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1.
Ren Fail ; 46(2): 2371059, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38946402

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have been shown to play critical roles in the initiation and progression of chronic glomerulonephritis (CGN), while their role from mesangial cells in contributing to the pathogenesis of CGN is rarely understood. Our study aims to explore the potential functions of mesangial cell-derived circRNAs using RNA sequencing (RNA-seq) and bioinformatics analysis. METHODS: Mouse mesangial cells (MMCs) were stimulated by lipopolysaccharide (LPS) to establish an in vitro model of CGN. Pro-inflammatory cytokines and cell cycle stages were detected by Enzyme-linked immunosorbent assay (ELISA) and Flow Cytometry experiment, respectively. Subsequently, differentially expressed circRNAs (DE-circRNAs) were identified by RNA-seq. GEO microarrays were used to identify differentially expressed mRNAs (DE-mRNAs) between CGN and healthy populations. Weighted co-expression network analysis (WGCNA) was utilized to explore clinically significant modules of CGN. CircRNA-associated CeRNA networks were constructed by bioinformatics analysis. The hub mRNAs from CeRNA network were identified using LASSO algorithms. Furthermore, utilizing protein-protein interaction (PPI), gene ontology (GO), pathway enrichment (KEGG), and GSEA analyses to explore the potential biological function of target genes from CeRNA network. In addition, we investigated the relationships between immune cells and hub mRNAs from CeRNA network using CIBERSORT. RESULTS: The expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α was drastically increased in LPS-induced MMCs. The number of cells decreased significantly in the G1 phase but increased significantly in the S/G2 phase. A total of 6 DE-mRNAs were determined by RNA-seq, including 4 up-regulated circRNAs and 2 down-regulated circRNAs. WGCNA analysis identified 1747 DE-mRNAs of the turquoise module from CGN people in the GEO database. Then, the CeRNA networks, including 6 circRNAs, 38 miRNAs, and 80 mRNAs, were successfully constructed. The results of GO and KEGG analyses revealed that the target mRNAs were mainly enriched in immune, infection, and inflammation-related pathways. Furthermore, three hub mRNAs (BOC, MLST8, and HMGCS2) from the CeRNA network were screened using LASSO algorithms. GSEA analysis revealed that hub mRNAs were implicated in a great deal of immune system responses and inflammatory pathways, including IL-5 production, MAPK signaling pathway, and JAK-STAT signaling pathway. Moreover, according to an evaluation of immune infiltration, hub mRNAs have statistical correlations with neutrophils, plasma cells, monocytes, and follicular helper T cells. CONCLUSIONS: Our findings provide fundamental and novel insights for further investigations into the role of mesangial cell-derived circRNAs in CGN pathogenesis.


Assuntos
Biologia Computacional , Glomerulonefrite , Células Mesangiais , RNA Circular , RNA Circular/genética , RNA Circular/metabolismo , Animais , Camundongos , Células Mesangiais/metabolismo , Glomerulonefrite/genética , Glomerulonefrite/metabolismo , Análise de Sequência de RNA , Redes Reguladoras de Genes , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Mapas de Interação de Proteínas/genética , Doença Crônica , Citocinas/metabolismo , Lipopolissacarídeos/farmacologia , Perfilação da Expressão Gênica , Modelos Animais de Doenças
2.
Lupus ; 32(2): 239-251, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36480924

RESUMO

OBJECTIVE: Despite widespread recognition, the mechanisms underlying the relationship between systemic lupus erythematosus (SLE) and atherosclerosis (AS) are still unclear. Our study aimed to explore the shared genetic signature and molecular mechanisms of SLE and AS using a bioinformatics approach. METHODS: Gene expression profiles of GSE50772 (contains peripheral blood mononuclear cells from 61 SLE patients and 20 normal samples) and GSE100927 (contains 69 AS plaque tissue samples and 35 control samples) were downloaded from the Gene Expression Database (GEO) before the differentially expressed genes were obtained using the "limma" package in R. The differential genes were then subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the DAVID online platform to annotate their functions. The intersection targets of PPI and WGCNA were used as key shared genes for SLE and AS with their diagnostic value as shared genes being verified through ROC curves. Finally, Cytoscape 3.7.2 software was used to construct a miRNA-mRNA network map associated with the shared genes. RESULTS: A total of 246 DEGs were identified, including 189 upregulated genes and 57 downregulated genes, which were mainly enriched in signaling pathways such as TNF signaling pathway, IL-17 signaling pathway, and NF-kB signaling pathway. The molecular basis for the relationship between SLE and AS may be the aforementioned signaling pathways. Following ROC curve validation, the intersection of PPI and WGCNA, as well as AQP9, CCR1, CD83, CXCL1, and FCGR2A, resulted in the identification of 15 shared genes. CONCLUSION: The study provided a new perspective on the common molecular mechanisms between SLE and AS, and the key genes and pathways that were identified as being part of these pathways may offer fresh perspectives and suggestions for further experimental research.


