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1.
Nat Commun ; 15(1): 7652, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39227563

RESUMEN

P2X receptors, a subfamily of ligand-gated ion channels activated by extracellular ATP, are implicated in various physiopathological processes, including inflammation, pain perception, and immune and respiratory regulations. Structural determinations using crystallography and cryo-EM have revealed that the extracellular three-dimensional architectures of different P2X subtypes across various species are remarkably identical, greatly advancing our understanding of P2X activation mechanisms. However, structural studies yield paradoxical architectures of the intracellular domain (ICD) of different subtypes (e.g., P2X3 and P2X7) at the apo state, and the role of the ICD in P2X functional regulation remains unclear. Here, we propose that the P2X3 receptor's ICD has an apo state conformation similar to the open state but with a less tense architecture, containing allosteric sites that influence P2X3's physiological and pathological roles. Using covalent occupancy, engineered disulfide bonds and voltage-clamp fluorometry, we suggested that the ICD can undergo coordinated motions with the transmembrane domain of P2X3, thereby facilitating channel activation. Additionally, we identified a novel P2X3 enhancer, PSFL77, and uncovered its potential allosteric site located in the 1α3ß domain of the ICD. PSFL77 modulated pain perception in P2rx3+/+, but not in P2rx3-/-, mice, indicating that the 1α3ß, a "tunable" region implicated in the regulation of P2X3 functions. Thus, when P2X3 is in its apo state, its ICD architecture is fairly ordered rather than an unstructured outward folding, enabling allosteric modulation of the signaling of P2X3 receptors.


Asunto(s)
Sitio Alostérico , Dominios Proteicos , Receptores Purinérgicos P2X3 , Animales , Receptores Purinérgicos P2X3/metabolismo , Receptores Purinérgicos P2X3/química , Receptores Purinérgicos P2X3/genética , Humanos , Ratones , Células HEK293 , Adenosina Trifosfato/metabolismo , Masculino , Ratones Endogámicos C57BL , Regulación Alostérica
2.
ACS Nano ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39297802

RESUMEN

The application of nanosized active particles in Li-ion batteries has been the subject of intense investigation, yielding mixed results in terms of overall benefits. While nanoparticles have shown promise in improving rate performance and reducing issues related to cracking, they have also faced criticism due to side reactions, low packing density, and consequent subpar volumetric battery performance. Interesting processes such as self-assembly have been proposed to increase packing density, but these tend to be incompatible with scalable processes such as roll-to-roll coating, which are essential to manufacture electrodes at scale. Addressing these challenges, this research demonstrates the long-range self-assembly of carbon-decorated V2O5 nanofiber cathodes as a model system. These nanorods are closely packed into thick electrode films, exhibiting a high volumetric capacity of 205 mA h cm-3at 0.2 C. This surpasses the volumetric capacity of unaligned V2O5 nanofiber electrodes (82 mA h cm-3) under the same cycling conditions. We also demonstrate that these energy-dense electrodes retain an excellent capacity of up to 190.4 mA h cm-3(<2% loss) over 500 cycles without needing binders. Finally, we demonstrate that the proposed self-assembly process is compatible with roll-to-roll coating. This work contributes to the development of energy-dense coatings for next-generation battery electrodes with high volumetric energy density.

3.
J Nanobiotechnology ; 22(1): 560, 2024 Sep 14.
Artículo en Inglés | MEDLINE | ID: mdl-39272197

RESUMEN

Intravesical therapy (IT) is widely used to tackle various urological diseases. However, its clinical efficacy is decreased by the impermeability of various barriers presented on the bladder luminal surface, including the urinary mucus layer and the densely packed tissue barrier. In this study, we report a mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery. Upon intravesical instillation, its poloxamer 407 (PLX) hydrogel gelated and adhered to the urothelium to prolong its intravesical retention. The urea afterwards diffused into the hydrogel, thus generating a concentration gradient. Urease-powered membrane nanomotors (UMN) without asymmetric surface engineering could catalyze the urea and migrate down this concentration gradient to deeply and unidirectionally penetrate the urothelial barrier. Moreover, the intravesical hybrid system-delivered gemcitabine could effectively inhibit the bladder tumor growth without inducing any side effect. Therefore, our mucoadhesive-to-penetrating nanomotors-in-hydrogel system could serve as an alternative to IT to meet the clinical need for more efficacious therapeutics for urological diseases.


