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2.
Food Chem ; 460(Pt 2): 140661, 2024 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-39089019

RESUMEN

This study investigated the effect of calcium chloride (CaCl2) combined with acetic acid (AA) pretreatment on the oil absorption of potato chips and explored the possible mechanisms influencing oil absorption. Results indicated that compared with hot water blanching, the combination of 0.3% CaCl2 blanching and AA soaking for 2-8 h pretreatment was found to reduce oil content by 10.52%-12.68% and significantly improve the crispness and color of fried potato chips. Microstructural and textural analyses revealed that the main reason for the reduction in oil content was the promotion of pectin gelation in the cell wall by CaCl2 and AA. However, it was observed that prolonged AA soaking time and high-concentration CaCl2 blanching led to an increase in total oil content and decrease in brittleness. Based on the results of surface roughness and moisture content analyses, it was suggested that the CaCl2 and AA pretreatments affected surface roughness and moisture content, thereby increasing oil absorption and reducing brittleness during frying.


Asunto(s)
Ácido Acético , Cloruro de Calcio , Culinaria , Solanum tuberosum , Ácido Acético/química , Solanum tuberosum/química , Cloruro de Calcio/química , Aceites de Plantas/química , Calor , Manipulación de Alimentos , Absorción
3.
JAMA Surg ; 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39110467

RESUMEN

This case series evaluates changes in numeric pain scores, opioid use, and other measures before, during, and 30 days after computed tomography­guided percutaneous cryoneurolysis in patients with rib injury.

4.
J Colloid Interface Sci ; 677(Pt A): 941-952, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39128288

RESUMEN

Prodrug nanoassemblies combine the advantages of prodrug strategies and nanotechnology have been widely utilized for delivering antitumor drugs. These prodrugs typically comprise active drug modules, response modules, and modification modules. Among them, the modification modules play a critical factor in improving the self-assembly ability of the parent drug. However, the impact of the specific structure of the modification modules on prodrug self-assembly remains elusive. In this study, two gemcitabine (GEM) prodrugs are developed using 2-octyl-1-dodecanol (OD) as flexible modification modules and cholesterol (CLS) as rigid modification modules. Interestingly, the differences in the chemical structure of modification modules significantly affect the assembly performance, drug release, cytotoxicity, tumor accumulation, and antitumor efficacy of prodrug nanoassemblies. It is noteworthy that the prodrug nanoassemblies constructed with flexible modifying chains (OD) exhibit improved stability, faster drug release, and enhanced antitumor effects. Our findings elucidate the significant impact of modification modules on the construction of prodrug nanoassemblies.

5.
Cell Signal ; 122: 111340, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39127135

RESUMEN

Obesity and its complications have become a global health problem that needs to be addressed urgently. White adipose tissue (WAT) browning contributes to consuming excess energy in WAT, which is important for improving obesity and maintaining a healthy energy homeostasis. Mitochondria, as the energy metabolism center of cells, are extensively involved in many metabolic processes, including the browning of WAT. NADH: Ubiquinone oxidoreductase subunit A8 (NDUFA8) is a constituent subunit of respiratory chain complex I (CI), which has been found to participate in a wide range of physiological processes by affecting the activity of respiratory CI. However, the regulatory effect of Ndufa8 on the browning of WAT has not been reported. Here, we used ß3-adrenergic agonis CL316, 243 to construct WAT browning models in vivo and in vitro to investigate the role and mechanism of Ndufa8 in the regulation of WAT browning. Briefly, Ndufa8 significantly increased CI activity and suppressed mitochondrial ROS levels in vitro, thereby improving mitochondrial function. Ndufa8 also increased the transcriptional levels and protein levels of UCP1 in vitro and in vivo, which promoted WAT browning. Our findings provide a new molecular approach for the research of browning of WAT in animals, as well as a new target for animal metabolism improvement and obesity treatments.


