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Pre-babbling infants can track nonadjacent dependencies (NADs) in the auditory domain. While this forms a crucial prerequisite for language acquisition, the neurodevelopmental origins of this ability remain unknown. We applied functional near-infrared spectroscopy in neonates and 6- to 7-month-old infants to investigate the neural substrate supporting NAD learning and detection using tone sequences in an artificial grammar learning paradigm. Detection of NADs was indicated by left prefrontal activation in neonates while by left supramarginal gyrus (SMG), superior temporal gyrus (STG), and inferior frontal gyrus activation in 6- to 7-month-olds. Functional connectivity analyses further indicated that the neonate activation pattern during the test phase benefited from a brain network consisting of prefrontal regions, left SMG and STG during the rest and learning phases. These findings suggest a left-hemispheric learning-related functional brain network may emerge at birth and serve as the foundation for the later engagement of these regions for NAD detection, thus, providing a neural basis for language acquisition.
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Encéfalo , Desenvolvimento da Linguagem , Aprendizagem , Espectroscopia de Luz Próxima ao Infravermelho , Humanos , Lactente , Masculino , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Feminino , Encéfalo/fisiologia , Aprendizagem/fisiologia , Recém-Nascido , Mapeamento Encefálico/métodos , Lobo Temporal/fisiologia , Lobo Temporal/diagnóstico por imagem , Idioma , Córtex Pré-Frontal/fisiologiaRESUMO
This study investigates neural processes in infant speech processing, with a focus on left frontal brain regions and hemispheric lateralization in Mandarin-speaking infants' acquisition of native tonal categories. We tested 2- to 6-month-old Mandarin learners to explore age-related improvements in tone discrimination, the role of inferior frontal regions in abstract speech category representation, and left hemisphere lateralization during tone processing. Using a block design, we presented four Mandarin tones via [ta] and measured oxygenated hemoglobin concentration with functional near-infrared spectroscopy. Results showed age-related improvements in tone discrimination, greater involvement of frontal regions in older infants indicating abstract tonal representation development and increased bilateral activation mirroring native adult Mandarin speakers. These findings contribute to our broader understanding of the relationship between native speech acquisition and infant brain development during the critical period of early language learning.
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Percepção da Fala , Fala , Adulto , Lactente , Humanos , Idoso , Percepção da Fala/fisiologia , Percepção da Altura Sonora/fisiologia , Desenvolvimento da Linguagem , Encéfalo/diagnóstico por imagem , Encéfalo/fisiologiaRESUMO
Potato is the third most important food crop worldwide. Potato production suffers from severe diseases caused by multiple detrimental plant pathogens, and broad-spectrum disease resistance genes are rarely identified in potato. Here we identified the potato non-specific lipid transfer protein StLTPa, which enhances species none-specific disease resistance against various pathogens, such as the oomycete pathogen Phytophthora infestans, the fungal pathogens Botrytis cinerea and Verticillium dahliae, and the bacterial pathogens Pectobacterium carotovorum and Ralstonia solanacearum. The StLTPa overexpression potato lines do not show growth penalty. Furthermore, we provide evidence that StLTPa binds to lipids present in the plasma membrane (PM) of the hyphal cells of P. infestans, leading to an increased permeability of the PM. Adding of PI(3,5)P2 and PI(3)P could compete the binding of StLTPa to pathogen PM and reduce the inhibition effect of StLTPa. The lipid-binding activity of StLTPa is essential for its role in pathogen inhibition and promotion of potato disease resistance. We propose that StLTPa enhances potato broad-spectrum disease resistance by binding to, and thereby promoting the permeability of the PM of the cells of various pathogens. Overall, our discovery illustrates that increasing the expression of a single gene in potato enhances potato disease resistance against different pathogens without growth penalty.
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Proteínas de Transporte , Membrana Celular , Resistência à Doença , Phytophthora infestans , Doenças das Plantas , Proteínas de Plantas , Solanum tuberosum , Solanum tuberosum/microbiologia , Solanum tuberosum/genética , Solanum tuberosum/metabolismo , Solanum tuberosum/imunologia , Resistência à Doença/genética , Doenças das Plantas/microbiologia , Doenças das Plantas/imunologia , Membrana Celular/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Phytophthora infestans/patogenicidade , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Ralstonia solanacearum/patogenicidade , Ralstonia solanacearum/fisiologia , Botrytis , Plantas Geneticamente Modificadas , Pectobacterium carotovorumRESUMO
The prevention and control of human immunodeficiency virus and sexually transmitted infections (HIV/STI) face challenges worldwide, especially in China. Prediction tools, which analyze medical data and information to make future predictions, were once mainly used in HIV/STI research to help make diagnostic or prognostic decisions, has have now extended to the public as a freely accessible tool. This article provides an overview of the different roles of prediction tools in preventing and controlling HIV/STI from the perspectives of individuals, healthcare providers, and policymakers. For individuals, prediction tools serve as a risk assessment solution that assess their risk and consciously improve risk reception or change risky behaviors. For researchers, prediction tools are powerful for assisting in identifying risk factors and predicting patients' infection risk, which can inform timely and accurate intervention planning in the future. In order to achieve the best performance, current research increasingly underscores the necessity of considering multiple levels of information, such as socio-behavioral data, in developing a robust prediction tool. In addition, it is also crucial to conduct trials in clinical settings to validate the effectiveness of prediction tools. Many studies only use theoretical parameters such as model accuracy to estimate its predictive. If these improvements are made, the application of prediction tools could be a potentially inspiring solution in the prevention and control of HIV/STI, and an opportunity for achieving the World Health Organization's agenda to end the HIV/STI epidemic by 2030.