Asunto(s)
Sistemas de Liberación de Medicamentos , Hidrogeles , Poloxámero , Neoplasias de la Vejiga Urinaria , Urotelio , Urotelio/metabolismo , Animales , Hidrogeles/química , Sistemas de Liberación de Medicamentos/métodos , Administración Intravesical , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismo , Ratones , Poloxámero/química , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Desoxicitidina/administración & dosificación , Gemcitabina , Vejiga Urinaria/metabolismo , Humanos , Femenino , Línea Celular Tumoral , Adhesividad
4.
Foods ; 13(17)2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39272595

RESUMEN

The variety and content of high-quality proteins in sunflower seeds are higher than those in other cereals. However, sunflower seeds can suffer from abnormalities, such as breakage and deformity, during planting and harvesting, which hinder the development of the sunflower seed industry. Traditional methods such as manual sensory and machine sorting are highly subjective and cannot detect the internal characteristics of sunflower seeds. The development of spectral imaging technology has facilitated the application of terahertz waves in the quality inspection of sunflower seeds, owing to its advantages of non-destructive penetration and fast imaging. This paper proposes a novel terahertz image classification model, MobileViT-E, which is trained and validated on a self-constructed dataset of sunflower seeds. The results show that the overall recognition accuracy of the proposed model can reach 96.30%, which is 4.85%, 3%, 7.84% and 1.86% higher than those of the ResNet-50, EfficientNeT, MobileOne and MobileViT models, respectively. At the same time, the performance indices such as the recognition accuracy, the recall and the F1-score values are also effectively improved. Therefore, the MobileViT-E model proposed in this study can improve the classification and identification of normal, damaged and deformed sunflower seeds, and provide technical support for the non-destructive detection of sunflower seed quality.

5.
Light Sci Appl ; 13(1): 246, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39251581

RESUMEN

Quasicrystal metasurfaces, a kind of two-dimensional artificial optical materials with subwavelength meta-atoms arranged in quasi-periodic tiling schemes, have attracted extensive attentions due to their novel optical properties. In a recent work, a dual-functional quasicrystal metasurface, which can be used to simultaneously generate the diffraction pattern and holographic image, is experimentally demonstrated. The proposed method expands the manipulation dimensions for multi-functional quasicrystal metasurfaces and may have important applications in microscopy, optical information processing, optical encryption, etc.

6.
Exp Eye Res ; 248: 110096, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278392

RESUMEN

PURPOSE: This study focused on the mechanisms of pyroptosis and oxidative damage exacerbation by NOD-like receptor thermal protein domain associated protein 3 (NLRP3) during the infection of canine corneal epithelial cells (CCECs) with Staphylococcus pseudintermedius. METHODS: The CCECs treated with dimethyl fumarate (DMF), recombinant high mobility group protein 1 (HMGB1), or N-acetylcysteine (NAC). The gasdermin (GSDM) family and HMGB1 mRNA expression levels were detected using quantitative reverse transcription polymerase chain reaction. Lactate dehydrogenase activity, bacterial counts, the pyroptosis rate, reactive oxygen species (ROS) content, and antioxidant enzyme activity were used to reflect pyroptosis and oxidation level. RESULTS: Regulation of NLRP3 significantly affected the pyroptosis rate and GSDMD-N expression levels during S. pseudintermedius infection. Inhibition of GSDMD-N protein activation by DMF reversed the exacerbation of pyroptosis induced by NLRP3 overexpression and reduced the levels of cleaved interleukin-1ß (IL-1ß), cleaved cysteinyl aspartate-specific protease-1, and NLRP3. In addition, NLRP3 was found to target the HMGB1 promoter and regulate its protein expression, to increase ROS accumulation and GSDMD-N expression levels, and activate the NLRP3-HMGB1-ROS-GSDMD signaling axis to aggravate pyroptosis during infection. CONCLUSIONS: NLRP3 aggravates pyroptosis and oxidative damage associated with the activation of NLRP3-GSDMD and NLRP3-HMGB1-ROS-GSDMD signaling pathways during the infection of CCECs with S. pseudintermedius.

