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1.
PLoS Pathog ; 20(4): e1012142, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38574111

RESUMO

RNA viruses and viroids exist and evolve as quasispecies due to error-prone replication. Quasispecies consist of a few dominant master sequences alongside numerous variants that contribute to genetic diversity. Upon environmental changes, certain variants within quasispecies have the potential to become the dominant sequences, leading to the emergence of novel infectious strains. However, the emergence of new infectious variants remains unpredictable. Using mutant pools prepared by saturation mutagenesis of selected stem and loop regions, our study of potato spindle tuber viroid (PSTVd) demonstrates that mutants forming local three-dimensional (3D) structures similar to the wild type (WT) are more likely to accumulate in PSTVd quasispecies. The selection mechanisms underlying this biased accumulation are likely associated with cell-to-cell movement and long-distance trafficking. Moreover, certain trafficking-defective PSTVd mutants can be spread by functional sister genomes in the quasispecies. Our study reveals that the RNA 3D structure of stems and loops constrains the evolution of viroid quasispecies. Mutants with a structure similar to WT have a higher likelihood of being maintained within the quasispecies and can potentially give rise to novel infectious variants. These findings emphasize the potential of targeting RNA 3D structure as a more robust approach to defend against viroid infections.


Assuntos
Vírus de Plantas , Solanum tuberosum , Viroides , Viroides/genética , Solanum tuberosum/genética , RNA Viral/genética , RNA Viral/química , Quase-Espécies , Mutagênese , Doenças das Plantas , Vírus de Plantas/genética
2.
Neuroimage ; 292: 120608, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38626817

RESUMO

The morphological analysis and volume measurement of the hippocampus are crucial to the study of many brain diseases. Therefore, an accurate hippocampal segmentation method is beneficial for the development of clinical research in brain diseases. U-Net and its variants have become prevalent in hippocampus segmentation of Magnetic Resonance Imaging (MRI) due to their effectiveness, and the architecture based on Transformer has also received some attention. However, some existing methods focus too much on the shape and volume of the hippocampus rather than its spatial information, and the extracted information is independent of each other, ignoring the correlation between local and global features. In addition, many methods cannot be effectively applied to practical medical image segmentation due to many parameters and high computational complexity. To this end, we combined the advantages of CNNs and ViTs (Vision Transformer) and proposed a simple and lightweight model: Light3DHS for the segmentation of the 3D hippocampus. In order to obtain richer local contextual features, the encoder first utilizes a multi-scale convolutional attention module (MCA) to learn the spatial information of the hippocampus. Considering the importance of local features and global semantics for 3D segmentation, we used a lightweight ViT to learn high-level features of scale invariance and further fuse local-to-global representation. To evaluate the effectiveness of encoder feature representation, we designed three decoders of different complexity to generate segmentation maps. Experiments on three common hippocampal datasets demonstrate that the network achieves more accurate hippocampus segmentation with fewer parameters. Light3DHS performs better than other state-of-the-art algorithms.


Assuntos
Hipocampo , Imageamento Tridimensional , Imageamento por Ressonância Magnética , Hipocampo/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento Tridimensional/métodos , Redes Neurais de Computação , Aprendizado Profundo , Algoritmos
3.
N Engl J Med ; 385(12): 1067-1077, 2021 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-34459569

RESUMO

BACKGROUND: Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain. METHODS: We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia. RESULTS: A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76). CONCLUSIONS: Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).


Assuntos
Doenças Cardiovasculares/prevenção & controle , Dieta Hipossódica , Hipertensão/dietoterapia , Acidente Vascular Cerebral/prevenção & controle , Idoso , Doenças Cardiovasculares/epidemiologia , China , Dieta Hipossódica/efeitos adversos , Feminino , Humanos , Hiperpotassemia/complicações , Hipertensão/complicações , Hipertensão/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade , Potássio na Dieta/efeitos adversos , Prevenção Secundária , Acidente Vascular Cerebral/epidemiologia
4.
Mol Carcinog ; 63(8): 1542-1558, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38751015

