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1.
ACS Appl Mater Interfaces ; 16(27): 34510-34523, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38946393

RESUMO

Photoluminescence (PL) metal nanoclusters (NCs) have attracted extensive attention due to their excellent physicochemical properties, good biocompatibility, and broad application prospects. However, developing water-soluble PL metal NCs with a high quantum yield (QY) and high stability for visual drug delivery remains a great challenge. Herein, we have synthesized ultrabright l-Arg-ATT-Au/Ag NCs (Au/Ag NCs) with a PL QY as high as 73% and excellent photostability by heteroatom doping and surface rigidization in aqueous solution. The as-prepared Au/Ag NCs can maintain a high QY of over 61% in a wide pH range and various ionic environments as well as a respectable resistance to photobleaching. The results from structure characterization and steady-state and time-resolved spectroscopic analysis reveal that Ag doping into Au NCs not only effectively modifies the electronic structure and photostability but also significantly regulates the interfacial dynamics of the excited states and enhances the PL QY of Au/Ag NCs. Studies in vitro indicate Au/Ag NCs have a high loading capacity and pH-triggered release ability of doxorubicin (DOX) that can be visualized from the quenching and recovery of PL intensity and lifetime. Imaging-guided experiments in cancer cells show that DOX of Au/Ag NCs-DOX agents can be efficiently delivered and released in the nucleus with preferential accumulation in the nucleolus, facilitating deep insight into the drug action sites and pharmacological mechanisms. Moreover, the evaluation of anticancer activity in vivo reveals an outstanding suppression rate of 90.2% for mice tumors. These findings demonstrate Au/Ag NCs to be a superior platform for bioimaging and visual drug delivery in biomedical applications.


Assuntos
Doxorrubicina , Ouro , Nanopartículas Metálicas , Prata , Água , Ouro/química , Prata/química , Prata/farmacologia , Humanos , Animais , Doxorrubicina/química , Doxorrubicina/farmacologia , Nanopartículas Metálicas/química , Camundongos , Água/química , Sistemas de Liberação de Medicamentos , Células HeLa , Portadores de Fármacos/química , Solubilidade , Liberação Controlada de Fármacos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Luminescência
2.
Toxicon ; 247: 107850, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38971137

RESUMO

BACKGROUND: Enterobacter cloacae insecticidal proteins have been reported to kill Galleria mellonella larvae through affecting their midgut microbiome. However, the mechanisms involved remain unclear. Here we aim to investigate how the insecticidal proteins act on the midgut Duox-ROS system and microbial community of G. mellonella larvae. METHODS: Reverse transcription qPCR and fluorescence probes were utilized to assess the Duox expression levels and to evaluate quantitative changes of the ROS levels. Sequencing of the 16S rRNA gene sequences of the midgut bacteria of G. mellonella larvae was conducted for further analyses of bacterial diversity, composition, and abundance. RESULTS: After the injection of the insecticidal proteins, the Duox expression levels first increased within 28 h, then dramatically peaked at 36 h, and slowly decreased thereafter. Simultaneously, the ROS levels increased significantly at 36 h, peaked at 48 h, and rapidly declined to the normal level at 60 h. Responsive to the change of the ROS levels, the structure of the midgut microbial community was altered substantially, compared to that of the untreated larvae. The relative abundance of Enterobacteriaceae and other specific pathogenic bacteria increased significantly, whereas that of Lactobacillus decreased sharply. Importantly, notable shifts were observed in the crucial midgut predicted metabolic functions, including membrane transportation, carbohydrate metabolism, and amino acid metabolism. CONCLUSION: Insecticidal proteins of E. cloacae kill G. mellonella larvae mainly through generation of high oxidative stress, alterations of the midgut microbial community and function, and damage to the physiological functions. These findings provide insights into the inhibition mechanism of E. cloacae insecticidal proteins to G. mellonella larvae.

