization of hypertensive patients, ensuring individualized therapy.
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Doenças Cardiovasculares , Hipertensão , Humanos , Pressão Sanguínea , Anti-Hipertensivos , Fatores de Risco , Resultado do Tratamento , Hipertensão/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológicoRESUMO
The challenge of mitigating the decline in both yield and fruit quality due to the intrusion of powdery mildew (PM) fungus looms as a pivotal concern in the domain of bitter melon cultivation. Yet, the intricate mechanisms that underlie resistance against this pathogen remain inscrutable for the vast majority of bitter melon variants. In this inquiry, we delve deeply into the intricate spectrum of physiological variations and transcriptomic fluctuations intrinsic to the PM-resistant strain identified as '04-17-4' (R), drawing a sharp contrast with the PM-susceptible counterpart, designated as '25-15' (S), throughout the encounter with the pathogenic agent Podosphaera xanthii. In the face of the challenge presented by P. xanthii, the robust cultivar displays an extraordinary capacity to prolong the initiation of the pathogen's primary growth stage. The comprehensive exploration culminates in the discernment of 6635 and 6954 differentially expressed genes (DEGs) in R and S strains, respectively. Clarification through the lens of enrichment analyses reveals a prevalence of enriched DEGs in pathways interconnected with phenylpropanoid biosynthesis, the interaction of plants with pathogens, and the signaling of plant hormones. Significantly, in the scope of the R variant, DEGs implicated in the pathways of plant-pathogen interaction phenylpropanoid biosynthesis, encompassing components such as calcium-binding proteins, calmodulin, and phenylalanine ammonia-lyase, conspicuously exhibit an escalated tendency upon the encounter with P. xanthii infection. Simultaneously, the genes governing the synthesis and transduction of SA undergo a marked surge in activation, while their counterparts in the JA signaling pathway experience inhibition following infection. These observations underscore the pivotal role played by SA/JA signaling cascades in choreographing the mechanism of resistance against P. xanthii in the R variant. Moreover, the recognition of 40 P. xanthii-inducible genes, encompassing elements such as pathogenesis-related proteins, calmodulin, WRKY transcription factors, and Downy mildew resistant 6, assumes pronounced significance as they emerge as pivotal contenders in the domain of disease control. The zenith of this study harmonizes multiple analytical paradigms, thus capturing latent molecular participants and yielding seminal resources crucial for the advancement of PM-resistant bitter melon cultivars.
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Momordica charantia , Humanos , Momordica charantia/genética , Transcriptoma , Calmodulina , Transdução de Sinais , ErysipheRESUMO
STUDY QUESTION: Does intrauterine infusion of granulocyte colony-stimulating factor (G-CSF) prevent adhesion reformation and promote endometrial growth after hysteroscopic adhesiolysis? SUMMARY ANSWER: Intrauterine perfusion of G-CSF can increase endometrial thickness but does not prevent the recurrence of intrauterine adhesions (IUAs) in patients with Asherman syndrome (AS) after surgery. WHAT IS KNOWN ALREADY: Intrauterine infusion of G-CSF has been used in attempts to treat patients with recurrent miscarriage and an idiopathic thin endometrium for either fresh or frozen-thawed embryo transfer cycles but without uniform efficacy. There have been no reports on the effect of G-CSF on the recurrence of IUAs, endometrial regrowth or pregnancy results in specific populations with AS. STUDY DESIGN, SIZE, DURATION: This two-center prospective double-blind randomized controlled trial ran between April 2016 and August 2021. In it, 245 patients with moderate to severe AS were randomized to G-CSF and control groups at a 1:1 ratio; 229 women were included in the adhesion recurrence analysis; and 164 patients were analyzed for pregnancy outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS: All eligible patients received the first hysteroscopic adhesion separation and balloon placement procedure. Patients who met our inclusion and exclusion criteria were randomized after surgery. These patients returned for balloon removal and underwent intrauterine perfusion with 300 µg (1.8 ml) G-CSF or 1.8 ml normal saline according to randomization at 7 days after surgery. A second-look hysteroscopy was carried out 1-2 months later. The primary outcome was the rate of formation of new adhesions at the second hysteroscopy. The secondary outcomes included endometrial thickness in the periovulatory period after surgery, as well as the clinical pregnancy and live birth rates. MAIN RESULTS AND THE ROLE OF CHANCE: Age, menstrual cycle characteristics, pregnancy history and IUA score before surgery were similar between groups. There were no statistically significant differences in the adhesion reformation rate or median adhesion score reduction. However, G-CSF perfusion significantly improved endometrial thickness (7.91 ± 2.12 mm vs 7.22 ± 2.04 mm; P = 0.019, 95% CI for difference: -1.26 to -0.12), as well as cumulative pregnancy and live birth rate over time (P = 0.017 and P = 0.042). Furthermore, multivariate logistic regression analysis showed that postoperative endometrial thickness was an independent prognostic factor for pregnancy and live birth rates. LIMITATIONS, REASONS FOR CAUTION: These results cannot be extended to older patients or those without AS, as our subjects had moderate or severe AS and were aged <40 years. The low number of patients included in the fertility analysis could lead to biased results. WIDER IMPLICATIONS OF THE FINDINGS: Intrauterine perfusion of G-CSF could be an effective adjuvant therapy for patients with AS to increase endometrial thickness. