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OBJECTIVE: To investigate the risk factors for Adverse pregnancy outcome (APOs) in patients with new-onset SLE during pregnancy. METHODS: Eighty-five patients with new-onset SLE during pregnancy were analyzed retrospectively. Univariate and multivariate logistic regression were used to identify risk factors for different APOs (pregnancy loss, preterm birth, fetal growth restriction, and eclampsia/preeclampsia). A two-sided p-value below 0.05 was considered significant, and two-sided 95% confidence intervals (CIs) are reported. RESULTS: Multivariate analysis indicated that renal involvement (aOR: 7.356; 95%CI:1.516,35.692) and greater SLE disease activity index (SLEDAI) grade (aOR:5.947;95%CI: 1.586,22.294) increased the risk for composite APO, and that use of heparin therapy (aOR: 0.081; 95%CI: 0.012, 0.532) was a protective factor. Advanced gestational age at disease onset (aOR: 0.879; 95%CI: 0.819,0.943) and high serum albumin level (aOR: 0.908,95%CI: 0.831,0.992) protected against pregnancy loss. Renal involvement increased the risk for preterm birth (aOR: 2.272; 95%CI: 1.030,7.222) and fetal growth restriction (aOR: 9.070; 95%CI: 1.131,72.743). Hypertension (aOR: 19.185; 95%CI: 3.921,93.868), renal involvement (aOR: 8.380, 95%CI: 1.944,74.376) increased the risk for eclampsia/preeclampsia. CONCLUSION: New onset SLE during pregnancy increased the risk for multiple APOs. Timely management of the risk factors identified here may help to improve pregnancy outcomes in these patients.
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Lúpus Eritematoso Sistêmico/complicações , Resultado da Gravidez , Adulto , Feminino , Humanos , Lúpus Eritematoso Sistêmico/fisiopatologia , Gravidez , Complicações na Gravidez/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de DoençaRESUMO
INTRODUCTION: To improve the accuracy of ultrasound techniques for the assessment of carotid stenosis, we designed a novel carotid artery stenosis ultrasound scale (CASUS), and evaluated its accuracy, reliability, and its value in predicting the occurrence of cardiovascular and cerebrovascular diseases in a prospective study. METHODS: A total of 750 patients with first-time ischemic stroke and hospitalized within 24 h were enrolled in the study. Using color Doppler ultrasound (CDUS), the degree of stenosis and blood flow (BF) in bilateral internal carotid arteries (ICA) and the V1-V3 segment of vertebral arteries (VA) was assessed. Cubic simulation curves for BF and global blood flow (GBF) over the stenosis score (SS), total stenosis score (TSS), and radiological imaging- total stenosis score (RI-TSS) were fitted and compared. The receiver operating characteristic (ROC) curves using TSS, RI-TSS, or GBF to predict various ischemic stroke endpoints were also analyzed and compared. RESULTS: There was a linear relationship between SS and BF both ICA and VA (R2 were 0.734 and 0.783, respectively, both P < 0.05). Both TSS and RI-TSS with GBF showed an inverse "S" curve relationship (R2 was 0.839 and 0.843, all P < 0.05). The AUC values of TSS-based and RI-TSS-based predictions of each endpoint were all greater than 0.7 (all P < 0.05), but the differences of the AUC values between TSS, RI-TSS, and GBF were not statistically significant (all P > 0.05). CONCLUSIONS: The novel CASUS can better reflect the level of cerebral reperfusion in patients with ischemic stroke and can better predict the occurrence of cardiovascular and cerebrovascular diseases.
