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1.
J Clin Ultrasound ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39304526

RESUMEN

This study explored echocardiography's role in diagnosing and managing pediatric pulmonary artery sling (PAS). Data from 145 patients (January 2017 to December 2023) were analyzed, including echocardiography, CT angiography, bronchoscopy, and surgical records. Results indicated echocardiography accurately diagnosed PAS in 98.62% cases, with 1.38% misdiagnosed. Tracheal compression was common (95.86%), along with intracardiac anomalies (73.79%). Combined vascular ring types were found, notably PAS with left aortic arch and aberrant right subclavian artery (LAA-ARSA) and PAS with double aortic arch (DAA). Echocardiography's effectiveness underscores its crucial role in clinical management and surgical planning for these complex conditions.

2.
JAMA Netw Open ; 7(9): e2432862, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39264627

RESUMEN

Importance: Thrombotic microangiopathy (TMA) on kidney biopsy is a pattern of endothelial injury commonly seen in malignant hypertension (mHTN), but treatment strategies are not well established. Objective: To evaluate the kidney outcomes of angiotensin receptor-neprilysin inhibitor (ARNI), specifically sacubitril/valsartan, vs angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) therapy for patients with mHTN-associated TMA. Design, Setting, and Participants: This single-center cohort study enrolled consecutive patients in China diagnosed with mHTN-associated TMA through kidney biopsy from January 2008 to June 2023. Follow-up was conducted until the conclusion of the study period. Data were analyzed in September 2023. Exposures: Treatment with sacubitril/valsartan or ACEI/ARBs during hospitalization and after discharge. Main Outcomes and Measures: The primary outcome was a composite of kidney recovery: a 50% decrease in serum creatinine level, decrease in serum creatinine levels to the reference range, or kidney survival free from dialysis for more than 1 month. The secondary and tertiary outcomes were a 15% increase in the estimated glomerular filtration rate (eGFR) relative to baseline and kidney survival free from dialysis, respectively. Propensity score matching (PSM) and Cox proportional hazards regression analysis were used to evaluate the association between sacubitril/valsartan and ACEI/ARB therapy with kidney recovery outcomes. Results: Among the 217 patients (mean [SD] age, 35.9 [8.8] years; 188 men [86.6%]) included in the study, 66 (30.4%) received sacubitril/valsartan and 151 (69.6%) received ACEI/ARBs at baseline. Sacubitril/valsartan treatment was associated with shorter time to the primary outcome compared with ACEI/ARB treatment (20 of 63 [31.7%] vs 38 of 117 [32.5%]; adjusted hazard ratio [aHR], 1.85; 95% CI, 1.05-3.23). Sacubitril/valsartan treatment was independently associated with shorter time to a 15% increase in eGFR (15 of 46 [32.6%] vs 46 of 83 [55.4%]; aHR, 2.13; 95% CI, 1.09-4.17) and kidney survival free from dialysis (11 of 23 [47.8%] vs 16 of 57 [28.1%]; aHR, 2.63; 95% CI, 1.15-5.88) compared with ACEI/ARB treatment. These differences remained significant in the PSM comparison. Conclusions and Relevance: In this cohort study, sacubitril/valsartan treatment was associated with a potential kidney function benefit in patients with mHTN-associated TMA compared with ACEI/ARB treatment. The findings suggested that sacubitril/valsartan could be a superior therapeutic approach for managing this serious condition in terms of kidney recovery.


Asunto(s)
Aminobutiratos , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Compuestos de Bifenilo , Combinación de Medicamentos , Microangiopatías Trombóticas , Valsartán , Humanos , Masculino , Femenino , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Microangiopatías Trombóticas/tratamiento farmacológico , Persona de Mediana Edad , Valsartán/uso terapéutico , Compuestos de Bifenilo/uso terapéutico , Aminobutiratos/uso terapéutico , Adulto , Hipertensión Maligna/tratamiento farmacológico , Riñón/efectos de los fármacos , Riñón/fisiopatología , Neprilisina/antagonistas & inhibidores , Estudios de Cohortes , China , Tetrazoles/uso terapéutico , Resultado del Tratamiento , Tasa de Filtración Glomerular/efectos de los fármacos
3.
ACS Appl Mater Interfaces ; 16(37): 49349-49361, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39230248

