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1.
Angew Chem Int Ed Engl ; : e202414073, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39248641

RESUMEN

Local enrichment of free radicals at the electrode interface may open new opportunities for the development of electrochemiluminescence (ECL) applications. The sensing platform was constructed by assembling ECL-emitting luminol derived carbon dots (Lu CDs) onto the heterojunction Tungsten disulfide/Covalent organic frameworks (WS2@COF) for the first time, establishing a nanoconfinement-reactor with significantly heightened ECL intensity and stability compared to the Lu CDs-H2O2 system. This enhanced performance is credited to the COF domain's restricted pore environment, where WS2@COF exhibits a more negative adsorption energy for H2O2, effectively enriching H2O2 in the catalytic edge sites of WS2. Furthermore, the internal electric field at the WS2 and COF interface accelerates electron flow, boosting WS2's catalytic activity and achieving domain-limited catalytic enhancement of ECL. Self-designed DNA nanomachines combined with cascading molecular keypad locking mechanisms are integrated into the biosensors, effectively guaranteeing the accuracy of the sensing process while providing crucial safeguards for molecular diagnostics and information security applications. In essence, this innovative approach represents the first system to enhance local free radical concentrations by enriching co-reactants on the electrode surface through nanoconfinement catalysis, yielding heightened ECL luminescence intensity. The potential impact of this novel strategy and sensing mechanism on real-bioanalysis applications is promising.

2.
Cancer Nurs ; 2024 Jul 22.
Artículo en Inglés | MEDLINE | ID: mdl-39037416

RESUMEN

BACKGROUND: Numerous physical and psychological symptoms experienced by cancer patients seriously affect their normal lives. Many academics and medical professionals have attempted to use aromatherapy in this situation to help cancer patients manage their physical and emotional problems. OBJECTIVE: To systematically investigate the efficacy of aromatherapy on physical and psychological symptoms in cancer patients. METHODS: A systematic review and meta-analysis of randomized controlled trials was performed. Four electronic databases were searched. The review process followed a registered priori review protocol and was reported using Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines. Data extraction and quality assessment were performed in parallel. RESULTS: Twenty-six studies with 2912 subjects were included. Meta-analysis showed that aromatherapy significantly improved sleep quality, fatigue, anxiety, and depression. We performed a subgroup analysis according to the different plant or animal aromatics contained in the oil, which found that lavender oil significantly reduced preoperative anxiety. In addition, aromatherapy massage was superior to inhaled aromatherapy in reducing anxiety. Moreover, cancer patients who used aromatherapy reduced the frequency of vomiting in 24 hours. CONCLUSIONS: Aromatherapy is a useful treatment for improving sleep quality and reducing symptoms of fatigue, anxiety, and depression in cancer patients, as well as the frequency of vomiting over 24 hours. IMPLICATIONS FOR PRACTICE: Healthcare providers can use aromatherapy to alleviate psychological and physical symptoms in cancer patients. The use of lavender oil and massage is recommended in clinical settings to improve anxiety symptoms in cancer patients.

3.
Sci Rep ; 14(1): 17204, 2024 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-39060352

RESUMEN

The association between composite dietary antioxidant index (CDAI) and asthma remains unclear. Our study aimed to investigate the association of CDAI with asthma in children aged 3-18 years in the United States. Cross-sectional analyses were carried out on 18,118 children aged 3-18 years old. Data was obtained from the National Health and Nutrition Examination Survey (NHANES) conducted between 2003 and 2020. The Composite Dietary Antioxidant Index (CDAI) was measured by assessing the consumption of six dietary antioxidants (vitamin A, vitamin C, vitamin E, zinc, selenium and carotenoids). The association between CDAI and asthma was explored using multivariate weighted logistic regression, subgroup analyses, and sensitivity analyses. Among the 18,118 participants, 2045 (11.3%) reported a diagnosis of asthma by a healthcare provider. In both the crude and adjusted models, the odds ratios (ORs) for asthma with CDAI were not significant. Specifically, in the fully adjusted model, the OR for T2 was 0.98 (95% CI 0.83, 1.17) and the OR for T3 was 1.00 (95% CI 0.76, 1.31). Subgroup analyses by sex, age and BMI category also showed no significant associations. Sensitivity analyses, including weighted logistic multivariate analyses adjusting for family history of asthma, confirmed the absence of a significant association between CDAI and asthma. Our study showed no significant association between CDAI and asthma in children and adolescents.


