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1.
J Am Stat Assoc ; 119(546): 851-863, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39371422

RESUMO

Brain functional connectivity or connectome, a unique measure for brain functional organization, provides a great potential to explain the neurobiological underpinning of behavioral profiles. Existing connectome-based analyses highly concentrate on brain activities under a single cognitive state, and fail to consider heterogeneity when attempting to characterize brain-to-behavior relationships. In this work, we study the complex impact of multi-state functional connectivity on behaviors by analyzing the data from a recent landmark brain development and child health study. We propose a nonparametric, Bayesian supervised heterogeneity analysis to uncover neurodevelopmental subtypes with distinct effect mechanisms. We impose stochastic block structures to identify network-based functional phenotypes and develop a variational expectation-maximization algorithm to facilitate an efficient posterior computation. Through integrating resting-state and task-related functional connectomes, we dissect heterogeneous effect mechanisms on children's fluid intelligence from the functional network phenotypes including Fronto-parietal Network and Default Mode Network under different cognitive states. Based on extensive simulations, we further confirm the superior performance of our method on uncovering brain-to-behavior relationships.

2.
BMC Pregnancy Childbirth ; 24(1): 630, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354371

RESUMO

BACKGROUND: The childbirth experience of primipara profoundly impacts her future physical and mental health, reproductive intention, and choice of childbirth mode. This study aimed to explore the current situation of primipara's childbirth experience, to analyze the factors influencing negative childbirth experience, and to explore the relationship between childbirth experience and reproductive intention. METHODS: A cross-sectional survey of a convenience sample of 522 primipara 1-5 days postpartum was conducted at five hospitals in Guangdong Province (May to July 2024). Data were collected using the General Information Questionnaire, the Social Support Rating Scale, the Childbirth Readiness Scale, the Caring Behaviors Inventory Scale, the Wijma Delivery Experience Questionnaire, and the Questionnaire on Reproduction Intention of Primipara. RESULTS: The mean score of fear of childbirth was 68.86 ± 17.68. A total of 137 respondents met the clinical criteria for fear of childbirth (≥ 85 points), indicating that 26.2% of primipara had a negative experience of childbirth. Binary logistic regression model showed that elderly primipara [odds ratio (OR) (95% confidence interval (CI)): 11.167 (2.737-45.559)], pregnancy comorbidities or maternal childbirth complications [OR (95%CI): 6.596 (3.046-14.287)], childbirth intervention [OR (95%CI): 6.168 (2.869-13.258)], and severe pain [OR (95%CI): 4.660 (2.197-9.882)] were risk factors for negative childbirth experience. Childbirth accompaniment [OR (95%CI): 0.081 (0.018-0.368)], high level of social support [OR (95%CI): 0.768 (0.704-0.839)], and high level of childbirth readiness [OR (95%CI): 0.878 (0.812-0.950)] protected against a negative birth experience. There was a negative correlation between the fear of childbirth score and reproduction intention scores. CONCLUSIONS: Childbirth accompaniment and high levels of social support and childbirth readiness can reduce primipara's perception of negative childbirth experience. Negative childbirth experience can reduce reproduction intention.


Assuntos
Medo , Intenção , Parto , Humanos , Feminino , Estudos Transversais , Parto/psicologia , Adulto , Gravidez , Inquéritos e Questionários , Medo/psicologia , China , Paridade , Adulto Jovem , Apoio Social , Parto Obstétrico/psicologia
3.
J Ethnopharmacol ; 337(Pt 3): 118941, 2024 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-39427735

