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1.
Br J Cancer ; 130(3): 358-368, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38097742

RESUMO

BACKGROUND: This study aimed to investigate the underlying mechanisms of matricellular protein periostin (POSTN) on tumour-stroma crosstalk in the liver metastatic microenvironment of colorectal cancer (CRC). METHODS: Postn-knockout mice and hepatic Postn-overexpressing mice were used to investigate the functions of POSTN on the formation of fibrotic microenvironment and the tumour-stroma crosstalk in the liver metastatic microenvironment of CRC. Clinical samples and database were analyzed to show the correlation between POSTN expression and fibrotic features and TGF-ß signalling in metastatic livers of CRC. RESULTS: POSTN deficiency reduced hepatic stellate cell (HSC) activation and liver metastasis, whereas POSTN overexpression in the liver significantly augmented the formation of a fibrotic microenvironment to support the liver metastatic growth of CRC cells in mice. Moreover, HSC-derived POSTN promoted TGF-ß1 expression in CRC cells through the integrin/FAK/ERK/STAT3 pathway; conversely, tumour cell-derived TGF-ß1 induced POSTN expression in HSCs via the Smad pathway. POSTN levels correlated with fibrotic features and TGF-ß signalling in metastatic liver tissues of CRC patients. CONCLUSIONS: POSTN and TGF-ß1 cooperatively contribute to the tumour-stroma crosstalk by forming a supporting fibrotic microenvironment to promote liver metastasis of CRC cells via the POSTN/integrin/FAK/ERK/STAT3/TGF-ß axis in tumour cells and TGF-ß/Smad/POSTN signalling in activated HSCs.


Assuntos
Neoplasias Colorretais , Neoplasias Hepáticas , Animais , Humanos , Camundongos , Neoplasias Colorretais/patologia , Integrinas/metabolismo , Fígado/metabolismo , Neoplasias Hepáticas/patologia , Periostina , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , Microambiente Tumoral
2.
BMC Plant Biol ; 24(1): 263, 2024 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-38594616

RESUMO

BACKGROUND: In agricultural production, fungal diseases significantly impact the yield and quality of cotton (Gossypium spp.) with Verticillium wilt posing a particularly severe threat. RESULTS: This study is focused on investigating the effectiveness of endophytic microbial communities present in the seeds of disease-resistant cotton genotypes in the control of cotton Verticillium wilt. The technique of 16S ribosomal RNA (16S rRNA) amplicon sequencing identified a significant enrichment of the Bacillus genus in the resistant genotype Xinluzao 78, which differed from the endophytic bacterial community structure in the susceptible genotype Xinluzao 63. Specific enriched strains were isolated and screened from the seeds of Xinluzao 78 to further explore the biological functions of seed endophytes. A synthetic microbial community (SynCom) was constructed using the broken-rod model, and seeds of the susceptible genotype Xinluzao 63 in this community that had been soaked with the SynCom were found to significantly control the occurrence of Verticillium wilt and regulate the growth of cotton plants. Antibiotic screening techniques were used to preliminarily identify the colonization of strains in the community. These techniques revealed that the strains can colonize plant tissues and occupy ecological niches in cotton tissues through a priority effect, which prevents infection by pathogens. CONCLUSION: This study highlights the key role of seed endophytes in driving plant disease defense and provides a theoretical basis for the future application of SynComs in agriculture.