Asunto(s)
Antioxidantes , Asma , Dieta , Encuestas Nutricionales , Humanos , Asma/epidemiología , Niño , Preescolar , Masculino , Femenino , Adolescente , Estudios Transversales , Antioxidantes/análisis , Antioxidantes/administración & dosificación , Estados Unidos/epidemiología , Vitamina E/administración & dosificación , Selenio/administración & dosificación , Oportunidad Relativa
4.
Sci Rep ; 14(1): 16924, 2024 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-39043841

RESUMEN

The current research focuses on the effects of nutritional supplementation and exercise on dialysis patients, but whether physical activity (PA) can reduce the risk of adverse outcomes for patients with different nutritional status is not clear. The maintenance hemodialysis (MHD) patients were recruited from April 2021 to April 2022. The information of PA was obtained from the international physical activity questionnaire (IPAQ). The outcomes were cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death. We used COX proportional risk model to estimate the association between PA and the outcomes of MHD patients. Patients are classified into two groups based on geriatric nutritional risk index (GNRI) and classified by age, and we used COX proportional risk model to estimate the association of PA and outcomes in subgroups. The isotemporal substitution model (ISM) was used to estimate the effects of replacing light physical activity (LPA) with moderate physical activity (MPA) or vigorous physical activity (VPA) on risk of cardiovascular events, tumors, and all-cause death in different subgroups. The effects of PA on ankle-brachial index (ABI) and body fat content were analyzed in different IPAQ groups. A total of 241 maintenance hemodialysis patients were included, 105 peoples developed cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death (43.6%). The median follow-up time was 12 months. MPA reduced the risk of outcome in MHD patients or high GNRI patients (40% vs 39%).In MHD patients who was under 65 years with high GNRI, MPA reduced cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor and all-cause death by 55%.PA reduced the risk of cardiovascular event by 65%, but did not reduce the risk of tumor or all-cause death. Replacing LPA with VPA did not improve clinical outcomes. It actually increases the risk of heart failure 0.4%. MPA reduced the risk of cardiovascular death, myocardial infarction, stroke, heart failure, atrial fibrillation, tumor, all-cause death in MHD patients under 65 years, while VPA had no health benefit.Trial registration: ChiCTR210050998.


Asunto(s)
Enfermedades Cardiovasculares , Ejercicio Físico , Neoplasias , Estado Nutricional , Diálisis Renal , Humanos , Masculino , Diálisis Renal/efectos adversos , Femenino , Persona de Mediana Edad , Anciano , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/etiología , Neoplasias/mortalidad , Causas de Muerte , Factores de Riesgo , Modelos de Riesgos Proporcionales
5.
ACS Sens ; 9(6): 3387-3393, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38850514

RESUMEN

Fatty acid amide hydrolase (FAAH) plays a crucial role in the metabolism of the endocannabinoid system by hydrolyzing a series of bioactive amides, whose abnormal levels are associated with neuronal disorders including Alzheimer's disease (AD). However, due to the lack of suitable quantitative sensing tools, real-time and accurate monitoring of the activity of FAAH in living systems remains unresolved. Herein, a novel enzyme-activated near-infrared two-photon ratiometric fluorescent probe (CANP) based on a naphthylvinylpyridine monofluorophore is successfully developed, in which the electron-withdrawing amide moiety is prone to be hydrolyzed to an electron-donating amine group under the catalysis of FAAH, leading to the activation of the intramolecular charge transfer process and the emergence of a new 80 nm red-shifted emission, thereby achieving a ratiometric luminescence response. Benefiting from the high selectivity, high sensitivity, and ratiometric response to FAAH, the probe CANP is successfully used to quantitatively monitor and image the FAAH levels in living neurons, by which an amyloid ß (Aß)-induced upregulation of endogenous FAAH activity is observed. Similar increases in FAAH activity are found in various brain regions of AD model mice, indicating a potential fatty acid amide metabolite-involved pathway for the pathological deterioration of AD. Moreover, our quantitative FAAH inhibition experiments further demonstrate the great value of CANP as an efficient visual probe for in situ and precise assessment of FAAH inhibitors in complex living systems, assisting the discovery of FAAH-related therapeutic agents.


