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1.
J Youth Adolesc ; 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730128

RESUMO

Although family and school experiences play an important role in adolescents' adjustment during the transition to high school, most prior studies investigated the effects of these experiences in isolation; their joint implications for both adolescents' concurrent and long-term adjustment outcomes are less clear, and the potential role of individual characteristics within such associations remains understudied. Based on 525 10th graders (Mage = 15.48, SDage = 0.71, 43.6% boys) who participated in a longitudinal study, the present research aimed to identify distinct family and school experience profiles among first-year high school students and examine their associations with adolescents' internalizing problems and externalizing problems, both concurrently and 18 months later. Latent profile analysis revealed four distinctive profiles: thriving, low resources-moderate family risk, developmental stress-high parental conflicts, and developmental stress-high peer victimization profiles. The other three profiles (vs. the thriving profile) reported significantly higher levels of concurrent internalizing problems; while these differences diminished after 18 months. However, the enduring impacts of these profiles on internalizing problems persisted among adolescents with higher levels of environmental sensitivity. Additionally, adolescents characterized by two developmental stress profiles (vs. the thriving profile) exhibited significantly higher levels of externalizing problems both currently and longitudinally. Findings underscore the importance of identifying at-risk populations among adolescents during the transition to high school by including both family and school experiences when examining environmental influence on their adjustment, as well as the necessity to take individual environmental sensitivity into account when examining these associations.

2.
Immunol Cell Biol ; 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714318

RESUMO

The development of in vitro models is essential for a comprehensive understanding and investigation of pulmonary fibrosis (PF) at both cellular and molecular levels. This study presents a literature review and an analysis of various cellular models used in scientific studies, specifically focusing on their applications in elucidating the pathogenesis of PF. Our study highlights the importance of taking a comprehensive approach to studing PF, emphasizing the necessity of considering multiple cell types and organs and integrating diverse analytical perspectives. Notably, primary cells demonstrate remarkable cell growth characteristics and gene expression profiles; however, their limited availability, maintenance challenges, inability for continuous propagation and susceptibility to phenotypic changes over time significantly limit their utility in scientific investigation. By contrast, immortalized cell lines are easily accessible, cultured and continuously propagated, although they may have some phenotypic differences from primary cells. Furthermore, in vitro coculture models offer a more practical and precise method to explore complex interactions among cells, tissues and organs. Consequently, when developing models of PF, researchers should thoroughly assess the advantages, limitations and relevant mechanisms of different cell models to ensure their selection is consistent with the research objectives.

3.
Sci Total Environ ; 931: 172899, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38692328

RESUMO

Emerging contaminants (ECs) are widely sourced persistent pollutants that pose a significant threat to the environment and human health. Their footprint spans global ecosystems, making their remediation highly challenging. In recent years, a significant amount of literature has focused on the use of biochar for remediation of heavy metals and organic pollutants in soil and water environments. However, the use of biochar for the remediation of ECs in agricultural soils has not received as much attention, and as a result, there are limited reviews available on this topic. Thus, this review aims to provide an overview of the primary types, sources, and hazards of ECs in farmland, as well as the structure, functions, and preparation types of biochar. Furthermore, this paper emphasizes the importance and prospects of three remediation strategies for ECs in cropland: (i) employing activated, modified, and composite biochar for remediation, which exhibit superior pollutant removal compared to pure biochar; (ii) exploring the potential synergistic efficiency between biochar and compost, enhancing their effectiveness in soil improvement and pollution remediation; (iii) utilizing biochar as a shelter and nutrient source for microorganisms in biochar-mediated microbial remediation, positively impacting soil properties and microbial community structure. Given the increasing global prevalence of ECs, the remediation strategies provided in this paper aim to serve as a valuable reference for future remediation of ECs-contaminated agricultural lands.

4.
J Hazard Mater ; 471: 134384, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38663292

RESUMO

Addressing the challenge of accurately monitoring polycyclic aromatic hydrocarbons (PAHs) in aquatic systems, this study employed diffusive gradients in thin-films (DGT) technique to achieve methods detection limits as low as 0.02 ng L-1 to 0.05 ng L-1 through in situ preconcentration and determination of time-integrated concentrations. The efficacy of the developed DGT samplers was validated under diverse environmental conditions, demonstrating independence from factors such as pH (5.03-9.01), dissolved organic matter (0-20 mg L-1), and ionic strength (0.0001-0.6 M). Notably, the introduction of a novel theoretical approach to calculate diffusion coefficients based on solvent-accessible volume tailored for PAHs significantly enhanced the method's applicability, particularly for organic pollutants with low solubility. Field deployments in coastal zones validated the DGT method against traditional grab sampling, with findings advocating a 4 to 7-day optimal deployment duration for balancing sensitivity and mitigating lag time effects. These results provide a sophisticated, efficient solution to the persistent challenge of monitoring hydrophobic organic pollutants in aquatic environments, broadening the scope and applicability of DGT in environmental science and providing a robust tool for researchers.

