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Tumor metastasis is the major cause of breast cancer morbidity and mortality. It has been reported that the F-box protein FBXO3 functions as an E3 ubiquitin ligase in regulating various biological processes, including host autoimmune, antiviral innate immunity, and inflammatory response. However, the role of FBXO3 in tumor metastasis remains elusive. We have previously shown that ΔNp63α is a common inhibitory target in oncogene-induced cell motility and tumor metastasis. In this study, we show that FBXO3 plays a vital role in PI3K-mediated breast cancer metastasis independent of its E3 ligase activity and ΔNp63α in breast cancer cells and in mouse. FBXO3 can bind to and stabilize USP4, leading to Twist1 protein stabilization and increased breast cancer cell migration and tumor metastasis. Mechanistically, FBXO3 disrupts the interaction between USP4 and aspartyl aminopeptidase (DNPEP), thereby protecting USP4 from DNPEP-mediated degradation. Furthermore, p110αH1047R facilitates the phosphorylation and stabilization of FBXO3 in an ERK1-dependent manner. Knockdown of either FBXO3 or USP4 leads to significant inhibition of PI3K-induced breast cancer metastasis. Clinically, elevated expression of p110α/FBXO3/USP4/Twist1 is associated with poor overall survival (OS) and recurrence-free survival (RFS) of breast cancer patients. Taken together, this study reveals that the FBXO3-USP4-Twist1 axis is pivotal in PI3K-mediated breast tumor metastasis and that FBXO3/USP4 may be potential therapeutic targets for breast cancer treatment.
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Neoplasias da Mama , Melanoma , Neoplasias Cutâneas , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Fosfatidilinositol 3-Quinases/metabolismo , Proteína 1 Relacionada a Twist/genética , Proteína 1 Relacionada a Twist/metabolismo , Proteases Específicas de Ubiquitina/metabolismo , UbiquitinaçãoRESUMO
The 2019 coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has brought an enormous public health burden to the global society. The duration of the epidemic, the number of infected people, and the widespread of the epidemic are extremely rare in modern society. In the initial stage of infection, people generally show fever, cough, and dyspnea, which can lead to pneumonia, acute respiratory syndrome, kidney failure, and even death in severe cases. The strong infectivity and pathogenicity of SARS-CoV-2 make it more urgent to find an effective treatment. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with the potential for self-renewal and multi-directional differentiation. They are widely used in clinical experiments because of their low immunogenicity and immunomodulatory function. Mesenchymal stem cell-derived exosomes (MSC-Exo) can play a physiological role similar to that of stem cells. Since the COVID-19 pandemic, a series of clinical trials based on MSC therapy have been carried out. The results show that MSCs are safe and can significantly improve patients' respiratory function and prognosis of COVID-19. Here, the effects of MSCs and MSC-Exo in the treatment of COVID-19 are reviewed, and the clinical challenges that may be faced in the future are clarified.