Asunto(s)
Tejido Adiposo Pardo , Tejido Adiposo Blanco , Complejo I de Transporte de Electrón , Ratones Endogámicos C57BL , Mitocondrias , Obesidad , Animales , Complejo I de Transporte de Electrón/metabolismo , Obesidad/metabolismo , Tejido Adiposo Blanco/metabolismo , Ratones , Mitocondrias/metabolismo , Tejido Adiposo Pardo/metabolismo , Masculino , Especies Reactivas de Oxígeno/metabolismo , Proteína Desacopladora 1/metabolismo , Proteína Desacopladora 1/genética , Dioxoles/farmacología , Dieta Alta en Grasa , Termogénesis
6.
J Control Release ; 374: 489-504, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39182692

RESUMEN

Multimodal treatment of cancer is an unstoppable revolution in clinical application. However, designing a platform that integrates therapeutic modalities with different pharmacokinetic characteristics remains a great challenge. Herein, we designed a universal lipid nanoplatform equipping a ROS-cleavable docetaxel prodrug (DTX-L-DTX) and an NF-E2-related factor 2 (NRF2) inhibitor (clobetasol propionate, CP). This simply fabricated nanomedicine enables superior synergistic molecularly targeted/chemo/radio therapy for lung cancer cascade by a transcription factor-driven ROS self-sustainable motion. Chemotherapy is launched via ROS-triggered DTX release. Subsequently, CP inhibits the expression of NRF2 target genes, resulting in efficient targeted therapy, meanwhile inducing sustained ROS generation which in turn facilitates chemotherapy by overcoming ROS consumption during the DTX release process. Finally, the introduction of radiotherapy further amplifies ROS, offering continuous mutual feedback to amplify the ultimate treatment performance. This strategy is conceptually and operationally simple, providing solutions to challenges in clinical cancer treatment and beyond.


Asunto(s)
Antineoplásicos , Docetaxel , Neoplasias Pulmonares , Factor 2 Relacionado con NF-E2 , Profármacos , Especies Reactivas de Oxígeno , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Humanos , Animales , Profármacos/uso terapéutico , Profármacos/administración & dosificación , Antineoplásicos/administración & dosificación , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Docetaxel/administración & dosificación , Docetaxel/uso terapéutico , Docetaxel/farmacología , Docetaxel/farmacocinética , Factor 2 Relacionado con NF-E2/metabolismo , Nanopartículas , Terapia Combinada , Ratones Desnudos , Ratones Endogámicos BALB C , Línea Celular Tumoral , Células A549 , Liberación de Fármacos , Femenino
7.
World J Clin Cases ; 12(22): 5032-5041, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39109041

RESUMEN

BACKGROUND: More and more evidence-based practices are emerging, but researchers mostly focus on short-term effects, resulting in evidence-based practices not being applied in the clinic in the long term. In this study, we took the evidence-based practice of perioperative airway management in elderly fracture patients as an example and adopted a descriptive phenomenological approach to understand the influencing factors of its sustainability to provide a reference basis for promoting the continuity of evidence-based practice in the clinic. AIM: To explore factors influencing the persistence of evidence-based practice in perioperative airway management in elderly patients with fractures. METHODS: This study was qualitative research. Nine nurses who implemented evidence-based practice in the orthopedic ward of a tertiary comprehensive hospital in Shanghai from September 2023 to October 2023 were selected using purposive sampling as research subjects. Semi-structured interviews were conducted with them, and the data were analyzed using the Colaizzi phenomenological analysis method based on the three dimensions and ten factors of the NHS sustainability model. RESULTS: Three main themes and ten subthemes were identified: Process aspects (benefits to patients, benefits to nurses, lack of follow-up, complex processes); staff aspects (insufficient human resources, inadequate training and education, lack of leadership support); and organizational environment aspects (inadequate infrastructure, poor patient compliance, poor doctor cooperation). CONCLUSION: Human resources, training and education, leadership support, infrastructure, and patient-physician collaboration are important factors influencing the sustainability of evidence-based practice for perioperative airway management in older patients with fractures.