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Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , AVC Isquêmico/diagnóstico por imagem , Ultrassonografia Doppler , Artéria Vertebral/diagnóstico por imagem , Idoso , Artéria Carótida Interna/patologia , Feminino , Humanos , AVC Isquêmico/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Artéria Vertebral/patologiaRESUMO
The hydropower generator unit (HGU) is a vital piece of equipment for frequency and peaking modulation in the power grid. Its vibration signal contains a wealth of information and status characteristics. Therefore, it is important to predict the vibration tendency of HGUs using collected real-time data, and achieve predictive maintenance as well. In previous studies, most prediction methods have only focused on enhancing the stability or accuracy. However, it is insufficient to consider only one criterion (stability or accuracy) in vibration tendency prediction. In this paper, an intelligence vibration tendency prediction method is proposed to simultaneously achieve strong stability and high accuracy, where vibration signal preprocessing, feature selection and prediction methods are integrated in a multi-objective optimization framework. Firstly, raw sensor signals are decomposed into several modes by empirical wavelet transform (EWT). Subsequently, the refactored modes can be obtained by the sample entropy-based reconstruction strategy. Then, important input features are selected using the Gram-Schmidt orthogonal (GSO) process. Later, the refactored modes are predicted through kernel extreme learning machine (KELM). Finally, the parameters of GSO and KELM are synchronously optimized by the multi-objective salp swarm algorithm. A case study and analysis of the mixed-flow HGU data in China was conducted, and the results show that the proposed model performs better in terms of predicting stability and accuracy.
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OBJECTIVE: To explore the strategies of preserving urinary continence in transurethral plasmakinetic enucleation of the prostate (PKEP) for benign prostate hyperplasia (BPH). METHODS: We treated 65 BPH patients by PKEP with preservation of urinary continence (UC-PKEP), which involved protection of the external urethral sphincter in the beginning of surgery, proper preservation of the anterior lobe of the prostate to protect the internal urethral sphincter in the middle, and preservation of the integrity of the bladder neck towards the end. We compared the postoperative status of urinary continence of the patients with that of the 54 BPH cases treated by complete plasmakinetic enucleation of the prostate (Com-PKEP). RESULTS: All the operations were performed successfully with the urinary catheters removed at 5 days after surgery. In comparison with Com-PKEP, UC-PKEP achieved evidently lower incidence rates of urinary incontinence at 24 hours (31.49% vs 13.85%, P <0.05), 1 week (18.52% vs 4.62%, P <0.05), 2 weeks (14.81% vs 3.08%, P <0.05), 1 month (3.70% vs 1.54%, P >0.05), and 3 months (3.70% vs 0%, P >0.05) after catheter removal. Compared with the baseline, the maximum urinary flow rate (Qmax) was significantly improved postoperatively in both the Com-PKEP (ï¼»7.43 ± 3.26ï¼½ vs ï¼»20.58 ± 3.22ï¼½ ml, P <0.05) and the UC-PKEP group (ï¼»8.04 ± 2.28ï¼½ vs ï¼»20.66 ± 3.08ï¼½ ml, P <0.05). CONCLUSIONS: Transurethral PKEP is a safe and effective method for the management of BPH, during which the strategies of avoiding blunt or sharp damage to the external urethral sphincter in the beginning, properly preserving the anterior lobe of the prostate in the middle and preserving the integrity of the bladder neck towards the end may help to achieve rapid recovery of urinary continence.