Assuntos
Microbiota , Verticillium , Verticillium/fisiologia , Gossypium/genética , Gossypium/microbiologia , RNA Ribossômico 16S/genética , Bactérias/genética , Sementes/genética , Doenças das Plantas/microbiologia , Resistência à Doença/genética
3.
Langmuir ; 40(16): 8654-8664, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38588599

RESUMO

Biofouling and bacterial infections are significant challenges in biomedical devices. In this study, a biocompatible dual-functional coating with antimicrobial and antifouling properties is developed by co-depositing the zwitterionic copolymer and silver nanoparticles via a dopamine-assisted strategy. Inspired by mussel adhesion, the coating exhibits substrate-independent adhesion as a result of the formation of irreversible covalent bonds. The zwitterionic copolymer in the dual coating plays a crucial role in improving surface wettability and reducing protein adsorption and platelet and bacterial adhesion, thereby improving its antifouling property significantly. The silver nanoparticles reduced by self-polymerized polydopamine without the addition of any chemical reductants can effectively improve the antimicrobial activity. Furthermore, as the zwitterion content in the zwitterion polymer increases, the antibacterial and antifouling properties of the coating can be further advanced. The simple and effective approach presented here provides a promising pathway for constructing potent antibacterial and antifouling surfaces, demonstrating great potential for clinical applications in implanted materials.

4.
Risk Anal ; 44(1): 40-53, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37038093

RESUMO

The prevention and control of infectious disease epidemic (IDE) is an important task for every country and region. Risk assessment is significant for the prevention and control of IDE. Fuzzy Bayesian networks (FBN) can capture complex causality and uncertainty. The study developed a novel FBN model, integrating grounded theory, interpretive structural model, and expert weight determination algorithm for the risk assessment of IDE. The algorithm is proposed by the authors for expert weighting in fuzzy environment. The proposed FBN model comprehensively takes into account the risk factors and the interaction among them, and quantifies the uncertainty of IDE risk assessment, so as to make the assessment results more reliable. Taking the epidemic situation of COVID-19 in Wuhan as a case, the application of the proposed model is illustrated. And sensitivity analysis is performed to identify the important risk factors of IDE. Moreover, the effectiveness of the model is checked by the three-criterion-based quantitative validation method including variation connection, consistent effect, and cumulative limitation. Results show that the probability of the outbreak of COVID-19 in Wuhan is as high as 82.26%, which is well-matched with the actual situation. "Information transfer mechanism," "coordination and cooperation among various personnel," "population flow," and "ability of quarantine" are key risk factors. The constructed model meets the above three criteria. The application potential and effectiveness of the developed FBN model are demonstrated. The study provides decision support for preventing and controlling IDE.


Assuntos
COVID-19 , Doenças Transmissíveis , Humanos , Teorema de Bayes , Lógica Fuzzy , COVID-19/epidemiologia , Medição de Risco/métodos , Fatores de Risco
5.
Anal Chem ; 95(15): 6203-6211, 2023 04 18.
Artigo em Inglês | MEDLINE | ID: mdl-37023366

RESUMO

Drug combinations are commonly used to treat various diseases to achieve synergistic therapeutic effects or to alleviate drug resistance. Nevertheless, some drug combinations might lead to adverse effects, and thus, it is crucial to explore the mechanisms of drug interactions before clinical treatment. Generally, drug interactions have been studied using nonclinical pharmacokinetics, toxicology, and pharmacology. Here, we propose a complementary strategy based on metabolomics, which we call interaction metabolite set enrichment analysis, or iMSEA, to decipher drug interactions. First, a digraph-based heterogeneous network model was constructed to model the biological metabolic network based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Second, treatment-specific influences on all detected metabolites were calculated and propagated across the whole network model. Third, pathway activity was defined and enriched to quantify the influence of each treatment on the predefined functional metabolite sets, i.e., metabolic pathways. Finally, drug interactions were identified by comparing the pathway activity enriched by the drug combination treatments and the single drug treatments. A data set consisting of hepatocellular carcinoma (HCC) cells that were treated with oxaliplatin (OXA) and/or vitamin C (VC) was used to illustrate the effectiveness of the iMSEA strategy for evaluation of drug interactions. Performance evaluation using synthetic noise data was also performed to evaluate sensitivities and parameter settings for the iMSEA strategy. The iMSEA strategy highlighted synergistic effects of combined OXA and VC treatments including the alterations in the glycerophospholipid metabolism pathway and glycine, serine, and threonine metabolism pathway. This work provides an alternative method to reveal the mechanisms of drug combinations from the viewpoint of metabolomics.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Metabolômica/métodos , Redes e Vias Metabólicas , Interações Medicamentosas
6.
Anal Chem ; 95(46): 16830-16839, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37943818