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from the National Key Research and Development Program of China (2018YFC1004800), the National Natural Science Foundation of China (82001624 and 81871209), the Natural Science Foundation of Zhejiang Province (LQ20H040004) and the provincial and ministerial construction project of Zhejiang Province (2017 WKJ-ZJ-1721). The authors declare that they have no conflicts of interest regarding this work. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov (NCT02855632). TRIAL REGISTRATION DATE: 4 March 2016. DATE OF FIRST PATIENT'S ENROLMENT: 13 April 2016.
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Ginatresia , Doenças Uterinas , Adulto , Endométrio/cirurgia , Feminino , Fator Estimulador de Colônias de Granulócitos/farmacologia , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Ginatresia/cirurgia , Humanos , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Doenças Uterinas/cirurgiaRESUMO
The present study explored the correlation between the hydrodynamic size(i.e., hydrated particle size) and the surface component distribution of spray-dried powder based on the binary system model of berberine hydrochloride and dextran. A variety of mixture solutions containing substances of different proportions were prepared, and the hydrated particle sizes of the solutions were measured by laser light scattering technique. Then the effects of molecular weight and mixing proportion on the particle size were analyzed. After the solutions were spray-dried, the surface components of spray-dried powder were determined by X-ray photoelectron spectroscopy. The changes of hydrated particle size of the two substances in different solutions were measured with the altered solution environments, and the distribution of surface components after spray-drying was observed. The results of particle size measurement showed that different solution environments would change the hydrodynamic size of substances. Specifically, the particle size of berberine hydrochloride increased with the increase in ionic strength and solution pH, while the particle size of dextran decreased with the increase in ionic strength and increased with the increase in solution pH. The results of surface components of the spray-dried powder indicated that berberine hydrochloride was prone to accumulate on the surface of particles during spray-drying because of its large hydrodynamic size. Therefore, hydrodynamic size is considered an important factor affecting the surface component distribution of spray-dried powder. As revealed by scanning electron microscopy of the particle morphology of spray-dried powder, the particles of berberine hydrochloride spray-dried powder were irregularly elliptic, and the particles of dextran and mixture spray-dried powders were irregularly spherical with the shrunken surface. Finally, the FT4 powder rheometer and DVS instrument were used to determine the stability, adhesion, and hygroscopicity of the powder. The results showed that when berberine hydrochloride was enriched on the surface, the adhesion of the mixture increased and the fluidity became worse, but the hygroscopicity was improved to a certain extent. In addition, as found by hygroscopic kinetic curve fitting of spray-dried powder, the hygroscopic behaviors of all spray-dried powder conformed to the double exponential function.
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Berberina , Administração por Inalação , Aerossóis/química , Dextranos , Inaladores de Pó Seco/métodos , Hidrodinâmica , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Pós/químicaRESUMO
Enzymes are still indispensable for bio-assaying methods in biomolecule detection by far. The unsatisfied long-term instability, high cost, and susceptibility to the physical environment of natural enzymes are obvious weak points. Here, we developed peroxidase-like heterostructured nanozyme, vertically arraying molybdenum disulfide nanosheets on a substrate layer of nitrogen-doped reduced graphene oxide (MoS2/N-rGO), with a well-pleasing stability that is characterized by the retained enzymatic activity and maintained structure after 2 years of casual storage at ambient temperatures or 80 cycles of catalytic reaction. The catalytic kinetics of the as-prepared heterostructured nanozyme was superior to some reported nanozymes and even horse radish peroxidase, which was demonstrated due to the defect-rich MoS2 with Mo and S vacancies and nitrogen-doped rGO experimentally and theoretically. The vertically heterostructured nanozyme exhibited adequate analytical performance in sensitive and quantitative detection of glucose and glutathione (GSH), with a large dynamic sensing range and extremely low limit of detection (0.02 and 0.12 µM (3σ/slope) for glucose and GSH, respectively). We hope this inspired artificial nanozyme will contribute to the future development in sensitive detection of other biomolecules in physiological conditions.
