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1.
J Sci Food Agric ; 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39101210

RESUMEN

BACKGROUND: A water-in-oil-in-water (W/O/W) double emulsion can simultaneously load hydrophilic and hydrophobic substances due to its unique two-membrane, three-phase structure. However, thermodynamic instability greatly limits the application of double emulsions in food processing. Further development of Pickering emulsions based on proteins, etc., can improve the stability and loading capacity. It is of great significance to promote their practical application. RESULTS: Herein, we prepared ultrasound pretreatment complex glycation-modified phycocyanin (UMPC) to stabilize a W/O/W Pickering emulsion for the codelivery of vitamin B12 (VB12) and vitamin E (VE). First, an inner water phase and oil phase containing polyglycerin polyricinoleate were homogenized to prepare a W/O emulsion. Subsequently, the W/O emulsion was homogenized with an outer water phase containing UMPC to obtain a W/O/W Pickering emulsion. A gel-like inner phase emulsion with excellent storage and thermal stabilities was obtained under the condition that the W/O emulsion volume ratio was 80% and the UMPC was stabilized by 10 g kg-1. The double emulsion after loading VB12 and VE showed good encapsulation effect during the storage period, the encapsulation rate could reach more than 90%, it also showed excellent protection effect under long-time storage and UV irradiation and the retention rate increased by more than 65%. In addition, the bioavailability of VB12 and VE significantly increased during simulated gastrointestinal digestion and reached 46.02% and 52.43%, respectively. CONCLUSION: These results indicate that the UMPC-stabilized W/O/W Pickering emulsion is an effective carrier for the codelivery of hydrophilic and hydrophobic bioactive molecules and also provides a means for useful exploration of an efficient and stable emulsion system stabilized by biological macromolecules. © 2024 Society of Chemical Industry.

2.
Clin Nucl Med ; 49(9): 817-821, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39086048

RESUMEN

PURPOSE: To investigate the role of CXCR4-targeted 68 Ga-pentixafor PET/CT imaging in inflammatory bowel disease (IBD). METHODS: Five IBD patients and 12 control subjects performing 68 Ga-pentixafor PET/CT examinations were included. 68 Ga-pentixafor PET/CT imaging and endoscopic findings were recorded and compared. The semiquantitative parameters of 68 Ga-pentixafor uptake by the lesion segments in IBD patients and the normal intestines in the control were investigated. RESULTS: Among these 5 IBD patients, endoscopy successfully examined a total of 26 intestinal segments, with 13 segments showing endoscopic lesions. 68 Ga-pentixafor PET/CT was positive in all endoscopy-proven lesions (13/13). Additionally, 68 Ga-pentixafor PET/CT revealed the lesions in small intestines and colons that cannot be reached by endoscopy due to severe stenosis, and mesenteric lymphadenitis accompanied IBD. The SUV max of the lesion segments in IBD patients was significantly higher than that of the normal intestines in the control group (median, 3.15 [range, 1.61-6.26] vs 1.67 [1.18-2.29], P < 0.001). Moreover, the SUV max ratios of the lesion segments/liver or blood pool were higher when compared with the control (2.20 [1.13-3.26] vs 0.85 [0.54-1.20]; 1.66 [0.94-2.95] vs 0.67 [0.52-1.04]; P ≤ 0.001). CONCLUSIONS: 68 Ga-pentixafor PET/CT can be a potentially valuable tool to assess the active intestinal lesions of IBD with high sensitivity. Moreover, this noninvasive approach does not require fasting or bowel preparation, offering good tolerance and safety.