Asunto(s)
Amidohidrolasas , Encéfalo , Colorantes Fluorescentes , Neuronas , Amidohidrolasas/metabolismo , Animales , Colorantes Fluorescentes/química , Colorantes Fluorescentes/síntesis química , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Neuronas/metabolismo , Ratones , Péptidos beta-Amiloides/metabolismo , Péptidos beta-Amiloides/análisis , Humanos , Piridinas/química , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/diagnóstico por imagen , Fotones
6.
Materials (Basel) ; 17(10)2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38793328

RESUMEN

High-entropy alloys are promising candidates expected to be applied in transportation equipment serving in extreme environments due to their excellent properties. CoCrFeMnNi high-entropy alloy is a typical representative of them, and its low temperature performance is excellent. In this study, to evaluate the feasibility of forming HEA shells, the deformation behavior of CoCrFeMnNi under a plane-stress state at lower temperatures was thoroughly studied. Firstly, a thin-walled HEA tube was fabricated using hot extrusion and further formed into a thin shell for uniaxial tensile and biaxial bulging tests. Subsequently, uniaxial tensile tests at cryogenic temperatures were conducted. Both the strength and the ductility improves as the temperature decreases from -160 °C to -196 °C. Then, a systematic low-temperature bulging test was performed using isothermal dome tests and the thickness uniformity analysis of the bulged specimens was carried out. In addition, grain microstructural observation using EBSD was characterized analyze the possible deformation mechanism at the cryogenic temperature under the biaxial stress state. This study, for the first time, investigated the biaxial deformation behavior of HEA. Considering the plane-stress state deformation is the dominant type in the thin-walled shell deformation, this study enables us to provide direct guidance for various sheet-forming processes of HEAs.

7.
Front Genet ; 15: 1335223, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38596213

RESUMEN

An increasing number of studies point to an association between mitochondrial proteins (MPs) and lung cancer (LC). However, the causal relationship between MPs and LC remains unclear. Consequently, our study employed a bidirectional Mendelian randomization (MR) analysis to explore the causal association between MPs and different pathological types of LC. A two-sample MR study was performed using the genome-wide association study (GWAS) data publicly available. We applied the primary inverse variance weighted (IVW) method along with additional MR methods to validate the causality between MPs and different pathological types of LC. To ensure the robustness of our findings, sensitivity analyses were employed. Moreover, we performed a bi-directional MR analysis to determine the direction of the causal association. We identified a total of seven MPs had significant causal relationships on overall LC, lung squamous cell carcinoma (LUSC), and small cell lung carcinoma (SCLC). We found two MPs had significant associations with overall LC, four MPs had significant associations with LUSC, and four MPs had significant associations with SCLC. Additionally, an MP was found to have a nominal relationship with LUSC. Moreover, no causality was found between MPs and lung adenocarcinoma (LUAD). Bidirectional MR showed no reverse effect between identified MPs and different pathological types of LC. In general, our findings of this MR study suggest causal associations of specific MPs with overall LC, LUSC, and SCLC. However, no such causality was found in LUAD.

8.
Ecotoxicol Environ Saf ; 277: 116389, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38657458

RESUMEN

Microplastics (MPs), recognized as an emerging environmental menace, have been extensively investigated in both marine and terrestrial fauna. This study is comprehensive to investigate how polystyrene (PS) affects ruminant animals. The experimental design comprised 24 individually housed lambs, divided into a CON group (diet without PS) and three PS-exposed (25 µm, 50 µm, 100 µm) groups, each with six lambs, the exposure of PS was 100 mg/day, and the duration of exposure was 60 days. The study yielded noteworthy results: (ⅰ) PS leads to a decrease in average daily gain along with an increase in feed conversion rate. (ⅱ) PS decreases rumen ammonia nitrogen. The rumen microbiota diversity remains consistent. However, the relative abundance of Bacteroidetes and Actinobacteria increased in the PS-exposed groups, while the relative abundance of Coriobacteriales_incertae_Sedis and Prevotellaceae_YAB2003_group decreased. (ⅲ) PS leads to decrease in hemoglobin, thrombocytocrit, and albumin levels in lamb blood, thus triggering oxidative stress accumulation, along with swelling of the kidneys and liver. (ⅳ) PS inflicts severe damage to jejunum, consequently impacting digestion and absorption. (ⅴ) PS reduces meat quality and the nutritional value. In conclusion, PS-exposure inhibited lambs' digestive function, adversely affects blood and organs' health status, reducing average daily gain and negatively influencing meat quality. PS particles of 50-100 µm bring worse damage to lambs. This research aims to fill the knowledge void concerning MPs' influences on ruminant animals, with a specific focus on the meat quality of fattening lambs.