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Tomada de Decisões , Infecções por HIV , Pessoal de Saúde , Infecções Sexualmente Transmissíveis , Humanos , Infecções por HIV/diagnóstico , Infecções por HIV/prevenção & controle , Infecções Sexualmente Transmissíveis/diagnóstico , Infecções Sexualmente Transmissíveis/prevenção & controle , Pessoal Administrativo , Medição de RiscoRESUMO
BACKGROUND: Insulin resistance (IR) is linked to both the complexity of coronary artery lesions and the prognosis of acute coronary syndrome (ACS). However, the precise extent of this correlation and its impact on adverse cardiovascular outcomes in ACS patients remain unclear. Therefore, this study aims to investigate the intricate relationship between IR, coronary artery lesion complexity, and the prognosis of ACS through a cohort design analysis. METHOD: A total of 986 patients with ACS who underwent percutaneous coronary intervention (PCI) were included in this analysis. IR was assessed using the triglyceride-glucose (TyG) index, while coronary artery lesion complexity was evaluated using the SYNTAX score. Pearson's correlation coefficients were utilized to analyze the correlations between variables. The association of the TyG index and SYNTAX score with major adverse cardiovascular events (MACEs) in ACS was investigated using the Kaplan-Meier method, restricted cubic splines (RCS), and adjusted Cox regression. Additionally, a novel 2-stage regression method for survival data was employed in mediation analysis to explore the mediating impact of the SYNTAX score on the association between the TyG index and adverse cardiovascular outcomes, including MACEs and unplanned revascularization. RESULTS: During a median follow-up of 30.72 months, 167 cases of MACEs were documented, including 66 all-cause deaths (6.69%), 26 nonfatal myocardial infarctions (MIs) (2.64%), and 99 unplanned revascularizations (10.04%). The incidence of MACEs, all-cause death, and unplanned revascularization increased with elevated TyG index and SYNTAX score. Both the TyG index (non-linear, P = 0.119) and SYNTAX score (non-linear, P = 0.004) displayed a positive dose-response relationship with MACEs, as illustrated by the RCS curve. Following adjustment for multiple factors, both the TyG index and SYNTAX score emerged as significant predictors of MACEs across the total population and various subgroups. Mediation analysis indicated that the SYNTAX score mediated 25.03%, 18.00%, 14.93%, and 11.53% of the correlation between the TyG index and MACEs in different adjusted models, respectively. Similar mediating effects were observed when endpoint was defined as unplanned revascularization. CONCLUSION: Elevated baseline TyG index and SYNTAX score were associated with a higher risk of MACEs in ACS. Furthermore, the SYNTAX score partially mediated the relationship between the TyG index and adverse cardiovascular outcomes.