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COVID-19 , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , SARS-CoV-2 , Humanos , COVID-19/terapia , Células-Tronco Mesenquimais/citologia , Transplante de Células-Tronco Mesenquimais/métodos , ExossomosRESUMO
The intricacy and multifaceted nature of Alzheimer's disease (AD) necessitate therapies that target multiple aspects of the disease. Mesenchymal stromal cells (MSCs) emerge as potential agents to mitigate AD symptoms; however, whether their therapeutic efficacy involves modulation of gut microbiota and the microbiome-gut-brain axis (MGBA) remains unexplored. In this study, we evaluated the effects of three distinct MSCs types-derived from the umbilical cord (UCMSC), dental pulp (SHED), and adipose tissue (ADSC)-in an APP/PS1 mouse model of AD. In comparison to saline control, MSCs administration resulted in a significant reduction of behavioral disturbances, amyloid plaques, and phosphorylated tau in the hippocampus and frontal cortex, accompanied by an increase in neuronal count and Nissl body density across AD-afflicted brain regions. Through 16S rRNA gene sequencing, we identified partial restoration of gut microbial balance in AD mice post-MSCs treatment, evidenced by the elevation of neuroprotective Akkermansia and reduction of the AD-associated Sphingomonas. To examine whether gut microbiota involved in MSCs efficacy in treating AD, SHED with better anti-inflammatory and gut microbiota recovery effects among three MSCs, and another AD model 5â¯×â¯FAD mice with earlier and more pathological proteins in brain than APP/PS1, were selected for further studies. Antibiotic-mediated gut microbial inactivation attenuated MSCs efficacy in 5â¯×â¯FAD mice, implicating the involvement of gut microbiota in the therapeutic mechanism. Functional analysis of altered gut microbiota and targeted bile acid metabolism profiling revealed a significant enhancement in bile acid variety following MSCs therapy. A chief bile acid constituent, taurocholic acid (TCA), was orally administered to AD mice and similarly abated AD symptoms. Nonetheless, the disruption of intestinal neuronal integrity with enterotoxin abrogated the ameliorative impact of both MSCs and TCA treatments. Collectively, our findings substantiate that MSCs confer therapeutic benefits in AD within a paradigm that primarily involves regulation of gut microbiota and their metabolites through the MGBA.
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Craniotomy, an essential neurosurgical operation, poses distinct difficulties in the realm of post-operative care, specifically with regard to the management of wounds. Efficient wound management is critical in order to optimize the surgical outcomes, reduce complications and facilitate a speedier recovery. The purpose of this comprehensive review was to assess contemporary wound management approaches as they pertain to improved recovery following craniotomy. This was achieved by contrasting conventional methods with more recent and innovative techniques and analysing the effects of these approaches on patient recovery and surgical results. An exhaustive literature search was undertaken, comprising narrative reviews, clinical studies, peer-reviewed articles and expert opinions. The emphasis was on the evolution of wound management strategies and techniques utilized after cranial section, as well as their contributions to patient recovery. The analysis reveals that while conventional wound management methods, including suturing and antiseptics, continue to be essential, innovative strategies such as negative pressure wound therapy, skin adhesives and advanced pain management protocols are becoming increasingly recognized. It has been demonstrated that these novel approaches improve recovery by decreasing the incidence of infections, enhancing patient comfort and producing superior cosmetic results. Nevertheless, obstacles continue to endure, including patient-specific variables, technological and financial considerations and the enduring consequences of recovery. Thus the treatment of wounds during craniotomy recuperation necessitates an integrated strategy that incorporates conventional techniques alongside contemporary advancements. Progress in this domain necessitates the customization of approaches to suit the unique requirements of each patient, the resolution of identified obstacles and an emphasis on ongoing investigation and interdisciplinary cooperation. The ever-changing terrain of wound management approaches underscores the ever-changing character of neurosurgical treatment and the continuous endeavour to enhance patient results following cranial resection.
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Adesivos , Craniotomia , Humanos , Cuidados Pós-Operatórios , Resultado do TratamentoRESUMO
Herein, an efficient method to prepare sulfonated polyether ether ketone (SPEEK) based cation exchange membranes (CEMs) is developed, where polyethersulfone (PES) is used as an additive. The optimized membrane of 30 wt.%PES/SPEEK-M exhibits a rather low anion permeability and a high ionic conductivity of 9.52 mS cm-1 together with low volume swelling in water. Meanwhile, tensile strength of the membrane is as high as 31.4 MPa with a tensile strain of 162%. As separators for aqueous K-ion batteries (AKIBs) with decoupled gel electrolytes (Zn anode in alkaline and Prussian blue (FeHCF) cathode in neutral). Discharge voltage of the AKIB can reach 2.3 V. Meanwhile, Zn dendrites can be effectively suppressed in the gel anolyte. Specific capacities of the FeHCF cathode are 116.7 mAh g-1 at 0.3 A g-1 (close to its theoretical value), and 95.0 mAh g-1 at 1.0 A g-1 , indicating good rate performance. Capacity retention of the cathode is as high as 91.2% after 1000 cycles' cycling owing to the well remained neutral environment of the catholyte. There is almost no pH change for the catholyte after cycling, indicating good anion-blocking or cation-selecting ability of the 30 wt.%PES/SPEEK-M, much better than other membranes.
