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1.
Nature ; 631(8022): 826-834, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38987597

RESUMO

Glutamate is traditionally viewed as the first messenger to activate NMDAR (N-methyl-D-aspartate receptor)-dependent cell death pathways in stroke1,2, but unsuccessful clinical trials with NMDAR antagonists implicate the engagement of other mechanisms3-7. Here we show that glutamate and its structural analogues, including NMDAR antagonist L-AP5 (also known as APV), robustly potentiate currents mediated by acid-sensing ion channels (ASICs) associated with acidosis-induced neurotoxicity in stroke4. Glutamate increases the affinity of ASICs for protons and their open probability, aggravating ischaemic neurotoxicity in both in vitro and in vivo models. Site-directed mutagenesis, structure-based modelling and functional assays reveal a bona fide glutamate-binding cavity in the extracellular domain of ASIC1a. Computational drug screening identified a small molecule, LK-2, that binds to this cavity and abolishes glutamate-dependent potentiation of ASIC currents but spares NMDARs. LK-2 reduces the infarct volume and improves sensorimotor recovery in a mouse model of ischaemic stroke, reminiscent of that seen in mice with Asic1a knockout or knockout of other cation channels4-7. We conclude that glutamate functions as a positive allosteric modulator for ASICs to exacerbate neurotoxicity, and preferential targeting of the glutamate-binding site on ASICs over that on NMDARs may be strategized for developing stroke therapeutics lacking the psychotic side effects of NMDAR antagonists.


Assuntos
Canais Iônicos Sensíveis a Ácido , Isquemia Encefálica , Ácido Glutâmico , Animais , Feminino , Humanos , Masculino , Camundongos , 2-Amino-5-fosfonovalerato/efeitos adversos , 2-Amino-5-fosfonovalerato/metabolismo , 2-Amino-5-fosfonovalerato/farmacologia , Canais Iônicos Sensíveis a Ácido/química , Canais Iônicos Sensíveis a Ácido/deficiência , Canais Iônicos Sensíveis a Ácido/efeitos dos fármacos , Canais Iônicos Sensíveis a Ácido/genética , Canais Iônicos Sensíveis a Ácido/metabolismo , Regulação Alostérica/efeitos dos fármacos , Sítios de Ligação/genética , Isquemia Encefálica/induzido quimicamente , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Ácido Glutâmico/análogos & derivados , Ácido Glutâmico/metabolismo , Ácido Glutâmico/farmacologia , Ácido Glutâmico/toxicidade , Camundongos Knockout , Mutagênese Sítio-Dirigida , Prótons , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Receptores de N-Metil-D-Aspartato/química , Receptores de N-Metil-D-Aspartato/metabolismo
2.
Nat Methods ; 19(11): 1472-1479, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36203018

RESUMO

Imaging technologies are increasingly used to generate high-resolution reference maps of brain structure and function. Comparing experimentally generated maps to these reference maps facilitates cross-disciplinary scientific discovery. Although recent data sharing initiatives increase the accessibility of brain maps, data are often shared in disparate coordinate systems, precluding systematic and accurate comparisons. Here we introduce neuromaps, a toolbox for accessing, transforming and analyzing structural and functional brain annotations. We implement functionalities for generating high-quality transformations between four standard coordinate systems. The toolbox includes curated reference maps and biological ontologies of the human brain, such as molecular, microstructural, electrophysiological, developmental and functional ontologies. Robust quantitative assessment of map-to-map similarity is enabled via a suite of spatial autocorrelation-preserving null models. neuromaps combines open-access data with transparent functionality for standardizing and comparing brain maps, providing a systematic workflow for comprehensive structural and functional annotation enrichment analysis of the human brain.