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Síndrome Coronariana Aguda , Biomarcadores , Glicemia , Doença da Artéria Coronariana , Resistência à Insulina , Intervenção Coronária Percutânea , Humanos , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/mortalidade , Síndrome Coronariana Aguda/terapia , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/epidemiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Glicemia/metabolismo , Fatores de Tempo , Biomarcadores/sangue , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/terapia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/diagnóstico , Triglicerídeos/sangue , Estudos Retrospectivos , Valor Preditivo dos TestesRESUMO
BACKGROUND: Atrial fibrillation (AF) is acknowledged as a disease continuum. Despite catheter ablation being recommended as a primary therapy for AF, the high recurrence rates have tempered the initial enthusiasm. Insulin resistance (IR) has been established as an independent predictor for the onset of AF. However, the correlation between non-insulin-based IR indices and late AF recurrence in patients undergoing radiofrequency catheter ablation remains unknown. METHODS: A retrospective cohort of 910 AF patients who underwent radiofrequency catheter ablation was included in the analysis. The primary endpoint was late AF recurrence during the follow-up period after a defined blank period. The relationship between non-insulin-based IR indices and the primary endpoint was assessed using multivariate Cox hazards regression models and restricted cubic splines (RCS). Additionally, the net reclassification improvement and integrated discrimination improvement index were calculated to further evaluate the additional predictive value of the four IR indices beyond established risk factors for the primary outcome. RESULTS: During a median follow-up period of 12.00 months, 189 patients (20.77%) experienced late AF recurrence, which was more prevalent among patients with higher levels of IR. The multivariate Cox hazards regression analysis revealed a significant association between these IR indices and late AF recurrence. Among the four indices, METS-IR provided the most significant incremental effect on the basic model for predicting late AF recurrence. Multivariable-adjusted RCS curves illustrated a nonlinear correlation between METS-IR and late AF recurrence. In subgroup analysis, METS-IR exhibited a significant correlation with late AF recurrence in patients with diabetes mellitus (HR: 1.697, 95% CI 1.397 - 2.063, P < 0.001). CONCLUSION: All the four non-insulin-based IR indices were significantly associated with late AF recurrence in patients undergoing radiofrequency catheter ablation. Addressing IR could potentially serve as a viable strategy for reducing the late AF recurrence rate.
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Fibrilação Atrial , Ablação por Cateter , Resistência à Insulina , Recidiva , Humanos , Fibrilação Atrial/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Masculino , Feminino , Ablação por Cateter/efeitos adversos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Idoso , Fatores de Tempo , Medição de Risco , Resultado do Tratamento , Biomarcadores/sangue , Valor Preditivo dos Testes , Glicemia/metabolismoRESUMO
BACKGROUND: Xeligekimab (GR1501) is a fully human monoclonal antibody that selectively neutralizes interleukin (IL)-17A and has shown potential efficacy in treating moderate-to-severe psoriasis in preliminary trials. OBJECTIVES: To evaluate the efficacy and safety of xeligekimab in Chinese patients with moderate-to-severe psoriasis. METHODS: A total of 420 Chinese patients were randomized to 200â mg xeligekimab every 2 weeks (n = 281) or placebo (n = 139) for the first 12 weeks, followed by an extension of the treatment schedule to xeligekimab every 4 weeks for a further 40 weeks. Efficacy was assessed by evaluating achievement of Physician Global Assessment (PGA) 0/1 and 75%, 90% and 100% improvement in Psoriasis Area and Severity Index (PASI 75, PASI 90 and PASI 100, respectively). The safety profile was also evaluated. RESULTS: At week 12, PASI 75, PASI 90 and PASI 100 were achieved in 90.7%, 74.4% and 30.2% of patients in the xeligekimab group vs. 8.6%, 1.4% and 0% of patients in the placebo group, respectively. PGA 0/1 was achieved in 74.4% patients in the xeligekimab group and 3.6% of patients in the placebo group. PASI 75 and PGA 0/1 were maintained until week 52. No unexpected adverse events were recorded. CONCLUSIONS: Xeligekimab showed high efficacy and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.
Psoriasis is a skin disease characterized by scaly and raised patches of skin on any part of the body. The condition can be caused by a combination of how a person's immune system works, their genes and their environment. A cytokine is a substance secreted by certain cells of the immune system that have an effect on other cells. One such cytokine, called IL-17A, has been associated with different inflammatory diseases, including psoriasis. We conducted a large trial in Chinese people with moderate-to-severe psoriasis to look at the efficacy (ability to produce the intended result) and safety of a medicine called xeligekimab (known as a 'monoclonal antibody') which works by targeting IL-17A. We randomly assigned 420 Chinese patients to receive 200â mg of xeligekimab every 2 weeks or a 'placebo' (no active medicine) for the first 12 weeks. We extended the treatment schedule of xeligekimab to every 4 weeks for a further 40 weeks. To assess how the medicine worked, we measured people's psoriasis symptoms and severity. To assess how safe the medicine was, we looked at the side-effects (or 'adverse events'). The results of this trial showed that xeligekimab improved people's psoriasis and itching starting at week 4 of receiving treatment, and more than 60% of people achieved improvement or remission by week 6, which was sustained up to week 52. The safety of xeligekimab was similar to another medicine classed as a monoclonal antibody (called secukinumab) and there were no new or unexpected adverse events reported. Overall, our findings suggest that xeligekimab is a safe and effective medicine for the treatment of psoriasis in Chinese people.