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BACKGROUND: We compared plasma metabolites of amino acid oxidation and the tricarboxylic acid (TCA) cycle in youth with and without type 1 diabetes mellitus (T1DM) and related the metabolites to glomerular filtration rate (GFR), renal plasma flow (RPF), and albuminuria. Metabolites associated with impaired kidney function may warrant future study as potential biomarkers or even future interventions to improve kidney bioenergetics. METHODS: Metabolomic profiling of fasting plasma samples using a targeted panel of 644 metabolites and an untargeted panel of 19,777 metabolites was performed in 50 youth with T1DM ≤ 10 years and 20 controls. GFR and RPF were ascertained by iohexol and p-aminohippurate clearance, and albuminuria calculated as urine albumin to creatinine ratio. Sparse partial least squares discriminant analysis and moderated t tests were used to identify metabolites associated with GFR and RPF. RESULTS: Adolescents with and without T1DM were similar in age (16.1 ± 3.0 vs. 16.1 ± 2.9 years) and BMI (23.4 ± 5.1 vs. 22.7 ± 3.7 kg/m2), but those with T1DM had higher GFR (189 ± 40 vs. 136 ± 22 ml/min) and RPF (820 ± 125 vs. 615 ± 65 ml/min). Metabolites of amino acid oxidation and the TCA cycle were significantly lower in adolescents with T1DM vs. controls, and the measured metabolites were able to discriminate diabetes status with an AUC of 0.82 (95% CI: 0.71, 0.93) and error rate of 0.21. Lower glycine (r:-0.33, q = 0.01), histidine (r:-0.45, q < 0.001), methionine (r: -0.29, q = 0.02), phenylalanine (r: -0.29, q = 0.01), serine (r: -0.42, q < 0.001), threonine (r: -0.28, q = 0.02), citrate (r: -0.35, q = 0.003), fumarate (r: -0.24, q = 0.04), and malate (r: -0.29, q = 0.02) correlated with higher GFR. Lower glycine (r: -0.28, q = 0.04), phenylalanine (r:-0.3, q = 0.03), fumarate (r: -0.29, q = 0.04), and malate (r: -0.5, q < 0.001) correlated with higher RPF. Lower histidine (r: -0.28, q = 0.02) was correlated with higher mean ACR. CONCLUSIONS: In conclusion, adolescents with relatively short T1DM duration exhibited lower plasma levels of carboxylic acids that associated with hyperfiltration and hyperperfusion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03618420 and NCT03584217 A higher resolution version of the Graphical abstract is available as Supplementary information.
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Diabetes Mellitus Tipo 1 , Insuficiência Renal , Adolescente , Humanos , Albuminúria , Ácidos Carboxílicos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/diagnóstico , Fumaratos , Taxa de Filtração Glomerular , Glicina , Histidina , Rim , Malatos , Fenilalanina , Insuficiência Renal/complicaçõesRESUMO
Aqueous zinc-ion batteries (ZIBs) have attracted widespread attention due to the intrinsic features of Zn-based anodes, mainly including high capacity, low cost, and low working potential together with high over-potential for hydrogen evolution reaction. Aqueous ZIBs are considered to be strong competitors and substitutes for lead-acid, nickel-metal hydrogen, nickel-cadmium, and even lithium-ion batteries. Great efforts have been made in the past few years towards the issues existed in aqueous ZIBs, mainly including alkaline and mild acidic systems. In this perspective, we illustrate the advantages, the main challenges, and the corresponding solution strategies of Zn-based anodes in various aqueous rechargeable ZIBs with alkaline and mild acidic electrolytes. Furthermore, feasible aqueous ZIBs for practical use are prospected.