Assuntos
Aterosclerose , Lúpus Eritematoso Sistêmico , MicroRNAs , Humanos , Leucócitos Mononucleares , Lúpus Eritematoso Sistêmico/genética , Transcriptoma , Aterosclerose/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica
3.
Geriatr Nurs ; 52: 115-120, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37290216

RESUMO

There is limited evidence on the diagnostic accuracy of the FRAIL scale in community-dwelling older adults with diabetes. This study aimed to validate the diagnostic accuracy and determine the optimal cutoff point of the FRAIL scale in community-dwelling older adults with diabetes using the Fried Frailty Phenotype as the reference standard. A total of 489 community-dwelling older adults with diabetes aged 60 or above were recruited in this cross-sectional study. The FRAIL scale showed good diagnostic accuracy for frailty screening. The optimal cutoff point for frailty screening in older adults with diabetes was 2. The agreement between the FRAIL scale and the Fried Frailty Phenotype was substantial. The FRAIL scale classified more participants as frail (29.24%) than the Fried Frailty Phenotype (22.09%). These findings provide evidence that the FRAIL scale is a valid tool that can be applied to community-dwelling older adults with diabetes.


Assuntos
Diabetes Mellitus , Fragilidade , Idoso , Humanos , Fragilidade/diagnóstico , Idoso Fragilizado , Vida Independente , Estudos Transversais , Avaliação Geriátrica , Diabetes Mellitus/diagnóstico
4.
Angew Chem Int Ed Engl ; 62(6): e202215741, 2023 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-36478512

RESUMO

A gold nanocluster Au17 Cd2 (PNP)2 (SR)12 (PNP=2,6-bis(diphenylphosphinomethyl)pyridine, SR=4-MeOPhS) consisting of an icosahedral Au13 kernel, two Au2 CdS6 staple motifs, and two PNP pincer ligands has been designed, synthesized and well characterized. This cadmium and PNP pincer ligand co-modified gold nanocluster showed high catalytic efficiency in the KA2 reaction, featuring high TON, mild reaction conditions, broad substrate scope as well as catalyst recyclability. Comparison of the catalytic performance between Au17 Cd2 (PNP)2 (SR)12 and the structurally similar single cadmium (or PNP) modified gold nanoclusters demonstrates that the co-existence of the cadmium and PNP on the surface is crucial for the high catalytic activity of the gold nanocluster. This work would be enlightening for developing efficient catalysts for cascade reactions and discovering the catalytic potential of metal nanoclusters in organic transformations.

5.
J Opt Soc Am A Opt Image Sci Vis ; 39(12): 2186-2192, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36520733

RESUMO

In this paper, the rigorous coupled-wave analysis (RCWA) is extended for general multi-layer deformable gratings with arbitrary numbers of layers, surface profiles, layer offsets, and materials. The contribution from the offset between grating layers and/or due to the movement of the deformable grating layer is included in the expansion of the relative permittivity by the Fourier series, enabling the calculations of deformable gratings commonly used in many optical-based displacement sensing devices. The accuracy and efficiency of the extended RCWA are verified by a number of grating models. It is found that the numerical results are in excellent agreement with those from the finite element method, while the RCWA method costs only ∼1/10 in computation time when compared to its counterpart. Our approach can be used for fast calculation and optimization of multi-layer deformable gratings for optical displacement sensing applications.

