RESUMEN

Severe acute pancreatitis (SAP) is characterized by acute inflammation of the pancreas. The transcription factor BTB and CNC homology 1 (BACH1) has been implicated in various biological processes, including oxidative stress, apoptosis, and cell cycle regulation. However, its involvement in the pathogenesis of SAP remains relatively understudied. In the present work, our data demonstrated that BACH1 level was significantly increased in SAP patients, cellular, and animal models, while heat shock protein B1 (HSPB1) expression was weakened. Mechanistic assays validated that BACH1 acted as a transcriptional inhibitor of HSPB1. Moreover, HPDE6-C7 cells were stimulated with cerulein (Cer) and LPS to mimic the pathological stages of SAP in vitro. Depletion of BACH1 remarkably improved cell survival and alleviated the oxidative stress, ferroptosis, and inflammatory responses in SAP cell models. However, these changes were dramatically reversed upon co-inhibition of HSPB1. Animal findings confirmed that loss of BACH1 decreased pancreatic injury, inflammatory responses, and ferroptosis, but these effects were weakened by HSPB1 silence. Overall, these findings elucidate that the overexpression of BACH1 favors the ferroptosis and inflammation by transcriptionally inhibiting HSBP1, thereby exacerbating SAP progression.

Asunto(s)

Factores de Transcripción con Cremalleras de Leucina de Carácter Básico , Ferroptosis , Pancreatitis , Ferroptosis/efectos de los fármacos , Humanos , Animales , Pancreatitis/genética , Pancreatitis/metabolismo , Pancreatitis/inducido químicamente , Ratones , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/genética , Factores de Transcripción con Cremalleras de Leucina de Carácter Básico/metabolismo , Masculino , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Epigénesis Genética , Chaperonas Moleculares/genética , Proteínas de Choque Térmico HSP27/genética , Proteínas de Choque Térmico HSP27/metabolismo , Ratones Endogámicos C57BL , Línea Celular , Modelos Animales de Enfermedad

RESUMEN

The aim of this study was to investigate whether the protective effect of 2-deoxyglucose (2-DG) on lung ischemia/reperfusion (I/R) injury is mediated by inhibiting nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-mediated pyroptosis in rats. Male Sprague-Dawley rats were randomly divided into control group, 2-DG group, lung I/R injury group (I/R group) and 2-DG+I/R group. 2-DG (0.7 g/kg) was intraperitoneally injected 1 h prior to lung ischemia. The tissue structure was measured under light microscope. Lung injury parameters were detected. The contents of malondialdehyde (MDA), myeloperoxidase (MPO) and lactate were determined by commercially available kits. ELISA was used to detect the levels of IL-1ß and IL-18. Western blot, qRT-PCR and immunofluorescence staining were used to measure the expression changes of glycolysis and pyroptosis related indicators. The results showed that there was no significant difference in the parameters between the control group and the 2-DG group. However, the lung injury parameters, oxidative stress response, lactic acid content, IL-1ß, and IL-18 levels were significantly increased in the I/R group. The protein expression levels of glycolysis and pyroptosis related indicators including hexokinase 2 (HK2), pyruvate kinase 2 (PKM2), NLRP3, Gasdermin superfamily member GSDMD-N, cleaved-Caspase1, cleaved-IL-1ß and cleaved-IL-18, and the gene expression levels of HK2, PKM2 and NLRP3 were markedly up-regulated in the I/R group compared with those in the control group. The expression of HK2 and NLRP3 was also increased detected by immunofluorescence staining. Compared with the I/R group, the 2-DG+I/R group exhibited significantly improved alveolar structure and inflammatory infiltration, reduced lung injury parameters, and decreased expression of glycolysis and pyroptosis related indicators. These results suggest that 2-DG protects against lung I/R injury possibly by inhibiting NLRP3-mediated pyroptosis in rats.