Asunto(s)
Enfermedades Inflamatorias del Intestino , Tomografía Computarizada por Tomografía de Emisión de Positrones , Receptores CXCR4 , Humanos , Masculino , Femenino , Enfermedades Inflamatorias del Intestino/diagnóstico por imagen , Persona de Mediana Edad , Receptores CXCR4/metabolismo , Adulto , Anciano , Complejos de Coordinación , Péptidos Cíclicos/farmacocinética
3.
MedComm (2020) ; 5(8): e679, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39132510

RESUMEN

Precise diagnostic biomarkers of anticitrullination protein antibody (ACPA)-negative and early-stage RA are still to be improved. We aimed to screen autoantibodies in ACPA-negative patients and evaluated their diagnostic performance. The human genome-wide protein arrays (HuProt arrays) were used to define specific autoantibodies from the sera of 182 RA patients and 261 disease and healthy controls. Statistical analysis was performed with SPSS 17.0. In Phase I study, 51 out of 19,275 recombinant proteins covering the whole human genome were selected. In Phase II validation study, anti-ANAPC15 (anaphase promoting complex subunit 15) exhibited 41.8% sensitivity and 91.5% specificity among total RA patients. There were five autoantibodies increased in ACPA-negative RA, including anti-ANAPC15, anti-LSP1, anti-APBB1, anti-parathymosin, and anti-UBL7. Anti-parathymosin showed the highest prevalence of 46.2% (p = 0.016) in ACPA-negative early stage (<2 years) RA. To further improve the diagnostic efficacy, a prediction model was constructed with 44 autoantibodies. With increased threshold for RA calling, the specificity of the model is 90.8%, while the sensitivity is 66.1% (87.8% in ACPA-positive RA and 23.8% in ACPA-negative RA) in independent testing patients. Therefore, HuProt arrays identified RA-associated autoantibodies that might become possible diagnostic markers, especially in early stage ACPA-negative RA.

4.
Small ; : e2404171, 2024 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-39185810

RESUMEN

All-solid-state lithium sulfide-based batteries (ASSLSBs) have drawn much attention due to their intrinsic safety and excellent performance in overcoming the polysulfide shuttle effect. However, the sluggish kinetics of Li2S cathode severely impede commercial utilization. Here, a Cu+, I- co-doping strategy is employed to activate the kinetics of Li2S to construct high-performance ASSLSBs. The electronic conductivity and Li-ion diffusion coefficient of the co-doped Li2S are increased by five and two orders of magnitude, respectively. Cu+ as a redox medium greatly improves the reaction kinetics, which is supported by ex situ X-ray photoelectron spectroscopy. Density functional theory calculation (DFT) shows that Cu+, I- co-doping reduces the Li-ions diffusion energy barrier. The co-doped Li2S exhibits a remarkable improvement in capacity (1165.23 mAh g-1 (6.65 times that of pristine Li2S) at 0.02 C and 592.75 mAh g-1 at 2 C), and excellent cycling stability (84.58% capacity retention after 6200 cycles at 2 C) at room temperature. Moreover, an ASSLSB, fabricated with a lithium-free (Si─C) anode, obtains a high specific capacity of 1082.7 mAh g-1 at 0.05 C and 97% capacity retention after 400 cycles at 0.5 C. This work provides a broad prospect for the development of ASSLSBs with practical energy density exceeding that of traditional lithium-ion batteries.

5.
JCI Insight ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39163137

RESUMEN

Palatine tonsils are the only air-contacted lymphoid organs that constantly engage in crosstalk with commensal microorganisms and serve as the first handling sites against microbial antigens. While tonsil inflammations have been implicated in various autoimmune diseases, including rheumatoid arthritis (RA), the precise role of tonsillar microbiota in autoimmune pathogenesis remains inadequately characterized. In this study, we conducted a profiling of the tonsillar microbiota and identified a notable dysbiosis in RA patients, particularly within the Streptococcus genus. Specifically, RA patients exhibited an enrichment of pathogenic Streptococcus species, including S. pyogenes, S. dysgalactiae, and S. agalactiae. Colonization with these bacteria significantly exacerbated arthritis severity and increased autoimmune responses in collagen-induced arthritis (CIA). Furthermore, immunization with peptides derived from these pathogenic Streptococcus species directly induced experimental arthritis. Conversely, RA patients demonstrated a marked deficiency in commensal Streptococcus members, notably S. salivarius. Treatment of CIA mice with S. salivarius attenuated the progression of arthritis and downregulated autoimmune responses. These findings highlight a functional link between tonsillar microbiota and RA, shedding light on their contribution to autoimmunity.