6.
J Clin Lab Anal ; 36(2): e24200, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34957609

RESUMO

BACKGROUND: The roles of PD-1+ CXCR5+ follicular helper CD8+ T cell were reported in different disease conditions, but their roles in transplantation are unclear. In this study, the association between PD-1+ CXCR5+ follicular helper CD8+ T cell and renal allograft dysfunction in kidney transplant recipients (KTRs) was investigated. METHODS: 82 KTRs were enrolled in this study. 45 KTRs were included in the chronic allograft dysfunction (CAD) group, and 37 KTRs were included in the stable recipients group. Among the CAD group, 12 cases of antibody-mediated rejection (ABMR) and 4 cases of T cell-mediated rejection (TCMR) were diagnosed by biopsy. The percentage of CXCR5+ CD8+ T cells and the co-expression of signal transducers and activators of transcription 4 (STAT4), STAT5, and PD-1 in peripheral blood were determined by flow cytometry. RESULTS: The expression of CXCR5 on CD3+ CD8+ T cells and the percentage of STAT5+ CXCR5+ cells in the CD3+ CD8+ T-cell population were significantly lower in the CAD group (p < 0.05), while the expression of PD-1+ CXCR5+ CD8+ T cells was significantly higher (p < 0.05). Through logistic regression analysis, we concluded that the percentage of PD-1+ CXCR5+ CD8+ T cells was an independent risk factor for renal dysfunction. Grouping by pathological type, PD-1+ CXCR5+ CD8+ T cells showed relatively good diagnostic efficacy for ABMR by ROC analysis. CONCLUSIONS: Our results suggested that PD-1+ CXCR5+ CD8+ T cells were a promising biomarker for distinguishing renal allograft dysfunction and different allograft pathological types. Also, our findings may provide new ways of identifying and treating allograft rejection.


Assuntos
Transplante de Rim , Rim/fisiopatologia , Receptor de Morte Celular Programada 1/metabolismo , Células T Auxiliares Foliculares/fisiologia , Adulto , Aloenxertos , Biomarcadores , Linfócitos T CD8-Positivos/fisiologia , Feminino , Rejeição de Enxerto/diagnóstico , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Receptor de Morte Celular Programada 1/fisiologia , Curva ROC , Receptores CXCR5/metabolismo , Células T Auxiliares Foliculares/metabolismo
7.
Opt Lett ; 46(16): 3945-3948, 2021 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-34388781

RESUMO

An in-plane displacement sensor based on an asymmetric extrinsic fiber Fabry-Perot interferometer (EFPI) is proposed and demonstrated. The asymmetric EFPI composed of a step-shaped external reflector and a cleaved fiber end face can be equivalent to two parallel FPIs with slightly different cavity lengths. By calculating the peak intensity difference of the two FPIs, the in-plane displacement can be demodulated with enhanced sensitivity and suppressed common mode noise. Both theoretical analyses and experimental results show that the sensitivity and the linear range of the in-plane displacement sensor are dependent on the cavity length. A displacement resolution of 5 nm and a linear range of ±7µm under the cavity length of 250 µm are achieved in the experiment. The proposed in-plane displacement sensor with a nanometric resolution and compact size can be widely used in the fields of metrology, accelerometers, and semiconductor manufacture.

8.
Anal Biochem ; 620: 114138, 2021 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-33639112

RESUMO

A fluorescent sensor based on coumarin-maleimide conjugate was developed for efficient discrimination of Cys from Hcy and GSH in both organic and aqueous solution. Addition of Cys to the non-fluorescent sensor solution in DMF induced bright blue fluorescence and enhanced the fluorescence intensity by 320-fold while other amino acids and biothiols (Gly, Hcy, GSH, Glu, Val, Tyr, Arg, Trp, Lys, His, Leu, Phe, Asp and Met) did not bring about remarked change. The sensor responds to Cys extremely rapidly. If Cys was added to the sensor solution, the fluorescence intensity increased by 170-fold immediately and attained the maximum value in 5 min. A linear relationship was observed between Cys concentration within 2-20 µM and the fluorescence intensity of the sensor solution. The detection limit of the sensor toward Cys is as low as 4.7 nM. The sensor is also effective for specific detection of Cys in aqueous (DMF/H2O = 9:1, v/v) solution. Practical application of the sensor to drug analysis and bioimaging of living Hela cells has been verified. Possible sensing mechanism of the sensor toward Cys has been proposed.