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Tratamentos com Preservação do Órgão/métodos , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/métodos , Uretra , Bexiga Urinária , Incontinência Urinária/prevenção & controle , Humanos , Masculino , Período Pós-Operatório , Qualidade de Vida , Ressecção Transuretral da Próstata/efeitos adversos , Resultado do Tratamento , Cateterismo UrinárioRESUMO
OBJECTIVE: To evaluate the clinical features and pregnancy outcomes in patients experiencing recurrent miscarriage (RM) with either low-titer or medium-high titer positivity of antiphospholipid antibodies (aPL). METHODS: A retrospective review of medical records was conducted for patients with aPL positivity and recurrent miscarriage between 2018 and 2022. The clinical features, treatment strategies, outcomes were compared between the patients with low (n = 92) and medium (n = 32) titer of aPL. RESULTS: A total of 118 patients, resulting in 124 obstetric episodes (pregnancies), with a mean age of 33. 15 ± 4.56 and 31.47 ± 4.41 years between the two groups. The low-titer group exhibited a higher frequency of anti-cardiolipin antibodies IgM (P < 0.001), whereas the medium-high titer group demonstrated a higher frequency of anti-ß2-glycoprotein 1 antibodies IgG (P < 0.001) and IgM (P = 0.032). Moreover, the medium-high titer group displayed a significantly elevated erythrocyte sedimentation rate compared to the low-titer group (P < 0.05). In the low-titer group, 71 patients (77.2%) received appropriate treatment, resulting in 48 live births (67.6%) and 23 repeat abortions (32.4%). In the medium-high titer group, 29 patients (90.6%) received relevant treatment, leading to 23 live births (79.3%) and 6 repeat abortions (20.7%). No significant differences were observed in live births or maternal-fetal complications between the two groups (all P > 0.05). CONCLUSION: Noteworthy distinctions in laboratory parameters were identified between the low-titer and medium-high titer groups. However, when appropriately treated, the fetal-maternal outcomes were comparable in both groups. Timely intervention by clinicians is imperative to enhance pregnancy outcomes in patients experiencing recurrent miscarriage with low levels of aPL. Key Points ⢠This study challenges the conventional belief that only the higher antiphospholipid antibodies (aPL) titers directly correlated with worse pregnancy outcomes, which emphasized the importance of patients with low titer positive aPL-positive RM. ⢠The results underscore the need for timely intervention in women with low titer aPL-positive RM, as it leads to favorable maternal-fetal outcomes.
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Aborto Habitual , Anticorpos Antifosfolipídeos , Gravidez , Humanos , Feminino , Adulto , Anticorpos Anticardiolipina , Nascido Vivo , Imunoglobulina MRESUMO
Whether coexisting microplastics (MPs) affect the ecological and health risks of cadmium (Cd) in soils is a cutting-edge scientific issue. In this study, four typical Chinese soils were prepared as artificially Cd-contaminated soils with/without aged polystyrene (PS). TCLP and in vitro PBET model were used to determine the leachability (ecological risk) and oral bioaccessibility (human health risk) of soil Cd. The mechanisms by which MPs influence soil Cd were discussed from direct and indirect perspectives. Results showed that there was no significant difference in the leachability of soil Cd with/without aged PS. Additionally, aged PS led to a significant decrease in the bioaccessibility of soil Cd in gastric phase, but not in small intestinal phase. The increase in surface roughness and the new characteristic peaks (e.g., Si-O-Si) of aged PS directly accounted for the change in Cd bioaccessibility. The change in organic matter content indirectly accounted for the exceptional increase in Cd bioaccessibility of black soil with aged PS in small intestinal phase. Furthermore, the changes in cation exchange capacity and Cd mobility factor caused by aged PS explained the change in Cd leachability. These results contribute to a deeper understanding about environmental and public health in complicated emerging scenarios.
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Cádmio , Poluentes do Solo , Humanos , Idoso , Cádmio/toxicidade , Cádmio/análise , Microplásticos/toxicidade , Plásticos , Poliestirenos/toxicidade , Solo , Poluentes do Solo/toxicidade , Poluentes do Solo/análise , Disponibilidade BiológicaRESUMO
Arsenic (As)-contaminated soil poses great health risk to human mostly through inadvertent oral exposure. We investigated CaAl-layered double hydroxide (CaAl-LDH), a promising immobilising agent, for the remediation of As-contaminated Chinese soils. The effects on specific soil properties and As fractionation were analyzed, and changes in the health risk of soil As were accurately assessed by means of advanced in vivo mice model and in vitro PBET-SHIME model. Results showed that the application of CaAl-LDH significantly increased soil pH and concentration of Fe and Al oxides, and effectively converted active As fractions into the most stable residual fraction, guaranteeing long-term remediation stability. Based on in vivo test, As relative bioavailability was significantly reduced by 37.75%. Based on in vitro test, As bioaccessibility in small intestinal and colon phases was significantly reduced by 25.65% and 28.57%, respectively. Furthermore, As metabolism (reduction and methylation) by the gut microbiota inhabiting colon was clearly observed. After immobilisation with CaAl-LDH, the concentration of bioaccessible As(â ¤) in the colon fluid was significantly reduced by 61.91%, and organic As (least toxic MMA(V) and DMA(V)) became the main species, which further reduced the health risk of soil As. In summary, CaAl-LDH proved to be a feasible option for immobilisation remediation of As-contaminated soils, and considerable progress was made in relevant health risk assessment.