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Anticorpos Monoclonais Humanizados , Psoríase , Humanos , Psoríase/tratamento farmacológico , Masculino , Método Duplo-Cego , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/administração & dosagem , Feminino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Fármacos Dermatológicos/efeitos adversos , Fármacos Dermatológicos/uso terapêutico , Fármacos Dermatológicos/administração & dosagem , Esquema de Medicação , Interleucina-17/antagonistas & inibidores , Índice de Gravidade de Doença , Idoso , Adulto JovemRESUMO
Graphene, serving as electrodes, is widely applied in electronic and optoelectronic devices. Work function as one of the fundamental intrinsic characteristics of graphene directly affects the interfacial properties of the electrodes, thereby affecting the performance of the devices. Much work has been done to regulate the work function of graphene to expand its application fields, and doping has been demonstrated as an effective method. However, the numerous types of doped graphene make the investigation of its work function time-consuming and labor-intensive. In order to quickly obtain the relationship between the structure and property, a deep learning method is employed to predict the work function in this study. Specifically, a data set of over 30,000 compositions with the work function on boron-doped graphene at different concentrations and doping positions via density functional theory simulations was established through ab initio calculations. Then, a novel fusion model (GT-Net) combining transformers and graph neural networks (GNNs) was proposed. After that, improved effective GNN-based descriptors were developed. Finally, three different GNN methods were compared, and the results show that the proposed method could accurately predicate the work function with the R2 = 0.975 and RMSE = 0.027. This study not only provides the possibility of designing materials with specific properties at the atomic level but also demonstrates the performance of GNNs on graph-level tasks with the same graph structure and atomic number.
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RATIONALE: Myocardial infarction (MI) is one of the most dangerous adverse cardiovascular events. Our previous study found that lysophosphatidic acid (LPA) is increased in human peripheral blood after MI, and LPA has a protective effect on the survival and proliferation of various cell types. However, the role of LPA and its receptors in MI is less understood. OBJECTIVES: To study the unknown role of LPA and its receptors in heart during MI. METHODS AND RESULTS: In this study, we found that mice also had elevated LPA level in peripheral blood, as well as increased cardiac expression of its receptor LPA2 in the early stages after MI. With adult and neonate MI models in global Lpar2 knockout (Lpar2-KO) mice, we found Lpar2 deficiency increased vascular leak leading to disruption of its homeostasis, so as to impaired heart function and increased early mortality. Histological examination revealed larger scar size, increased fibrosis, and reduced vascular density in the heart of Lpar2-KO mice. Furthermore, Lpar2-KO also attenuated blood flow recovery after femoral artery ligation with decreased vascular density in gastrocnemius. Our study revealed that Lpar2 was mainly expressed and altered in cardiac endothelial cells during MI, and use of endothelial-specific Lpar2 knockout mice phenocopied the global knockout mice. Additionally, adenovirus-Lpar2 and pharmacologically activated LPA2 significantly improved heart function, reduced scar size, increased vascular formation, and alleviated early mortality by maintaining vascular homeostasis owing to protecting vessels from leakage. Mechanistic studies demonstrated that LPA-LPA2 signaling could promote endothelial cell proliferation through PI3K-Akt/PLC-Raf1-Erk pathway and enhanced endothelial cell tube formation via PKD1-CD36 signaling. CONCLUSIONS: Our results indicate that endothelial LPA-LPA2 signaling promotes angiogenesis and maintains vascular homeostasis, which is vital for restoring blood flow and repairing tissue function in ischemic injuries. Targeting LPA-LPA2 signal might have clinical therapeutic potential to protect the heart from ischemic injury.
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Infarto do Miocárdio , Receptores de Ácidos Lisofosfatídicos , Animais , Cicatriz , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Homeostase , Humanos , Lisofosfolipídeos , Camundongos , Camundongos Knockout , Infarto do Miocárdio/genética , Fosfatidilinositol 3-Quinases , Receptores de Ácidos Lisofosfatídicos/genética , Receptores de Ácidos Lisofosfatídicos/metabolismo , Remodelação VentricularRESUMO
PURPOSE: Endosome associated trafficking regulator 1 (ENTR1) is a novel endosomal protein, which can affect multiple cellular biological behavior by remodeling plasma membrane structures. However, little is known regarding its function and underlying mechanisms in glioblastoma multiforme. METHODS: Expression profile and clinical signature were obtained from The Public Database of human tumor. Immunohistochemical staining and western blotting assays were used to measure ENTR1 expression level. Human primary GBM tumor cells and human GBM cell lines A172, U87 and U251 were used to clarify the precise role of ENTR1. CCK-8 assays, wound healing and transwell invasion assays were designed to investigate cell viability, invasion and migration of GBM cells, respectively. Underlying molecular mechanisms of ENTR1 were determined via RNA-seq analysis. Tumor formation assay was used to validate the influence of ENTR1 in vivo. RESULTS: Compared with normal brain tissues, ENTR1 was highly expressed in gliomas and correlated with malignant grades of gliomas and poor overall survival time. The proliferation and invasion of GBM cells could be weaken and the sensitivity to temozolomide (TMZ) chemotherapy increased after knocking down ENTR1. Overexpression of ENTR1 could reverse this effect. RNA-seq analysis showed that tumor necrosis factor (TNF) signaling pathway might be a putative regulatory target of ENTR1. Tumor formation assay validated that ENTR1 was a significant factor in tumor growth. CONCLUSION: Our results indicated that ENTR1 played an important role in cell proliferation, invasion and chemotherapeutic sensitivity of GBM, suggesting that ENTR1 might be a novel prognostic marker and significant therapeutic target for GBM.