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Grafite , Molibdênio , Catálise , PeroxidasesRESUMO
Pulmonary fibrosis (PF) is a kind of interstitial lung disease with the features of progressive and often fatal dyspnea. Tetrandrine (TET) is the major active constituent of Chinese herbal Stephania tetrandra S. Moore, which has already applied clinically to treat rheumatism, lung cancer, and silicosis. In this work, a tetrandrine-hydroxypropyl-ß-cyclodextrin inclusion compound (TET-HP-ß-CD) was developed for the treatment of pulmonary fibrosis via inhalation administration. TET-HP-ß-CD was prepared by the freeze-drying method and identified using the cascade impactor, differential scanning calorimetry (DSC), X-ray diffraction (XRD), and Fourier transform infrared spectrum (FT-IR). A bleomycin-induced pulmonary fibrosis rat model was used to assess the effects of inhaled TET and TET-HP-ß-CD. Animal survival, hydroxyproline content in the lungs, and lung histology were detected. The results showed that inhalation of TET-HP-ß-CD alleviated inflammation and fibrosis, limited the accumulation of hydroxyproline in the lungs, regulated protein expression in PF development, and improved postoperative survival. Moreover, nebulized delivery of TET-HP-ß-CD accumulated chiefly in the lungs and limited systemic distribution compared with intravenous administration. The present results indicated that inhalation of TET-HP-ß-CD is an attractive candidate for the treatment of pulmonary fibrosis.
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2-Hidroxipropil-beta-Ciclodextrina/química , Benzilisoquinolinas/química , Fibrose Pulmonar/tratamento farmacológico , 2-Hidroxipropil-beta-Ciclodextrina/administração & dosagem , 2-Hidroxipropil-beta-Ciclodextrina/farmacocinética , Administração por Inalação , Animais , Benzilisoquinolinas/administração & dosagem , Benzilisoquinolinas/farmacocinética , Modelos Animais de Doenças , Pulmão/metabolismo , Pulmão/patologia , Masculino , Fibrose Pulmonar/mortalidade , Fibrose Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Fator de Necrose Tumoral alfa/análiseRESUMO
Biomineralization is characterized by the fact that the crystallization of inorganic minerals is guided by an in vivo biological interface. However, the interfaces that direct calcification are widely debated up to date. In this paper, it was found that the two-dimensional (2D) immiscible domain of cholesterol in the lipid bilayer can induce the deposition of calcium phosphate by rapidly promoting the nucleation of the hydroxyapatite (001) plane. This promotion effect is related to the high lattice matching degree between the 2D cholesterol immiscible domain and the (001) plane of hydroxyapatite (HAP), which leads to the heteroepitaxy of HAP. The lipid bilayer derived from cells or vesicles is the largest biological interface in the body, thus revealing whether the lipid bilayer can induce the deposition of calcium phosphate will facilitate the understanding of the important role of cells or vesicles in calcification.
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Renal cell carcinomas are a group of most common renal malignancies whose clinical intervention is complicated by the lack of early diagnosis and reliable prognosis biomarkers, insensitive radiotherapy and chemotherapy and expensive molecular-targeted drugs. Transcriptional coactivator TAZ has been implicated in the formation and development of various malignancies. However, the biological characteristics and function of TAZ in renal cell carcinoma are still unclear. We attempted to evaluate the potential of TAZ as a promising diagnostic and prognostic molecular marker for renal cell carcinoma. In our study, we confirmed that TAZ was frequently elevated in renal cancer tissues and cells, consistent with the results of the publicly available cancer database. Moreover, elevated TAZ expression was positively correlated with poor overall survival time, high Fuhrman grade and distant metastasis. Our receiver operating characteristic curves analysis showed that high TAZ expression could distinguish renal cancer patients from normal persons (pâ¯<â¯0.0001). Kaplan-Meier curves demonstrated that high TAZ expression predicted poor overall survival (pâ¯<â¯0.0001). Multivariate regression analysis indicated that TAZ expression could be an independent prognostic factor (pâ¯=â¯0.002) in patients with renal cancer. Finally, the functional roles of TAZ knockdown were examined in renal cancer cell lines and nude mice subcutaneous tumor models. In conclusion, our results suggest that TAZ may serve as a promising diagnostic and prognostic molecular marker for patients with renal cancer. Moreover, TAZ may represent a novel clinical therapeutic target.
