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1.
ACS Sens ; 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39254107

RESUMEN

The performance of semiconductor sensors is determined by reaction kinetics, conductivity, and electron mobility, which are undoubtedly closely related to the electron motion behavior. Therefore, the effective regulation of electronic states is crucial for improving gas sensing properties. Previous methods of enhancing the gas-sensing performance have induced complex material modifications, and the extent of performance improvement is usually very limited. Further optimization of the gas sensing performance requires continuous efforts to advance new technologies. Toward this issue, a novel magnetic field-induced strategy is adopted to boost the carrier transfer efficiency of nonferromagnetic semiconductors. The gas sensing investigation results manifest that the applied magnetic field can effectively enhance the sensitivity and reduce the baseline resistance. The In2O3 NC-2 (In2O3 nanocubes) with an applied magnetic field have a greatly enhanced response of 161.4 toward 100 ppm formaldehyde, which is 2.5 times higher than that without magnetic field. The enhanced gas sensing properties can be mainly attributed to magnetization of reactive materials, which makes the orientation of electronic magnetic moments consistent, thus greatly contributing to reactivity. This work introduces a practical approach to effectively improve gas sensing performance without further morphology optimization, noble metal catalysis, structural modification, and material cladding. The results of this study provide new insights for designing novel gas sensors to improve the gas sensing performance.

2.
Ann Surg ; 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-39247951

RESUMEN

OBJECTIVE: Evaluating the safety and efficacy of implanting a liver with islet grafts into patients with end-stage liver disease and diabetes mellitus (DM). BACKGROUND: DM and end-stage liver diseases are significant health concern worldwide, often coexisting and mutually influencing each other. Addressing both diseases simultaneously is paramount. METHODS: We utilized the islet transplantation combined ischemia-free liver transplantation (ITIFLT) technique to treat a patient with hepatocellular carcinoma (HCC) and type 2 diabetes mellitus (T2DM). The liver was procured and preserved using the ischemia-free liver transplantation (IFLT) technique, and during normothermic machine perfusion (NMP), isolated and purified islet grafts were transplanted into the liver through the portal vein. Finally, the liver, incorporating with the transplant islet grafts, was implanted into the recipient without interruption of blood supply. RESULTS: The patient received both liver and islet graft from the same donor. The patient achieved insulin-independence by post-transplant day (PTD) 9, and both liver and islet function remained robust. The patient was discharged on PTD 18 and experienced no surgical or transplantation-related complications during the follow-up period. Furthermore, islet grafts presence was observed in liver biopsies after islet transplantation. CONCLUSIONS: This landmark case marks the inaugural application of ITIFLT in humans, signifying its potential as a promising treatment modality for end-stage liver disease with DM.

3.
Phytochem Anal ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39233523

RESUMEN

INTRODUCTION: Insight into comparing key active ingredients of Radix Bupleuri (RB) based on different processing technologies is a key step to reveal the material basis of drug efficacy and a challenging task for developing traditional Chinese medicine (TCM). OBJECTIVE: This work aims to establish a comprehensive comparative analysis method of TCM and its processed products, which can be used to analyze the changing trend of active components of RB before and after processing. METHODS: First, RB was processed with rice vinegar, rice wine, and honey. Then, ultra-high-performance liquid chromatography (UHPLC) and gas chromatography (GC) coupled with mass spectrometry (MS) technology as well as multiple statistical analyses were used to comprehensively evaluate the compositional variation of polar and volatile compounds in RB under different processing processes. Meanwhile, in UHPLC-MS, a sequential window acquisition of all theoretical fragment ion spectral and information-dependent acquisition mutual authentication (SIMA) was developed. RESULTS: A total of 30 polar components and 33 volatile components were identified as chemical markers (mainly type II saikosaponins, terpenes, and fatty acid esters). These may be the material basis for giving unique pharmacological activities to RB and its processed products. CONCLUSIONS: These findings provided a solid foundation for the differentiated clinical application of RB, and the SIMA method held great potential for achieving accurate analysis of TCM processing ingredients.