Asunto(s)
Poliestirenos , Rumen , Animales , Ovinos , Poliestirenos/toxicidad , Enfermedades Gastrointestinales/inducido químicamente , Enfermedades Gastrointestinales/veterinaria , Inflamación/inducido químicamente , Carne , Microbioma Gastrointestinal/efectos de los fármacos , Aumento de Peso/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Microplásticos/toxicidad
9.
J Clin Nurs ; 33(5): 1958-1975, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38439168

RESUMEN

AIMS AND OBJECTIVES: To examine the effectiveness of family-centred interventions among family caregivers. BACKGROUND: Family-centred interventions are an emerging form of intervention that can be effective at improving physical and mental health outcomes for patients and family caregivers. To date, no reviews have examined the effectiveness of family-centred interventions for family caregivers. DESIGN: A systematic review, including a meta-analysis, was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA 2020) checklist. METHODS: Seven English and two Chinese electronic databases were compressively searched from the outset to March 2023. Two researchers independently reviewed the abstracts and full texts, extracted the data and assessed the risk of bias independently by using the Cochrane 'Risk of bias assessment tool'. RESULTS: This systematic review and meta-analysis included 20 articles. The results of the meta-analysis showed that family-centred interventions could significantly improve caregiver burden (p=0.003), quality of life (p = 0.007), depression (p = 0.0002), and stress (p < 0.0001) but not anxiety or family functioning. According to our subgroup analysis, the family-centred empowerment model (p = 0.009) was superior to the other family intervention (p=0.004) in reducing caregiver burden. Family-centred interventions are more effective at reducing the burden of caregiving on family caregivers of adolescent patients (SMD=-0.79, 95% CI[-1.22,-0.36], p = 0.0003) than on adult patients (SMD=-0.37, 95% CI [-0.61,-0.12], p = 0.004). CONCLUSIONS: Family-centred interventions could enhance family caregivers' burden, quality of life, stress and depression but had no significant impact on anxiety or family functioning. RELEVANCE TO CLINICAL PRACTICE: Family-centred interventions have the potential to improve the health status and caregiving burden of family caregivers. Rigorous and high-quality evidence is needed to confirm the long-term effects of these interventions on family caregivers. TRIAL REGISTRATION DETAILS: The protocol has been registered in the PROSPERO international prospective register of systematic reviews (Protocol registration ID: CRD42023453607).


Asunto(s)
Cuidadores , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Cuidadores/psicología , Calidad de Vida/psicología , Familia/psicología , Femenino , Estrés Psicológico , Masculino , Adulto , Carga del Cuidador/psicología
10.
Plants (Basel) ; 13(5)2024 Feb 29.
Artículo en Inglés | MEDLINE | ID: mdl-38475539

RESUMEN

The water conservation capacity of the litter and soil layers of forest ecosystems improves the function of forest ecosystems in conserving soil and water. Plantation restoration plays a key role in preventing soil erosion. In order to evaluate the water conservation capacity of plantation restoration in Latosol soil-eroded region, we analyzed the litter thickness and mass, water absorption process, water holding recovery process, and soil water holding capacity of five restoration types (Hevea brasiliensis, Acacia mangium, Eucalyptus robusta, Acacia-Eucalyptus, and Acacia-Hevea) in the Mahuangling Watershed, Hainan province. The results showed that the thickness of the litter ranged from approximately 3.42 ± 0.24 to 4.73 ± 0.81 cm, and the litter mass ranged from 5.04 ± 1.52 t·ha-1 to 13.16 ± 1.76 t·ha-1, with higher litter mass in the SL layer than in the UL layer. The litter mass of A. mangium was higher than that of H. brasiliensis, E. robusta, Acacia-Eucalyptus, and Acacia-Hevea, which was 3.16 ± 1.76 t·ha-1. A. mangium forest was significantly higher than other plantation restoration types in terms of the maximum water retention capacity (Qmax) and the effective water retention capacity (Qeff). The soil bulk weight ranged from approximately 1.52 ± 0.09 to 1.59 ± 0.08 g·cm-3, and porosity ranged from 31.77 ± 4.72 to 35.62 ± 3.02%, both of which increased with the depth of the soil layer. The water holding capacity of 0-60 cm soil varied from approximately 12.94 ± 7.91 to 45.02 ± 31.79 t·ha-1, with A. mangium having the best soil permeability and the strongest soil water holding capacity. The entropy weight method was used to conduct a comprehensive evaluation, and the results showed that the water conservation capacity of the soil layer was 1.26 times higher than that of the litter layer, in which the water conservation capacity of A. mangium was the strongest, with a comprehensive evaluation value of 0.2854, which effectively intercepted rainfall and reduced surface runoff. Hence, we suggest that the planting of A. mangium should be considered in future ecological restoration projects of the erosion area of Mahuangling in order to improve the function of conserving soil and water in a restoration forest ecosystem.