6.
PLoS One ; 19(8): e0307494, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39141652

RESUMEN

Global warming has increased the probability of extreme climate events, with compound extreme events having more severe impacts on socioeconomics and the environment than individual extremes. Utilizing the Coupled Model Intercomparison Project Phase 6 (CMIP6), we predicted the spatiotemporal variations of compound extreme precipitation-high temperature events in China under three Shared Socioeconomic Pathways (SSPs) across two future periods, and analyzed the changes in exposed populations and identified influencing factors. From the result, we can see that, the CMIP6 effectively reproduces precipitation patterns but exhibits biases. The frequency of compound event rises across SSPs, especially under high radiative forcing, with a stronger long-term upward trend. Furthermore, the economically developed areas, notably China's southeastern coast and North China Plain, will be hotspots for frequent and intense compound extreme events, while other regions will see reduced exposure. Finally, in the long-term future (2070-2100), there is a noteworthy shift in population exposure to compound events, emphasizing the increasing influence of population factors over climate factors. This highlights the growing importance of interactions between population and climate in shaping exposure patterns.


Asunto(s)
Lluvia , Análisis Espacio-Temporal , China , Humanos , Calentamiento Global , Cambio Climático , Calor
7.
Acta Biomater ; 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-39168421

RESUMEN

The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) offers a promising antimicrobial strategy for periodontitis, yet faces challenges like complex material structure and limited NIR-I light penetration. Additionally, low endogenous H2O2 levels in biofilm and a focus on bacterial eradication over colonization prevention limit current treatments. To address these issues, we newly introduce a single-material system (Cu3P@PAH@Lox) that integrates dual functionalities to synergistically enhance antimicrobial effects and significantly reduce pathogen co-aggregation. This system utilizes PTT to increase local temperature, boosting •OH production in CDT while downregulating heat shock proteins to enhance PTT efficacy, forming a self-reinforcing feedback loop. Lactate oxidase (Lox) is employed to convert lactate-a metabolite in periodontal biofilm-into H2O2, further amplifying CDT's potential. In vitro Cu3P@PAH@Lox demonstrates a remarkable synergistic effect against dual-species biofilms by more than 2-log reduction of colony-forming unit. Moreover, Cu3P@PAH@Lox exhibits outstanding synergistic antibacterial performances to alleviate inflammation and destruction of tissue in vivo periodontitis model. Furthermore, the mechanism of pathogen co-aggregation disruption by PTT is verified via the Cbe-Ltp1-Ptk1-fimA signaling pathway. This single-material multimodal system we have herein demonstrated for the first time marks a significant advancement in periodontitis treatment, eradicating microbes and preventing bacterial colonization, offering a path to comprehensive periodontal care. STATEMENT OF SIGNIFICANCE: The synergy between chemodynamic therapy (CDT) and photothermal therapy (PTT) has been considered a promising therapy for periodontitis. Yet, facing challenges, the complex material structure, limited NIR-I light penetration, low endogenous H2O2 level in biofilm, and a focus on bacterial eradication over colonization prevention are still insufficient. This study pioneers a unique, single-material system (Cu3P@PAH@Lox) that synergistically enhances antimicrobial effects and substantially curtails pathogen co-aggregation, advancing periodontitis therapy. By exploiting PTT to elevate local temperatures, thereby increasing hydroxyl radical production in CDT and concurrently suppressing heat shock proteins, the system establishes a potent, self-enhancing loop. Furthermore, lactate oxidase is innovatively utilized to convert lactate from periodontal biofilm into hydrogen peroxide, augmenting the efficacy of CDT. The introduction of Cu3P@PAH@Lox is poised to revolutionize periodontitis treatment, eliminating microbes and impeding bacterial colonization, thereby charting a course for comprehensive periodontal management.