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of Shaoyao decoction (SYD), a traditional Chinese medicine prescription, in alleviating colonic mucosal inflammation in ulcerative colitis (UC) has been established. However, the specific mechanism underlying the therapeutic effects of SYD on UC is not clear. AIM OF STUDY: In this study, we demonstrated the therapeutic effect of SYD on the polarization of M1 macrophages and elucidated the underlying mechanism. MATERIALS AND METHODS: UC mice were induced with 3% DSS for one week and subsequently treated with SYD for another week. The composition of SYD was determined by HPLC. To assess the therapeutic efficacy of SYD, key parameters, including body weight changes, DAI scores, colon length, and histological alterations in colonic tissues, were monitored. ELISA was performed to quantify inflammatory cytokines, while Western blotting and immunofluorescence analyses were performed to quantify tight junction protein expression and M1 macrophage infiltration, respectively. Functional assessments focused on lysosomal activity and glucose oxidation in primary macrophages and RAW 264.7 cells exposed to LPS, IL-17a, and SYD using dedicated kits. To elucidate the mechanisms underlying the action of SYD, the data derived from TMT-based proteomics were analyzed to screen and predict its potential targets and regulated pathways. RESULTS: After treatment for seven days, SYD significantly mitigated colitis symptoms in mice, as determined by a decrease in body weight loss, an increase in colon length, and a decrease in disease activity index (DAI) score. The results of histopathological analysis showed substantial improvements in the integrity of colonic tissue. Additionally, SYD treatment significantly decreased the levels of proinflammatory cytokines, including IL-17a, IL-6, IL-1ß, and TNF-α. This effect was accompanied by a reduction in the infiltration of CD86+ macrophages and restoration of occludin and ZO-1 levels, thus improving colonic mucosal permeability. SYD treatment also reversed the upregulation of cathepsin (CTS) E, CTSS, lysosomal-associated membrane protein (LAMP)-1, and LAMP-2 expression observed in CD86+ macrophages and RAW 264.7 cells treated with IL-17a. These changes were accompanied by an increase in lysosomal acidification and the enzymatic activities of CTSE and CTSS, suggesting that SYD can restore lysosomal function. SYD also corrected the metabolic alterations in M1 macrophages, characterized by an increase in the extracellular acidification rate (ECAR) and a decrease in oxygen consumption rate (OCR). This was confirmed by a decrease in the ADP/ATP ratio, downregulation of pyruvate dehydrogenase kinase 4 (PDK4) and lactate dehydrogenase (LDH) expression, and a decrease in the concentrations of intracellular pyruvate and lactate. These findings showed that SYD promotes glucose oxidation in macrophages. The data derived from TMT-based proteomics showed that the PPAR pathway was a key target in regulating the polarization of M1 macrophages. SYD was also found to regulate the expression of the PPAR-α, PPAR-γ, and PPAR-δ proteins. CONCLUSION: SYD inhibited the polarization of M1 macrophages induced by IL-17a. This effect occurred due to the restoration of lysosomal activity and glucose oxidation via activation of the PPAR/NF-κB pathway. Our findings provided novel insights into the mechanisms underlying the therapeutic effects of SYD in UC.

4.
Medicine (Baltimore) ; 103(35): e39401, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-39213206

RESUMO

To develop a set of cognitive behavioral therapies (CBTs) to alleviate anxiety in orthopedic surgery (OS) patients, to explore the intervention effects of CBTs on the indicators of anxiety, sleep quality, and pain sensation in OS patients, and to promote them. A total of 68 qualified subjects were selected from among the 103 patients with orthopedic diseases who were hospitalized in the orthopedic department of the hospital between June 2022 and November 2023. According to the different nursing methods, they were divided into a psychological intervention (PI) group and a control intervention group. Among them, 34 patients received hospital-developed CBT for OS in the PI group, and 34 patients received standard orders from the medical staff in the control intervention group. Tools such as self-assessment of anxiety, Athens insomnia scale, state anxiety scale, visual analog pain method, and self-management level scale were utilized to assess the change in anxiety levels, sleep quality, pain perception, and self-management level of the 2 groups of patients before and after the surgery. Following the CBT intervention, patients in the PI group had significantly lower Athens insomnia scale (5.32 ±â€…0.42), state anxiety scale (38.21 ±â€…1.12), and visual analog pain method (3.93 ±â€…1.24) scores than those in the control intervention group. This difference was statistically significant (P < .05). In the meantime, patients in the PI group had a substantially higher correct rate of illness cognition assessment (98.21%) than patients in the control intervention group (65.12%), and this difference was statistically significant (P < .05). The study collated the factors affecting anxiety in OS patients through questionnaire survey and statistical analysis experiment and then formulated a detailed CBT strategy for specific problems. Finally, CBT is a valuable tool for reducing anxiety in OS patients. As such, it deserves to be promoted and used in clinical settings.