3.
Antib Ther ; 7(2): 177-186, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38933532

RESUMO

Cancer immunotherapy represents a paradigm shift in oncology, offering a superior anti-tumor efficacy and the potential for durable remission. The success of personalized vaccines and cell therapies hinges on the identification of immunogenic epitopes capable of eliciting an effective immune response. Current limitations in the availability of immunogenic epitopes restrict the broader application of such therapies. A critical criterion for serving as potential cancer antigens is their ability to stably bind to the major histocompatibility complex (MHC) for presentation on the surface of tumor cells. To address this, we have developed a comprehensive database of MHC epitopes, experimentally validated for their MHC binding and cell surface presentation. Our database catalogs 451 065 MHC peptide epitopes, each with experimental evidence for MHC binding, along with detailed information on human leukocyte antigen allele specificity, source peptides, and references to original studies. We also provide the grand average of hydropathy scores and predicted immunogenicity for the epitopes. The database (MHCepitopes) has been made available on the web and can be accessed at https://github.com/jcm1201/MHCepitopes.git. By consolidating empirical data from various sources coupled with calculated immunogenicity and hydropathy values, our database offers a robust resource for selecting actionable tumor antigens and advancing the design of antigen-specific cancer immunotherapies. It streamlines the process of identifying promising immunotherapeutic targets, potentially expediting the development of effective antigen-based cancer immunotherapies.

4.
BMC Public Health ; 24(1): 1613, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886687

RESUMO

BACKGROUND: the salutogenic theory is essential to explain an individual's ability to maintain health during the perinatal period. While previous studies mainly focused on the perspectives from a family-level orientation and a global orientation, the purpose of the present study was to develop and validate a scale, the childbearing sense of coherence scale (CSOC-scale) from the individual's perceptions of the stresses, resources, and meaningfulness of childbearing. METHODS: A total of 3 separate studies contributed to the development of the CSOC-scale between July 2022 and February 2023. In study 1, the initial item pool based on the conceptual framework of the childbearing sense of coherence and the salutogenic theory was developed. Delphi expert consultation was conducted to revise and improve items. Studies 2 and 3 were cross-sectional studies. In study 2, item analysis and explore factor analysis (EFA) (N = 351 for women, N = 256 for men) were used to screen items. In study 3, confirmatory factor analysis (CFA) and reliability analysis (N = 366 for women, N = 308 for men) were used to test the fit indices and reliability of the final scale. RESULTS: final analysis suggested the CSOC-scale includes three factors, consisting of 13 items. Confirmatory factor analysis demonstrated good model fit (χ2 = 157.448, df = 62, χ2/ df = 2.539, RMSEA = 0.065, CFI = 0.974, TLI = 0.968, SRMR = 0.029 for women; χ2 = 181.363, df = 62, χ2/ df = 2.925, RMSEA = 0.079, CFI = 0.968, TLI = 0.960, SRMR = 0.033 for men) and high factor loadings (from 0.751 to 0.929 for women; from 0.746 to 0.947 for men). Internal consistency (Cronbach's α ranging from 0.895 to 0.933 for women and 0.881 to 0.945 for men in three dimensions; Cronbach's α was 0.919 for women and 0.821 for men in the entire instrument) and split-half reliability (Spearman-Brown coefficients ranging from 0.876 to 0.921 for women and 0.841 to 0.937 for men in three dimensions; Spearman-Brown coefficient was 0.744 for women and 0.785 for men in the entire instrument) were excellent. CONCLUSIONS: the CSOC-scale has robust psychometric properties. It is reliable and valid in evaluating the childbearing sense of coherence in women and men during pregnancy. Utilisation of this scale can help healthcare professionals understand the health maintenance competencies of couples during the transition of parenthood and provide health promotion services from a salutogenic perspective.


Assuntos
Psicometria , Senso de Coerência , Humanos , Feminino , Masculino , Adulto , Reprodutibilidade dos Testes , Análise Fatorial , Inquéritos e Questionários/normas , Estudos Transversais , Técnica Delphi , Adulto Jovem , Gravidez , Pessoa de Meia-Idade
5.
Environ Sci Pollut Res Int ; 31(29): 41980-41989, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38856857