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Arsênio , Poluentes do Solo , Animais , Humanos , Camundongos , Arsênio/química , Disponibilidade Biológica , Poluentes do Solo/análise , Solo/química , Medição de RiscoRESUMO
Arsenic (As) mobilisation assists in remediating As-contaminated soils but might increase ecological and health risks. In this study, risks of applying two mobilising agents were assessed, i.e. an emerging reducing-chelating composite agent [dithionite (Na2S2O4)-EDTA] and a classical low-molecular-weight organic acid (LMWOA) [citric acid (C6H8O7)]. Results showed that both agents induced sharp increase in leachability-based ecological risk of As. Interestingly, the two agents had opposite performances regarding health risks. Na2S2O4-EDTA significantly increased As relative bioavailability (RBA) to 1.83 times that in controls based on in vivo mouse model, and As bioaccessibility to 1.96, 1.65 and 1.20 times in gastric, small intestinal and colon phases based on in vitro PBET-SHIME model. Besides, it caused significant increase of highly toxic As(â ¢) in colon fluid. In contrast, C6H8O7 significantly reduced RBA and bioaccessibility of soil As in colon by 44.44% and 14.65%, respectively. Importantly, C6H8O7 restrained bioaccessible As(V) reduction and promoted bioaccessible As(â ¢) methylation, further reducing health risk. The phenomena could mainly be attributed to excessive metal components release from soil by C6H8O7 and gut microbiota metabolism of C6H8O7. In summary, C6H8O7 and similar LMWOAs are recommended. The study contributes to mobilising agent selection and development and provides a reference for managing remediation sites.
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Arsênio , Animais , Camundongos , Ditionita , Arsênio/toxicidade , Disponibilidade Biológica , Ácido Cítrico , Ácido Edético , SoloRESUMO
The trophodynamics of toxic trace metals is significant for assessing the threat of toxic trace metals to the aquatic ecosystem and human safety. However, due to the difficulty of accurately calculating the trophic positions of freshwater aquatic organisms in the food web, the comprehensive process of trophodynamics of toxic trace metals in freshwater ecosystems was still rarely known. By integrating the compound-specific nitrogen stable isotopic analysis of amino acids (CSIA-AAs) and the Bayesian stable isotope mixing model (SIMM) as a novel approach, the present study investigated the trophodynamics of five toxic trace metals (Zn, As, Cr, Cu, and Hg) in the food web of the YangZong Lake, a plateau freshwater lake that was once heavily polluted by arsenic in Yunnan Province, China. The results revealed that Hg tended to be efficiently biomagnified in the food web with a trophic magnification factor of 1.75; As, Cr, and Cu were biodiluted significantly, while Zn showed no biomagnification or biodilution trends. The dietary health risk assessment indicated the potential health risk of toxic trace metals for the local residents of long-term fish consumption. The present work highlights the accuracy and reliability of the novel CSIA-AAS+SIMM approach in the calculation of the trophic positions of freshwater organisms.