RESUMO

Metabolite isomers play diverse and crucial roles in various metabolic processes. However, in untargeted metabolomics analysis, it remains a great challenge to distinguish between the constitutional isomers and enantiomers of amine-containing metabolites due to their similar chemical structures and physicochemical properties. In this work, the triplex stable isotope N-phosphoryl amino acids labeling (SIPAL) is developed to identify and relatively quantify the amine-containing metabolites and their isomers by using chiral phosphorus reagents coupled with high-resolution tandem mass spectroscopy. The constitutional isomers could be effectively distinguished with stereo isomers by using the diagnosis ions in MS/MS spectra. The in-house software MS-Isomerism has been parallelly developed for high-throughput screening and quantification. The proposed strategy enables the unbiased detection and relative quantification of isomers of amine-containing metabolites. Based on the characteristic triplet peaks with SIPAL tags, a total of 854 feature peaks with 154 isomer groups are successfully recognized as amine-containing metabolites in liver cells, in which 37 amine-containing metabolites, including amino acids, polyamines, and small peptides, are found to be significantly different between liver cancer cells and normal cells. Notably, it is the first time to identify S-acetyl-glutathione as an endogenous metabolite in liver cells. The SIPAL strategy could provide spectacular insight into the chemical structures and biological functions of the fascinating amine-containing metabolite isomers. The feasibility of SIPAL in isomeric metabolomics analysis may reach a deeper understanding of the mirror-chemistry in life and further advance the discovery of novel biomarkers for disease diagnosis.


Assuntos
Aminoácidos , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Indicadores e Reagentes , Isomerismo , Cromatografia Líquida/métodos , Aminoácidos/química , Metabolômica/métodos , Poliaminas
7.
New Phytol ; 240(1): 207-223, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37434324

RESUMO

Plant somatic embryogenesis (SE) is a multifactorial developmental process where embryos that can develop into whole plants are produced from somatic cells rather than through the fusion of gametes. The molecular regulation of plant SE, which involves the fate transition of somatic cells into embryogenic cells, is intriguing yet remains elusive. We deciphered the molecular mechanisms by which GhRCD1 interacts with GhMYC3 to regulate cell fate transitions during SE in cotton. While silencing of GhMYC3 had no discernible effect on SE, its overexpression accelerated callus formation, and proliferation. We identified two of GhMYC3 downstream SE regulators, GhMYB44 and GhLBD18. GhMYB44 overexpression was unconducive to callus growth but bolstered EC differentiation. However, GhLBD18 can be triggered by GhMYC3 but inhibited by GhMYB44, which positively regulates callus growth. On top of the regulatory cascade, GhRCD1 antagonistically interacts with GhMYC3 to inhibit the transcriptional function of GhMYC3 on GhMYB44 and GhLBD18, whereby a CRISPR-mediated rcd1 mutation expedites cell fate transition, resembling the effects of GhMYC3 overexpression. Furthermore, we showed that reactive oxygen species (ROS) are involved in SE regulation. Our findings elucidated that SE homeostasis is maintained by the tetrapartite module, GhRCD1-GhMYC3-GhMYB44-GhLBD18, which acts to modulate intracellular ROS in a temporal manner.