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Cadmium (Cd), a ubiquitous toxic heavy metal, with the intractable trait of low degradation, can induce multiple organ damage. Whereas, far less is known about its neurotoxicity and the specific mechanism in the chronic low Cd exposure. To investigate the chronic neurotoxicity of Cd2+ , we traced its effects for up to 30 months in mice which were exposed to Cd2+ by drinking the mimicking Cd-polluted water. We found the toxicity of chronic Cd exposure was a process associated with the transition from autophagy to apoptosis, and the switch of autophagy-apoptosis was Cd dose-dependent with the threshold of [Cd2+ ] 0.04 mg/L. Furthermore, JNK was found to be a hub molecule orchestrated the switch of autophagy-apoptosis by interacting with Sirt1 and p53. At last, the hippocampus-dependent learning and memory was damaged by continuous neuron apoptosis rather than deficit of neurogenesis. Therefore, elucidation of the effect, process, and potential molecular mechanism of the chronic low Cd2+ exposure is important for controlling of the environmental-pollutant Cd.
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Cádmio , Neurogênese , Animais , Apoptose , Cádmio/metabolismo , Cádmio/toxicidade , Hipocampo/metabolismo , Transtornos da Memória/induzido quimicamente , CamundongosRESUMO
Serological test is a valuable diagnostic tool for coronavirus disease 2019 (COVID-19). However, considerable improvements to these tests are needed, especially in the detection sensitivity. In this study, six recombinant nucleocapsid and spike proteins of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were prepared and evaluated, including three prokaryotic expression nucleocapsid proteins (rN, rN1, rN2) and three eukaryotic expression spike proteins (rS1, rS-RBD, rS-RBD-mFc). The recombinant proteins with the highest ELISA titers (rS1 and rS-RBD-mFc) were selected to develop a double-antigen sandwich colloidal gold immunochromatography assay (GICA) to detect total antibodies against SARS-CoV-2. The clinical evaluation results showed that the sensitivity and specificity of GICA were 92.09% (419/455) and 99.44% (706/710), respectively. Moreover, a significant number (65.63%, 21/32) of COVID-19 patients with undetectable viral RNA were correctly diagnosed by the GICA method. In conclusion, the eukaryotic expression spike proteins (rS1 and rS-RBD-mFc) are more suitable than the prokaryotic expression nucleocapsid proteins for serological diagnosis of SARS-CoV-2. The proposed GICA for detection of total antibodies could be a powerful complement to the current RNA tests for COVID-19.
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Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , SARS-CoV-2/isolamento & purificação , Glicoproteína da Espícula de Coronavírus/imunologia , Anticorpos Antivirais/sangue , COVID-19/sangue , Teste de Ácido Nucleico para COVID-19 , Proteínas do Nucleocapsídeo de Coronavírus/genética , Proteínas do Nucleocapsídeo de Coronavírus/imunologia , Humanos , Imunoensaio , Fosfoproteínas/genética , Fosfoproteínas/imunologia , RNA Viral/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/genéticaRESUMO
Root-derived mobile signals play critical roles in coordinating a shoot's response to underground conditions. However, the identification of root-to-shoot long-distance mobile signals has been scant. In this study, we aimed to characterize root-to-shoot endogenous mobile miRNAs by using an Arabidopsis/Nicotiana interfamilial heterograft in which these two taxonomically distant species with clear genetic backgrounds had sufficient diversity in differentiating miRNA sources. Small RNA deep sequencing analysis revealed that 82 miRNAs from the Arabidopsis scion could travel through the graft union to reach the rootstock, whereas only a very small subset of miRNA (6 miRNAs) preferred the root-to-shoot movement. We demonstrated in an ex vivo RNA imaging experiment that the root-to-shoot mobile Nb-miR164, Nb-miR395 and Nb-miR397 were targeted to plasmodesmata using the bacteriophage coat protein MS2 system. Furthermore, the Nb-miR164 was shown to move from the roots to the shoots to induce phenotypic changes when its overexpressing line was used as rootstock, strongly supporting that root-derived Nb-miR164 was able to modify the scion trait via its long-distance movement.