8.
Front Neurol ; 15: 1428867, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39036638

RESUMEN

Background and objective: Enlarged perivascular spaces in basal ganglia (BG-EPVS) are considered an imaging marker of cerebral small vessel disease (CSVD), but its pathogenesis and pathophysiological process remain unclear. While decreased cerebral perfusion is linked to other CSVD markers, the relationship between BG-EPVS and cerebral perfusion remains ambiguous. This study aimed to explore this association. Methods: Elderly individuals with severe BG-EPVS (n = 77) and age/sex-matched controls (n = 89) underwent head CT perfusion imaging. The cerebral perfusion parameters including mean transit time (MTT), time to maximum (TMAX), cerebral blood flow (CBF), and cerebral blood volume (CBV) were quantitatively measured by symmetric regions of interest plotted in the basal ganglia region. Point-biserial correlation and logistics regression analysis were performed to investigate the association between BG-EPVS and cerebral perfusion. Results: There were no significant differences in MTT, TMAX, or CBF between BG-EPVS group and control group. CBV was significantly lower in the BG-EPVS group (p = 0.035). Point-biserial correlation analysis showed a negative correlation between BG-EPVS and CBV (r = -0.198, p = 0.011). BG-EPVS group and control group as the dependent variable, binary logistics regression analysis showed that CBV was not an independent risk factor for severe BG-EPVS (p = 0.448). All enrolled patients were divided into four groups according to the interquartile interval of CBV. The ordered logistic regression analysis showed severe BG-EPVS was an independent risk factor for decreased CBV after adjusting for confounding factors (OR = 2.142, 95%CI: 1.211-3.788, p = 0.009). Conclusion: Severe BG-EPVS is an independent risk factor for decreased CBV in the elderly, however, the formation of BG-EPVS is not solely dependent on changes in CBV in this region. This finding provides information about the pathophysiological consequence caused by severe BG-EPVS.

9.
World J Gastroenterol ; 30(22): 2893-2901, 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38947295

RESUMEN

BACKGROUND: This study employed a phenomenological research approach within qualitative research to explore the challenges encountered by elderly individuals with temporary colostomies in managing their daily lives and care needs. Protecting the anus surgery combined with temporary colostomy has emerged as a prevalent treatment modality for low rectal cancer. However, the ileostomy is susceptible to peri-stoma skin complications, as well as fluid, electrolyte, and nutritional imbalances, posing challenges to effective management. The successful self-management of patients is intricately linked to their adjustment to temporary colostomy; nonetheless, there remains a dearth of research examining the factors influencing self-care among temporary colostomy patients and the obstacles they confront. AIM: To investigate the lived experiences, perceptions, and care requirements of temporary colostomy patients within their home environment, with the ultimate goal of formulating a standardized management protocol. METHODS: Over the period of June to August 2023, a purposive sampling technique was utilized to select 12 patients with temporary intestinal stomas from a tertiary hospital in Shanghai, China. Employing a phenomenological research approach, a semi-structured interview guide was developed, and qualitative interviews were conducted using in-depth interview techniques. The acquired data underwent coding, analysis, organization, and summarization following Colaizzi's seven-step method. RESULTS: The findings of this study revealed that the experiences and needs of patients with temporary intestinal stomas can be delineated into four principal themes: Firstly, Temporary colostomy patients bear various burdens and concerns about the uncertainty of disease progression; secondly, patients exhibit limited self-care capabilities and face information deficits, resulting in heightened reliance on healthcare professionals; thirdly, patients demonstrate the potential for internal motivation through proactive self-adjustment; and finally, patients express a significant need for emotional and social support. CONCLUSION: Home-living patients with temporary intestinal stomas confront multifaceted challenges encompassing burdens, inadequate self-care abilities, informational deficits, and emotional needs. Identifying factors influencing patients' self-care at home and proposing strategies to mitigate barriers can serve as a foundational framework for developing and implementing nursing interventions tailored to the needs of patients with temporary intestinal stomas.