Asunto(s)

Desoxiglucosa , Pulmón , Proteína con Dominio Pirina 3 de la Familia NLR , Piroptosis , Ratas Sprague-Dawley , Daño por Reperfusión , Animales , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Masculino , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Ratas , Pulmón/metabolismo , Pulmón/patología , Desoxiglucosa/farmacología , Interleucina-1beta/metabolismo , Interleucina-18/metabolismo , Lesión Pulmonar/metabolismo , Lesión Pulmonar/prevención & control , Lesión Pulmonar/etiología , Estrés Oxidativo

RESUMEN

Migration and homing of immune cells are critical for immune surveillance. Trafficking is mediated by combinations of adhesion and chemokine receptors that guide immune cells, in response to chemokine signals, to specific locations within tissues and the lymphatic system to support tissue-localized immune reactions and systemic immunity1,2. Here we show that disruption of leukaemia inhibitory factor (LIF) production from group 2 innate lymphoid cells (ILC2s) prevents immune cells leaving the lungs to migrate to the lymph nodes (LNs). In the absence of LIF, viral infection leads to plasmacytoid dendritic cells (pDCs) becoming retained in the lungs where they improve tissue-localized, antiviral immunity, whereas chronic pulmonary allergen challenge leads to marked immune cell accumulation and the formation of tertiary lymphoid structures in the lung. In both cases immune cells fail to migrate to the lymphatics, leading to highly compromised LN reactions. Mechanistically, ILC2-derived LIF induces the production of the chemokine CCL21 from lymphatic endothelial cells lining the pulmonary lymphatic vessels, thus licensing the homing of CCR7+ immune cells (including dendritic cells) to LNs. Consequently, ILC2-derived LIF dictates the egress of immune cells from the lungs to regulate tissue-localized versus systemic immunity and the balance between allergen and viral responsiveness in the lungs.

Asunto(s)

Movimiento Celular , Inmunidad Innata , Factor Inhibidor de Leucemia , Pulmón , Linfocitos , Animales , Femenino , Masculino , Ratones , Alérgenos/inmunología , Movimiento Celular/inmunología , Quimiocina CCL21/metabolismo , Quimiocina CCL21/inmunología , Células Dendríticas/citología , Células Dendríticas/inmunología , Células Endoteliales/inmunología , Células Endoteliales/metabolismo , Inmunidad Innata/inmunología , Factor Inhibidor de Leucemia/metabolismo , Factor Inhibidor de Leucemia/inmunología , Pulmón/inmunología , Pulmón/virología , Ganglios Linfáticos/citología , Ganglios Linfáticos/inmunología , Vasos Linfáticos/citología , Vasos Linfáticos/inmunología , Vasos Linfáticos/metabolismo , Linfocitos/clasificación , Linfocitos/citología , Linfocitos/inmunología , Ratones Endogámicos C57BL , Receptores CCR7/metabolismo , Receptores CCR7/inmunología

RESUMEN

Intracranial aneurysm (IA) is a common cerebrovascular disease. Immune system disorders and endothelial dysfunction are essential mechanisms of its pathogenesis. This study aims to explore the therapeutic effect and mechanism of Geniposide (Gen) on IA, which has a protective impact on endothelial cells and cardiovascular and cerebrovascular diseases. IA mouse models were administered intraperitoneal injections of geniposide for 2 weeks following elastase injection into the right basal ganglia of the brain for intervention. The efficacy of Gen in treating IA was evaluated through pathological testing and transcriptome sequencing analysis of Willis ring vascular tissue. The primary mechanism of action was linked to the expression of GSK3ß in Th17 cells. The percentage of splenic Th17 cell differentiation in IA mice was significantly inhibited by Gen. GSK3ß/STAT3, and other pathway protein expression levels were also significantly inhibited by Gen. Additionally, TNF-α and IL-23 cytokine contents were significantly downregulated after Gen treatment. These results indicated that Gen significantly inhibited the percentage of Th17 cell differentiation, an effect that was reversed upon overexpression of the GSK3B gene. Furthermore, Gen-treated, Th17 differentiation-inducing cell-conditioned medium significantly up-regulated the expression of tight junction proteins ZO-1, Occludin, and Claudin-5 in murine aortic endothelial cells. Administering the GSK3ß inhibitor Tideglusib to IA mice alleviated the severity of IA disease pathology and up-regulated aortic tight junction protein expression. In conclusion, Gen inhibits Th17 cell differentiation through GSK3ß, which reduces endothelial cell injury and up-regulates tight junction protein expression.

