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Acute Myocardial Infarction (AMI) has seen rising cases, particularly in younger people, leading to public health concerns. Standard treatments, like coronary artery recanalization, often don't fully repair the heart's microvasculature, risking heart failure. Advances show that Mesenchymal Stromal Cells (MSCs) transplantation improves cardiac function after AMI, but the harsh microenvironment post-AMI impacts cell survival and therapeutic results. MSCs aid heart repair via their membrane proteins and paracrine extracellular vesicles that carry microRNA-125b, which regulates multiple targets, preventing cardiomyocyte death, limiting fibroblast growth, and combating myocardial remodeling after AMI. This study introduces ultrasound-responsive phase-change bionic nanoparticles, leveraging MSCs' natural properties. These particles contain MSC membrane and microRNA-125b, with added macrophage membrane for stability. Using Ultrasound Targeted Microbubble Destruction (UTMD), this method targets the delivery of MSC membrane proteins and microRNA-125b to AMI's inflamed areas. This aims to enhance cardiac function recovery and provide precise, targeted AMI therapy.
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Células Madre Mesenquimatosas , MicroARNs , Infarto del Miocardio , Nanopartículas , Infarto del Miocardio/terapia , Animales , Nanopartículas/química , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/citología , MicroARNs/metabolismo , MicroARNs/genética , Masculino , Recuperación de la Función , Trasplante de Células Madre Mesenquimatosas/métodos , Humanos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacología , Ratones , Microburbujas , Ondas UltrasónicasRESUMEN
PURPOSE: This study aimed to identify ultrasound and clinicopathological characteristics related to recurrence in HER2-positive (HER2+) breast cancer, and to develop nomograms for predicting recurrence. METHODS: In this dual-center study, we retrospectively enrolled 570 patients with HER2+ breast cancer. The ultrasound and clinicopathological characteristics of hormone receptor (HR)-/HER2+ patients and HR+/HER2+ patients were analyzed separately according to HR status. Eighty percent of the original samples from HR-/HER2+ and HR+/HER2+ patients were extracted by bootstrap sampling as the training cohorts, while the remaining 20% were used as the external validation cohorts. Informative characteristics were screened through univariate and multivariable Cox regression in the training cohorts and used to develop nomograms for predicting recurrence. The predictive accuracy was calculated using Harrell's C-index and calibration curves. RESULTS: Three informative characteristics (axillary nodal status, calcification, and Adler degree) were identified in HR-/HER2+ patients, and another three (histological grade, axillary nodal status, and echogenic halo) in HR+/HER2+ patients. Based on these, two separate nomograms were constructed to assess recurrence risk. In the training cohorts, the C-index was 0.740 (95% CI: 0.667-0.811) for HR-/HER2+ nomogram, and 0.749 (95% CI: 0.679-0.820) for HR+/HER2+ nomogram. In the validation cohorts, the C-index was 0.708 (95% CI: 0.540-0.877) for HR-/HER2+ group, and 0.705 (95% CI: 0.557-0.853) for HR+/HER2+ group. The calibration curves also indicated the excellent accuracy of the nomograms. CONCLUSIONS: Ultrasound performance of HER2+ breast cancers with different HR status was significantly different. Nomograms integrating ultrasound and clinicopathological characteristics exhibited favorable performance and have the potential to serve as a reliable method for predicting recurrence in heterogeneous breast cancer.