RESUMEN

With the intensification of global environmental pollution and resource scarcity, hydrogen has garnered significant attention as an ideal alternative to fossil fuels due to its high energy density and nonpolluting nature. Consequently, the urgent development of electrocatalytic water-splitting electrodes for hydrogen production is imperative. In this study, a superwetting selenide catalytic electrode with a peony-flower-shaped micronano array (MoS2/Co0.8Fe0.2Se2/NixSey/nickel foam (NF)) was synthesized on NF via a two-step hydrothermal method. The optimal catalytic activity of cobalt-iron selenide was achieved by adjusting the Co/Fe ratio. The intrinsic catalytic activity of the electrodes was enhanced by incorporating transition metal selenides, which then served as a precursor for the subsequent loading of MoS2 nanoflowers on the surface to fully expose the active sites. Furthermore, the superwetting properties of the electrode accelerated electrolyte penetration and electron/mass transfer, while also facilitating bubble detachment from the electrode surface, thereby preventing "bubble shielding effect". This resulted in superior oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) performance, as well as overall water splitting capabilities. In a 1.0 M KOH solution, the electrode required only 166 and 195 mV overpotential to achieve a current density of 10 mA cm-2 for OER and HER, respectively. When functioning as a bifunctional catalytic electrode, only 1.60 V of voltage was necessary to drive the electrolyzer to reach a current density of 10 mA cm-2. Moreover, laboratory simulations of wind and solar energy-driven water splitting validated the feasibility of establishing a sustainable energy-to-hydrogen production chain. This work provides new insights into the preparation of low-overpotential, high-catalytic-activity superhydrophilic and underwater superaerophobic catalytic electrodes by rationally adjusting elemental ratios and exploring changes in electrode surface wettability.

4.
Curr Res Food Sci ; 9: 100820, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39263205

RESUMEN

Ophiocordyceps sinensis is a genus of ascomycete fungi that has been widely used as a valuable tonic or medicine. However, due to over-exploitation and the destruction of natural ecosystems, the shortage of wild O. sinensis resources has led to an increase in artificially cultivated O. sinensis. To rapidly and accurately identify the molecular differences between cultivated and wild O. sinensis, this study employs surface-enhanced Raman spectroscopy (SERS) combined with machine learning algorithms to distinguish the two O. sinensis categories. Specifically, we collected SERS spectra for wild and cultivated O. sinensis and validated the metabolic profiles of SERS spectra using Ultra-Performance Liquid Chromatography coupled with Orbitrap High-Resolution Mass Spectrometry (UPLC-Orbitrap-HRMS). Subsequently, we constructed machine learning classifiers to mine potential information from the spectral data, and the spectral feature importance map is determined through an optimized algorithm. The results indicate that the representative characteristic peaks in the SERS spectra are consistent with the metabolites identified through metabolomics analysis, confirming the feasibility of the SERS method. The optimized support vector machine (SVM) model achieved the most accurate and efficient capacity in discriminating between wild and cultivated O. sinensis (accuracy = 98.95%, 5-fold cross-validation = 98.38%, time = 0.89s). The spectral feature importance map revealed subtle compositional differences between wild and cultivated O. sinensis. Taken together, these results are expected to enable the application of SERS in the quality control of O. sinensis raw materials, providing a foundation for the efficient and rapid identification of their quality and origin.

5.
ACS Biomater Sci Eng ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39226188

RESUMEN

Acute kidney injury (AKI) is a disease that is characterized by a rapid decline in renal function and has a relatively high incidence in hospitalized patients. Sepsis, renal hypoperfusion, and nephrotoxic drug exposure are the main causes of AKI. The major therapy measures currently include supportive treatment, symptomatic treatment, and kidney transplantation. These methods are supportive treatments, and their results are not satisfactory. Fortunately, many new treatments that markedly improve the AKI therapy efficiency are emerging. These include antioxidant therapy, ferroptosis therapy, anti-inflammatory therapy, autophagy therapy, and antiapoptotic therapy. In addition, the development of nanotechnology has further promoted therapeutic effects on AKI. In this review, we highlight recent advances in the development of nanocarriers for AKI drug delivery. Emphasis has been placed on the latest developments in nanocarrier modification and design. We also summarize the applications of different nanocarriers in AKI treatment. Finally, the advantages and challenges of nanocarrier applications in AKI are summarized, and several nanomedicines that have been approved for clinical trials to treat diverse kidney diseases are listed.