Assuntos
Mapeamento Encefálico , Encéfalo , Humanos , Mapeamento Encefálico/métodos , Encéfalo/fisiologia
3.
Exp Cell Res ; 437(1): 114007, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38499142

RESUMO

Gastric cancer metastasis is a major cause of poor prognosis. Our previous research showed that methionine restriction (MR) lowers the invasiveness and motility of gastric carcinoma. In this study, we investigated the particular mechanisms of MR on gastric carcinoma metastasis. In vitro, gastric carcinoma cells (AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45) were grown in an MR medium for 24 h. In vivo, BALB/c mice were given a methionine-free (Met-) diet. Transwell assays were used to investigate cell invasion and migration. The amounts of Krüppel like factor 10 (KLF10) and cystathionine ß-synthase (CBS) were determined using quantitative real-time PCR and Western blot. To determine the relationship between KLF10 and CBS, chromatin immunoprecipitation and a dual-luciferase reporter experiment were used. Hematoxylin-eosin staining was used to detect lung metastasis. Liquid chromatography-mass spectrometry was used to determine cystathionine content. MR therapy had varying effects on the invasion and migration of gastric carcinoma cells AGS, SNU-5, MKN7, KATO III, SNU-1, and MKN45. KLF10 was highly expressed in AGS cells but poorly expressed in KATO III cells. KLF10 improved MR's ability to prevent gastric carcinoma cell invasion and migration. In addition, KLF10 may interact with CBS, facilitating transcription. Further detection revealed that inhibiting the KLF10/CBS-mediated trans-sulfur pathway lowered Met-'s inhibitory effect on lung metastasis development. KLF10 transcription activated CBS, accelerated the trans-sulfur pathway, and increased gastric carcinoma cells' susceptibility to MR.


Assuntos
Carcinoma , Neoplasias Pulmonares , Neoplasias Gástricas , Camundongos , Animais , Metionina/metabolismo , Cistationina beta-Sintase/genética , Cistationina beta-Sintase/metabolismo , Neoplasias Gástricas/patologia , Racemetionina , Enxofre , Neoplasias Pulmonares/genética , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição de Resposta de Crescimento Precoce/metabolismo
4.
Genome Res ; 31(7): 1150-1158, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34155038

RESUMO

Protein-truncating variants (PTVs) have important impacts on phenotype diversity and disease. However, their population genetics characteristics in more globally diverse populations are not well defined. Here, we describe patterns of PTVs in 1320 genes sequenced in 10,539 healthy controls and 9434 patients with psoriasis, all of Han Chinese ancestry. We identify 8720 PTVs, of which 77% are novel, and estimate 88% of all PTVs are deleterious and subject to purifying selection. Furthermore, we show that individuals with psoriasis have a significantly higher burden of PTVs compared to controls (P = 0.02). Finally, we identified 18 PTVs in 14 genes with unusually high levels of population differentiation, consistent with the action of local adaptation. Our study provides insights into patterns and consequences of PTVs.

5.
BMC Plant Biol ; 24(1): 457, 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38797823

RESUMO

BACKGROUND: Cotton is globally important crop. Verticillium wilt (VW), caused by Verticillium dahliae, is the most destructive disease in cotton, reducing yield and fiber quality by over 50% of cotton acreage. Breeding resistant cotton cultivars has proven to be an efficient strategy for improving the resistance of cotton to V. dahliae. However, the lack of understanding of the genetic basis of VW resistance may hinder the progress in deploying elite cultivars with proven resistance. RESULTS: We planted the VW-resistant Gossypium hirsutum cultivar Zhongzhimian No.2 (ZZM2) in an artificial greenhouse and disease nursery. ZZM2 cotton was subsequently subjected to transcriptome sequencing after Vd991 inoculation (6, 12, 24, 48, and 72 h post-inoculation). Several differentially expressed genes (DEGs) were identified in response to V. dahliae infection, mainly involved in resistance processes, such as flavonoid and terpenoid quinone biosynthesis, plant hormone signaling, MAPK signaling, phenylpropanoid biosynthesis, and pyruvate metabolism. Compared to the susceptible cultivar Junmian No.1 (J1), oxidoreductase activity and reactive oxygen species (ROS) production were significantly increased in ZZM2. Furthermore, gene silencing of cytochrome c oxidase subunit 1 (COX1), which is involved in the oxidation-reduction process in ZZM2, compromised its resistance to V. dahliae, suggesting that COX1 contributes to VW resistance in ZZM2. CONCLUSIONS: Our data demonstrate that the G. hirsutum cultivar ZZM2 responds to V. dahliae inoculation through resistance-related processes, especially the oxidation-reduction process. This enhances our understanding of the mechanisms regulating the ZZM2 defense against VW.