4.
Sci Rep ; 14(1): 20342, 2024 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-39223272

RESUMEN

The correlation between diabetes and coronary artery disease (CAD) is well established. Insulin resistance (IR) is considered a primary contributor to elevated CAD risk in diabetic individuals. The triglyceride-glucose (TyG) index serves as a straightforward surrogate marker for insulin resistance. However, few studies have explored their correlations with myocardial infarction and CAD severity. Therefore, our study aimed to investigate the association between the TyG index and the occurrence of myocardial infarction, as well as the severity of coronary artery disease. We conducted a retrospective study involving 3865 consecutive patients who underwent coronary angiography at the First Affiliated Hospital of Zhejiang University, School of Medicine. Of these, 1724 patients were diagnosed with coronary artery disease. Demographic, biochemical, clinical, and angiographic data were gathered. A robust correlation exists between the TyG index and CAD subtypes, suggesting its potential as an independent clinical diagnostic marker. Moreover, the TyG index exhibited a significant positive correlation with disease severity, as assessed by the Gensini score. Elevated TyG index was associated with an increased predisposition to severe CAD, as indicated by the Gensini score, and myocardial infarction, even after adjusting for well-established cardiovascular risk factors.


Asunto(s)
Glucemia , Angiografía Coronaria , Enfermedad de la Arteria Coronaria , Índice de Severidad de la Enfermedad , Triglicéridos , Humanos , Masculino , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/diagnóstico , Triglicéridos/sangre , Persona de Mediana Edad , Glucemia/análisis , Glucemia/metabolismo , Estudios Retrospectivos , Anciano , Infarto del Miocardio/sangre , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Biomarcadores/sangre , Resistencia a la Insulina , Factores de Riesgo
5.
J Colloid Interface Sci ; 678(Pt B): 1061-1072, 2024 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-39276515

RESUMEN

Breathing and urination, are vital physiological activities of the human body, continuous real-time monitoring of these physiological behaviors could offer timely feedback on an individual's health status. However, current monitoring techniques predominantly rely on cumbersome and intricate medical apparatuses, posing challenges in adapting to the diverse requirements of multi-scenario detection. Consequently, there is a growing interest in developing wearable devices capable of monitoring breathing and urination. In this work, we developed a multifunctional sensor integrating humidity and pressure sensing modes using a simple dip-coating process. By introducing sodium carboxymethyl cellulose and conductive polyaniline hybrid intercalation between MXene layers, a stable conductive network is established through hydrogen bonds and electrostatic interactions among materials. The overall electromechanical properties of the composites will be well improved. And, the effects of different conductive filler ratios and the number of dipping times on the construction of conductive networks are investigated. The multifunctional sensor exhibited improved sensing characteristics, including detecting pressures up to 532 kPa and a sensitivity of 19.58 kPa-1. Furthermore, it also demonstrates good humidity-sensing capabilities. Tests on volunteers demonstrated the potential in the detection of breathing and urination. In addition, the sensors are capable of transmitting Morse code. This interesting application will offer the possibility of normal communication for people with speech impairments. Given its utility and sustainability, the sensor has potential for applications in wearable health monitoring, intelligent life and telemedicine.

6.
Plant Commun ; : 101133, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39277791

RESUMEN

Proper mitochondrial function is crucial to plant growth and development. Inhibition of mitochondrial translation leads to mitochondrial proteotoxic stress, which triggers a protective transcriptional response that regulates nuclear gene expression, commonly referred to as the mitochondrial unfolded protein response (UPRmt). Although UPRmt has been extensively studied in yeast and mammals, very little is known about UPRmt in plants. Here, we show that mitochondrial translational stress inhibits plant growth and development by inducing jasmonic acid (JA) biosynthesis and signaling. The inhibitory effect of mitochondrial translational stress on plant growth was alleviated in JA signaling defective mutants coi1-2, myc2, and myc234. Genetic analysis indicates that Arabidopsis mitochondrial ribosomal protein L1 (MRPL1), a key factor in UPRmt, regulates plant growth in a CORONATINE-INSENSITIVE1 (COI1)-dependent manner. Moreover, under mitochondrial translational stress, MYC2 showed direct binding to G-boxes in the ETHYLENE RESPONSE FACTOR 109 (ERF109) promoter. The induction of ERF109 expression enhances hydrogen peroxide (H2O2) production, which acts as a feedback loop to inhibit root growth. In addition, mutation of MRPL1 increases JA accumulation, reduces plant growth, and enhances biotic stress resistance. Overall, our findings reveal that JA plays an important role in mediating retrograde signaling under mitochondrial translational stress to balance plant growth and defense.

