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Harvest season exerts great influence on tea quality. Herein, the variations in non-volatile flavor substances in spring and summer fresh tea leaves of four varieties were comprehensively investigated by integrating UHPLC-Q-Exactive based lipidomics and metabolomics. A total of 327 lipids and 99 metabolites were detected, among which, 221 and 58 molecules were significantly differential. The molecular species of phospholipids, glycolipids and acylglycerolipids showed most prominent and structure-dependent seasonal changes, relating to polar head, unsaturation and total acyl length. Particularly, spring tea contained higher amount in aroma precursors of highly unsaturated glycolipids and phosphatidic acids. The contents of umami-enhancing amino acids and phenolic acids, e.g., theanine, theogallin and gallotannins, were increased in spring. Besides, catechins, theaflavins, theasinensins and flavone/flavonol glycosides showed diverse changes. These phytochemical differences covered key aroma precursors, tastants and colorants, and may confer superior flavor of black tea processed using spring leaves, which was verified by sensory evaluation.
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Camellia sinensis , Aromatizantes , Lipidómica , Espectrometría de Masas , Metabolómica , Hojas de la Planta , Estaciones del Año , Camellia sinensis/química , Camellia sinensis/metabolismo , Hojas de la Planta/química , Hojas de la Planta/metabolismo , Cromatografía Líquida de Alta Presión , Aromatizantes/química , Aromatizantes/metabolismo , Humanos , Gusto , Odorantes/análisis , Lípidos/análisis , Lípidos/químicaRESUMEN
The heart relies on various defense mechanisms, including metabolic plasticity, to maintain its normal structure and function under high-altitude hypoxia. Pioglitazone, a peroxisome proliferator-activated receptor γ (PPARγ), sensitizes insulin, which in turn regulates blood glucose levels. However, its preventive effects against hypoxia-induced cardiac dysfunction at high altitudes have not been reported. In this study, pioglitazone effectively prevented cardiac dysfunction in hypoxic mice for 4 weeks, independent of its effects on insulin sensitivity. In vitro experiments demonstrated that pioglitazone enhanced the contractility of primary cardiomyocytes and reduced the risk of QT interval prolongation under hypoxic conditions. Additionally, pioglitazone promoted cardiac glucose metabolic reprogramming by increasing glycolytic capacity; enhancing glucose oxidation, electron transfer, and oxidative phosphorylation processes; and reducing mitochondrial reactive ROS production, which ultimately maintained mitochondrial membrane potential and ATP production in cardiomyocytes under hypoxic conditions. Notably, as a PPARγ agonist, pioglitazone promoted hypoxia-inducible factor 1α (HIF-1α) expression in hypoxic myocardium. Moreover, KC7F2, a HIF-1α inhibitor, disrupted the reprogramming of cardiac glucose metabolism and reduced cardiac function in pioglitazone-treated mice under hypoxic conditions. In conclusion, pioglitazone effectively prevented high-altitude hypoxia-induced cardiac dysfunction by reprogramming cardiac glucose metabolism.
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Glucosa , Hipoxia , Miocitos Cardíacos , PPAR gamma , Pioglitazona , Pioglitazona/farmacología , Pioglitazona/uso terapéutico , Animales , PPAR gamma/metabolismo , PPAR gamma/agonistas , Ratones , Glucosa/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Hipoxia/complicaciones , Hipoxia/metabolismo , Masculino , Ratones Endogámicos C57BL , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Tiazolidinedionas/farmacología , Tiazolidinedionas/uso terapéutico , Especies Reactivas de Oxígeno/metabolismoRESUMEN
With rapidly evolving high-throughput technologies and consistently decreasing costs, collecting multimodal omics data in large-scale studies has become feasible. Although studying multiomics provides a new comprehensive approach in understanding the complex biological mechanisms of human diseases, the high dimensionality of omics data and the complexity of the interactions among various omics levels in contributing to disease phenotypes present tremendous analytical challenges. There is a great need of novel analytical methods to address these challenges and to facilitate multiomics analyses. In this paper, we propose a multimodal functional deep learning (MFDL) method for the analysis of high-dimensional multiomics data. The MFDL method models the complex relationships between multiomics variants and disease phenotypes through the hierarchical structure of deep neural networks and handles high-dimensional omics data using the functional data analysis technique. Furthermore, MFDL leverages the structure of the multimodal model to capture interactions between different types of omics data. Through simulation studies and real-data applications, we demonstrate the advantages of MFDL in terms of prediction accuracy and its robustness to the high dimensionality and noise within the data.