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Neoplasias de la Mama , Recurrencia Local de Neoplasia , Nomogramas , Receptor ErbB-2 , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/metabolismo , Femenino , Receptor ErbB-2/metabolismo , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico por imagen , Recurrencia Local de Neoplasia/patología , Estudios Retrospectivos , Adulto , Anciano , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Biomarcadores de Tumor/metabolismo , Ultrasonografía Mamaria/métodosRESUMEN
During myocardial ischaemiaâreperfusion injury (MIRI), the accumulation of damaged mitochondria could pose serious threats to the heart. The migrasomes, newly discovered mitocytosis-mediating organelles, selectively remove damaged mitochondria to provide mitochondrial quality control. Here, we utilised low-intensity pulsed ultrasound (LIPUS) on MIRI mice model and demonstrated that LIPUS reduced the infarcted area and improved cardiac dysfunction. Additionally, we found that LIPUS alleviated MIRI-induced mitochondrial dysfunction. We provided new evidence that LIPUS mechanical stimulation facilitated damaged mitochondrial excretion via migrasome-dependent mitocytosis. Inhibition the formation of migrasomes abolished the protective effect of LIPUS on MIRI. Mechanistically, LIPUS induced the formation of migrasomes by evoking the RhoA/Myosin II/F-actin pathway. Meanwhile, F-actin activated YAP nuclear translocation to transcriptionally activate the mitochondrial motor protein KIF5B and Drp1, which are indispensable for LIPUS-induced mitocytosis. These results revealed that LIPUS activates mitocytosis, a migrasome-dependent mitochondrial quality control mechanism, to protect against MIRI, underlining LIPUS as a safe and potentially non-invasive treatment for MIRI.
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Modelos Animales de Enfermedad , Daño por Reperfusión Miocárdica , Animales , Ratones , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/terapia , Ondas Ultrasónicas , Masculino , Ratones Endogámicos C57BL , Mitocondrias/metabolismoRESUMEN
Bisphenols (BPs), including BPA, BPF, BPS, and BPAF, are synthetic phenolic organic compounds and endocrine-disrupting chemicals. These organics have been broadly utilized to produce epoxy resins, polycarbonate plastics, and other products. Mounting evidence has shown that BPs, especially BPA, may enter into the human body and participate in the development of human diseases mediated by nuclear hormone receptors. Moreover, BPA may negatively affect human health at the epigenetic level through processes such as DNA methylation and histone acetylation. Recent studies have demonstrated that, as part of epigenetics, noncoding RNAs (ncRNAs), including microRNAs (miRNAs), long noncoding RNAs (lncRNAs), circular RNAs (circRNAs), and small nucleolar RNAs (snoRNAs), have vital impacts on BP-related diseases, such as reproductive system diseases, nervous system diseases, digestive system diseases, endocrine system diseases, and other diseases. Moreover, based on the bioinformatic analysis, changes in ncRNAs may be relevant to normal activities and functions and BP-induced diseases. Thus, we conducted a meta-analysis to identify more promising ncRNAs as biomarkers and therapeutic targets for BP exposure and relevant human diseases. In this review, we summarize the regulatory functions of ncRNAs induced by BPs in human diseases and latent molecular mechanisms, as well as identify prospective biomarkers and therapeutic targets for BP exposure and upper diseases.
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Compuestos de Bencidrilo , Disruptores Endocrinos , Fenoles , ARN no Traducido , Fenoles/toxicidad , Compuestos de Bencidrilo/toxicidad , Humanos , Disruptores Endocrinos/toxicidad , ARN no Traducido/genética , Epigénesis Genética/efectos de los fármacos , MicroARNs/genética , MicroARNs/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismoRESUMEN
Myocardial infarction (MI) is a leading cause of death worldwide. Few drugs hold the ability to depress cardiac electrical and structural remodeling simultaneously after MI, which is crucial for the treatment of MI. The aim of this study is to investigate an effective therapy to improve both electrical and structural remodeling of the heart caused by MI. Here, an "ion cocktail therapy" is proposed to simultaneously reverse cardiac structural and electrical remodeling post-MI in rats and minipigs by applying a unique combination of silicate, strontium (Sr) and copper (Cu) ions due to their specific regulatory effects on the behavior of the key cells involved in MI including angiogenesis of endothelial cells, M2 polarization of macrophages and apoptosis of cardiomyocyte. The results demonstrate that ion cocktail treatment attenuates structural remodeling post-MI by ameliorating infarct size, promoting angiogenesis in both peri-infarct and infarct areas. Meantime, to some extent, ion cocktail treatment reverses the deteriorative electrical remodeling by reducing the incidence rate of early/delayed afterdepolarizations and minimizing the heterogeneity of cardiac electrophysiology. This ion cocktail therapy reveals a new strategy to effectively treat MI with great clinical translation potential due to the high effectiveness and safety of the ion cocktail combination.