7.
Photodiagnosis Photodyn Ther ; : 104332, 2024 Sep 13.
Artículo en Inglés | MEDLINE | ID: mdl-39278300

RESUMEN

BACKGROUND: As a rare subcutaneous infection, protothecosis is easily misdiagnosed. Similar to other subcutaneous infection, there is no unified standard for treatment, for cases not suitable for surgery, clinicians often use antifungal drugs based on their experience, and the course of treatment varies from several months to several years. Based on the fact that there are few relevant materials and researches on photodynamic therapy (PDT), we conducted a study based on a clinical case that used oral itraconazole combined with 5-aminolevylinic acid photodynamic therapy (ALA-PDT) to treat a patient with cutaneous protothecosis caused by Prototheca wicherhamii. METHODS: Different concentrations of ALA and different light doses were used to investigate the effects of ALA-PDT on the growth inhibition of P. wickerhamii in vitro with Colony-counting Methods. And we used transmission electron microscopy (TEM) to visualize the structural changes and the effects of ALA-PDT treating on cellular structures of the P. wickerhamii. Futher, we performed the susceptibility test of P. wickerhamii to itraconazole before and after ALA-PDT in vitro. RESULTS: We have successfully treated a patient with cutaneous protothecosis caused by P. wickerhamii by using combination therapy in a total of 9-week course of treatment. In vitro, ALA-PDT can inhibit the growth of P. wickerhamii when the ALA concentration was 5mg/mL (P < 0.01), and this effect became stronger as the concentration of ALA or light dose is increased. Using TEM, we confirmed that ALA-PDT can disrupt the cell wall structure and partition structure of P. wickerhamii, which may contribute to its inhibitory effect. Further studies showed that the MIC of itraconazole for P. wickerhamii was decreased after ALA-PDT. CONCLUSIONS: ALA-PDT combined with oral itraconazole can be used to treat cutaneous protothecosis. Accordingly, ALA-PDT can destroy the cell wall and partition structure of P. wickerhamii leading to an inhibitory effect on it in vitro, and the effect is enhanced with the increase of ALA concentration and light dose. Also, the sensitivity of P. wickerhamii to itraconazole is observed increased after ALA-PDT. So our study provides a theoretical basis for the promising treatment against cutaneus protothecosis.

8.
Entropy (Basel) ; 26(8)2024 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-39202105

RESUMEN

The integration of terrestrial- and satellite-based quantum key distribution (QKD) experiments has markedly advanced global-scale quantum networks, showcasing the growing maturity of quantum technologies. Notably, the use of unmanned aerial vehicles (UAVs) as relay nodes has emerged as a promising method to overcome the inherent limitations of fiber-based and low-Earth orbit (LEO) satellite connections. This paper introduces a protocol for measurement-device-independent QKD (MDI-QKD) using photon orbital angular momentum (OAM) encoding, with UAVs as relay platforms. Leveraging UAV mobility, the protocol establishes a secure and efficient link, mitigating threats from untrusted UAVs. Photon OAM encoding addresses reference frame alignment issues exacerbated by UAV jitter. A comprehensive analysis of atmospheric turbulence, state-dependent diffraction (SDD), weather visibility, and pointing errors on free-space OAM-state transmission systems was conducted. This analysis elucidates the relationship between the key generation rate and propagation distance for the proposed protocol. Results indicate that considering SDD significantly decreases the key rate, halving previous data results. Furthermore, the study identifies a maximum channel loss capacity of 26 dB for the UAV relay platform. This result is pivotal in setting realistic parameters for the deployment of UAV-based quantum communications and lays the foundation for practical implementation strategies in the field.