8.
J Imaging Inform Med ; 2024 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-39299958

RESUMEN

Diabetic retinopathy (DR) is a retinal disease caused by diabetes. If there is no intervention, it may even lead to blindness. Therefore, the detection of diabetic retinopathy is of great significance for preventing blindness in patients. Most of the existing DR detection methods use supervised methods, which usually require a large number of accurate pixel-level annotations. To solve this problem, we propose a self-supervised Equivariant Refinement Classification Network (ERCN) for DR classification. First, we use an unsupervised contrast pre-training network to learn a more generalized representation. Secondly, the class activation map (CAM) is refined by self-supervision learning. It first uses a spatial masking method to suppress low-confidence predictions, and then uses the feature similarity between pixels to encourage fine-grained activation to achieve more accurate positioning of the lesion. We propose a hybrid equivariant regularization loss to alleviate the degradation caused by the local minimum in the CAM refinement process. To further improve the classification accuracy, we propose an attention-based multi-instance learning (MIL), which weights each element of the feature map as an instance, which is more effective than the traditional patch-based instance extraction method. We evaluate our method on the EyePACS and DAVIS datasets and achieved 87.4% test accuracy in the EyePACS dataset and 88.7% test accuracy in the DAVIS dataset. It shows that the proposed method achieves better performance in DR detection compared with other state-of-the-art methods in self-supervised DR detection.

9.
Front Nutr ; 11: 1461224, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39267861

RESUMEN

Background: Hulatang is a traditional specialty snack in Henan, China, and is well known for its unique flavor. Methods: In this study, the volatile organic compounds (VOCs) in four kinds of Hulatang from two representative regions in Henan Province (Xiaoyaozhen and Beiwudu) were evaluated using headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS). Results: The results showed that Xiaoyaozhen Hulatang exhibited more ethers, fewer terpenes and ketones than Beiwudu Hulatang. Additionally, Hulatang from different regions were classified using the orthogonal partial least squares-discriminant analysis (OPLS-DA) based on GC-IMS data. Twenty aroma substances were selected as the potential markers using the variable importance in the projection (VIP) variable selection method. Additionally, fifteen aroma components significantly contributing to the aroma of Hulatang were screened using the relative odor activity value (ROAV) (ROAV > 1). Combined with the sensory score results, twelve key substances with significant correlation with odor perception were selected. The flavor characteristics of the key substances revealed that the flavor of Hulatang was mainly composed of volatile components with camphor, green, almond, fatty, spicy, herbal, vegetable, fruity, floral, musty, and solvent aromas. Conclusion: Overall, the experimental results provide a theoretical basis for evaluating the flavor characteristics of Hulatang from different regions using GC-IMS.