RESUMO

Ovarian cancer (OC) is among the most common and deadly solid malignancies in women. Despite many advances in OC research, the incidence of OC continues to rise, and its pathogenesis remains largely unknown. Herein, we elucidated the function of hsa_circ_0061179 in OC. The levels of hsa_circ_0061179, miR-143-3p, TIMELESS, and DNA damage repair-related proteins in OC or normal ovarian tissues and cells were measured using real-time quantitative polymerase chain reaction and immunoblotting. The biological effects of hsa_circ_0061179 and miR-143-3p on proliferation, clone formation, DNA damage, and apoptosis of OC cells were detected by the cell counting kit-8 assay, 5-methylethyl-2'-deoxyuridine, flow cytometry, the comet assay, and immunofluorescence staining combined with the confocal microscopy. The interaction among hsa_circ_0061179, miR-143-3p, and TIMELESS was validated by the luciferase reporter assay. Mice tumor xenograft models were used to evaluate the influence of hsa_circ_0061179 on OC growth in vivo. We found that human OC biospecimens expressed higher levels of hsa_circ_0061179 and lower levels of miR-143-3p. Hsa_circ_0061179 was found to bind with miR-143-3p, which directly targets TIMELESS. Hsa_circ_0061179 knockdown or miR-143-3p overexpression suppressed the proliferation and clone formation of OC cells and increased DNA damage and apoptosis of OC cells via the miR-143-3p/TIMELESS axis. Furthermore, we demonstrated that METTL3 could direct the formation of has_circ_0061179 through a specific m6A modification site. YTHDC1 facilitated the cytoplasmic transfer of has_circ_0061179 by directly binding to the modified m6A site. Our findings suggest that hsa_circ_0061179 acts as the sponge of miR-143-3p to activate TIMELESS signaling and inhibits DNA damage and apoptosis in OC cells.


Assuntos
Apoptose , Proliferação de Células , Dano ao DNA , Regulação Neoplásica da Expressão Gênica , MicroRNAs , Neoplasias Ovarianas , RNA Circular , Humanos , MicroRNAs/genética , Feminino , Animais , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Camundongos , Linhagem Celular Tumoral , RNA Circular/genética , Camundongos Nus , Ensaios Antitumorais Modelo de Xenoenxerto , Camundongos Endogâmicos BALB C , Adenosina/análogos & derivados , Metiltransferases
5.
Blood ; 139(18): 2770-2781, 2022 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-35226739

RESUMO

Small ubiquitin-like modifier (SUMO) is a member of a ubiquitin-like protein superfamily. SUMOylation is a reversible posttranslational modification that has been implicated in the regulation of various cellular processes including inflammatory responses and expression of type 1 interferons (IFN1). In this report, we have explored the activity of the selective small molecule SUMOylation inhibitor subasumstat (TAK-981) in promoting antitumor innate immune responses. We demonstrate that treatment with TAK-981 results in IFN1-dependent macrophage and natural killer (NK) cell activation, promoting macrophage phagocytosis and NK cell cytotoxicity in ex vivo assays. Furthermore, pretreatment with TAK-981 enhanced macrophage phagocytosis or NK cell cytotoxicity against CD20+ target cells in combination with the anti-CD20 antibody rituximab. In vivo studies demonstrated enhanced antitumor activity of TAK-981 and rituximab in CD20+ lymphoma xenograft models. Combination of TAK-981 with anti-CD38 antibody daratumumab also resulted in enhanced antitumor activity. TAK-981 is currently being studied in phase 1 clinical trials (#NCT03648372, #NCT04074330, #NCT04776018, and #NCT04381650; www.clinicaltrials.gov) for the treatment of patients with lymphomas and solid tumors.


Assuntos
Linfoma , Sumoilação , Citotoxicidade Celular Dependente de Anticorpos , Antígenos CD20 , Linhagem Celular Tumoral , Humanos , Células Matadoras Naturais , Linfoma/tratamento farmacológico , Linfoma/metabolismo , Macrófagos/metabolismo , Rituximab/metabolismo , Rituximab/farmacologia , Rituximab/uso terapêutico
6.
Cancer Control ; 31: 10732748241256819, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38755968

