Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 213
Filtrar
1.
Mar Drugs ; 22(4)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38667778

RESUMO

Bacillus cereus, a common food-borne pathogen, forms biofilms and generates virulence factors through a quorum sensing (QS) mechanism. In this study, six compounds (dankasterone A, demethylincisterol A3, zinnimidine, cyclo-(L-Val-L-Pro), cyclo-(L-Ile-L-Pro), and cyclo-(L-Leu-L-Pro)) were isolated from the endophytic fungus Pithomyces sacchari of the Laurencia sp. in the South China Sea. Among them, demethylincisterol A3, a sterol derivative, exhibited strong QS inhibitory activity against B. cereus. The QS inhibitory activity of demethylincisterol A3 was evaluated through experiments. The minimum inhibitory concentration (MIC) of demethylincisterol A3 against B. cereus was 6.25 µg/mL. At sub-MIC concentrations, it significantly decreased biofilm formation, hindered mobility, and diminished the production of protease and hemolysin activity. Moreover, RT-qPCR results demonstrated that demethylincisterol A3 markedly inhibited the expression of QS-related genes (plcR and papR) in B. cereus. The exposure to demethylincisterol A3 resulted in the downregulation of genes (comER, tasA, rpoN, sinR, codY, nheA, hblD, and cytK) associated with biofilm formation, mobility, and virulence factors. Hence, demethylincisterol A3 is a potentially effective compound in the pipeline of innovative antimicrobial therapies.


Assuntos
Antibacterianos , Bacillus cereus , Biofilmes , Testes de Sensibilidade Microbiana , Percepção de Quorum , Percepção de Quorum/efeitos dos fármacos , Bacillus cereus/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Antibacterianos/farmacologia , Laurencia/microbiologia , Fatores de Virulência , China , Endófitos
2.
J Org Chem ; 89(6): 4085-4097, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38394366

RESUMO

A palladium-catalyzed annulative π-extension reaction of bay-iodinated triphenylenes with aryl iodides/o-chloroaromatic carboxylic acids was developed. This approach enabled the synthesis of diverse polycyclic aromatic compounds, including dibenzo[fg,op]tetracenes, azadibenzo[fg,op]tetracenes, and tribenzo[a,g,m]coronenes. Initial studies indicate that the resulting product, 2,3,8,9,14,15-hexakis(decyloxy)tribenzo[a,g,m]coronene, exhibits good liquid-crystalline properties.

3.
Chem Soc Rev ; 53(7): 3350-3383, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38406832

RESUMO

Super-resolution imaging has rapidly emerged as an optical microscopy technique, offering advantages of high optical resolution over the past two decades; achieving improved imaging resolution requires significant efforts in developing super-resolution imaging agents characterized by high brightness, high contrast and high sensitivity to fluorescence switching. Apart from technical requirements in optical systems and algorithms, super-resolution imaging relies on fluorescent dyes with special photophysical or photochemical properties. The concept of aggregation-induced emission (AIE) was proposed in 2001, coinciding with unprecedented advancements and innovations in super-resolution imaging technology. AIE probes offer many advantages, including high brightness in the aggregated state, low background signal, a larger Stokes shift, ultra-high photostability, and excellent biocompatibility, making them highly promising for applications in super-resolution imaging. In this review, we summarize the progress in implementation methods and provide insights into the mechanism of AIE-based super-resolution imaging, including fluorescence switching resulting from photochemically-converted aggregation-induced emission, electrostatically controlled aggregation-induced emission and specific binding-regulated aggregation-induced emission. Particularly, the aggregation-induced emission principle has been proposed to achieve spontaneous fluorescence switching, expanding the selection and application scenarios of super-resolution imaging probes. By combining the aggregation-induced emission principle and specific molecular design, we offer some comprehensive insights to facilitate the applications of AIEgens (AIE-active molecules) in super-resolution imaging.

