RESUMEN
BACKGROUND: In daily life, people often follow others' gaze direction to infer their attention and mental state. This phenomenon is known as gaze following. OBJECTIVE: This study aimed to explore whether gaze following in different age groups is influenced by celebrity identity. METHODS: We recruited 70 participants, including 35 older adults and 35 young adults. The experimental materials consisted of three faces with different identity information (a political leader, a movie star, and an ordinary person). Each face had left and right gaze conditions. Targets and cues were presented with both longer and shorter stimulus onset asynchrony (SOA) conditions. RESULTS: Both older adults and young adults exhibited similar gaze following behaviors. Importantly, the celebrity effect on gaze following was observed in both groups, with stronger effects induced by the leader's and star's gazes compared to the ordinary person's gaze. Older adults showed a larger facilitation effect under the longer SOA condition compared to the shorter SOA, while no such SOA-related facilitation effect was found for young adults. CONCLUSION: These findings suggest that older adults can integrate social information from others' faces (celebrity identity) into the process of gaze following as effectively as young adults.
RESUMEN
Electrical stimulation therapy is effective in promoting wound healing by rescuing the decreased endogenous electrical field, where self-powered and miniaturized devices such as nanogenerators become the emerging trends. While high-voltage and unidirectional electric field may pose thermal effect and damage to the skin, nanogenerators with lower voltages, pulsed or bidirectional currents, and less invasive electrodes are preferred. Herein, we construct a polydopamine (PDA)-modified poly-L-lactic acid (PLLA) /MXene (PDMP/MXene) nanofibrous composite membrane that generates piezoelectric voltages matching the transepithelial potential (TEP) to accelerate wound healing. PDA coating not only enhances the piezoelectricity of PLLA by dipole attraction and alignment, but also increases its hydrophilicity and facilitates subsequent MXene adhesion for electrical conductivity and stability in physiological environment. When applied as wound dressings in mice, the PDMP/MXene membranes act as a nanogenerators with reduced internal resistances and satisfactory piezoelectric performances that resemble bioelectric potentials (~10 mV) responding to physical activities. The membrane significantly accelerates wound closure by facilitating fibroblast migration, collagen deposition and angiogenesis, and suppressing the expression of inflammatory responses. This piezoelectric fibrous membrane therefore provides a convenient solution for speeding up wound healing by sustained low voltage mimicking bioelectricity, better cell affinity.
RESUMEN
The need for novel anti-thyroid cancer (TC) medications is urgent due to the rising incidence and metastatic rates of malignant TC. In this study, we investigated the effect of Polyphyllin VII (PPVII) to TC cells, and explored their potential mechanism. B-CPAP and TPC-1 cells, were used to analyze the antitumor activity of PPVII by quantifying cell growth and metastasis as well as to study the effect on epithelial mesenchymal transition (EMT). The results showed that PPVII dramatically reduced the capacity of B-CPAP and TPC-1 cells to proliferate and migrate in a dose-response manner. Following PPVII treatment of TC cells, the expression levels of E-cadherin progressively increased and were higher than the control group, while the expression levels of EMT-related genes Vimentin, N-cadherin, Slug, Zeb-1, and Foxe1 gradually declined and were lower than the control group. It was proposed that PPVII might prevent TC from undergoing EMT. The Foxe1 gene was shown to be significantly expressed in TC, and a statistically significant variation in Foxe1 expression was observed across clinical stages of the disease, according to a bioinformatics database study. There was a strong link between the expression of the Foxe1 gene and the EMT-related gene. In the meantime, TC cells' expression of Foxe1 can be inhibited by PPVII. In conclusion, our results showed that PPVII may as a potential medication for targeting EMT in thyroid cancer.