RESUMO

Ovarian cancer (OC) is the most lethal gynecological tumor, characterized by its insidious and frequently recurring metastatic progression. Owing to limited early screening methods, over 70% of OC cases are diagnosed at advanced stages, typically stage III or IV. Recently, N6-methyladenosine (m6A) modification has emerged as a hotspot of epigenetic research, representing a significant endogenous RNA modification in higher eukaryotes. Numerous studies have reported that m6A-related regulatory factors play pivotal roles in tumor development through diverse mechanisms. Moreover, recent studies have indicated the aberrant expression of multiple regulatory factors in OC. Therefore, this paper comprehensively reviews research advancements concerning m6A in OC, aiming to elucidate the regulatory mechanism of m6A-associated regulators on pivotal aspects, such as proliferation, invasion, metastasis, and drug resistance, in OC. Furthermore, it discusses the potential of m6A-associated regulators as early diagnostic markers and therapeutic targets, thus contributing to the diagnosis and treatment of OC.


Ovarian cancer (OC) presents a formidable challenge in the medical field, often detected at advanced stages, necessitating urgent exploration of diagnostic and therapeutic avenues. This review delves into the intricate role of N6-methyladenosine (m6A) RNA modification in OC, a dynamic epigenetic process increasingly recognized for its regulatory role in cancer biology. Highlighting recent advancements, the review sheds light on how m6A-related factors influence crucial aspects of OC progression, including tumor growth, metastasis, and resistance to treatment. Specifically, m6A methyltransferases, binding proteins, and demethylases exert multifaceted effects on OC progression, influencing the expression of pivotal oncogenes and tumor suppressors. While promising, translating these insights into effective therapies requires further investigation. By comprehensively understanding the influence of m6A on OC, there lies hope for developing improved diagnostic techniques and novel treatment strategies to combat this complex disease.


Assuntos
Adenosina , Neoplasias Ovarianas , Humanos , Adenosina/análogos & derivados , Adenosina/metabolismo , Feminino , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/metabolismo , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética
7.
Inorg Chem ; 63(12): 5365-5377, 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38466201

RESUMO

Herein, Bi3+/Mn4+ doped Ca2LaTaO6 phosphors with a double-perovskite structure were successfully synthesized with solid-state reaction at high temperature. The photoluminescence (PL) performances were investigated in detail. The blue radiation (∼465 nm) from the Bi3+ ion and the red radiation (∼686 nm) originating from the Mn4+ ion were obtained under 313 nm excitation. Especially, the pathway of energy transfer (Bi3+ → Mn4+) contributes to enhance the red emission intensity (Mn4+: ∼686 nm) in Ca2LaTaO6:Bi3+/Mn4+ system. The PL mechanism of Ca2LaTaO6:Bi3+/Mn4+ was analyzed through luminescence lifetimes and PL spectra. Moreover, the emitting bands of Ca2LaTaO6:Bi3+/Mn4+ were primarily matched with the absorbing bands of carotenoids and phytochrome PFR on behalf of plant growth, so the phosphors were suitable for the design of a plant growth light under near-ultraviolet to blue excitation. At last, the optical temperature dependent performances of the Ca2LaTaO6:Bi3+/Mn4+ were analyzed with luminescence intensity ratio technology. The sample has presented excellent temperature measuring relative sensitivity (SR = 2.106% K-1). The results illustrated that the Ca2LaTaO6:Bi3+/Mn4+ phosphor also can be used to develop an optical temperature sensor.

8.
Appl Microbiol Biotechnol ; 108(1): 31, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38175233

RESUMO

A complete catalase-encoding gene, designated soiCat1, was obtained from soil samples via metagenomic sequencing, assembly, and gene prediction. soiCat1 showed 73% identity to a catalase-encoding gene of Mucilaginibacter rubeus strain P1, and the amino acid sequence of soiCAT1 showed 99% similarity to the catalase of a psychrophilic bacterium, Pedobacter cryoconitis. soiCAT1 was identified as a psychrophilic enzyme due to the low optimum temperature predicted by the deep learning model Preoptem, which was subsequently validated through analysis of enzymatic properties. Experimental results showed that soiCAT1 has a very narrow range of optimum temperature, with maximal specific activity occurring at the lowest test temperature (4 °C) and decreasing with increasing reaction temperature from 4 to 50 °C. To rationally design soiCAT1 with an improved temperature range, soiCAT1 was engineered through site-directed mutagenesis based on molecular evolution data analyzed through position-specific amino acid possibility calculation. Compared with the wild type, one mutant, soiCAT1S205K, exhibited an extended range of optimum temperature ranging from 4 to 20 °C. The strategies used in this study may shed light on the mining of genes of interest and rational design of desirable proteins. KEY POINTS: • Numerous putative catalases were mined from soil samples via metagenomics. • A complete sequence encoding a psychrophilic catalase was obtained. • A mutant psychrophilic catalase with an extended range of optimum temperature was engineered through site-directed mutagenesis.