4.
Nat Hum Behav ; 8(4): 779-793, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38182882

RESUMO

Despite its crucial role in the regulation of vital metabolic and neurological functions, the genetic architecture of the hypothalamus remains unknown. Here we conducted multivariate genome-wide association studies (GWAS) using hypothalamic imaging data from 32,956 individuals to uncover the genetic underpinnings of the hypothalamus and its involvement in neuropsychiatric traits. There were 23 significant loci associated with the whole hypothalamus and its subunits, with functional enrichment for genes involved in intracellular trafficking systems and metabolic processes of steroid-related compounds. The hypothalamus exhibited substantial genetic associations with limbic system structures and neuropsychiatric traits including chronotype, risky behaviour, cognition, satiety and sympathetic-parasympathetic activity. The strongest signal in the primary GWAS, the ADAMTS8 locus, was replicated in three independent datasets (N = 1,685-4,321) and was strengthened after meta-analysis. Exome-wide association analyses added evidence to the association for ADAMTS8, and Mendelian randomization showed lower ADAMTS8 expression with larger hypothalamic volumes. The current study advances our understanding of complex structure-function relationships of the hypothalamus and provides insights into the molecular mechanisms that underlie hypothalamic formation.


Assuntos
Estudo de Associação Genômica Ampla , Hipotálamo , Humanos , Hipotálamo/metabolismo , Hipotálamo/diagnóstico por imagem , Masculino , Feminino , Adulto , Transtornos Mentais/genética , Proteínas ADAMTS/genética , Pessoa de Meia-Idade , Análise da Randomização Mendeliana
5.
World J Hepatol ; 15(11): 1196-1209, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38075004

RESUMO

Chronic liver disease (CLD) imposes a heavy burden on millions of people worldwide. Despite substantial research on the pathogenesis of CLD disorders, no optimal treatment is currently available for some diseases, such as liver cancer. Exosomes, which are extracellular vesicles, are composed of various cellular components. Exosomes have unique functions in maintaining cellular homeostasis and regulating cell communication, which are associated with the occurrence of disease. Furthermore, they have application potential in diagnosis and treatment by carrying diverse curative payloads. Hepatic macrophages, which are key innate immune cells, show extraordinary heterogeneity and polarization. Hence, macrophage-derived exosomes may play a pivotal role in the initiation and progression of various liver diseases. This review focuses on the effects of macrophage-derived exosomes on liver disease etiology and their therapeutic potential, which will provide new insights into alleviating the global pressure of CLD.

6.
Front Microbiol ; 14: 1269869, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38075878

RESUMO

Scytovirin (SVN) is a lectin from cyanobacteria which has a strong inhibitory activity against Ebola virus infection. We engineered scytovirin as the inhibitor for surface display of lactic acid bacteria to block Ebola virus infection. Two different bacterial strains (Lactobacillus casei and Lactococcus lactis) were successfully engineered for scytovirin expression on the bacterial surface. These bacteria were found to be effective at neutralizing pseudotyped Ebolavirus in a cell-based assay. This approach can be utilized for prophylactic prevention, as well as for treatment. Since lactic acid bacteria can colonize the human body, a long-term efficacy could be achieved. Furthermore, this approach is also simple and cost-effective and can be easily applied in the regions of Ebola outbreaks in the developing countries.

7.
Front Cell Infect Microbiol ; 13: 1332786, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38106469

RESUMO

[This corrects the article DOI: 10.3389/fcimb.2023.1145824.].

8.
J Phys Chem Lett ; 14(41): 9183-9191, 2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37800664

RESUMO

Oxidizing species or radicals generated in water are of vital importance in catalysis, the environment, and biology. In addition to several related reactive oxygen species, using electron paramagnetic resonance (EPR), we present a nontrapping chemical transformation pathway to track water radical cation (H2O+•) species, whose formation is very sensitive to the conditioning environments, such as light irradiation, mechanical action, and gas/chemical introduction. We reveal that H2O+• can oxidize the 5,5-dimethyl-1-pyrroline N-oxide (DMPO) to the crucial epoxy hydroxylamine (HDMP=O) intermediate, which further reacts with the hydroxyl radical (•OH) for the formation of the EPR-active sextet radical (DMPO=O•). Interestingly, we uncover that H2O+• can react with dimethyl methylphosphonate (DMMP), 2-methyl-2-nitrosopropane (MNP), 5-tert-butoxycarbonyl-5-methyl-1-pyrroline N-oxide (BMPO), and α-phenyl-N-tert-butylnitrone (PBN) which contain a double-bond structure to produce corresponding derivatives as well. It is thus expected that both H2O+• and •OH are ubiquitous in nature and in various water-containing experimental systems. These findings provide a novel perspective on radicals for water redox chemistry.