Assuntos
Regulação da Expressão Gênica de Plantas , Espécies Reativas de Oxigênio , Diferenciação Celular
8.
Anal Chem ; 94(42): 14522-14529, 2022 10 25.
Artigo em Inglês | MEDLINE | ID: mdl-36223650

RESUMO

Spatial segmentation is a critical procedure in mass spectrometry imaging (MSI)-based biochemical analysis. However, the commonly used unsupervised MSI segmentation methods may lead to inappropriate segmentation results as the MSI data is characterized by high dimensionality and low signal-to-noise ratio. This process can be improved by the incorporation of precise prior knowledge, which is hard to obtain in most cases. In this study, we show that the incorporation of partial or coarse prior knowledge from different sources such as reference images or biological knowledge may also help to improve MSI segmentation results. Here, we propose a novel interactive segmentation strategy for MSI data called iSegMSI, which incorporates prior information in the form of scribble-regularization of the unsupervised model to fine-tune the segmentation results. By using two typical MSI data sets (including a whole-body mouse fetus and human thyroid cancer), the present results demonstrate the effectiveness of the iSegMSI strategy in improving the MSI segmentations. Specifically, the method can be used to subdivide a region into several subregions specified by the user-defined scribbles or to merge several subregions into a single region. Additionally, these fine-tuned results are highly tolerant to the imprecision of the scribbles. Our results suggest that the proposed iSegMSI method may be an effective preprocessing strategy to facilitate the analysis of MSI data.


Assuntos
Feto , Processamento de Imagem Assistida por Computador , Animais , Humanos , Camundongos , Espectrometria de Massas , Processamento de Imagem Assistida por Computador/métodos , Diagnóstico por Imagem
9.
Anal Bioanal Chem ; 414(20): 6069-6076, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35689117

RESUMO

We developed an effective and specific colorimetric strategy to detect Salmonella typhimurium (S. typhimurium) based on hexadecyl trimethyl ammonium bromide (CTAB)-induced supramolecular assembly of ß-cyclodextrin-capped gold nanoparticles (ß-CD-AuNPs). In this study, ssDNA aptamer of S. typhimurium could combine with CTAB to form the supramolecular ssDNA-CTAB composite, so the ssDNA aptamer was applied to control the concentration of CTAB. In the presence of S. typhimurium, ssDNA aptamers selectively bound to S. typhimurium but not to CTAB, leading to the host-guest chemistry reaction of CTAB and ß-CD resulting in ß-CD-AuNP supramolecular assembly aggregation with an obvious color change. The ratio of absorption at 650 and 520 nm (A650nm/A520nm) has a linear correlation to the log scale of the concentration of the bacteria (1 × 102-1 × 107 CFU/mL) with a low limit of detection (LOD) of 13 CFU/mL. In addition, this optical sensor has good selectivity and practicability. In milk samples, the recovery was 93.55-111.32%, which suggested its potential application in real samples.


Assuntos
Aptâmeros de Nucleotídeos , Técnicas Biossensoriais , Nanopartículas Metálicas , beta-Ciclodextrinas , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Cetrimônio , Colorimetria/métodos , Ouro/química , Nanopartículas Metálicas/química , Salmonella typhimurium
10.
J Cell Physiol ; 236(10): 6836-6851, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33855709

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a disease of progressive scarring caused by excessive extracellular matrix (ECM) deposition and activation of α-SMA-expressing myofibroblasts. Human antigen R (HuR) is an RNA binding protein that promotes protein translation. Upon translocation from the nucleus to the cytoplasm, HuR functions to stabilize messenger RNA (mRNA) to increase protein levels. However, the role of HuR in promoting ECM production, myofibroblast differentiation, and lung fibrosis is unknown. Human lung fibroblasts (HLFs) treated with transforming growth factor ß1 (TGF-ß1) showed a significant increase in translocation of HuR from the nucleus to the cytoplasm. TGF-ß-treated HLFs that were transfected with HuR small interfering RNA had a significant reduction in α-SMA protein as well as the ECM proteins COL1A1, COL3A, and FN1. HuR was also bound to mRNA for ACTA2, COL1A1, COL3A1, and FN. HuR knockdown affected the mRNA stability of ACTA2 but not that of the ECM genes COL1A1, COL3A1, or FN. In mouse models of pulmonary fibrosis, there was higher cytoplasmic HuR in lung structural cells compared to control mice. In human IPF lungs, there was also more cytoplasmic HuR. This study is the first to show that HuR in lung fibroblasts controls their differentiation to myofibroblasts and consequent ECM production. Further research on HuR could assist in establishing the basis for the development of new target therapy for fibrotic diseases, such as IPF.