8.
Clin Exp Med ; 24(1): 201, 2024 Aug 28.
Artículo en Inglés | MEDLINE | ID: mdl-39196452

RESUMEN

Behcet's syndrome (BS) is a vasculitis characterized by immune dysregulation. Biomarkers are valuable for assessing clinically atypical pathogenesis. We aimed to investigate the distribution of different biomarkers and their effects on the clinical features of patients with BS in a large-scale, real-world study. This is a retrospective, single-center study. In total, 502 patients diagnosed with BS were enrolled in this study. We analyzed the clinical features of this cohort and divided patients' symptoms into six categories, including mucocutaneous, articular, neurological, gastrointestinal, vascular, and ocular involvements. HLA-B51 cells, autoantibodies, and subsets of immune cells from the patients were tested. Pearson's correlation, Wilcoxon rank sum test and multivariate logistic regression were used for data analysis. Various autoantibodies were detected in the serum of 40.8% of patients with BS. The positivity rate of anti-endothelial cell antibodies (AECA) was the highest among autoantibodies and was found in 23.5% (118/502) of patients with BS. The positivity rate of HLA-B51 in patients with BS was 27.1%. Tumor necrosis factor (TNF)-α, IL-2, and IL-4 producing CD4+ T cells were positively correlated with the gastrointestinal BS. Increased IL-4+CD4+ T cell was a risk factor for gastrointestinal BS (P = 0.006, Overall rate [OR] = 2.491, 95% Confidence interval [CI]: [1.317, 5.100]). Various autoantibodies can be detected in patients with BS. HLA-B51 and AECA are the most common biomarkers. Increased IL-4+ CD4+ T cell was a risk factor for gastrointestinal involvement in BS.


Asunto(s)
Autoanticuerpos , Síndrome de Behçet , Biomarcadores , Humanos , Síndrome de Behçet/sangre , Síndrome de Behçet/inmunología , Síndrome de Behçet/diagnóstico , Masculino , Femenino , Adulto , Biomarcadores/sangre , Estudios Retrospectivos , Autoanticuerpos/sangre , Persona de Mediana Edad , Antígeno HLA-B51/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto Joven , Linfocitos T CD4-Positivos/inmunología , Interleucina-4/sangre
9.
Natl Sci Rev ; 11(8): nwae225, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39071842

RESUMEN

Periodontitis involves hyperactivated stromal cells that recruit immune cells, exacerbating inflammation. This study presents an ATP-responsive metal-organic framework (Mg/Zn-MOF) designed for periodontitis treatment, utilizing ion interference to modulate immune responses and prevent tissue destruction. Addressing the challenges of synergistic ion effects and targeted delivery faced by traditional immunomodulatory nanomaterials, the Mg/Zn-MOF system is activated by extracellular ATP-a pivotal molecule in periodontitis pathology-ensuring targeted ion release. Magnesium and zinc ions released from the framework synergistically inhibit membrane pore formation by attenuating Gasdermin D (GSDMD) expression and activation. This action curtails pyroptosis, lactate dehydrogenase and IL-1ß release, thwarting the onset of inflammatory cascades. Mechanistically, Mg/Zn-MOF intervenes in both the NLRP3/Caspase-1/GSDMD and Caspase-11/GSDMD pathways to mitigate pyroptosis. In vivo assessments confirm its effectiveness in diminishing inflammatory cell infiltration and preserving collagen integrity, thereby safeguarding against periodontal tissue damage and bone loss. This investigation highlights the promise of ion-interference strategies in periodontitis immunotherapy, representing a significant stride in developing targeted therapeutic approaches.