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Biomarcadores Tumorais/metabolismo , Neoplasias Renais/diagnóstico , Transativadores/metabolismo , Animais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Progressão da Doença , Feminino , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Renais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica , Estadiamento de Neoplasias , Transplante de Neoplasias , Prognóstico , Transativadores/genética , Proteínas com Motivo de Ligação a PDZ com Coativador TranscricionalRESUMO
A biosensor for hydrogen peroxide (H2O2) has been developed based on the use of MoS2 nanosheets and graphite that are assembled to form a microfiber hybrid structure. The MoS2 nanosheets are synthesized in situ on a graphite microfiber. The chemical composition and surface morphology of the microfiber hybrid structure has been characterized. The microfiber is shown to display peroxidase-mimicking activity. In the next step, horseradish peroxidase, methylene blue, and chitosan are co-immobilized on the microfiber electrode. The use of MoS2 nanosheets warrants high electrochemical activity of immobilized enzyme on the electrode surface. The modified microfiber electrode, best operated at a voltage of - 0.3 V (vs. Ag/AgCl), can be used to sense H2O2 with a linear response in the 0.1 to 90 µM concentration range and with a determination limit of 30 nM (at S/N = 3). The good response is attributed to the synergistic enhancement of the synthetic nanozymes (few-layered MoS2 nanosheets) and immobilized natural horseradish peroxidase (HRP). Grapical abstract.
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Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Peroxidase do Rábano Silvestre/química , Peróxido de Hidrogênio/análise , Nanoestruturas/química , Armoracia/enzimologia , Catálise , Quitosana/química , Dissulfetos/química , Enzimas Imobilizadas/química , Grafite/química , Peróxido de Hidrogênio/química , Indicadores e Reagentes/química , Azul de Metileno/química , Molibdênio/química , Oxirredução , Reprodutibilidade dos TestesRESUMO
Dissolution behavior of isolated and aggregated hematite particles in 10, 36, and 103 nm, respectively, was investigated using in situ liquid cell transmission microscopy (LCTEM). The high spatial and temporal resolution of LCTEM enables us to differentiate the respective effects of primary particle size, crystal defects, and aggregation state on particle dissolution. At similar electron-beam irradiation parameters, the initial surface-area normalized dissolution rates ( RSA,Int) of isolated 10, 36, and 103 nm particles are 4.64 ± 3.60, 0.91 ± 0.44, and 0.24 ± 0.04 mg m-2 s-1, respectively. Interface free energy, calculated from the measured RSA,Int, decreases with the decreasing primary particle size. No preferential etching occurs on 10 nm, defect-free nanoparticles, whereas dissolution preferentially originates from crystal defects on 103 nm particles. In dissolution of aggregated particles, dissolution occurs more rapidly on the particles that are more accessible to bulk solution than the others inside the aggregate. As dissolution proceeds, dendritic aggregates break into several smaller aggregates that respectively shrink into even smaller and more compact aggregates, followed by reaggregation together. This study directly shows microscopic dissolution behavior of isolated and aggregated particles in different primary particle sizes, which is important to understand bioavailability, transport, and fate of nanoparticles in aquatic systems.
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Compostos Férricos , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , SolubilidadeRESUMO
Curcumin( Cur) is a natural active substance extracted from the roots or tubers of traditional Chinese medicinal materials. It has anti-inflammatory and anti-tumor activities on brain diseases. Due to the poor stability,low solubility,poor absorption and low bioavailability of curcumin,N-acetyl-L-cysteine( NAC) was used as an absorption enhancer and mixed with curcumin to improve the absorption of curcumin in the body. In this paper,curcumin was smashed by airflow pulverization,and Cur-NAC mixtures were prepared by being grinded with liquid. Then,the raw material and the product were analyzed by differential scanning calorimetry( DSC),X-ray diffraction( XRD) for structural characterization. The dissolution was determined by high performance liquid chromatography( HPLC) analysis. The characteristic peaks of the samples prepared by grinding method were similar to those of the raw materials,while the melting temperature and the accumulated dissolution degree were not significantly changed. The crystal forms of the products were not changed,and no new crystal form was formed after grinding. After the administration of intranasal powder,blood samples were collected from the orbit,while the whole brain tissues were removed from the skull and dissected into 10 anatomical regions. The concentrations of curcumin in these samples were determined by UPLC-MS/MS. The concentrations of curcumin in plasma and brain were compared at different time points. After intranasal administration of two drugs,it was found that the concentration of curcumin after sniffing up the mixtures in plasma was high,and the concentration of the drug in the olfactory bulb,hippocampus,and pons was increased significantly. Within 0. 083-0. 5 h,the olfactory bulb,piriform lobe and hippocampus remained high concentrations,the endodermis,striatum,hypothalamus and midbrain reached high concentrations within 1-3 h; and the cerebellum,pons and brain extension maintained relatively high concentrations within 3-7 h. The experiment showed that nasal administration of Cur-NAC mixtures can significantly improve the bioavailability of curcumin,and lead to significant differences in brain tissue distribution.