Assuntos
Cumarínicos/química , Cisteína/análise , Corantes Fluorescentes/química , Maleimidas/química , Imagem Óptica , Corantes Fluorescentes/síntese química , Células HeLa , Humanos , Estrutura Molecular
9.
Cell Commun Signal ; 18(1): 66, 2020 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-32312253

RESUMO

BACKGROUND: Anti-nerve growth factor (NGF) monoclonal antibodies (anti-NGF mAbs) have been reported to significantly attenuate pain, but the mechanism involved has not been fully elucidated, and the serious adverse events associated with mAbs seriously limit their clinical use. This study further investigated the mechanism by which peripheral NGF is involved in neuropathic pain and found safe, natural compounds that target NGF to attenuate neuropathic pain. METHODS: Nociception was assessed by the Von Frey hair and Hargreaves' methods. Western-blotting, qPCR and immunofluorescence were used to detect the cell signaling pathway. RAW264.7 macrophages and RSC96 Schwann cells were cultured for in vitro evaluation. RESULTS: Intraplantar administration of anti-NGF mAbs suppressed the expression of phosphorylated transforming growth factor-ß-activated kinase 1 (TAK1) in the dorsal root ganglion (DRG) and sciatic nerve. Intraplantar administration of a TAK1 inhibitor attenuated CCI-induced neuropathic pain and suppressed the expression of phosphorylated mitogen-activated protein kinases (MAPKs) in the DRG and sciatic nerve. Perisciatic nerve administration of levo-corydalmine (l-CDL) on the operated side obviously attenuated CCI-induced neuropathic pain and suppressed the expression of mNGF and proNGF. In addition, l-CDL-induced antinociception was reversed by intraplantar administration of NGF. Further results indicated that l-CDL-induced suppression of phosphorylated TAK1, MAPKs, and p65 and expression of the proinflammatory cytokines TNF-α and IL-1ß in the DRG and sciatic nerve were all abolished by NGF. In addition, in vitro experiments indicated that l-CDL suppressed the secretion of NGF and proNGF in RAW264.7 macrophages and RSC96 Schwann cells, which was abolished by AP-1 and CREB agonists, respectively. CONCLUSIONS: This study showed NGF inhibition suppressed TAK1 in the periphery to attenuate CCI-induced neuropathic pain through inhibition of downstream MAPK and p65 signaling. The natural compound l-CDL inhibited NGF secretion by macrophages and Schwann cells and downstream TAK1-MAPK/NF-κB signaling in the periphery to attenuate CCI-induced neuropathic pain. Video abstract Proposed mechanisms underlying the effect of l-CDL in periphery of CCI rats. In CCI rats, macropahages and Schwann cells could secret NGF to act on the receptors in the periphery to activate TAK1-MAPK/NF-κB axis and promote the release of proinflammatory cytokines, including TNF-α and IL-1ß to promote neuropathic pain. l-CDL decreased the secretion of NGF through inhibiting AP-1 and CREB respectively in RAW264.7 and RSC96 Schwann cells to attenuate CCI-induced neuropathic pain by inhibiting the TAK1-p38 MAPK/NF-κB signaling pathway.


Assuntos
Anticorpos Monoclonais , MAP Quinase Quinase Quinases , Fator de Crescimento Neural , Neuralgia/tratamento farmacológico , Extratos Vegetais , Animais , Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Corydalis/química , MAP Quinase Quinase Quinases/antagonistas & inibidores , MAP Quinase Quinase Quinases/metabolismo , Camundongos , Fator de Crescimento Neural/antagonistas & inibidores , Fator de Crescimento Neural/imunologia , Fator de Crescimento Neural/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Células RAW 264.7 , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
10.
J Surg Res ; 251: 329-339, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32208196

RESUMO

BACKGROUND: Acral lentiginous melanoma (ALM) is one of the four major subtypes in cutaneous malignant melanoma (CMM). We aimed to study the incidence and survival of ALM in the United States in recent 10 y and compare the survival between ALM and nonacral CMM. In the meantime, racial disparity and prognostic factors associated with survival were investigated. METHODS: All the cases of ALM registered in the Surveillance, Epidemiology, and End Results registry from 2006 to 2015 were retrieved, including non-Hispanic whites (NHW), black Americans (blacks), Asian/Pacific Islanders, and Hispanic whites. Age-adjusted incidence was calculated. Clinicopathologic data, including age, gender, race, geographic location, Breslow thickness, ulceration, pathologic staging, sentinel lymph node status, and surgical approach, were collected and analyzed. Melanoma-specific survival (MSS) was analyzed in patients with ALM and CMM. The Kaplan-Meier method was used to estimate the influence of clinicopathologic data on ALM MSS. Only cases with complete staging and active follow-up were included in prognostic factor analysis. RESULTS: A total of 1724 ALM and 87,442 nonacral CMM patients were included in the study. For ALM patients, the age-adjusted incidence rate was 2.0 per million person-years. The proportion of ALM among all melanoma subtypes was greatest in blacks (32.6%). The 5-y MSS rates of ALM were lower than CMM overall (80.6% versus 93.0%, P < 0.001, respectively). When controlled by stage, the difference was significant in patients diagnosed at stages I and III. ALM 5-y MSS rates were highest (84.3%) in NHW, intermediate in Asian/Pacific Islanders (76.6%), Hispanic white (72.0%), and lowest in blacks (66.9%). Blacks were elderly, male predominant, located in East and Middle American, and had thicker, more ulcerated, advanced disease as compared with NHWs. When controlled by stage, survival difference was significant between NHWs and blacks in stage I (P = 0.004) and stage III (P = 0.005) patients. Gender, race, sentinel lymph node status, and pathologic stage were identified as independent risk factors in multivariate analysis. CONCLUSIONS: The incidence of ALM has been steady in recent 10 y and more prevalent in aged people. ALM is associated with a worse prognosis than CMM. Black Americans have the worst prognosis, and survival difference is significant between NHW and blacks.