5.
J Virol ; 98(5): e0195923, 2024 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-38634598

RESUMO

The role of Culex mosquitoes in the transmission of Japanese encephalitis virus (JEV) is crucial, yet the mechanisms of JEV infection in these vectors remain unclear. Previous research has indicated that various host factors participate in JEV infection. Herein, we present evidence that mosquito sialic acids enhance JEV infection both in vivo and in vitro. By treating mosquitoes and C6/36 cells with neuraminidase or lectin, the function of sialic acids is effectively blocked, resulting in significant inhibition of JEV infection. Furthermore, knockdown of the sialic acid biosynthesis genes in Culex mosquitoes also leads to a reduction in JEV infection. Moreover, our research revealed that sialic acids play a role in the attachment of JEV to mosquito cells, but not in its internalization. To further explore the mechanisms underlying the promotion of JEV attachment by sialic acids, we conducted immunoprecipitation experiments to confirm the direct binding of sialic acids to the last α-helix in JEV envelope protein domain III. Overall, our study contributes to a molecular comprehension of the interaction between mosquitoes and JEV and offers potential strategies for preventing the dissemination of flavivirus in natural environments.IMPORTANCEIn this study, we aimed to investigate the impact of glycoconjugate sialic acids on mosquito infection with Japanese encephalitis virus (JEV). Our findings demonstrate that sialic acids play a crucial role in enhancing JEV infection by facilitating the attachment of the virus to the cell membrane. Furthermore, our investigation revealed that sialic acids directly bind to the final α-helix in the JEV envelope protein domain III, thereby accelerating virus adsorption. Collectively, our results highlight the significance of mosquito sialic acids in JEV infection within vectors, contributing to a better understanding of the interaction between mosquitoes and JEV.


Assuntos
Culex , Vírus da Encefalite Japonesa (Espécie) , Encefalite Japonesa , Mosquitos Vetores , Ácidos Siálicos , Ligação Viral , Vírus da Encefalite Japonesa (Espécie)/fisiologia , Vírus da Encefalite Japonesa (Espécie)/metabolismo , Animais , Culex/virologia , Culex/metabolismo , Encefalite Japonesa/virologia , Encefalite Japonesa/metabolismo , Mosquitos Vetores/virologia , Ácidos Siálicos/metabolismo , Linhagem Celular , Proteínas do Envelope Viral/metabolismo , Proteínas do Envelope Viral/genética , Internalização do Vírus , Camundongos , Neuraminidase/metabolismo , Neuraminidase/genética
6.
Front Immunol ; 15: 1320880, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38633257

RESUMO

Objectives: Nephritis is a life-threatening complication of primary Sjögren's syndrome (pSS), with membranous nephropathy (MN) being prevalent. Renal biopsy is the gold standard for MN diagnosis, but it is invasive and cannot be repeatedly performed. This study aimed to develop a nomogram for the prediction of MN in patients with pSS. Methods: This retrospective study included patients with pSS admitted to the Rheumatology and Immunology Department of the First Affiliated Hospital of China Medical University between January 2015 and January 2021. A nomogram was developed using multivariable logistic regression analysis and evaluated using receiver operating characteristic (ROC) curve analysis. Bootstrap resampling analysis (1,000 times) was performed to evaluate the nomogram for discrimination and the calibration curve for consistency. Results: A total of 237 patients with pSS [aged 53.00 (44.00, 61.00) years] were included, with 35 pSS-MN patients. Based on clinical practice and multivariable logistic regression analysis, seven variables associated with pSS-MN were selected, including white blood cells, creatine, complement 3, rheumatoid factor, antinuclear antibodies, anti-SSA antibody, and interstitial lung disease. The area under the ROC curve was 0.860 (95% confidence interval: 0.796-0.919), indicating good predictive power. In addition, the nomogram exhibited excellent performance, as demonstrated by the calibration curve and decision curve analysis. Conclusion: This study developed a risk prediction nomogram for MN in patients with pSS, with high predictive power. It may be used to improve the management of patients with pSS.