RESUMO

Coal is one of the primary energy sources in China and is widely used for electricity generation. Crops growing in overlapped areas of farmland and coal resources (OAFCR) suffer from coal fly ash stress, especially during stem elongation, which is a key stage that impacts wheat yield and is sensitive to environmental stress. As a primary food crop of China, wheat is essential for food security. However, the characteristics of wheat under the combined stress of fly ash and various heavy metals have not been sufficiently investigated. In this study, we explored the response of stem elongation in wheat to different levels of coal fly ash stress and determined the content of heavy metals (HMs) in wheat leaves. We found that with an increase in fly ash content, the Cu content in the shoots increased, while that in the roots decreased. Coal fly ash exposure reduced the proportions of Pb and Zn in the cytoderm, and the proportion of Cu in the soluble constituents decreased from 58.3% to 45.7%. Total chlorophyll, chlorophyll a, and chlorophyll b levels decreased significantly, whereas peroxidase (POD) and catalase (CAT) activities generally increased with increasing fly ash dose. Meanwhile, chloroplasts, mitochondria, and their internal structures were damaged, and the cell structures of leaves, such as the internal membrane structure, were damaged.


Assuntos
Cinza de Carvão , Metais Pesados , Fotossíntese , Triticum , Fotossíntese/efeitos dos fármacos , Carvão Mineral , Folhas de Planta , Caules de Planta/efeitos dos fármacos , Clorofila , China , Estresse Fisiológico
6.
Int J Biol Macromol ; 273(Pt 1): 132966, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38851620

RESUMO

The multifunctionality of advanced laundry detergents primarily relies on the inclusion of functional solid particles, such as pearlescent powder, enzymes, and perfume microcapsules. However, the high-content surfactants in these detergents can render most existing suspending rheology modifiers ineffective, making it challenging to achieve uniform suspension of these functional particles. This compromises the overall functionality of laundry products. To address this, we have developed a binary rheology modifier comprising cellulose microgel and HPMC (hydroxypropyl methylcellulose), acting as the "island" and "chain," respectively. Together, they form an interconnected dynamic network that effectively "encapsulates" the functional particles. Furthermore, the cellulose microgel/HPMC rheology modifier demonstrates versatility, proving effective with various surfactants. Despite its potential, the suspension mechanism of cellulose microgel/HPMC remains elusive. Therefore, we conducted a comprehensive investigation, fabricating cellulose microgels with varying nanofabrication degrees and surface charges through TEMPO oxidation. Our findings highlight the critical role of the surficial structure of T-Microgel, specifically its nanofabrication degree, in influencing the dynamic network's fabrication, thereby impacting yield and thixotropic properties. The surface charge of T-microgel does not significantly influence the process. This research not only elucidates the intricate dynamics of cellulose microgel/HPMC interaction but also provides fundamental insights essential for the development of innovative rheology modifiers tailored for high-content surfactant applications.


Assuntos
Celulose , Microgéis , Reologia , Celulose/química , Microgéis/química , Tensoativos/química , Derivados da Hipromelose/química , Óxidos N-Cíclicos/química
7.
J Magn Reson Imaging ; 2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38722187

RESUMO

BACKGROUND: White matter hyperintensity (WMH) burden may lead to poor clinical outcomes after endovascular thrombectomy (EVT). But the relationship between WMH burden and cerebral edema (CED) is unclear. PURPOSE: To examine the association between WMH burden and CED and functional outcome in patients treated with EVT. STUDY TYPE: Retrospective. SUBJECT: 344 patients with acute anterior circulation large-vessel occlusion stroke who received EVT at two comprehensive stroke centers. Mean age was 62.6 ± 11.6 years and 100 patients (29.1%) were female. FIELD STRENGTH/SEQUENCE: 3T, including diffusion-weighted imaging and fluid-attenuated inversion recovery (FLAIR) images. ASSESSMENT: The severity of WMH was evaluated using the Fazekas scale on a FLAIR sequence before EVT. The severity of CED was assessed using CED score (three for malignant cerebral edema [MCE]) and net water uptake (NWU)/time on post-EVT cranial CT. The impact of WMH burden on MCE, NWU/time, and 3-month poor outcome (modified Rankin scale >2) after EVT were assessed. STATISTICAL TESTS: Pearson's chi-squared test, Fisher exact test, 2-tailed t test, Mann-Whitney U test, multivariable logistic regression, multivariate regression analysis, Sobel test. A P value <0.05 was considered statistically significant. RESULTS: WMH burden was not significantly associated with MCE and parenchymal hemorrhage (PH) in the whole population (P = 0.072; P = 0.714). WMH burden was significantly associated with an increased risk of MCE (OR, 1.550; 95% CI, 1.128-2.129), higher NWU/time (Coefficient, 0.132; 95% CI, 0.012-0.240), and increased risk of 3-month poor outcome (OR, 1.434; 95% CI, 1.110-1.853) in the subset of patients without PH. Moreover, the connection between WMH burden and poor outcome was partly mediated by CED in patients without PH (regression coefficient changed by 29.8%). DATA CONCLUSION: WMH burden is associated with CED, especially MCE, and poor outcome in acute ischemic stroke patients treated with EVT. The association between WMH burden and poor outcome may partly be attributed to postoperative CED. TECHNICAL EFFICACY: Stage 5.