Asunto(s)
Colostomía , Investigación Cualitativa , Autocuidado , Humanos , Femenino , Anciano , Masculino , Colostomía/psicología , China/epidemiología , Persona de Mediana Edad , Anciano de 80 o más Años , Ileostomía/psicología , Ileostomía/efectos adversos , Calidad de Vida , Entrevistas como Asunto , Neoplasias del Recto/psicología , Neoplasias del Recto/cirugía , Neoplasias del Recto/terapia , Neoplasias del Recto/patología , Adaptación Psicológica
10.
World J Clin Cases ; 12(18): 3417-3427, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38983437

RESUMEN

BACKGROUND: The emergency department (ED) plays a critical role in establishing artificial airways and implementing mechanical ventilation. Managing airbags in the ED presents a prime opportunity to mitigate the risk of ventilator-associated pneumonia. Nonetheless, existing research has largely overlooked the understanding, beliefs, and practical dimensions of airway airbag management among ED nurses, with a predominant focus on intensive care unit nurses. AIM: To investigate the current status of ED nurses' knowledge, beliefs, and practical behaviors in airway airbag management and their influencing factors. METHODS: A survey was conducted from July 10th to August 10th, 2023, using convenience sampling on 520 ED nurses from 15 tertiary hospitals and 5 sary hospitals in Shanghai. Pathway analysis was utilized to analyze the influencing factors. RESULTS: The scores for ED nurses' airway airbag management knowledge were 60.26 ± 23.00, belief was 88.65 ± 13.36, and behavior was 75.10 ± 19.84. The main influencing factors of airbag management knowledge included participation in specialized nurse or mechanical ventilation training, department, and work experience in the department. Influencing factors of airbag management belief comprised knowledge, department, and participation in specialized nurse or mechanical ventilation training. Primary influencing factors of airbag management behavior included knowledge, belief, department, participation in specialized nurse or mechanical ventilation training, and professional title. The belief in airbag management among ED nurses acted as a partial mediator between knowledge and behavior, with a total effect value of 0.513, and an indirect effect of 0.085, constituting 16.6% of the total effect. CONCLUSION: ED nurses exhibit a positive attitude toward airbag management with relatively standardized practices, yet there remains room for improvement in their knowledge levels. Nursing managers should implement interventions tailored to the characteristics of ED nurses' airbag management knowledge, beliefs, and practices to enhance their airbag management proficiency.

11.
Int J Biol Macromol ; 275(Pt 1): 133557, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38955293

RESUMEN

Autologous or allogeneic bone tissue grafts remain the mainstay of treatment for clinical bone defects. However, the risk of infection and donor scarcity in bone grafting pose challenges to the process. Therefore, the development of excellent biomaterial grafts is of great clinical importance for the repair of bone defects. In this study, we used gas-assisted microfluidics to construct double-cross-linked hydrogel microspheres with good biological function based on the ionic cross-linking of Cu2+ with alginate and photo-cross-linking of gelatin methacryloylamide (GelMA) by loading vascular endothelial growth factor (VEGF) and His-tagged bone morphogenetic protein-2 (BMP2) (AGMP@VEGF&BMP2). The Cu2+ component in the microspheres showed good antibacterial and drug-release behavior, whereas VEGF and BMP2 effectively promoted angiogenesis and bone tissue repair. In in vitro and in vivo experiments, the dual cross-linked hydrogel microspheres showed good biological function and biocompatibility. These results demonstrate that AGMP@VEGF&BMP2 microspheres could be used as a bone defect graft substitute to promote effective healing of bone defects and may be applied to other tissue engineering studies.


Asunto(s)
Alginatos , Antibacterianos , Proteína Morfogenética Ósea 2 , Regeneración Ósea , Gelatina , Microesferas , Gelatina/química , Gelatina/farmacología , Alginatos/química , Alginatos/farmacología , Regeneración Ósea/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Animales , Proteína Morfogenética Ósea 2/farmacología , Proteína Morfogenética Ósea 2/química , Factor A de Crecimiento Endotelial Vascular/farmacología , Factor A de Crecimiento Endotelial Vascular/química , Factor A de Crecimiento Endotelial Vascular/metabolismo , Metacrilatos/química , Metacrilatos/farmacología , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Humanos , Liberación de Fármacos
12.
Biochem Pharmacol ; 227: 116451, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39059771