RESUMEN

mRNA therapeutics have shown great potential for a broad spectrum of disease treatment. However, the challenges of mRNA's inherent instability and difficulty in cellular entry have hindered its progress in the biomedical field. To address the cellular barriers and deliver mRNA to cells of interest, various delivery systems are designed. Among these, lipid nanoparticles (LNPs) stand out as the most extensively used mRNA delivery systems, particularly following the clinical approvals of corona virus disease 2019 (COVID-19) mRNA vaccines. LNPs are comprised of ionizable cationic lipids, phospholipids, cholesterol, and polyethylene glycol derived lipids (PEG-lipids). In this review, we primarily summarize the recent advancements of the LNP mRNA delivery technology, focusing on the structures of four lipid constituents and their biomedical applications. We delve into structure-activity relationships of the lipids, while also exploring the future prospects and challenges in developing more efficacious mRNA delivery systems. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Biology-Inspired Nanomaterials > Lipid-Based Structures Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Asunto(s)

Lípidos , Nanopartículas , ARN Mensajero , Humanos , Nanopartículas/química , ARN Mensajero/metabolismo , Lípidos/química , Animales , SARS-CoV-2 , COVID-19 , Sistemas de Liberación de Medicamentos , Vacunas contra la COVID-19/química , Liposomas

RESUMEN

Fully targeted mRNA therapeutics necessitate simultaneous organ-specific accumulation and effective translation. Despite some progress, delivery systems are still unable to fully achieve this. Here, we reformulate lipid nanoparticles (LNPs) through adjustments in lipid material structures and compositions to systematically achieve the pulmonary and hepatic (respectively) targeted mRNA distribution and expression. A combinatorial library of degradable-core based ionizable cationic lipids is designed, following by optimisation of LNP compositions. Contrary to current LNP paradigms, our findings demonstrate that cholesterol and phospholipid are dispensable for LNP functionality. Specifically, cholesterol-removal addresses the persistent challenge of preventing nanoparticle accumulation in hepatic tissues. By modulating and simplifying intrinsic LNP components, concurrent mRNA accumulation and translation is achieved in the lung and liver, respectively. This targeting strategy is applicable to existing LNP systems with potential to expand the progress of precise mRNA therapy for diverse diseases.

Asunto(s)

Lípidos , Hígado , Pulmón , Nanopartículas , ARN Mensajero , ARN Mensajero/metabolismo , ARN Mensajero/genética , Nanopartículas/química , Animales , Hígado/metabolismo , Pulmón/metabolismo , Lípidos/química , Humanos , Ratones , Colesterol/metabolismo , Colesterol/química , Biosíntesis de Proteínas , Ratones Endogámicos C57BL , Fosfolípidos/química , Fosfolípidos/metabolismo , Liposomas

RESUMEN

Metal-organic frameworks (MOFs) have emerged as attractive candidates for Li+ conducting electrolytes due to their regular channels and controllable morphology, making their presence prominent in the field of solid-state lithium batteries. However, most MOF-based electrolytes are researched at or near room temperature, which poses a challenge to their practical applications at low temperatures. Herein, a thin layer flower-shaped 2D Cu-MOF (CuBDC-10)-based solid-state electrolytes (SSEs) for lithium-ion batteries (LIBs) are developed for facilitating Li+ transport at lower temperatures, which achieve an ion conductivity of 10-4 S cm-1 at -30 °C. The CuBDC-10-based SSE exhibits outstanding ionic conductivity over a wide temperature range of -40 to 100 °C (0.073-3.68 × 10-3 S cm-1). This work provides strategies for exploring MOF-based SSEs with high ionic transport performances at low temperatures.