Assuntos
Ansiedade , Terapia Cognitivo-Comportamental , Procedimentos Ortopédicos , Humanos , Terapia Cognitivo-Comportamental/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Ansiedade/terapia , Ansiedade/etiologia , Ansiedade/prevenção & controle , Procedimentos Ortopédicos/métodos , Procedimentos Ortopédicos/psicologia , Adulto , Qualidade do Sono , Intervenção Psicossocial/métodos , Medição da Dor , Idoso
5.
Clin Case Rep ; 12(6): e8998, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38799535

RESUMO

Key Clinical Message: Administering azathioprine or infliximab for UC and AS treatment carries a significant risk of adverse reactions. Here, we present the case diagnosed with UC and AS, who received treatment with azathioprine and infliximab for 10 months, and subsequently developed drug-induced myopathy affecting the right vastus medialis muscle. Abstract: Drug-induced myopathy is an uncommon form of muscle injury that can arise in patients without preexisting muscle conditions when exposed to therapeutic doses of certain medications. Administering azathioprine or infliximab for ulcerative colitis (UC) and ankylosing spondylitis (AS) treatment carries a significant risk of adverse reactions, including drug-induced myopathy and increased susceptibility to opportunistic infections. However, occurrences of myopathy induced by the combination of azathioprine and infliximab are rarely reported in clinical practice. Here, we present the case of a 37-year-old male patient diagnosed with UC and AS, who received treatment with azathioprine and infliximab for 10 months. Despite the resolution of symptoms and improvement in intestinal mucosal inflammation observed via endoscopy, the patient subsequently developed drug-induced myopathy affecting the right vastus medialis muscle.

6.
PLoS One ; 19(4): e0299530, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38662787

RESUMO

Typhoons are natural disasters characterized by their high frequency of occurrence and significant impact, often leading to secondary disasters. In this study, we propose a prediction model for the trend of typhoon disasters. Utilizing neural networks, we calculate the forgetting gate, update gate, and output gate to forecast typhoon intensity, position, and disaster trends. By employing the concept of big data, we collected typhoon data using Python technology and verified the model's performance. Overall, the model exhibited a good fit, particularly for strong tropical storms. However, improvements are needed to enhance the forecasting accuracy for tropical depressions, typhoons, and strong typhoons. The model demonstrated a small average error in predicting the latitude and longitude of the typhoon's center position, and the predicted path closely aligned with the actual trajectory.


Assuntos
Big Data , Tempestades Ciclônicas , Previsões , Previsões/métodos , Redes Neurais de Computação , Desastres , Humanos , Planejamento em Desastres/métodos
7.
MicroPubl Biol ; 20242024.
Artigo em Inglês | MEDLINE | ID: mdl-38660567

RESUMO

ProQ is a FinO-domain protein found in E. coli and other proteobacteria that has a global RNA-binding profile. In order to probe the detailed mechanism of RNA interactions, we have developed a collection of 13 E. coli ProQ variants that possess single-cysteine residues at varied positions on the surface of the N-terminal FinO domain and retain the ability to bind well to RNA. This set of variant ProQ proteins will support future biochemical and biophysical studies to map the orientation of bound RNAs to different sites around the ProQ protein, shedding light on the mechanism of ProQ-RNA interactions.

