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1.
J Colloid Interface Sci ; 678(Pt B): 20-29, 2025 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-39236351

RESUMEN

The off-stoichiometric compound Na3.12Fe2.44(P2O7)2 (NFPO) is a highly promising, cost-effective, and structurally robust cathode material for sodium-ion batteries (SIBs). However, the slowing Na-ion migration kinetics and poor interface stability have seriously limited its rate capability and air stability. In this work, we successfully synthesis a sodium titanium pyrophosphate (NaTiP2O7 donated as NTPO) coating NFPO (denoted as NFPO-NTPO) cathode material via a liquid phase coating method for SIBs. After optimizing NTPO content, at 0.1C, NFPO-NTPO-4 % cathode achieves a reversible specific capacity of 108.4 mAh g-1. Remarkably, it maintains 88.39 % capacity at 10C comparing to 0.1C and stabilizes over 3000 cycles with 92.66 % retention rate. Moreover, it retains 88.89 % capacity after 5000 cycles at 20C, even after 28 days of air exposure. The NFPO-Ti cathode, alongside the complete battery system, exhibits remarkable electrochemical performance across a broad temperature range spanning from -40 to 60 ℃.

2.
Cell Death Discov ; 10(1): 431, 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39384750

RESUMEN

Persistent macrophage activation and cytokine storms are critical causes for the rapid disease progression and high mortality rate of Secondary Hemophagocytic lymphohistiocytosis (sHLH). Identification of key regulatory factors that govern the activation of macrophages is vital. Plasma exosomal circular RNAs (circRNAs) are considered important biomarkers and potential therapeutic targets for various diseases, however, their function in sHLH is still unclear. In this study, we demonstrated for the first time that circMETTL3, derived from METTL3, is upregulated in sHLH patient plasma exosomes, which may plays an important role in the diagnosis of sHLH. Significantly, we also revealed that a novel peptide encoded by circMETTL3, METTL3-156aa, is an inducer of M1 macrophage polarization, which is responsible for the development of cytokine storms during sHLH. We then identified that METTL3-156aa binding with lactate dehydrogenase A (LDHA) and promotes M1 macrophage polarization by enhancing macrophage glycolysis. Additionally, the glycolysis metabolite lactate upregulates the cleavage factor SRSF10 expression by lactylation. This results in increased splicing of the pre-METTL3 mRNA, leading to an enchance in the production of cirMETTL3. Therefore, our results suggest that the circMETTL3/METTL3-156aa/LDHA/Lactate/SRSF10 axis forms a positive feedback loop and may be a novel therapeutic target for the treatment of sHLH.

3.
Int Immunopharmacol ; 143(Pt 2): 113335, 2024 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-39423662

RESUMEN

BACKGROUND: There is a significant global demand for precise diagnosis and effective treatment of IgA nephropathy (IgAN), with innate immunity, particularly the complement system, exerting a profound influence on its pathogenesis. Additionally, the gut-kidney axis pathway is vital in the emergence and development of IgAN. METHODS: We conducted a comprehensive search in the Web of Science database, spanning from January 1, 2000 to December 18, 2023. The gathered literature underwent a visual examination through CiteSpace, VOSviewer, and Scimago Graphica to delve into authors, nations, organizations, key terms, and other pertinent elements. RESULT: Between 2000 and 2023, a total of 720 publications were identified, out of which 436 publications underwent screening for highly relevant literature analysis. The average annual number of articles focusing on IgAN, innate immunity, and the gut-kidney axis is approximately 31, with an upward trend observed. In terms of research impact encompassing publication count and authorship, the United States emerged as the leading contributor. Prominent keywords included "complement", "activation", "microbe", "gut-kidney axis", "C4d deposition", "alternative pathway" and "B cells" along with other prospective hot topics. CONCLUSION: The correlation between IgAN and innate immunity is a focal point in current scientific research. Recent literature underscores the significance of the gut-kidney axis, where intestinal microorganisms and metabolites may influence IgAN. The complement system, a key component of innate immunity, also has a crucial function.Advancements in prevention, diagnosis, and treatment hinge on unraveling this intricate relationship.