6.
Front Immunol ; 15: 1428653, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39185404

RESUMEN

The p53 protein, encoded by TP53, is a tumor suppressor that plays a critical role in regulating apoptosis, cell cycle regulation, and angiogenesis in tumor cells via controlling various downstream signals. Natural killer (NK) cell-mediated immune surveillance is a vital self-defense mechanism against cancer and other diseases, with NK cell activity regulated by various mechanisms. Among these, p53 plays a significant role in immune regulation by maintaining the homeostasis and functionality of NK cells. It enhances the transcriptional activity of NK cell-activating ligands and downregulates inhibitory ligands to boost NK cell activation and tumor-killing efficacy. Additionally, p53 influences NK cell cytotoxicity by promoting apoptosis, autophagy, and ferroptosis in different tumor cells. p53 is involved in the regulation of NK cell activity and effector functions through multiple pathways. p53 also plays a pivotal role in the tumor microenvironment (TME), regulating the activity of NK cells. NK cells are critical components of the TME and are capable of directly killing tumor cells. And p53 mutates in numerous cancers, with the most common alteration being a missense mutation. These mutations are commonly associated with poor survival rates in patients with cancer. This review details p53's role in NK cell tumor immunosurveillance, summarizing how p53 enhances NK cell recognition and tumor destruction. We also explore the potential applications of p53 in tumor immunotherapy, discussing strategies for modulating p53 to enhance NK cell function and improve the efficacy of tumor immunotherapy, along with the associated challenges. Understanding the interaction between p53 and NK cells within the TME is crucial for advancing NK cell-based immunotherapy and developing p53-related novel therapeutics.


Asunto(s)
Células Asesinas Naturales , Neoplasias , Microambiente Tumoral , Proteína p53 Supresora de Tumor , Humanos , Células Asesinas Naturales/inmunología , Células Asesinas Naturales/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/inmunología , Neoplasias/inmunología , Microambiente Tumoral/inmunología , Animales , Inmunoterapia/métodos , Citotoxicidad Inmunológica
7.
Int J Biol Macromol ; 279(Pt 1): 135039, 2024 Aug 27.
Artículo en Inglés | MEDLINE | ID: mdl-39197609

RESUMEN

Seahorses exhibit the unique characteristic of male pregnancy, which incubates numerous embryos in a brood pouch that plays an essential role in enhancing offspring survivability. The pot-belly seahorse (Hippocampus abdominalis) possesses the largest body size among seahorses and is a significant species in Chinese aquaculture. In this study, we revealed the cytological and morphological characteristics, as well as regulatory mechanisms, throughout the entire brood pouch development in H. abdominalis. The brood pouch originated from the abdominal dermis, extending towards the ventral midline. As the dermal layers thicken, the inner epithelium folds, the stroma loosens, and vascularization occurs, culminating in the formation of the brood pouch. Furthermore, through transcriptomic analysis of brood pouches at various developmental stages, 8 key genes (tgfb3, fgf2, wnt7a, pgf, mycn, tln2, jund, ccn4) closely related to the development of brood pouch were identified in the MAPK, Rap1, TGF-ß, and Wnt signaling pathways. These genes were highly expressed in the pseudoplacenta and dermal layers at the newly formed stage as examined by in situ hybridization (ISH). The angiogenesis, densification of collagen fibers, and proliferation of fibroblasts and endothelial cells in seahorse brood pouch formation may be regulated by these genes and pathways. Additionally, the expression of the androgen receptor gene (ar) was significantly upregulated during the formation of the brood pouch, and ISH confirmed the expression of the ar gene in the dermis and pseudoplacenta of the brood pouch, highlighting its role in the developmental process. Androgen and flutamide (androgen receptor antagonist) treatments significantly accelerated the formation of the brood pouch and completely inhibited its occurrence respectively, concomitant to the upregulated expression of differentially expressed genes involved above signaling pathways. These findings demonstrated that formation of the brood pouch is determined by androgen and the androgen receptor activates the above signaling pathways in the brood pouch through the regulation of fgf2, tgfb3, pgf, and wnt7a. Interestingly, androgen even induced the formation of the brood pouch in females. We firstly elucidated the formation of the seahorse brood pouch, demonstrating that androgens and their receptors directly induce the thickening, folding, and vascularization of the abdominal dermal layer into a placenta-like structure through multiple signaling pathways. These findings provide foundational insights to further exploring the evolution of male pregnancy and adaptive convergence in viviparity across vertebrates.