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Mercúrio , Oligoelementos , Poluentes Químicos da Água , Animais , Organismos Aquáticos/metabolismo , Teorema de Bayes , China , Ecossistema , Monitoramento Ambiental/métodos , Cadeia Alimentar , Humanos , Lagos/química , Mercúrio/metabolismo , Reprodutibilidade dos Testes , Medição de Risco , Oligoelementos/metabolismo , Poluentes Químicos da Água/análiseRESUMO
It has been verified that, as an emerging contaminant, microplastics are capable of adsorbing certain traditional contaminants like the heavy metal Cd. However, the majority of previous studies only focused on certain types of virgin microplastics, especially for PE and PS. In addition, this adsorption process might be affected by microplastics inevitably undergoing aging and consequent changes in the natural environment. Unfortunately, the relevant reports on aging effects were mainly about organic pollutants, rather than heavy metals. By far, there have been few comprehensive and mechanistic studies on the key aging effects on the Cd adsorption by various types of microplastics. In this study, five representative types of microplastics (i.e., PS, ABS, PP, PVC, and PET) were selected for aging by ultraviolet radiation, and the physicochemical properties of virgin and aged microplastics were thoroughly compared, including specific surface area, crystallinity, surface functional groups, and surface elements. Accordingly, the changes in adsorption isotherms of Cd by microplastics were discussed. The results showed that:â aging induced non-significant changes in specific surface area but a significant decrease in crystallinity. Surface functional groups also changed, including the emergence of a C=O functional group on PS and ABS, the decrease in C=C absorption peak intensity on ABS, and the increase in absorption peak intensities of C=O, C-O, and polar ester groups on PET. Regarding surface C content, C=C/C-C decreased, whereas C-O and O-C=O increased. The total O content and O/C significantly increased as well. â¡ The Langmuir model well-fitted the adsorption isotherms of Cd by virgin and aged microplastics. Aging significantly expanded the adsorption capacity of Cd by microplastics, as the order of saturated adsorption capacity before aging was ABS (0.2284 mg·g-1)>PVC (0.1360 mg·g-1)>PS (0.1286 mg·g-1)>PP (0.1005 mg·g-1)>PET (0.0462 mg·g-1) and then became PS (0.2768 mg·g-1)>ABS (0.2586 mg·g-1)>PVC (0.1776 mg·g-1)>PP (0.1721 mg·g-1)>PET (0.0951 mg·g-1) after aging. ⢠Both crystallinity and surface functional groups played key roles in the adsorption of Cd by microplastics. As for virgin microplastics, crystallinity was negatively correlated with the saturated adsorption capacity of Cd, because the amorphous regions contributed most to Cd adsorption. Aging brought about the decrease in crystallinity and the increase in amorphous regions, which further promoted the oxidation reaction on microplastics. Consequently, oxygen-containing functional groups increased on the surface and eventually expanded the adsorption capacity of Cd by microplastics. Note that certain specific functional groups of various microplastics also had impacts on the adsorption process. These results provide valuable information about the environmental behaviors and interactions of microplastics and heavy metals in nature.
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Metais Pesados , Poluentes Químicos da Água , Adsorção , Cádmio , Microplásticos , Plásticos/química , Cloreto de Polivinila , Raios Ultravioleta , Poluentes Químicos da Água/análiseRESUMO
The proteasome has been validated as an anticancer drug target, while the role of a subunit of proteasome, PSMC6, in lung adenocarcinoma (LUAD) has not been fully unveiled. In this study, we observed that both the RNA and protein of PSMC6 were highly upregulated in LUAD compared with the adjacent normal tissues. Moreover, a high PSMC6 expression was associated with poor prognosis. In accordance with this finding, PSMC6 was associated with poor tumor differentiation. Furthermore, the silence of PSMC6 by small interference RNAs (siRNAs) could significantly inhibit cell growth, migration, and invasion in lung cancer cell lines, suggesting that PSMC6 might serve as a promising therapeutic target in LUAD. To further explore the molecular mechanism of PSMC6 in LUAD, we observed that the proteasome subunits, such as PSMD10, PSMD6, PSMD9, PSMD13, PSMB3, PSMB1, PSMA4, PSMC1, PSMC2, PSMD7, and PSMD14, were highly correlated with PSMC6 expression. Based on the gene set enrichment analysis, we observed that these proteasome subunits were involved in the degradation of AXIN protein. The correlation analysis revealed that the positively correlated genes with PSMC6 were highly enriched in WNT signaling-related pathways, demonstrating that the PSMC6 overexpression may activate WNT signaling via degrading the AXIN protein, thereby promoting tumor progression. In summary, we systematically evaluated the differential expression levels and prognostic values of PSMC6 and predicted its biological function in LUAD, which suggested that PSMC6 might act as a promising therapeutic target in LUAD.