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Regulação da Expressão Gênica de Plantas , MicroRNAs/genética , Nicotiana/genética , Raízes de Plantas/genética , Brotos de Planta/genética , RNA de Plantas/genética , Raízes de Plantas/crescimento & desenvolvimento , Brotos de Planta/crescimento & desenvolvimento , Nicotiana/crescimento & desenvolvimentoRESUMO
[Purpose] We aimed to investigate the changes in the swallowing sounds of healthy adults during neuromuscular joint facilitation treatment using neck patterns. [Participants and Methods] A total of 20 healthy adults (10 males and 10 females; mean age, 29.2 ± 6.3 years) swallowed 10â mL of water four times under three conditions (after the neuromuscular joint facilitation neck-flexion resistance pattern, after the Shaker-type exercise, and during relaxed sitting without prior exercise [control]), randomly ordered with an interval greater than 3 days. Swallowing sounds for each water swallow were recorded using cervical auscultation. [Results] The mean amplitude of swallowing sound intensity and the mean spectral frequency were significantly higher after the neuromuscular joint facilitation neck-flexion resistance pattern and the Shaker-type exercise, in comparison with those in the control group. [Conclusion] Neuromuscular joint facilitation training with the neck-flexion resistance pattern influenced swallowing sounds to the same degree as the Shaker-type exercise, implying that this resistance pattern may enhance suprahyoid muscle contraction.
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BACKGROUND: The estimated glomerular filtration rate (eGFR) is frequently used to monitor progression of kidney disease. Multiple values have to be obtained, sometimes over years to determine the rate of decline in kidney function. Recent data suggest that functional MRI (fMRI) methods may be able to predict loss of eGFR. In a prior study, baseline data with multi-parametric MRI in individuals with diabetes and moderate CKD was reported. This report extends our prior observations in order to evaluate the temporal variability of the fMRI measurements over 36 months and their association with annual change in eGFR. METHODS: Twenty-four subjects with moderate CKD completed 3 sets of MRI scans over a 36-month period. Blood oxygenation level-dependent (BOLD), arterial spin labeling perfusion, and diffusion MRI images were acquired using a 3 T scanner. Coefficients of variation was used to evaluate variability between subjects at each time point and temporal variability within each subject. We have conducted mixed effects models to examine the trajectory change in GFR over time using time and MRI variables as fixed effects and baseline intercept as random effect. Associations of MRI image markers with annual change in eGFR were evaluated. RESULTS: Multi-parametric functional renal MRI techniques in individuals with moderate CKD showed higher temporal variability in R2* of medulla compared to healthy individuals. This was consistent with the significant lower R2* in medulla observed at 36 months compared to baseline values. The results of linear mixed model showing that R2*_Medulla was the only predictor associated with change in eGFR over time. Furthermore, a significant association of medullary R2* with annual loss of eGFR was observed at all the 3 time points. CONCLUSIONS: The lower R2* values and the higher temporal variability in the renal medulla over time suggest the ability to monitor progressive CKD. These were confirmed by the fact that reduced medullary R2* was associated with higher annual loss in eGFR. These data collectively emphasize the need for inclusion of medulla in the analysis of renal BOLD MRI studies.