Assuntos
Melanoma/mortalidade , Neoplasias Cutâneas/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Incidência , Masculino , Melanoma/etnologia , Melanoma/patologia , Pessoa de Meia-Idade , Programa de SEER , Pele/patologia , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/patologia , Estados Unidos/epidemiologia , Adulto Jovem , Melanoma Maligno Cutâneo
11.
Med Sci Monit ; 26: e919454, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32009129

RESUMO

BACKGROUND Non-small-cell lung cancer (NSCLC) is predominant and has low 5-year relative survival rate. Therefore, the mechanisms of NSCLC tumorigenesis must be comprehensively elucidated. MicroRNA-323-3p (miR-323-3p) has been widely explored and found to exert functions in tumorigenesis of several cancer types. However, the expression pattern and biological function of miR-323-3p and the molecular mechanism underlying NSCLC development and progression remain unclear. MATERIAL AND METHODS Quantitative reverse-transcription polymerase chain reaction was used to detect the expression of miR-323-3p and TMEFF2 in NSCLC cell lines (A549, NCI-H3255, and H1299) and normal cell line (BEAS-2B). Methylthiazolyl tetrazolium, colony formation, and flow cytometry assays were performed to evaluate the effects of miR-323-3p and TMEFF2 on cell proliferation. Transwell assay was conducted to determine the effects of TMEFF2 on cell migration and invasion. Dual-luciferase reporter assay was used to verify whether TMEFF2 is a target of miR-323-3p. Western blot analysis was performed to analyze protein expression. RESULTS The expression of miR-323-3p increased in the 3 NSCLC cell lines (A549, NCI-H3255, and H1299). miR-323-3p regulated cellular progression by directly suppressing TMEFF2 expression and indirectly prohibited the activation of AKT and ERK pathways in NSCLC. CONCLUSIONS Overall, miR-323-3p was considered a lung cancer oncogene and could be a valuable target for NSCLC therapy.


Assuntos
Apoptose , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células A549 , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Movimento Celular/genética , Proliferação de Células/genética , Regulação para Baixo/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Invasividade Neoplásica , Regulação para Cima/genética
12.
Vascular ; 28(4): 450-456, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32122275

RESUMO

OBJECTIVE: Pancreatic cancer is a kind of high malignant tumor with a poor prognosis. The aim is to determine whether the dilated bile duct can be used to reconstruct the vessels. METHODS: An animal model of jugular vein and portal vein reconstruction was established using the bile duct. A total of 20 landrace pigs were selected to undergo jugular vein reconstruction or portal vein reconstruction using the bile duct as a patch or bridge. The patency was evaluated by color Doppler, the reconstructed segments were removed and examined macroscopically and histologically at specified intervals, and the results were compared with synthetic vessels (IMPRA straight, 10s03-19). RESULTS: The lumen was patent, although a low level thrombosis was observed when jugular or portal vein patching was used. For bridging, stenosis of the lumen was observed, and necrosis appeared when the bile duct was used for bridging, indicating that it is feasible to reconstruct the jugular vein and portal vein with a bile duct patch. However, the bridge was not feasible possibly due to loss of blood supply, and consequent necrosis and fibrosis. CONCLUSION: The bile duct is technically feasible, but the outcomes are unsatisfactory.