11.
Medicine (Baltimore) ; 103(8): e36897, 2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38394497

RESUMEN

BACKGROUND: Atopic dermatitis (AD) is a common and recurrent inflammatory disease with strong genetic susceptibility. The abnormal production of chemokines plays an important role in the occurrence and development of AD. METHODS: A comprehensive online literature search was performed in databases of China National Knowledge Infrastructure, Wanfang, VIP China Science and Technology Journal Database, China Biomedical Literature Database, PubMed, Embase and Cochrane Library to retrieve relevant articles published from January 2000 to October 2022. The odds ratio (OR) with its 95% confidence interval (CI) was employed to calculate this relationship. RESULTS: A total of 7 studies were finally screened out, including 1316 AD patients and 1099 controls. There were 3 studies for CC chemokine ligand 5 (CCL5) polymorphisms, 2 for CCL11 polymorphisms, and 2 for CCL17 polymorphisms, respectively. The meta-analysis revealed a significant association between the CCL5 - 403G/A polymorphism and AD under the allelic model (A vs G: OR = 1.25, 95% CI = 1.02-1.52, P = .03), heterozygous model (AG vs GG: OR = 1.40, 95% CI = 1.08-1.80, P = .01) and dominant model (AA + AG vs GG: OR = 1.38, 95% CI = 1.08-1.76, P = .01) in a fixed-effect model. The allelic model (G vs C: OR = 1.46, 95% CI = 1.07-1.98, P < .01) and dominant model (GG + GC vs CC: OR = 1.74, 95% CI = 1.23-2.47, P < .001) of the CCL5 - 28C/G polymorphism were also associated with an increased risk of AD. However, this significant association was not found in other alleles and genotypes (P > .05). CONCLUSION: Our results show that the A allele, AG and AA + AG genotypes of the CCL5 - 403G/A polymorphism, the G allele and GG + GC genotype of the CCL5 - 28C/G polymorphism are risk factors for AD. Future studies with large population are still needed to further explore those correlations.


Asunto(s)
Quimiocina CCL11 , Quimiocina CCL17 , Quimiocina CCL5 , Dermatitis Atópica , Humanos , Quimiocina CCL11/genética , Quimiocina CCL17/genética , Quimiocina CCL5/genética , Dermatitis Atópica/genética , Predisposición Genética a la Enfermedad , Genotipo , Ligandos , Polimorfismo de Nucleótido Simple , Factores de Riesgo
12.
PLoS One ; 19(2): e0298303, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38358983

RESUMEN

The plant growth-promoting rhizobacterium Tsukamurella tyrosinosolvens P9 can improve peanut growth. In this study, a co-culture system of strain P9 and peanut was established to analyze the transcriptome of peanut roots interacting with P9 for 24 and 72 h. During the early stage of co-culturing, genes related to mitogen-activated protein kinase (MAPK) and Ca2+ signal transduction, ethylene synthesis, and cell wall pectin degradation were induced, and the up-regulation of phenylpropanoid derivative, flavonoid, and isoflavone synthesis enhanced the defense response of peanut. The enhanced expression of genes associated with photosynthesis and carbon fixation, circadian rhythm regulation, indoleacetic acid (IAA) synthesis, and cytokinin decomposition promoted root growth and development. At the late stage of co-culturing, ethylene synthesis was reduced, whereas Ca2+ signal transduction, isoquinoline alkaloid synthesis, and ascorbate and aldarate metabolism were up-regulated, thereby maintaining root ROS homeostasis. Sugar decomposition and oxidative phosphorylation and nitrogen and fatty acid metabolism were induced, and peanut growth was significantly promoted. Finally, the gene expression of seedlings inoculated with strain P9 exhibited temporal differences. The results of our study, which explored transcriptional alterations of peanut root during interacting with P9, provide a basis for elucidating the growth-promoting mechanism of this bacterial strain in peanut.