8.
Food Sci Nutr ; 12(8): 5271-5284, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39139935

RESUMEN

Cardiovascular diseases (CVDs) affect the quality of life or are fatal in the worst cases, resulting in a significant economic and social burden. Therefore, there is an urgent need to invent functional products or drugs for improving patient health and alleviating and controlling these diseases. Marine bioactive peptides reduce and control CVDs. Many of the predisposing factors triggering CVDs can be alleviated by consuming functional foods containing marine biopeptides. Therefore, improving CVD incidence through the use of effective biopeptide foods from marine sources has attracted increasing interest and attention. This review reports information on bioactive peptides derived from various marine organisms, focusing on the process of the separation, purification, and identification of biological peptides, biological characteristics, and functional food for promoting cardiovascular health. Increasing evidence shows that the bioactivity and safety of marine peptides significantly impact their storage, purification, and processing. It is feasible to develop further strategies involving functional foods to treat CVDs through effective safety testing methods. Future work should focus on producing high-quality marine peptides and applying them in the food and drug industry.

9.
J Vis Exp ; (210)2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39158276

RESUMEN

Endometrial organoids offer valuable insights into the development and pathophysiology of endometrial diseases and serve as platforms for drug testing. While human and mouse endometrial organoids have been developed, research on rat endometrial organoids remains limited. Given that rats can better simulate certain endometrial pathologies, such as intrauterine adhesions, this study aimed to establish rat endometrial organoids. We present a detailed protocol for the isolation and culture of rat endometrial epithelial stem cells (reESCs) and the generation of rat endometrial organoids. Using a refined reESCs expansion medium, we successfully isolated and stably expanded reESCs, demonstrating their long-term culture potential. The reESC-generated organoids exhibited typical structural and functional characteristics of the endometrium, including hormone responsiveness. Our results showed that rat endometrial organoids could be cultured over a long term with stable proliferation, maintaining the glandular structure, cell polarity, and functional characteristics of the endometrial epithelium. This novel rat-derived endometrial organoid model provides a valuable platform for studying endometrial diseases and testing therapeutic interventions, with potential applications across various mammalian species.


Asunto(s)
Endometrio , Células Epiteliales , Organoides , Animales , Femenino , Organoides/citología , Ratas , Endometrio/citología , Células Epiteliales/citología , Células Madre/citología , Útero/citología
10.
Heliyon ; 10(14): e34011, 2024 Jul 30.
Artículo en Inglés | MEDLINE | ID: mdl-39100456