Assuntos
Aprendizado Profundo , Catalase/genética , Sequência de Aminoácidos , Aminoácidos , Solo
9.
Lipids Health Dis ; 23(1): 103, 2024 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615017

RESUMO

BACKGROUND: Previous studies have demonstrated the relationship between adipocyte factors, insulin resistance, and other indicators with telomere length. However, these studies did not consider the influence of changes in different indicators on telomere length over time. Therefore, the aim of this study is to elucidate the impact of changes in adipocyte factors, HOMA-IR, and other indicators on the dynamic variation of telomere length. METHODS: The data were from a cohort study conducted in Ningxia, China. A total of 1624 subjects were analyzed. Adipokines and relative leukocyte telomere length (RLTL) were measured, and changes in Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), Homeostatic Model Assessment for ß-Cell Function (HOMA-ß), and Quantitative Insulin Sensitivity Check Index (QUICKI) were calculated. Generalized linear models evaluated associations between changes in adipokines and RLTL changes. Furthermore, univariate analyses examined the effects of changes in adipokines and insulin resistance indicators on ΔRLTL. RESULTS: The research findings indicate that females generally have shorter telomeres compared to males. In comparison to the low-level group of Δleptin (LEP), the high-level group of ΔLEP shows a negative correlation with ΔRLTL (B=-1.32, 95% CI (-2.38, -0.27)). Even after multivariable adjustments, this relationship persists (B=-1.31, 95% CI (-2.24, -0.23)). Further analysis reveals that after adjusting for ΔHOMA-IR, ΔHOMA-ß, and ΔQUICKI, the high-level group of ΔLEP still exhibits a significant negative correlation with ΔRLTL (B=-1.37, 95% CI (-2.43, -0.31)). However, the interaction effects between ΔHOMA-IR, ΔHOMA-ß, ΔQUICKI, and ΔLEP do not affect ΔRLTL. CONCLUSIONS: Elevated levels of leptin were significantly correlated with shortened telomere length. This suggests that increased leptin levels may impact overall individual health by affecting telomere length, underscoring the importance of measures to reduce leptin levels to mitigate the onset and progression of related diseases.


Assuntos
Resistência à Insulina , Leptina , Feminino , Masculino , Humanos , Leptina/genética , Estudos de Coortes , Resistência à Insulina/genética , População Rural , Encurtamento do Telômero , Telômero/genética , Adipocinas , China , Leucócitos
10.
Int J Mol Sci ; 25(13)2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-39000008

RESUMO

RNC1, a plant-specific gene, is known for its involvement in splicing group II introns within maize chloroplast. However, its role in chloroplast development and global gene expression remains poorly understood. This study aimed to investigate the role of RNC1 in chloroplast development and identify the genes that mediate its function in the development of entire tomato plants. Consistent with findings in maize, RNC1 silencing induced dwarfism and leaf whitening in tomato plants. Subcellular localization analysis revealed that the RNC1 protein is localized to both the nucleus and cytoplasm, including the stress granule and chloroplasts. Electron microscopic examination of tomato leaf transverse sections exposed significant disruptions in the spatial arrangement of the thylakoid network upon RNC1 silencing, crucial for efficient light energy capture and conversion into chemical energy. Transcriptome analysis suggested that RNC1 silencing potentially impacts tomato plant development through genes associated with all three categories (biological processes, cellular components, and molecular functions). Overall, our findings contribute to a better understanding of the critical role of RNC1 in chloroplast development and its significance in plant physiology.