4.
Gastrointest Endosc ; 2024 Oct 18.
Artículo en Inglés | MEDLINE | ID: mdl-39427992

RESUMEN

BACKGROUND AND AIMS: The integrity of image acquisition is critical for biliopancreatic Endoscopic Ultrasonography (EUS) reporting, significantly affecting the quality of EUS examinations and disease-related decision-making. However, the quality of EUS reports varies among endoscopists. To address this, we developed a deep learning-based EUS automatic image reporting system (EUS-AIRS), aiming to achieve automatic photodocumentation in real-time during EUS, including capturing standard stations, lesions, and puncture procedures. METHODS: Eight deep learning models trained and tested using 235,784 images were integrated to construct the EUS-AIRS. We tested the performance of EUS-AIRS through man-machine comparison at two levels: retrospective test (include internal and external test), and prospective test. From May 2023 to October 2023, 114 patients undergoing EUS at Renmin Hospital of Wuhan University were consecutively recruited for prospective test. The primary outcome was the completeness of the EUS-AIRS for capturing standard stations. RESULTS: In terms of completeness in capturing biliopancreatic standard stations, EUS-AIRS exceeds the capabilities of endoscopists at all levels of expertise in retrospective internal (90.8% [95%CI 88.7%-92.9%] vs. 70.5% [95%CI 67.2%-73.8%], p<0.001), and external test (91.4% [95%CI 88.4%-94.4%] vs 68.2% [95%CI 63.3%-73.2%], p<0.001). EUS-AIRS demonstrated high accuracy and completeness in capturing standard station images. The completeness significantly outperformed manual endoscopist reports: 91.4% [95%CI, 89.4% - 93.4%] vs. 78.1% [95%CI, 75.1% - 81.0%), p<0.001. CONCLUSIONS: EUS-AIRS exhibits exceptional capabilities in real-time capturing high-quality and high-integrity biliopancreatic EUS images, showcasing the potential of applying an artificial intelligence image reporting system in the EUS field.

5.
Front Med (Lausanne) ; 11: 1400166, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39371337

RESUMEN

Introduction: Sepsis poses a serious threat to individual life and health. Early and accessible diagnosis and targeted treatment are crucial. This study aims to explore the relationship between microbes, metabolic pathways, and blood test indicators in sepsis patients and develop a machine learning model for clinical diagnosis. Methods: Blood samples from sepsis patients were sequenced. α-diversity and ß-diversity analyses were performed to compare the microbial diversity between the sepsis group and the normal group. Correlation analysis was conducted on microbes, metabolic pathways, and blood test indicators. In addition, a model was developed based on medical records and radiomic features using machine learning algorithms. Results: The results of α-diversity and ß-diversity analyses showed that the microbial diversity of sepsis group was significantly higher than that of normal group (p < 0.05). The top 10 microbial abundances in the sepsis and normal groups were Vitis vinifera, Mycobacterium canettii, Solanum pennellii, Ralstonia insidiosa, Ananas comosus, Moraxella osloensis, Escherichia coli, Staphylococcus hominis, Camelina sativa, and Cutibacterium acnes. The enriched metabolic pathways mainly included Protein families: genetic information processing, Translation, Protein families: signaling and cellular processes, and Unclassified: genetic information processing. The correlation analysis revealed a significant positive correlation (p < 0.05) between IL-6 and Membrane transport. Metabolism of other amino acids showed a significant positive correlation (p < 0.05) with Cutibacterium acnes, Ralstonia insidiosa, Moraxella osloensis, and Staphylococcus hominis. Ananas comosus showed a significant positive correlation (p < 0.05) with Poorly characterized and Unclassified: metabolism. Blood test-related indicators showed a significant negative correlation (p < 0.05) with microorganisms. Logistic regression (LR) was used as the optimal model in six machine learning models based on medical records and radiomic features. The nomogram, calibration curves, and AUC values demonstrated that LR performed best for prediction. Discussion: This study provides insights into the relationship between microbes, metabolic pathways, and blood test indicators in sepsis. The developed machine learning model shows potential for aiding in clinical diagnosis. However, further research is needed to validate and improve the model.