8.
Front Pharmacol ; 15: 1396616, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38813109

RESUMO

Adiponectin is a pleiotropic cytokine predominantly derived from adipose tissue. In addition to its role in regulating energy metabolism, adiponectin may also be related to estrogen-dependent diseases, and many studies have confirmed its involvement in mediating diverse biological processes, including apoptosis, autophagy, inflammation, angiogenesis, and fibrosis, all of which are related to the pathogenesis of endometriosis. Although many researchers have reported low levels of adiponectin in patients with endometriosis and suggested that it may serve as a protective factor against the development of the disease. Therefore, the purpose of this review was to provide an up-to-date summary of the roles of adiponectin and its downstream cytokines and signaling pathways in the aforementioned biological processes. Further systematic studies on the molecular and cellular mechanisms of action of adiponectin may provide novel insights into the pathophysiology of endometriosis as well as potential therapeutic targets.

9.
Nat Med ; 30(5): 1395-1405, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38693247

RESUMO

Cerebral palsy (CP) is the most common motor disability in children. To ascertain the role of major genetic variants in the etiology of CP, we conducted exome sequencing on a large-scale cohort with clinical manifestations of CP. The study cohort comprised 505 girls and 1,073 boys. Utilizing the current gold standard in genetic diagnostics, 387 of these 1,578 children (24.5%) received genetic diagnoses. We identified 412 pathogenic and likely pathogenic (P/LP) variants across 219 genes associated with neurodevelopmental disorders, and 59 P/LP copy number variants. The genetic diagnostic rate of children with CP labeled at birth with perinatal asphyxia was higher than the rate in children without asphyxia (P = 0.0033). Also, 33 children with CP manifestations (8.5%, 33 of 387) had findings that were clinically actionable. These results highlight the need for early genetic testing in children with CP, especially those with risk factors like perinatal asphyxia, to enable evidence-based medical decision-making.


Assuntos
Paralisia Cerebral , Variações do Número de Cópias de DNA , Sequenciamento do Exoma , Heterogeneidade Genética , Humanos , Paralisia Cerebral/genética , Feminino , Masculino , Criança , Pré-Escolar , Variações do Número de Cópias de DNA/genética , Exoma/genética , Lactente , Testes Genéticos , Estudos de Coortes , Predisposição Genética para Doença , Recém-Nascido
10.
Pain Ther ; 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38805167