Assuntos
Glomerulonefrite Membranosa , Síndrome de Sjogren , Humanos , Estudos Retrospectivos , Glomerulonefrite Membranosa/complicações , Nomogramas , Anticorpos Antinucleares
7.
J Youth Adolesc ; 53(6): 1287-1300, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38580892

RESUMO

The reciprocity and variation of values and beliefs are dynamic features of the parent-child relationship. Parents and adolescents may hold congruent or incongruent views regarding the malleability of socioeconomic status (mindset of SES), potentially influencing adolescents' psychological and physiological stress outcomes, as reflected in stress perceptions and the hypothalamic-pituitary-adrenal (HPA) axis functioning. The current study investigated how patterns of parent-adolescent congruence and incongruence in mindset of SES were associated with adolescents' perceived stress and diurnal cortisol patterns four months later. A total of 253 adolescents (Mage = 12.60, 46.2% girls) and their parents (Mage = 40.09 years, 59.5% mothers) participated in this study. Polynomial regression analyses and response surface analyses showed that adolescents perceived lower levels of stress when they themselves or their parents reported a stronger growth mindset of SES. Additionally, adolescents with a stronger growth mindset of SES also exhibited a steeper diurnal cortisol slope. Moreover, parents' mindset significantly interacted with adolescents' mindset to influence adolescents' diurnal cortisol patterns such that when adolescents hold weaker growth mindset of SES, those with higher parental growth mindsets had significantly higher cortisol awakening response and steeper diurnal cortisol slope. Furthermore, adolescents who showed incongruence with their parents but had averagely stronger growth mindsets of SES reported a significantly steeper diurnal cortisol slope than those who had averagely weaker growth mindsets with their parents. The findings point to the beneficial impacts of the growth mindset of SES on stress-related outcomes among adolescents, as well as the significance of considering both parents' and adolescents' mindsets when exploring these associations.


Assuntos
Hidrocortisona , Relações Pais-Filho , Classe Social , Estresse Psicológico , Humanos , Feminino , Adolescente , Masculino , Estresse Psicológico/psicologia , Hidrocortisona/metabolismo , Hidrocortisona/análise , Adulto , Pais/psicologia , Sistema Hipotálamo-Hipofisário , Criança , Saliva/química , Sistema Hipófise-Suprarrenal , Comportamento do Adolescente/psicologia
8.
J Inflamm Res ; 17: 2245-2256, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38623469

RESUMO

Background: Dorsal root ganglia (DRGs) contain sensory neurons that innervate intervertebral discs (IVDs) and may play a critical role in mediating low-back pain (LBP), but the potential pathophysiological mechanism needs to be clarified. Methods: A discogenic LBP model in rats was established by penetration of a lumbar IVD. The severity of LBP was evaluated through behavioral analysis, and the gene and protein expression levels of pro-algesic peptide substance P (SP) and calcitonin gene-related peptide (CGRP) in DRGs were quantified. The level of reactive oxygen species (ROS) in bilateral lumbar DRGs was also quantified using dihydroethidium staining. Subsequently, hydrogen peroxide solution or N-acetyl-L-cysteine was injected into DRGs to evaluate the change in LBP, and gene and protein expression levels of transient receptor potential vanilloid-1 (TRPV1) in DRGs were analyzed. Finally, an inhibitor or activator of TRPV1 was injected into DRGs to observe the change in LBP. Results: The rats had remarkable LBP after disc puncture, manifesting as mechanical and cold allodynia and increased expression of the pro-algesic peptides SP and CGRP in DRGs. Furthermore, there was significant overexpression of ROS in bilateral lumbar DRGs, while manipulation of the level of ROS in DRGs attenuated or aggravated LBP in rats. In addition, excessive ROS in DRGs stimulated upregulation of TRPV1 in DRGs. Finally, activation or inhibition of TRPV1 in DRGs resulted in a significant increase or decrease of discogenic LBP, respectively, suggesting that ROS-induced TRPV1 has a strong correlation with discogenic LBP. Conclusion: Increased ROS in DRGs play a primary pathological role in puncture-induced discogenic LBP, and excessive ROS-induced upregulation of TRPV1 in DRGs may be the underlying pathophysiological mechanism to cause nerve sensitization and discogenic LBP. Therapeutic targeting of ROS or TRPV1 in DRGs may provide a promising method for the treatment of discogenic LBP.