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ATPases Associadas a Diversas Atividades Celulares/genética , Adenocarcinoma de Pulmão/metabolismo , Inativação Gênica , Neoplasias Pulmonares/metabolismo , Complexo de Endopeptidases do Proteassoma/genética , Células A549 , ATPases Associadas a Diversas Atividades Celulares/metabolismo , Adenocarcinoma de Pulmão/genética , Diferenciação Celular , Movimento Celular , Proliferação de Células , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Humanos , Neoplasias Pulmonares/genética , Invasividade Neoplásica , Metástase Neoplásica , Modelos de Riscos Proporcionais , Complexo de Endopeptidases do Proteassoma/metabolismo , RNA Interferente Pequeno/metabolismo , Transdução de SinaisRESUMO
Two new troponoides (1-2) were isolated from a 95% ethanol extract of the stems of Juniperus formosana (Cupressaceae), together with six known compounds (3-8). The structures of the new compounds were comprehensively characterized by high resolution electrospray ionization-mass spectrometry (HR-ESI-MS), 1D and 2D nuclear magnetic resonance (NMR). Compounds 1-7 were evaluated for their anti-inflammatory against the expression of IL-1ß, IL-6 and TNF-α in lipopolysaccharide (LPS)-induced RAW 264.7 macrophages. The new compounds showed moderate anti-inflammatory effect, while other compounds did show no activity.
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Juniperus , Animais , Anti-Inflamatórios/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos , Camundongos , Extratos Vegetais/farmacologia , Células RAW 264.7RESUMO
The title compound, C(14)H(18)O(2), was obtained as a by-product during the preparation of carbofuran phenol. The two dihydro-furan rings are in envelope conformations.
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In this report, we gave the first case of successful treatment for laryngeal NMC, which is exceedingly rare with dismal prognosis. intensity-modulated radiation therapy accompanied by traditional Chinese medicine was administrated for the young woman, instead of radical resection, and she got continuous remission for more than 2 years, with no recurrence detected.
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BACKGROUND: The conventional procedure for screening bioactive components from traditional Chinese medicine is time-consuming, expensive and low efficient. Therefore, some alternative strategies are needed urgently. A novel method for screening anti-platelet aggregation components from oleoresins was developed using chicken thrombocyte extract and high performance liquid chromatography. METHODS: The anti-platelet aggregation components of oleoresins were combined with receptors, channels and enzymes of chicken thrombocytes under physiological environment. Unbound substances were washed away and bound compounds were eluted using specific phosphate buffered solution (PBS). Compounds released from target sites were collected and analyzed by high performance liquid chromatography and LC-MS. The activity of three compounds which were screened from this model was confirmed using platelet aggregation pharmacology in vivo. RESULTS: There were four typical compounds that bound to the thrombocytes: 6-gingerol, 8-gingerol, 6-shogaol and 10-gingerol, and all had shown anti-platelet aggregation activities. Eight-gingerol displayed the best anti-platelet aggregation effect. CONCLUSIONS: Chicken thrombocyte extract can be used to isolate chemicals that are ligands of the receptor or other bio-targets on the platelet. This may therefore be a simple and efficient method to screen for anti-platelet aggregation compounds from traditional Chinese medicine.
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Cromatografia Líquida de Alta Pressão/métodos , Inibidores da Agregação Plaquetária/isolamento & purificação , Zingiber officinale/química , Animais , Catecóis/isolamento & purificação , Catecóis/farmacologia , Galinhas , Álcoois Graxos/isolamento & purificação , Álcoois Graxos/farmacologia , Medicina Tradicional Chinesa , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Inibidores da Agregação Plaquetária/farmacologia , Rizoma/química , Linfócitos T/metabolismoRESUMO
The first Rh-catalyzed enantioselective synthesis of a 3,4-polyfused oxindole ring system enabled by carboacylation of acrylic amides based on C-C activation is reported. This transformation provides a new entry to access 3,4-polyfused oxindoles bearing quaternary stereocenters. Tri- to pentacyclic 3,4-fused oxindoles were asymmetrically generated in good yields (up to 95%) with good to excellent enantioselectivity (88%-97% ee). Application in the first total synthesis of xylanigripones A was completed in 6 steps with a 14% overall yield.