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Aprendizaje Profundo , Genómica , Humanos , Genómica/métodos , Biología Computacional/métodos , Redes Neurales de la Computación , Algoritmos , MultiómicaRESUMEN
Peptidylarginine deiminase 4 (PAD4)-dependent neutrophil extracellular trap (NET) formation is a new neutrophil death mechanism. Increased NET formation has been demonstrated to be associated with gouty inflammation. Macrophages release proinflammatory mediators and chemokines in acute gouty inflammation and subsequently lead to inflammatory cascades. However, whether NETs regulate macrophage function and polarization and further contribute to gout development remains unclear. Herein, we investigated the relationship between monosodium urate (MSU) crystal-induced NETs and macrophages and the associated mechanisms in gouty inflammation. Elevated NET formation and CD86+ macrophage infiltration were observed in human gouty arthritis (GA). In vitro, MSU crystal-induced NETs or NET-associated histone H3 treatments modulated nod-like receptor protein 3 (NLRP3) inflammasome activation, M1 polarization, and metabolic changes in macrophages. These effects were eliminated by hexokinase-2 (HK-2) silencing. Moreover, NET formation and inflammation were significantly reduced in PAD4-/- GA mice. Pharmacological inhibition of NET formation with Cl-Amidine or NET degradation with DNase â significantly reduced M1 polarization of macrophages and ameliorated inflammation in GA mice. In sum, MSU crystal-induced NETs promote M1 polarization and NLRP3 activation in macrophages via targeting HK-2. Cell-free DNA and histone H3 may be the driving elements behind the NET-induced M1 macrophage polarization, NLRP3 activation, and metabolic changes. Targeting NETs could be a potential therapeutic strategy for gout flare.
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To understand the prevalence of cognitive impairment (CI) in middle-aged and elderly individuals in Anhui Province and to develop a CI risk prediction model. From May to June 2022, a multistage, stratified cluster-sampling method was used to select 3200 middle-aged and elderly people over 45 years old in Anhui Province for a questionnaire survey, and the Chinese version of the Mini-Mental State Examination (MMSE) was used to assess cognitive function. SPSS 25.0 was used for univariate and multivariate analyses, and R software was used to establish and validate the nomogram. A total of 3059 valid questionnaires were included, of which 384 were from participants who were diagnosed with CI, and the prevalence rate was 12.6%. Multivariate logistic analysis showed that female sex, advanced age, family history, etc., were closely related to the occurrence of CI. The area under curve (AUC) values in the modeling and validation groups were 0.845 (95% CI: 0.822-0.868) and 0.868 (95% CI: 0.835-0.902), respectively, indicating that the predictive ability of the model was good. The Hosmer-Lemeshow test suggested that the model had good goodness-of-fit, and the decision-curve evaluation nomogram had a high benefit within the threshold, which had a certain clinical importance. The prevalence rate of CI among middle-aged and elderly individuals in Anhui Province was 12.6%. Female sex, elderly age, family history, low educational status, current smoking status, sleep disorders, hypertension, stroke, and diabetes were shown to be risk factors for CI, while exercise was shown to be a protective factor.