6.
Ann Hematol ; 2024 Oct 27.
Artículo en Inglés | MEDLINE | ID: mdl-39463183

RESUMEN

Understanding the early features and characteristics of hemophagocytic lymphohistiocytosis (HLH) is essential for identifying high-risk individuals and also providing valuable pathological insights. This study aims to investigate the characteristics and trends of blood and hepatic parameters before an HLH diagnosis was established. Longitudinal hematological and hepatic test results from pediatric patients with HLH and an age- and sex-matched control group were analyzed. According to the length of time between hospital admission and the establishment of the HLH diagnosis, the HLH cases were divided into early-onset (≤ 7 days) and late-onset (> 7days) groups. Among the 229 pediatric HLH patients, the length of time between hospital admission and the establishment of an HLH diagnosis ranged from 0 to 41 days (median = 4 days). Over 80% of pediatric HLH patients presented abnormal laboratory results for aspartate aminotransferase (AST), triglycerides, lactate dehydrogenase (LDH), and hemoglobin at admission. The abnormal rates in the initial platelet count, neutrophil count, and fibrinogen tests were 67.3%, 48.3%, and 52.2%, respectively. The initial test results for AST, alanine aminotransferase (ALT), LDH, serum sodium, and albumin showed AUCs > 80% for discriminating early-onset HLH. For the discrimination of late-onset HLH, the performance of initial test results was poor. To conclude, abnormalities in AST, triglycerides, LDH, and hemoglobin are early presentations of pediatric HLH; platelet, neutrophil, and fibrinogen levels may become abnormal at a relatively late stage of the HLH disease trajectory; and the initial test results for AST, ALT, LDH, serum sodium, and albumin can be used to identify suspected early-onset HLH.

7.
Stem Cell Res Ther ; 15(1): 383, 2024 Oct 29.
Artículo en Inglés | MEDLINE | ID: mdl-39468666

RESUMEN

BACKGROUND: The prevalence of age-related disorders, particularly in neurological and cardiovascular systems, is an increasing global health concern. Mesenchymal stem cell (MSC) therapy, particularly using human umbilical cord-derived MSCs (HUCMSCs), has shown promise in mitigating these disorders. This study investigates the effects of HUCMSCs on aging-related conditions in a senescence-accelerated mouse model (SAMP8), with a focus on DNA damage, gut microbiota alterations, and metabolic changes. METHODS: SAMP8 mice were treated with clinical-grade HUCMSCs via intraperitoneal injections. Behavioral and physical assessments were conducted to evaluate cognitive and motor functions. The Single-Strand Break Mapping at Nucleotide Genome Level (SSiNGLe) method was employed to assess DNA single-strand breaks (SSBs) across the genome, with particular attention to exonic regions and transcription start sites. Gut microbiota composition was analyzed using 16S rRNA sequencing, and carboxyl metabolomic profiling was performed to identify changes in circulating metabolites. RESULTS: HUCMSC treatment significantly improved motor coordination and reduced anxiety in SAMP8 mice. SSiNGLe analysis revealed a notable reduction in DNA SSBs in MSC-treated mice, especially in critical genomic regions, suggesting that HUCMSCs may mitigate age-related DNA damage. The functional annotation of the DNA breaktome indicated a potential link between reduced DNA damage and altered metabolic pathways. Additionally, beneficial alterations in gut microbiota were observed, including an increase in short-chain fatty acid (SCFA)-producing bacteria, which correlated with improved metabolic profiles. CONCLUSION: The administration of HUCMSCs in SAMP8 mice not only reduces DNA damage but also induces favorable changes in gut microbiota and metabolism. The observed alterations in DNA break patterns, along with specific changes in microbiota and metabolic profiles, suggest that these could serve as potential biomarkers for evaluating the efficacy of HUCMSCs in treating age-related disorders. This highlights a promising avenue for the development of new therapeutic strategies that leverage these biomarkers, to enhance the effectiveness of HUCMSC-based treatments for aging-associated diseases.