Assuntos
Resistência à Doença , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Gossypium , Doenças das Plantas , Gossypium/genética , Gossypium/microbiologia , Gossypium/imunologia , Doenças das Plantas/microbiologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Resistência à Doença/genética , Ascomicetos/fisiologia , Regulação da Expressão Gênica de Plantas , Transcriptoma , Verticillium
6.
Biol Chem ; 405(4): 257-265, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37943731

RESUMO

The prevention and treatment of gastric cancer has been the focus and difficulty of medical research. We aimed to explore the mechanism of inhibiting migration and invasion of gastric cancer cells by methionine restriction (MR). The human gastric cancer cell lines AGS and MKN45 cultured with complete medium (CM) or medium without methionine were used for in vitro experiments. MKN45 cells were injected tail vein into BALB/c nude mice and then fed with normal diet or methionine diet for in vivo experiments. MR treatment decreased cell migration and invasion, increased E-cadherin expression, decreased N-cadherin and p-p65 expressions, and inhibited nuclear p65 translocation of AGS and MKN45 cells when compared with CM group. MR treatment increased IκBα protein expression and protein stability, and decreased IκBα protein ubiquitination level and TRIM47 expression. TRIM47 interacted with IκBα protein, and overexpression of TRIM47 reversed the regulatory effects of MR. TRIM47 promoted lung metastasis formation and partially attenuated the effect of MR on metastasis formation in vivo compared to normal diet group mice. MR reduces TRIM47 expression, leads to the degradation of IκBα, and then inhibits the translocation of nuclear p65 and the migration and invasion of gastric cancer cells.


Assuntos
Neoplasias Gástricas , Animais , Humanos , Camundongos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Metionina/metabolismo , Metionina/farmacologia , Camundongos Nus , Proteínas de Neoplasias/metabolismo , Inibidor de NF-kappaB alfa/metabolismo , Inibidor de NF-kappaB alfa/farmacologia , Proteínas Nucleares/metabolismo , Racemetionina/metabolismo , Racemetionina/farmacologia , Neoplasias Gástricas/metabolismo , Proteínas com Motivo Tripartido/metabolismo
7.
Alzheimers Dement ; 20(5): 3364-3377, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38561254

RESUMO

INTRODUCTION: We assessed whether macro- and/or micro-structural white matter properties are associated with cognitive resilience to Alzheimer's disease pathology years prior to clinical onset. METHODS: We examined whether global efficiency, an indicator of communication efficiency in brain networks, and diffusion measurements within the limbic network and default mode network moderate the association between amyloid-ß/tau pathology and cognitive decline. We also investigated whether demographic and health/risk factors are associated with white matter properties. RESULTS: Higher global efficiency of the limbic network, as well as free-water corrected diffusion measures within the tracts of both networks, attenuated the impact of tau pathology on memory decline. Education, age, sex, white matter hyperintensities, and vascular risk factors were associated with white matter properties of both networks. DISCUSSION: White matter can influence cognitive resilience against tau pathology, and promoting education and vascular health may enhance optimal white matter properties. HIGHLIGHTS: Aß and tau were associated with longitudinal memory change over ∼7.5 years. White matter properties attenuated the impact of tau pathology on memory change. Health/risk factors were associated with white matter properties.