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Disfunción Cognitiva , Humanos , Femenino , Disfunción Cognitiva/epidemiología , Masculino , China/epidemiología , Prevalencia , Persona de Mediana Edad , Anciano , Factores de Riesgo , Pruebas de Estado Mental y Demencia , Encuestas y Cuestionarios , Nomogramas , Anciano de 80 o más Años , Factores de Edad , Factores Sexuales , Estudios TransversalesRESUMEN
Nerve invasion (NI) is a characteristic feature of pancreatic cancer. Traditional dichotomous statements on the presence of NI are unreasonable because almost all cases exhibit NI when sufficient pathological sections are examined. The critical implications of NI in pancreatic cancer highlight the need for a more effective criterion. This study included 511 patients, who were categorized into a training group and a testing group at a ratio of 7:3. According to the traditional definition, NI was observed in 91.2 % of patients using five pathological slides in our study. The prevalence of NI increased as more pathological slides were used. The criterion of 'two points of intraneural (endoneural) invasion in the case of four pathological slides' has the highest receiver operating characteristic (ROC) score. Based on this new criterion, NI was proved to be an independent prognostic factor for overall survival (OS) and disease-free survival (DFS) and was also correlated with tumor recurrence (P = 0.004). Interestingly, gemcitabine-based chemotherapy regimen is an independent favorable factor for patients with high NI. In the high NI group, patients who received a gemcitabine-based regimen exhibited a better prognosis than those who did not receive the gemcitabine-based regimen for OS (P = 0.000) and DFS (P = 0.001). In conclusion, this study establishes assessment criteria to evaluate the severity of NI in order to predict patient outcomes.
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Invasividad Neoplásica , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/cirugía , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Adulto , Supervivencia sin Enfermedad , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapéutico , Gemcitabina , Curva ROC , Anciano de 80 o más Años , PronósticoRESUMEN
BACKGROUND: Patients with psoriatic arthritis (PsA) often suffer from anxiety disorders. While upadacitinib has shown effectiveness in reducing various disease activity indicators in active PsA, its impact on anxiety disorders in PsA patients needs further investigation. METHODS: In this 12-week randomized, open-label, controlled trial, PsA patients with coexisting anxiety were randomly assigned to either the upadacitinib group or the adalimumab group in a 1:1 ratio. The upadacitinib group received a daily dose of 15 mg, while the adalimumab group received 40 mg every 2 weeks. The primary outcome measured the change in Hospital Anxiety Self-Assessment Scale (HADS-A) total scores after the 12-week intervention. Secondary outcomes included changes in the Health Assessment Questionnaire-Disability Index (HAQ-DI), the percentage of participants meeting the ACR20 criteria compared to baseline after 12 weeks, and the percentage of participants achieving a grade 0 or 1 in the psoriasis static Investigator's overall assessment (sPGA) at week 12 with an improvement of at least 2 points from baseline (sPGA 0/1). One-way analysis of variance (ANOVA) was used to compare the means of normally distributed variables between the upadacitinib and adalimumab groups. DISCUSSION: The impact of upadacitinib on anxiety in PsA patients remains uncertain. This 12-week open randomized controlled trial aims to provide insights into disease progression and underscore the importance of addressing PsA-related anxiety during treatment. TRIAL REGISTRATION: ChiCTR2400079755. Registered on January 11, 2024, with ChiCTR. https://www.chictr.org.cn/showproj.html?proj=216538.
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Adalimumab , Ansiedad , Artritis Psoriásica , Compuestos Heterocíclicos con 3 Anillos , Humanos , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/psicología , Adalimumab/uso terapéutico , Ansiedad/tratamiento farmacológico , Ansiedad/psicología , Ansiedad/diagnóstico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Resultado del Tratamiento , Ensayos Clínicos Controlados Aleatorios como Asunto , Masculino , Femenino , Persona de Mediana Edad , Adulto , Antirreumáticos/uso terapéutico , Antirreumáticos/efectos adversos , Factores de TiempoRESUMEN