10.
Rev Sci Instrum ; 95(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39248625

RESUMEN

To enhance the efficiency of the Stinger Polycrystalline Diamond Compact (PDC) cutter in breaking hard rocks, this study focuses on optimizing the cutter intrusion-cutting rock breaking parameters. A numerical calculation model for the rotational breaking of granite by a Stinger PDC cutter was established. A comprehensive statistical examination was performed to assess the influence of various factors on intrusion ability (IA), tangential force (TF), and mechanical specific energy (MSE). The Taguchi method was used to determine the optimal settings for each factor, while analysis of variance was employed to assess the significance and relative impact of these factors on the target outcomes. In addition, the multi-objective function was optimized using the gray relational analysis method. The primary process parameters obtained for the various performance characteristics are the cone top angle (α), the cone top radius (r), the cutter diameter (d), the cutter back inclination angle (ß), and weight on bit (P). The impact ratios of these parameters are 6.20%, 7.66%, 3.93%, 17.20%, and 65.02%, respectively. The optimal geometrical parameters are α = 60°, r = 2 mm, and d = 15 mm, while the optimal working parameters are ß = 30° and P = 800 N. In the optimal case, IA and MSE were reduced by 55.335% and 15.809%, respectively, compared to the initial case. Despite a 15.706% increase in TF, the overall GRG increased for all three evaluation criteria, with an overall increase in efficiency of 18.229%. The results of this paper can provide guidance for the design of Stinger cutter PDC drill bits.

11.
Cell Death Discov ; 10(1): 395, 2024 Sep 05.
Artículo en Inglés | MEDLINE | ID: mdl-39237520

RESUMEN

Abdominal aortic aneurysms (AAA) are a significant health concern in developed countries due to their considerable mortality rate. The crucial factor of the progression of AAA is the release of neutrophils and neutrophil extracellular traps (NETs). Magnetic particle imaging (MPI) is a new imaging technique that offers the capability to detect superparamagnetic iron oxide nanoparticles (SPION) with exceptional sensitivity. We aimed to investigate the functional imaging of MPI for the detection and monitoring of neutrophil infiltration within AAA. A novel multimodal imaging agent targeting neutrophils, PEG-Fe3O4-Ly6G-Cy7 nanoparticles (Ly6G NPs), were designed by coupling Fe3O4 nanoparticles with Ly6G antibodies and Cy7. The targeting and sensitivity of Ly6G NPs were assessed using MPI and fluorescence imaging (FLI) in the AAA mouse model. After the inhibition of NETosis, the degree of neutrophil infiltration and AAA severity were assessed using MPI with Ly6G NPs. Ly6G NPs accurately localized and quantitatively analyzed AAA lesion sites in mice using MPI/FLI/CT. Compared to the control group, elevated MPI and FLI signal intensities were detected at the abdominal aortic lesion site, and neutrophil infiltration and NETs accumulation were detected by histological analysis in the AAA models. After the inhibition of NETs accumulation in vivo, pathological damage in the abdominal aorta was significantly reduced, along with a decrease in the accumulation of Ly6G NPs and MPI signals. This multimodal MPI strategy revealed that nanoparticles targeting Ly6G can be used to detect neutrophil infiltration within AAA and monitor AAA severity.

12.
J Anim Sci ; 2024 Sep 02.
Artículo en Inglés | MEDLINE | ID: mdl-39219376

RESUMEN

Stress and infection seriously threaten the reproductive performance and health of dairy cows. Various perinatal stresses increase plasma cortisol concentrations in cows, and chronically high cortisol levels may increase the incidence and severity of the uterine diseases. Selenium (Se) enhances antioxidant capacity of cows. The aim of this study was to explore how Se affects the oxidative stress of primary bovine endometrial stromal cells (BESC) with high cortisol background. The levels of reactive oxygen species (ROS) and other biomarkers of oxidative stress were measured using flow cytometry and assay kits. The changes in nuclear NF-E2-related factor 2 (Nrf2) pathway were detected by Western blot, qPCR, and immunofluorescence. The result showed that lipopolysaccharide (LPS) increased (P < 0.01) ROS and malondialdehyde (MDA) content and reduced (P <0.01) superoxide dismutase (SOD) concentration, provoking BESC oxidative stress. The elevated levels of cortisol resulted in the accumulation (P < 0.05) of ROS and MDA and inhibition (P < 0.05) of SOD in unstimulated BESC, but demonstrated an antioxidative effect in LPS-stimulated cells. Pretreatment with Se reduced (P < 0.01) the levels of ROS and MDA, while increasing (P < 0.05) the antioxidant capacities and the relative abundance of gene transcripts and proteins related to the Nrf2 pathway in BESC. This antioxidant effect was more pronounced in the presence of high cortisol level. Se alleviated the LPS-induced cellular oxidative stress, which is probably achieved through activating Nrf2 pathway. At high cortisol levels, Se supplement has a more significant protective effect on BESC oxidative stress. This study provided evidence for the protective role of Se in bovine endometrial oxidative damage of stressed animals and suggested the potential regulatory mechanism in vitro.