RESUMO

INTRODUCTION: Patients frequently suffer from debilitating chronic postsurgical pain (CPSP) subsequent to thoracoscopic surgery. The impact of postoperative dexmedetomidine infusion on CPSP remains elusive. This study aimed to scrutinize the effect of dexmedetomidine on both 1-year incidence of CPSP and the quality of recovery after thoracoscopic pulmonary nodule surgery. METHODS: This retrospective analysis encompassed clinical and follow-up data from 1148 patients undergoing thoracoscopic pulmonary nodule surgery at our institution between September 2021 and August 2022. Depending on whether dexmedetomidine was infused intravenously or not on the first night after surgery, patients were stratified into the dexmedetomidine group or the control group, with propensity score matching applied to harmonize baseline characteristics. Comparative analysis sought to delineate distinctions of CPSP and recovery quality 1 year after surgery. RESULTS: Following propensity score matching, a cohort of 258 patients in each group underwent analysis. Comparisons after matching revealed no statistically significant disparities in 1-year CPSP incidence [76/258 (29.5%) versus 78/258 (30.2%), P = 0.847], moderate-to-severe pain occurrence [17/76 (22.4%) versus 22/78 (28.2%), P = 0.405], neuropathic pain occurrence [11/76 (14.5%) versus 11/78 (14.1%), P = 0.948], and postoperative recovery quality assessed by 12-Item Short Form Health Survey (SF-12) score (113.1 [107.2, 116.0] versus 113.0 [107.4, 116.0], P = 0.328). Multivariate logistic regression analysis encompassing the entire cohort identified being female [odds ratio (OR) 2.10, 95% confidence interval (CI) 1.59-2.79, P < 0.001) and postoperative rescue analgesia (OR 1.47, 95% CI 1.09-1.96, P = 0.010) as risk factors for CPSP, while intraoperative fentanyl dosage (OR 0.92, 95% CI 0.87-0.98, P = 0.006) emerged as a protective factor. CONCLUSION: The prolonged administration of dexmedetomidine did not yield discernible amelioration in either 1-year CPSP or the recovery quality after thoracoscopic surgery. Noteworthy risk factors for CPSP encompassed female sex, postoperative rescue analgesia, and diminished fentanyl dosage intraoperatively.

11.
Nurse Educ Today ; 139: 106223, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38657481

RESUMO

BACKGROUND: The current shortage and loss of nurses has become a significant problem in healthcare systems around the world. Professional commitment is essential to prevent the loss of nursing staff and stabilize the nursing workforce. OBJECTIVES: This study aimed to explore the unique relationship between school educational atmosphere, learning engagement, and professional commitment, and whether learning engagement would mediate the relationship between educational atmosphere and professional commitment. DESIGN: A cross-sectional study design was used. SETTINGS: The participants came from six schools in four cities in Hubei Province, China. PARTICIPANTS: A total of 1009 nursing students above the first year of undergraduate studies were included by convenient sampling method. METHODS: Data were collected using the Educational Climate Inventory, the Utrecht Work Engagement Scale-student, and the Professional Commitment Scale. Pearson correlation was used to examine the relationship between educational atmosphere, learning engagement, and professional commitment. Mediation analysis was used to test whether learning engagement mediated the relationship between educational atmosphere and professional commitment. RESULTS: A positive educational atmosphere was associated with a high level of learning engagement, which was associated with a higher level of professional commitment. Learning engagement mediated the relationship between educational atmosphere and professional commitment. CONCLUSIONS: The findings provide empirical evidence for promoting professional commitment in nursing students. Learning engagement is an important mediating variable connecting educational atmosphere and professional commitment. In order to stabilize the career choices of nursing students, it is necessary to take measures to improve their learning engagement during school.


Assuntos
Bacharelado em Enfermagem , Aprendizagem , Estudantes de Enfermagem , Humanos , Estudos Transversais , Estudantes de Enfermagem/psicologia , Estudantes de Enfermagem/estatística & dados numéricos , Feminino , Masculino , China , Inquéritos e Questionários , Bacharelado em Enfermagem/métodos , Adulto , Adulto Jovem
12.
Int J Biol Macromol ; 267(Pt 2): 131666, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38636755

RESUMO

Natural Rubber Latex (NRL) has shown to be a promising biomaterial for use as a drug delivery system to release various bioactive compounds. It is cost-effective, easy to handle, biocompatible, and exhibits pro-angiogenic and pro-healing properties for both soft and hard tissues. NRL releases compounds following burst and sustained release kinetics, exhibiting first-order release kinetics. Moreover, its pore density can be adjusted for tailored kinetics profiles. In addition, biotechnological applications of NRL in amblyopia, smart mattresses, and neovaginoplasty have demonstrated success. This comprehensive review explores NRL's diverse applications in biotechnology and biomedicine, addressing challenges in translating research into clinical practice. Organized into eight sections, the review emphasizes NRL's potential in wound healing, drug delivery, and metallic nanoparticle synthesis. It also addresses the challenges in enhancing NRL's physical properties and discusses its interactions with the human immune system. Furthermore, examines NRL's potential in creating wearable medical devices and biosensors for neurological disorders. To fully explore NRL's potential in addressing important medical conditions, we emphasize throughout this review the importance of interdisciplinary research and collaboration. In conclusion, this review advances our understanding of NRL's role in biomedical and biotechnological applications, offering insights into its diverse applications and promising opportunities for future development.