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Current guidelines encourage large studies in a diverse population to establish normal reference ranges for three-dimensional (3D) echocardiography for different ethnic groups. This study was designed to establish the normal values of 3D-left ventricular (LV) and left atrial (LA) volume and function in a nationwide, population-based cohort of healthy Han Chinese adults. A total of 1117 healthy volunteers aged 18-89 years were enrolled from 28 collaborating laboratories in China. Two sets of 3D echocardiographic instruments were used, and full-volume echocardiographic images were recorded and transmitted to a core laboratory for image analysis with a vendor-independent off-line workstation. Finally, 866 volunteers (mean age of 48.4 years, 402 men) were qualified for final analysis. Most parameters exhibited substantial differences between different sex and age groups, even after indexation by body surface area. The normal ranges of 3D-LV and 3D-LA volume and function differed from those recommended by the American Society of Echocardiography and the European Association of Cardiovascular Imaging guidelines, presented by the World Alliance Societies of Echocardiography (WASE) study, and from the 2D values in the EMINCA study. The normal reference values of 3D echocardiography-derived LV and LA volume and function were established for the first time in healthy Han Chinese adults. Normal ranges of 3D-LV and 3D-LA echocardiographic measurements stratified with sex, age, and race should be recommended for clinical applications.
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Ecocardiografía Tridimensional , Atrios Cardíacos , Ventrículos Cardíacos , Humanos , Persona de Mediana Edad , Masculino , Adulto , Ecocardiografía Tridimensional/métodos , Femenino , Anciano , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/anatomía & histología , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/anatomía & histología , China , Valores de Referencia , Adulto Joven , Adolescente , Anciano de 80 o más Años , Pueblo Asiatico , Función Ventricular Izquierda , Función del Atrio Izquierdo , Pueblos del Este de AsiaRESUMEN
Bartonella is an intracellular parasitic zoonotic pathogen that can infect animals and cause a variety of human diseases. This study investigates Bartonella prevalence in small mammals in Yunnan Province, China, focusing on tissue tropism. A total of 333 small mammals were sampled from thirteen species, three orders, four families, and four genera in Heqing and Gongshan Counties. Conventional PCR and real-time quantitative PCR (qPCR) were utilized for detection and quantification, followed by bioinformatic analysis of obtained DNA sequences. Results show a 31.5% detection rate, varying across species. Notably, Apodemus chevrieri, Eothenomys eleusis, Niviventer fulvescens, Rattus tanezumi, Episoriculus leucops, Anourosorex squamipes, and Ochotona Thibetana exhibited infection rates of 44.4%, 27.7%, 100.0%, 6.3%, 60.0%, 23.5%, and 22.2%, respectively. Genetic analysis identified thirty, ten, and five strains based on ssrA, rpoB, and gltA genes, with nucleotide identities ranging from 92.1% to 100.0%. Bartonella strains were assigned to B. grahamii, B. rochalimae, B. sendai, B. koshimizu, B. phoceensis, B. taylorii, and a new species identified in Episoriculus leucops (GS136). Analysis of the different tissues naturally infected by Bartonella species revealed varied copy numbers across different tissues, with the highest load in spleen tissue. These findings underscore Bartonella's diverse species and host range in Yunnan Province, highlighting the presence of extensive tissue tropism in Bartonella species naturally infecting small mammalian tissues.