Asunto(s)
Envejecimiento , Modelos Animales de Enfermedad , Células Madre Mesenquimatosas , Cordón Umbilical , Animales , Ratones , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , Humanos , Cordón Umbilical/citología , Cordón Umbilical/metabolismo , Trasplante de Células Madre Mesenquimatosas/métodos , Microbioma Gastrointestinal , Masculino , Daño del ADN , Multiómica
9.
Artículo en Inglés | MEDLINE | ID: mdl-39222242

RESUMEN

Obesity increases the risk of kidney injury, involving various pathological events such as inflammation, insulin resistance, lipid metabolism disorders, and hemodynamic changes, making it a significant risk factor for the development and progression of chronic kidney disease. Diosmin, a natural flavonoid glycoside, exhibits anti-inflammatory, antioxidant, anti-lipid, and vasodilatory effects. However, whether diosmin has a protective effect on obesity-related kidney injury remains unclear. The molecular formula of diosmin was obtained, and diosmin and target genes related to obesity-related kidney injury were screened. The interaction between overlapping target genes was analyzed. GO functional enrichment and KEGG pathway enrichment analyses were performed on overlapping target genes. Molecular docking was employed to assess the binding strength between overlapping target genes. Palmitic acid-induced damage to HK-2 cells, which were then treated with diosmin. Subsequently, the expression levels of relevant mRNAs and proteins were measured. Network analysis identified 219 potential diosmin target genes, 6800 potential target genes related to obesity-related kidney injury, and 93 potential overlapping target genes. Protein-protein interaction networks and molecular docking results revealed that AKT1, TNF-α, SRC, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2 were identified as key therapeutic targets, and they exhibited stable binding with diosmin. GO analysis indicated that these key targets may participate in inflammation, chemical stress, and protein phosphorylation. KEGG revealed that pathways in cancer, AGE-RAGE signaling pathway, PI3K-AKT signaling pathway, PPAR signaling pathway, and insulin resistance as crucial in treating obesity-related kidney injury. CCK-8 assay showed that diosmin significantly restored the viability of HK-2 cells affected by palmitic acid. Oil Red O staining demonstrated that diosmin significantly improved lipid deposition in HK-2 cells induced by palmitic acid. PCR results showed that diosmin inhibited the mRNA levels of AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, GSK-3ß, and MMP2 while promoting the mRNA level of PPAR-γ. Western blot analysis revealed that diosmin restored PPAR-γ protein expression, inhibited NF-kB p-p65 protein expression, and reduced TNF-α protein expression. Diosmin demonstrated multi-target and multi-pathway effects in the treatment of obesity-associated renal injury, with key targets including AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3ß, and MMP2. The mechanism may be through the modulation of the PPAR-γ/NF-κB signaling pathway, which can attenuate inflammatory responses and protect the kidney.

10.
Crit Rev Biotechnol ; : 1-16, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39266251

RESUMEN

Geraniol, an acyclic monoterpene alcohol, has significant potential applications in various fields, including: food, cosmetics, biofuels, and pharmaceuticals. However, the current sources of geraniol mainly include plant tissue extraction or chemical synthesis, which are unsustainable and suffer severely from high energy consumption and severe environmental problems. The process of microbial production of geraniol has recently undergone vigorous development. Particularly, the sustainable construction of recombinant Escherichia coli (13.2 g/L) and Saccharomyces cerevisiae (5.5 g/L) laid a solid foundation for the microbial production of geraniol. In this review, recent advances in the development of geraniol-producing strains, including: metabolic pathway construction, key enzyme improvement, genetic modification strategies, and cytotoxicity alleviation, are critically summarized. Furthermore, the key challenges in scaling up geraniol production and future perspectives for the development of robust geraniol-producing strains are suggested. This review provides theoretical guidance for the industrial production of geraniol using microbial cell factories.