Assuntos
Materiais Biocompatíveis , Sistemas de Liberação de Medicamentos , Látex , Medicina Regenerativa , Borracha , Humanos , Materiais Biocompatíveis/química , Látex/química , Medicina Regenerativa/métodos , Borracha/química , Cicatrização/efeitos dos fármacos
13.
Sci Rep ; 14(1): 8503, 2024 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-38605222

RESUMO

This study explored the relationship between parenting stress, parenting style, parenting quality, and young children's executive function. In total, 243 firstborns aged 2-9 years old (SD = 3.82) and their parents from two-child families in Beijing participated in the study, which used executive function tasks and parenting questionnaires. The results found that (1) parenting stress negatively predicted parenting quality; (2) parenting style partially mediated the relationship between parenting stress and parenting quality; (3) children's executive function partially mediated the relationship between parenting stress and parenting quality; and (4) the spoiled, democratic, permissive, and authoritarian parenting styles each play a chain mediating role with young children's executive function between parenting stress and parenting quality. Taken together, these findings provide implications for scientific parenting of children with different psychological characteristics (such as executive function) in multiple-child families under Parenting stress.


Assuntos
Função Executiva , Poder Familiar , Humanos , Pré-Escolar , Criança , Poder Familiar/psicologia , Pais/psicologia , Inquéritos e Questionários , Comportamento Infantil/psicologia , Relações Pais-Filho
14.
J Sci Food Agric ; 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619112

RESUMO

BACKGROUND: The adhesion of probiotics to the intestine is crucial for their probiotic function. In previous studies, Tremella polysaccharides (TPS) (with sodium casein) have shown the potential to encapsulate probiotics and protect them in a simulated gastrointestinal tract. This study explored the effect of TPS (with sodium casein) on the adhesion of probiotics. RESULTS: Lactobacillus plantarum was coated with TPS and sodium casein in different proportions, and was freeze-dried. The rheological properties of the mixture of probiotics powder and mucin solution were determined by static and dynamic rheological analysis. Aqueous solutions of probiotic powder and mucin mixture exhibited pseudoplastic fluid rheological properties. The higher the proportion of TPS content, the higher the apparent viscosity and yield stress. The mixed bacterial powder and mucin fluid displayed thixotropy and was in accordance with the Herschel-Bulkley model. The TPS increased the bio-adhesive force of the probiotic powder and mucin. When using TPS as the only carbon source, the adhesion of L. plantarum to Caco-2 cells increased by 228% in comparison with glucose in vitro. Twelve adhesive proteins were also detected in the whole-cell proteome of L. plantarum. Among them, ten adhesive proteins occurred abundantly when grown with TPS as a carbon source. CONCLUSION: Tremella polysaccharides therefore possess probiotic properties and can promote the intestinal adhesion of L. plantarum. © 2024 Society of Chemical Industry.

15.
Cell Mol Neurobiol ; 44(1): 36, 2024 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-38637346

RESUMO

Surgical brain injury (SBI), induced by neurosurgical procedures or instruments, has not attracted adequate attention. The pathophysiological process of SBI remains sparse compared to that of other central nervous system diseases thus far. Therefore, novel and effective therapies for SBI are urgently needed. In this study, we found that neutrophil extracellular traps (NETs) were present in the circulation and brain tissues of rats after SBI, which promoted neuroinflammation, cerebral edema, neuronal cell death, and aggravated neurological dysfunction. Inhibition of NETs formation by peptidylarginine deiminase (PAD) inhibitor or disruption of NETs with deoxyribonuclease I (DNase I) attenuated SBI-induced damages and improved the recovery of neurological function. We show that SBI triggered the activation of cyclic guanosine monophosphate-adenosine monophosphate synthase stimulator of interferon genes (cGAS-STING), and that inhibition of the cGAS-STING pathway could be beneficial. It is worth noting that DNase I markedly suppressed the activation of cGAS-STING, which was reversed by the cGAS product cyclic guanosine monophosphate-adenosine monophosphate (cGMP-AMP, cGAMP). Furthermore, the neuroprotective effect of DNase I in SBI was also abolished by cGAMP. NETs may participate in the pathophysiological regulation of SBI by acting through the cGAS-STING pathway. We also found that high-dose vitamin C administration could effectively inhibit the formation of NETs post-SBI. Thus, targeting NETs may provide a novel therapeutic strategy for SBI treatment, and high-dose vitamin C intervention may be a promising translational therapy with an excellent safety profile and low cost.