Assuntos
Cloroplastos , Regulação da Expressão Gênica de Plantas , Proteínas de Plantas , Solanum lycopersicum , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Solanum lycopersicum/crescimento & desenvolvimento , Cloroplastos/metabolismo , Cloroplastos/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Folhas de Planta/metabolismo , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Perfilação da Expressão Gênica
11.
Environ Geochem Health ; 46(2): 51, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38227065

RESUMO

The previous studies have shown that iron-manganese co-oxide film (MeOx) could simultaneously remove ammonium, manganese ion and bisphenol A. In this study, the removal of fulvic acid (FA) was explored by adding potassium ferrate (K2FeO4) to heighten the catalytic activity of MeOx. After adding about 3.0 mg/L potassium ferrate, the elimination efficiency of 7.0 mg/L FA by the MeOx increased from 20 to 50%. The effects of temperature and ammonium on the elimination of FA were investigated. Higher temperature (above 22 °C) and higher ammonium concentration (above 2.0 mg/L) caused a decrease in FA removal. Most of FA combined with the ferric hydroxide colloid produced by K2FeO4 in water to form macromolecular groups, and they were subsequently absorbed and covered on the surface of MeOx. Scanning electron microscope showed that more viscous flocs appeared on the surface of MeOx, and the film thickness became thicker. Electron energy-dispersive spectrometer analysis revealed a notable increased in the C-O element ratio and a significant decreased in the Mn-Fe element ratio on the surface of MeOx. From Fourier transform infrared spectroscopy, the content of transition metal carbonyl compounds increased in the surface of MeOx. XPS analysis confirmed that the presence of Fe3O4, FeO, Mn2O3 and Mn3O4 along with functional group substances of FA attached on the surface of MeOx. The removal mechanism of FA was studied.


Assuntos
Compostos de Amônio , Benzopiranos , Compostos de Ferro , Ferro , Compostos de Manganês , Compostos de Potássio , Água , Manganês , Óxidos , Carbono
12.
Aust Crit Care ; 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38969541

RESUMO

OBJECTIVES: Advances in critical care technology have lowered mortality rates among critically ill individuals. Nonetheless, survivors and their families may develop new physical, mental, cognitive, and social challenges due to paediatric intensive care unit (PICU) treatments, impacting their quality of life. The aim of this study was to investigate the survival journey and post-traumatic growth process of children and their families following PICU admission within the Chinese cultural context. METHODS: Twenty-six children who have been or are currently admitted to the PICU, alongside their parents and three PICU nurses, were chosen through purposive and theoretical sampling. Data collection involved face-to-face interviews and observations, with data analysis conducted through continuous comparison, open coding, and selective coding techniques. FINDINGS: A model outlining the survival journey and post-traumatic growth process of critically ill children and their families post PICU admission has been established. This model encompasses two central trajectories: an upward trajectory consisting of confusion, charging, action, and sublimation phases and a downward trajectory comprising confusion, doubt and fear, inhibition (including confrontation and avoidance), and drowning phases. CONCLUSIONS: Critically ill children and their families encounter diverse survival experiences and psychological journeys following traumatic events in the PICU. The survival experience has alternative upwards or downwards trajectories that are flexible/adaptable. Hence, offering timely psychological support can alter their developmental trajectories and foster post-traumatic growth.

13.
Circulation ; 145(20): 1534-1541, 2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35311346

RESUMO

BACKGROUND: SSaSS (Salt Substitute and Stroke Study), a 5-year cluster randomized controlled trial, demonstrated that replacing regular salt with a reduced-sodium, added-potassium salt substitute reduced the risks of stroke, major adverse cardiovascular events, and premature death among individuals with previous stroke or uncontrolled high blood pressure living in rural China. This study assessed the cost-effectiveness profile of the intervention. METHODS: A within-trial economic evaluation of SSaSS was conducted from the perspective of the health care system and consumers. The primary health outcome assessed was stroke. We also quantified the effect on quality-adjusted life-years (QALYs). Health care costs were identified from participant health insurance records and the literature. All costs (in Chinese yuan [¥]) and QALYs were discounted at 5% per annum. Incremental costs, stroke events averted, and QALYs gained were estimated using bivariate multilevel models. RESULTS: Mean follow-up of the 20 995 participants was 4.7 years. Over this period, replacing regular salt with salt substitute reduced the risk of stroke by 14% (rate ratio, 0.86 [95% CI, 0.77-0.96]; P=0.006), and the salt substitute group had on average 0.054 more QALYs per person. The average costs (¥1538 for the intervention group and ¥1649 for the control group) were lower in the salt substitute group (¥110 less). The intervention was dominant (better outcomes at lower cost) for prevention of stroke as well as for QALYs gained. Sensitivity analyses showed that these conclusions were robust, except when the price of salt substitute was increased to the median and highest market prices identified in China. The salt substitute intervention had a 95.0% probability of being cost-saving and a >99.9% probability of being cost-effective. CONCLUSIONS: Replacing regular salt with salt substitute was a cost-saving intervention for the prevention of stroke and improvement of quality of life among SSaSS participants.