11.
ACS Appl Mater Interfaces ; 16(38): 51542-51553, 2024 Sep 25.
Artículo en Inglés | MEDLINE | ID: mdl-39262374

RESUMEN

Conductive hydrogels have been increasingly employed to construct wearable mechanosensors due to their excellent mechanical flexibility close to that of soft tissues. In this work, piezoelectric hydrogels are prepared through free radical copolymerization of acrylamide (AM) and acrylonitrile (AN) and further utilized in assembling flexible wearable mechanosensors. Introduction of the polyacrylonitrile (PAN) component in the copolymers endows the hydrogels with excellent piezoelectric properties. Meanwhile, significant enhancement of mechanical properties has been accessed by forming dipole-dipole interactions, which results in a tensile strength of 0.51 MPa. Flexible wearable mechanosensors are fabricated by utilizing piezoelectric hydrogels as key signal converting materials. Self-powered piezoelectric pressure sensors are assembled with a sensitivity (S) of 0.2 V kPa-1. Additionally, resistive strain sensors (gauge factor (GF): 0.84, strain range: 0-250%) and capacitive pressure sensors (S: 0.23 kPa-1, pressure range: 0-8 kPa) are fabricated by utilizing such hydrogels. These flexible wearable mechanosensors can monitor diverse body movements such as joint bending, walking, running, and stair climbing. This work is anticipated to offer promising soft materials for efficient mechanical-to-electrical signal conversion and provides new insights into the development of various wearable mechanosensors.


Asunto(s)
Resinas Acrílicas , Hidrogeles , Dispositivos Electrónicos Vestibles , Hidrogeles/química , Resinas Acrílicas/química , Humanos , Resistencia a la Tracción , Acrilamida/química
12.
J Mol Model ; 30(9): 320, 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39223357

RESUMEN

CONTEXT: This work introduces a method for generating generalized structures of amorphous polymers using simulated polymerization and molecular dynamics equilibration, with a particular focus on amorphous polymers. The techniques and algorithms used in this method are described in the main text, and example input scripts are provided for the GMXPolymer code, which is based on the GROMACS molecular dynamics package. To demonstrate the efficacy of our method, we apply it to different glassy polymers exhibiting varying degrees of functionality, polarity, and rigidity. The reliability of the method is validated by comparing simulation results with experimental data in various structural and thermal properties, both of which show excellent agreement. METHODS: This work implements the GMXPolymer simulated polymerization algorithm on the GROMACS program. GMXPolymer code controls the main polymerization loop. The energy minimizations and molecular dynamics simulations use the GROMACS program called by the GMXPolymer code. A new ITP file is generated when a new bond is formed, and the necessary additions to the ITP file are made to include new bonds, angles, and dihedrals. In preparing the ITP file of the monomer, the charge of the reactive atom must be modified before the code runs so that it is a correct value after bonding.

13.
Microbiol Spectr ; 12(10): e0125724, 2024 Oct 03.
Artículo en Inglés | MEDLINE | ID: mdl-39166855

RESUMEN

Cell therapy represents a promising treatment modality. A critical component in the production of cell therapy products is maintaining the sterility of cell therapy clean rooms (CTCRs). This study aimed to evaluate the environmental microbial load within CTCRs. We systematically monitored microbial load in CTCRs, following established guidelines. Cultured microbial samples underwent metagenomic sequencing, and alpha and beta diversity analyses, functional annotation, and resistance gene profiling were performed using various bioinformatics tools to assess microbial diversity and function. From November 2023 to January 2024, we collected 42 environmental microbial colony samples from various sources within the CTCR and performed metagenomic sequencing on 39 samples. Alpha diversity analysis revealed no significant differences among surface, settle_plate, and airborne categories, but significant disparities within surface subgroups were revealed. Beta diversity analysis showed notable differences between surface and airborne categories and among surface subgroups. Species distribution analysis identified Bacillus as the predominant genus on surfaces. Functional annotation and resistance gene analysis indicated distinct resistance patterns, with significant variations between subgroups, such as microscopes and transfer windows, and hands and other Grade_B environments. Resistance to hydrogen peroxide was notably higher in the transfer window group. These findings highlight the importance of stringent disinfection protocols and enhanced hand hygiene to maintain sterility in CTCRs. These findings provide valuable insights for implementing effective measures to maintain cleanliness throughout CTCRs. The annotation and study of resistance genes can help rapidly identify methods to control cellular contamination under circumstances of environmental microbial pollution.IMPORTANCEMaintaining the sterility of cell therapy clean rooms (CTCRs) is crucial for the production of safe and effective cell therapy products. Our study systematically evaluated the environmental microbial load within CTCRs, revealing significant microbial diversity and distinct resistance patterns to disinfection methods. These findings underscore the need for stringent disinfection protocols and enhanced hand hygiene practices to ensure CTCR sterility. By identifying key microbial species and their resistance genes, our research provides essential insights into controlling contamination and safeguarding the production environment, ultimately contributing to the reliability and success of cell therapy treatments.