9.
Nat Methods ; 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38649742

RESUMO

Automated detection of specific cells in three-dimensional datasets such as whole-brain light-sheet image stacks is challenging. Here, we present DELiVR, a virtual reality-trained deep-learning pipeline for detecting c-Fos+ cells as markers for neuronal activity in cleared mouse brains. Virtual reality annotation substantially accelerated training data generation, enabling DELiVR to outperform state-of-the-art cell-segmenting approaches. Our pipeline is available in a user-friendly Docker container that runs with a standalone Fiji plugin. DELiVR features a comprehensive toolkit for data visualization and can be customized to other cell types of interest, as we did here for microglia somata, using Fiji for dataset-specific training. We applied DELiVR to investigate cancer-related brain activity, unveiling an activation pattern that distinguishes weight-stable cancer from cancers associated with weight loss. Overall, DELiVR is a robust deep-learning tool that does not require advanced coding skills to analyze whole-brain imaging data in health and disease.

10.
J Youth Adolesc ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38622470

RESUMO

Social mobility beliefs play a significant role in shaping adolescents' adaptive developmental outcomes, including well-being and academic functioning. Nevertheless, existing research may not cast light on the distinct trajectories and potential protective factors of social mobility beliefs. The present study aims to identify heterogeneity in trajectory patterns of social mobility beliefs among Chinese adolescents (Mage = 12.45, SDage = 2.60; 55.1% boys; 40.0% rural adolescents) in a four-wave (i.e., fall 2017, fall 2018, spring 2019, and fall 2019) longitudinal design, and examines the protective roles of parental academic involvement and adolescent future orientation. Three distinct trajectories of social mobility beliefs were identified: high-increasing (35.1%; a positive trajectory with the best developmental outcomes, including the lowest problem behaviors and depression symptoms, and the highest life satisfaction and academic competence), moderate-stable (49.8%), and low-decreasing (15.1%; a negative trajectory with the worst developmental outcomes, including the highest problem behaviors and depression symptoms, and the lowest life satisfaction and academic competence). Apart from the main effects of parental academic involvement and future orientation, a significant interaction effect of these two protective factors and adolescent group was detected, and only rural adolescents who reported both high levels of parental academic involvement and future orientation have a greater chance of being placed in the high-increasing trajectory than the low-decreasing trajectory. These findings highlight the significance of clarifying individual differences in the dynamic process of social mobility beliefs during adolescence, and elucidate rural-urban disparities in the influences of protective factors on social mobility beliefs trajectories, and inform individualized intervention strategies.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38625459

RESUMO

There is growing support for the dual-continua model of mental health, which emphasizes psychopathology and well-being as related but distinct dimensions. Yet, little is known about how these dimensions co-develop from childhood to early adolescence and what factors predict their different trajectories. The current study aimed to identify distinct patterns of mental health in Chinese early adolescents, focusing on both psychopathological symptoms (i.e., depressive symptoms and self-harm behaviors) and subjective well-being (i.e., life satisfaction and affect balance). This study also examined the contributions of school climate and future orientation to these trajectories. A total of 1,057 students (Mage = 11.88, SDage = 1.67; 62.1% boys) completed four assessments over two years, with six-month intervals. Using parallel-process latent class growth modeling, we identified four groups: Flourishing (32.5%), Languishing (43.8%), Troubled with Stable Depressive Symptoms (16.1%), and Troubled with Increasing Self-Harm Risk (7.6%). Furthermore, school climate and future orientation contributed to adolescents' membership in these trajectories, either independently or jointly. Specifically, higher levels of future orientation combined with higher school climate were associated with a lower likelihood of belonging to the Troubled with Increasing Self-Harm Risk trajectory, compared to the Flourishing group. Our findings identified four distinct mental health trajectories consistent with the dual-continua model, and demonstrated that the development of psychopathology and well-being were not always inversely related (e.g., the Languishing group). Adolescents with unique developmental profiles may benefit from tailored intervention strategies that build on the personal and environmental assets of the adolescent.