BACKGROUND: This study investigates the molecular mechanisms of CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and sorafenib (SF) for improving hepatitis B virus-related hepatocellular carcinoma (HBV-HCC). METHODS: A dataset of 44 HBV-HCC patients and their survival information was selected from the TCGA database. Immune genes related to survival status were identified using the ImmPort database and WGCNA analysis. A prognostic risk model was constructed and analyzed using Lasso regression. Differential analysis was performed to screen key genes, and their significance and predictive accuracy for HBV-HCC were validated using Kaplan-Meier survival curves, ROC analysis, CIBERSORT analysis, and correlation analysis. The correlation between AC099850.3 and the gene expression matrix was calculated, followed by GO and KEGG enrichment analysis using AC099850.3 and its co-expressed genes. HepG2.2.15 cells were selected for in vitro validation, and lentivirus interference, cell cycle determination, CCK-8 experiments, colony formation assays, Transwell experiments, scratch experiments, and flow cytometry were performed to investigate the effects of key genes on HepG2.2.15 cells. A subcutaneous transplanted tumor model in mice was constructed to verify the inhibitory effect of key genes on HBV-HCC tumors. Subsequently, pH-triggered drug release NPs (CC@AC&SF@PP) were prepared, and their therapeutic effects on HBV-HCC in situ tumor mice were studied. RESULTS: A prognostic risk model (AC012313.9, MIR210HG, AC099850.3, AL645933.2, C6orf223, GDF10) was constructed through bioinformatics analysis, showing good sensitivity and specificity in diagnostic prediction. AC099850.3 was identified as a key gene, and enrichment analysis revealed its impact on cell cycle pathways. In vitro cell experiments demonstrated that AC099850.3 promotes HepG2.2.15 cell proliferation and invasion by regulating immune checkpoint CD276 expression and cell cycle progression. In vivo, subcutaneously transplanted tumor experiments showed that AC099850.3 promotes the growth of HBV-HCC tumors in nude mice. Furthermore, pH-triggered drug release NPs (CC@AC&SF@PP) loaded with AC099850.3 siRNA and SF were successfully prepared and delivered to the in situ HBV-HCC, enhancing the effectiveness of combined therapy for HBV-HCC. CONCLUSIONS: AC099850.3 accelerates the cell cycle progression and promotes the occurrence and development of HBV-HCC by upregulating immune checkpoint CD276 expression. CC@AC&SF@PP NPs loaded with AC099850.3 siRNA and SF improve the effectiveness of combined therapy for HBV-HCC.
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Antígenos B7 , Carcinoma Hepatocelular , Proliferación Celular , Virus de la Hepatitis B , Neoplasias Hepáticas , Invasividad Neoplásica , Sorafenib , Humanos , Sorafenib/farmacología , Sorafenib/uso terapéutico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/virología , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/virología , Proliferación Celular/efectos de los fármacos , Animales , Antígenos B7/metabolismo , Antígenos B7/genética , Células Hep G2 , Virus de la Hepatitis B/efectos de los fármacos , Ratones Desnudos , Ratones , Quitosano/química , Quitosano/farmacología , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Masculino , Hepatitis B/tratamiento farmacológico , Hepatitis B/virología , Ratones Endogámicos BALB CRESUMEN
Nitrites (NO2-/HONO), as the primary source of hydroxyl radicals (â¢OH) in the atmosphere, play a key role in atmospheric chemistry. However, the current understanding of the source of NO2-/HONO is insufficient and therefore hinders the accurate quantification of atmospheric oxidation capacity. Herein, we highlighted an overlooked HONO source by the reaction between nitrophenols (NPs) and â¢OH in the aqueous phase and provided kinetic data to better evaluate the contribution of this process to atmospheric HONO. Three typical NPs, including 4-nitrophenol (4NP), 2-nitrophenol (2NP), and 4-nitrocatechol (4NC), underwent a denitration process to form aqueous NO2- and gaseous HONO through the â¢OH oxidation, with the yield of NO2-/HONO varied from 15.0 to 33.5%. According to chemical composition and structure analysis, the reaction pathway, where the ipso addition of â¢OH to the NO2 group on 4NP generated hydroquinone, can contribute to more than 61.9% of the NO2-/HONO formation. The aqueous photooxidation of NPs may account for HONO in the atmosphere, depending on the specific conditions. The results clearly suggest that the photooxidation of NPs should be considered in the field observation and calculation to better evaluate the HONO budget in the atmosphere.