Asunto(s)
Cadherinas , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Saponinas , Neoplasias de la Tiroides , Transición Epitelial-Mesenquimal/efectos de los fármacos , Transición Epitelial-Mesenquimal/genética , Humanos , Neoplasias de la Tiroides/tratamiento farmacológico , Neoplasias de la Tiroides/patología , Neoplasias de la Tiroides/genética , Proliferación Celular/efectos de los fármacos , Cadherinas/metabolismo , Cadherinas/genética , Saponinas/farmacología , Saponinas/uso terapéutico , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Relación Dosis-Respuesta a Droga , Expresión Génica/efectos de los fármacos , Terapia Molecular Dirigida , Antineoplásicos/farmacologíaRESUMEN
BACKGROUND: Activation of the NLRP3 inflammasome is critical in the inflammatory response to gout. Potassium ion (K+) efflux mediated by the TWIK2 channel is an important upstream mechanism for NLRP3 inflammasome activation. Therefore, the TWIK2 channel may be a promising therapeutic target for MSU crystal-induced inflammation. In the present study, we investigated the effect of ML335, a known K2P channel modulator, on MSU crystal-induced inflammatory responses and its underlying molecular mechanisms. METHODS: By molecular docking, we calculated the binding energies and inhibition constants of five K2P channel modulators (Hydroxychloroquine, Fluoxetine, DCPIB, ML365 and ML335) with TWIK2. Intracellular potassium ion concentration and mitochondrial function were assessed by flow cytometry. The interaction between MARCH5 and SIRT3 was demonstrated by immunoprecipitation and Western blotting assay. MSU suspensions were injected into mouse paw and peritoneal cavity to induce acute gout model. RESULTS: ML335 has the highest binding energy and the lowest inhibition constant with TWIK2 in the five calculated K2P channel modulators. In comparison, among these five compounds, ML335 efficiently inhibited the release of IL-1ß from MSU crystal-treated BMDMs. ML335 decreased MSU crystal-induced K+ efflux mainly dependent on TWIK2 channel. More importantly, ML335 can effectively inhibit the expression of the mitochondrial E3 ubiquitin ligase MARCH5 induced by MSU crystals, and MARCH5 can interact with the SIRT3 protein. ML335 blocked MSU crystal-induced ubiquitination of SIRT3 protein by MARCH5. In addition, ML335 improved mitochondrial dynamics homeostasis and mitochondrial function by inhibiting MARCH5 protein expression. ML335 attenuated the inflammatory response induced by MSU crystals in vivo and in vitro. CONCLUSION: Inhibition of TWIK2-mediated K+ efflux by ML335 alleviated mitochondrial injury via suppressing March5 expression, suggesting that ML335 may be an effective candidate for the future treatment of gout.
Asunto(s)
Inflamación , Mitocondrias , Potasio , Animales , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Inflamación/patología , Potasio/metabolismo , Ratones Endogámicos C57BL , Simulación del Acoplamiento Molecular , Masculino , Gota/metabolismo , Gota/patología , Gota/tratamiento farmacológico , Ratones , Ubiquitina-Proteína Ligasas/metabolismo , Canales de Potasio/metabolismo , Sirtuina 3/metabolismo , Interleucina-1beta/metabolismo , Inflamasomas/metabolismo , HumanosRESUMEN
Objective: Subcutaneous Immunotherapy (SCIT) is the long-lasting causal treatment of allergic rhinitis (AR). How to enhance the adherence of patients to maximize the benefit of allergen immunotherapy (AIT) plays a crucial role in the management of AIT. This study aims to leverage novel machine learning models to precisely predict the risk of non-adherence of AR patients and related local symptom scores in 3 years SCIT. Methods: The research develops and analyzes two models, sequential latent-variable model (SLVM) of Stochastic Latent Actor-Critic (SLAC) and Long Short-Term Memory (LSTM). SLVM is a probabilistic model that captures the dynamics of patient adherence, while LSTM is a type of recurrent neural network designed to handle time-series data by maintaining long-term dependencies. These models were evaluated based on scoring and adherence prediction capabilities. Results: Excluding the biased samples at the first time step, the predictive adherence accuracy of the SLAC models is from 60% to 72%, and for LSTM models, it is 66%-84%, varying according to the time steps. The range of Root Mean Square Error (RMSE) for SLAC models is between 0.93 and 2.22, while for LSTM models it is between 1.09 and 1.77. Notably, these RMSEs are significantly lower than the random prediction error of 4.55. Conclusion: We creatively apply sequential models in the long-term management of SCIT with promising accuracy in the prediction of SCIT nonadherence in AR patients. While LSTM outperforms SLAC in adherence prediction, SLAC excels in score prediction for patients undergoing SCIT for AR. The state-action-based SLAC adds flexibility, presenting a novel and effective approach for managing long-term AIT.