9.
Global Spine J ; : 21925682241270036, 2024 Aug 07.
Artículo en Inglés | MEDLINE | ID: mdl-39109794

RESUMEN

STUDY DESIGN: Cross-sectional study. OBJECTIVES: Imaging classification of adolescent idiopathic scoliosis (AIS) is directly related to the surgical strategy, but the artificial classification is complex and depends on doctors' experience. This study investigated deep learning-based automated classification methods (DL group) for AIS and validated the consistency of machine classification and manual classification (M group). METHODS: A total of 506 cases (81 males and 425 females) and 1812 AIS full spine images in the anteroposterior (AP), lateral (LAT), left bending (LB) and right bending (RB) positions were retrospectively used for training. The mean age was 13.6 ± 1.8. The mean maximum Cobb angle was 46.8 ± 12.0. U-Net semantic segmentation neural network technology and deep learning methods were used to automatically segment and establish the alignment relationship between multiple views of the spine, and to extract spinal features such as the Cobb angle. The type of each test case was automatically calculated according to Lenke's rule. An additional 107 cases of adolescent idiopathic scoliosis imaging were prospectively used for testing. The consistency of the DL group and M group was compared. RESULTS: Automatic vertebral body segmentation and recognition, multi-view alignment of the spine and automatic Cobb angle measurement were implemented. Compare to the M group, the consistency of the DL group was significantly higher in 3 aspects: type of lateral convexity (0.989 vs 0.566), lumbar curvature modifier (0.932 vs 0.738), and sagittal plane modifier (0.987 vs 0.522). CONCLUSIONS: Deep learning enables automated Cobb angle measurement and automated Lenke classification of idiopathic scoliosis whole spine radiographs with higher consistency than manual measurement classification.

10.
Artículo en Inglés | MEDLINE | ID: mdl-39137088

RESUMEN

Understanding the intricate regulatory relationships among genes is crucial for comprehending the development, differentiation, and cellular response in living systems. Consequently, inferring gene regulatory networks (GRNs) based on observed data has gained significant attention as a fundamental goal in biological applications. The proliferation and diversification of available data present both opportunities and challenges in accurately inferring GRNs. Deep learning, a highly successful technique in various domains, holds promise in aiding GRN inference. Several GRN inference methods employing deep learning models have been proposed; however, the selection of an appropriate method remains a challenge for life scientists. In this survey, we provide a comprehensive analysis of 12 GRN inference methods that leverage deep learning models. We trace the evolution of these major methods and categorize them based on the types of applicable data. We delve into the core concepts and specific steps of each method, offering a detailed evaluation of their effectiveness and scalability across different scenarios. These insights enable us to make informed recommendations. Moreover, we explore the challenges faced by GRN inference methods utilizing deep learning and discuss future directions, providing valuable suggestions for the advancement of data scientists in this field.

11.
Biochim Biophys Acta Mol Basis Dis ; 1870(8): 167456, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39122223

RESUMEN

Myocardial fibroblasts transform into myofibroblasts during the progression of cardiac fibrosis, together with excessive cardiac fibroblast proliferation. Hence, the prevention and treatment of cardiac fibrosis are significant factors for inhibiting the development of heart failure. P-element Induced WImpy testis-interacting RNAs (PiRNA) are widely expressed in the heart, but their involvement in cardiac fibrosis has not yet been confirmed. We identified differentially expressed PiRNAs using Arraystar PiRNA expression profiling in Angiotensin II models of cardiac fibrosis in vivo and in vitro. We then explored cardiac-fibrosis-associated PiRNA-related proteins, RNA-protein interactomes, immunoprecipitation, and pulldown. We detected fibrosis markers and pathway-related proteins using immunofluorescence, qRT-PCR, and Western blot. We uncovered cardiac fibrosis associated PiRNA (CFAPIR) that was obviously dysregulated during cardiac fibrosis, whereas its overexpression reversed fibrosis in vivo and in vitro. Mechanistically, CFAPIR competitively bound muscleblind like protein 2 (MBNL2) and the cyclin-dependent kinase inhibitor P21 to regulate the TGF-ß1/SMAD3 signaling pathway.