Assuntos
Transdiferenciação Celular , Proteína Semelhante a ELAV 1/metabolismo , Matriz Extracelular/metabolismo , Fibroblastos/metabolismo , Fibrose Pulmonar Idiopática/metabolismo , Pulmão/metabolismo , Miofibroblastos/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Transdiferenciação Celular/efeitos dos fármacos , Células Cultivadas , Modelos Animais de Doenças , Proteína Semelhante a ELAV 1/genética , Matriz Extracelular/efeitos dos fármacos , Matriz Extracelular/patologia , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Fibroblastos/efeitos dos fármacos , Fibroblastos/patologia , Regulação da Expressão Gênica , Humanos , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Camundongos , Miofibroblastos/patologia , Fator de Crescimento Transformador beta1/farmacologia
11.
Biochem Biophys Res Commun ; 549: 47-53, 2021 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-33662668

RESUMO

OBJECTIVE: To study the effects of CX3CR1 on white matter injury, neurofunction, recognition, and expression of the CD36/15LO/NR4A1 signal in mice with traumatic brain injury (TBI). METHODS: CX3CR1GFP/GFP, CX3CR1GFP/+ and C57BL/6 male mice were randomly divided into 3 groups. We used a controlled cortical impact (CCI) to establish a TBI model and T2wt MRI to detect the TBI lesion. FA and DTI allowed for quantitative evaluation of the structural integrity of white matter tracts. Several behavior tests were used to investigate nerve function; a computer-based tracing system was used to trace and analyze dendrites and cell bodies of microglia and astrocytes in the peri-lesional brain areas. We also used RT-PCR and western blot to detect the effect of CX3CL1/CX3CR1 axis on CD36/15LO/NR4A1 signal. RESULTS: The fractional anisotropy (FA) at the corpus callosum area of brain was decreased at 3 days post TBI, the average lesion volume CX3CR1GFP/GFP group was increased, and the neurologic deficit scores of mice of Cx3Cr1GFP/+ and wild-type groups were significantly increased compared to Cx3Cr1GFP/GFP group mice. In the Corner turn test, TBI induced impairments in forelimb function that were more severe than Cx3Cr11GFP/+ and wild-type TBI mice. We operated the Y-maze at 3 days post-TBI and the NOR test at 28 days after TBI. There was a significant TBI effect induced in decreased percentage entries into the novel arm in Cx3Cr1GFP/+ and wild-type TBI mice, compared with Cx3Cr1GFP/GFP; Cx3Cr1GFP/+. Wild-type mice showed decreased exploration time in new objects compared with Cx3Cr1GFP/GFP. Those two behavior tests demonstrated that Cx3Cr1 knock-out increased the damage caused by TBI to memory. In the tail suspension and force swimming tests, there was no significant difference between those three groups. CD36 increased in Cx3Cr1GFP/GFP compared with the other three groups at 3 days after TBI. TBI inhibited the expression of NR4A1 at 3 d after damage. Cx3Cr1 deficiency can induce high expression of 15LO, this was unaffected by TBI. CONCLUSION: CX3CR1 deletion can enhance white matter injury. It increased the expression of CD36 and 15LO and increased expression of NR4A1. The lack of CX3CR1 can affect the recovery of nerve function.