Assuntos
Hipertensão , Acidente Vascular Cerebral , Análise Custo-Benefício , Humanos , Qualidade de Vida , Anos de Vida Ajustados por Qualidade de Vida , Cloreto de Sódio na Dieta/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
14.
Small ; 19(43): e2303034, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37365695

RESUMO

Rapid and accurate imaging of the BCR/ABL fusion gene isoforms (e.g., e13a2, e14a2 and co-expression type) of chronic myeloid leukemia (CML) is of vital importance to first-line drug selection, but there is no assay that meets clinical needs (e.g., clinical kits > 18 h without isoforms information). Herein, an in situ imaging platform is developed for the rapid and accurate detection of CML fusion gene isoforms using asymmetric sequence-enhanced hairpins DNA encapsulated silver nanoclusters (ADHA) and catalyzed hairpin assembly (CHA). The specific detection of e13a2 and e14a2 fusion gene isoforms with detection limits of 19.2 am (11.558 copies µL-1 ) and 32.56 am (19.601 copies µL-1 ) in one-pot is achieved. The feasibility of the developed assay for real-world applications are demonstrated by one-step fluorescence imaging (40 min) of e13a2, e14a2 and co-expression type in bone marrow quantitatively (International Standard: 15.66%-168.878%) and further validated by cDNA-sequencing. This work suggests that the developed imaging platform holds great potential for rapid identification of the fusion gene isoforms and isoform related treatment monitoring.


Assuntos
Proteínas de Fusão bcr-abl , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Proteínas de Fusão bcr-abl/genética , Proteínas de Fusão bcr-abl/uso terapêutico , Medula Óssea , Prata/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Isoformas de Proteínas/genética , DNA Complementar , Imagem Óptica
15.
Crit Rev Food Sci Nutr ; : 1-15, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38032232

RESUMO

The impacts of probiotics on maintaining the host's intestinal health have been extensively confirmed. Organoid technology revolutionizes intestinal health research by providing a unique platform to study the effects of probiotics. It overcomes challenges posed by animal models and 2D cell models in accurately simulating the in vivo environment. This review summarizes the development of intestinal organoid technology and its potential applications in intestinal health research as well as highlights the regulatory mechanisms of probiotics on intestinal health, which have been revealed using intestinal organoid technology. Furthermore, an overview of its potential applications in probiotic research has also been provided. This review aims to improve the understanding of intestinal organoid technology's applications in this field as well as to contribute to its further development.