12.
BMC Plant Biol ; 24(1): 776, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-39143536

RESUMEN

High temperature stress is one of the most severe forms of abiotic stress in alfalfa. With the intensification of climate change, the frequency of high temperature stress will further increase in the future, which will bring challenges to the growth and development of alfalfa. Therefore, untargeted metabolomic and RNA-Seq profiling were implemented to unravel the possible alteration in alfalfa seedlings subjected to different temperature stress (25 ℃, 30 ℃, 35 ℃, 40 ℃) in this study. Results revealed that High temperature stress significantly altered some pivotal transcripts and metabolites. The number of differentially expressed genes (DEGs) markedly up and down-regulated was 1876 and 1524 in T30_vs_CK, 2, 815 and 2667 in T35_vs_CK, and 2115 and 2, 226 in T40_vs_CK, respectively. The number for significantly up-regulated and down-regulated differential metabolites was 173 and 73 in T30_vs_CK, 188 and 57 in T35_vs_CK, and 220 and 66 in T40_vs_CK, respectively. It is worth noting that metabolomics and transcriptomics co-analysis characterized enriched in plant hormone signal transduction (ko04705), glyoxylate and dicarboxylate metabolism (ko00630), from which some differentially expressed genes and differential metabolites participated. In particular, the content of hormone changed significantly under T40 stress, suggesting that maintaining normal hormone synthesis and metabolism may be an important way to improve the HTS tolerance of alfalfa. The qRT-PCR further showed that the expression pattern was similar to the expression abundance in the transcriptome. This study provides a practical and in-depth perspective from transcriptomics and metabolomics in investigating the effects conferred by temperature on plant growth and development, which provided the theoretical basis for breeding heat-resistant alfalfa.


Asunto(s)
Medicago sativa , Metabolómica , Transcriptoma , Medicago sativa/genética , Medicago sativa/metabolismo , Medicago sativa/fisiología , Perfilación de la Expresión Génica , Metaboloma , Regulación de la Expresión Génica de las Plantas , Calor , Estrés Fisiológico/genética , Plantones/genética , Plantones/metabolismo , Plantones/fisiología , Plantones/crecimiento & desarrollo , Respuesta al Choque Térmico/genética
13.
Nutr Metab Cardiovasc Dis ; 34(10): 2305-2314, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39004593

RESUMEN

BACKGROUND AND AIMS: The inflammatory nutritional status is widely associated with the long-term prognosis of non-fatal stroke. The objective of this study is to examine the correlation between the C-reactive protein to albumin ratio (CAR), a new marker indicating both inflammatory and nutritional status, and the overall mortality rate among stroke patients. METHODS AND RESULTS: Data were obtained from the National Health and Nutrition Examination Survey (NHANES) database and corresponding public-use mortality data from the linked National Death Index (NDI). The study utilized maximally selected rank statistics to determine the optimal cutoff points for the CAR. Subsequently, participants were stratified into higher- and lower-CAR groups based on these cutoff points. The Kaplan-Meier survival method was used to study overall survival probability. Multivariable Cox proportional regression models were employed to calculate the Hazard Ratio (HR) and corresponding confidence interval (CI). Restricted cubic spline (RCS) model was applied to detect potential non-linear relationship between CAR and mortality risk. Furthermore, stratified and sensitive analyses were performed to examine the robustness and reliability of the results. The study, encompassing 1043 participants with an average age of 64.61 years, identified a cutoff value of 0.32 for CAR, with notable variances observed across gender and age cohorts. Over an average follow-up period of 116 months, 679 instances of all-cause mortality were documented. Kaplan-Meier survival analysis unveiled noteworthy disparities in survival probabilities between groups categorized by high and low CAR levels (p = 0.00081). Continuous CAR analysis consistently demonstrated a positive correlation between elevated CAR values and heightened risk (HR = 1.78 (1.36, 2.33)) of all-cause mortality among stroke patients. Similarly, individuals in the high CAR group exhibited adjusted HR of 1.34 (0.96, 1.89) for all-cause mortality compared to their low CAR counterparts. Subgroup and sensitive analysis consistently reinforced these findings. Smoothing curve fitting further validated CAR's significance as a prognostic indicator of all-cause mortality, indicating a linear relationship. CONCLUSION: Elevated CAR is associated with increased long-term risk of mortality for individuals who have experienced a stroke, suggesting that CAR could serve as a survival indicator.