9.
Anal Chem ; 95(40): 15125-15132, 2023 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-37774402

RESUMO

An ultralow-potential electrochemiluminescence (ECL) aptasensor has been designed for zearalenone (ZEN) assay based on a resonance energy transfer (RET) system with SnS2 QDs/g-C3N4 as a novel luminophore and CuO/NH2-UiO-66 as a dual-quencher. SnS2 QDs were loaded onto g-C3N4 nanosheets and enhanced the ECL luminescence via strong synergistic effects under an ultralow potential. The UV-vis absorption spectrum of CuO/NH2-UiO-66 exhibits considerable overlap with the ECL emission spectrum of SnS2 QDs/g-C3N4, an important consideration for the RET process. In order to stimulate RET, the ZEN aptamer and complementary DNA are introduced for conjugation between the donor and the acceptor. With the binding interaction between ZEN by its aptamer, CuO/NH2-UiO-66 is removed from the electrode surface, resulting in the inhibition of the RET system and an increase in the ECL signal. Under optimal conditions, the as-prepared aptasensor quantified ZEN from 0.5 µg·mL-1 to 0.1 fg·mL-1 with a low limit of detection of 0.085 fg·mL-1, and it exhibited good stability, excellent specificity, high reproducibility, and desirable practicality. The sensing strategy provides a method for mycotoxins assay to monitor food safety.

10.
Eur Radiol ; 33(12): 9063-9073, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37439940

RESUMO

OBJECTIVES: To establish a computed tomography (CT)-based scale to evaluate the resectability of locally advanced thyroid cancer. METHODS: This twin-centre retrospective study included 95 locally advanced thyroid cancer patients from the 1st centre as the training cohort and 31 patients from the 2nd centre as the testing cohort, who were categorised into the resectable and unresectable groups. Three radiologists scored the CT scans of each patient by evaluating the extension to the recurrent laryngeal nerve (RLN), trachea, oesophagus, artery, vein, soft tissue, and larynx. A 14-score scale (including all comprised structures) and a 12-score scale (excluding larynx) were developed. Receiver-operating characteristic (ROC) analysis was used to evaluate the performance of the scales. Stratified fivefold cross-validation and external verification were used to validate the scale. RESULTS: In the training cohort, compromised RLN (p < 0.001), trachea (p = 0.001), oesophagus (p = 0.002), artery (p < 0.001), vein (p = 0.005), and soft tissue (p < 0.001) were predictors for unresectability, while compromised larynx (p = 0.283) was not. The 12-score scale (AUC = 0.882, 95%CI: 0.812-0.952) was not inferior to the 14-score scale (AUC = 0.891, 95%CI: 0.823-0.960). In subgroup analysis, the AUCs of the 12-score scale were 0.826 for treatment-naïve patients and 0.976 for patients with prior surgery. The 12-score scale was further validated with a fivefold cross-validation analysis, with an overall accuracy of 78.9-89.4%. Finally, external validation using the testing cohort showed an AUC of 0.875. CONCLUSIONS: The researchers built a CT-based 12-score scale to evaluate the resectability of locally advanced thyroid cancer. Validation with a larger sample size is required to confirm the efficacy of the scale. CLINICAL RELEVANCE STATEMENT: This 12-score CT scale would help clinicians evaluate the resectability of locally advanced thyroid cancer. KEY POINTS: • The researchers built a 12-score CT scale (including recurrent laryngeal nerve, trachea, oesophagus, artery, vein, and soft tissue) to evaluate the resectability of locally advanced thyroid cancer. • This scale has the potential to help clinicians make treatment plans for locally advanced thyroid cancer.