Assuntos
Substância Branca , Proteínas tau , Idoso , Feminino , Humanos , Masculino , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Encéfalo/patologia , Cognição/fisiologia , Disfunção Cognitiva/patologia , Imagem de Tensor de Difusão , Testes Neuropsicológicos , Fatores de Risco , Proteínas tau/metabolismo , Substância Branca/patologia , Tauopatias/patologia
8.
Molecules ; 29(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38893566

RESUMO

DFT and TD-DFT were used in this article to investigate the effects of different substitutions at multiple sites on the photophysical mechanism of bis-HBX in the gas phase. Four different substitution modes were selected, denoted as A1 (X=Me, Y=S), A2 (X=OMe, Y=S), B1 (X=Me, Y=NH), and C1 (X=Me, Y=O). The geometric parameters proved that the IHBs enhanced after photoexcitation, which was conducive to promote the ESIPT process. Combining the analysis of the PECs, it was revealed that the bis-HBX molecule underwent the ESIPT process, and the ease of the ESIPT process was in the order of A1 > A2> B1 > C1. In particular, the TICT process in A1 and B1 promoted the occurrence of the ESIPT process. In addition, the IC process was identified, particularly in C1. Meanwhile, the calculation of fluorescence lifetime and fluorescence rate further confirmed that A1 was the most effective fluorescent probe molecule. This theoretical research provides an innovative theoretical reference for regulating ESIPT reactions and optimizing fluorescent probe molecules.

9.
Neuroimage ; 278: 120276, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37451374

RESUMO

The relationship between structural and functional connectivity in the brain is a key question in connectomics. Here we quantify patterns of structure-function coupling across the neocortex, by comparing structural connectivity estimated using diffusion MRI with functional connectivity estimated using both neurophysiological (MEG-based) and haemodynamic (fMRI-based) recordings. We find that structure-function coupling is heterogeneous across brain regions and frequency bands. The link between structural and functional connectivity is generally stronger in multiple MEG frequency bands compared to resting state fMRI. Structure-function coupling is greater in slower and intermediate frequency bands compared to faster frequency bands. We also find that structure-function coupling systematically follows the archetypal sensorimotor-association hierarchy, as well as patterns of laminar differentiation, peaking in granular layer IV. Finally, structure-function coupling is better explained using structure-informed inter-regional communication metrics than using structural connectivity alone. Collectively, these results place neurophysiological and haemodynamic structure-function relationships in a common frame of reference and provide a starting point for a multi-modal understanding of structure-function coupling in the brain.


Assuntos
Conectoma , Neocórtex , Humanos , Magnetoencefalografia/métodos , Encéfalo/fisiologia , Imageamento por Ressonância Magnética/métodos , Mapeamento Encefálico/métodos , Conectoma/métodos , Hemodinâmica , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiologia
10.
Small ; 19(44): e2303820, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37381641

RESUMO

Functional thin fabric with highly efficient cold protection properties are attracting the great attention of long-term dressing in a cold environment. Herein, a tri-layered bicomponent microfilament composite fabric comprised of a hydrophobic layer of PET/PA@C6 F13 bicomponent microfilament webs, an adhesive layer of LPET/PET fibrous web, and a fluffy-soft layer of PET/Cellulous fibrous web is designed and also successfully been fabricated through a facile process of dipping, combined with thermal belt bonding. The prepared samples exhibit a large resistance to wetting of alcohol, a high hydrostatic pressure of 5530 Pa, and brilliant water slipping properties, owing to the presence of dense micropores ranging from 25.1 to 70.3 µm, as well as to the smooth surface with an arithmetic mean deviation of surface roughness (Sa) ranging from 5.112 to 4.369 µm. Besides, the prepared samples exhibited good water vapor permeability, and a tunable CLO value ranging from 0.569 to 0.920, in addition to the fact that it exhibited a very suitable working temperature range of -5 °C to 15 °C. Additionally, it also showed excellent clothing tailorability including high mechanical strength with a remarkably soft texture and lightweight foldability that suitable for cold outdoor clothing applications.