RESUMEN

The increasing threat of antibiotic resistance among pathogenic microorganisms and the urgent demand for new antibiotics require immediate attention. Antimicrobial peptides exhibit effectiveness against microorganisms, fungi, viruses, and protozoa. The discovery of human ß-defensins represents a major milestone in biomedical research, opening new avenues for scientific investigation into the innate immune system and its resistance mechanisms against pathogenic microorganisms. Multiple defensins present a promising alternative in the context of antibiotic abuse. However, obstacles to the practical application of defensins as anti-infective therapies persist due to the unique properties of human ß-defensins themselves and serious pharmacological and technical challenges. To overcome these challenges, diverse delivery vehicles have been developed and progressively improved for the conjugation or encapsulation of human ß-defensins. This review briefly introduces the biology of human ß-defensins, focusing on their multistage structure and diverse functions. It also discusses several heterologous systems for producing human ß-defensins, various delivery systems created for these peptides, and patent applications related to their utilization, concluding with a summary of current challenges and potential solutions.


Asunto(s)
beta-Defensinas , Humanos , beta-Defensinas/química , beta-Defensinas/farmacología , beta-Defensinas/administración & dosificación , Animales , Sistemas de Liberación de Medicamentos/métodos , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antiinfecciosos/administración & dosificación
13.
BMC Med Educ ; 24(1): 692, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38926701

RESUMEN

BACKGROUND: Medical professionalism is a core competency for medical students during clerkships for further professional development. Given that the behavior-based framework could provide clear insight and is easy to assess, the study aimed to create a self-administered scale to measure the professional behaviors of medical students during their clerkships. METHODS: A comprehensive literature review on medical professional behaviors in English or Chinese and Delphi interviews were used to develop the initial version of the Self-Administered Scale for Professional Behavior of Medical Students During Clerkships. The reliability and validity analysis based on a survey of medical students from China, Cronbach's α calculations, and Confirmatory Factor Analysis (CFA) specifically were conducted to finalize the scale. The associations of professional behaviors with gender, medical programs, and clerkship duration were examined using Wilcoxon rank-sum tests. RESULTS: We included 121 studies and extracted 57 medical professionalism assessment tools, initially forming a pool of 48 items. To refine these items, eighteen experts participated in two rounds of Delphi interviews, ultimately narrowing down the item pool to 24 items. A total of 492 participants effectively completed the questionnaire. One item was removed due to its correlated item-total correlation (CITC) value, resulting in a final scale containing 23 items with six domains: Respect, Altruism, Communication and Collaboration, Integrity, Duty, and Excellence. The overall Cronbach's alpha value was 0.98, ranging from 0.88 to 0.95 for each domain. The fit indices (χ2/df = 4.07, CFI = 0.96, TLI = 0.95, RMSEA = 0.08, and SRMR = 0.02) signified a good fit for the six-domain model. Medical students' professional behavior was significantly associated with gender (p = 0.03) and clerkship duration (p = 0.001). CONCLUSION: The scale was demonstrated to be reliable and valid in assessing the professional behaviors of Chinese medical students during clerkships.


Asunto(s)
Prácticas Clínicas , Profesionalismo , Estudiantes de Medicina , Humanos , Estudiantes de Medicina/psicología , Femenino , Masculino , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Técnica Delphi , China , Psicometría , Adulto , Competencia Clínica
14.
Cell Death Differ ; 31(9): 1140-1156, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38816578