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Nitrofenoles , Oxidación-Reducción , Nitrofenoles/química , Nitritos/química , Atmósfera/química , Radical Hidroxilo/química , Agua/química , CinéticaRESUMEN
Rationale: Cardiomyocytes (CMs) undergo dramatic structural and functional changes in postnatal maturation; however, the regulatory mechanisms remain greatly unclear. Cypher/Z-band alternatively spliced PDZ-motif protein (ZASP) is an essential sarcomere component maintaining Z-disc stability. Deletion of mouse Cypher and mutation in human ZASP result in dilated cardiomyopathy (DCM). Whether Cypher/ZASP participates in CM maturation and thereby affects cardiac function has not been answered. Methods: Immunofluorescence, transmission electron microscopy, real-time quantitative PCR, and Western blot were utilized to identify the role of Cypher in CM maturation. Subsequently, RNA sequencing and bioinformatics analysis predicted serum response factor (SRF) as the key regulator. Rescue experiments were conducted using adenovirus or adeno-associated viruses encoding SRF, both in vitro and in vivo. The molecular mechanisms were elucidated through G-actin/F-actin fractionation, nuclear-cytoplasmic extraction, actin disassembly assays, and co-sedimentation assays. Results: Cypher deletion led to impaired sarcomere isoform switch and morphological abnormalities in mitochondria, transverse-tubules, and intercalated discs. RNA-sequencing analysis revealed significant dysregulation of crucial genes related to sarcomere assembly, mitochondrial metabolism, and electrophysiology in the absence of Cypher. Furthermore, SRF was predicted as key transcription factor mediating the transcriptional differences. Subsequent rescue experiments showed that SRF re-expression during the critical postnatal period effectively rectified CM maturation defects and notably improved cardiac function in Cypher-depleted mice. Mechanistically, Cypher deficiency resulted in the destabilization of F-actin and a notable increase in G-actin levels, thereby impeding the nuclear localisation of myocardin-related transcription factor A (MRTFA) and subsequently initiating SRF transcription. Conclusion: Cypher/ZASP plays a crucial role in CM maturation through actin-mediated MRTFA-SRF signalling. The linkage between CM maturation abnormalities and the late-onset of DCM is suggested, providing further insights into the pathogenesis of DCM and potential treatment strategies.
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Actinas , Cardiomiopatía Dilatada , Miocitos Cardíacos , Factor de Respuesta Sérica , Transducción de Señal , Transactivadores , Animales , Miocitos Cardíacos/metabolismo , Factor de Respuesta Sérica/metabolismo , Factor de Respuesta Sérica/genética , Ratones , Actinas/metabolismo , Transactivadores/metabolismo , Transactivadores/genética , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/patología , Sarcómeros/metabolismo , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Humanos , Ratones NoqueadosRESUMEN
Purpose: Kidney transplantation (KT) has the potential to reverse the cardiac changes caused by end-stage renal disease, and it may be inaccurate to analysis the left ventricular function by conventional echocardiography due to afterload. This study aimed to investigate the utility of pressure strain loops (PSLs) in evaluating left ventricular performance in patients underwent KT. Methods: We enrolled 60 patients with end-stage renal disease who underwent KT between January 2022 and July 2023, and 60 healthy controls with a similar distribution of gender and age to the patients. All participants underwent conventional echocardiography and three-dimensional speckle tracking echocardiography (3D-STE). Long axis, short axis, and four cavity images were collected and cardiac parameters were measured. The echocardiographic changes of cardiac structure and function of all patients before KT and about 12 months after KT were recorded. Left ventricular myocardial work parameters were acquired by PSLs, including the global work index (GWI), global constructive work (GCW), global wasted work (GWW), global work efficiency (GWE) and global longitudinal strain (GLS). In addition, the correlation between PSLs and clinical data were explored. Results: Compared with controls, the conventional echocardiographic parameters, myocardial function indicators GWI and GCW appeared no difference in post-KT group, while the GWE and GLS decreased (p < 0.05), and the GWW increased (p < 0.05). Compared with pre-KT, the GLS, GWI, GCW and GWE increased in post-KT group, while the GWW decreased (all p < 0.05). The above indicators were correlated with left ventricular GLS and left ventricular ejection fraction. Conclusion: PSLs were more sensitive than traditional echocardiographic indicators in detecting changes in myocardial work and predicting left ventricular myocardial damage. This indicator could quantitatively evaluate myocardial work and provide a new and reliable non-invasive reference for clinical diagnosis and treatment of patients underwent KT.