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Medula Renal/irrigação sanguínea , Imageamento por Ressonância Magnética , Oxigênio/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico por imagem , Idoso , Progressão da Doença , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/fisiopatologia , Índice de Gravidade de Doença , Fatores de TempoRESUMO
OBJECTIVE: Blood oxygenation level dependent (BOLD) MRI technique is used to evaluate changes in intra-renal oxygenation in chronic kidney disease (CKD). The purpose of this study was to evaluate if the novel twelve layer concentric objects (TLCO) method has advantages over the manually defined regions of interest (ROI) analysis. METHODS AND MATERIALS: Existing renal BOLD MRI data acquired before and after furosemide on a 3 T scanner from 41 CKD patients and 13 age matched healthy controls were analyzed using TLCO method and compared with previously reported ROI analysis. RESULTS: Regional R2* measurements were strongly correlated between the two methods, while ΔR2* was moderately correlated. Medullary R2* by ROI analysis showed higher values compared to R2*_Inner by TLCO, probably due to the contributions from the cortex to R2*_Inner. R2*_Slope and Δ(R2*_Slope), unique parameters based on the TLCO method provided the most significant differences between stage 3a CKD patients and controls and were correlated with eGFR. DISCUSSION: There was a high degree of agreement between the two methods in terms of regional R2* measurements and both methods did not show differences between moderate CKD patients and controls. However, R2*_Slope and Δ(R2*_Slope) showed the largest sensitivity in distinguishing CKD from controls.
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Diagnóstico por Computador/métodos , Furosemida/farmacologia , Falência Renal Crônica/diagnóstico por imagem , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética , Oxigênio/metabolismo , Idoso , Estudos de Casos e Controles , Feminino , Taxa de Filtração Glomerular , Humanos , Processamento de Imagem Assistida por Computador/métodos , Córtex Renal , Masculino , Pessoa de Meia-Idade , Reconhecimento Automatizado de Padrão , Estudo de Prova de Conceito , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To explore the genetic basis for a patient with Leydig cell hypoplasia. METHODS: Whole exome sequencing was used to detect genetic variants in the patient. Suspect variants were verified by PCR and Sanger sequencing of the family members. RESULTS: The patient was found to carry two novel variants, namely c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala), of the luteinizing hormone receptor gene (LHCGR), where were respectively inherited from her father and mother. Upon prenatal diagnosis, the fetus was found to be a heterozygous carrier of the c.265A>T (p.Ile189Leu) variant. CONCLUSION: The compound heterozygous variants of c.265A>T (p.Ile189Leu) and c.422T>C (p.Val141Ala) of the LHCGR gene probably underlie the Leydig cell hypoplasia in the patient.
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Transtorno 46,XY do Desenvolvimento Sexual/genética , Receptores do LH/genética , Testículo/anormalidades , Feminino , Humanos , Masculino , Mutação , Gravidez , Diagnóstico Pré-NatalRESUMO
BACKGROUND: Chronic hypoxia is a well-recognized factor in the pathogenesis of chronic kidney disease (CKD). Loss of microcirculation is thought to lead to enhanced renal hypoxia, which in turn results in the development of fibrosis, a hallmark of progressive CKD. To evaluate the role of functional magnetic resonance imaging (MRI), we performed perfusion, oxygenation, and diffusion MRI measurements in individuals with diabetes and stage 3 CKD. METHODS: Fifty-four subjects (41 individuals with diabetes and stage 3 CKD and 13 healthy controls) participated in this study. Data with blood oxygenation level dependent (BOLD), arterial spin labeling perfusion and diffusion MRI were acquired using a 3T scanner. RESULTS: Renal cortical perfusion was reduced in CKD compared to the controls (109.54 ± 25.38 vs. 203.17 ± 27.47 mL/min/100 g; p < 0.001). Cortical apparent diffusion coefficient showed no significant reduction in CKD compared to controls (1,596.10 ± 196.64 vs. 1,668.72 ± 77.29 × 10-6 mm2/s; p = 0.45) but was significantly associated with perfusion. Cortical R2* values were modestly increased in CKD (20.76 ± 4.08 vs. 18.74 ± 2.37 s-1; p = 0.12). Within the CKD group, R2*_Medulla and R2*_Kidney were moderately and negatively associated with estimated glomerular filtration rate. There was a significant association between cortical perfusion and medullary response to furosemide with annual loss of renal function, used as an estimate of CKD progression. CONCLUSIONS: Subjects with a moderate degree of CKD had significantly lower renal perfusion. Diffusion and BOLD MRI showed more modest differences between the groups. Individuals with progressive CKD had lower perfusion and response to furosemide.