RESUMEN

Cancer is widely regarded as a leading cause of death in humans, with colon adenocarcinoma (COAD) ranking among the most prevalent types. Cuproptosis is a novel form of cell death mediated by protein lipoylation. Cuproptosis-related genes (CRGs) participate in tumourigenesis and development. Their role in pan-cancer and COAD require further investigation. This study comprehensively evaluated the relationship among CRGs, pan-cancer, and COAD. Our research revealed the differential expression of CRGs and the cuproptosis potential index (CPI) between normal and tumour tissues, and further explored the correlation of CRGs or CPI with prognosis, immune infiltration, tumor mutant burden(TMB), microsatellite instability (MSI), and drug sensitivity in pan-cancer. Gene set enrichment analysis (GSEA) revealed that oxidative phosphorylation and fatty acid metabolism pathways were significantly enriched in the high CPI group of most tumours. FDX1 and CDKN2A were chosen for further exploration, and we found an independent association between FDX1 and CDKN2A and prognosis, immune infiltration, TMB, and MSI in pan-cancer. Furthermore, a prognostic risk model based on the association between CRGs and COAD was built, and the correlations between the risk score and prognosis, immune-related characteristics, and drug sensitivity were analysed. COAD was then divided into three subtypes using cluster analysis, and the differences among the subtypes in prognosis, CPI, immune-related characteristics, and drug sensitivity were determined. Due to the level of LIPT1 was notably positive related with the risk score, the cytological identification was carried out to identify the association of LIPT1 with proliferation and migration of colon cancer cells. In summary, CRGs can be used as potential prognostic biomarkers to predict immune infiltration levels in patients with pan-cancer. In addition, the risk model could more accurately predict the prognosis and immune infiltration levels of COAD and better guide the direction of clinical medication. Thus, FDX1, CDKN2A, and LIPT1 may serve as prospective new targets for cancer therapy.

11.
Small ; : e2403991, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-39136429

RESUMEN

Acquiring a highly efficient electrocatalyst capable of sustaining prolonged operation under high current density is of paramount importance for the process of electrocatalytic water splitting. Herein, Fe-doped phosphide (Fe-Ni5P4) derived from the NiFc metal-organic framework (NiFc-MOF) (Fc: 1,1'-ferrocene dicarboxylate) shows high catalytic activity for overall water splitting (OWS). Fe-Ni5P4||Fe-Ni5P4 exhibits a low voltage of 1.72 V for OWS at 0.5 A cm-2 and permits stable operation for 2700 h in 1.0 m KOH. Remarkably, Fe-Ni5P4||Fe-Ni5P4 can sustain robust water splitting at an extra-large current density of 1 A cm-2 for 1170 h even in alkaline seawater. Theoretical calculations confirm that Fe doping simultaneously reduces the reaction barriers of coupling and desorption (O*→OOH*, OOH*→O2 *) in the oxygen evolution reaction (OER) and regulates the adsorption strength of the intermediates (H2O*, H*) in the hydrogen evolution reaction (HER), enabling Fe-Ni5P4 to possess excellent dual functional activity. This study offers a valuable reference for the advancement of highly durable electrocatalysts through the regulation derived from coordination frameworks, with significant implications for industrial applications and energy conversion technologies.

12.
Angew Chem Int Ed Engl ; : e202410938, 2024 Aug 02.
Artículo en Inglés | MEDLINE | ID: mdl-39092496

RESUMEN

The electrocatalytic C-N coupling from CO2 and nitrate emerges as one of the solutions for waste upgrading and urea synthesis. In this work, we constructed electron-deficient Cu sites by the strong metal-polymer semiconductor interaction, to boost efficient and durable urea synthesis. In situ Raman spectroscopy identified the existence of electron-deficient Cu sites and was able to withstand electrochemical reduction conditions. Operando synchrotron-radiation Fourier transform infrared spectroscopy and theoretical calculations disclosed the vital role of electron-deficient Cu in adsorption and C-N coupling of oxygen-containing species. The electron-deficient Cu displayed a high urea yield rate of 255.0 mmol h-1 g-1 at -1.4 V versus the reversible hydrogen electrode and excellent electrochemical durability, superior than that of non-electron-deficient counterpart with conductive carbon material as the support. It can be concluded that the regulation of site electronic structure is more important than the optimization of catalyst conductive properties in the C-N coupling reactions.