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The present study focused on the efficacy and role of triptolide (TPL) in relieving symptoms of acute gouty arthritis (AGA) in vivo and in vitro. The effects of TPL in AGA were investigated in monosodium urate (MSU)-treated rat ankles, RAW264.7 macrophages, and neutrophils isolated from mouse peritoneal cavity. Observation of pathological changes in the ankle joint of rats. Enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (RT-qPCR) were performed to detect the expression levels of inflammatory factors and chemokines. The levels of the indicators of macrophage M1/M2 polarization, and the mechanistic targets of Akt and rapamycin complex 2, were determined via western blotting and RT-qPCR. The expression levels of CD86 and CD206 were detected using immunohistochemistry. Neutrophil migration was observed via air pouch experiments in vivo and Transwell cell migration assay in vitro. Myeloperoxidase (MPO) and Neutrophil elastase (NE) release was analyzed by via immunohistochemistry and immunofluorescence. The expression levels of beclin-1, LC3B, Bax, Bcl-2, and cleaved caspase-3 in neutrophils were determined via western blotting and immunofluorescence. Neutrophil apoptosis was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Our results suggest that TPL inhibited inflammatory cell infiltration in rat ankle joints and inflammatory factor and chemokine secretion in rat serum, regulated macrophage polarization through the PI3K/AKT signaling pathway, suppressed inflammatory factor and chemokine expression in neutrophils, and inhibited neutrophil migration, neutrophil extracellular trap formation, transitional autophagy, and apoptosis. This suggests that TPL can prevent and treat MSU-induced AGA by regulating macrophage polarization through the PI3K/Akt pathway and modulating neutrophil activity.
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Artritis Gotosa , Diterpenos , Compuestos Epoxi , Macrófagos , Neutrófilos , Fenantrenos , Ácido Úrico , Animales , Diterpenos/farmacología , Diterpenos/uso terapéutico , Neutrófilos/inmunología , Neutrófilos/efectos de los fármacos , Neutrófilos/metabolismo , Ratas , Fenantrenos/farmacología , Fenantrenos/uso terapéutico , Artritis Gotosa/tratamiento farmacológico , Artritis Gotosa/inducido químicamente , Artritis Gotosa/metabolismo , Artritis Gotosa/inmunología , Macrófagos/inmunología , Macrófagos/metabolismo , Macrófagos/efectos de los fármacos , Ratones , Compuestos Epoxi/farmacología , Masculino , Modelos Animales de Enfermedad , Células RAW 264.7 , Transducción de Señal/efectos de los fármacos , Activación de Macrófagos/efectos de los fármacos , Apoptosis/efectos de los fármacos , Activación Neutrófila/efectos de los fármacos , Humanos , Ratas Sprague-Dawley , Movimiento Celular/efectos de los fármacosRESUMEN
Cell death constitutes a critical component of the pathophysiology of cardiovascular diseases. A growing array of non-apoptotic forms of regulated cell death (RCD)-such as necroptosis, ferroptosis, pyroptosis, and cuproptosis-has been identified and is intimately linked to various cardiovascular conditions. These forms of RCD are governed by genetically programmed mechanisms within the cell, with epigenetic modifications being a common and crucial regulatory method. Such modifications include DNA methylation, RNA methylation, histone methylation, histone acetylation, and non-coding RNAs. This review recaps the roles of DNA methylation, RNA methylation, histone modifications, and non-coding RNAs in cardiovascular diseases, as well as the mechanisms by which epigenetic modifications regulate key proteins involved in cell death. Furthermore, we systematically catalog the existing epigenetic pharmacological agents targeting novel forms of RCD and their mechanisms of action in cardiovascular diseases. This article aims to underscore the pivotal role of epigenetic modifications in precisely regulating specific pathways of novel RCD in cardiovascular diseases, thus offering potential new therapeutic avenues that may prove more effective and safer than traditional treatments.