Asunto(s)
Bacterias , Tratamiento Basado en Trasplante de Células y Tejidos , Microbiología Ambiental , Humanos , Tratamiento Basado en Trasplante de Células y Tejidos/métodos , Bacterias/genética , Bacterias/clasificación , Bacterias/aislamiento & purificación , Hospitales , Desinfección/métodos , Ambiente Controlado , Laboratorios
14.
J Int Med Res ; 52(8): 3000605241274591, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39188138

RESUMEN

Renal calyceal neck atresia is a rare disorder. There is no clear guidance for standard treatment of this condition. The Memokath™ 045 temperature-controlled memory alloy stent is commonly used in the treatment of urethral strictures, but it has not been used for treating calyceal neck atresia. We present a case of a 44-year-old female patient with left lumbar pain who underwent two stages of treatment to resolve calyceal neck atresia located at the upper calyx of her left kidney. The first procedure was transurethral ureteroscopy combined with percutaneous recanalization of the left upper calyx calyceal neck atresia. One 6 F internal stent and one 8 F internal stent were placed, and she was discharged with a left nephrostomy tube. After her urinary tract infection was fully resolved, the patient returned for the second procedure of percutaneous upper renal calyx calyceal neck metal stent implantation. The temporary stents and nephrostomy tube were successfully removed. Our findings suggest that the Memokath™ 045 temperature-controlled memory alloy stent is an effective choice for treating calyceal neck atresia.


Asunto(s)
Aleaciones , Cálices Renales , Stents , Humanos , Femenino , Adulto , Cálices Renales/cirugía , Cálices Renales/anomalías , Temperatura , Resultado del Tratamiento
15.
BMC Cardiovasc Disord ; 24(1): 411, 2024 Aug 08.
Artículo en Inglés | MEDLINE | ID: mdl-39118024

RESUMEN

AIMS: To assess the correlation between high-sensitivity C-reactive protein (Hs-CRP) and the prevalence of cardiovascular disease (CVD) among individuals with diabetes. METHODS: A total of 1,555 participants from the National Health and Nutrition Examination Survey were enrolled in this cross-sectional study after excluding individuals without diabetes and those who lacked data on Hs-CRP, diabetes and CVD. All participants were divided into four groups based on quartiles of Hs-CRP: Q1 (≤ 1.20 mg/L), Q2 (1.20-2.86 mg/L), Q3 (2.86-6.40 mg/L), and Q4 (> 6.40 mg/L). Logistic regression analysis, subgroup analysis and restricted cubic spline (RCS) analysis were used to evaluate the correlation between Hs-CRP and the prevalence of CVD in individuals with diabetes. RESULTS: In univariate logistic regression analysis, a higher level of Hs-CRP was associated with a higher prevalence of CVD (P < 0.05). In the multivariate logistic regression analysis adjusting for confounders, the correlation between Hs-CRP and the prevalence of CVD remained significant (Q3 vs. Q1, OR: 1.505, 95% CI: 1.056-2.147, P = 0.024; Q4 vs. Q1, OR: 1.711, 95% CI: 1.171-2.499, P = 0.006; log10(Hs-CRP), OR: 1.504, 95% CI: 1.168-1.935, P = 0.002). Further subgroup analysis showed that a higher Hs-CRP was independently associated with a higher prevalence of CVD in the < 60 years, male, non-hypertension and non-hypercholesterolemia subgroups (P < 0.05). Additionally, RCS analysis revealed a linear positive correlation between Hs-CRP and CVD prevalence (P for nonlinearity = 0.244). CONCLUSION: A higher level of Hs-CRP was closely related to a higher prevalence of CVD in people with diabetes.