11.
Small ; 19(29): e2207436, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37026417

RESUMO

Bimetallic nanomaterials (BNMs) have been used in sensing, biomedicine, and environmental remediation, but their multipurpose and comprehensive applications in molecular logic computing and information security protection have received little attention. Herein, This synthesis method is achieved by sequentially adding reactants under ice bath conditions. Interestingly, Ag-Cr NPs can dynamically selectively sense anions and reductants in multiple channels. Especially, ClO- can be quantitatively detected by oxidizing Ag-Cr NPs with detection limits of 98.37 nM (at 270 nm) and 31.83 nM (at 394 nm). Based on sequential-dependent synthesis process of Ag-Cr NPs, Boolean logic gates and customizable molecular keypad locks are constructed by setting the reactants as the inputs, the states of the resulting solutions as the outputs. Furthermore, dynamically selective response patterns of the Ag-Cr NPs can be converted into binary strings to exploit molecular crypto-steganography to encode, store, and hide information. By integrating the three dimensions of authorization, encryption, and steganography, 3 in 1 advanced information protection based on Ag-Cr nanosensing system can be achieved, which can enhance the anti-cracking ability of information. This research will promote the development and application of nanocomposites in the field of information security and deepen the connection between molecular sensing and the information world.

12.
Brain ; 145(5): 1743-1756, 2022 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34910119

RESUMO

Parkinson's disease is a progressive neurodegenerative disorder characterized by the intracellular accumulation of insoluble alpha-synuclein aggregates into Lewy bodies and neurites. Increasing evidence indicates that Parkinson's disease progression results from the spread of pathologic alpha-synuclein through neuronal networks. However, the exact mechanisms underlying the propagation of abnormal proteins in the brain are only partially understood. The objective of this study was first to describe the long-term spatiotemporal distributions of Lewy-related pathology in mice injected with alpha-synuclein preformed fibrils and then to recreate these patterns using a computational model that simulates in silico the spread of pathologic alpha-synuclein. In this study, 87 2-3-month-old non-transgenic mice were injected with alpha-synuclein preformed fibrils to generate a comprehensive post-mortem dataset representing the long-term spatiotemporal distributions of hyperphosphorylated alpha-synuclein, an established marker of Lewy pathology, across the 426 regions of the Allen Mouse Brain Atlas. The mice were injected into either the caudoputamen, nucleus accumbens or hippocampus, and followed over 24 months with pathologic alpha-synuclein quantified at seven intermediate time points. The pathologic patterns observed at each time point in this high-resolution dataset were then compared to those generated using a Susceptible-Infected-Removed (SIR) computational model, an agent-based model that simulates the spread of pathologic alpha-synuclein for every brain region taking simultaneously into account the effect of regional brain connectivity and Snca gene expression. Our histopathological findings showed that differentially targeted seeding of pathological alpha-synuclein resulted in unique propagation patterns over 24 months and that most brain regions were permissive to pathology. We found that the SIR model recreated the observed distributions of pathology over 24 months for each injection site. Null models showed that both Snca gene expression and connectivity had a significant influence on model fit. In sum, our study demonstrates that the combination of normal alpha-synuclein concentration and brain connectomics contributes to making brain regions more vulnerable to the pathological process, providing support for a prion-like spread of pathologic alpha-synuclein. We propose that this rich dataset and the related computational model will help test new hypotheses regarding mechanisms that may alter the spread of pathologic alpha-synuclein in the brain.


Assuntos
Doença de Parkinson , alfa-Sinucleína , Animais , Encéfalo/patologia , Humanos , Corpos de Lewy/patologia , Camundongos , Neurônios/metabolismo , Doença de Parkinson/metabolismo , alfa-Sinucleína/metabolismo
13.
Intern Med J ; 53(11): 2085-2092, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36504292