Asunto(s)
Actinobacteria , Arachis , Calcio , Arachis/metabolismo , Calcio/metabolismo , Plantones/metabolismo , Etilenos/metabolismo , Raíces de Plantas/metabolismo , Regulación de la Expresión Génica de las Plantas
13.
Environ Sci Pollut Res Int ; 31(7): 10689-10701, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38206462

RESUMEN

The frozen period interaction of groundwater and lakes is crucial for hydrological properties and aquatic ecology in cold and arid regions. In this study, we investigate the spatial hydrochemical characteristics, influencing factors in the Hulun Lake basin. The hydrochemical type of lake water exhibits Na-HCO3-SO4-Cl, while river shows a primary classification of Na-Ca-HCO3. Groundwater in the eastern and western regions is characterized by Na-SO4-Cl and Na-HCO3, respectively. Silicic acid and ion exchange predominantly influence groundwater chemistry in the western region, whereas evaporation and concentration play a major role in the eastern region. Total dissolved solids, Cl-, and F- emerge as the primary influencing factors of hydrochemical components in the Hulun Lake basin. Ion content decreased from the southern to the northern region, with the lowest value occurring near the Urson River. The high-temperature water body is primarily distributed in the central and southern regions of the lake. Based on characteristic ions and partial characteristics of ice surface temperature, the potential groundwater discharge areas near the inlet of the Xinkai River, the central and southern region are determined. This study reveals the hydrochemical characteristics, vertical ice distribution, and provides a scientific foundation for water resource management in cold and arid regions.


Asunto(s)
Agua Subterránea , Contaminantes Químicos del Agua , Lagos , Monitoreo del Ambiente , Hielo , Tecnología de Sensores Remotos , Contaminantes Químicos del Agua/análisis , Agua Subterránea/química , Calidad del Agua , China
14.
Cell Mol Immunol ; 21(3): 213-226, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38177245

RESUMEN

Despite the tremendous progress of chimeric antigen receptor T (CAR-T) cell therapy in hematological malignancies, their application in solid tumors has been limited largely due to T-cell exhaustion in the tumor microenvironment (TME) and systemic toxicity caused by excessive cytokine release. As a key regulator of the immunosuppressive TME, TGF-ß promotes cytokine synthesis via the NF-κB pathway. Here, we coexpressed SMAD7, a suppressor of TGF-ß signaling, with a HER2-targeted CAR in engineered T cells. These novel CAR-T cells displayed high cytolytic efficacy and were resistant to TGF-ß-triggered exhaustion, which enabled sustained tumoricidal capacity after continuous antigen exposure. Moreover, SMAD7 substantially reduced the production of inflammatory cytokines by antigen-primed CAR-T cells. Mechanistically, SMAD7 downregulated TGF-ß receptor I and abrogated the interplay between the TGF-ß and NF-κB pathways in CAR-T cells. As a result, these CAR-T cells persistently inhibited tumor growth and promoted the survival of tumor-challenged mice regardless of the hostile tumor microenvironment caused by a high concentration of TGF-ß. SMAD7 coexpression also enhanced CAR-T-cell infiltration and persistent activation in patient-derived tumor organoids. Therefore, our study demonstrated the feasibility of SMAD7 coexpression as a novel approach to improve the efficacy and safety of CAR-T-cell therapy for solid tumors.


Asunto(s)
Neoplasias , Receptores Quiméricos de Antígenos , Animales , Humanos , Ratones , Citocinas/metabolismo , Inmunoterapia Adoptiva , Neoplasias/terapia , FN-kappa B/metabolismo , Receptores Quiméricos de Antígenos/genética , Receptores Quiméricos de Antígenos/metabolismo , Proteína smad7/genética , Proteína smad7/metabolismo , Linfocitos T , Factor de Crecimiento Transformador beta/metabolismo , Microambiente Tumoral
15.
J Am Chem Soc ; 145(43): 23832-23841, 2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37850961

RESUMEN

Norepinephrine (NE) is a key neurotransmitter in the central and sympathetic nervous systems, whose content fluctuates dynamically and rapidly in various brain regions during different physiological and pathophysiological processes. However, it remains a great challenge to directly visualize and precisely quantify the transient NE dynamics in living systems with high accuracy, specificity, sensitivity, and, in particular, high temporal resolution. Herein, we developed a series of small-molecular probes that can specifically detect NE through a sequential nucleophilic substitution-cyclization reaction, accompanied by a ratiometric near-infrared fluorescence response, within an impressively short time down to 60 ms, which is 3 orders of magnitude faster than that of present small-molecular probes. A unique water-promoted intermolecular proton transfer mechanism is disclosed, which dramatically boosted the recognition kinetics by ∼680 times. Benefiting from these excellent features, we quantitatively imaged the transient endogenous NE dynamics under external stimuli at the single living neuron level and further revealed the close correlations between NE fluctuations and Parkinson's disease pathology at the level of acute brain slices and live mouse brains in vivo.