RESUMEN
Radiation resistance is a crucial factor influencing therapeutic outcomes in colorectal cancer (CRC). Baicalein (BE), primarily derived from Scutellaria baicalensis, has demonstrated anti-CRC properties. However, the impact of BE on the radiosensitivity of CRC remains unclear. This study aimed to evaluate the radiosensitization effects of BE and elucidate its mechanism in CRC radiotherapy. We established an in vitro radioresistant cell model (CT26-R) using parental CRC cells (CT26) subjected to ionizing radiation (IR). CT26-R cells were pretreated with or without BE, followed by transfection with pcDNA-NC and pcDNA-JAK2. The proliferation of CT26-R cells treated with BE and IR was assessed using a colony formation assay. A CRC animal model was developed in BALB/c mice via CT26-R cell transplantation. The radiosensitizing effect of BE on CRC was evaluated in vivo. TUNEL assay was conducted to detect apoptosis in tumor tissue. The expression levels of p-STAT3, JAK2, PD-L1, and SOCS3 in vitro and in vivo were measured by western blotting. Our results demonstrated that BE significantly increased radiosensitivity in vitro and in vivo and enhanced apoptosis in tumor tissues. Additionally, BE significantly downregulated the expression of p-STAT3, JAK2, and PD-L1, and significantly upregulated SOCS3 expression. These in vivo effects were reversed by pcDNA-JAK2. In summary, our data suggest that BE enhances CRC radiosensitivity by inhibiting the JAK2/STAT3 pathway.
Asunto(s)
Apoptosis , Neoplasias Colorrectales , Flavanonas , Janus Quinasa 2 , Ratones Endogámicos BALB C , Tolerancia a Radiación , Factor de Transcripción STAT3 , Transducción de Señal , Janus Quinasa 2/metabolismo , Flavanonas/farmacología , Flavanonas/química , Flavanonas/uso terapéutico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/patología , Neoplasias Colorrectales/radioterapia , Animales , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/antagonistas & inhibidores , Ratones , Tolerancia a Radiación/efectos de los fármacos , Línea Celular Tumoral , Transducción de Señal/efectos de los fármacos , Apoptosis/efectos de los fármacos , Humanos , Proliferación Celular/efectos de los fármacos , Fármacos Sensibilizantes a Radiaciones/farmacología , Fármacos Sensibilizantes a Radiaciones/uso terapéutico , Fármacos Sensibilizantes a Radiaciones/químicaRESUMEN
Breast cancer is a common malignant tumor, whose incidence is increasing year by year, and it has become the malignant tumor with the highest incidence rate in women. Purine ligand-gated ion channel 7 receptor (P2X7R) is a cation channel receptor with Adenosine triphosphate ( ATP) as a ligand, which is widely distributed in cells and tissues, and is closely related to tumorigenesis and progression. P2X7R plays an important role in cancer by interacting with ATP. Studies have shown that P2X7R is up-regulated in breast cancer and can promote tumor invasion and metastasis by activating the protein kinase B (AKT) signaling pathway, promoting epithelial-mesenchymal transition (EMT), controlling the generation of extracellular vesicle (EV), and regulating the expression of the inflammatory protein cyclooxygenase 2 (COX-2). Furthermore, P2X7R was proven to play an essential role in the proliferation and apoptosis of breast cancer cells. Recently, inhibitors targeting P2X7R have been found to inhibit the progression of breast cancer. Natural P2X7R antagonists, such as rhodopsin, and the isoquinoline alkaloid berberine, have also been shown to be effective in inhibiting breast cancer progression. In this article, we review the research progress of P2X7R and breast cancer intending to provide new targets and directions for breast cancer treatment.