Asunto(s)
Biomarcadores , Proteína C-Reactiva , Estado Nutricional , Albúmina Sérica Humana , Accidente Cerebrovascular , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Biomarcadores/sangre , Proteína C-Reactiva/análisis , Causas de Muerte , Bases de Datos Factuales , Mediadores de Inflamación/sangre , Encuestas Nutricionales , Valor Predictivo de las Pruebas , Pronóstico , Medición de Riesgo , Factores de Riesgo , Albúmina Sérica Humana/análisis , Accidente Cerebrovascular/mortalidad , Accidente Cerebrovascular/sangre , Accidente Cerebrovascular/diagnóstico , Factores de Tiempo , Estados Unidos/epidemiología
14.
Microbiol Resour Announc ; 13(8): e0039424, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-38967470

RESUMEN

Bifidobacterium, a class of strictly anaerobic Gram-positive bacteria, existed mainly in the gut of humans and many mammals. Here, we report the complete genome sequence of Bifidobacterium animalis B01, whose genome length is 1,935,423 bp with a GC content of 60.49%.

15.
Microbiol Resour Announc ; 13(8): e0039524, 2024 Aug 13.
Artículo en Inglés | MEDLINE | ID: mdl-38975776

RESUMEN

Enterococcus faecalis, a gram-positive bacterium, is the main intestinal bacteria in humans and animals. We report here the complete genome sequence of E. faecalis B05, whose genome length is 2,745,741 bp, containing 2,503 protein-coding genes, with a GC content of 37.64%.

16.
Mikrochim Acta ; 191(8): 450, 2024 07 06.
Artículo en Inglés | MEDLINE | ID: mdl-38970684

RESUMEN

Gold nanoclusters (AuNCs) possess weak intrinsic fluorescence, limiting their sensitivity in biosensing applications. This study addresses these limitations by developing a spatially confined dual-emission nanoprobe composed of silicon nanoparticles (SiNPs) and AuNCs. This amplified and stabilized fluorescence mechanism overcomes the limitations associated with using AuNCs alone, achieving superior sensitivity in the sensing platform. The nanoprobe was successfully employed for ratiometric detection of bleomycin (BLM) in serum samples, operating at an excitation wavelength of 365 nm, with emission wavelengths at 480 nm and 580 nm. The analytical performance of the system is distinguished by a linear detection range of 0-3.5 µM, an impressive limit of detection (LOD) of 35.27 nM, and exceptional recoveries ranging from 96.80 to 105.9%. This innovative approach significantly enhances the applicability and reliability of AuNC-based biosensing in complex biological media, highlighting its superior analytical capabilities.


Asunto(s)
Técnicas Biosensibles , Oro , Límite de Detección , Nanopartículas del Metal , Silicio , Oro/química , Silicio/química , Técnicas Biosensibles/métodos , Nanopartículas del Metal/química , Nanopartículas/química , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia/métodos , Humanos
17.
iScience ; 27(7): 110163, 2024 Jul 19.
Artículo en Inglés | MEDLINE | ID: mdl-38974966