Assuntos
Laringe , Neoplasias da Glândula Tireoide , Humanos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Neoplasias da Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/cirurgia
11.
Sci Rep ; 13(1): 11601, 2023 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-37463966

RESUMO

The aim was to investigate the association between mixed exposure to phthalates and serum thyroid function among US adolescents. The study used 2007-2008 survey data from the National Health and Nutrition Examination Survey (NHANES). Data on urinary phthalates metabolites and serum thyroid function indicators were collected. The weighted multivariable linear regression models and Bayesian kernel machine regression (BKMR) analyses were used to analyze the relationship between phthalates metabolites and thyroid function. A total of 356 adolescents aged 12-19 years were included in the analysis. Linear regression models showed that mono-(carboxyisoctyl) phthalate (MCOP) was positively correlated with total triiodothyronine (TT3) (ß = 0.045, 95% confidence interval [CI] 0.022, 0.068) and thyroid stimulating hormone (TSH) (ß = 0.1461, 95% CI 0.059, 0.232), while mono-(carboxyisononyl) phthalate (MCNP) was negatively correlated with TSH (ß = - 0.119, 95% CI - 0.196, - 0.042). BKMR analyses showed phthalate metabolites mixtures have significantly positive overall effect on TT3. Exposure to phthalate mixtures might be positively correlated with increased TT3 serum level in US adolescents. The study provided evidence for the association between mixed phthalates exposure and thyroid health in adolescent population.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Adolescente , Humanos , Glândula Tireoide/metabolismo , Inquéritos Nutricionais , Poluentes Ambientais/análise , Teorema de Bayes , Ácidos Ftálicos/metabolismo , Tireotropina , Exposição Ambiental/efeitos adversos , Exposição Ambiental/análise
12.
Curr Med Imaging ; 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37287309

RESUMO

INTRODUCTION: To explore the feasibility of applying computed tomography perfusion (CTP) imaging-guided mechanical thrombectomy in acute ischemic stroke patients with large vessel occlusion beyond the therapeutic time window. METHODS: The clinical data of acute cerebral infarction patients with large vessel occlusion who were beyond the therapeutic time window and admitted to Handan Central Hospital from January 2021 to March 2022 were retrospectively analyzed. All patients were assessed by the National Institutes of Health Stroke Scale (NIHSS) and were examined by one-stop CTP imaging. The preoperative onset time of the disease was more than 6 h. Fourteen patients underwent magnetic resonance imaging examination at the same time. Fifty-four patients were retrospectively divided into two groups based on the treatment methods: the mechanical thrombectomy group had 21 patients and the conservative treatment group had 33 patients. NIHSS scoring and computed tomography scan were performed before treatment, 6 h, 24 h, 7 days, and 30 days after treatment. RESULTS: The NIHSS scores of the patients with acute cerebral large vessel occlusion who underwent CTP imaging-guided mechanical thrombectomy at 6 h, 24 h, 7 days, and 30 days after treatment were compared with those of the conventional treatment group. The NIHSS score of the mechanical thrombectomy group was significantly better, and the difference was statistically significant (P < 0.05). In terms of the prognosis rate and expansion rate of infarct core volume, the patients of the mechanical thrombectomy group had a better prognosis, and the difference was statistically significant (P < 0.05). Artificial intelligence-assisted CTP diagnosis can facilitate the automatic evaluation of diseases and enable quick judgments that are independent of radiologists' evaluation, but it may pose a problem in the determination of infarct core volume (either being too high or too low). CONCLUSION: It is of great significance to apply CTP imaging in guiding the mechanical thrombectomy procedure in acute stroke patients with large vessel occlusion who are beyond the therapeutic time window.