10.
Int Immunopharmacol ; 139: 112690, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39053227

RESUMEN

The pathogenesis of SSc pulmonary fibrosis is complex and prognosis is poor. In order to find biomarkers to provide assistance in the diagnosis and treatment of systemic sclerosis (SSc), this study explored the role of SSc-related differentially expressed circRNAs in the fibrosis process. This study explored whether circular RNA (circRNA) mediated the mTOR signaling pathway by interacting with the eukaryotic translation initiation factor eIF4E-binding protein 1 (4E-BP1), participated in a competing endogenous RNA (ceRNA) network, and regulated the mechanism of pulmonary fibrosis in systemic sclerosis (SSc). The results showed that the expression of mmu_circ_0005373 was reduced, and mmu_circ_0005373 may regulate the mTOR signaling pathway by inhibiting the interacting with 4E-BP1 protein in the lung of SSc mice, and promote fibrosis in SSc. Hsa_circ_0136255, which is homologous to mmu_circ_0005373, is also reduced in SSc peripheral blood mononuclear cells, and predicted to interact with 4E-BP1 protein. Hsa_circ_0136255/hsa-miR-330-3p/TNFAIP3 ceRNA network had biological significance in SSc, and correlated with clinical data, including high-resolution CT, average expiratory flow at 25% vital capacity, neutrophil count, lymphocyte percentage, standard deviation of red blood cell distribution width, coefficient of variation of red blood cell distribution width, platelet distribution width, glutamic transaminase, γ-glutamyl transpeptidase, lymphocyte percentage, basophils percentage, red blood cell, plateletcrit, cholinesterase, and mean corpuscular hemoglobin concentration. Hsa_circ_0136255, hsa-miR-330-3p, and TNFAIP3 may be used as biomarkers for clinical diagnosis and treatment of SSc.


Asunto(s)
Fibrosis Pulmonar , ARN Circular , Esclerodermia Sistémica , Esclerodermia Sistémica/genética , Esclerodermia Sistémica/patología , Humanos , Animales , ARN Circular/genética , Fibrosis Pulmonar/genética , Ratones , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Masculino , Transducción de Señal , Femenino , Serina-Treonina Quinasas TOR/metabolismo , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Pulmón/patología , MicroARNs/genética , Biomarcadores , Persona de Mediana Edad
11.
Anal Bioanal Chem ; 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38916795

RESUMEN

Carbon-based nanozymes are synthetic nanomaterials that are predominantly constituted of carbon-based materials, which mimic the catalytic properties of natural enzymes, boasting features such as tunable catalytic activity, robust regenerative capacity, and exceptional stability. Due to the impressive enzymatic performance similar to various enzymes such as peroxidase, superoxide dismutase, and oxidase, they are widely used for detecting and degrading pollutants in the environment. This paper presents an exhaustive review of the fundamental design principles, catalytic mechanisms, and prospective applications of carbon-based nanozymes in the environmental field. These studies not only serve to augment the comprehension on the intricate operational mechanism inherent in these synthetic nanostructures, but also provide essential guidelines and illuminating perspectives for advancing their development and practical applications. Future studies that are imperative to delve into the untapped potential of carbon-based nanozymes within the environmental domain was needed to be explored to fully harness their ability to deliver broader and more impactful environmental preservation and management outcomes.

13.
Biosens Bioelectron ; 260: 116414, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38815463

RESUMEN

Surface-enhanced Raman spectroscopy (SERS) is a powerful optical technique for non-invasive and label-free bioanalysis of liquid biopsy, facilitating to diagnosis of potential diseases. Neuropsychiatric systemic lupus erythematosus (NPSLE) is one of the subgroups of systemic lupus erythematosus (SLE) with serious manifestations for a high mortality rate. Unfortunately, lack of well-established gold standards results in the clinical diagnosis of NPSLE being a challenge so far. Here we develop a novel Raman fingerprinting machine learning (ML-) assisted diagnostic method. The microsphere-coupled SERS (McSERS) substrates are employed to acquire Raman spectra for analysis via convolutional neural network (CNN). The McSERS substrates demonstrate better performance to distinguish the Raman spectra from serums between SLE and NPSLE, attributed to the boosted signal-to-noise ratio of Raman intensities due to the multiple optical regulation in microspheres and AuNPs. Eight statistically-significant (p-value <0.05) Raman shifts are identified, for the first time, as the characteristic spectral markers. The classification model established by CNN algorithm demonstrates 95.0% in accuracy, 95.9% in sensitivity, and 93.5% in specificity for NPSLE diagnosis. The present work paves a new way achieving clinical label-free serum diagnosis of rheumatic diseases by enhanced Raman fingerprints with machine learning.