13.
Nat Commun ; 15(1): 6650, 2024 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-39103370

RESUMEN

The oxygen reduction reaction (ORR) catalyzed by efficient and economical catalysts is critical for sustainable energy devices. Although the newly-emerging atomically dispersed platinum catalysts are highly attractive for maximizing atomic utilization, their catalytic selectivity and durability are severely limited by the inflexible valence transformation between Pt and supports. Here, we present a structure by anchoring Pt atoms onto valence-adjustable CuOx/Cu hybrid nanoparticle supports (Pt1-CuOx/Cu), in which the high-valence Cu (+2) in CuOx combined with zero-valent Cu (0) serves as a wide-range valence electron reservoir (0‒2e) to dynamically adjust the Pt 5d valence states during the ORR. In situ spectroscopic characterizations demonstrate that the dynamic evolution of the Pt 5d valence electron configurations could optimize the adsorption strength of *OOH intermediate and further accelerate the dissociation of O = O bonds for the four-electron ORR. As a result, the Pt1-CuOx/Cu catalysts deliver superior ORR performance with a significantly enhanced four-electron selectivity of over 97% and long-term durability.

14.
Acad Radiol ; 2024 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-39183131

RESUMEN

RATIONALE AND OBJECTIVES: This study aims to explore the feasibility of the deep learning radiomics nomogram (DLRN) for predicting tumor status and axillary lymph node metastasis (ALNM) after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Additionally, we employ a Cox regression model for survival analysis to validate the effectiveness of the fusion algorithm. MATERIALS AND METHODS: A total of 243 patients who underwent NAC were retrospectively included between October 2014 and July 2022. The DLRN integrated clinical characteristics as well as radiomics and deep transfer learning features extracted from ultrasound (US) images. The diagnostic performance of DLRN was evaluated by constructing ROC curves, and the clinical usefulness of models was assessed using decision curve analysis (DCA). A survival model was developed to validate the effectiveness of the fusion algorithm. RESULTS: In the training cohort, the DLRN yielded area under the receiver operating characteristic curve values of 0.984 and 0.985 for the tumor and LNM, while 0.892 and 0.870, respectively, in the test cohort. The consistency indices (C-index) of the nomogram were 0.761 and 0.731, respectively, in the training and test cohorts. The Kaplan-Meier survival curves showed that patients in the high-risk group had significantly poorer overall survival than patients in the low-risk group (P < 0.05). CONCLUSION: The US-based DLRN model could hold promise as clinical guidance for predicting the status of tumors and LNM after NAC in patients with breast cancer. This fusion model can also predict the prognosis of patients, which could help clinicians make better clinical decisions.

15.
J Am Chem Soc ; 146(35): 24570-24579, 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39169610

RESUMEN

The electrocatalytic hydrogenation (ECH) of furfural (FF) to furfuryl alcohol, which does not require additional hydrogen or high pressure, is a green and promising production route. In this study, we explore the effects of anions on FF ECH in two buffer electrolytes (KHCO3 and phosphate-buffered saline [PBS]). Anions influence the yield of furfuryl alcohol through molecular activation and adsorption. Molecular dynamics simulations show that bicarbonate is present in the first shell layer of the FF molecule and induces strong hydrogen bonding interactions. In contrast, hydrogen phosphate is present only in the second shell layer, resulting in weak hydrogen bonding interactions. Owing to the interfacial anions and hydrogen bonding, FF molecules exhibit strong flat adsorption on the electrode surface in the KHCO3 solution, while weak adsorption is observed in the PBS solution, as confirmed by operando synchrotron-radiation Fourier-transform infrared spectroscopy and in situ Raman spectroscopy. Density-functional theory calculations reveal that the overall anionic hydrogen bonding network promotes the activation of the carbonyl group in the FF molecule in KHCO3, whereas electrophilic activity is inhibited in PBS. Consequently, FF ECH demonstrates much faster kinetics in KHCO3, while it exhibits sluggish ECH kinetics and a severe hydrogen evolution reaction in PBS. This work introduces a new strategy to optimize the catalytic process through the modulation of the microenvironment.