RESUMEN

BACKGROUND: Depression poses a major threat to public health with an increasing prevalence in the United States. Mindfulness-based interventions, such as mindfulness-based cognitive therapy (MBCT), are effective methods for managing depression symptoms and may help fortify existing efforts to address the current disease burden. The in-person group format of MBCT, however, incurs barriers to care such as expenses, childcare needs, and transportation issues. Alternate delivery modalities such as MBCT delivered via the web can be investigated for their capacity to overcome these barriers and still reduce symptoms of depression with adequate feasibility and efficacy. OBJECTIVE: This study protocol aims to examine the feasibility and efficacy of MBCT delivered via the web for the treatment of depression. METHODS: To attain study aims, 2 phases will be implemented using a waitlist control design. A total of 128 eligible participants will be randomized into either an 8-week MBCT intervention group plus treatment as usual (MBCT + TAU; group 1) or an 8-week waitlist control group (group 2). In phase I (8 weeks), group 1 will complete the intervention and group 2 will proceed with TAU. In phase II (8 weeks), group 2 will complete the intervention and group 1 will continue with TAU until reaching an 8-week follow-up. TAU may consist of receiving psychotherapy, pharmacotherapy, or combined treatment. Data collection will be completed at baseline, 8 weeks (postintervention for group 1 and preintervention for group 2), and 16 weeks (follow-up for group 1, postintervention for group 2). The primary outcomes will include (1) current, residual, or chronic depression symptoms and (2) psychiatric distress. Secondary outcomes will include perceived stress and facets of mindfulness. The feasibility will be measured by assessing protocol adherence, retention, attendance, and engagement. Finally, the extent of mindfulness self-practice and executive functioning skills will be assessed as mediators of intervention outcomes. RESULTS: This study began screening and recruitment in December 2022. Data collection from the first cohort occurred in January 2023. By November 2023, a total of 30 participants were enrolled out of 224 who received screening. Data analysis began in February 2024, with an approximate publication of results by August 2024. Institutional review board approval took place on September 11, 2019. CONCLUSIONS: This trial will contribute to examining mindfulness-based interventions, delivered via the web, for improving current, residual, or chronic depression symptoms. It will (1) address the feasibility of MBCT delivered via the web; (2) contribute evidence regarding MBCT's efficacy in reducing depression symptoms and psychiatric distress; and (3) assess the impact of MBCT on several important secondary outcomes. Findings from this study will develop the understanding of the causal pathways between MBCT delivered via the web and depression symptoms further, elucidating the potential for future larger-scale designs. TRIAL REGISTRATION: ClinicalTrials.gov NCT05347719; https://www.clinicaltrials.gov/ct2/show/NCT05347719. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53966.

Asunto(s)

Terapia Cognitivo-Conductual , Depresión , Atención Plena , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Terapia Cognitivo-Conductual/métodos , Depresión/terapia , Internet , Intervención basada en la Internet , Atención Plena/métodos , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto

RESUMEN

There is a lack of literature examining the engagement in strength activities of people with disabilities (PWD) using and not using wearable devices. The objectives of the current study were to determine the prevalence of strength activity engagement among wearable device users with disabilities, and to compare strength activity engagement between wearable device users and non-users with and without disabilities. Wearable device users and non-users with and without disabilities from eight states of the CDC's 2017 Behavioral Risk Factor Surveillance were included in the analysis. Linear regression was used to examine the association between wearable device use and disability status and the interaction term for frequency of strength activity per week, while logistic regression was used to determine the association between the two variables and the interaction term for strength activity engagement and meeting strength activity guidelines. 7055 wearable device users and non-users with and without disabilities were included in the analysis. No interaction effects were found between wearable device use and disability status. In unadjusted logistic regressions, wearable device users were more likely to engage in strength activity (OR = 1.16, 95% CI [1.16, 2.20]) and meet strength activity guidelines (OR = 1.50, 95% CI [1.07, 2.09]), whereas PWDs were less likely to engage in strength activity (OR = 0.57, 95% CI [0.44, 0.75]) and meet strength activity guidelines (OR = 0.72, 95% CI [0.53, 0.98]). The use of wearable devices could lead to engagement in strength activity. However, further research is needed to determine its effectiveness in PWD.