RESUMEN
BACKGROUND: Fewer studies have examined the relationship between air pollution and depressive or anxiety symptoms in rural residents. Social economic status (SES), as an important indicator of the current state of socioeconomic development, we know little about how it modifies the relationship between air pollution and symptoms of depression or anxiety. METHODS: The patient health questionnaire (PHQ-2) and generalized anxiety scale (GAD-2) were used to learn about the prevalence of depressive and anxiety symptoms, the social economic status of the participants was categorized into two levels: lower and higher, and a binary logistic regression model was used to analyze the relationship between air pollution and residents' symptoms of depression or anxiety. RESULTS: A total of 10,670 adults were enrolled in this study, of which a total of 1292 participants suffered from depressive symptoms and 860 suffered from anxiety symptoms. Short-term exposure to PM2.5 and O3, singly or in combination, may be associated with the onset of depression symptoms, and there was a significant interaction between SES and exposure to PM2.5 or O3. Residents of areas with higher SES may have a lower risk of suffering from anxiety symptoms after O3 exposure compared to participants living in lower SES. LIMITATIONS: The study was a cross-sectional study, which may have lowered the quality level of the evidence. CONCLUSIONS: Short-term PM2.5 and O3 exposure may be associated with an increased prevalence risk of depressive symptoms. Higher levels of SES may reduce the adverse effects of air pollution on depressive or anxiety symptoms.
Asunto(s)
Contaminación del Aire , Ansiedad , Depresión , Población Rural , Humanos , Femenino , Estudios Transversales , Masculino , China/epidemiología , Contaminación del Aire/efectos adversos , Contaminación del Aire/estadística & datos numéricos , Depresión/epidemiología , Depresión/psicología , Adulto , Población Rural/estadística & datos numéricos , Persona de Mediana Edad , Ansiedad/epidemiología , Ansiedad/psicología , Clase Social , Material Particulado/efectos adversos , Prevalencia , Ozono/efectos adversos , Exposición a Riesgos Ambientales/efectos adversos , Exposición a Riesgos Ambientales/estadística & datos numéricos , AncianoRESUMEN
Biomass burning (BB) is the largest contributor to carbonaceous aerosols globally. Specific organic tracers can track BB particles and identify BB types. At present, there is limited information on the composition of BB tracers on a continental scale. In this study, we conducted year-round sampling of particulate matter (PM) at 12 sites in China. Nine BB tracers were measured in PM with aerodynamic diameters <1.1 µm (PM<1.1), in the range of 1.1-3.3 µm (PM1.1-3.3), and > 3.3 µm (PM>3.3). The annual average concentration of these nine BB tracers (∑9 BB tracers) in the total PM was 366 ng m-3 with the majority of levoglucosan (66 %). The concentration of ∑9 BB tracers was higher in northern China than in southern China, especially in winter. ∑9 BB tracers were most enriched in PM<1.1 (50-61 % in mass), followed by PM1.1-3.3 and PM>3.3. The highest concentrations of ∑9 BB tracers were observed in winter, while satellite-recorded fire spots were intensive in autumn and spring. The mismatch of seasonal trends between them indicated that the high levels of BB tracers in winter was not due to open BB. The composition of 4-hydroxybenzoic acid, syringic acid and vanillic acid suggested that the burning of crop residues and softwoods were the major BB types in China. The ratio of levoglucosan to mannosan could neither identify the major BB types in China nor distinguish between BB and coal combustion. Correlation analysis and the PMF model demonstrated that non-BB sources contributed 7 %-58 % to levoglucosan at the 12 sites, with coal combustion being the predominant non-BB source in China, especially in northern urban sites during winter. Our findings suggest that caution should be taken in application of these organic tracers to identify BB types and estimate BB aerosols.