13.
Phytomedicine ; 134: 155961, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39178679

RESUMEN

BACKGROUND: The rapid acceleration of female reproductive aging has become a major public health concern. He's Yangchao formula (HSYC), a compound comprising eight herbs, has demonstrated efficacy in enhancing ovarian function. Thus, an in-depth study of its anti-ovarian aging mechanism is required. PURPOSE: To evaluate the anti-ovarian aging effect of HSYC in naturally aged mice and investigate the underlying mechanism by analyzing the gut microbiota (GM), metabolome, and transcriptome. METHODS: Young and advanced maternal age (AMA) mice were selected for this study. Hematoxylin and eosin staining, fluorescence staining, western blotting, and qPCR analyses were used to detect the phenotypes associated with ovarian aging. Subsequently, analyses of the GM, transcriptome, and metabolome analyses were performed to explore the potential mechanisms of action of HSYC. Finally, in vivo and in vitro experiments were performed to verify potential therapeutic mechanisms. RESULTS: HSYC promoted follicular development in AMA mice and ameliorated age-related mitochondrial dysfunction, apoptosis, and defects in DNA damage repair. GM analysis revealed that HSYC treatment significantly increased the abundance of Akkermansia and Turicibacter. Transcriptome and metabolome analyses showed that HSYC might mitigate ovarian aging by regulating metabolic pathways, amino acid metabolism, glutathione metabolism, and the synthesis of pantothenic acid and coenzyme A. Combined transcriptomic and metabolomic analyses identified the glutathione metabolic pathway as the key pathway through which HSYC counteracts ovarian aging. Additional experimental verification confirmed that HSYC upregulated the glutathione metabolic genes GPX8, GSTA1, and GSTA4, increased glutathione-related products (GSH), and reduced ROS levels. CONCLUSIONS: HSYC exerts beneficial therapeutic effects on ovarian aging by regulating multiple endogenous metabolites, targets, and metabolic pathways, with an emphasis on its anti-ovarian aging effects through the glutathione metabolic pathway. These findings underscore the innovative potential of HSYC in addressing ovarian aging and offer a novel therapeutic approach that targets multiple biological pathways to improve the reproductive health of women with AMA..


Asunto(s)
Envejecimiento , Medicamentos Herbarios Chinos , Microbioma Gastrointestinal , Ovario , Animales , Femenino , Ratones , Envejecimiento/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Ovario/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacos , Transcriptoma/efectos de los fármacos , Metaboloma/efectos de los fármacos , Apoptosis/efectos de los fármacos , Daño del ADN/efectos de los fármacos , Multiómica
14.
Sci Prog ; 107(3): 368504241257129, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39196602

RESUMEN

Langerhans cell histiocytosis (LCH) is a neoplastic disease characterized by aberrant proliferation of the mononuclear phagocyte system, predominantly affecting children under the age of 3 years. Although LCH can affect almost all organs, sinus involvement is rare. This case report documents a 9-year-old boy presented with vision impairment and intermittent headache on the right side. The CT scan and MRI examination revealed the presence of a soft mass in the right atrium of sphenoid sinus, which impacted the right optic canal. Biopsy results confirmed the presence of LCH. Considering the involvement of optic canal and vision impairment, meticulous debridement was performed followed by a 12-month standard chemotherapy. After 2 years of follow-up, the patient showed significant improvement, despite the presence of an encapsulated cyst in the right sphenoid sinus. This case highlights the importance of considering LCH when encountering an isolated soft mass accompanied by decreased vision in the sphenoid sinus. A thorough physical examination, laboratory tests, and imaging methods should be performed, with a biopsy being necessary to confirm the type of lesion and guide the appropriate treatment.