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Spin-reorientation-induced magnetodielectric coupling effects were discovered in two layered perovskite magnets, [C6H5CH2CH2NH3]2[MCl4] (M = Mn2+ and Cu2+), via isothermal magnetodielectric measurements on single-crystal samples. Specifically, peak-like dielectric anomalies and spin-flop transitions appeared simultaneously at around ±34 kOe for the canted antiferromagnet (M = Mn2+) at below 44.3 K, while a low-field (1 kOe) controlled magnetodielectric effect was observed in the "soft" ferromagnet (M = Cu2+) at below 9.5 K. These isothermal magnetodielectric effects are highly reproducible and synchronous with the field-induced magnetization at different temperatures, well confirming the essential role of spin reorientation on inducing magnetodielectric coupling effects. These findings strongly imply that the layered perovskite magnets are new promising organic-inorganic hybrid systems to host magnetodielectric coupling effects.
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OBJECTIVE: To determine the role and mechanism of EphB4 in dasatinib (DAS) resistance in advanced chronic myeloid leukemia (CML), we explored the EphB4-mediated apoptotic and matrix microenvironment pathway in human CML and K562 cell lines. METHOD: Heparinized bone marrow samples were obtained from enrolled five patients (identified as A to E and visits identified by number) at initial diagnosis (A1-E1) and in the DAS-resistance advanced phase (A2-E2). Meanwhile, highly DAS-resistant cells, named K562-R cells, were obtained from K562-W cells with increasing concentrations of DAS. Stable under-expressing EphB4 cells (K562-R-EphB4-sh) were obtained from K562-R cells by RNA interference. K562-W, K562-R and K562-R-EphB4-sh cells (108) were respectively injected subcutaneously on the dorsal surface of BALB/C female nude mice to establish the xenografts models. RESULT: The mRNA/protein of EphB4 was overexpressed in the DAS-resistant A2-E2 in comparison with the A1-E1 human cell lines. Further, compared with K562-R cells, the expressions of EphB4 and p-Rac1/Cdc42 protein/mRNA were significantly downregulated in K562-R-EphB4-sh cells (P<0.01). K562-R cells showed the highest DAS resistance (IC50 10.54±0.67µg/ml), but K562-R-EphB4-sh cells became sensitive to DAS (IC50 1.02±0.1µg/ml, P<0.01). The expression of EphB4/p-RhoA/MCL-1 protein was gradually increased in the stimulating of EphrinB2-Fc, which partly made K562-R-EphB4-sh cells restore sensitivity to DAS (4.18±0.30µg/ml). Meanwhile, the K562-R-EphB4-sh xenografts group had relatively good efficacy compared to K562-R xenografts nude mice receiving the same dose of DAS. The analysis of xenografts tissue also suggested parallel results with the overexpression of EphB4/RhoA/ROCK1/PTEN/MCL-1 in K562-R xenografts, which decreased in the A2-R-EphB4-sh xenografts (P<0.01). CONCLUSIONS: The present study found that a new DAS resistance pathway of EphB4 overexpression was triggered by EphrinB2-Fc, which induced the resistance to DAS by activating RhoA/ROCK1/PTEN/MCL-1 signaling.
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Apoptose , Dasatinibe/farmacologia , Resistencia a Medicamentos Antineoplásicos , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Receptor EphB4/metabolismo , Adulto , Idoso , Animais , Antineoplásicos/farmacologia , Proliferação de Células , Feminino , Humanos , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
An organic-inorganic hybrid compound, [C6H5CH2CH2NH3]2[CdI4], exhibits a reversible ferroelectric phase transition at 301/297 K. Switchable dielectric constant, second harmonic generation, and pyroelectricity were synchronously observed accompanied by the order-disorder phase transition. This finding promotes research on molecular ferroelectrics to search for promising multifunctional switching materials at near room temperature.