RESUMEN
Aerobic glycolysis has been recognized as a hallmark of human cancer. G protein pathway suppressor 2 (GPS2) is a negative regulator of the G protein-MAPK pathway and a core subunit of the NCoR/SMRT transcriptional co-repressor complex. However, how its biological properties intersect with cellular metabolism in breast cancer (BC) development remains poorly elucidated. Here, we report that GPS2 is low expressed in BC tissues and negatively correlated with poor prognosis. Both in vitro and in vivo studies demonstrate that GPS2 suppresses malignant progression of BC. Moreover, GPS2 suppresses aerobic glycolysis in BC cells. Mechanistically, GPS2 destabilizes HIF-1α to reduce the transcription of its downstream glycolytic regulators (PGK1, PGAM1, ENO1, PKM2, LDHA, PDK1, PDK2, and PDK4), and then suppresses cellular aerobic glycolysis. Notably, receptor for activated C kinase 1 (RACK1) is identified as a key ubiquitin ligase for GPS2 to promote HIF-1α degradation. GPS2 stabilizes the binding of HIF-1α to RACK1 by directly binding to RACK1, resulting in polyubiquitination and instability of HIF-1α. Amino acid residues 70-92 aa of the GPS2 N-terminus bind RACK1. A 23-amino-acid-long GPS2-derived peptide was developed based on this N-terminal region, which promotes the interaction of RACK1 with HIF-1α, downregulates HIF-1α expression and significantly suppresses BC tumorigenesis in vitro and in vivo. In conclusion, our findings indicate that GPS2 decreases the stability of HIF-1α, which in turn suppresses aerobic glycolysis and tumorigenesis in BC, suggesting that targeting HIF-1α degradation and treating with peptides may be a promising approach to treat BC.
Asunto(s)
Neoplasias de la Mama , Regulación Neoplásica de la Expresión Génica , Glucólisis , Subunidad alfa del Factor 1 Inducible por Hipoxia , Proteínas de Neoplasias , Receptores de Cinasa C Activada , Humanos , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Receptores de Cinasa C Activada/metabolismo , Receptores de Cinasa C Activada/genética , Femenino , Animales , Ratones , Proteínas de Neoplasias/metabolismo , Proteínas de Neoplasias/genética , Proteolisis , Proliferación Celular , Línea Celular Tumoral , Ratones Desnudos , Ensayos Antitumor por Modelo de Xenoinjerto , Ubiquitinación , PronósticoRESUMEN
Artificial light at night (ALAN) may pose threat to rotifer Brachionus plicatilis. Additionally, the food of rotifer, i.e. algal community composition, often fluctuates. Thus, we selected five wavelengths of ALAN (purple, blue, green, red, white) and a three-colored light flashing mode (3-Flash) to test their impacts on life history traits of B. plicatilis with different food experiences, including those feeding Chlorella vulgaris (RC) or Phaeocystis globosa (RP). Results indicated purple ALAN promoted RC development, white ALAN inhibited RC development, while 3-Flash and white ALAN promoted RP development. Under red and white ALAN, RP increased fecundity but decreased lifespan. High-quality food enhanced rotifer's resistance to the impact of ALAN on lifespan. ALAN and food experience interacted on B. plicatilis. The effect of blue ALAN has less negative effects on B. plicatilis, based on hierarchical cluster analysis. Such findings are helpful to evaluate the potential impact of ALAN on marine zooplankton.