Assuntos
Lesões Encefálicas , Armadilhas Extracelulares , Animais , Ratos , Encéfalo , Lesões Encefálicas/tratamento farmacológico , Ácido Ascórbico , Desoxirribonuclease I/farmacologia
16.
J Multidiscip Healthc ; 17: 1653-1662, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38646019

RESUMO

Background: Psoriasis is a chronic autoimmune inflammatory skin condition characterized by erythema, papules, and scales. It imposes a heavy psychological and social strain on both patients and their families. Surprisingly, there's limited research delving into the disease burden and coping strategies of spouses contending with psoriasis. Objective: The objective is to explore the disease burden faced and coping strategies utilized by spouses of individuals living with psoriasis. This exploration aims to offer insights crucial for devising mental health support and intervention strategies. Methods: The research methodology employed in this study was phenomenological, a qualitative approach. A total of fifteen spouses of patients with psoriasis were selected using an objective sampling method for in-depth, semi-structured interviews. Thematic analysis was then applied to the recorded interview data to derive meaningful themes. Results: This study has identified and analyzed three core themes concerning the disease burden and coping strategies of spouses of patients with psoriasis: Overwhelming disease burden; Lack of support system; Coping strategies (Problem - centered coping strategies: Proactive acquisition of disease knowledge; Active confrontation of illness - related issues; Behavioral habit alteration; and Emotional - centered coping strategies: Active acceptance and normalization; Passive acceptance and internalized stigma; Avoidance of disease - related problems). Conclusion: This study adds valuable insights into comprehending the disease burden encountered by spouses of patients with psoriasis and sheds light on the coping strategies they employ. Healthcare providers should proactively recognize and address the burden experienced by spouses early on. Establishing a robust support network is crucial, and promoting adaptive coping strategies can significantly aid spouses in effectively navigating and managing the complexities associated with psoriasis.

17.
Comput Biol Med ; 174: 108443, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38608328

RESUMO

Retinal vessel segmentation based on deep learning is an important auxiliary method for assisting clinical doctors in diagnosing retinal diseases. However, existing methods often produce mis-segmentation when dealing with low contrast images and thin blood vessels, which affects the continuity and integrity of the vessel skeleton. In addition, existing deep learning methods tend to lose a lot of detailed information during training, which affects the accuracy of segmentation. To address these issues, we propose a novel dual-decoder based Cross-patch Feature Interactive Net with Edge Refinement (CFI-Net) for end-to-end retinal vessel segmentation. In the encoder part, a joint refinement down-sampling method (JRDM) is proposed to compress feature information in the process of reducing image size, so as to reduce the loss of thin vessels and vessel edge information during the encoding process. In the decoder part, we adopt a dual-path model based on edge detection, and propose a Cross-patch Interactive Attention Mechanism (CIAM) in the main path to enhancing multi-scale spatial channel features and transferring cross-spatial information. Consequently, it improve the network's ability to segment complete and continuous vessel skeletons, reducing vessel segmentation fractures. Finally, the Adaptive Spatial Context Guide Method (ASCGM) is proposed to fuse the prediction results of the two decoder paths, which enhances segmentation details while removing part of the background noise. We evaluated our model on two retinal image datasets and one coronary angiography dataset, achieving outstanding performance in segmentation comprehensive assessment metrics such as AUC and CAL. The experimental results showed that the proposed CFI-Net has superior segmentation performance compared with other existing methods, especially for thin vessels and vessel edges. The code is available at https://github.com/kita0420/CFI-Net.