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Mucus hypersecretion resulting from excessive proliferation and metaplasia of goblet cells in the airways is the pathological foundation for Chronic obstructive pulmonary disease (COPD). Clinical trials have confirmed the clinical efficacy of pulsed electric field ablation (PFA) for COPD, but its underlying mechanisms is poorly understood. Cellular and animal models of COPD (rich in goblet cells) were established in this study to detect goblet cells' sensitivity to PFA. Schwan's equation was adopted to calculate the cells' transmembrane potential and the electroporation areas in the cell membrane. We found that goblet cells are more sensitive to low-intensity PFA (250 V/cm-500 V/cm) than BEAS-2B cells. It is attributed to the larger size of goblet cells, which allows a stronger transmembrane potential formation under the same electric field strength. Additionally, the transmembrane potential of larger-sized cells can reach the cell membrane electroporation threshold in more areas. Trypan blue staining confirmed that the cells underwent IRE rate was higher in goblet cells than in BEAS-2B cells. Animal experiments also confirmed that the airway epithelium of COPD is more sensitive to PFA. We conclude that lower-intensity PFA can selectively kill goblet cells in the COPD airway epithelium, ultimately achieving the therapeutic effect of treating COPD.
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Electroporación , Células Caliciformes , Enfermedad Pulmonar Obstructiva Crónica , Células Caliciformes/patología , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Enfermedad Pulmonar Obstructiva Crónica/terapia , Animales , Humanos , Electroporación/métodos , Línea Celular , Potenciales de la Membrana , Masculino , Técnicas de Ablación/métodos , Electricidad , RatonesRESUMEN
Chronic obstructive pulmonary disease (COPD) is projected to become the third leading cause of death globally by 2030. Despite the limited treatment options available for advanced COPD, which are mostly restricted to costly lung transplants, physical ablation therapy offers promising alternatives. This technique focuses on ablating lesioned airway epithelium, reducing secretions and obstructions, and promoting normal epithelial regeneration, demonstrating significant therapeutic potential. Physical ablation therapy primarily involves thermal steam ablation, cryoablation, targeted lung denervation, and high-voltage pulsed electric field ablation. These methods help transform the hypersecretory phenotype, alleviate airway inflammation, and decrease the volume of emphysematous lung segments by targeting goblet cells and damaged lung areas. Compared to traditional treatments, endoscopic physical ablation offers fewer injuries, quicker recovery, and enhanced safety. However, its application in COPD remains limited due to inconsistent clinical outcomes, a lack of well-understood mechanisms, and the absence of standardized guidelines. This review begins by exploring the development of these ablation techniques and their current clinical uses in COPD treatment. It then delves into the therapeutic effects reported in recent clinical studies and discusses the underlying mechanisms. Finally, the review assesses the future prospects and challenges of employing ablation technology in COPD clinical practice, aiming to provide a practical reference and a theoretical basis for its use and inspire further research.
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Técnicas de Ablación , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Pulmonar Obstructiva Crónica/cirugía , Humanos , Técnicas de Ablación/métodos , Pulmón , AnimalesRESUMEN
AIMS: CD4+ T cells are activated during inflammatory dilated cardiomyopathy (iDCM) development to induce immunogenic responses that damage the myocardium. Low-intensity pulsed ultrasound (LIPUS), a novel physiotherapy for cardiovascular diseases, has recently been shown to modulate inflammatory responses. However, its efficacy in iDCM remains unknown. Here, we investigated whether LIPUS could improve the severity of iDCM by orchestrating immune responses and explored its therapeutic mechanisms. METHODS AND RESULTS: In iDCM mice, LIPUS treatment reduced cardiac remodelling and dysfunction. Additionally, CD4+ T-cell inflammatory responses were suppressed. LIPUS increased Treg cells while decreasing Th17 cells. LIPUS mechanically stimulates endothelial cells, resulting in increased secretion of extracellular vesicles (EVs), which are taken up by CD4+ T cells and alter their differentiation and metabolic patterns. Moreover, EVs selectively loaded with microRNA (miR)-99a are responsible for the therapeutic effects of LIPUS. The hnRNPA2B1 translocation from the nucleus to the cytoplasm and binding to caveolin-1 and miR-99a confirmed the upstream mechanism of miR-99a transport. This complex is loaded into EVs and taken up by CD4+ T cells, which further suppress mTOR and TRIB2 expression to modulate cellular differentiation. CONCLUSION: Our findings revealed that LIPUS uses an EVs-dependent molecular mechanism to protect against iDCM progression. Therefore, LIPUS is a promising new treatment option for iDCM.