Asunto(s)
Histiocitosis de Células de Langerhans , Seno Esfenoidal , Trastornos de la Visión , Humanos , Histiocitosis de Células de Langerhans/complicaciones , Histiocitosis de Células de Langerhans/diagnóstico por imagen , Histiocitosis de Células de Langerhans/patología , Histiocitosis de Células de Langerhans/diagnóstico , Masculino , Seno Esfenoidal/diagnóstico por imagen , Seno Esfenoidal/patología , Niño , Trastornos de la Visión/etiología , Trastornos de la Visión/patología , Imagen por Resonancia Magnética , Tomografía Computarizada por Rayos X
15.
BMC Vet Res ; 20(1): 383, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39192330

RESUMEN

BACKGROUND: An elevated endogenous cortisol level due to the peripartum stress is one of the risk factors of postpartum bovine uterine infections. Selenium is a trace element that elicits anti-inflammation and antioxidation properties. This study aimed to reveal the modulatory effect of selenium on the inflammatory response of primary bovine endometrial stromal cells in the presence of high-level cortisol. The cells were subjected to lipopolysaccharide to establish cellular inflammation. The mRNA expression of toll-like receptor 4 (TLR4), proinflammatory factors, and selenoproteins was measured with qPCR. The activation of NF-κB and MAPK signalling pathways was detected with Western blot and immunofluorescence. RESULTS: The pretreatment with sodium selenite (2 and 4 µΜ) resulted in a down-regulation of TLR4 and genes encoding proinflammatory factors, including interleukin (IL)-1ß, IL-6, IL-8, tumour necrosis factor α, cyclooxygenase 2, and inducible nitric oxide synthase. Selenium inhibited the activation of NF-κB and the phosphorylation of mitogen-activated protein kinase kinase, extracellular signal-regulated kinase, p38MAPK and c-Jun N-terminal kinase/stress-activated protein kinase. The suppression of those genes and pathways by selenium was more significant in the presence of high cortisol level (30 ng/mL). Meanwhile the gene expression of glutathione peroxidase 1 and 4 was promoted by selenium, and was even higher in the presence of cortisol and selenium. CONCLUSIONS: The anti-inflammatory action of selenium is probably mediated through NF-κB and MAPK, and is augmented by cortisol in primary bovine endometrial stromal cells.


Asunto(s)
Antiinflamatorios , Endometrio , Hidrocortisona , Selenio , Células del Estroma , Animales , Bovinos , Femenino , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Endometrio/citología , Hidrocortisona/farmacología , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Selenio/farmacología , Antiinflamatorios/farmacología , FN-kappa B/metabolismo , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Células Cultivadas , Lipopolisacáridos/farmacología
16.
Rev Cardiovasc Med ; 25(7): 236, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39139430