Asunto(s)
Biomarcadores , Proteína C-Reactiva , Enfermedades Cardiovasculares , Diabetes Mellitus , Encuestas Nutricionales , Humanos , Masculino , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Persona de Mediana Edad , Femenino , Estudios Transversales , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/diagnóstico , Prevalencia , Diabetes Mellitus/epidemiología , Diabetes Mellitus/sangre , Diabetes Mellitus/diagnóstico , Biomarcadores/sangre , Adulto , Anciano , Factores de Riesgo , Modelos Lineales , Análisis Multivariante , Modelos Logísticos , Regulación hacia Arriba , Oportunidad Relativa , Medición de Riesgo
16.
Eur J Med Chem ; 277: 116769, 2024 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-39163778

RESUMEN

Phosphodiesterases (PDEs) constitute a family of enzymes that play a pivotal role in the regulation of intracellular levels of cyclic nucleotides, including cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP). Dysregulation of PDE activity has been implicated in diverse pathological conditions encompassing cardiovascular disorders, pulmonary diseases, and neurological disorders. Small-molecule inhibitors targeting PDEs have emerged as promising therapeutic agents for the treatment of these ailments, some of which have been approved for their clinical use. Despite their success, challenges such as resistance mechanisms and off-target effects persist, urging continuous research for the development of next-generation PDE inhibitors. The objective of this review is to provide an overview of the synthesis and clinical application of representative approved small-molecule PDE inhibitors, with the aim of offering guidance for further advancements in the development of novel PDE inhibitors.


Asunto(s)
Inhibidores de Fosfodiesterasa , Hidrolasas Diéster Fosfóricas , Bibliotecas de Moléculas Pequeñas , Animales , Humanos , Estructura Molecular , Inhibidores de Fosfodiesterasa/farmacología , Inhibidores de Fosfodiesterasa/síntesis química , Inhibidores de Fosfodiesterasa/química , Hidrolasas Diéster Fosfóricas/metabolismo , Bibliotecas de Moléculas Pequeñas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/síntesis química , Relación Estructura-Actividad , AMP Cíclico/química , AMP Cíclico/metabolismo , AMP Cíclico/farmacología
17.
J Am Chem Soc ; 146(36): 24871-24883, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39213650

RESUMEN

Organic room-temperature phosphorescence (RTP) and afterglow materials hold great potential for various applications, but there remain inherent trade-offs between the afterglow efficiency and the lifetime. Here, we propose a dual-mechanism design strategy, leveraging the RTP or thermally activated delayed fluorescence (TADF) mechanism for a high afterglow efficiency and the organic long-persistent luminescence (OLPL) mechanism for a prolonged afterglow duration. The intramolecular charge transfer (ICT)-type difluoroboron ß-diketonate molecules with a large S1 dipole moment are doped as the luminescent component into the organic matrix with a large dipole moment, and a series of TADF-type afterglow materials can be achieved with an afterglow efficiency of up to 88.7% and an afterglow lifetime of 200 ms. To prolong the afterglow duration, an electron donor is introduced as the third component to generate traps and facilitate charge separation. The obtained materials exhibit a dual afterglow mechanism, first exhibiting a TADF/RTP afterglow with an afterglow efficiency of up to 50.9%, followed by an hours-long OLPL afterglow emission with an afterglow efficiency of up to 13.1%. Further investigations reveal that an appropriate heavy-atom effect can facilitate the intersystem crossing process, which can promote the charge separation process and thus improve the OLPL afterglow performance. Additionally, rare-earth upconversion materials are introduced into OLPL materials to enable their near-infrared excitation properties, showcasing their potential applications in bioimaging.

18.
Front Biosci (Landmark Ed) ; 29(8): 283, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-39206889

RESUMEN

BACKGROUND: Humankind have been struggling with colorectal cancer (CRC) for long period with its rapid progression and invasive metastasis. By hyperactivating IL-6/STAT3 signaling, CRC facilitates the capacity of angiogenesis to plunder massive nutrients and develops gradually under harsh condition. METHODS: The Cancer Genome Atlas database was analyzed for acquiring interferon-γ inducible protein 10 (IFITM10) expression levels and their correlation with clinical outcomes. The cell angiogenic ability were assessed by Cell Counting Kit-8 (CCK-8) and tube formation assay. Immunofluorescence, Western blot, and enzyme-linked immunosorbent assay (ELISA) assay were using to assess potential mechanism. RESULTS: In our study, we find that IFITM10 is upregulated in CRC and is positively related with tumor angiogenesis. We also find that IFITM inhibition decreased STAT3 phosphorylation level and IFITM10-mediated angiogenesis depends on STAT3 activation. Furthermore, our data suggests that IFITM10 may be a key prognostic biomarker in colorectal cancer. CONCLUSION: Together, our study suggests that IFITM10 enhance angiogenesis through STAT3 activation during CRC progression, which highlighting its potency as a therapeutic target for colorectal cancer.