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Taxa de Filtração Glomerular/fisiologia , Córtex Renal/irrigação sanguínea , Túbulos Renais/fisiopatologia , Insuficiência Renal Crônica/fisiopatologia , Idoso , Hipóxia Celular , Imagem de Difusão por Ressonância Magnética , Progressão da Doença , Feminino , Furosemida/administração & dosagem , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Córtex Renal/diagnóstico por imagem , Túbulos Renais/diagnóstico por imagem , Túbulos Renais/efeitos dos fármacos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Oxigênio/sangue , Consumo de Oxigênio/fisiologia , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/diagnóstico por imagem , Insuficiência Renal Crônica/tratamento farmacológicoRESUMO
BACKGROUND: Identification of patients with progressive chronic kidney disease (CKD) and those likely to respond to candidate therapeutics is urgently needed. Functional MRI measurements have shown promise. However, knowledge about the consistency of the measurements is essential to conduct longitudinal studies. PURPOSE/HYPOTHESIS: To investigate the consistency of repeated functional MRI measurements in healthy subjects. STUDY TYPE: Prospective, longitudinal study. SUBJECTS: Seventeen healthy subjects were examined on two different occasions, 18 months apart. FIELD STRENGTH/SEQUENCE: Multiple gradient-recalled-echo, 2D navigator-gated flow-sensitive alternating inversion recovery True-FISP and spin-echo planar diffusion-weighted sequences were used on a 3T scanner. Images were acquired on two different scanner configurations. ASSESSMENT: Blood oxygenation level-dependent (BOLD) R2*, arterial spin labeling (ASL) perfusion-derived blood flow (BF) and apparent diffusion coefficient (ADC) maps were analyzed using a custom image processing toolbox. Regions of interest (ROIs) were placed on renal cortex, medulla, and whole kidney. Multiple researchers were involved in defining the ROIs. STATISTICAL TESTS: Intra- and intersubject coefficients of variation (CV) and Bland-Altman plots were used to measure consistency and evaluate bias in the measurements. A nonparametric Wilcoxon test was used to compare differences between two timepoints. RESULTS: The intrasubject CV for R2* and ADC were 6.8% and 5.3% with small (-3.8 and 5.3%) bias, respectively, comparing baseline and 18-month data. Intrasubject CV for renal cortex BF was higher (18.7%) compared to R2* and ADC, but comparable to prior literature values over shorter durations. It also exhibited a larger bias (-15.4%) between two timepoints and significantly lower values (P = 0.022) at 18-month data. DATA CONCLUSION: All three MRI parameters over 18 months, even with a scanner upgrade and involving multiple observers, showed good consistency. These results are useful for the interpretation of longitudinal data and support the use of these methods to monitor progression in patients with CKD. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 1 J. MAGN. RESON. IMAGING 2018;48:514-521.