Assuntos
Aprendizado Profundo , Vasos Retinianos , Vasos Retinianos/diagnóstico por imagem , Humanos , Processamento de Imagem Assistida por Computador/métodos , Algoritmos
18.
Proc Natl Acad Sci U S A ; 121(19): e2402045121, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38683998

RESUMO

Phytophagous insects have evolved sophisticated detoxification systems to overcome the antiherbivore chemical defenses produced by many plants. However, how these biotransformation systems differ in generalist and specialist insect species and their role in determining insect host plant range remains an open question. Here, we show that UDP-glucosyltransferases (UGTs) play a key role in determining the host range of insect species within the Spodoptera genus. Comparative genomic analyses of Spodoptera species that differ in host plant breadth identified a relatively conserved number of UGT genes in generalist species but high levels of UGT gene pseudogenization in the specialist Spodoptera picta. CRISPR-Cas9 knockouts of the three main UGT gene clusters of Spodoptera frugiperda revealed that UGT33 genes play an important role in allowing this species to utilize the poaceous plants maize, wheat, and rice, while UGT40 genes facilitate utilization of cotton. Further functional analyses in vivo and in vitro identified the UGT SfUGT33F32 as the key mechanism that allows generalist S. frugiperda to detoxify the benzoxazinoid DIMBOA (2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3(4H)-one), a potent insecticidal phytotoxin produced by poaceous plants. However, while this detoxification capacity is conserved in several generalist Spodoptera species, Spodoptera picta, which specializes on Crinum plants, is unable to detoxify DIMBOA due to a nonfunctionalizing mutation in SpUGT33F34. Collectively, these findings provide insight into the role of insect UGTs in host plant adaptation, the mechanistic basis of evolutionary transitions between generalism and specialism and offer molecular targets for controlling a group of notorious insect pests.


Assuntos
Spodoptera , Animais , Spodoptera/genética , Glicosiltransferases/genética , Glicosiltransferases/metabolismo , Especificidade de Hospedeiro/genética , Difosfato de Uridina/metabolismo , Proteínas de Insetos/genética , Proteínas de Insetos/metabolismo , Filogenia
19.
Acta Biomater ; 173: 231-246, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38465268

RESUMO

Enterocutaneous fistula (ECF) is a severe medical condition where an abnormal connection forms between the gastrointestinal tract and skin. ECFs are, in most cases, a result of surgical complications such as missed enterotomies or anastomotic leaks. The constant leakage of enteric and fecal contents from the fistula site leads to skin breakdown and increases the risk of infection. Despite advances in surgical techniques and postoperative management, ECF accounts for significant mortality rates, estimated between 15-20%, and causes debilitating morbidity. Therefore, there is a critical need for a simple and effective method to seal and heal ECF. Injectable hydrogels with combined properties of robust mechanical properties and cell infiltration/proliferation have the potential to block and heal ECF. Herein, we report the development of an injectable nanoengineered adhesive hydrogel (INAH) composed of a synthetic nanosilicate (Laponite®) and a gelatin-dopamine conjugate for treating ECF. The hydrogel undergoes fast cross-linking using a co-injection method, resulting in a matrix with improved mechanical and adhesive properties. INAH demonstrates appreciable blood clotting abilities and is cytocompatible with fibroblasts. The adhesive properties of the hydrogel are demonstrated in ex vivo adhesion models with skin and arteries, where the volume stability in the hydrated internal environment facilitates maintaining strong adhesion. In vivo assessments reveal that the INAH is biocompatible, supporting cell infiltration and extracellular matrix deposition while not forming fibrotic tissue. These findings suggest that this INAH holds promising translational potential for sealing and healing ECF.


Assuntos
Fístula Intestinal , Adesivos Teciduais , Humanos , Hidrogéis/farmacologia , Adesivos , Gelatina , Fístula Intestinal/terapia
20.
Dalton Trans ; 53(14): 6184-6189, 2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38511430

RESUMO

A series of highly reduced Mo red clusters {Mo28} (1), {Mo30} (2), and {Mo40} (3) are synthesized from the rational assembly of planar {MoV4} building blocks and employed for proton conduction. 3 exhibits the best conductivity of 7.56 × 10-3 S cm-1 under optimal conditions due to the most efficient hydrogen-bonding network.

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