Asunto(s)
Neoplasias Colorrectales , Progresión de la Enfermedad , Neovascularización Patológica , Factor de Transcripción STAT3 , Factor de Transcripción STAT3/metabolismo , Humanos , Neovascularización Patológica/metabolismo , Neovascularización Patológica/genética , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/irrigación sanguínea , Línea Celular Tumoral , Transducción de Señal , Regulación Neoplásica de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Fosforilación , Pronóstico , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Angiogénesis , Antígenos de Diferenciación
19.
bioRxiv ; 2024 Aug 11.
Artículo en Inglés | MEDLINE | ID: mdl-39211188

RESUMEN

Glycogen-autophagy ('glycophagy') is a selective autophagy process involved in delivering glycogen to the lysosome for bulk degradation. Glycophagy protein intermediaries include STBD1 as a glycogen tagging receptor, delivering the glycogen cargo into the forming phagosome by partnering with the Atg8 homolog, GABARAPL1. Glycophagy is emerging as a key process of energy metabolism and development of reliable tools for assessment of glycophagy activity is an important priority. Here we show that antibodies raised against the N-terminus of the GABARAPL1 protein (but not the full-length protein) detected a specific endogenous GABARAPL1 immunoblot band at 18kDa. A stable GFP-GABARAPL1 cardiac cell line was used to quantify GABARAPL1 lysosomal flux via measurement of GFP puncta in response to lysosomal inhibition with bafilomycin. Endogenous glycophagy flux was quantified in primary rat ventricular myocytes by the extent of glycogen accumulation with bafilomycin combined with chloroquine treatment (no effect observed with bafilomycin or chloroquine alone). In wild-type isolated mouse hearts, bafilomycin alone and bafilomycin combined with chloroquine (but not chloroquine alone) elicited a significant increase in glycogen content signifying basal glycophagy flux. Collectively, these methodologies provide a comprehensive toolbox for tracking cardiac glycophagy activity to advance research into the role of glycophagy in health and disease.

20.
Artículo en Inglés | MEDLINE | ID: mdl-39166764

RESUMEN

BACKGROUND: A precise model for predicting outcomes is needed to guide perioperative management. With the developments of liver transplantation (LT) discipline, previous models may become inappropriate or noncomprehensive. Thus, we aimed to develop a novel model integrating variables from donors and recipients for quick assessment of transplant outcomes. METHODS: The risk model was based on Cox regression in a randomly selected derivation cohort and verified in a validation cohort. Perioperative data and overall survival were compared between stratifications grouped by X-tile. Receiver operating characteristic curve and decision curve analysis were used to compare the models. Violin and raincloud plots were generated to present post-LT complications distributed in different stratifications. RESULTS: Overall, 528 patients receiving LT from 2 centers were included with 2/3 in the derivation cohort and 1/3 in the validation cohort. Cox regression analysis showed that cold ischemia time (CIT) (P=0.012) and the Model for End-Stage Liver Disease (MELD) (P=0.007) score were predictors of survival. After comparison with the logarithmic models, the primitive algorithms of CIT and MELD were defined as the CIT-MELD Index (CMI). CMI was stratified by X-tile (grade 1 ≤1.06, 1.06< grade 2 ≤1.87, grade 3 >1.87). In both cohorts, CMI performed better in calculating transplant outcomes than the balance of risk score, including perioperative incidents and prevalence of complications. CONCLUSIONS: Model integrating variables from graft and recipient made the prediction more accurate and available. CMI provided new sight in outcome evaluation and risk factor management of LT.

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