13.
Alzheimers Res Ther ; 15(1): 109, 2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-37312172

RESUMO

BACKGROUND: The correlations between genetic risk for Alzheimer's disease (AD) with comprehensive brain regions at a regional scale are still not well understood. We aim to explore whether these associations vary across different age stages. METHODS: This study used large existing genome-wide association datasets to calculate polygenic risk score (PRS) for AD in two populations from the UK Biobank (N ~ 23 000) and Adolescent Brain Cognitive Development Study (N ~ 4660) who had multimodal macrostructural and microstructural magnetic resonance imaging (MRI) metrics. We used linear mixed-effect models to assess the strength of the association between AD PRS and multiple MRI metrics of regional brain structures at different stages of life. RESULTS: Compared to those with lower PRSs, adolescents with higher PRSs had thinner cortex in the caudal anterior cingulate and supramarginal. In the middle-aged and elderly population, AD PRS had correlations with regional structure shrink primarily located in the cingulate, prefrontal cortex, hippocampus, thalamus, amygdala, and striatum, whereas the brain expansion was concentrated near the occipital lobe. Furthermore, both adults and adolescents with higher PRSs exhibited widespread white matter microstructural changes, indicated by decreased fractional anisotropy (FA) or increased mean diffusivity (MD). CONCLUSIONS: In conclusion, our results suggest genetic loading for AD may influence brain structures in a highly dynamic manner, with dramatically different patterns at different ages. This age-specific change is consistent with the classical pattern of brain impairment observed in AD patients.


Assuntos
Doença de Alzheimer , Adolescente , Pessoa de Meia-Idade , Humanos , Adulto , Idoso , Criança , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/genética , Estudo de Associação Genômica Ampla , Encéfalo/diagnóstico por imagem , Cognição , Tonsila do Cerebelo
14.
Environ Sci Pollut Res Int ; 30(27): 70519-70527, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37148507

RESUMO

Phthalates are widely used as plasticizer or fragrance ingredients in various consumer products worldwide. However, evidence for the overall effects of mixed exposure to phthalate on kidney function has not been widely investigated. The purpose of this article was to assess the association of urine phthalate metabolite levels and kidney injury parameters in adolescents. We used data from the combined 2007-2016 National Health and Nutrition Examination Survey (NHANES). We fitted weighted linear regressions and Bayesian kernel machine regressions (BKMR) models to explore the association of urinary phthalate metabolites with four parameters of kidney function after adjusting for covariates. Weighted linear regression models showed that MiBP (ß = 8.057; PFDR = 0.016) was significantly positively associated with eGFR and MEP (ß = -0.799; PFDR < 0.001) was significantly negatively correlated with BUN. BKMR analysis showed that the higher the concentration of phthalate metabolite mixture, the higher eGFR in adolescents. Based on the results of these two models, our findings revealed that mixed exposure to phthalates was associated with elevated eGFR in adolescents. However, as the study is cross-sectional, reverse causality is possible, and altered kidney function may impact the concentration of phthalate metabolites in urine.


Assuntos
Poluentes Ambientais , Ácidos Ftálicos , Humanos , Adolescente , Exposição Ambiental/análise , Poluentes Ambientais/análise , Inquéritos Nutricionais , Teorema de Bayes , Estudos Transversais , Ácidos Ftálicos/urina , Rim/química
15.
JACS Au ; 3(3): 905-918, 2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37006754

RESUMO

CO2 can be electrochemically reduced to different products depending on the nature of catalysts. In this work, we report comprehensive kinetic studies on catalytic selectivity and product distribution of the CO2 reduction reaction on various metal surfaces. The influences on reaction kinetics can be clearly analyzed from the variation of reaction driving force (binding energy difference) and reaction resistance (reorganization energy). Moreover, the CO2RR product distributions are further affected by external factors such as electrode potential and solution pH. A potential-mediated mechanism is found to determine the competing two-electron reduction products of CO2 that shifts from thermodynamics-controlled product formic acid at less negative electrode potentials to kinetic-controlled product CO at more negative electrode potentials. Based on detailed kinetic simulations, a three-parameter descriptor is applied to identify the catalytic selectivity of CO, formate, hydrocarbons/alcohols, as well as side product H2. The present kinetic study not only well explains the catalytic selectivity and product distribution of experimental results but also provides a fast way for catalyst screening.