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In conventional knowledge, ferroelectric solid solutions were formed between members belonging to the same crystal structure family. Since both tungsten bronze and perovskite structures are constructed by connecting the corner-sharing oxygen octahedra, it offers a possibility for formatting an unusual solid solution between these two families. Herein, (1 - x)Sr0.6Ba0.4Nb2O6-xBaTiO3, (1 - x)SBN-xBT, solid solutions were synthesized and the solution mechanism was resolved from a structure viewpoint. With increasing BT content, the solid solution persists of tetragonal tungsten bronze structure, but the lattice parameter a (= b) decreases whereas c increases, resulting in the significant reduction of grains anisotropy. The ferroelectric-relaxor phase transition temperature shows a monotonic increase as x increases. However, the ferroelectricity evolution is not monotonous as a function of BT content because of the competitive effects of Ba and Ti on the property. As a result, the x = 0.10 ceramic shows the strongest ferroelectricity and a remarkable electrocaloric effect of 1.4 K near room temperature. This work challenges the traditional view of solid solution formation and provides an alternative way to modulate the structure and properties of ferroelectrics.
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Background: The global incidence of neurological diseases has been on the rise, creating an urgent need for a validated marker. Neurofilament Light Chain (NfL) holds promise as such a marker and has garnered significant attention in the field of neurological diseases over the past decades. Methods: Corresponding articles from 2013 to 2023 were collected from the Web of Science database, and data were analyzed by CiteSpace and VOSviewer software. Results: A total of 1350 articles were collected from 296 countries/regions, involving 7246 research organizations. Since 2013, among the top ten institutions and authors with the highest number of published papers, the most are from the US and the UK. The United States leads in the number of published papers, but England holds a more momentous position, because it has higher IF. Henrik Zetterberg is the most influential scholar in the field. Conclusions: The output of papers mainly relies on researchers from developed countries, and scholars from the United States and England have contributed the largest number of papers. Until now, the importance of NfL in neurological diseases has attracted global attention. In addition, NfL contributes to the potential diagnosis of various neurological disorders and can be used to improve the accuracy of differential diagnosis and prognostic assessment as well as predict the response to treatments. More and more in-depth studies are highly needed in the future.
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Diaryl-substituted vinyl boronates as potent building modules are challenging to synthesize. Herein, we present a convenient strategy based on a gold-catalyzed Hiyama arylation of (Z)-ß-(borylvinyl)silanes which are easily accessible by hydroboration of silylalkynes. By exploiting the highly electronegative nature of the Au(III) intermediate (which is accessed by the light-assisted oxidation with aryl diazonium salts), a selective activation of the silyl group in the presence of the boron moiety is achieved. This opens a route to selectively synthesize diaryl-substituted vinyl boronates. The reaction shows a broad substrate range, excellent functional group tolerance and perfect chemo-selectivity. Experimental studies and DFT calculations allowed us to elucidate the mechanism of the reaction, the synthetic potential was demonstrated by downstream transformations providing a facile route to bifunctional phenanthrenes and triaryl-substituted olefins.
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Steroid hormones exhibit potent endocrine disrupting activity and have been shown to disrupt the equilibrium of aquatic ecosystems and pose a threat to public health through their persistent and carcinogenic effects. Pontibacillus chungwhensis HN14, a moderately halophilic bacterium with the capacity to effectively degrade various polycyclic aromatic hydrocarbons and other organic pollutants, was previously isolated. Additionally, the strain HN14 showed strong environmental adaptability under various environmental stress conditions. In this study, the steroid degradation by strain HN14 was studied for the first time. We demonstrated that strain HN14 could degrade estradiol (E2) to maintain the growth of the strain and could convert E2 to estrone. Additionally, the efficient substrate degradation efficiency of P. chungwhensis HN14 under high salinity and high substrate concentration conditions was demonstrated. Furthermore, a 17ß-hydroxysteroid dehydrogenase, 17ß-HSD(HN14), was identified in strain HN14. Comparative analysis reveals that 17ß-HSD(HN14) shares approximately 38% sequence identity with 17ß-HSDx from Rhodococcus sp. P14. In addition, 100 µg of purified 17ß-HSD(HN14) could effectively convert about 40% of 0.25 mM of E2 within 1 h period, with an enzyme activity of 17.5 U/mg, and catalyze the dehydrogenation of E2 and testosterone at the C-17 position. The characterization of purified enzyme properties reveals that 17ß-HSD(HN14) exhibits exceptional structural robustness and enzymatic efficacy even under high salinity conditions of up to 20%. Overall, this study enhances our comprehension of steroid biodegradation in strain HN14 and contributes novel ideas and theoretical underpinnings for advancing bioremediation technologies targeting steroid pollution in high-saline environments.