RESUMEN

There is a lack of effective treatments to overcome resistance to EGFR-TKIs in EGFR mutant tumors. A deeper understanding of resistance mechanisms can provide insights into reducing or eliminating resistance, and can potentially deliver targeted treatment measures to overcome resistance. Here, we identified that the dynamic changes of the tumor immune environment were important extrinsic factors driving tumor resistance to EGFR-TKIs in EGFR mutant cell lines and syngeneic tumor-bearing mice. Our results demonstrate that the acquired resistance to EGFR-TKIs is accompanied by aberrant expression of PD-L2, leading a dynamic shift from an initially favorable tumor immune environment to an immunosuppressive phenotype. PD-L2 expression significantly affected EGFR mutant cell apoptosis that depended on the proportion and function of CD8+ T cells in the tumor immune environment. Combined with single-cell sequencing and experimental results, we demonstrated that PD-L2 specifically inhibited the proliferation of CD8+ T cells and the secretion of granzyme B and perforin, leading to reduced apoptosis mediated by CD8+ T cells and enhanced immune escape of tumor cells, which drives EGFR-TKIs resistance. Importantly, we have identified a potent natural small-molecule inhibitor of PD-L2, zinc undecylenate. In vitro, it selectively and potently blocks the PD-L2/PD-1 interaction. In vivo, it abolishes the suppressive effect of the PD-L2-overexpressing tumor immune microenvironment by blocking PD-L2/PD-1 signaling. Moreover, the combination of zinc undecylenate and EGFR-TKIs can synergistically reverse tumor resistance, which is dependent on CD8+ T cells mediating apoptosis. Our study uncovers the PD-L2/PD-1 signaling pathway as a driving factor to mediate EGFR-TKIs resistance, and identifies a new naturally-derived agent to reverse EGFR-TKIs resistance.


Asunto(s)
Resistencia a Antineoplásicos , Proteína 2 Ligando de Muerte Celular Programada 1 , Microambiente Tumoral , Animales , Femenino , Humanos , Ratones , Apoptosis/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inhibidores , Terapia Molecular Dirigida , Proteína 2 Ligando de Muerte Celular Programada 1/metabolismo , Proteína 2 Ligando de Muerte Celular Programada 1/genética , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Microambiente Tumoral/efectos de los fármacos
15.
Cancer Cell Int ; 24(1): 164, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38730293

RESUMEN

Kidney Clear Cell Carcinoma (KIRC), the predominant form of kidney cancer, exhibits a diverse therapeutic response to Immune Checkpoint Inhibitors (ICIs), highlighting the need for predictive models of ICI efficacy. Our study has constructed a prognostic model based on 13 types of Programmed Cell Death (PCD), which are intertwined with tumor progression and the immune microenvironment. Validated by analyses of comprehensive datasets, this model identifies seven key PCD genes that delineate two subtypes with distinct immune profiles and sensitivities to anti-PD-1 therapy. The high-PCD group demonstrates a more immune-suppressive environment, while the low-PCD group shows better responses to PD-1 treatment. In particular, TOP2A emerged as crucial, with its inhibition markedly reducing KIRC cell growth and mobility. These findings underscore the relevance of PCDs in predicting KIRC outcomes and immunotherapy response, with implications for enhancing clinical decision-making.

16.
PLoS One ; 19(5): e0303847, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38753823

RESUMEN

Digital rural construction is a key strategic direction to promote China's rural revitalization and alleviate global climate problems. In order to put forward feasible suggestions for the subsequent development and ensure the smooth development of digital village construction, how to reflect the development level of the digital village through scientific and reasonable comprehensive evaluation has become an urgent problem to be solved. This paper establishes a comprehensive evaluation index system through the Delphi method and principal component analysis method, then assigns weights to the evaluation indicators based on the improved CRITIC-G1 method, and then grades the development level of digital villages according to the extension matter element method. Finally, taking Jiangxi Province in China as an example, the overall development level of digital villages in Jiangxi Province is evaluated from the provincial level according to the proposed method. And put forward the corresponding countermeasures and suggestions. Results: Firstly, the development level of digital villages in Jiangxi Province is good, and there is a trend of excellent development level. Secondly, from different aspects of digital rural development, the digitalization of infrastructure, services, economy, and green production in Jiangxi Province is at a good level, and the digitalization of life has reached an excellent level. Thirdly, from the perspective of development trends, the digitization of infrastructure has a progressive trend towards an excellent level of development, while the digitization of services, economy and green production has signs of development regression. According to the analysis results, the relevant countermeasures and suggestions are put forward from four aspects: talent, capital, governance system and development planning. Other regions can evaluate the development level of the digital village according to the evaluation model proposed in this paper so as to analyze the existing problems and put forward targeted solutions to promote the construction of the digital village.