RESUMO

BACKGROUND: The 2018 Australian Heart Failure (HF) guidelines strongly recommended commencing sodium-glucose co-transporter-2 inhibitors (SGLT-2is) in HF patients with type 2 diabetes mellitus (T2DM). The uptake of SGLT-2is for HF patients with T2DM in our health service is unknown. AIMS: To determine the adoption of the 2018 HF guidelines by assessing the temporal trends of SGLT-2is' usage in HF patients with T2DM at Metro South Health (MSH) hospitals, in South-East Queensland. METHODS: Retrospective analysis of all HF patients (ejection fraction (EF) < 50%) with T2DM who were managed within MSH hospitals between June 2018 and June 2021. RESULTS: A total of 666 patients met the inclusion criteria with 918 HF encounters. Mean age was 72 years and 71% were male (473/666). Mean EF was 30% (SD ± 11%), and mean estimated glomerular filtration rate was 48 mL/min/1.73 m2 (SD ± 25). Fifty-four per cent (362/666) had contraindications to SGLT-2is. Among those without contraindications, there was a five-fold increase in the utility of SGLT-2is, 7% (2/29) before versus 38% (103/275) after implementation of the HF guidelines (P < 0.001). Patients on SGLT-2is were younger (64 years vs 69 years, P = 0.002) and had a lower number of HF hospitalisations (1.1 vs 2.1, P = 0.01). CONCLUSIONS: During the study period, 54% of our HF patients with T2DM were not on SGLT-2is due to prescribing guidelines/limitations in the Australian context. We observed a five-fold significant increase in the uptake of SGLT-2is before and after implementation of HF guidelines among patients without contraindications to SGLT-2is. There were significantly fewer HF hospitalisations among patients on SGLT-2is compared to those without.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Masculino , Idoso , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Hipoglicemiantes , Queensland/epidemiologia , Estudos Retrospectivos , Austrália , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Hospitais
14.
J Asian Nat Prod Res ; 25(10): 999-1011, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36899456

RESUMO

Osthole is the prominent active ingredient isolated from Cnidium. The role of osthole in chronic obstructive pulmonary disease (COPD) was investigated herein. Bronchial epithelial 16HBE cells were exposed to cigarette smoke extract (CSE) to generate injury models. The concentration of CSE had an inverse correlation with cell viability. Osthole suppressed inflammation, oxidative stress, apoptosis, and pyroptosis in 16HBE cells, along with a decrease in RIPK2 level. RIPK2 overexpression reversed the effects of osthole on the abovementioned aspects. This study found that the osthole could reduce RIPK2 level, inhibit pyroptosis, and alleviate the damage in 16HBE cells under CSE stimulation.


Assuntos
Cnidium , Piroptose , Linhagem Celular , Apoptose , Nicotiana , Células Epiteliais
15.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 45(4): 591-596, 2023 Aug.
Artigo em Zh | MEDLINE | ID: mdl-37654139

RESUMO

Objective To analyze the expression of cyclooxygenase-2 (COX-2) in the patients with snow-white sign of advanced colorectal adenoma (ACA) and explore its clinical significance.Method Western blotting was employed to determine the expression of COX-2 in the adenoma tissue and the normal tissue adjacent to the adenoma tissue (>5 cm away from the distal end of the adenoma tissue) of 40 ACA patients with snow-white sign and 40 ACA patients without snow-white sign.Results The appearance of snow-white sign in ACA patients was associated with patient age (P=0.001) and not associated with sex,smoking history,drinking history,ethnic groups,family history of colorectal cancer,abdominal pain,diarrhea,constipation,fecal occult blood,or tumor markers (all P>0.05).Snow-white sign mainly appeared in the ACA patients with multiple adenomas (P=0.004),large adenomas (P=0.006),adenomas in distal colon (P=0.015),protruding polyps (P=0.044),and late-stage pathology (P=0.010).The occurrence of snow-white sign showed no difference in the ACA patients with different results of Japan NBI Expert Team classification (P=0.502).The expression of COX-2 in the adenoma tissue was higher than that in the adjacent normal tissue in the patients with and without snow-white sign (P<0.001,P=0.004).The patients with snow-white sign had higher expression of COX-2 protein in the adenoma tissue than the patients without snow-white sign (P=0.001).The expression of COX-2 protein in the adjacent healthy tissue had no significant difference between the patients with and without snow-white sign (P=0.603).Conclusions Snow-white sign is more like to appear in the ACA patients with young age,multiple and large adenomas,adenomas in distal colon,protruding polyps,and late-stage pathology.Moreover,the expression of COX-2 in the ACA patients with snow-white sign is significantly higher than that in the ACA patients without snow-white sign.The adults with snow-white sign are prone to cancerization than those without snow-white sign.