Assuntos
Bioprótese , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Ducto Colédoco/transplante , Veias Jugulares/cirurgia , Pâncreas/cirurgia , Veia Porta/cirurgia , Animais , Implante de Prótese Vascular/efeitos adversos , Ducto Colédoco/patologia , Ducto Colédoco/fisiopatologia , Estudos de Viabilidade , Feminino , Fibrose , Sobrevivência de Enxerto , Veias Jugulares/patologia , Veias Jugulares/fisiopatologia , Masculino , Modelos Animais , Necrose , Veia Porta/patologia , Veia Porta/fisiopatologia , Sus scrofa , Fatores de Tempo , Grau de Desobstrução Vascular
13.
Sensors (Basel) ; 20(4)2020 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-32098077

RESUMO

Capacitive MEMS accelerometers with area-variable periodic-electrode displacementtransducers found wide applications in disaster monitoring, resource exploration and inertialnavigation. The bonding-induced warpage, due to the difference in the coefficients of thermalexpansion of the bonded slices, has a negative influence on the precise control of the interelectrodespacing that is essential to the sensitivity of accelerometers. In this work, we propose the theory,simulation and experiment of a method that can alleviate both the stress and the warpage byapplying different bonding temperature on the bonded slices. A quasi-zero warpage is achievedexperimentally, proving the feasibility of the method. As a benefit of the flat surface, the spacing ofthe capacitive displacement transducer can be precisely controlled, improving the self-noise of theaccelerometer to 6 ng/√Hz @0.07 Hz, which is about two times lower than that of the accelerometerusing a uniform-temperature bonding process.

14.
Int J Cancer ; 144(9): 2227-2238, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30374974

RESUMO

Vasculogenic mimicry (VM) is a special vascular pattern in malignant tumors, which is composed of highly aggressive tumor cells. This tumor cell-mediated blood supply pattern is closely associated with a poor prognosis in cancer patients. The interaction of axon guidance factor Sema4D and its high affinity receptor plexinB1 could activate small GTPase RhoA and its downstream ROCKs; this process has an active role in the migration of endothelial cells and tumor angiogenesis. Here, we have begun to uncover the role of this pathway in VM formation in non-small cell lung cancer (NSCLC). First, we confirmed this special form of vasculature in NSCLC tissues and found the existence of VM channels in tumor tissues was correlated with Sema4D expression. Further, we found that inhibition of Sema4D in the human NSCLC cells H1299 and HCC827 reduces VM formation both in vitro and in vivo. Moreover, we demonstrated that downregulating the expression of plexinB1 by siRNA expressing vectors and inhibiting the RhoA/ROCK signaling pathway using fasudil can reduce VM formation of H1299 and HCC827 cells. Finally, we found that suppression of Sema4D leads to less stress fibers and depleted the motility of H1299 and HCC827 cells. Collectively, our study implicates Sema4D plays an important role in the process of VM formation in NSCLC through activating the RhoA/ROCK pathway and regulating tumor cell plasticity and migration. Modulation of the Sema4D/plexinB1 and downstream RhoA/ROCK pathway may prevent the tumor blood supply through the VM pattern, which may eventually halt growth and metastasis of NSCLC.


Assuntos
Antígenos CD/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Neovascularização Patológica/patologia , Proteínas do Tecido Nervoso/metabolismo , Receptores de Superfície Celular/metabolismo , Semaforinas/metabolismo , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Células A549 , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Células Endoteliais/fisiologia , Ativação Enzimática , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Proteínas do Tecido Nervoso/genética , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , RNA Interferente Pequeno/genética , Receptores de Superfície Celular/genética , Semaforinas/antagonistas & inibidores , Quinases Associadas a rho/metabolismo , Proteína rhoA de Ligação ao GTP/metabolismo
15.
Clin Sci (Lond) ; 133(7): 905-917, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30957778

RESUMO

Gut microbiota alterations manifest as intermittent hypoxia and fragmented sleep, thereby mimicking obstructive sleep apnea-hypopnea syndrome (OSAHS). Here, we sought to perform the first direct survey of gut microbial dysbiosis over a range of apnea-hypopnea indices (AHI) among patients with OSAHS. We obtained fecal samples from 93 patients with OSAHS [5 < AHI ≤ 15 (n=40), 15 < AHI ≤ 30 (n=23), and AHI ≥ 30 (n=30)] and 20 controls (AHI ≤ 5) and determined the microbiome composition via 16S rRNA pyrosequencing and bioinformatics analysis of variable regions 3-4. We measured fasting levels of homocysteine (HCY), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α). Results revealed gut microbial dysbiosis in several patients with varying severities of OSAHS, reliably separating them from controls with a receiver operating characteristic-area under the curve (ROC-AUC) of 0.789. Functional analysis in the microbiomes of patients revealed alterations; additionally, decreased in short-chain fatty acid (SCFA)-producing bacteria and increased pathogens, accompanied by elevated levels of IL-6. Lactobacillus levels correlated with HCY levels. Stratification analysis revealed that the Ruminococcus enterotype posed the highest risk for patients with OSAHS. Our results show that the presence of an altered microbiome is associated with HCY among OSAHS patients. These changes in the levels of SCFA affect the levels of pathogens that play a pathophysiological role in OSAHS and related metabolic comorbidities.