Asunto(s)
Encéfalo , Norepinefrina , Animales , Ratones , Encéfalo/diagnóstico por imagen , Sondas Moleculares , Imagen Óptica , Neuronas
16.
Anim Sci J ; 94(1): e13871, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37720923

RESUMEN

Our objective was to determine effects of feeding lamb's peony byproducts, including stem and leaves (PSL), root (PR), and seeds meal (PSM), on growth, rumen fermentation, slaughter parameters, and meat quality. Sixty-four lambs (14.0 ± 2.1 kg) were allocated into eight treatments based on BW: no additives (CON), 0.15% aureomycin (CONA), low/high levels of PSL (5%/10% PSL replaced 5%/10% Chinese hay), PR (basal diet with 0.5%/1.0% PR), PSM (5%/10% PSM replaced 5%/10% soybean meal). Growth, digestibility, and rumen fermentation had dose responses whereas slaughter parameters, meat quality, or amino acids indexes were not. Peony byproducts increased DMI (p < 0.001) compared to CON, but higher levels were more advantageous (p = 0.003). However, low levels of peony byproducts decreased the NH3 -N concentration, but increased total volatile fatty acids mole percent more than high levels of that (p < 0.001). All peony byproducts increased dressing percentage (p < 0.05), increased pH and tenderness than CON (p < 0.05). In addition, PSL and PSM improved amino acid profiles of meat compared to CON, and were even better than CONA (p < 0.05). Therefore, peony byproducts not only improved animal growth but also reduced the frequency of antibiotic use in animal feeding.


Asunto(s)
Paeonia , Rumen , Ovinos , Animales , Rumen/metabolismo , Fermentación , Antibacterianos/farmacología , Oveja Doméstica , Carne/análisis , Dieta/veterinaria , Alimentación Animal/análisis , Digestión
17.
Pediatr Allergy Immunol ; 34(9): e14024, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37747750

RESUMEN

BACKGROUND: Asthma is an inflammatory disease. The potential of n-3 polyunsaturated fatty acids (PUFAs) to alleviate asthma symptoms through their anti-inflammatory effects and immune modulation has been explored. However, the precise role of dietary n-3 PUFAs in childhood and adolescent asthma remains unclear. OBJECTIVE: This study aimed to evaluate the association between dietary n-3 PUFAs intake and asthma in children and adolescents in the United States. METHODS: We conducted a cross-sectional analysis of 8543 children and adolescents from the National Health and Nutrition Examination Survey (NHANES) between 2013 and 2020 by adjusting for covariates and using multivariate logistic regression, restricted cubic spline, threshold effects, and subgroup analyses. RESULTS: Among 8354 participants, 1456 (16.5%) self-reported diagnosis of asthma by a healthcare provider. After adjusting for potential confounding factors, compared with individuals in the lowest n-3 PUFA consumption group (T1, <26.07 mg/kg/day), the adjusted odds ratio (OR) for asthma was 0.71 (95% CI: 0.6-0.84, p < .001) in the second group (T2, 26.07-48.93 mg/kg/day) and 0.58 (95% CI: 0.47-0.73, p < .001) in the third group (T3, >48.93 mg/kg/day). Furthermore, a nonlinear (L-shaped) relationship was observed between n-3 PUFA intake and asthma (p = .009), with subgroup and sensitivity analyses confirming the stability of the results. In the threshold analysis, a critical turning point was observed at approximately 59.0 mg/kg/day (OR = 0.984, 95% CI: 0.977-0.991, p < .001). CONCLUSION: Dietary intake of n-3 PUFAs exhibited an L-shaped relationship with asthma in children and adolescents in the United States, with a critical turning point observed at approximately 59.0 mg/kg/day.


Asunto(s)
Asma , Ácidos Grasos Omega-3 , Adolescente , Humanos , Niño , Estudios Transversales , Encuestas Nutricionales , Asma/epidemiología , Ácidos Grasos
18.
Arch Med Sci ; 19(5): 1270-1280, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37732066