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Acetilcisteína/farmacologia , Química Encefálica , Curcumina/farmacocinética , Administração Intranasal , Animais , Disponibilidade Biológica , Encéfalo , Cromatografia Líquida , Ratos , Espectrometria de Massas em Tandem , Distribuição TecidualRESUMO
Caveolin-1 (CAV1) has been identified to be up-regulated in many cancers, including clear cell renal cell carcinoma (ccRCC). However, its potential function is still unclear in ccRCC. In this study, we demonstrated that CAV1 was frequently overexpressed in renal cell carcinoma tissues and cells, and was significantly associated with various clinicopathological parameters. In addition, high CAV1 expression was associated with poor disease-free survival (DFS) rate and could serve as a useful diagnostic indicator in ccRCC patients with different clinicopathological stages. Functional experiments demonstrated that CAV1 knockdown inhibited cell migration and invasion, whereas overexpression of CAV1 promoted cell migration and invasion in ccRCC. Moreover, CAV1 expression was up-regulated in sunitinib-resistant renal cancer cell lines, and its overexpression promoted sunitinib resistance. In general, our results confirm that CAV1 plays an important role in the metastasis of kidney cancer and induces sunitinib resistance, so CAV1 function suppression may become a promising clinical treatment strategy during renal cell carcinoma metastasis and sunitinib resistance.
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Carcinoma de Células Renais/metabolismo , Caveolina 1/metabolismo , Movimento Celular/fisiologia , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica/genética , Indóis/farmacologia , Neoplasias Renais/metabolismo , Pirróis/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Caveolina 1/genética , Proliferação de Células/genética , Proliferação de Células/fisiologia , Feminino , Técnicas de Silenciamento de Genes/métodos , Humanos , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Sunitinibe , Adulto JovemRESUMO
PURPOSE: The question of whether orthotopic neobladder (ONB) reconstruction is superior to ileal conduit diversion (ICD) with respect to health-related quality of life (HRQoL) remains controversial. The goal of this study is to perform a meta-analysis to compare post-ICD and post-ONB HRQoL in patients with bladder cancer. METHODS: A systematic search of Medline, Embase, the Cochrane Central Register of Controlled Trials, and the annual congress abstracts of the European Association of Urology (EAU), the American Urological Association (AUA) and the Société Internationale d'Urologie (SIU) up to June 2017 was conducted to identify all relevant clinical trials using validated questionnaires to assess HRQoL. A systematic review and meta-analysis were then performed. RESULTS: A total of 2507 patients from 26 eligible studies were included. Meta-analyses showed significant differences favouring ONB patients in global health status (WMD + 9.13, p = 0.004), physical functioning (WMD + 11.57, p = 0.0001), role functioning (WMD + 9.64, p = 0.002), and social functioning (WMD + 6.81, p = 0.03) based on the EORTC-QLQ-C30 questionnaire and in the total score of FACT questionnaire (WMD + 6.80, p = 0.001). However, ONB patients were more likely to have postoperative urinary symptoms than ICD patients (WMD - 22.19, p = 0.0001). CONCLUSIONS: ONB patients are more likely to have a better global health status than ICD patients. Regardless of the type of urinary diversion (UD) surgery, a gradual improvement in HRQoL over preoperative status tended to stabilise after 12 months postoperatively.