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Cardiomiopatía Dilatada , Modelos Animales de Enfermedad , Vesículas Extracelulares , Ratones Endogámicos C57BL , MicroARNs , Transducción de Señal , Terapia por Ultrasonido , Función Ventricular Izquierda , Animales , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/trasplante , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/terapia , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/inmunología , Cardiomiopatía Dilatada/fisiopatología , MicroARNs/metabolismo , MicroARNs/genética , Ondas Ultrasónicas , Remodelación Ventricular , Masculino , Células Th17/inmunología , Células Th17/metabolismo , Linfocitos T Reguladores/inmunología , Linfocitos T Reguladores/metabolismo , Caveolina 1/metabolismo , Caveolina 1/genética , Serina-Treonina Quinasas TOR/metabolismo , Células Cultivadas , Humanos , RatonesRESUMEN
Three-dimensional (3D) echocardiography is an emerging technique for assessing right ventricular (RV) volume and function, but 3D-RV normal values from a large Chinese population are still lacking. The aim of the present study was to establish normal values of 3D-RV volume and function in healthy Chinese volunteers. A total of 1117 Han Chinese volunteers from 28 laboratories in 20 provinces of China were enrolled, and 3D-RV images of 747 volunteers with optimal image quality were ultimately analyzed by a core laboratory. Both vendor-dependent and vendor-independent software platforms were used to analyze the 3D-RV images. We found that men had larger RV volumes than women did in the whole population, even after indexing to body surface area, and older individuals had smaller RV volumes. The normal RV volume was significantly smaller than that recommended by the American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines in both sexes. There were significant differences in 3D-RV measurements between the two vendor ultrasound systems and the different software platforms. The echocardiographic measurements in normal Chinese adults II study revealed normal 3D-RV volume and function in a large Chinese population, and there were significant differences between the sexes, ages, races, and vendor groups. Thus, normal 3D-RV values should be stratified by sex, age, race, and vendor.
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The number of people suffering from scrub typhus, which is not of concern, is increasing year by year, especially in Yunnan Province, China. From June 1, 2021 to August 15, 2022, a total of 505 mammalian samples were collected from farm, forest, and residential habitats with high incidence of scrub typhus in Yunnan, China, for nPCR (nested PCR) and qPCR (quantitative real-time PCR) detection of Orientia tsutsugamushi. A total of 4 orders of murine-like animals, Rodentia (87.52%, n = 442), Insectivora (10.29%, n = 52), Lagomorpha (1.79%, n = 9) and Scandentia (0.40%, n = 2) were trapped. Comparing the qPCR infection rates in the three habitats, it was no significant difference that the infection rate of residential habitat (44.44%) and that of the farm habitat (45.05%, P>0.05), which is much larger than that of the forest habitat (3.08%) (P<0.001). Three genotypes (Karp-like, Kato-like and TA763-like) of O. tsutsugamushi were found from Yunnan, China in this study.