Assuntos
Bactérias/isolamento & purificação , Microbioma Gastrointestinal , Intestinos/microbiologia , Doenças Metabólicas/microbiologia , Apneia Obstrutiva do Sono/microbiologia , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Comorbidade , Disbiose , Fezes/microbiologia , Feminino , Homocisteína/sangue , Interações Hospedeiro-Patógeno , Humanos , Masculino , Doenças Metabólicas/sangue , Doenças Metabólicas/diagnóstico , Doenças Metabólicas/epidemiologia , Pessoa de Meia-Idade , Apneia Obstrutiva do Sono/sangue , Apneia Obstrutiva do Sono/diagnóstico , Apneia Obstrutiva do Sono/epidemiologia
16.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 904-909, 2019 Sep.
Artigo em Zh | MEDLINE | ID: mdl-31506151

RESUMO

OBJECTIVE: To investigate the effect of augmented renal clearance (ARC) on plasma concentration of vancomycin, bacteriological outcome, and clinical outcome in children with methicillin-resistant Staphylococcus aureus (MRSA) infection treated by vancomycin. METHODS: A retrospective analysis was performed for the clinical data of 60 critically ill children who were treated with vancomycin due to MRSA infection from January 2013 to July 2017 and underwent plasma concentration monitoring. According to estimated glomerular filtration rate, these children were divided into an ARC group with 19 children and a normal renal function group with 41 children. The two groups were compared in terms of the use of vancomycin, plasma concentration of vancomycin, and treatment outcome. RESULTS: The children in the ARC group had an age of 1-12 years, and the ARC group had significantly higher body weight and body surface area than the normal renal function group (P<0.05). Compared with the normal renal function group, the ARC group had a significantly lower initial trough concentration of vancomycin and a significantly lower proportion of children who achieved the effective trough concentration of vancomycin (10-20 mg/L) (P<0.05). There were no significant differences in bacteriological outcome and clinical outcome between the two groups (P>0.05), but the ARC group had significantly longer length of stay in the pediatric intensive care unit (PICU) and length of hospital stay than the normal renal function group (P<0.05). CONCLUSIONS: ARC can significantly reduce the trough concentration of vancomycin and prolong the length of PICU stay and the length of hospital stay in children with MRSA infection. Idividualized medication should be administered to children with ARC.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Vancomicina/uso terapêutico , Antibacterianos , Criança , Pré-Escolar , Humanos , Lactente , Meticilina , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Resultado do Tratamento
17.
J Cell Biochem ; 119(8): 6391-6397, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29091305

RESUMO

Cancer susceptibility candidate 2 (CASC2), a recently discovered long non-coding RNA (lncRNA), was confirmed to play numerous roles in several human cancers. However, the involvement and concrete mechanism of CASC2 in hepatocellular carcinoma (HCC) still need to be further elucidated. The relative expressions of CASC2 and miR-24-3p in HCC tissue and cell lines were determined by quantitative real-time PCR (qRT-PCR). The effects of CASC2 and miR-24-3p on HCC cells were further assessed via cell viability and apoptosis. In vivo tumorigenesis assay was performed to verify the inhibition effect of CASC2 on the tumor growth and further clarify the important role of miR-24-3p in this mechanism. Compared with the paired normal tissues, the relative expression of CASC2 significantly reduced in the HCC tissues, while miR-24-3p as determined by qRT-PCR obviously increased in the HCC tissues. This observation was also found in HCC cell lines. Meanwhile, the expression of CASC2 was negatively related to miR-24-3p expression in the HCC tissues (r = -0.804, P < 0.001). CASC2 could negatively regulate the expression of miR-24-3p in vitro. Moreover, CASC2 overexpression resulted in the growth inhibitory and apoptosis-inducing effects on HCC cells, but the up-regulation of miR-24-3p greatly eliminated the CASC2-induced effects. The tumorigenesis of HCC cells was restrained significantly by CASC2 overexpression as shown by decreased tumor volume and growth rate. However, miR-24-3p up-regulation rescued the inhibition of CASC2 on the tumor growth in tumor-bearing mice. LncRNA CASC2 inhibited the viability and induced the apoptosis of HCC cells through regulating miR-24-3p.