8.
PeerJ ; 12: e16960, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38436017

RESUMO

Important transformations of the pectoral girdle are related to the appearance of flight capabilities in the Dinosauria. Previous studies on this topic focused mainly on paravians yet recent data suggests flight evolved in dinosaurs several times, including at least once among non-avialan paravians. Thus, to fully explore the evolution of flight-related avian shoulder girdle characteristics, it is necessary to compare morphology more broadly. Here, we present information from pennaraptoran specimens preserving pectoral girdle elements, including all purportedly volant taxa, and extensively compare aspects of the shoulder joint. The results show that many pectoral girdle modifications appear during the evolution from basal pennaraptorans to paravians, including changes in the orientation of the coracoid body and the location of the articulation between the furcula and scapula. These modifications suggest a change in forelimb range of motion preceded the origin of flight in paravians. During the evolution of early avialans, additional flight adaptive transformations occur, such as the separation of the scapula and coracoid and reduction of the articular surface between these two bones, reduction in the angle between these two elements, and elongation of the coracoid. The diversity of coracoid morphologies and types of articulations joining the scapula-coracoid suggest that each early avialan lineage evolved these features in parallel as they independently evolved more refined flight capabilities. In early ornithothoracines, the orientation of the glenoid fossa and location of the acrocoracoid approaches the condition in extant birds, suggesting a greater range of motion in the flight stroke, which may represent the acquisition of improved powered flight capabilities, such as ground take-off. The formation of a new articulation between the coracoid and furcula in the Ornithuromorpha is the last step in the formation of an osseous triosseal canal, which may indicate the complete acquisition of the modern flight apparatus. These morphological transitions equipped birds with a greater range of motion, increased and more efficient muscular output and while at the same time transmitting the increased pressure being generated by ever more powerful flapping movements in such a way as to protect the organs. The driving factors and functional adaptations of many of these transitional morphologies are as yet unclear although ontogenetic transitions in forelimb function observed in extant birds provide an excellent framework through which we can explore the behavior of Mesozoic pennaraptorans.


Assuntos
Dinossauros , Articulação do Ombro , Animais , Extremidade Superior , Membro Anterior , Aves , Escápula
9.
Heliyon ; 10(4): e26112, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38390135

RESUMO

Online learning has evolved as an attractive and viable option for education, yet there is a need for further research to investigate the factors contributing to students' online learning anxiety regarding the college English course. Based on Keegan's distance education framework, this study examines the factors impacting online learning anxiety among English as foreign language (EFL) students in the Chinese context during the post-COVID-19 era. Data were collected from 899 EFL students across different regions of China through an online survey. Follow-up interviews with ten students provided additional insights into the association between online English learning and anxiety. The collected data underwent descriptive analysis, exploratory factor analysis, reliability analysis, and multiple linear regression analysis to examine the relationship between online learning anxiety and the identified factors. The results of our study indicate that many Chinese EFL students experienced different degrees of anxiety, ranging from mild to moderate or severe. Moreover, online learning anxiety among Chinese EFL students was positively predicted by a lack of learning motivation, separation from instructors, separation from peers, and technological challenges, while a lack of two-way communication negatively predicted it. The findings underscore the importance of taking effective measures and offering psychological guidance for Chinese EFL students to alleviate anxiety and facilitate their successful adaptation to the new normal of online learning.

10.
Genome Res ; 34(1): 20-33, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38190638

RESUMO

As an essential part of the central nervous system, white matter coordinates communications between different brain regions and is related to a wide range of neurodegenerative and neuropsychiatric disorders. Previous genome-wide association studies (GWASs) have uncovered loci associated with white matter microstructure. However, GWASs suffer from limited reproducibility and difficulties in detecting multi-single-nucleotide polymorphism (multi-SNP) and epistatic effects. In this study, we adopt the concept of supervariants, a combination of alleles in multiple loci, to account for potential multi-SNP effects. We perform supervariant identification and validation to identify loci associated with 22 white matter fractional anisotropy phenotypes derived from diffusion tensor imaging. To increase reproducibility, we use United Kingdom (UK) Biobank White British (n = 30,842) data for discovery and internal validation, and UK Biobank White but non-British (n = 1927) data, Europeans from the Adolescent Brain Cognitive Development study (n = 4399) data, and Europeans from the Human Connectome Project (n = 319) data for external validation. We identify 23 novel loci on the discovery set that have not been reported in the previous GWASs on white matter microstructure. Among them, three supervariants on genomic regions 5q35.1, 8p21.2, and 19q13.32 have P-values lower than 0.05 in the meta-analysis of the three independent validation data sets. These supervariants contain genetic variants located in genes that have been related to brain structures, cognitive functions, and neuropsychiatric diseases. Our findings provide a better understanding of the genetic architecture underlying white matter microstructure.