12.
Zhongguo Zhong Yao Za Zhi ; 49(5): 1225-1239, 2024 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-38621969

RESUMO

Ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was employed to investigate the impacts of Pruni Semen processed with different methods(raw and fried) on the liver and spleen metabolism in mice. A total of 24 male mice were randomly assigned to three groups: raw Pruni Semen group, fried Pruni Semen group, and control(deionized water) group. Mice in the three groups were orally administrated with 0.01 g·mL~(-1) Pruni Semen decoction or deionized water for one week. After that, the liver and spleen tissues were collected, and liquid chromatography-mass spectrometry(LC-MS)-based metabolomic analysis was carried out to investigate the impact of Pruni Semen on the liver and spleen metabolism in mice. Compared with thte control group, the raw Pruni Semen group showed up-regulation of 11 metabolites and down-regulation of 57 metabolites in the spleen(P<0.05), as well as up-regulation of 15 metabolites and down-regulation of 58 metabolites in the liver(P<0.05). The fried Pruni Semen group showed up-regulation of 31 metabolites and down-regulation of 10 metabolites in the spleen(P<0.05), along with up-regulation of 26 metabolites and down-regulation of 61 metabolites in the liver(P<0.05). The differential metabolites identified in the raw Pruni Semen group were primarily associated with alanine, aspartate, and glutamate metabolism, purine metabolism, amino sugar and nucleotide sugar metabolism, and D-glutamine and D-glutamate metabolism. The differential metabolites identified in the fried Pruni Semen group predominantly involved riboflavin metabolism, amino sugar and nucleotide sugar metabolism, purine metabolism, alanine, aspartate, and glutamate metabolism, D-glutamine and D-glutamate metabolism, and glutathione metabolism. The findings suggest that both raw and fried Pruni Semen have the potential to modulate the metabolism of the liver and spleen in mice by influencing the glutamine and glutamate metabolism.


Assuntos
Ácido Glutâmico , Baço , Camundongos , Masculino , Animais , Sêmen , Glutamina , Ácido Aspártico , Metabolômica/métodos , Fígado/metabolismo , Alanina/metabolismo , Amino Açúcares/metabolismo , Água/metabolismo , Nucleotídeos/metabolismo , Purinas/metabolismo , Açúcares , Cromatografia Líquida de Alta Pressão , Biomarcadores/metabolismo
13.
Artigo em Inglês | MEDLINE | ID: mdl-38564352

RESUMO

Zero-shot relation extraction (ZSRE) is shown to become more significant in the current information extraction system, which aims at predicting relation classes that lack annotations or have just never appeared during training. Previous works focus on projecting sentences with their corresponding relation descriptions to an intermediate semantic space and searching the nearest semantic for predicting unseen classes. Though these methods can achieve sound performance, they only obtain inferior semantic information via a trivial distance metric and neglect the interaction in the instance representations. We are thus motivated to tackle these issues and propose a hierarchical contrastive learning (HCL) framework for ZSRE including projection-level and instance-level modules. Specifically, the projection-level component replaces the distance score function by contrastive loss to connect the input sentence with the relation semantic space. And the instance-level component integrates the external knowledge from sentence entities to establish new contrastive pairs for efficiently learning representations from mutual information. The experimental results on three well-known datasets demonstrate that our model surpasses the existing SOTA by at most 18.97% improvement on the F1 score when unseen classes are 15 . Moreover, our model can achieve more competitive performance alone with the increasing number of unseen classes.

14.
Shanghai Kou Qiang Yi Xue ; 33(1): 6-12, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38583018

RESUMO

PURPOSE: Bioactive magnesium ions were successfully incorporated into the nanoporous titanium base coating by micro-arc oxidation(MAO), and its physical properties and osteogenic effects were explored. METHODS: Non-magnesium-containing and magnesium-containing titanium porous titanium coatings(MAO, MAO-mg) were prepared by changing the composition of MAO electrolyte and controlling the doping of magnesium in porous titanium coatings. The samples were characterized by scanning electron microscope (SEM), roughness, contact angle and energy dispersive X-ray spectrometer (EDS). Mg2+ release ability of magnesium-doped nanoporous titanium coatings was determined by inductively coupled plasma/optical emission spectrometer(ICP-OES). The structure of the cytoskeleton was determined by live/dead double staining, CCK-8 detection of material proliferation-toxicity, and staining of ß-actin using FITC-phalloidin. The effects of the coating on osteogenic differentiation in vitro were determined by alizarin red (ARS), alkaline phosphatase (ALP) staining and real-time polymerase chain reaction (qRT-PCR). SPSS 25.0 software package was used for statistical analysis. RESULTS: The MAO electrolyte with magnesium ions did not change the surface characteristics of the porous titanium coating. Each group prepared by MAO had similar microporous structure(P>0.05). There was no significant difference in surface roughness and contact angle between MAO treatment group (MAO, MAO-mg)(P>0.05), but significantly higher than that of Ti group (P<0.05). With the passage of cell culture time, MAO-mg group promoted cell proliferation (P<0.05). MAO-mg group was significantly higher than other groups in ALP and ARS staining. The expression of Runx2 mRNA (P<0.05), ALP(P<0.05) and osteocalcin OCN(P<0.05) in MAO-mg group was significantly higher than that in Ti and MAO groups. CONCLUSIONS: MAO successfully prepared magnesium-containing nanoporous titanium coating, and showed a significant role in promoting osteogenic differentiation.