Asunto(s)
Población Rural , China , Humanos , Análisis de Componente Principal , Técnica Delphi
18.
Chemosphere ; 357: 141957, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38641296

RESUMEN

The current study aimed to explore whether bisphenol A (BPA) exposure aggravated the decrease in Tregs induced by ovalbumin (OVA) in adolescent female mouse models of asthma, and whether the process was associated with mTOR-mediated signaling pathways and DNA methylation levels. A total of 40 female C57BL/6 mice at the age of four weeks were used and divided into five groups after 1 week of domestication. Each group consisted of eight mice: the control group, OVA group, OVA + BPA (0.1 µg mL-1) group, OVA + BPA (0.2 µg mL-1) group, and OVA + BPA (0.4 µg mL-1) group. Results revealed that Foxp3 protein levels decreased in the spleens of mice exposed to BPA compared to those in the OVA group. After an elevation in BPA dose, the mRNAs of methyltransferases (Dnmt1, Dnmt3a, and Dnmt3b) were gradually upregulated. The mechanism was related to the activity of TLR4/NF-κB and PI3K/Akt/mTOR signaling pathways and the enhancement of Foxp3 DNA methylation. Our results, collectively, provided a new view for studying the mechanisms underlying BPA exposure-induced immune dysfunction. Investigation of the regulatory mechanisms of DNA methylation in the abnormal Th immune response caused by BPA exposure could help reveal the causes and molecular mechanisms underlying the high incidence of allergic diseases in children in recent years.


Asunto(s)
Compuestos de Bencidrilo , Metilación de ADN , Fenoles , Transducción de Señal , Linfocitos T Reguladores , Animales , Femenino , Ratones , Asma/inducido químicamente , Compuestos de Bencidrilo/toxicidad , Metilación de ADN/efectos de los fármacos , Factores de Transcripción Forkhead/metabolismo , Factores de Transcripción Forkhead/genética , Ratones Endogámicos C57BL , Ovalbúmina , Fenoles/toxicidad , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/metabolismo , Linfocitos T Reguladores/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Regulación hacia Arriba/efectos de los fármacos
20.
EMBO Mol Med ; 16(4): 885-903, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38448544

RESUMEN

Cancer is a heterogeneous disease. Although both tumor metabolism and tumor immune microenvironment are recognized as driving factors in tumorigenesis, the relationship between them is still not well-known, and potential combined targeting approaches remain to be identified. Here, we demonstrated a negative correlation between the expression of NAMPT, an NAD+ metabolism enzyme, and PD-L1 expression in various cancer cell lines. A clinical study showed that a NAMPTHigh PD-L1Low expression pattern predicts poor prognosis in patients with various cancers. In addition, pharmacological inhibition of NAMPT results in the transcription upregulation of PD-L1 by SIRT-mediated acetylation change of NF-κB p65, and blocking PD-L1 would induce NAMPT expression through a HIF-1-dependent glycolysis pathway. Based on these findings, we designed and synthesized a dual NAMPT/PD-L1 targeting compound, LZFPN-90, which inhibits cell growth in a NAMPT-dependent manner and blocks the cell cycle, subsequently inducing apoptosis. Under co-culture conditions, LZFPN-90 treatment contributes to the proliferation and activation of T cells and blocks the growth of cancer cells. Using mice bearing genetically manipulated tumors, we confirmed that LZFPN-90 exerted target-dependent antitumor activities, affecting metabolic processes and the immune system. In conclusion, our results demonstrate the relevance of NAD+-related metabolic processes in antitumor immunity and suggest that co-targeting NAD+ metabolism and PD-L1 represents a promising therapeutic approach.


Asunto(s)
Antígeno B7-H1 , Neoplasias , Humanos , Animales , Ratones , NAD , Neoplasias/patología , Proliferación Celular , Apoptosis , Línea Celular Tumoral , Microambiente Tumoral
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