16.
Eur Radiol ; 33(4): 2954-2964, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36418619

RESUMO

OBJECTIVES: To establish a breast lesion risk stratification system using ultrasound images to predict breast malignancy and assess Breast Imaging Reporting and Data System (BI-RADS) categories simultaneously. METHODS: This multicenter study prospectively collected a dataset of ultrasound images for 5012 patients at thirty-two hospitals from December 2018 to December 2020. A deep learning (DL) model was developed to conduct binary categorization (benign and malignant) and BI-RADS categories (2, 3, 4a, 4b, 4c, and 5) simultaneously. The training set of 4212 patients and the internal test set of 416 patients were from thirty hospitals. The remaining two hospitals with 384 patients were used as an external test set. Three experienced radiologists performed a reader study on 324 patients randomly selected from the test sets. We compared the performance of the DL model with that of three radiologists and the consensus of the three radiologists. RESULTS: In the external test set, the DL model achieved areas under the receiver operating characteristic curve (AUCs) of 0.980 and 0.945 for the binary categorization and six-way categorizations, respectively. In the reader study set, the DL BI-RADS categories achieved a similar AUC (0.901 vs. 0.933, p = 0.0632), sensitivity (90.98% vs. 95.90%, p = 0.1094), and accuracy (83.33% vs. 79.01%, p = 0.0541), but higher specificity (78.71% vs. 68.81%, p = 0.0012) than those of the consensus of the three radiologists. CONCLUSIONS: The DL model performed well in distinguishing benign from malignant breast lesions and yielded outcomes similar to experienced radiologists. This indicates the potential applicability of the DL model in clinical diagnosis. KEY POINTS: • The DL model can achieve binary categorization for benign and malignant breast lesions and six-way BI-RADS categorizations for categories 2, 3, 4a, 4b, 4c, and 5, simultaneously. • The DL model showed acceptable agreement with radiologists for the classification of breast lesions. • The DL model performed well in distinguishing benign from malignant breast lesions and had promise in helping reduce unnecessary biopsies of BI-RADS 4a lesions.


Assuntos
Neoplasias da Mama , Aprendizado Profundo , Humanos , Feminino , Neoplasias da Mama/patologia , Mama/diagnóstico por imagem , Ultrassonografia , Medição de Risco , Ultrassonografia Mamária/métodos , Estudos Retrospectivos
17.
Eur J Clin Pharmacol ; 79(1): 63-70, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36342528

RESUMO

PURPOSE: To comprehensively compare the efficacy of different antiplatelet therapies for secondary prevention of lacunar stroke (LS). METHODS: The relevant studies were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Collaboration Database up to May 2022. Cardiovascular and cerebrovascular events were chosen to evaluate the efficacy of antiplatelet therapy for secondary prevention. Loop-specific approach and node-splitting analysis were used to evaluate consistency and inconsistency, respectively. The value of the surface under the cumulative ranking (SUCRA) was calculated and ranked. Funnel-plot symmetry was used to evaluate publication bias. The meta-analysis was performed by using STATA 16.0. RESULTS: Thirteen studies with a total of 33,011 subjects were included in this network meta-analysis. Compared with placebo, aspirin, clopidogrel, cilostazol, ticlopidine, aspirin plus dipyridamole, and aspirin plus clopidogrel were associated with reducing cardiovascular and cerebrovascular events. The SUCRA estimated relative ranking of treatments showed that cilostazol may be the most effective (RR 0.56, 95% CI 0.42-0.74, SUCRA 95.8). No significant inconsistency or publication bias was found in the study. CONCLUSIONS: This meta-analysis suggests that cilostazol may be a priority option for secondary prevention of patients with LS. These findings still need further study in the future.


Assuntos
Acidente Vascular Cerebral Lacunar , Acidente Vascular Cerebral , Humanos , Inibidores da Agregação Plaquetária/uso terapêutico , Clopidogrel/uso terapêutico , Cilostazol/uso terapêutico , Prevenção Secundária , Metanálise em Rede , Acidente Vascular Cerebral Lacunar/prevenção & controle , Acidente Vascular Cerebral Lacunar/tratamento farmacológico , Aspirina/uso terapêutico , Quimioterapia Combinada , Acidente Vascular Cerebral/prevenção & controle , Acidente Vascular Cerebral/tratamento farmacológico
18.
BMC Pregnancy Childbirth ; 23(1): 399, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-37254065

RESUMO

BACKGROUND: Parenting sense of competence is not only indispensable to the wellbeing of the parents of premature infants, but is also pivotal to the overall development of these infants. This study examined the level of parenting sense of competence and its associated factors in Chinese parents of preterm infants. METHODS: This cross-sectional study was performed at a university teaching hospital in Fuzhou (China) from December 2021 to April 2022. Data were collected using the Parenting Sense of Competence Scale, Edinburgh Postnatal Depression Scale, Social Support Rating Scale, Parenting Care Knowledge Subscale, Parenting Care Skill Subscale, and a sociodemographic questionnaire. RESULTS: A total of 401 Chinese parents were included in the analysis. The average parenting sense of competence scale score was 70.93 ± 13.06. After controlling for demographic characteristics, parenting knowledge (ß = 0.149, P = 0.013), parenting skills (ß = 0.241, P < 0.001), social support (ß = 0.184, P < 0.001) and depression (ß = -0.272, P < 0.001), were significantly associated with the parenting sense of competence score, and explained 43.60% of the variance in this score. CONCLUSIONS: Chinese parents of preterm infants were found to have a moderate parenting sense of competence. This could be further improved through efforts aimed at reducing depressive symptoms and increasing parenting knowledge, parenting skills, and social support.