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Wearable devices can be used to track physical activity and strength activity engagement.Wearable device users were more likely to engage in vigorous activity and meet the vigorous activity guidelines of two times per week to obtain health-related benefits.People with disabilities were less likely to engage in strength activity and less likely to meet the strength activity guidelines of two times per week.Further research is needed to determine the effectiveness of using wearable devices to promote engagement in strength activity and their use in rehabilitation settings.There is potential use of wearable devices in promoting strength activity engagement among people with disabilities and in rehabilitation setting, but there is a need to determine how people with disabilities use wearable devices in rehabilitation setting.

RESUMEN

Innate lymphoid cells (ILCs) and adaptive T lymphocytes promote tissue homeostasis and protective immune responses. Their production depends on the transcription factor GATA3, which is further elevated specifically in ILC2s and T helper 2 cells to drive type-2 immunity during tissue repair, allergic disorders, and anti-helminth immunity. The control of this crucial up-regulation is poorly understood. Using CRISPR screens in ILCs we identified previously unappreciated myocyte-specific enhancer factor 2d (Mef2d)-mediated regulation of GATA3-dependent type-2 lymphocyte differentiation. Mef2d-deletion from ILC2s and/or T cells specifically protected against an allergen lung challenge. Mef2d repressed Regnase-1 endonuclease expression to enhance IL-33 receptor production and IL-33 signaling and acted downstream of calcium-mediated signaling to translocate NFAT1 to the nucleus to promote type-2 cytokine-mediated immunity.

Asunto(s)

Factor de Transcripción GATA3 , Inmunidad Innata , Interleucina-33 , Factores de Transcripción MEF2 , Factores de Transcripción NFATC , Neumonía , Células Th2 , Animales , Ratones , Factores de Transcripción MEF2/metabolismo , Factores de Transcripción MEF2/genética , Células Th2/inmunología , Interleucina-33/metabolismo , Factores de Transcripción NFATC/metabolismo , Neumonía/inmunología , Factor de Transcripción GATA3/metabolismo , Factor de Transcripción GATA3/genética , Ratones Endogámicos C57BL , Diferenciación Celular , Señalización del Calcio , Hipersensibilidad/inmunología , Pulmón/inmunología , Alérgenos/inmunología , Linfocitos/inmunología , Proteína 1 Similar al Receptor de Interleucina-1

RESUMEN

OBJECTIVE: To analyze the factors affecting overall survival (OS) of adult patients with core-binding factor acute myeloid leukemia (CBF-AML) and establish a prediction model. METHODS: A total of 216 newly diagnosed patients with CBF-AML in the First Affiliated Hospital of Zhengzhou University from May 2015 to July 2021 were retrospectively analyzed. The 216 CBF-AML patients were divided into the training and the validation cohort at 7∶3 ratio. The Cox regression model was used to analyze the clinical factors affecting OS. Stepwise regression was used to establish the optimal model and the nomogram. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the model performance. RESULTS: Age(≥55 years old), peripheral blood blast(≥80%), fusion gene (AML1-ETO), KIT mutations were identified as independent adverse factors for OS. The area under the ROC curve at 3-year was 0.772 and 0.722 in the training cohort and validation cohort, respectively. The predicted value of the calibration curve is in good agreement with the measured value. DCA shows that this model performs better than a single factor. CONCLUSION: This prediction model is simple and feasible, and can effectively predict the OS of CBF-AML, and provide a basis for treatment decision.