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Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células , Endossomos/metabolismo , Endossomos/patologia , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Transdução de SinaisRESUMO
A Gram-stain-negative, red pigment-producing, aerobic, and rod-shaped bacterial strain (A2-2T) was isolated from a bleached scleractinian coral (Porites lutea). Strain A2-2T grew with 1.0-7.0â% (w/v) NaCl (optimum, 3.0â%), at pH 6.0-11.0 (optimum, pH 8.0), and at 18-41â°C (optimum, 35â°C). Results of phylogenetic analysis based on 16S rRNA gene sequences suggested that strain A2-2T fell within the genus Spartinivicinus and was closely related to Spartinivicinus ruber S2-4-1HT (98.1â% sequence similarity) and Spartinivicinus marinus SM1973T (98.0â% sequence similarity). The predominant cellular fatty acids of strain A2-2T were C16â:â0 (31.0â%), summed feature 3 (29.0â%), summed feature 8 (11.7â%), C12â:â0 3-OH (6.4â%), and C10â:â0 3-OH (5.5â%), while the major respiratory quinone was Q-9. The polar lipids mainly comprised phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, and an unidentified phospholipid. The genome size of strain A2-2T was 6.8 Mb, with a G+C content of 40.2âmol%. The DNA-DNA hybridization value was 24.2â% between A2-2T and S. ruber S2-4-1HT and 36.9â% between A2-2T and S. marinus SM1973T, while the average nucleotide identity values were 80.1 and 88.8â%, respectively. Based on these findings, strain A2-2T could be recognized to represent a novel species of the genus Spartinivicinus, for which the name Spartinivicinus poritis sp. nov. is proposed. The type strain is A2-2T (=MCCC 1K08228T=KCTC 8323T).
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Antozoários , Técnicas de Tipagem Bacteriana , Composição de Bases , DNA Bacteriano , Ácidos Graxos , Filogenia , Pigmentos Biológicos , RNA Ribossômico 16S , Análise de Sequência de DNA , RNA Ribossômico 16S/genética , Animais , Antozoários/microbiologia , DNA Bacteriano/genética , Pigmentos Biológicos/metabolismo , Hibridização de Ácido Nucleico , FosfolipídeosRESUMO
The investigation of pharmaceuticals as emerging contaminants in marine biota has been insufficient. In this study, we examined the presence of 51 pharmaceuticals in edible oysters along the coasts of the East and South China Seas. Only nine pharmaceuticals were detected. The mean concentrations of all measured pharmaceuticals in oysters per site ranged from 0.804 to 15.1 ng g-1 of dry weight, with antihistamines being the most common. Brompheniramine and promethazine were identified in biota samples for the first time. Although no significant health risks to humans were identified through consumption of oysters, 100-1000 times higher health risks were observed for wildlife like water birds, seasnails, and starfishes. Specifically, sea snails that primarily feed on oysters were found to be at risk of exposure to ciprofloxacin, brompheniramine, and promethazine. These high risks could be attributed to the monotonous diet habits and relatively limited food sources of these organisms. Furthermore, taking chirality into consideration, chlorpheniramine in the oysters was enriched by the S-enantiomer, with a relative potency 1.1-1.3 times higher when chlorpheniramine was considered as a racemate. Overall, this study highlights the prevalence of antihistamines in seafood and underscores the importance of studying enantioselectivities of pharmaceuticals in health risk assessments.