Asunto(s)
Vasculitis por Lupus del Sistema Nervioso Central , Aprendizaje Automático , Microesferas , Espectrometría Raman , Humanos , Espectrometría Raman/métodos , Vasculitis por Lupus del Sistema Nervioso Central/sangre , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico , Técnicas Biosensibles/métodos , Nanopartículas del Metal/química , Oro/química , Redes Neurales de la Computación , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/diagnóstico
14.
Microorganisms ; 12(5)2024 Apr 24.
Artículo en Inglés | MEDLINE | ID: mdl-38792680

RESUMEN

Cysticercus pisiformis is a kind of tapeworm larvae of Taenia pisiformis, which parasitizes the liver envelope, omentum, mesentery, and rectum of rodents such as rabbits. Cysteine protease inhibitors derived from helminth were immunoregulatory molecules of intermediate hosts and had an immunomodulatory function that regulates the production of inflammatory factors. Thus, in the present research, the recombinant Stefin of C. pisiformis was confirmed to have the potential to fight inflammation in LPS-Mediated RAW264.7 murine macrophages. CCK8 test showed that rCpStefin below 50 µg/mL concentration did not affect cellular viability. Moreover, the NO production level determined by the Griess test was decreased. In addition, the secretion levels of IL-1ß, IL-6, and TNF-α as measured by ELISA were decreased. Furthermore, it exerted anti-inflammatory activity by decreasing the production of proinflammatory cytokines and proinflammatory mediators, including IL-1ß, IL-6, TNF-α, iNOS, and COX-2 at the gene transcription level, as measured by qRT-PCR. Therefore, Type I cystatin derived from C. pisiformis suppresses the LPS-Mediated inflammatory response of the intermediate host and is a potential candidate for the treatment of inflammatory diseases.

15.
Chem Commun (Camb) ; 60(44): 5703-5706, 2024 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-38738578

RESUMEN

A collaborative manipulation strategy of proper heat treatment and self-customized hydrofluoroether-based electrolyte design has been proposed for boosting the sodium-ion storage kinetics of Prussian white cathodes. Improved monoclinic phase stability and electrolyte-cathode compatibility are responsible for an impressive discharge capacity of 148.4 mA h g-1 and excellent electrode reversibility.

16.
Ann Biomed Eng ; 52(8): 2051-2064, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38615078

RESUMEN

Transcatheter heart valve replacements (TVR) are mostly designed in a closed position (c) with leaflets coaptating. However, recent literature suggests fabricating valves in semi-closed (sc) position to minimize pinwheeling. With about 100,000 children in need of a new pulmonary valve each year worldwide, this study evaluates both geometrical approaches in adult as well as pediatric size and condition. Three valves of each geometry were fabricated in adult (30 mm) and pediatric (15 mm) size, using porcine pericardium. To evaluate performance, the mean transvalvular pressure gradient (TPG), effective orifice area (EOA), and regurgitation fraction (RF) were determined in three different annulus geometries (circular, elliptic, and tilted). For both adult-sized valve geometries, the TPG (TPGC = 2.326 ± 0.115 mmHg; TPGSC = 1.848 ± 0.175 mmHg)* and EOA (EOAC = 3.69 ± 0.255 cm2; EOASC = 3.565 ± 0.025 cm2)* showed no significant difference. Yet the RF as well as its fluctuation was significantly higher for valves with the closed geometry (RFC = 12.657 ± 7.669 %; RFSC = 8.72 ± 0.977 %)*. Recordings showed that the increased backflow was caused by pinwheeling due to a surplus of tissue material. Hydrodynamic testing of pediatric TVRs verified the semi-closed geometry being favourable. Despite the RF (RFC = 7.721 ± 0.348 cm2; RFSC = 5.172 ± 0.679 cm2), these valves also showed an improved opening behaviour ((TPGC = 20.929 ± 0.497 cm2; TPGSC = 15.972 ± 1.158 cm2); (EOAC = 0.629 ± 0.017 cm2; EOASC = 0.731 ± 0.026 cm2)). Both adult and pediatric TVR with semi-closed geometry show better fluiddynamic functionality compared to valves with a closed design due to less pinwheeling. Besides improved short-term functionality, less pinwheeling potentially prevents early valve degeneration and improves durability. *Results are representatively shown for a circular annulus geometry.