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Orientia tsutsugamushi , Tifus por Ácaros , Humanos , Animales , Ratones , Tifus por Ácaros/diagnóstico , Granjas , China/epidemiología , Orientia tsutsugamushi/genética , Roedores/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Epidemiológicos , Bosques , Eulipotyphla/genéticaRESUMEN
Cardiovascular diseases (CVDs) are multifactorial chronic diseases and have the highest rates of morbidity and mortality worldwide. The ubiquitin-proteasome system (UPS) plays a crucial role in posttranslational modification and quality control of proteins, maintaining intracellular homeostasis via degradation of misfolded, short-lived, or nonfunctional regulatory proteins. Noncoding RNAs (ncRNAs, such as microRNAs, long noncoding RNAs, circular RNAs and small interfering RNAs) serve as epigenetic factors and directly or indirectly participate in various physiological and pathological processes. NcRNAs that regulate ubiquitination or are regulated by the UPS are involved in the execution of target protein stability. The cross-linked relationship between the UPS, ncRNAs and CVDs has drawn researchers' attention. Herein, we provide an update on recent developments and perspectives on how the crosstalk of the UPS and ncRNAs affects the pathological mechanisms of CVDs, particularly myocardial ischemia/reperfusion injury, myocardial infarction, cardiomyopathy, heart failure, atherosclerosis, hypertension, and ischemic stroke. In addition, we further envision that RNA interference or ncRNA mimics or inhibitors targeting the UPS can potentially be used as therapeutic tools and strategies.
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Enfermedades Cardiovasculares , MicroARNs , Humanos , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/patología , Ubiquitina , Ligasas , ARN no Traducido/genética , MicroARNs/genética , Complejo de la Endopetidasa ProteasomalRESUMEN
The line optical tweezers (LOT) has been proven to be an alternative technique to manipulating the biological cells because of the bigger potential compared with traditional optical tweezers with a highly focused spot. We deduce the 4 × 4 optical matrix of the astigmatic LOT to investigate the optical characteristics related to the systematic parameters. The comparison of the initial and scattered electric fields by the cell under the astigmatic and stigmatic LOT is implemented to illustrate that the forward scattered light from the astigmatic LOT is much stronger than that from the stigmatic LOT, so as to the cell deformations. It is demonstrated that the astigmatic LOT could provide a more efficient way to deform the cell not only in the focal plane, but also along the optical axis to screen large biomaterials in biomechanics.
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Doxorubicin-induced cardiotoxicity (DIC), which is a cardiovascular complication, has become the foremost determinant of decreased quality of life and mortality among survivors of malignant tumors, in addition to recurrence and metastasis. The limited ability to accurately predict the occurrence and severity of doxorubicin-induced injury has greatly hindered the prevention of DIC, but reducing the dose to mitigate side effects may compromise the effective treatment of primary malignancies. This has posed a longstanding clinical challenge for oncologists and cardiologists. Ferroptosis in cardiomyocytes has been shown to be a pivotal mechanism underlying cardiac dysfunction in DIC. Ferroptosis is influenced by multiple factors. The innate immune response, as exemplified by neutrophil extracellular traps (NETs), may play a significant role in the regulation of ferroptosis. Therefore, the objective of this study was to investigate the involvement of NETs in doxorubicin-induced cardiomyocyte ferroptosis and elucidate their regulatory role. This study confirmed the presence of NETs in DIC in vivo. Furthermore, we demonstrated that depleting neutrophils effectively reduced the occurrence of doxorubicin-induced ferroptosis and myocardial injury in DIC. Additionally, our findings showed the pivotal role of high mobility group box 1 (HMGB1) as a critical molecule implicated in DIC and emphasized its involvement in the modulation of ferroptosis subsequent to NETs inhibition. Mechanistically, we obtained preliminary evidence suggesting that doxorubicin-induced NETs could modulate yes-associated protein (YAP) activity by releasing HMGB1, which subsequently bound to toll like receptor 4 (TLR4) on the cardiomyocyte membrane, thereby influencing cardiomyocyte ferroptosis in vitro. Our findings suggest that doxorubicin-induced NETs modulate cardiomyocyte ferroptosis via the HMGB1/TLR4/YAP axis, thereby contributing to myocardial injury. This study offers a novel approach for preventing and alleviating DIC by targeting alterations in the immune microenvironment.