RESUMEN

Background: Atrial fibrillation (AF) can lead to a decline in left atrial appendage (LAA) function, potentially increasing the likelihood of LAA thrombus (LAAT) and spontaneous echo contrast (SEC). Measuring LAA flow velocity through transesophageal echocardiography (TEE) is currently the primary method for evaluating LAA function. This study aims to explore the potential correlation between anterior mitral annular plane systolic excursion (aMAPSE) and LAA stasis in patients with non-valvular atrial fibrillation (NVAF). Methods: A total of 465 patients with NVAF were enrolled between October 2018 and November 2021. Transthoracic echocardiography (TTE) and TEE were performed before scheduled electrical cardioversion. Propensity score matching (PSM) was used to balance confounders between the groups with and without LAAT/dense SEC. Results: Patients in the LAAT/dense SEC group showed increased left atrial (LA) diameter, LAA area, alongside reduced left ventricular ejection fraction (LVEF), LAA velocity, conjunction thickening ratio, aMAPSE, and LAA fraction area change (FAC) compared to those in the non-LAAT/dense SEC group. Multivariate logistic regression analysis identified aMAPSE and LAA FAC as independent predictors for LAAT/dense SEC. Specifically, an aMAPSE of < 6.76 mm and an LAA FAC of < 29.65% predicted LAAT/dense SEC with high diagnostic accuracy, demonstrated by an area under the curve (AUC) of 0.81 (sensitivity 0.81, specificity 0.80) for aMAPSE, and an AUC of 0.80 (sensitivity 0.70, specificity 0.84) for LAA FAC. Conclusions: Both aMAPSE and LAA FAC independently correlated with and accurately predict LAAT/dense SEC. Incorporating aMAPSE into routine TEE evaluations for LAA function alongside LAA flow velocity is recommended.

17.
Sci Adv ; 10(34): eadp3654, 2024 Aug 23.
Artículo en Inglés | MEDLINE | ID: mdl-39178258

RESUMEN

Introducing specific strains of probiotics into the gut microbiome is a promising way to modulate the intestinal microbiome to treat various health conditions clinically. However, oral probiotics typically have a temporary or limited impact on the gut microbiome and overall health benefits. Here, we reported a 3D printed cellulose-derived spiral tube-like scaffold that enabled high efficacy of the oral delivery of probiotics. Benefiting from the unique surface pattern, this system can effectively extend the retention time of loaded probiotics in the gut without invading nearby tissues, provide a favorable environment for the survival and long-term colonization of loaded probiotics, and influence the intestinal ecosystem as a dietary fiber after degradation. We demonstrate Roseburia intestinalis-loaded scaffold exerts noticeable impacts on the regulation of the gut microbiome to treat various gut-related diseases, including obesity and inflammatory bowel disease; thus, we provide a universal platform for oral delivery of probiotics.


Asunto(s)
Celulosa , Microbioma Gastrointestinal , Impresión Tridimensional , Probióticos , Probióticos/administración & dosificación , Celulosa/química , Administración Oral , Animales , Ratones , Humanos , Andamios del Tejido/química
18.
CNS Neurosci Ther ; 30(8): e70006, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39169794

RESUMEN

INTRODUCTION: Trigeminal neuralgia (TN), marked by chronic pain from neural damage, is closely associated with inflammation. The role of OTULIN, a key regulator in inflammation and autophagy, is not fully understood in TN. The regulatory mechanism of OTULIN, a key protein involved in modulating inflammatory responses and autophagy processes, remains incompletely elucidated, particularly in the context of TN and neuroinflammation. METHODS: An infraorbital nerve ligation-induced rat model of TN was used. OTULIN's expression was modulated using adenovirus vectors and short hairpin RNA. The impact on pain and inflammatory responses was assessed via quantitative real-time polymerase chain reaction, western blot, immunofluorescence, and transcriptomic analysis. RESULTS: Enhanced OTULIN expression significantly increased head withdrawal thresholds and reduced pain sensitivity and neuroinflammatory markers in the model. Conversely, silencing OTULIN exacerbated pain and inflammation. Transcriptomic data revealed OTULINs influence on both inflammatory and autophagy pathways, specifically in suppressing NLR family pyrin domain containing 3 (NLRP3) inflammasome and promoting autophagy. In vitro experiments demonstrated OTULIN's inhibition of inflammatory markers in microglia and neurons. CONCLUSION: OTULIN is crucial in modulating TN, reducing neuropathic pain and neuroinflammation by activating the autophagy pathway and inhibiting the NLRP3 inflammasome.