Assuntos
Araquidonato 15-Lipoxigenase/metabolismo , Antígenos CD36/metabolismo , Receptor 1 de Quimiocina CX3C/deficiência , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Transdução de Sinais , Substância Branca/lesões , Substância Branca/metabolismo , Animais , Anisotropia , Axônios/patologia , Comportamento Animal , Lesões Encefálicas Traumáticas/diagnóstico por imagem , Lesões Encefálicas Traumáticas/patologia , Lesões Encefálicas Traumáticas/fisiopatologia , Receptor 1 de Quimiocina CX3C/metabolismo , Imagem de Tensor de Difusão , Masculino , Camundongos Endogâmicos C57BL , Substância Branca/diagnóstico por imagem
12.
Small ; 17(20): e2006815, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33783975

RESUMO

The biofouling of ureteral stents and subsequent urinary tract infections mainly come from the adsorption and adhesion of proteins and microorganisms and their ensuing proliferation. Although general polycationic surfaces in implants have good antibacterial activities, they suffer from limited durability due to severe protein and bacterial adsorption. Here, a biodegradable and anti-biofilm fiber-membrane structured ureteral stent (FMBUS) with synergetic contact-killing antibacterial activity and antiprotein adsorption is described. The stent is prepared by generating hyperbranched poly(amide-amine)-grafted polydopamine microparticles (≈300 nm) on the surface of fibers by in situ polymerization and Schiff base reactions. The biomimetic surface endows the FMBUS with a positive charge (+21.36 mV) and superhydrophilicity (water contact angle: 0°). As a result, the stents fulfilled the following functions: i) reduced attachment of host protein due to superhydrophilicity (Lysozyme: 92.1%; human serum albumin: 39.4%); ii) high bactericidal activities against contact pathogenic bacteria (contact-killing rate: 99.9999% for both E. coli and S. aureus; antiadhesion rate: 99.2% for E. coli and 99.9999% for S. aureus); iii) biocompatibility in vitro (relative growth rate of L929: >90% on day 3) and in vivo; and iv) gradient biodegradability to avoid a second surgery of stent extraction 1-2 weeks after implantation.


Assuntos
Escherichia coli , Staphylococcus aureus , Antibacterianos/farmacologia , Biomimética , Humanos , Stents , Propriedades de Superfície
13.
BMC Gastroenterol ; 21(1): 169, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849450

RESUMO

BACKGROUND: Surgical resection remains the best option for long-term survival in colorectal cancer (CRC); however, surgery can lead to tumor cell release into the circulation. Previous studies have also shown that surgery can affect cancer cell growth. The role of perioperative factors influencing long-term survival in patients presenting for CRC surgery remains to be investigated. METHODS: This retrospective single-center cohort study was conducted to collect the clinical data of patients who underwent elective laparoscopic resection for CRC from January 2014 to December 2015, namely clinical manifestations, pathological results, and perioperative characteristics. Survival was estimated using the Kaplan-Meier log-rank test. Univariable and multivariable Cox regression models were used to compare hazard ratios (HR) for death. RESULTS: A total of 234 patients were eligible for analysis. In the multivariable Cox model, tumor-node-metastasis (TNM) stage (stage IV: HR 30.63, 95% confidence interval (CI): 3.85-243.65; P = 0.001), lymphovascular invasion (yes: HR 2.07, 95% CI 1.09-3.92; P = 0.027), inhalational anesthesia with isoflurane (HR 1.96, 95% CI 1.19-3.21; P = 0.008), and Klintrup-Makinen (KM) inflammatory cell infiltration grade (low-grade inflammation: HR 2.03, 95% CI 1.20-3.43; P = 0.008) were independent risk factors affecting 5-year overall survival after laparoscopic resection for CRC. CONCLUSIONS: TNM stage, lymphovascular invasion, isoflurane, and KM grade were independent risk factors affecting CRC prognosis. Sevoflurane and high-grade inflammation may be associated with improved survival in CRC patients undergoing resection.