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Trampas Extracelulares , Ferroptosis , Proteína HMGB1 , Cardiopatías , Humanos , Miocitos Cardíacos/metabolismo , Trampas Extracelulares/metabolismo , Proteína HMGB1/metabolismo , Receptor Toll-Like 4/metabolismo , Cardiotoxicidad/metabolismo , Calidad de Vida , Cardiopatías/metabolismo , Doxorrubicina/efectos adversosRESUMEN
OBJECTIVES: To investigate the association between duration of disability in activity of daily living (ADL) and overall survival in older individuals. DESIGN: A prospective cohort study. SETTING: Community-based data from Chinese Longitudinal Healthy Longevity Survey. PARTICIPANTS: In total, 13,560 participants without ADL disability and 2772 participants with ADL disability at baseline were included. MEASUREMENTS: ADL disability was assessed using Katz index scale, which included six essential ADLs: dressing, bathing, transferring, toileting, continence, and eating. Dependence of each item was scored on a scale of 1, the maximum total score was 6. At baseline, duration of ADL disability was defined as the maximum duration among the six items. The study outcome was overall survival. Accelerated failure time models were constructed to investigate the association between duration of ADL disability and overall survival. Subgroup analyses by sex, age, and multimorbidites, as well as sensitive analyses were conducted. RESULTS: During 81,868.7 person-years follow-up, 11,092 deaths were recorded. Overall, ADL disability was associated with lower overall survival compared to non-ADL disability. With duration of ADL disability extending, the overall survival strikingly dropped in the first 12 months, reaching its lowest point with adjusted time ratio (TR) at 0.66 (95%CI: 0.61-0.72, p < 0.001), then moderately grew until the 60th month, finally stayed constant thereafter. Participants with ADL scores of 1-3 had higher survival compared to those with scores of 4-6, and both groups followed a similar trend of varied survival to the whole cohort. Moreover, subgroup analyses and sensitivity analyses showed the robustness of these findings. CONCLUSIONS: Our findings first address a golden time window for the older individuals with ADL disability. More attention should be given to them, especially in the first 12 months since diagnosis, to reduce mortality and extend the lifespan.
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Actividades Cotidianas , Longevidad , Humanos , Anciano , Estudios Prospectivos , Estado de Salud , ChinaRESUMEN
PURPOSE: Immune checkpoint inhibitors (ICIs) have transformed traditional cancer treatments. Specifically, ICI-related myocarditis is an immune-related adverse event (irAE) with high mortality. ICIs activate CD4+ T-lymphocyte reprogramming, causing an imbalance between Th17 and Treg cell differentiation, ultimately leading to myocardial inflammatory damage. Low-intensity pulsed ultrasound (LIPUS) can limit inflammatory responses, with positive therapeutic effects across various cardiovascular inflammatory diseases; however, its role in the pathogenesis of ICI-related myocarditis and CD4+ T-cell dysfunction remains unclear. Accordingly, this study investigated whether LIPUS can alleviate ICI-related myocarditis inflammatory damage and, if so, aimed to elucidate the beneficial effects of LIPUS and its underlying molecular mechanisms. METHODS: An in vivo model of ICI-related myocarditis was obtained by intraperitonially injecting male A/J mice with an InVivoPlus anti-mouse PD-1 inhibitor. LIPUS treatment was performed via an ultrasound-guided application to the heart via the chest wall. The echocardiographic parameters were observed and cardiac function was assessed using an in vivo imaging system. The expression of core components of the HIPPO pathway was analyzed via western blotting. RESULTS: LIPUS treatment reduced cardiac immune responses and inflammatory cardiac injury. Further, LIPUS treatment alleviated the inflammatory response in mice with ICI-related myocarditis. Mechanistically, in the HIPPO pathway, the activation of Mst1-TAZ axis improved autoimmune inflammation by altering the interaction between the transcription factors FOXP3 and RORγt and regulating the differentiation of Treg and Th17 cells. CONCLUSION: LIPUS therapy was shown to reduce ICI-related myocarditis inflammatory damage and improve cardiac function, representing an exciting finding for irAEs treatment.