Asunto(s)
Enfermedades Neuroinflamatorias , Ratas Sprague-Dawley , Neuralgia del Trigémino , Animales , Neuralgia del Trigémino/metabolismo , Ratas , Enfermedades Neuroinflamatorias/metabolismo , Masculino , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Autofagia/fisiología , Microglía/metabolismo , Inflamación/metabolismo
19.
J Colloid Interface Sci ; 677(Pt A): 812-819, 2024 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-39121665

RESUMEN

Aqueous zinc-ion batteries (AZIBs) have become a research hotspot, but the inevitable zinc dendrites and parasitic reactions in the zinc anode seriously hinder their further development. In this study, three covalent triazine frameworks (DCPY-CTF, CTF-1 and FCTF) have been synthesized and used as artificial protective coatings, in which the fluorinated triazine framework (FCTF) increases the zinc-philic site, thus better promoting dendritic free zinc deposition and inhibiting hydrogen evolution reactions. Excitingly, both experimental results and theoretical calculations indicate that the FCTF interface adjusts the deposition of Zn2+ along the (002) plane, effectively alleviating the formation of zinc dendrites. As expected, Zn@FCTF symmetric cells exhibit cycling stability of over 4000 h (0.25 mA cm-2), meanwhile Zn@FCTF//NHVO full cells provide a high specific capacity of 280 mAh/g at 1.0 A/g, which are superior to those of bare Zn anode. This work provides new insights for suppressing hydrogen evolution and promoting dendrite-free zinc deposition to construct highly stable and reversible AZIBs.

20.
ACS Appl Mater Interfaces ; 16(33): 43364-43373, 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39105706

RESUMEN

Calcium-overload-mediated tumor therapy has received considerable interest in oncology. However, its efficacy has been proven to be inadequate due to insufficient calcium ion concentration at the tumor site coupled with challenges in facilitating efficient calcium uptake by tumors, leading to unsatisfactory therapeutic outcomes. In the present study, calcium carbonate nanoshell mineralized ferric polydopamine nanoparticles (Fe-PDA@CaCO3 NPs) were prepared for achieving Ca2+-overload-mediated tumor therapy. Upon entering the tumor site, the pH-responsive CaCO3 layer, acting as a "Ca2+ storage pool", rapidly degraded and released high quantities of free Ca2+ within the weakly acidic environment. The Fe-PDA core, with its excellent photothermal conversion properties, could significantly increase the temperature upon exposure to near-infrared (NIR) light irradiation, thereby activating the TRPV1 channel and leading to a large influx of released Ca2+ into the cytoplasm. Furthermore, the exposed Fe-PDA core could react with the tumor-overexpressed hydrogen peroxide (H2O2) to efficiently produce hydroxyl radicals (•OH), significantly increasing intracellular reactive oxygen species (ROS) levels and thus inhibiting the activity of the Ca2+ efflux pump, resulting in a high intracellular Ca2+ concentration. Ultimately, the increase in calcium/ROS levels could disrupt mitochondrial homeostasis and activate the apoptosis pathway. The current work presents a promising approach for tumor therapy using photothermal-enhanced calcium-overload-mediated ion interference therapy and chemodynamic therapy.


Asunto(s)
Carbonato de Calcio , Calcio , Indoles , Nanopartículas , Polímeros , Especies Reactivas de Oxígeno , Carbonato de Calcio/química , Indoles/química , Indoles/farmacología , Animales , Calcio/química , Calcio/metabolismo , Ratones , Polímeros/química , Polímeros/farmacología , Humanos , Nanopartículas/química , Especies Reactivas de Oxígeno/metabolismo , Concentración de Iones de Hidrógeno , Línea Celular Tumoral , Rayos Infrarrojos , Hierro/química , Terapia Fototérmica , Antineoplásicos/química , Antineoplásicos/farmacología , Peróxido de Hidrógeno/química , Ratones Endogámicos BALB C , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo
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