Asunto(s)

Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Pronóstico , Estudios Retrospectivos , Persona de Mediana Edad , Femenino , Masculino , Mutación , Curva ROC , Factores de Unión al Sitio Principal/genética , Nomogramas , Adulto , Proteína 1 Compañera de Translocación de RUNX1/genética , Proteínas Proto-Oncogénicas c-kit/genética , Modelos de Riesgos Proporcionales , Proteínas de Fusión Oncogénica/genética , Subunidad alfa 2 del Factor de Unión al Sitio Principal/genética

RESUMEN

BACKGROUND AND PURPOSE: Intracranial hemorrhage (ICH) in leukemia patients progresses rapidly with high mortality. Limited data are available on imaging studies in this population. The study aims to develop prediction models for 7-day and short-term mortality risk based on the non-contrast computed tomography (NCCT) image features. METHODS: The NCCT image features of ICH in 135 leukemia patients between 2007-2023 were retrospectively extracted using manual assessment and radiomics methods. After multiple imputation of missing laboratory data, univariate logistic regression and least absolute shrinkage and selection operator (LASSO) were used for feature selection. Random forest models were built with comprehensive evaluation and ranking of feature importance. RESULT: 135 and 129 patients were included in the studies for 7-day and short-term prognostic models, respectively. The median age of all enrolled patients was 35 years, and there were 86 male patients (63.7 %). Clinical models (validation: AUC [area under the curve] = 0.78, AUPRC [area under the precision-recall curve] = 0.73; AUC = 0.84, AUPRC = 0.86), radiomics models (validation: AUC = 0.82, AUPRC = 0.78; AUC = 0.75, AUPRC = 0.77), and the combined models (validation: AUC = 0.84, AUPRC = 0.83; AUC = 0.87, AUPRC = 0.89) predicted 7-day and short-term mortality with good predictive efficacy. Clinical decision curve analysis showed that the combined models predicted 7-day and 30-day risk of death would be more beneficial than other models. Shape features contributed significantly more than semantic features in both radiomics models and combined models (93.3 %, 52.1 %, as well as 85.2 %,37.4 %, respectively) for 7-day and 30-day mortality. CONCLUSIONS: Combined models constructed based on NCCT perform well in predicting the risk of 7-day and short-term mortality in ICH patients with leukemia. Shape features extracted by radiomics are important markers for modeling the prognosis.

Asunto(s)

Hemorragia Cerebral , Leucemia , Aprendizaje Automático , Tomografía Computarizada por Rayos X , Humanos , Masculino , Femenino , Adulto , Tomografía Computarizada por Rayos X/métodos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/complicaciones , Leucemia/complicaciones , Leucemia/diagnóstico por imagen , Estudios Retrospectivos , Pronóstico , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Anciano , Adolescente

RESUMEN

[This corrects the article DOI: 10.1016/j.apsb.2023.12.012.].

RESUMEN

Broccoli is a rich source of diverse bioactive compounds, but how their contents are influenced by different growing seasons and variations in broccoli head sizes remains elusive. To address this question, we quantified sixteen known bioactive compounds and seven minerals in broccoli with varying head sizes obtained in two different growing seasons. Our results suggest that the contents of vitamin C, total phenols, carotenoids, and glucoraphanin were significantly higher in samples from the summer-autumn season, showing increases of 157.46%, 34.74%, 51.80%, and 17.78%, respectively, compared with those from the winter-spring season. Moreover, chlorogenic acid is a phenolic compound with relatively high contents among the six detected, while beta-sitosterol is the sterol with relatively high contents. Further, principal component analysis was conducted to rank the comprehensive scores of the profiles of phenolic compounds, phytosterols, and minerals, demonstrating that the broccoli samples grown during the summer-autumn season achieved the highest composite scores. Our results indicate that broccoli heads from the summer-autumn season are richer in a combination of bioactive compounds and minerals than those from the winter-spring season based on the composite score. This study extends our understanding of the nutrition profiles in broccoli and also lays the foundation for breeding broccoli varieties with improved nutrition quality.