Assuntos
Nanoporos , Titânio , Titânio/farmacologia , Magnésio/química , Magnésio/farmacologia , Osteogênese/genética , Eletrólitos/farmacologia , Íons/farmacologia , Propriedades de Superfície , Materiais Revestidos Biocompatíveis/farmacologia , Materiais Revestidos Biocompatíveis/química
15.
Mikrochim Acta ; 191(5): 231, 2024 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-38565795

RESUMO

Blood stasis syndrome (BSS) has persistent health risks; however, its pathogenesis remains elusive. This obscurity may result in missed opportunities for early intervention, increased susceptibility to chronic diseases, and reduced accuracy and efficacy of treatments. Metabolomics, employing the matrix-assisted laser desorption/ionization (MALDI) strategy, presents distinct advantages in biomarker discovery and unraveling molecular mechanisms. Nonetheless, the challenge is to develop efficient matrices for high-sensitivity and high-throughput analysis of diverse potential biomarkers in complex biosamples. This work utilized nitrogen-doped porous transition metal carbides and nitrides (NP-MXene) as a MALDI matrix to delve into the molecular mechanisms underlying BSS pathogenesis. Structural optimization yielded heightened peak sensitivity (by 1.49-fold) and increased peak numbers (by 1.16-fold) in clinical biosamples. Validation with animal models and clinical serum biosamples revealed significant differences in metabolic fingerprints between BSS and control groups, achieving an overall diagnostic efficacy of 0.905 (95% CI, 0.76-0.979). Prostaglandin F2α was identified as a potential biomarker (diagnostics efficiency of 0.711, specificity = 0.7, sensitivity = 0.6), and pathway enrichment analysis disclosed disruptions in arachidonic acid metabolism in BSS. This innovative approach not only advances comprehension of BSS pathogenesis, but also provides valuable insights for personalized treatment and diagnostic precision.


Assuntos
Medicamentos de Ervas Chinesas , Animais , Dinoprosta , Retroalimentação , Nitrogênio , Porosidade , Compostos Orgânicos , Biomarcadores
16.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(2): 532-540, 2024 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-38660863

RESUMO

OBJECTIVE: To investigate the molecular mechanism of proteolytic cleavage of unusually large von Willebrand Factor(ULVWF) on endothelial cells by ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats-13) in the absence of fluid shear stress, so as to provide a theoretical basis for the pathogenesis of thrombotic thrombocytopenic purpura (TTP) and other thrombotic disorders. METHODS: The ADAMTS13-mediated proteolysis of ULVWF on the surface of endothelial cells in the absence of fluid shear stress was observed through immunofluorescence microscopy. The variation in VWF antigen levels in the conditioned media were determined by ELISA assay. The levels of VWF and the proteolytic fragments released into the conditioned media were determined by ELISA assay and Western blot in the absence and presence of fluid shear stress or FVIII. The effect of ADAMTS13-mediated ULVWF cleavage on the normal distribution of plasma VWF multimers was evaluated by multimer analysis. Histamine stimulated human umbilical vein endothelial cells (HUVECs) were incubated with ADAMTS13 and various N- and C-terminally truncated mutants. Then the ULVWF that maintained binding to the cells were observed through immunofluorescence microscopy and the soluble ULVWF released from endothelial cells was determined by ELISA, so as to demonstrate the domains of ADAMTS13 required for proteolysis of ULVWF on endothelial cells. RESULTS: The ULVWF strings on the endothelial cell surface were rapidly proteolyzed by recombinant and plasma ADAMTS13 in the absence of fluid shear stress. This proteolytic processing of ULVWF depended on incubation time and ADAMTS13 concentration, but not shear stress and FVIII. The distribution of VWF releaseded by ADAMTS13-mediated proteolysis was quite similar to that secreted by endothelial cells under histamine stimulation, suggesting the ULVWF cleavage occured at the cell surface. The proteolysis of the ULVWF on endothelial cells required the Cys-rich(CysR) and spacer domains, but not the TSP1 2-8 and CUB domains of ADAMTS13. CONCLUSION: The ULVWF polymers on endothelial cells are sensitive to ADAMTS13-mediated cleavage even in the absence of fluid shear stress. The findings provide novel insight into the molecular mechanism of ADAMTS13-mediated ULVWF cleavage at the cellular level and may contribute to understanding of the pathogenesis of TTP and other thrombotic disorders.