Assuntos
Neoplasias Colorretais , Estudos de Coortes , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Humanos , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Fatores de Risco
14.
Genomics ; 112(6): 5129-5135, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32937162

RESUMO

Family study is an effective way to identify disease-causing mutations (DCMs) and characterize the clinical phenotype of genetic diseases. In this study we recruited a Chinese primary open-angle glaucoma (POAG) family spanning six generations and consisting 112 individuals, in which 63 were participated in. Targeted exome sequencing on the proband identified a heterozygous mutation (c.752T>C, p.Val251Ala) in MYOC gene. Sanger sequencing performed on all participants found that fourteen family members carried this mutation. Ten (71.4%) of them were diagnosed with POAG, two (14.3%) with ocular hypertension (OHT) and two (14.3%) without manifestations of glaucoma. According to the results of ophthalmic examinations of the family members and their medical history, we found that the Val251Ala mutation was associated with clinical phenotype including intermediate penetrance, high intraocular pressure (IOP), severe visual defects and requirement of surgery.


Assuntos
Proteínas do Citoesqueleto/genética , Proteínas do Olho/genética , Glaucoma de Ângulo Aberto/genética , Glicoproteínas/genética , Adolescente , Adulto , Idoso , Alanina , Criança , China , Feminino , Genótipo , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Alinhamento de Sequência , Valina , Adulto Jovem
15.
Opt Express ; 28(26): 38934-38941, 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33379451

RESUMO

A deep-subwavelength metal spiral structure (MSS) waveguide with arbitrary bending angles was proposed and demonstrated to propagate magnetic localized surface plasmons (MLSPs) in theoretical, simulated and experimental ways. The uniform coupling strengths and frequencies for adjacent MSSs with different azimuthal angles represent a significant advancement in the development of structures supporting MLSPs over arbitrary bending angles. The consistency among spectra, dispersion, and field distributions for five MSSs indicates that backward propagation of MLSPs over arbitrary bending angles is possible. In addition, a long S-chain consisting of adjacent MSSs at various angles holds promise for applications involving long-distance MLSPs waveguides.

16.
Sensors (Basel) ; 20(24)2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33321709

RESUMO

The threshold of microfluidic inertial switch is excessively dependent on the size of the passive valve structure and the gas-liquid surface energy of working liquid. How to achieve high threshold and anti-high overload using liquid with low viscosity and low surface tension is a challenging work. Based on the designed U-type microfluidic inertial switch, the electrical characteristic of salt solution at microscale as well as the threshold and dynamic electrical performance of switch were studied. The VOF and CSD modules in CFD software were employed to analyze the dynamic flow process, and then the air-liquid surface moving displacement curve was compared by the theoretical model. A self-designed acceleration test platform was utilized to measure the static threshold, dynamic threshold, and anti-high overload of the inertial switch. The results show that the U-type microfluidics inertial switch using salt solution as sensitive electrode has better performance in power connection and anti-high overload. In particular, it also has the ability to achieve a range of dynamic threshold by changing the placement of the contact electrode, which can achieve rapid power on and off.

17.
Angew Chem Int Ed Engl ; 59(7): 2745-2749, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31814182

RESUMO

The aminoazanium of DABCO (H2 N-DABCO) has been developed as a general and practical amination reagent for the direct amination of alkyl and aryl pinacol boronates. This compound is stable and practical for use as a reagent. Various primary, secondary. and tertiary alkyl-Bpin and aryl-Bpin substrates were aminated to give the corresponding amine derivatives. The amination is stereospecific. The anti-Markovnikov hydroamination of olefins was easily achieved by catalytic hydroboration with HBpin and in subsequent situ amination using H2 N-DABCO. Moreover, the combination of 1,2-diboration of olefins, using B2 pin2 , with this amination process achieved the unprecedented 1,2-diamination of olefins. The amination protocol was also successfully extended to aryl pinacol boronates.