RESUMEN

Introduction: The present study aimed to investigate the differences in the proteomic expression between uncomplicated parapneumonic pleural effusion (UPPE) and complicated parapneumonic pleural effusion (CPPE). Material and methods: There were 10 patients with UPPE and 10 patients with CPPE. These patients were combined due to the complication of pleural effusion and further divided into group A and group B. An LC-MS analysis was conducted with the extraction of high-abundance proteins, and proteins with 1.5-fold or higher difference multiples were identified as differential proteins. Then, gene ontology (GO) and KEGG analyses were conducted on the differential proteins between the groups. Results: Compared with the UPPE group, there were 38 upregulated proteins and 29 downregulated proteins in the CPPE group. The GO analysis revealed that the CPPE group had enhanced expressions in monosaccharide biosynthesis, glucose catabolism, fructose-6-phosphate glycolysis, glucose-6-phosphate glycolysis, and NADH regeneration as well as reduced expressions in fibrinogen complexes, protein polymerization, and coagulation. Moreover, the KEGG analysis showed that the CPPE group had enhanced expressions in amino acid synthesis, the HIF-1 signalling pathway, and glycolysis/glycoisogenesis and decreased expressions in platelet activation and complement activation. Conclusions: In pleural effusion in patients with CPPE, there are enhanced expressions of proteins concerning glucose and amino acid metabolism, NADH regeneration, and HIF-1 signalling pathways together with decreased expressions of proteins concerning protein polymerization, blood coagulation, platelet activation, and complement activation.

19.
Sci Rep ; 13(1): 12076, 2023 07 26.
Artículo en Inglés | MEDLINE | ID: mdl-37495578

RESUMEN

Glaucoma is an acquired optic neuropathy, which can lead to irreversible vision loss. Deep learning(DL), especially convolutional neural networks(CNN), has achieved considerable success in the field of medical image recognition due to the availability of large-scale annotated datasets and CNNs. However, obtaining fully annotated datasets like ImageNet in the medical field is still a challenge. Meanwhile, single-modal approaches remain both unreliable and inaccurate due to the diversity of glaucoma disease types and the complexity of symptoms. In this paper, a new multimodal dataset for glaucoma is constructed and a new multimodal neural network for glaucoma diagnosis and classification (GMNNnet) is proposed aiming to address both of these issues. Specifically, the dataset includes the five most important types of glaucoma labels, electronic medical records and four kinds of high-resolution medical images. The structure of GMNNnet consists of three branches. Branch 1 consisting of convolutional, cyclic and transposition layers processes patient metadata, branch 2 uses Unet to extract features from glaucoma segmentation based on domain knowledge, and branch 3 uses ResFormer to directly process glaucoma medical images.Branch one and branch two are mixed together and then processed by the Catboost classifier. We introduce a gradient-weighted class activation mapping (Grad-GAM) method to increase the interpretability of the model and a transfer learning method for the case of insufficient training data,i.e.,fine-tuning CNN models pre-trained from natural image dataset to medical image tasks. The results show that GMNNnet can better present the high-dimensional information of glaucoma and achieves excellent performance under multimodal data.


Asunto(s)
Glaucoma , Metadatos , Humanos , Redes Neurales de la Computación , Interpretación de Imagen Asistida por Computador/métodos , Glaucoma/diagnóstico por imagen , Aprendizaje Automático
20.
Anal Chem ; 95(27): 10178-10185, 2023 07 11.
Artículo en Inglés | MEDLINE | ID: mdl-37368510

RESUMEN

It is significantly vital to develop a convenient assay method in clinical treatment due to an atypically low abundance (∼5 µM) of bleomycin (BLM) used in clinics. Herein, an electrochemiluminescence (ECL) biosensor using a zirconium-based metal-organic frameworks (Zr-MOFs) as an intramolecular coordination-induced electrochemiluminescence (CIECL) emitter was proposed for sensitive detection of BLM. Zr-MOFs were synthesized using Zr(IV) as metal ions and 4,4',4″-nitrilotribenzoic acid (H3NTB) as ligands for the first time. The H3NTB ligand not only acts as coordination units bonding with Zr(IV) but functions as a coreactant to enhance ECL efficiency rooted in its tertiary nitrogen atoms. Specifically, a long guanine-rich (G-rich) single-stranded DNA (ssDNA) was released by the target-BLM-controlled DNA machine that could perform π-π stacking with another G-quadruplex, ssDNA-rhodamine B (S-RB), by shearing DNA's fixed sites 5'-GC-3' and the auxiliary role of exonuclease III (Exo III). Finally, due to the quenching effect of rhodamine B, a negative correlation trend was obtained between ECL intensity and BLM concentration in the range from 5.0 nM to 50 µM and the limit of detection was 0.50 nM. We believe that it is a promising approach to guide the preparation of CIECL-based functional materials and establishment of analytical methods.


Asunto(s)
Técnicas Biosensibles , Estructuras Metalorgánicas , Técnicas Biosensibles/métodos , Circonio , Técnicas Electroquímicas , ADN/química , Bleomicina/análisis , Bleomicina/química
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