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Nível de Saúde , Qualidade de Vida , Neoplasias da Bexiga Urinária/cirurgia , Bexiga Urinária/cirurgia , Derivação Urinária/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Resultado do Tratamento , Coletores de UrinaRESUMO
In this study a laboratory-scale sequencing batch bioreactor was constructed, using phenanthrene/pyrene as the sole carbon-source, to demonstrate the removal efficiencies of polycyclic aromatic hydrocarbons (PAHs) and the evolution process of a functional bacterial community. The removal rates were: COD, 51.4 to 76.3%; phenanthrene, 63.5 to 92.4%; and pyrene, 65.9 to 90.1%. Quantification analysis indicated that in sludge samples from the phenanthrene/pyrene degradation stage, the contents of 16S rRNA and ring-hydroxylating dioxygenase genes of Gram-positive and Gram-negative bacteria were 10-and 72-, 102- and 1152-, 31- and 905-fold higher, respectively, than those in seed sludge samples. Clone sequencing and evolution analysis showed that genera Comamonas, Pseudomonas, and Mycobacterium were distributed across all samples and were significant PAH-degrading populations, but some genera, such as Polaromonas and Nocardioides, were substantially enriched only when phenanthrene/pyrene was fed. Correspondingly, the functional genes nidA3, phnAc, and ndoC2 were distributed across all samples, whereas nagAc, pdoA2, and pdoA were enriched only when phenanthrene/pyrene was fed.
Assuntos
Bactérias/genética , Bactérias/metabolismo , Reatores Biológicos , Hidrocarbonetos Policíclicos Aromáticos/metabolismo , Poluentes Químicos da Água/metabolismo , DNA Bacteriano/genética , Evolução Molecular , Filogenia , Hidrocarbonetos Policíclicos Aromáticos/química , RNA Bacteriano/genética , RNA Ribossômico/genética , Fatores de Tempo , Poluentes Químicos da Água/químicaRESUMO
The large nuclear mitotic apparatus (NuMA) protein is an essential player in mitotic spindle assembly and maintenance. We report here the identification of Astrin, a spindle- and kinetochore-associated protein, as a novel interactor of NuMA. We show that the C-terminal tail of NuMA can directly bind to the C terminus of Astrin and that this interaction helps to recruit Astrin to microtubules. Knockdown of NuMA by RNA interference dramatically impaired Astrin recruitment to the mitotic spindle. Overexpression of the N terminus of mammalian homologue of Drosophila Pins (LGN), which blocks the microtubule binding of NuMA and competes with Astrin for NuMA binding, also led to similar results. Furthermore, we found that cytoplasmic dynein is required for the spindle pole accumulation of Astrin, and dynein-mediated transport is important for balanced distribution of Astrin between spindle poles and kinetochores. On the other hand, if Astrin levels are reduced, then NuMA could not efficiently concentrate at the spindle poles. Our findings reveal a direct physical link between two important regulators of mitotic progression and demonstrate the critical role of the NuMA-Astrin interaction for accurate cell division.
Assuntos
Antígenos Nucleares/metabolismo , Proteínas de Ciclo Celular/metabolismo , Mitose/fisiologia , Proteínas Associadas à Matriz Nuclear/metabolismo , Fuso Acromático/metabolismo , Animais , Antígenos Nucleares/genética , Células COS , Proteínas de Ciclo Celular/genética , Chlorocebus aethiops , Drosophila melanogaster , Dineínas/genética , Dineínas/metabolismo , Técnicas de Silenciamento de Genes , Células HeLa , Humanos , Proteínas Associadas à Matriz Nuclear/genética , Domínios Proteicos , Homologia de Sequência de Aminoácidos , Fuso Acromático/genéticaRESUMO
BACKGROUND: Renal artery aneurysm (RAA) is rare and its incidence in the general population remains elusive. There have been few reports on the repair of multiple aneurysms conducted with the Da Vinci robot-assisted surgical platform (Intuitive Surgical Inc., Sunnyvale, CA, USA), especially for those located in renal artery primary bifurcations. CASE PRESENTATION: We report our experience in the surgical management of two expanding right-sided RAAs in a 64-year-old man using a robot-assisted laparoscopic approach. Two aneurysms were located in renal artery primary bifurcations, whose diameter was 1.8 and 1.2 cm. The aneurysms were resected and the renal artery branch reconstructed by in situ arteriorrhaphy. The operation lasted for 2 h and 35 min with a warm ischemia time of 26 min and estimated blood loss of 150 ml. The hospital stay was 6 days. The computed tomography (CT) scan performed 2 months after the surgery showed resolution of the aneurysms. Additionally, split renal function indicated the preservation of right renal function in the follow-up period. CONCLUSIONS: The robot-assisted laparoscopic procedure is a safe and effective surgical technique, which may be considered as an alternative to open surgery for complex multiple RAAs in the future.