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Monitoramento Ambiental , Ostreidae , Preparações Farmacêuticas , Poluentes Químicos da Água , Animais , Humanos , Bromofeniramina/análise , China , Clorfeniramina/análise , Antagonistas dos Receptores Histamínicos/análise , Oceanos e Mares , Ostreidae/química , Preparações Farmacêuticas/análise , Prometazina/análise , Poluentes Químicos da Água/análiseRESUMO
AIMS: Artificial reefs play a vital role in restoring and creating new habitats for marine species by providing suitable substrates, especially in areas where natural substrates have been degraded or lost due to declining water quality, destructive fishing practices, and coral diseases. Artificial reef restoration aimed at coral larval settlement is gaining prominence and initially depends on the development of biofilms on reef surfaces. In this study, we hypothesized that different artificial reef materials selectively influence the composition of biofilm bacterial communities, which in turn affected coral larval settlement and the overall success of coral rehabilitation efforts. To test this hypothesis, we evaluated the impact of six different reef-made materials (porcelain, granite, coral skeleton, calcium carbonate, shell cement, and cement) on the development of biofilm bacterial communities and their potential to support coral larval settlement. METHODS AND RESULTS: The biofilm bacterial communities were developed on different artificial reef materials and studied using 16S rRNA gene amplicon sequencing and analysis. The bacterial species richness and evenness were significantly (P < 0.05) low in the seawater, while these values were high in the reef materials. At the phylum level, the biofilm bacterial composition of all materials and seawater was majorly composed of Pseudomonadota, Cyanobacteria, and Bacteroidetes; however, significantly (P < 0.05) low Bacteroidetes were found in the seawater. At the genus level, Thalassomonas, Glaciecola, Halomicronema, Lewinella, Hyphomonas, Thalassospira, Polaribacter, and Tenacibaculum were significantly (P < 0.05) low in the coral skeleton and seawater, compared to the other reef materials. The genera Pseudoaltermonas and Thalassomonas (considered potential inducers of coral larval settlement) were highly abundant in the shell-cement biofilm, while low values were found in the biofilm of the other materials. CONCLUSION: The biofilm bacterial community composition can be selective for different substrate materials, such as shell cement exhibited higher abundances of bacteria known to facilitate coral larval settlement, highlighting their potential in enhancing restoration outcomes.
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Antozoários , Bactérias , Biofilmes , Recifes de Corais , RNA Ribossômico 16S , Água do Mar , Biofilmes/crescimento & desenvolvimento , Animais , Bactérias/genética , Bactérias/classificação , Bactérias/isolamento & purificação , Antozoários/microbiologia , Água do Mar/microbiologia , RNA Ribossômico 16S/genética , Larva/microbiologia , MicrobiotaRESUMO
The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 µm). It was found that scaffolds with a mesh size of 500 µm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration.
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Hidrogéis , Nanofibras , Impressão Tridimensional , Medicina Regenerativa , Engenharia Tecidual , Alicerces Teciduais , Nanofibras/química , Alicerces Teciduais/química , Engenharia Tecidual/métodos , Medicina Regenerativa/métodos , Hidrogéis/química , Animais , Camundongos , Macrófagos/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Células RAW 264.7 , HumanosRESUMO
BACKGROUND: Approximately 20%-40% of patients with von Hippel-Lindau (VHL) disease, an autosomal dominant hereditary disease, exhibit large deletions (LDs). Few studies have focused on this population. Hence, we aimed to elucidate the genotype-phenotype correlations and clinical outcomes in VHL patients with LDs. METHODS: In this retrospective study, we included 119 patients with VHL disease from 50 unrelated families in whom LDs were detected using traditional and next-generation sequencing methods. Other germline mutations were confirmed by Sanger sequencing. Genotype-phenotype correlations and survival were analysed in different groups using Kaplan-Meier and Cox regression. We also evaluated therapeutic response to tyrosine kinase inhibitor (TKI) therapy. RESULTS: The overall penetrance of patients aged <60 was 95.2%. Two VHL patients with LDs also carried CHEK2 and FLCN germline mutations. An earlier age of onset of retinal haemangioblastoma was observed in the next generation. Patients with exon 2 deletion of VHL had an earlier onset age of renal cell carcinoma and pancreatic lesions. The risk of renal cell carcinoma was lower in VHL patients with LDs and a BRK1 deletion. The group with earlier age of onset received poorer prognosis. Four of eight (50%) patients showed partial response to TKI therapy. CONCLUSION: The number of generations and the status of exon 2 could affect age of onset of VHL-related manifestations. Onset age was an independent risk factor for overall survival. TKI therapy was effective in VHL patients with LDs. Our findings would further support clinical surveillance and decision-making processes.