Asunto(s)
Prótesis Valvulares Cardíacas , Diseño de Prótesis , Humanos , Porcinos , Animales , Niño , Adulto , Modelos Cardiovasculares
17.
Arthritis Rheumatol ; 76(9): 1419-1430, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38589318

RESUMEN

OBJECTIVE: Glucocorticoid-induced tumor necrosis factor receptor superfamily-related protein (GITR), with its ligand (GITRL), plays an important role in CD4+ T cell-mediated autoimmunity. This study aimed to investigate the underlying mechanisms of GITRL in primary Sjögren syndrome (pSS). METHODS: Patients with pSS and healthy controls were recruited. Serum GITRL and Th17-related cytokines were determined. RNA sequencing was performed to decipher key signal pathways. Nonobese diabetes (NOD) mice were adopted as experimental Sjögren models and recombinant adeno-associated virus (rAAV) transduction was conducted to verify the therapeutic potentials of targeting GITRL in vivo. RESULTS: Serum GITRL was significantly higher in patients with pSS and showed a positive correlation with leukopenia, thrombocytopenia, autoantibodies, lung involvement, and disease activity. Serum GITRL was correlated with Th17-related cytokines. GITRL promoted the expansion of Th17 and Th17.1 cells. Expansion of granulocyte-macrophage colony-stimulating factor positive (GM-CSF+) CD4+ T cells induced by GITRL could be inhibited by blockade of GITRL. Moreover, GM-CSF could stimulate GITRL expression on monocytes. RNA sequencing revealed mammalian target of rapamycin complexes 1 (mTORC1) might be the key modulator. The increased phosphorylation of S6 and STAT3 and the expansion of Th17 and Th17.1 cells induced by GITRL were effectively inhibited by rapamycin, suggesting a GITRL-mTORC1-GM-CSF positive loop in pathogenic Th17 response in pSS. Administration of an rAAV vector expressing short hairpin RNA targeting GITRL alleviated disease progression in NOD mice. CONCLUSION: Our results identified the pathogenic role of GITRL in exacerbating disease activity and promoting pathogenic Th17 response in pSS through a GITRL-mTORC1-GM-CSF loop. These findings suggest GITRL might be a promising therapeutic target in the treatment of pSS.


Asunto(s)
Factor Estimulante de Colonias de Granulocitos y Macrófagos , Diana Mecanicista del Complejo 1 de la Rapamicina , Ratones Endogámicos NOD , Síndrome de Sjögren , Células Th17 , Factores de Necrosis Tumoral , Animales , Femenino , Humanos , Masculino , Ratones , Modelos Animales de Enfermedad , Diana Mecanicista del Complejo 1 de la Rapamicina/metabolismo , Síndrome de Sjögren/inmunología , Síndrome de Sjögren/genética , Células Th17/inmunología , Factores de Necrosis Tumoral/genética
18.
EJNMMI Phys ; 11(1): 40, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38662044