Assuntos
Substância Branca , Humanos , Adolescente , Substância Branca/diagnóstico por imagem , Imagem de Tensor de Difusão , Estudo de Associação Genômica Ampla , Reprodutibilidade dos Testes , Encéfalo/diagnóstico por imagem
11.
Clin Rheumatol ; 43(3): 1073-1082, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38206544

RESUMO

OBJECTIVE: To assess the long-term safety and efficacy of umbilical cord mesenchymal stem cells transplantation (UMSCT) in patients with systemic sclerosis (SSc). METHODS: Forty-one patients with moderate to severe SSc underwent UMSCT at the Affiliated Drum Tower Hospital of Nanjing University Medical School from 2009 to 2017. In this study, we conducted a longitudinal and retrospective analysis and compared the clinical and laboratory manifestations before and after UMSCT. The main outcome of the study was overall survival. We evaluated changes in the modified Rodnan Skin Score (mRSS), as well as the changes in the pulmonary examination by using high-resolution computed tomography (HRCT) and ultrasound cardiogram (UCG). Additionally, we assessed the Health Assessment Questionnaire-Disability Index (HAQ-DI) and the severity of peripheral vascular involvement during the first year after treatment. RESULTS: The overall 5-year survival rate was 92.7% (38 out of 41 patients). Following UMSCT, the mean mRSS significantly decreased from 18.68 (SD = 7.26, n = 41) at baseline to 13.95 (SD = 8.49, n = 41), 13.29 (SD = 7.67, n = 38), and 12.39 (SD = 8.49, n = 38) at 1, 3, and 5 years, respectively. Improvement or stability in HRCT images was observed in 72.0% of interstitial lung disease (ILD) patients. Pulmonary arterial hypertension (PAH) remained stable in 5 out of 8 patients at the 5-year follow-up. No adverse events related to UMSCT were observed in any of the patients during the follow-up period. CONCLUSION: UMSCT may provide a safe and feasible treatment option for patients with moderate to severe SSc based on long-term follow-up data. The randomized controlled study will further confirm the clinical efficacy of UMSCT in SSc. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00962923. Key Point • UMSCT is safe and effective for SSc patients.


Assuntos
Células-Tronco Mesenquimais , Escleroderma Sistêmico , Humanos , Seguimentos , Pulmão , Estudos Retrospectivos , Escleroderma Sistêmico/diagnóstico por imagem , Escleroderma Sistêmico/terapia
12.
Eval Rev ; 48(2): 312-345, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37350232

RESUMO

Economic corridors unlock new economic opportunities and tourism development in the region to achieve sustainable development goals. Green economic growth is conducive to environmental sustainability. Economic mega-projects of CPEC promote tourism that leads to communities' well-being and better quality of life. Modern infrastructure development contributes significantly to economic growth and tourism activities. This study's objectives emphasize exploring tourism and sustainable development pursuits under OBOR economic projects that open doors to improving residents' quality of life. The growing world is an eyewitness to a continuous rise in emissions and its severe consequences for humankind. It is necessary to show off the leading factors that result in tourism and economic activities causing environmental pollution rather than blame policymakers. Undoubtedly, many studies previously focused on demonstrating the influence of socio-economic factors that lead to better environmental quality. However, the empirical literature on tourism, social well-being, foreign direct investment, and the Environment in Belt and Road developed economies needed improvement. This research applied a series of advanced estimators that help demonstrate the study's probable results. This study explores the role of Social well-being (HDI), tourism development, FDI, renewable energy, information & communication technology (ICT), and urbanization on CO2 emissions in Belt and Road (BRI) developed economies.Estimated results exhibited the significant contribution of ICT and renewable energy to sustainability. Besides, FDI contributes to emissions reduction after its threshold level. Conversely, urbanization and tourism activities contribute to environmental pollution. The study outcomes stated inverted/EKC U-shaped hypotheses related to specified economies. Finally, the analysis based on the D-H panel causality test constructs exciting results.The present study concludes that economic corridor plays a vital role in tourism development, the community's well-being, and SDGs goals (sustainable development) impact on environmental safety. The findings suggest essential and applicable policies to attain the desired sustainability level. Findings contribute to the literature on tourism, well-being, and sustainability. Further studies can use insights using this methodology.