RESUMEN

Aging-related cardiac fibrosis represents the principal pathological progression in cardiovascular aging. The Muscleblind-like splicing regulator 2 (MBNL2) has been unequivocally established as being associated with cardiovascular diseases. Nevertheless, its role in aging-related cardiac fibrosis remains unexplored. This investigation revealed an elevation of MBNL2 levels in the aged heart and senescent cardiac fibroblasts. Notably, the inhibition of MBNL2 demonstrated a capacity to mitigate H2O2-induced myofibroblast transformation and aging-related cardiac fibrosis. Further mechanistic exploration unveiled that aging heightened the expression of SENP1 and impeded the SUMO1 binding with KLF4, and SUMOylation of KLF4 effectively increased by the inhibition of MBNL2. Additionally, the inhibition of TGF-ß1/SMAD3 signaling attenuated the impact of over-expression of MBNL2 in inducing senescence and cardiac fibrosis. MBNL2, by orchestrating SUMOylation of KLF4, upregulating the TGF-ß1/SMAD3 signaling pathway, emerges as a significant promoter of aging-related cardiac fibrosis. This discovery identifies a novel regulatory target for managing aging-related cardiac fibrosis.

18.
J Adv Res ; 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39019110

RESUMEN

INTRODUCTION: Lipid metabolism disorders have been confirmed to be closely related to kidney injury caused by adriamycin (ADR) and obesity, respectively. However, it has not been explored whether lipid metabolism disorders are related to kidney injury caused by ADR aggravated by obesity, and the specific molecular mechanism needs to be further clarified. OBJECTIVES: This study was designed to examine the role of p53-fibroblast growth factor 21 (FGF21) axis in ADR-induced renal injury aggravated by high fat diet (HFD). METHODS: We engineered Fgf21 KO mice and used long-term (4 months) and short-term (0.5 months) HFD feeding, and ADR-injected mice, as well as STZ-induced type 1 diabetic mice and type 2 (db/db) diabetic mice to produce a in vivo model of nephrotoxicity. The specific effects of p53/FGF21 on regulation of lipid metabolism disorders and its downstream mediators in kidney were subsequently elucidated using a combination of functional and pathological analysis, RNA-sequencing, molecular biology and in vitro approaches. RESULTS: Long-term HFD feeding mice exhibited compromised effects of FGF21 on alleviation of renal dysfunction and lipid accumulation following ADR administration. However, these impairments were reversed by p53 inhibitor (pifithrin-α, PFT-α). PFT-α sensitized FGF21 actions in kidney tissues, while knockout of Fgf21 impaired the protective effects of PFT-α on lipid metabolism. Mechanistically, p53 impaired the renal expression of FGF recepter-1 (FGFR1) and thereby developed gradually into FGF21 resistance via inhibiting hepatocyte nuclear factor alpha (HNF4α)-mediated transcriptional activation of Fgfr1. More importantly, exogenous supplementation of FGF21 or PFT-α could not only alleviate ADR-induced lipid metabolism disorder aggravated by HFD, but also reduce lipid accumulation caused by diabetic nephropathy. CONCLUSION: Given the difficulties in developing the long-acting recombinant FGF21 analogs for therapeutic applications, sensitizing obesity-impaired FGF21 actions by suppression of p53 might be a therapeutic strategy for maintaining renal metabolic homeostasis during chemotherapy.

20.
Molecules ; 29(13)2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38998939

RESUMEN

In this paper, four heteroleptic Ce(III) complexes, including Ce(thd)3-phen (thd = 2,2,6,6-tetramethyl-3,5-heptanedione, phen = 1, 10-phenanthroline (1), Ce(thd)3-MEDA (MEDA = N-Methylethylenediamine (2), Ce(thd)3-MOMA (MOMA = N-(2-Methoxyethyl)methylamine (3), and Ce(thd)3-DMDE (DMDE = N,N″-dimethyl ethanol amine (4), were synthesized and characterized with 1H-NMR, elemental analysis, and X-ray single-crystal diffraction. The thermogravimetric analysis and vapor pressure results indicated that the complexing ability of a nitrogen-containing bidentate ligand with a cerium ion was stronger than that of a mixed oxygen-nitrogen-containing bidentate ligand. Complex 2 was selected as an ALD precursor to deposit a CeO2 film on a SiO2/Si (100) wafer. The self-limited deposition results demonstrated that complex 2 was a potential ALD precursor.

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