Assuntos
Apoptose , Carcinoma Hepatocelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/metabolismo , MicroRNAs/biossíntese , RNA Longo não Codificante/metabolismo , RNA Neoplásico/metabolismo , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Neoplásico/genética
18.
J Nanosci Nanotechnol ; 18(3): 1675-1681, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29448644

RESUMO

Metal ions (Cr, Ni, Co) doped titania (M-TiO2) coupled with the long after glow phosphor MgAl2O4:(Pr3+, Dy3+) particles were synthesized by the sol-gel method, with the best mass ratio of MgAl2O4:(Pr3+, Dy3+) to M-TiO2 as 4:6. MgAl2O4:(Pr3+, Dy3+)/M-TiO2 had the persistent methyl orange (MO) photocatalytic degradation ability and the photocatalytic degradation went on reacting more than 90 min in dark after turning off the light. MgAl2O4:(Pr3+, Dy3+) emitted the light as a light source in dark which was absorbed by M-TiO2. The differences of MgAl2O4:(Pr3+, Dy3+)/Cr-TiO2, MgAl2O4:(Pr3+, Dy3+)/Ni-TiO2 and MgAl2O4:(Pr3+, Dy3+)/Co-TiO2 might be attributed to the difference in the metal ions doping. The composite MgAl2O4:(Pr3+, Dy3+)/Cr-TiO2 revealed the highest ability of persistent photocatalytic degradation methyl orange. Different metal ions doping made the TiO2 with different band gap.

19.
Sensors (Basel) ; 18(4)2018 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-29670021

RESUMO

A method for automatic compensation of misalignment angles during matching the scale factors of two pairs of the accelerometers in developing the rotating accelerometer gravity gradient instrument (GGI) is proposed and demonstrated in this paper. The purpose of automatic scale factor matching of the four accelerometers in GGI is to suppress the common mode acceleration of the moving-based platforms. However, taking the full model equation of the accelerometer into consideration, the other two orthogonal axes which is the pendulous axis and the output axis, will also sense the common mode acceleration and reduce the suppression performance. The coefficients from the two axes to the output are δO and δP respectively, called the misalignment angles. The angle δO, coupling with the acceleration along the pendulous axis perpendicular to the rotational plane, will not be modulated by the rotation and gives little contribution to the scale factors matching. On the other hand, because of coupling with the acceleration along the centripetal direction in the rotating plane, the angle δP would produce a component with 90 degrees phase delay relative to the scale factor component. Hence, the δP component coincides exactly with the sensitive direction of the orthogonal accelerometers. To improve the common mode acceleration rejection, the misalignment angle δP is compensated by injecting a trimming current, which is proportional to the output of an orthogonal accelerometer, into the torque coil of the accelerometer during the scale factor matching. The experimental results show that the common linear acceleration suppression achieved three orders after the scale factors balance and five orders after the misalignment angles compensation, which is almost down to the noise level of the used accelerometers of 1~2 × 10−7 g/√Hz (1 g ≈ 9.8 m/s²).

20.
Sensors (Basel) ; 17(9)2017 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-28930176

RESUMO

Encoder-like micro area-changed capacitive transducers are advantageous in terms of their better linearity and larger dynamic range compared to gap-changed capacitive transducers. Such transducers have been widely applied in rectilinear and rotational position sensors, lab-on-a-chip applications and bio-sensors. However, a complete model accounting for both the parasitic capacitance and fringe effect in area-changed capacitive transducers has not yet been developed. This paper presents a complete model for this type of transducer applied to a high-resolution micro accelerometer that was verified by both simulations and experiments. A novel optimization method involving the insertion of photosensitive polyimide was used to reduce the parasitic capacitance, and the capacitor spacing was decreased to overcome the fringe effect. The sensitivity of the optimized transducer was approximately 46 pF/mm, which was nearly 40 times higher than that of our previous transducer. The displacement detection resolution was measured as 50 pm/√Hz at 0.1 Hz using a precise capacitance detection circuit. Then, the transducer was applied to a sandwich in-plane micro accelerometer, and the measured level of the accelerometer was approximately 30 ng/√Hz at 1Hz. The earthquake that occurred in Taiwan was also detected during a continuous gravity measurement.

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