Assuntos
Adenoma , Neoplasias Colorretais , Adulto , Humanos , Ciclo-Oxigenase 2 , Neve
16.
Opt Express ; 30(4): 5095-5106, 2022 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-35209479

RESUMO

We theoretically investigate the photoelectron momentum distribution of He atoms by numerically solving the time-dependent Schro¨dinger equation (TDSE) in few-cycle ionization gating, which is synthesized by two linearly polarized laser pulses. When applying the TDSE, we can clearly see the spider-like structures in the photoelectron momentum spectra. We also find that the spider-like structures can be isolated by changing the relative phase. The directionality of the spider-like structure is changed from right-side to left-side and the ring-like interference structure gradually appears in the photoelectron momentum spectra when increasing the relative phase. The interference patterns observed in TDSE are recaptured well by the quantum-trajectory Monte Carlo (QTMC) model. We separate the ionization time window of the tunneling electron by analyzing the ionization rate. With the help of QTMC simulation, we illustrate the change of the interference structure and its directionality in the photoelectron momentum spectra. By changing the relative phase, the forward-backward asymmetry of the momentum distribution of the emitted electrons can also be controlled. Moreover, we find that the relative contribution of the nonrescattering and the rescattering trajectories can be controlled. These properties are beneficial for the application of photoelecron holography in probing atomic and molecular structures and dynamics.

17.
Rapid Commun Mass Spectrom ; 36(21): e9374, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-35933588

RESUMO

RATIONALE: The exact etiology and pathogenesis of congenital pseudarthrosis of tibia (CPT) are not clear. Quantitative proteomics analysis plays a vital role in disease pathology research. Tandem mass tag (TMT)-based proteomics techniques were employed to identify and analyze the differentially expressed proteins (DEP) in the tibia periosteum tissues of CPT patients. METHODS: The samples were divided into three groups: CPT with NF1 group, CPT without NF1 group (non-NF1-CPT), and control group (patients with open tibial fracture). A fold change ≥1.5 or ≤0.66 and P-value <0.05 were used as the thresholds to screen DEPs. Subsequently, bioinformatics resources such as online tools DAVID and String were used to generate gene ontology (GO) annotation, KEGG pathways enrichment, and protein-protein interaction (PPI) network for these DEPs. RESULTS: The results show that a total of 347 proteins were differentially expressed in NF1-CPT groups, 212 of which were upregulated and 135 were downregulated. There were more DEPs in non-NF1-CPT groups; we identified 467 DEPs, including 281 upregulated and 186 downregulated. Among them, NF1-CPT groups and non-NF1-CPT groups shared 231 DEPs, and the remaining 230 DEPs showed the same expression trend in the two disease groups, with 117 upregulated and 113 downregulated. In particular, 116 proteins were altered only in NF1-CPT groups (94 were upregulated and 22 were downregulated), whereas 236 proteins were altered only in non-NF1-CPT groups (164 were upregulated and 72 were downregulated). Finally, compared with non-NF1-CPT groups, 47 proteins changed 1.5-fold and P-value < 0.05 in NF1-CPT groups. CONCLUSIONS: To sum up, we found that common DEPS in periosteum of NF1-CPT and non-NF1-CPT groups are mainly involved in cell matrix assembly, cell adhesion, AKT-PI3K signal pathway activation, and vascular agglutination, which indicate that these are the pathological characteristics of CPT. The osteogenic ability is weak, the osteoclastic ability is strong, the vascular lumen is narrow, the invasive growth and the proliferation of fibroblasts are enhanced in CPT patients.