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Testes de Função Renal , Rim/diagnóstico por imagem , Imageamento por Ressonância Magnética , Adulto , Idoso , Índice de Massa Corporal , Progressão da Doença , Taxa de Filtração Glomerular , Voluntários Saudáveis , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estudos Prospectivos , Circulação Renal , Reprodutibilidade dos Testes , Marcadores de SpinRESUMO
The drift velocity for holes is strongly influenced by the electric field in the p-type hole injection layer for III-nitride based deep ultraviolet light-emitting diodes (DUV LEDs). In this work, we propose an electric-field reservoir (EFR) consisting of a p-AlxGa1-xN/p-GaN architecture to facilitate the hole injection and improve the internal quantum efficiency (IQE). The p-AlxGa1-xN layer in the EFR can well reserve the electric field that can moderately adjust the drift velocity and the kinetic energy for holes. As a result, we are able to enhance the thermionic emission for holes to cross over the p-EBL with a high Al composition provided that the composition in the p-AlxGa1-xN layer is properly optimized to avoid a complete hole depletion therein.
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In this work, III-nitride based â¼370 nm UVA light-emitting diodes (LEDs) grown on Si substrates are demonstrated. We also reveal the impact of the AlN composition in the AlGaN quantum barrier on the carrier injection for the studied LEDs. We find that, by properly increasing the AlN composition, both the electron and hole concentrations in the multiple quantum wells (MQWs) are enhanced. We attribute the increased electron concentration to the better electron confinement within the MQW region when increasing the AlN composition for the AlGaN barrier. The improved hole concentration in the MQW region is ascribed to the reduced hole blocking effect by the p-type electron blocking layer (p-EBL). This is enabled by the reduced density of the polarization-induced positive charges at the AlGaN last quantum barrier (LB)/p-EBL interface, which correspondingly suppresses the hole depletion at the AlGaN LB/p-EBL interface and decreases the valence band barrier height for the p-EBL. As a result, the optical power is improved.
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Silicon nanowires (SiNWs) are appealing building blocks in various applications, including photovoltaics, photonics, and sensors. Fabricating SiNW arrays with diameters <100 nm remains challenging through conventional top-down approaches. In this work, chemical etching and thermal oxidation are combined to fabricate vertically aligned, sub-20 nm SiNW arrays. Defect-free SiNWs with diameters between 95 and 200 nm are first fabricated by nanosphere (NS) lithography and chemical etching. The key aspects for defect-free SiNW fabrication are identified as: (1) achieving a high etching selectivity during NS size reduction; (2) retaining the circular NS shape with smooth sidewalls; and (3) using a directional metal deposition technique. SiNWs with identical spacing but variable diameters are demonstrated by changing the reactive ion etching power. The diameter of the SiNWs is reduced by thermal oxidation, where self-limiting oxidation is encountered after oxidizing the SiNWs at 950 °C for 1 h. A second oxidation is performed to achieve vertically aligned, sub-20 nm SiNW arrays. Si/SiO2 core/shell NWs are obtained before removing the oxidized shell. HRTEM imaging shows that the SiNWs have excellent crystallinity.
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The aim of the present work was to determine maternal and fetal outcomes of intrahepatic cholestasis of pregnancy (ICP) in twin pregnancies. All twin pregnancies delivered above 28 gestational weeks in West China Second University Hospital from January 2013 to May 2015 were included. Data on maternal demographics and obstetric complications together with fetal outcomes were collected. The risk of adverse maternal and fetal outcomes were determined in relation to ICP by crude odds ratios (OR) and adjusted ORs (aOR) with 95% confidence intervals (CI). Subgroup analysis concentrated on the effect of assisted reproductive technology (ART), ICP severity, and onset time. A total of 1,472 twin pregnancies were included, of which 362 were cholestasis patients and 677 were conceived by ART. Higher rates of preeclampsia (aOR 1.96; 95% CI 1.35, 2.85), meconium-stained amniotic fluid (aOR 3.10; 95% CI 2.10, 4.61), and preterm deliveries (aOR 3.20; 95% CI 2.35, 4.37) were observed in ICP patients. Subgroup analysis revealed higher incidences of adverse outcomes in severe and early onset ICP groups. In conclusion, adverse maternal and fetal outcomes were strongly associated with ICP in twin patients. Active management and close antenatal monitoring are needed, especially in the early onset and severe groups.