Asunto(s)
Luz , Rotíferos , Animales , Rotíferos/fisiología , Rasgos de la Historia de Vida , Chlorella vulgaris , Zooplancton , HaptophytaRESUMEN
Alkyl imidazolium ionic liquids (Cn[MIM]), initially heralded as eco-friendly green solvents for diverse industrial applications, have increasingly been recognized fortheir biodegradability challenges and multiple biotoxicity. Despite potential health risks, research into the effects of Cn[MIM] on human health remains scarce, particularly regarding their detection in biological serum samples. This study validated a matrix-matched calibration quantitative method that utilizes solid-phase extraction (SPE) coupled with ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The method was used to analyze the presence of 10 ionic liquids (ILs) with varying alkyl carbon chain lengths (C2-C12) across 300 human serum samples. Efficient separation was achieved using optimized SPE conditions and a BEH C18 column with an appropriate mobile phase. Results demonstrated a strong linear relationship (0.05-100 ng/mL; R2 = 0.995-0.999), with detection and quantification limits with detection and quantification limits ranging from 0.001 to 0.107 ng/mL and 0.003-0.355 ng/mL, respectively. Intraday and inter-day precisions were 0.85-6.99 % and 1.50-7.46 %, with recoveries between 82 and 113 %. The validated method detected C6MIM in 19 % of samples and C8MIM in 8.3 % of samples, with concentrations ranging from 0.02 to 111.70 µg/L and 0.09-16.99 µg/L, respectively, suggesting a potential risk of human exposure. This underscores the importance of robust detection methods in monitoring environmental and human health impacts of alkyl imidazolium compounds.
Asunto(s)
Imidazoles , Líquidos Iónicos , Espectrometría de Masas en Tándem , Humanos , Líquidos Iónicos/química , Espectrometría de Masas en Tándem/métodos , Imidazoles/química , Imidazoles/sangre , Monitoreo Biológico/métodos , Cromatografía Líquida de Alta Presión/métodos , Exposición a Riesgos Ambientales/análisis , Extracción en Fase Sólida , Límite de DetecciónRESUMEN
As a disease with high morbidity and high mortality, lung cancer has seriously harmed people's health. Therefore, early diagnosis and treatment are more important. PET/CT is usually used to obtain the early diagnosis, staging, and curative effect evaluation of tumors, especially lung cancer, due to the heterogeneity of tumors and the differences in artificial image interpretation and other reasons, it also fails to entirely reflect the real situation of tumors. Artificial intelligence (AI) has been applied to all aspects of life. Machine learning (ML) is one of the important ways to realize AI. With the help of the ML method used by PET/CT imaging technology, there are many studies in the diagnosis and treatment of lung cancer. This article summarizes the application progress of ML based on PET/CT in lung cancer, in order to better serve the clinical. In this study, we searched PubMed using machine learning, lung cancer, and PET/CT as keywords to find relevant articles in the past 5 years or more. We found that PET/CT-based ML approaches have achieved significant results in the detection, delineation, classification of pathology, molecular subtyping, staging, and response assessment with survival and prognosis of lung cancer, which can provide clinicians a powerful tool to support and assist in critical daily clinical decisions. However, ML has some shortcomings such as slightly poor repeatability and reliability.
RESUMEN
The increasing use of ultraviolet filters has become an emerging contaminant on the coast, posing potential ecological risks. Rotifers are essential components of marine ecosystems, serving as an association between primary producers and higher-level consumers. These organisms frequently encounter ultraviolet filters in coastal waters. This study aimed to assess the comprehensive effects of organic ultraviolet filters, specifically 2-ethylhexyl-4-methoxycinnamate (EHMC), and inorganic ultraviolet filters, namely, titanium dioxide nanoparticles (TiO2 NPs), on the rotifer Brachionus plicatilis. We exposed B. plicatilis to multiple combinations of different concentrations of EHMC and TiO2 NPs to observe changes in life history parameters and the expression of genes related to reproduction and antioxidant responses. Our findings indicated that increased EHMC concentrations significantly delayed the age at first reproduction, reduced the total offspring, and led to considerable alterations in the expression of genes associated with reproduction and stress. Exposure to TiO2 NPs resulted in earlier reproduction and decreased total offspring, although these changes were not synchronised in gene expression. The two ultraviolet filters had a significant interaction on the age at first reproduction and the total offspring of rotifer, with these interactions extending to the first generation. This research offers new insights into the comprehensive effects of different types of ultraviolet filters on rotifers by examining life history parameters and gene expression related to reproduction and stress, highlighting the importance of understanding the impacts of sunscreen products on zooplankton health.