Assuntos
Qualidade de Vida , Turismo , Dióxido de Carbono/análise , Energia Renovável , Poluição Ambiental/efeitos adversos , Poluição Ambiental/análise , Desenvolvimento Econômico
13.
Medicine (Baltimore) ; 102(50): e36202, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-38115372

RESUMO

There are no serum biomarkers available in nontraumatic osteonecrosis of the femoral head in clinical practice. This study aimed to evaluate the clinical value of serum glutathione peroxidase 4 in nontraumatic osteonecrosis of the femoral head. This retrospective study analyzed serum glutathione peroxidase 4 levels and clinical data of 80 patients with nontraumatic osteonecrosis of the femoral head and 80 healthy controls between August 2021 and May 2022. Serum glutathione peroxidase 4 levels were analyzed using an enzyme-linked immunosorbent assay. The Association Research Circulation Osseous classification system determined disease progression. Clinical severity was assessed by Harris hip score and visual analogue scale. Correlations between serum glutathione peroxidase 4 and disease progression as well as clinical severity were evaluated statistically. The diagnostic accuracy of serum glutathione peroxidase 4 in nontraumatic osteonecrosis of the femoral head was determined using receiver operating characteristic analysis. The baseline characteristics of participants between 2 groups were comparable. Patients with nontraumatic osteonecrosis of the femoral head displayed a decreased glutathione peroxidase 4 level compared with healthy controls (11.87 ±â€…2.76 µU/mL vs 16.54 ±â€…4.89 µU/mL, P < .01). The levels of glutathione peroxidase 4 were inversely correlated with Association Research Circulation Osseous stage (P < .01) and visual analogue scale scores (P < .01), and positively correlated with Harris score (P < .01). Receiver operating characteristic analyses showed that area under curves of glutathione peroxidase 4 was 0.808 (95% CI 0.721-0.858) and 0.847 (95% CI 0.743-0.951) with regard to diagnosis and collapse prediction in nontraumatic osteonecrosis of the femoral head, respectively. Serum glutathione peroxidase 4 could serve as a novel biomarker for diagnosing nontraumatic osteonecrosis of the femoral head and predicting collapse of the femoral head.


Assuntos
Necrose da Cabeça do Fêmur , Humanos , Biomarcadores , Estudos de Casos e Controles , Progressão da Doença , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/diagnóstico , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Estudos Retrospectivos
14.
Anat Rec (Hoboken) ; 2023 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-37905495

RESUMO

Dapingfangornis sentisorhinus, a small to medium-sized enantiornithine from the Lower Cretaceous Jiufotang Formation in Western Liaoning, China, stands as one of the earliest known enantiornithines with well-preserved ornamental tail feathers. However, the original holotype description was limited due to damage and matrix interference, which obscured crucial osteological details. Therefore, we provide an updated description of the holotype specimen of D. sentisorhinus with the aid of CT scanning to reveal new and revised osteological information. Furthermore, a phylogenetic analysis of newly acquired data situates Dapingfangornis within the Enantiornithes, closely aligned with Pterygornis and a few other taxa, which may represent a previously unrecognized clade of Early Cretaceous enantiornithines.