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Miocarditis , Masculino , Animales , Ratones , Miocarditis/inducido químicamente , Miocarditis/diagnóstico por imagen , Miocarditis/terapia , Inhibidores de Puntos de Control Inmunológico , Diferenciación Celular , Activación de Linfocitos , Linfocitos T CD4-PositivosRESUMEN
OBJECTIVE: To reduce the number of biopsies performed on benign breast lesions categorized as BI-RADS 4-5, we investigated the diagnostic performance of combined two-dimensional and three-dimensional shear wave elastography (2D + 3D SWE) with standard breast ultrasonography (US) for the BI-RADS assessment of breast lesions. METHODS: A total of 897 breast lesions, categorized as BI-RADS 3-5, were subjected to standard breast US and supplemented by 2D SWE only and 2D + 3D SWE analysis. Based on the malignancy rate of less than 2% for BI-RADS 3, lesions assessed by standard breast US were reclassified with SWE assessment. RESULTS: After standard breast US evaluation, 268 (46.1%) participants underwent benign biopsies in BI-RADS 4-5 lesions. By using separated cutoffs for upstaging BI-RADS 3 at 120 kPa and downstaging BI-RADS 4a at 90 kPa in 2D + 3D SWE reclassification, 123 (21.2%) participants underwent benign biopsy, resulting in a 54.1% reduction (123 versus 268). CONCLUSION: Combining 2D + 3D SWE with standard breast US for reclassification of BI-RADS lesions may achieve a reduction in benign biopsies in BI-RADS 4-5 lesions without sacrificing sensitivity unacceptably. CLINICAL RELEVANCE STATEMENT: Combining 2D + 3D SWE with US effectively reduces benign biopsies in breast lesions with categories 4-5, potentially improving diagnostic accuracy of BI-RADS assessment for patients with breast lesions. TRIAL REGISTRATION: ChiCTR1900026556 KEY POINTS: ⢠Reduce benign biopsy is necessary in breast lesions with BI-RADS 4-5 category. ⢠A reduction of 54.1% on benign biopsies in BI-RADS 4-5 lesions was achieved using 2D + 3D SWE reclassification. ⢠Adding 2D + 3D SWE to standard breast US improved the diagnostic performance of BI-RADS assessment on breast lesions: specificity increased from 54 to 79%, and PPV increased from 54 to 71%, with slight loss in sensitivity (97.2% versus 98.7%) and NPV (98.1% versus 98.7%).
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Neoplasias de la Mama , Diagnóstico por Imagen de Elasticidad , Femenino , Humanos , Mama/diagnóstico por imagen , Mama/patología , Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Diagnóstico Diferencial , Diagnóstico por Imagen de Elasticidad/métodos , Estudios Prospectivos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Ultrasonografía Mamaria/métodosRESUMEN
Over the past few decades, the food industry has undergone revolutionary changes due to the impacts of globalization, technological advancements, and ever-evolving consumer demands. Artificial intelligence (AI) and big data have become pivotal in strengthening food safety, production, and marketing. With the continuous evolution of AI technology and big data analytics, the food industry is poised to embrace further changes and developmental opportunities. An increasing number of food enterprises will leverage AI and big data to enhance product quality, meet consumer needs, and propel the industry toward a more intelligent and sustainable future. This review delves into the applications of AI and big data in the food sector, examining their impacts on production, quality, safety, risk management, and consumer insights. Furthermore, the advent of Industry 4.0 applied to the food industry has brought to the fore technologies such as smart agriculture, robotic farming, drones, 3D printing, and digital twins; the food industry also faces challenges in smart production and sustainable development going forward. This review articulates the current state of AI and big data applications in the food industry, analyses the challenges encountered, and discusses viable solutions. Lastly, it outlines the future development trends in the food industry.