Assuntos
Proteína ADAMTS13 , Células Endoteliais , Estresse Mecânico , Fator de von Willebrand , Humanos , Proteínas ADAM/metabolismo , Proteína ADAMTS13/metabolismo , Células Endoteliais/metabolismo , Células Endoteliais da Veia Umbilical Humana , Proteólise , Púrpura Trombocitopênica Trombótica/metabolismo , Fator de von Willebrand/química , Fator de von Willebrand/metabolismo
17.
J Agric Food Chem ; 72(17): 10089-10096, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38626386

RESUMO

Lactoferrin (LTF) has diverse biological activities and is widely used in functional foods and active additives. Nevertheless, evaluating the proteoform heterogeneity, conformational stability, and activity of LTF remains challenging during its production and storage processes. In this study, we describe the implementation of native mass spectrometry (nMS), glycoproteomics, and an antimicrobial activity assay to assess the quality of LTF. We systematically characterize the purity, glycosylation heterogeneity, conformation, and thermal stability of LTF samples from different sources and transient high-temperature treatments by using nMS and glycoproteomics. Meanwhile, the nMS peak intensity and antimicrobial activity of LTF samples after heat treatment decreased significantly, and the two values were positively correlated. The nMS results provide essential molecular insights into the conformational stability and glycosylation heterogeneity of different LTF samples. Our results underscore the great potential of nMS for LTF quality control and activity evaluation in industrial production.


Assuntos
Lactoferrina , Espectrometria de Massas , Lactoferrina/química , Lactoferrina/metabolismo , Glicosilação , Estabilidade Proteica , Animais , Conformação Proteica , Bovinos , Temperatura Alta
18.
Nat Neurosci ; 27(5): 1014-1018, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38467902

RESUMO

Large-scale imaging of neuronal activities is crucial for understanding brain functions. However, it is challenging to analyze large-scale imaging data in real time, preventing closed-loop investigation of neural circuitry. Here we develop a real-time analysis system with a field programmable gate array-graphics processing unit design for an up to 500-megabyte-per-second image stream. Adapted to whole-brain imaging of awake larval zebrafish, the system timely extracts activity from up to 100,000 neurons and enables closed-loop perturbations of neural dynamics.


Assuntos
Encéfalo , Neurônios , Peixe-Zebra , Animais , Neurônios/fisiologia , Encéfalo/fisiologia , Encéfalo/diagnóstico por imagem , Processamento de Imagem Assistida por Computador/métodos , Larva , Neuroimagem/métodos , Sistemas Computacionais
20.
Sci Total Environ ; 924: 171725, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38492604

RESUMO

Nitrogen (N) accumulation in landfills is a pressing environmental concern due to its diverse sources and significant environmental impacts. However, there is relatively limited attention and research focus on N in landfills as it is overshadowed by other more prominent pollutants. This study comprehensively examines the sources of N in landfills, including food waste contributing to 390 million tons of N annually, industrial discharges, and sewage treatment plant effluents. The environmental impacts of N in landfills are primarily manifested in N2O emissions and leachate with high N concentrations. To address these challenges, this study presents various mitigation and management strategies, including N2O reduction measures and novel NH4+ removal techniques, such as electrochemical technologies, membrane separation processes, algae-based process, and other advanced oxidation processes. However, a more in-depth understanding of the complexities of N cycling in landfills is required, due to the lack of long-term monitoring data and the presence of intricate interactions and feedback mechanisms. To ultimately achieve optimized N management and minimized adverse environmental impacts in landfill settings, future prospects should emphasize advancements in monitoring and modeling technologies, enhanced understanding of microbial ecology, implementation of circular economy principles, application of innovative treatment technologies, and comprehensive landfill design and planning.

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