15.
RNA ; 29(11): 1772-1791, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37607742

RESUMO

RNA-binding proteins play important roles in bacterial gene regulation through interactions with both coding and noncoding RNAs. ProQ is a FinO-domain protein that binds a large set of RNAs in Escherichia coli, though the details of how ProQ binds these RNAs remain unclear. In this study, we used a combination of in vivo and in vitro binding assays to confirm key structural features of E. coli ProQ's FinO domain and explore its mechanism of RNA interactions. Using a bacterial three-hybrid assay, we performed forward genetic screens to confirm the importance of the concave face of ProQ in RNA binding. Using gel shift assays, we directly probed the contributions of ten amino acids on ProQ binding to seven RNA targets. Certain residues (R58, Y70, and R80) were found to be essential for binding of all seven RNAs, while substitutions of other residues (K54 and R62) caused more moderate binding defects. Interestingly, substitutions of two amino acids (K35, R69), which are evolutionarily variable but adjacent to conserved residues, showed varied effects on the binding of different RNAs; these may arise from the differing sequence context around each RNA's terminator hairpin. Together, this work confirms many of the essential RNA-binding residues in ProQ initially identified in vivo and supports a model in which residues on the conserved concave face of the FinO domain such as R58, Y70, and R80 form the main RNA-binding site of E. coli ProQ, while additional contacts contribute to the binding of certain RNAs.


Assuntos
Proteínas de Escherichia coli , Escherichia coli , Escherichia coli/genética , Escherichia coli/metabolismo , Proteínas de Escherichia coli/metabolismo , RNA/metabolismo , Proteínas de Ligação a RNA/metabolismo , Aminoácidos/metabolismo , RNA Bacteriano/metabolismo
16.
bioRxiv ; 2023 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-37163069

RESUMO

RNA-binding proteins play important roles in bacterial gene regulation through interactions with both coding and non-coding RNAs. ProQ is a FinO-domain protein that binds a large set of RNAs in Escherichia coli , though the details of how ProQ binds these RNAs remain unclear. In this study, we used a combination of in vivo and in vitro binding assays to confirm key structural features of E. coli ProQ's FinO domain and explore its mechanism of RNA interactions. Using a bacterial three-hybrid assay, we performed forward genetic screens to confirm the importance of the concave face of ProQ in RNA binding. Using gel shift assays, we directly probed the contributions of ten amino acids on ProQ binding to seven RNA targets. Certain residues (R58, Y70, and R80) were found to be essential for binding of all seven RNAs, while substitutions of other residues (K54 and R62) caused more moderate binding defects. Interestingly, substitutions of two amino acids (K35, R69), which are evolutionarily variable but adjacent to conserved residues, showed varied effects on the binding of different RNAs; these may arise from the differing sequence context around each RNA's terminator hairpin. Together, this work confirms many of the essential RNA-binding residues in ProQ initially identified in vivo and supports a model in which residues on the conserved concave face of the FinO domain such as R58, Y70 and R80 form the main RNA-binding site of E. coli ProQ, while additional contacts contribute to the binding of certain RNAs.

17.
Molecules ; 28(6)2023 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-36985423

RESUMO

Non-magnetic metal nanoparticles have been previously applied for the growth of single-walled carbon nanotubes (SWNTs). However, the activation mechanisms of non-magnetic metal catalysts and chirality distribution of synthesized SWNTs remain unclear. In this work, the activation mechanisms of non-magnetic metal palladium (Pd) particles supported by the magnesia carrier and thermodynamic stabilities of nucleated SWNTs with different (n, m) are evaluated by theoretical simulations. The electronic metal-support interaction between Pd and magnesia upshifts the d-band center of Pd, which promotes the chemisorption and dissociation of carbon precursor molecules on the Pd surface, making the activation of magnesia-supported non-magnetic Pd catalysts for SWNT growth possible. To verify the theoretical results, a porous magnesia supported Pd catalyst is developed for the bulk synthesis of SWNTs by chemical vapor deposition. The chirality distribution of Pd-grown SWNTs is understood by operating both Pd-SWNT interfacial formation energy and SWNT growth kinetics. This work not only helps to gain new insights into the activation of catalysts for growing SWNTs, but also extends the use of non-magnetic metal catalysts for bulk synthesis of SWNTs.