16.
Atherosclerosis ; 396: 118531, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38996716

RESUMEN

BACKGROUND AND AIMS: Diabetes is one of the major causes of cardiovascular disease (CVD). As high as 29 % of patients with diabetes develop atherosclerosis. Vascular Smooth Muscle Cells (VSMCs) are a key mediator in the pathogenesis of atherosclerosis, generating pro-inflammatory and proliferative characteristics in atherosclerotic lesions. METHODS: We used human atherosclerotic samples, developed diabetes-induced atherosclerotic mice, and generated loss of function and gain of function in Klotho human aortic smooth muscle cells to investigate the function of Klotho in atherosclerosis. RESULTS: We found that Klotho expression is decreased in smooth muscle actin-positive cells in patients with diabetes and atherosclerosis. Consistent with human data, we found that Apoe knockout mice with streptozotocin-induced diabetes fed on a high-fat diet showed decreased expression of Klotho in SMCs. Additionally, these mice showed increased expression of TGF-ß, MMP9, phosphorylation of ERK and Akt. Further, we utilized primary Human Aortic Smooth Muscle Cells (HASMCs) with d-glucose under dose-response and in time-dependent conditions to study the role of Klotho in these cells. Klotho gain of function and loss of function studies showed that Klotho inversely regulated the expression of atherosclerotic markers TGF-ß, MMP2, MMP9, and Fractalkine. Further, High Glucose (HG) induced Akt, and ERK1/2 phosphorylation were enhanced or mitigated by endogenous Klotho deficiency or its overexpression respectively. PI3K/Akt and MAPK/ERK inhibition partially abolished the HG-induced upregulation of TGF-ß, MMP2, MMP9, and Fractalkine. Additionally, Klotho knockdown increased the proliferation of HASMCs and enhanced α-SMA and TGF-ß expression. CONCLUSIONS: Taken together, these results indicate that local vascular Klotho is involved in diabetes-induced atherosclerosis, which is via PI3K/Akt and ERK1/2-dependent signaling pathways.


Asunto(s)
Aterosclerosis , Diabetes Mellitus Experimental , Glucuronidasa , Proteínas Klotho , Ratones Noqueados para ApoE , Músculo Liso Vascular , Miocitos del Músculo Liso , Proteínas Klotho/metabolismo , Animales , Aterosclerosis/metabolismo , Aterosclerosis/patología , Aterosclerosis/genética , Glucuronidasa/metabolismo , Glucuronidasa/genética , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Masculino , Transducción de Señal , Células Cultivadas , Aorta/patología , Aorta/metabolismo , Sistema de Señalización de MAP Quinasas , Ratones , Enfermedades de la Aorta/patología , Enfermedades de la Aorta/metabolismo , Enfermedades de la Aorta/genética , Enfermedades de la Aorta/enzimología , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones Endogámicos C57BL , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proliferación Celular
17.
ACS Appl Mater Interfaces ; 16(29): 38269-38282, 2024 Jul 24.
Artículo en Inglés | MEDLINE | ID: mdl-38986605

RESUMEN

Triboelectric nanogenerator (TENG) has been demonstrated as a sustainable energy utilization method for waste mechanical energy and self-powered system. However, the charge dissipation of frictional layer materials in a humid environment severely limits their stable energy supply. In this work, a new method is reported for preparing polymer film as a hydrophobic negative friction material by solution blending poly(vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP) and polyvinyl chloride (PVC), doping with titanium dioxide (TiO2) nanoparticles, and further surface patterning modification. The P-TENG composed of the PVDF-HFP/PVC/TiO2 composite film with optimized hydrophobic performance (WCA = 124°) achieved an output voltage of 235 V and a short-circuit current of 35 µA, which is approximately three times that of the bare PVDF-HFP-based TENG. Under charge excitation, the transferred charge of the P-TENG can reach 35 nC. When the external load resistance is 5.5 MΩ, the output peak power density can reach 1.4 W m-2. Meanwhile, the hydrophobic surface layer with a rough surface structure enables the device to overcome the influence of water molecules on charge transfer in a humid environment, quickly recover, and maintain a high output. The P-TENG can effectively monitor finger flexibility and strength and realize real-time evaluation of the exercise state and hand fatigue of the elderly and rehabilitation trainers. It has broad application prospects in self-powered intelligent motion sensing, soft robotics, human-machine interaction, and other fields.