Assuntos
Recém-Nascido Prematuro , Poder Familiar , Humanos , Lactente , Recém-Nascido , Estudos Transversais , População do Leste Asiático , Pais
19.
BMC Womens Health ; 23(1): 491, 2023 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-37715186

RESUMO

BACKGROUND: Since the connection between muscle atrophy and vitamin D and estradiol status ambiguous, this study was thus conducted to determine whether low skeletal muscle mass (SMM) in middle-aged and elderly women was affected by estradiol and vitamin D levels together. METHODS: Baseline data from a sub-cohort of the China Northwest Natural Population Cohort: Ningxia Project (CNC-NX) were analyzed. Serum 25-hydroxyvitamin D (25(OH) D) and estradiol were measured by chemiluminescence immunoassay analyzer. Bivariate logistic regression and multiplicative interaction analyses were used to assess the impact of estradiol level and vitamin D status on low SMM, as well as the combined impact of estradiol and low vitamin D status on low SMM. RESULTS: A total of 287 (9.49%) participants had low SMM, which had lower levels of estradiol and vitamin D concentration than normal SMM group. While, after adjusting the confounding variables, these correlations were maintained in estradiol Q1, Q2, Q3 and vitamin D Q1. Furthermore, the significant combined effect of the highest quartile of estradiol concentrations and non-vitamin D deficiency, and interactions between vitamin D Q1 and estradiol Q2, vitamin D Q1 and estradiol Q3, vitamin D Q2 and estradiol Q1, vitamin D Q3 and estradiol Q3 on low SMM were stably reflected (P for interaction < 0.05). CONCLUSIONS: Estradiol and vitamin D were interrelated with low SMM in middle-aged and elderly women. Combination of estradiol and vitamin D supplements should be encouraged for middle-aged and elderly women who are at risk of muscle atrophy or experiencing muscle atrophy.


Assuntos
Calcifediol , Suplementos Nutricionais , Idoso , Pessoa de Meia-Idade , Feminino , Humanos , Estradiol , Músculo Esquelético , Atrofia Muscular
20.
Lipids Health Dis ; 22(1): 173, 2023 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-37853446

RESUMO

BACKGROUND AND AIMS: Leukocyte telomere length (LTL) as a 'biological clock' of aging is closely related to human health, its association with an aging-related disease, dyslipidemia, has been less studied and mainly focused on cross-sectional investigations. METHODS: Two rounds of information and blood collections were conducted on a cohort of 1624 individuals residing in rural Ningxia, located in northwest China, with an average time gap of 9.8 years. The relative telomere length (RTL) of peripheral blood leukocytes was assessed using real-time quantitative PCR. To investigate the association between dyslipidemia, blood lipid levels, and alterations in RTL, multiple linear regression and generalized linear models were employed. RESULTS: After conducting the follow-up analysis, it was observed that 83.3% of the participants in the study exhibited a reduction in telomere length, while 16.7% experienced an increase in telomere length. The results suggested that dyslipidemia at baseline or follow-up may increase longitudinal changes in telomere length, but it was more significant in the healthy group, especially in those aged ≥ 60 years. Furthermore, HDL-C levels in baseline and follow-up were found to be associated with longitudinal changes in telomere length, and lower HDL-C levels may be associated with increased longitudinal changes in telomere length. CONCLUSIONS: The change in telomere length is correlated with dyslipidemia and its lipid indicators especially HDL-C. Persistent dyslipidemia and a reduction in HDL-C levels may be associated with elevated longitudinal fluctuations in telomere length.


Assuntos
Envelhecimento , Leucócitos , Humanos , Estudos Transversais , Envelhecimento/genética , Reação em Cadeia da Polimerase em Tempo Real , Telômero/genética , Lipídeos , Estudos Longitudinais
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