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17-Hidroxiesteroide Deshidrogenasas , Biodegradación Ambiental , Salinidad , 17-Hidroxiesteroide Deshidrogenasas/metabolismo , 17-Hidroxiesteroide Deshidrogenasas/genética , Bacillaceae/enzimología , Bacillaceae/genética , Bacillaceae/metabolismo , Estradiol/metabolismo , Estrona/metabolismo , Filogenia , Disruptores Endocrinos/metabolismo , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Esteroides/metabolismoRESUMEN
Background: The increasing prevalence of depressive symptoms has emerged as a critical public health issue globally, highlighting the need for analyses of the factors contributing to depressive symptoms within the Chinese population and the development of targeted recommendations for improving mental well-being. We aimed to explore the correlation between internet use and depressive symptoms and the role of socioeconomic inequalities in this association. Methods: We included data on 8019 residents aged 18 years and above, which we retrieved from the 2018 and 2020 waves of the China Family Panel Studies. We used latent profile analysis to categorise individuals' internet usage patterns and multiple linear regression to determine their association with depressive symptoms. Results: Higher socioeconomic status (SES) was associated with fewer depressive symptoms (τ = -0.08; 95% confidence interval (CI) = -0.36, -0.18). Individuals in the high-dependence group presented a greater likelihood of developing depressive symptoms (τ = 0.04; 95% CI = 0.007, 0.66). We observed no significant difference in the interaction effect between individual-level SES and the four patterns of internet usage. However, compared with urban-dwelling respondents, those in rural areas had a stronger association between internet usage patterns and depressive symptoms, especially those in the high-dependence group (τ = -0.07; 95% CI = -1.47, -0.20). Conclusions: Our findings indicate a significant association between depressive symptoms and internet usage patterns, indicating a need for interventions related to internet use, especially those targeted at reducing the risk of depressive symptoms in individuals of lower SES.
Asunto(s)
Depresión , Uso de Internet , Factores Socioeconómicos , Humanos , Masculino , Femenino , China/epidemiología , Depresión/epidemiología , Adulto , Persona de Mediana Edad , Estudios Longitudinales , Adulto Joven , Uso de Internet/estadística & datos numéricos , Adolescente , Clase Social , Internet/estadística & datos numéricos , Anciano , Pueblos del Este de AsiaRESUMEN
Transferrin (TRF), recognized as a glycoprotein clinical biomarker and therapeutic target, has its concentration applicable for disease diagnosis and treatment monitoring. Consequently, this study developed boronic acid affinity magnetic surface molecularly imprinted polymers (B-MMIPs) with pH-responsitivity as the "capture probe" for TRF, which have high affinity similar to antibodies, with a dissociation constant of (3.82 ± 0.24) × 10-8 M, showing 7 times of reusability. The self-copolymerized imprinted layer synthesized with dopamine (DA) and 3-Aminophenylboronic acid (APBA) as double monomers avoided nonspecific binding sites and produced excellent adsorption properties. Taking the gold nanostar (AuNS) with a branch tip "hot spot" structure as the core, the silver-coated AuNS functionalized with the biorecognition element 4-mercaptophenylboronic acid (MPBA) was employed as a surface-enhanced Raman scattering (SERS) nanotag (AuNS@Ag-MPBA) to label TRF, thereby constructing a double boronic acid affinity "sandwich" SERS biosensor (B-MMIPs-TRF-SERS nanotag) for the highly sensitive detection of TRF. The SERS biosensor exhibited a detection limit for TRF of 0.004 ng/mL, and its application to spiked serum samples confirmed its reliability and feasibility, demonstrating significant potential for clinical TRF detection. Moreover, the SERS biosensor designed in this study offers advantages in stability, detection speed (40 min), and cost efficiency. The portable Raman instrument for SERS detection fulfills the requirements for point-of-care testing.