RESUMEN

PURPOSE: This study aimed to evaluate the feasibility of 11C-CFT PET brain imaging in Parkinson's Disease using a total-body PET/CT scanner and explore the optimal scan duration to guide the clinical practice. METHODS: Thirty-two patients with Parkinson's disease (PD) performing 11C-CFT PET/CT brain imaging using a total-body PET/CT scanner were retrospectively enrolled. The PET data acquired over a period of 900 s were reconstructed into groups of different durations: 900-s, 720-s, 600-s, 480-s, 300-s, 180-s, 120-s, 60-s, and 30-s (G900 to G30). The subjective image quality analysis was performed using 5-point scales. Semi-quantitative measurements were analyzed by SUVmean and dopamine transporter (DAT) binding of key brain regions implicated in PD, including the caudate nucleus and putamen. The full-time images (G900) were served as reference. RESULTS: The overall G900, G720, and G600 image quality scores were 5.0 ± 0.0, 5.0 ± 0.0, and 4.9 ± 0.3 points, respectively, and there was no significant difference among these groups (P > 0.05). A significant decrease in these scores at durations shorter than 600 s was observed when compared to G900 images (P < 0.05). However, all G300 image quality was clinically acceptable (≥ 3 points). As the scan duration reduced, the SUVmean and DAT binding of caudate nucleus and putamen decreased progressively, while there were no statistically significant variations in the SUVmean of the background among the different groups. Moreover, the changes in the lesion DAT binding (ΔDAT-binding) between the full-time reference G900 image and other reconstructed group G720 to G30 images generally increased along with the reduced scan time. CONCLUSION: Sufficient image quality and lesion conspicuity could be achieved at 600-s scan duration for 11C-CFT PET brain imaging in PD assessment using a total-body PET/CT scanner, while the image quality of G300 was acceptable to meet clinical diagnosis, contributing to improve patient compliance and throughput of PET brain imaging.

19.
ACS Appl Mater Interfaces ; 16(15): 18843-18854, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38586920

RESUMEN

Sulfide solid-state electrolytes have garnered considerable attention owing to their notable ionic conductivity and mechanical properties. However, achieving an electrolyte characterized by both high ionic conductivity and a stable interface between the electrode and electrolyte remains challenging, impeding its widespread application. In this work, we present a novel sulfide solid-state electrolyte, Li3.04P0.96Zn0.04S3.92F0.08, prepared through a solid-phase reaction, and explore its usage in all-solid-state lithium sulfur batteries (ASSLSBs). The findings reveal that the Zn, F co-doped solid-state electrolyte exhibits an ionic conductivity of 1.23 × 10-3 S cm-1 and a low activation energy (Ea) of 9.8 kJ mol-1 at room temperature, illustrating the aliovalent co-doping's facilitation of Li-ion migration. Furthermore, benefiting from the formation of a LiF-rich interfacial layer between the electrolyte and the Li metal anode, the Li/Li3.04P0.96Zn0.04S3.92F0.08/Li symmetrical cell exhibits critical current densities (CCDs) of up to 1 mA cm-2 and maintains excellent cycling stability. Finally, the assembled ASSLSBs exhibit an initial discharge capacity of 1295.7 mAh g-1 at a rate of 0.05 C and at room temperature. The cell maintains a capacity retention of 70.5% for more than 600 cycles at a high rate of 2 C, representing a substantial improvement compared to the cell with Li3PS4. This work provides a new idea for the design of solid-state electrolytes and ASSLSBs.

20.
Arthritis Res Ther ; 26(1): 76, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38515127

RESUMEN

BACKGROUND: Autoimmune responses have been suggested to involvement in patients with Behcet's syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA)+ regular T cells (Tregs) in autoimmune diseases. The role of CLA+ Tregs in BS is still uncertain. This study aims to clarify the impact of CLA+ Tregs on BS. METHODS: We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA+ Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4+ T cells were detected using flow cytometry and compared between patients and HCs. RESULTS: The absolute number and proportion of CLA+ Tregs among CD4+ T lymphocytes and CD4+ Tregs were lower in patients with BS than in HCs. CLA+ Tregs were positively related with NK cells (r = 0.500, P < 0.001) and B cells (r = 0.470, P < 0.001) and negatively related with effector T cells (r=-0.402, P < 0.001) in patients with BS. Patients with BS and arterial aneurysms had CLA+ Treg cell deficiency. A decreased proportion of CLA+ Tregs was associated with arterial aneurysms in patients with BS. The proportion of CLA+ Tregs in patients with BS increased with corticosteroids and immunosuppressants. CONCLUSION: CLA+ Tregs decrease in association with arterial aneurysm in patients with BS. CLA+ Tregs may be a predictor of response to BS treatment.


Asunto(s)
Aneurisma , Síndrome de Behçet , Antígeno Sialil Lewis X/análogos & derivados , Humanos , Relevancia Clínica , Oligosacáridos , Linfocitos T Reguladores
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