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Carcinoma de Células Renais , Neoplasias Renais , Doença de von Hippel-Lindau , Humanos , Doença de von Hippel-Lindau/complicações , Doença de von Hippel-Lindau/genética , Doença de von Hippel-Lindau/epidemiologia , Carcinoma de Células Renais/genética , Estudos Retrospectivos , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Estudos de Associação Genética , Neoplasias Renais/genéticaRESUMO
Epithelioid glioblastoma (Ep-GBM) is a rare variant of glioblastoma characterized by a high recurrence rate and poor prognosis. Currently, there is no established standard treatment for Ep-GBM. Therefore, we identified 58 Ep-GBM cases to investigate these characteristics and identify the possible prognostic factors of survival. There were 30 male and 28 female patients with a median age of 39 years. Headaches and dizziness were the most common clinical symptom. The tumor is most frequently located in the temporal lobe (36.2%). The positivity rate for BRAF-V600E is 56.9% (33/58), for MGMT is 56.9% (33/58), and for INI-1 is 75% (30/40). Tumor recurrence was observed in 39 patients. The median progression-free survival (PFS) of all patients was 12.7 months, while the median overall survival (OS) was 29.1 months. Additionally, the median survival time after recurrence was 14.3 months. Both univariate and multivariate COX regression analyses revealed that individuals who received more than six cycles of adjuvant oral temozolomide experienced a longer median PFS compared to those who received fewer cycles. Characteristics associated with poorer PFS included tumor dissemination prior to initial surgery. Additionally, both analyses identified tumor dissemination, radiotherapy and adjuvant oral temozolomide as predictors of OS. Notably, for patients with recurrent Ep-GBM, reoperation was shown to significantly increase survival time after recurrence. In conclusion, the standard Stupp regimen is also applicable to patients with Ep-GBM, extending adjuvant oral temozolomide could further improve survival for Ep-GBM patients, reoperation may also prolong survival for recurrent Ep-GBM.
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Neoplasias Encefálicas , Glioblastoma , Humanos , Masculino , Feminino , Glioblastoma/terapia , Glioblastoma/mortalidade , Glioblastoma/patologia , Adulto , Pessoa de Meia-Idade , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Idoso , Adulto Jovem , Recidiva Local de Neoplasia , Temozolomida/uso terapêutico , Adolescente , Antineoplásicos Alquilantes/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/genética , PrognósticoRESUMO
BACKGROUND: The internet has become an increasingly vital platform for health-related information, especially in upper-middle-income countries such as China. While previous research has suggested that online health information seeking (OHIS) can significantly impact individuals' engagement in health behaviors, most research focused on patient-centered health communication. OBJECTIVE: This study aims to examine how OHIS influences health behavior engagement among Chinese internet users, focusing on the role of eHealth literacy and perceived information quality in influencing relationships. METHODS: An online cross-sectional survey was conducted in November 2021 among 10,000 Chinese internet users, using quota sampling based on sex, age, and urban and rural residence, in line with the 48th Statistical Report on Internet Development of China. Nonparametric tests were used to examine the differences in eHealth literacy across sociodemographic groups. Partial correlation analysis and stepwise linear regression were conducted to test the associations between key variables. Confirmatory factor analysis and structural equation modeling were conducted to test the hypotheses. RESULTS: Our study identified significant disparities in functional and critical eHealth literacy between urban and rural residents across age groups, income levels, education backgrounds, and health conditions (all P<.001). In terms of sex and regional differences, we found higher functional literacy among female users than male users, and critical literacy varied significantly across different regions. The proposed structural model showed excellent fit (χ2404=4183.6, χ2404=10.4,P<.001; root mean square error of approximation value of 0.031, 95% CI 0.030-.031; standardized root mean square residual value of 0.029; and comparative fit index value of 0.955), highlighting reciprocal associations between 2 types of eHealth literacy and OHIS. Participants' functional eHealth literacy, critical eHealth literacy, and OHIS have positive impacts on their health behavioral engagement. Perceived information quality was found to mediate the influence of OHIS on health behavior (b=0.003, 95% CI 0.002-0.003; P<.001). CONCLUSIONS: The study revealed the pathways linking sociodemographic factors, eHealth literacy, OHIS, and perceived information quality and how they together influenced health outcomes. The findings underscore the significance of enhancing eHealth literacy and improving information quality to promote better health outcomes among Chinese internet users.
Assuntos
Comportamentos Relacionados com a Saúde , Letramento em Saúde , Comportamento de Busca de Informação , Internet , Telemedicina , Humanos , Estudos Transversais , Feminino , Masculino , China , Adulto , Letramento em Saúde/estatística & dados numéricos , Telemedicina/estatística & dados numéricos , Pessoa de Meia-Idade , Internet/estatística & dados numéricos , Adulto Jovem , Adolescente , Inquéritos e Questionários , População Rural/estatística & dados numéricos , População do Leste AsiáticoRESUMO
A novel molecularly imprinted electrochemical sensor (MIECS) was constructed for the specific detection of sulfadiazine (SDZ) in food. Niobium carbide (Nb2CTx) as a typical two-dimensional lamellar nanomaterial has good electrical conductivity and unique structure, which was assembled with one-dimensional silver nanowires (AgNWs) to form quasi-three-dimensional composite nanomaterials (Nb2CTx/AgNWs). As spacer material, AgNWs prevented the aggregation of Nb2CTx and the collapse of Nb2CTx layers. At the same time, a fast electron transport channel was constructed through the synergistic effect between nanomaterials the two. The Nb2CTx/AgNWs realized the enhancement of electrical signals. Molecularly imprinted polymers (MIPs) endowed the sensor with selectivity, achieving the specific detection of sulfadiazine. Under the optimal experimental conditions, the method has a wide linear range (1 × 10-8-1 × 10-4 mol L-1) and a low limit of detection (1.30 × 10-9 mol L-1). The sensor was used to detect sulfadiazine in pork, chicken, and feed samples, and the recovery was 82.61-94.87%. The results were in good agreement with the HPLC results, which proved the accuracy and practicability of the method.