16.
Front Cell Infect Microbiol ; 13: 1145824, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37077525

RESUMO

Background: Toxoplasmosis caused by Toxoplasma gondii is a globally distributed zoonosis. Most infections appear asymptomatic in immunocompetent individuals, but toxoplasmosis can be fatal in fetuses and immunocompromised adults. There is an urgent need to research and develop effective and low-toxicity anti-T. gondii drugs because of some defects in current clinical anti-T. gondii drugs, such as limited efficacy, serious side effects and drug resistance. Methods: In this study, 152 autophagy related compounds were evaluated as anti-T. gondii drugs. The activity of ß-galactosidase assay based on luminescence was used to determine the inhibitory effect on parasite growth. At the same time, MTS assay was used to further detect the effects of compounds with over 60% inhibition rate on host cell viability. The invasion, intracellular proliferation, egress and gliding abilities of T. gondii were tested to assess the inhibitory effect of the chosen drugs on the distinct steps of the T. gondii lysis cycle. Results: The results showed that a total of 38 compounds inhibited parasite growth by more than 60%. After excluding the compounds affecting host cell activity, CGI-1746 and JH-II-127 were considered for drug reuse and further characterized. Both CGI-1746 and JH-II-127 inhibited tachyzoite growth by 60%, with IC50 values of 14.58 ± 1.52 and 5.88 ± 0.23 µM, respectively. TD50 values were 154.20 ± 20.15 and 76.39 ± 14.32 µM, respectively. Further research found that these two compounds significantly inhibited the intracellular proliferation of tachyzoites. Summarize the results, we demonstrated that CGI-1746 inhibited the invasion, egress and especially the gliding abilities of parasites, which is essential for the successful invasion of host cells, while JH-II-127 did not affect the invasion and gliding ability, but seriously damaged the morphology of mitochondria which may be related to the damage of mitochondrial electron transport chain. Discussion: Taken together, these findings suggest that both CGI-1746 and JH-II-127 could be potentially repurposed as anti-T. gondii drugs, lays the groundwork for future therapeutic strategies.


Assuntos
Toxoplasma , Toxoplasmose , Adulto , Animais , Humanos , Toxoplasmose/tratamento farmacológico , Toxoplasmose/parasitologia , Zoonoses , Proliferação de Células
17.
Neuroimage ; 269: 119928, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36740028

RESUMO

BACKGROUND: The cerebellum is recognized as being involved in neurocognitive and motor functions with communication with extra-cerebellar regions relying on the white matter integrity of the cerebellar peduncles. However, the genetic determinants of cerebellar white matter integrity remain largely unknown. METHODS: We conducted a genome-wide association analysis of cerebellar white matter microstructure using diffusion tensor imaging data from 25,415 individuals from UK Biobank. The integrity of cerebellar white matter microstructure was measured as fractional anisotropy (FA) and mean diffusivity (MD). Identification of independent genomic loci, functional annotation, and tissue and cell-type analysis were conducted with FUMA. The linkage disequilibrium score regression (LDSC) was used to calculate genetic correlations between cerebellar white matter microstructure and regional brain volumes and brain-related traits. Furthermore, the conditional/conjunctional false discovery rate (condFDR/conjFDR) framework was employed to identify the shared genetic basis between cerebellar white matter microstructure and common brain disorders. RESULTS: We identified 11 genetic loci (P < 8.3 × 10-9) and 86 genes associated with cerebellar white matter microstructure. Further functional enrichment analysis implicated the involvement of GABAergic neurons and cholinergic pathways. Significant polygenetic overlap between cerebellar white matter tracts and their anatomically connected or adjacent brain regions was detected. In addition, we report the overall genetic correlation and specific loci shared between cerebellar white matter microstructural integrity and brain-related traits, including movement, cognitive, psychiatric, and cerebrovascular categories. CONCLUSIONS: Collectively, this study represents a step forward in understanding the genetics of cerebellar white matter microstructure and its shared genetic etiology with common brain disorders.