Assuntos
Pseudoartrose , Criança , Humanos , Periósteo/patologia , Fosfatidilinositol 3-Quinases , Proteômica , Proteínas Proto-Oncogênicas c-akt , Pseudoartrose/congênito , Pseudoartrose/genética , Pseudoartrose/patologia , Tíbia/patologia
18.
Genomics ; 113(4): 2377-2384, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34052317

RESUMO

The genetic factors of tuberculosis (TB) susceptibility have been widely recognized. Here we performed a two-stage study in 616 TB patients and 709 healthy controls to systematically identify the genetic markers of TB susceptibility. In the discovery stage, we identified 93 single nucleotide polymorphisms (SNPs) and 3 human leucocyte antigen (HLA) class II alleles that had potential associations with TB susceptibility. In the validation stage, we confirmed that 6 nominally significant SNPs, including 2 novel missense variants at RAB17 and DCTN4 (odds ratio (OR) = 1.40, P = 4.98 × 10-3 and OR = 2.30, P = 3.17 × 10-2 respectively), were associated with the predisposition to TB. Moreover, our study found that HLA-II allele DQA1*05:05 (P = 0.0011, OR = 1.44, 95%CI = 1.15-1.77) was a TB susceptibility locus for the first time. This study comprehensively investigated the genetic variants that were associated with TB susceptibility and provided insight into the tuberculosis pathogenesis.


Assuntos
Estudo de Associação Genômica Ampla , Tuberculose , Alelos , Estudos de Casos e Controles , China , Predisposição Genética para Doença , Genótipo , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Polimorfismo de Nucleotídeo Único , Tuberculose/genética
19.
Zhongguo Yi Liao Qi Xie Za Zhi ; 46(3): 254-258, 2022 May 30.
Artigo em Zh | MEDLINE | ID: mdl-35678431

RESUMO

The high incidence of cardiovascular diseases is a serious threat to human health, and endovascular surgery has become the standard treatment for most interventional cardiovascular diseases. The robotassisted endovascular surgery system further enhances surgeons' ability to perform minimally invasive endovascular procedures in interventional cardiology. This study presents a new robotic technique for coronary intervention from the perspective of clinical application. Aiming at clinical application scenarios, this scheme proposed an intuitive guide wire catheter mechanism design, which accurately and perfectly simulates the doctor's hand movements, realizes the positive and negative direction translation of the guide wire catheter, accurate torque control of the guide wire rotation and locking. The results of animal test showed that the R-OneTM has a high degree of dexterity, accuracy and stability,and meets the clinical needs.


Assuntos
Doenças Cardiovasculares , Procedimentos Cirúrgicos Robóticos , Robótica , Animais , Cateterismo , Desenho de Equipamento
20.
Small ; 17(50): e2103983, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34668311

RESUMO

Inspired by information exchange and logic functions of life based on molecular recognition and interaction networks, ongoing efforts are directed toward development of molecular or nanosystems for multiplexed chem/biosensing and advanced information processing. However, because of their preparation shortcomings, poor functionality, and limited paradigms, it is still a big challenge to develop advanced nanomaterials-based systems and comprehensively realize neuron-like functions from multimode sensing to molecular information processing and safety. Herein, using fish scales derived carbon nanoparticles (FSCN) as a reducing agent and stabilizer, a simple one-step synthesis method of multifunctional silver-carbon nanocomposites (AgNPs-FSCN) is developed. The prepared AgNPs-FSCN own wide antibacterial and multisignal response abilities in five channels (including color, Tyndall, absorption and fluorescence intensities, and absorption wavelength) for quantitative colorimetric and fluorescence sensing of H2 O2 , ascorbic acid, and dopamine. Benefiting from its multicoding stimuli-responsive ability, molecular concealment, and programmability, AgNPs-FSCN can be abstracted as nanoneurons for implementing batch and parallel molecular logic computing, steganography, and cryptography. This research will promote the preparation of advanced multifunctional nanocomposites and the development of their multipurpose applications, including the multireadout-guided multianalyte intelligent sensing and sophisticated molecular computing, communication, and security.


Assuntos
Nanopartículas Metálicas , Nanocompostos , Animais , Carbono , Dopamina , Lógica , Prata
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