RESUMO
A photoactivated bone scaffold integrated with minimally invasive implantation and mild thermal-stimulation capability shows great promise in the repair and regeneration of irregularly damaged bone tissues. Developing multifunctional photothermal biomaterials that can simultaneously serve as both controllable thermal stimulators and biodegradable engineering scaffolds for integrated immunomodulation, infection therapy, and impaired bone repair remains an enormous challenge. Herein, an injectable and photocurable hydrogel therapeutic platform (AMAD/MP) based on alginate methacrylate, alginate-graft-dopamine, and polydopamine (PDA)-functionalized Ti3C2 MXene (MXene@PDA) nanosheets is rationally designed for near-infrared (NIR)-mediated bone regeneration synergistic immunomodulation, osteogenesis, and bacterial elimination. The optimized AMAD/MP hydrogel exhibits favorable biocompatibility, osteogenic activity, and immunomodulatory functions in vitro. The proper immune microenvironment provided by AMAD/MP could further modulate the balance of M1/M2 phenotypes of macrophages, thereby suppressing reactive oxygen species-induced inflammatory status. Significantly, this multifunctional hydrogel platform with mild thermal stimulation efficiently attenuates local immune reactions and further promotes new bone formation without the addition of exogenous cells, cytokines, or growth factors. This work highlights the potential application of an advanced multifunctional hydrogel providing photoactivated on-demand thermal cues for bone tissue engineering and regenerative medicine.
Assuntos
Hidrogéis , Osteogênese , Hidrogéis/farmacologia , Regeneração Óssea , Materiais Biocompatíveis , Engenharia Tecidual , Alicerces TeciduaisRESUMO
BACKGROUND: The Triglyceride-glucose (TyG) index, as a surrogate marker of insulin resistance, is independently associated with the severity of coronary artery lesions and the prognosis of coronary heart disease. The investigation aimed to explore the relationship between the TyG index and recurrent revascularization in individuals with type 2 diabetes mellitus (T2DM) resulting from the progression of lesions or in-stent restenosis (ISR) after percutaneous coronary intervention (PCI). METHOD: A total of 633 patients who met the inclusion and exclusion criteria were enrolled and divided into three groups based on the tertiles of the TyG index. The primary endpoint was recurrent revascularization resulting from the progression of lesions or ISR. All-cause death was considered as the competing risk event. Competing risk analysis and Cox regression analysis for predicting recurrent revascularization after PCI were conducted stepwise. Variables were standardized to make the hazard ratio (HR), subdistribution hazard ratio (SHR) and corresponding 95% CI more consistent prior to being used for fitting the multivariate risk model. The predictive ability of the TyG index was evaluated using several measures, including the ROC curve, likelihood ratio test, Akaike's information criteria, category-free continuous net reclassification improvement (cNRI > 0), and integrated discrimination improvement (IDI). Internal validation was conducted through bootstrapping with 1000 resamples. RESULTS: During a median follow-up period of 18.33 months, a total of 64 (10.11%) patients experienced recurrent revascularization, including 55 cases of lesion progression and 9 cases of in-stent restenosis. After controlling for competitive risk events, the TyG index was independently associated with a higher risk of recurrent revascularization [SHR:1.4345, (95% CI 1.1458-1.7959), P = 0.002]. The likelihood ratio test and Akaike's information criteria showed that the TyG index significantly improves the prognostic ability. Additionally, adding the TyG index improved the ability of the established risk model in predicting recurrent revascularization, indicated by a C-index of 0.759 (95% CI 0.724-0.792, P < 0.01), with a cNRI > 0 of 0.170 (95% CI 0.023-0.287, P < 0.05), and an IDI of 0.024 (95% CI 0.009-0.039, P = 0.002). These results remained consistent when the models containing TyG index were confirmed using an internal bootstrap validation method. CONCLUSION: The findings highlight the potential of the TyG index as a predictor of recurrent revascularization. Lesion progression emerged as the primary contributor to recurrent revascularization instead of in-stent restenosis. The incorporation of the TyG index into risk prediction models is likely to be beneficial for accurate risk stratification in order to improve prognosis.