RESUMEN

OBJECTIVES: To investigate the relationships among caregiver burden, family resilience, and caregiver capacity in the care of stroke survivors. We hypothesised that family resilience would mediate the relationship between caregiver burden and caregiver capacity. DESIGN: A cross-sectional study design was used. SETTING: The study was conducted in a tertiary care setting in Ningbo City, Zhejiang Province, China. PARTICIPANTS: The study involved 413 stroke survivors and their primary caregivers. OUTCOME MEASURES: The primary caregivers completed the Shortened Chinese Version of the Family Resilience Assessment Scale, Zarit Caregiver Burden Interview and Family Caregiver Task Inventor and provided their sociodemographic information. Stroke survivors were assessed for activities of daily living, and their sociodemographic information was provided. Data were analysed, controlling for sociodemographic variables and focusing on the mediating effect of family resilience. RESULTS: Caregiver burden was influenced by the activities of daily living of stroke survivors, caregiver age and caregiver health status (p<0.05). Higher caregiver burden was associated with lower family resilience (p<0.01). Lower caregiver capacity corresponded to heavier caregiver burden (p<0.01). Family resilience mediated the relationship between caregiver burden and caregiver capacity (b=0.1568; 95% CI: 0.1063 to 0.2385). CONCLUSIONS: Enhancing family resilience can reduce caregiver burden and improve caregiver capacity in stroke care. These findings underscore the importance of developing interventions focused on nursing skills and family resilience.

Asunto(s)

Actividades Cotidianas , Carga del Cuidador , Cuidadores , Resiliencia Psicológica , Accidente Cerebrovascular , Sobrevivientes , Humanos , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Accidente Cerebrovascular/psicología , Accidente Cerebrovascular/enfermería , China , Cuidadores/psicología , Anciano , Sobrevivientes/psicología , Carga del Cuidador/psicología , Adulto , Familia/psicología , Adaptación Psicológica

RESUMEN

A brand-new procedure for the synthesis of 3-alkynylated 3,3-disubstituted isoindolinones has been disclosed via a HOTf or Fe(OTf)3-catalyzed dehydrative alkynylation of 3-hydroxyisoindolinones with terminal alkynes. Aryl, alkenyl and alkyl terminal alkynes are suitable to couple with a broad range of 3-hydroxyisoindolinones to afford the desired products in moderate to good yields. This protocol features the use of an inexpensive catalyst, mild reaction conditions, broad substrate scope and easy elaboration of the products.

RESUMEN

Unlocking the full potential of mRNA immunotherapy necessitates targeted delivery to specific cell subsets in the spleen. Four-component lipid nanoparticles (LNPs) utilized in numerous clinical trials are primarily limited in hepatocyte and muscular targeting, highlighting the imperative demand for targeted and simplified non-liver mRNA delivery systems. Herein, we report the rational design of one-component ionizable cationic lipids to selectively deliver mRNA to the spleen and T cells with high efficacy. Unlike the tertiary amine-based ionizable lipids involved in LNPs, the proposed cationic lipids rich in secondary amines can efficiently deliver mRNA both in vitro and in vivo as the standalone carriers. Furthermore, these vectors facilitate efficacious mRNA delivery to the T cell subsets following intravenous administration, demonstrating substantial potential for advancing immunotherapy applications. This straightforward strategy extends the utility of lipid family for extrahepatic mRNA delivery, offering new insights into vector development beyond LNPs to further the field of precise mRNA therapy.

Asunto(s)

Cationes , Lípidos , ARN Mensajero , Bazo , Linfocitos T , Bazo/metabolismo , Bazo/citología , ARN Mensajero/administración & dosificación , ARN Mensajero/genética , Lípidos/química , Cationes/química , Animales , Linfocitos T/metabolismo , Ratones , Nanopartículas/química , Humanos