18.
Genet Epidemiol ; 47(3): 215-230, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36691909

RESUMO

Analysis of host genetic components provides insights into the susceptibility and response to viral infection such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19). To reveal genetic determinants of susceptibility to COVID-19 related mortality, we train a deep learning model to identify groups of genetic variants and their interactions that contribute to the COVID-19 related mortality risk using the UK Biobank data (28,097 affected cases and 1656 deaths). We refer to such groups of variants as super variants. We identify 15 super variants with various levels of significance as susceptibility loci for COVID-19 mortality. Specifically, we identify a super variant (odds ratio [OR] = 1.594, p = 5.47 × 10-9 ) on Chromosome 7 that consists of the minor allele of rs76398985, rs6943608, rs2052130, 7:150989011_CT_C, rs118033050, and rs12540488. We also discover a super variant (OR = 1.353, p = 2.87 × 10-8 ) on Chromosome 5 that contains rs12517344, rs72733036, rs190052994, rs34723029, rs72734818, 5:9305797_GTA_G, and rs180899355.


Assuntos
COVID-19 , Aprendizado Profundo , Humanos , SARS-CoV-2 , Bancos de Espécimes Biológicos , Modelos Genéticos , Reino Unido
19.
Quant Imaging Med Surg ; 13(1): 384-393, 2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36620160

RESUMO

Background: To quantify the association between the free distal segment length of the internal carotid artery (FDS-ICA) and permanent cranial nerve injury (p-CNI) following carotid body tumor (CBT) resection. Methods: This study is a case-control study. We surveyed 109 consecutive patients who underwent CBT resection between June 2015 and June 2020 at our single center. A total of 89 patients met the inclusion criteria and were selected for analysis. The FDS-ICA was measured by image post-processing software for computed tomography angiography (CTA). Postoperative p-CNI complications were evaluated using comprehensive statistical approaches. Results: The cohort was divided into 2 groups depending on the presence of p-CNI, namely the p-CNI group (n=17) and the non-CNI group (n=79). The average FDS-ICA of patients with p-CNI complications was shorter than that of those without p-CNI complications (P<0.001). For every 1 mm increase in FDS-ICA, there was an associated decrease of 8% in the risk of p-CNI (0.92, 95% CI: 0.85 to 0.98, P<0.05). Threshold effect analysis of the FDS-ICA on p-CNI identified that the FDS-ICA was 28.7 (95% CI: 23.8 to 30.9) mm. Conclusions: The results of this study revealed a significant independent association between FDS-ICA and permanent postoperative cranial nerve injury complications of CBTs. Further study is warranted to confirm these results in a larger patient cohort.

20.
Environ Res ; 216(Pt 2): 114565, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36243052

RESUMO

Rotenone is a botanical pesticide and has long been used for control of insect pests and also as a natural piscicide for management of fish populations in many countries. Field application for pest control, however, often encounters the movement of rotenone into surface water due to spray drift or surface runoff after rainfall, which could potentially result in water pollution and unexpected death of fishes. To minimize its effect on freshwater and the problem of fish dying, one solution was to encapsulate rotenone in specific microspheres, limiting its release and reducing its toxicity since rotenone can be quickly degraded under sunlight. In this study, pH-responsive alginate-based microspheres were synthesized to encapsulating rotenone, which were designated as rotenone beads. The rotenone beads, along with alginate beads (devoid of rotenone) were characterized and evaluated for their responses to pH and effects on zebrafish. Results showed that the microspheres had high loading efficiency (4.41%, w/w) for rotenone, and rotenone beads well responded to solution pH levels. The cumulative release rates of rotenone from the beads were 27.91%, 42.72%, and 90.24% at pH 5.5, 7.0, and 9.0, respectively. Under acidic conditions, the rotenone release rate was lower due to hydrogen bonding. On the contrary, rotenone became more quickly released at the high pH due to intermolecular repulsion. The toxicity of rotenone beads to zebrafish and fish embryos at a pH of 5.5 was reduced by 2- and 4-fold than chemical rotenone. Since pH levels in most freshwater lakes, ponds, and streams vary from 6 to 8, rotenone release from the beads in such freshwater could be limited. Thus, the synthesized rotenone beads could be relatively safely used for pest control with limited effects on freshwater fishers.


Assuntos
Alginatos , Peixe-Zebra , Animais , Alginatos/química , Microesferas , Rotenona/toxicidade , Ácidos Hexurônicos/toxicidade , Ácidos Hexurônicos/química , Ácido Glucurônico/toxicidade , Ácido Glucurônico/química , Concentração de Íons de Hidrogênio
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