18.
J Cell Mol Med ; 23(1): 155-166, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30370662

RESUMO

Matriptase is an epithelia-specific membrane-anchored serine protease, and its dysregulation is highly related to the progression of a variety of cancers. Hepatocyte growth factor activator inhibitor-1 (HAI-1) inhibits matriptase activity through forming complex with activated matriptase. The balance of matriptase activation and matriptase/HAI-1 complex formation determines the intensity and duration of matriptase activity. 3-Cl-AHPC, 4-[3-(1-adamantyl)-4-hydroxyphenyl]-3-chlorocinnamic acid, is an adamantly substituted retinoid-related molecule and a ligand of retinoic acid receptor γ (RARγ). 3-Cl-AHPC is of strong anti-cancer effect but with elusive mechanisms. In our current study, we show that 3-Cl-AHPC time- and dose- dependently induces matriptase/HAI-1 complex formation, leading to the suppression of activated matriptase in cancer cells and tissues. Furthermore, 3-Cl-AHPC promotes matriptase shedding but without increasing the activity of shed matriptase. Moreover, 3-Cl-AHPC inhibits matriptase-mediated cleavage of pro-HGF through matriptase/HAI-1 complex induction, resulting in the suppression of pro-HGF-stimulated signalling and cell scattering. Although 3-Cl-AHPC binds to RARγ, its induction of matriptase/HAI-1 complex is not RARγ dependent. Together, our data demonstrates that 3-Cl-AHPC down-regulates matriptase activity through induction of matriptase/HAI-1 complex formation in a RARγ-independent manner, providing a mechanism of 3-Cl-AHPC anti-cancer activity and a new strategy to inhibit abnormal matriptase activity via matriptase/HAI-1 complex induction using small molecules.


Assuntos
Adamantano/análogos & derivados , Antineoplásicos/farmacologia , Cinamatos/farmacologia , Fator de Crescimento de Hepatócito/metabolismo , Precursores de Proteínas/metabolismo , Proteínas Secretadas Inibidoras de Proteinases/metabolismo , Serina Endopeptidases/metabolismo , Adamantano/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , Humanos , Masculino , Camundongos Nus , Complexos Multiproteicos/metabolismo , Proteínas Secretadas Inibidoras de Proteinases/genética , Receptores do Ácido Retinoico/metabolismo , Serina Endopeptidases/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Receptor gama de Ácido Retinoico
19.
Sensors (Basel) ; 19(19)2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31546674

RESUMO

To autonomously move and operate objects in cluttered indoor environments, a service robot requires the ability of 3D scene perception. Though 3D object detection can provide an object-level environmental description to fill this gap, a robot always encounters incomplete object observation, recurring detections of the same object, error in detection, or intersection between objects when conducting detection continuously in a cluttered room. To solve these problems, we propose a two-stage 3D object detection algorithm which is to fuse multiple views of 3D object point clouds in the first stage and to eliminate unreasonable and intersection detections in the second stage. For each view, the robot performs a 2D object semantic segmentation and obtains 3D object point clouds. Then, an unsupervised segmentation method called Locally Convex Connected Patches (LCCP) is utilized to segment the object accurately from the background. Subsequently, the Manhattan Frame estimation is implemented to calculate the main orientation of the object and subsequently, the 3D object bounding box can be obtained. To deal with the detected objects in multiple views, we construct an object database and propose an object fusion criterion to maintain it automatically. Thus, the same object observed in multi-view is fused together and a more accurate bounding box can be calculated. Finally, we propose an object filtering approach based on prior knowledge to remove incorrect and intersecting objects in the object dataset. Experiments are carried out on both SceneNN dataset and a real indoor environment to verify the stability and accuracy of 3D semantic segmentation and bounding box detection of the object with multi-view fusion.

20.
Org Biomol Chem ; 16(24): 4439-4442, 2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29855642

RESUMO

A novel [3 + 2] cycloaddition reaction of azaoxyallyl cations and aromatic ethylenes has been developed to afford multi-substituted pyrrolidinones in moderate to good yields. This method not only further expands the synthetic utility of α-halo hydroxamates, but also provides an alternative method for the synthesis of bioactive molecules containing pyrrolidinones.

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