RESUMEN

Enhancing the flame retardancy of electrolytes and the stability of lithium anodes is of great significance to improve the safety performance of lithium-sulfur (Li-S) batteries. It is well known that the most commonly used ether based electrolyte solvents in Li-S batteries have a lower flash point and higher volatility than the ester electrolyte solvents in Li-ion batteries. Hence, lithium-sulfur batteries have greater safety risks than lithium-ion batteries. Herein, ethoxy(pentafluoro)cyclotriphosphazene (PFPN), which is commonly used as a flame retardant for ester electrolytes in lithium-ion batteries, is utilized as both a film-forming electrolyte additive and a flame retardant additive for the ether electrolyte to investigated its applicability in Li-S batteries. It is found that the ether electrolyte containing PFPN not only has good flame retardant properties and a wide potential window of about 5 V, but also can form a stable SEI film on the surface of a lithium anode. As a result, with the ether-based electrolyte containing 10 wt% PFPN, Li-Cu and Li-S batteries all delivered a stable cycling performance with a high coulombic Efficiency and a long-lifespan performance, which were all superior to the batteries using the ether-based electrolyte without PFPN. This study demonstrates an effective solution to solve the problems of flammable ether-based electrolytes and reactive lithium anodes, and it may contribute to the development of safe Li-S batteries.

RESUMEN

Immune-mediated liver injury (ILI) is a condition where an aberrant immune response due to various triggers causes the destruction of hepatocytes. Fibroblast growth factor 4 (FGF4) was recently identified as a hepatoprotective cytokine; however, its role in ILI remains unclear. In patients with autoimmune hepatitis (type of ILI) and mouse models of concanavalin A (ConA)- or S-100-induced ILI, we observed a biphasic pattern in hepatic FGF4 expression, characterized by an initial increase followed by a return to basal levels. Hepatic FGF4 deficiency activated the mitochondria-associated intrinsic apoptotic pathway, aggravating hepatocellular apoptosis. This led to intrahepatic immune hyper-reactivity, inflammation accentuation, and subsequent liver injury in both ILI models. Conversely, administration of recombinant FGF4 reduced hepatocellular apoptosis and rectified immune imbalance, thereby mitigating liver damage. The beneficial effects of FGF4 were mediated by hepatocellular FGF receptor 4, which activated the Ca2+/calmodulin-dependent protein kinasekinase 2 (CaMKKß) and its downstream phosphatase and tensin homologue-induced putative kinase 1 (PINK1)-dependent B-cell lymphoma 2-like protein 1-isoform L (Bcl-XL) signalling axis in the mitochondria. Hence, FGF4 serves as an early response factor and plays a protective role against ILI, suggesting a therapeutic potential of FGF4 and its analogue for treating clinical immune disorder-related liver injuries.

RESUMEN

Carbon materials with full sp2-hybridized buckling is a major challenge pervading fundamental nanoscience and nanotechnology research. Carbon atoms that are sp2 hybridized prefer to form hexagonal rings, such as in carbon nanotubes and graphene, which are low-dimensional materials. The incorporation of heptagonal, octagonal, and/or larger rings into a hexagonal sp2 carbon meshwork has been identified as a strategy for assembling three-dimensional (3D) sp2 carbon crystals, and one of the typical representatives are Schwarzite carbons, which possess a negative surface Gaussian curvature as well as unique physical properties. Herein, a 3D Schwarzite carbon consisting of only sp2-buckled heptagonal carbon rings, which is referred to as Hepta-carbon, is proposed based on first-principles calculations. Hepta-carbon is mechanically and thermodynamically stable, and energetically more favourable than experimental graphdiyne, fullerene C20 and most Schwarzite carbons under ambient conditions. Molecular dynamics simulations indicate that Hepta-carbon exhibits high-temperature thermostability up to 1500 K. Band structure and mechanical property simulations indicate that Hepta-carbon is a semi-metallic material with electron conduction and exhibits impressive mechanical properties such as high strength with quasi-isotropy, high incompressibility similar to diamonds, elastic deformation behaviour under uniaxial stress, and high ductility. Hepta-carbon presents a porous network with a low mass density of 1.84 g cm-3 and connected channels with diameters of 3.3-6.1 Å. Theoretical simulations of gas adsorption energy demonstrate that Hepta-carbon can effectively adsorb and stabilize greenhouse gases, including N2O, CO2, CH4, and SF6.