18.
J Am Chem Soc ; 146(28): 19572-19579, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-38973100

RESUMEN

Hexamethylenetetramine (HMTA) is extensively used in the defense industry, medicines, food, plastics, rubber, and other applications. Traditional organic synthesis of HMTA relies on ammonia derived from the Haber process at high temperatures and pressures. In contrast, electrochemical methods enable a safe and green one-pot synthesis of HMTA from waste NO3-. However, HMTA synthesis through the electrochemical method is challenging owing to the complex reaction pathways involving C-N bond construction and ring formation. In this study, HMTA was efficiently synthesized over electrochemical oxidation-derived copper (e-OD-Cu), with a yield of 76.8% and a Faradaic efficiency of 74.9% at -0.30 VRHE. The catalytic mechanism and reaction pathway of HMTA synthesis on e-OD-Cu were investigated through a series of in situ characterization methods and density-functional theory calculations. The results demonstrated that the electrocatalytic synthesis of HMTA involved a tandem electrochemical-chemical reaction. Additionally, the results indicated that the presence of Cu vacancies enhanced substrate adsorption and inhibited the further hydrogenation of C═N. Overall, this study provides an electrocatalytic method for HMTA synthesis and an electrochemical strategy for constructing multiple C-N bonds.

19.
Animals (Basel) ; 14(14)2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-39061514

RESUMEN

Guanidinoacetic acid (GAA) can effectively improve the metabolism of energy and proteins by stimulating creatine biosynthesis. We present a study exploring the impact of GAA on production performance, serum biochemistry, meat quality and rumen fermentation in Hu sheep. A total of 144 weaned male Hu sheep (body weight 16.91 ± 3.1 kg) were randomly assigned to four groups with three replicates of twelve sheep in each group. The diets were supplemented with 0 (CON), 500 (GAA-1), 750 (GAA-2) and 1000 mg/kg (GAA-3) of GAA (weight of feed), respectively. After a comprehensive 90-day experimental period, we discovered that the supplementation of GAA had a remarkable impact on various muscle parameters. Specifically, it significantly enhanced the average daily growth (ADG) of the animals and improved the shear force and fiber diameter of the muscle, while also reducing the drip loss and muscle fiber density. Furthermore, the addition of GAA to the feed notably elevated the serum concentrations of high-density lipoprotein cholesterol (HDL-C), total protein (TP) and globulin (GLB), as well as the enzyme activity of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Concurrently, there was a decrease in the levels of triglycerides (TG) and malondialdehyde (MDA) in the serum. In addition, GAA decreased the pH and the acetate-to-propionate ratio and increased the total volatile fatty acids (TVFA) and ammoniacal nitrogen (NH3-N) levels of rumen fluid. Additionally, GAA upregulated acetyl-CoA carboxylase (ACC) gene expression in the Hu sheep's muscles. In conclusion, our findings suggest that GAA supplementation not only enhances muscle quality but also positively affects serum biochemistry and ruminal metabolism, making it a potential candidate for improving the overall health and performance of Hu sheep.

20.
Animals (Basel) ; 14(13)2024 Jun 29.
Artículo en Inglés | MEDLINE | ID: mdl-38998047

RESUMEN

Organic iodine is a new trace element additive that is highly efficient in regulating cell growth, function, and metabolism. This study demonstrated that organic iodine improves the growth performance and gut health of Fujian yellow rabbits. A total of 160 healthy rabbits of similar weight were randomly divided into four groups, which were treated with organic iodine (0, 0.5, 1.0, and 1.5 mg/kg) for 60 days. Our results indicated that organic iodine improved the growth performance, including significantly increased BW, ADG, and ADFI, and decreased F/G notably. Organic iodine improved the content of T3, T4, IgM, IgA, and IgM in serum, and intestinal mucosal immunity (IL-1α, IL-2, and sIgA). Organic iodine supplementation ameliorated gut morphometry and morphology, such as higher villus height and lower crypt depth. Organic iodine increased the amount of goblet cells significantly. The 0.5 mg/kg organic iodine most increased the activities of amylase, cellulase, and trypsin in caecum. Organic iodine induced more active caecum fermentation, higher NH3-N, acetic acid, propionic acid, and butyric acid, while lowering PH. In conclusion, organic iodine improved the growth performance and gut morphometry and morphology, and increased caecum enzyme activities, active caecum fermentation, and intestinal immunity of Fujian yellow rabbits.

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