Assuntos
Encefalopatias , Substância Branca , Humanos , Imagem de Tensor de Difusão , Estudo de Associação Genômica Ampla , Encéfalo , Anisotropia
18.
Sci Adv ; 9(4): eade2708, 2023 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-36706192

RESUMO

Membrane proteins expressed on the surface of enveloped viruses are conformational antigens readily recognized by B cells of the immune system. An effective vaccine would require the synthesis and delivery of these native conformational antigens in lipid membranes that preserve specific epitope structures. We have created an extracellular vesicle-based technology that allows viral membrane antigens to be selectively recruited onto the surface of WW domain-activated extracellular vesicles (WAEVs). Budding of WAEVs requires secretory carrier-associated membrane protein 3, which through its proline-proline-alanine-tyrosine motif interacts with WW domains to recruit fused viral membrane antigens onto WAEVs. Immunization with influenza and HIV viral membrane proteins displayed on WAEVs elicits production of virus-specific neutralizing antibodies and, in the case of influenza antigens, protects mice from the lethal viral infection. WAEVs thus represent a versatile platform for presenting and delivering membrane antigens as vaccines against influenza, HIV, and potentially many other viral pathogens.


Assuntos
Vesículas Extracelulares , Infecções por HIV , Vacinas contra Influenza , Influenza Humana , Animais , Camundongos , Humanos , Antígenos Virais , Domínios WW , Antígenos , Prolina
19.
Chinese Journal of Epidemiology ; (12): 386-392, 2023.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-969918

RESUMO

Objective: To investigate the distribution of chronic kidney disease (CKD) in participants from the China Kadoorie Biobank (CKB) study and evaluate the association between lifestyle risk factors and CKD. Methods: Based on the baseline survey data and follow-up data (as of December 31, 2018) of the CKB study, the differences in CKD cases' area and population distributions were described. Cox proportional hazards regression model was used to estimate the association between lifestyle risk factors and the risk of CKD. Results: A total of 505 147 participants, 4 920 cases of CKD were recorded in 11.26 year follow up with a incidence rate of 83.43/100 000 person-years. Glomerulonephropathy was the most common type. The incidence of CKD was higher in the urban area, men, and the elderly aged 60 years and above (87.83/100 000 person-years, 86.37/100 000 person-years, and 132.06/100 000 person-years). Current male smokers had an increased risk for CKD compared with non-smokers or occasional smokers (HR=1.18, 95%CI: 1.05-1.31). The non-obese population was used as a control group, both general obesity determined by BMI (HR=1.19, 95%CI: 1.10-1.29) and central obesity determined by waist circumference (HR=1.27, 95%CI: 1.19-1.35) were associated with higher risk for CKD. Conclusion: The risks for CKD varied with area and population in the CKB cohort study, and the risk was influenced by multiple lifestyle factors.


Assuntos
Idoso , Adulto , Humanos , Masculino , Estudos de Coortes , Prevalência , Estudos Prospectivos , Fatores de Risco , Obesidade/epidemiologia , Insuficiência Renal Crônica/epidemiologia , China/epidemiologia , Estilo de Vida , Índice de Massa Corporal
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-993137

RESUMO

Objective:To evaluate the effects of split-filter dual-energy CT (SF-DECT) in improving image quality at low doses in the process of abdominal examinations for children.Methods:A preliminary study was conducted using child phantoms. Furthermore, 20 children aged 4-6 years were recruited prospectively for clinical validation from June 2020 to December 2020. Conventional single-energy CT (SECT) and SF-DECT were employed to scan the abdominal areas of the phantoms and children. Then, the CT values, image noise, contrast to noise ratios (CNRs), and image subjective scores of SF-DECT and SECT were compared under various doses (1, 2, 3, and 4 mGy).Results:For the phantoms under doses of 3 and 4 mGy, SF-DECT decreased the image noise by 18.9% and 23.6%, respectively, and increased the liver and kidney CNRs (CNR liv and CNR kid) by 12.8% and 31.9% at most, respectively, compared to SECT ( Z = 3.00, 5.17, P < 0.001). For children, SF-DECT decreased image noise ( Z = 4.64, P < 0.001) and increased CNR liv and CNR kid ( Z = 3.78, 3.39, P < 0.001). For both the phantoms and the children, the subjective scores of images scanned using the SF-DECT were higher than those scanned using the SECT ( Z = 1.96-3.80, P < 0.05). Conclusions:Compared with SECT, SF-DECT can improve the quality of children′s abdominal images. This technique has a certain prospect of optimizing abdominal CT for children. However, it is necessary to conduct in-depth clinical research to verify the result.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...