Asunto(s)
Reproducción , Rotíferos , Titanio , Rayos Ultravioleta , Contaminantes Químicos del Agua , Animales , Rotíferos/genética , Rotíferos/efectos de los fármacos , Titanio/toxicidad , Contaminantes Químicos del Agua/toxicidad , Reproducción/efectos de los fármacos , Cinamatos , Protectores Solares/toxicidad , Expresión Génica/efectos de los fármacos , Nanopartículas/toxicidadRESUMEN
AIMS: The vascular aging process accelerated by type 2 diabetes mellitus (T2DM) is responsible for the elevated risk of associated cardiovascular diseases (CVDs). Metabolic disorder-induced immune senescence has been implicated in multi-organ/tissue damage. Herein, we sought to determine the role of immunosenescence in diabetic vascular aging and to investigate the underlying mechanisms. METHODS AND RESULTS: Aging hallmarks of the immune system appear prior to the vasculature in streptozotocin (STZ)/high-fat diet (HFD)-induced T2DM mice or db/db mice. Transplantation of aged splenocytes or diabetic splenocytes into young mice triggered vascular senescence and injury compared to normal control splenocyte transfer. RNA-seq profile and validation in immune tissues revealed that the Toll-like receptor 4 (TLR4)- Nuclear factor-kappa B (NF-κB) -NLRP3 axis might be the mediator of diabetic premature immunosenescence. The absence of Nlrp3 attenuated immune senescence and vascular aging during T2DM. Importantly, senescent immune cells, particularly T cells, provoked perivascular adipose tissue (PVAT) dysfunction and alternations in its secretome, which in turn impair vascular biology. In addition, senescent immune cells may uniquely affect vasoconstriction via influencing PVAT. Lastly, rapamycin alleviated diabetic immune senescence and vascular aging, which may be partly due to NLRP3 signaling inhibition. CONCLUSION: These results indicated that NLRP3 inflammasome-mediated immunosenescence precedes and drives diabetic vascular aging. The contribution of senescent immune cells to vascular aging is a combined effect of their direct effects and induction of PVAT dysfunction, the latter of which can uniquely affect vasoconstriction. We further demonstrated that infiltration of senescent T cells in PVAT was increased and associated with PVAT secretome alterations. Our findings suggest that blocking the NLRP3 pathway may prevent early immunosenescence and thus mitigate diabetic vascular aging and damage, and targeting senescent T cells or PVAT might also be the potential therapeutic approach.
RESUMEN
Breast cancer (BC) is the most prominent form of cancer among females all over the world. The current methods of BC detection include X-ray mammography, ultrasound, computed tomography, magnetic resonance imaging, positron emission tomography and breast thermographic techniques. More recently, machine learning (ML) tools have been increasingly employed in diagnostic medicine for its high efficiency in detection and intervention. The subsequent imaging features and mathematical analyses can then be used to generate ML models, which stratify, differentiate and detect benign and malignant breast lesions. Given its marked advantages, radiomics is a frequently used tool in recent research and clinics. Artificial neural networks and deep learning (DL) are novel forms of ML that evaluate data using computer simulation of the human brain. DL directly processes unstructured information, such as images, sounds and language, and performs precise clinical image stratification, medical record analyses and tumour diagnosis. Herein, this review thoroughly summarizes prior investigations on the application of medical images for the detection and intervention of BC using radiomics, namely DL and ML. The aim was to provide guidance to scientists regarding the use of artificial intelligence and ML in research and the clinic.
Asunto(s)
Neoplasias de la Mama , Aprendizaje Automático , Humanos , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/diagnóstico por imagen , Femenino , Redes Neurales de la Computación , Mamografía/métodos , Aprendizaje Profundo , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Rayos X/métodosRESUMEN
The purpose of this study was to determine the effect of pre-rigor salting on the quality characteristics of surimi gels prepared from snakehead fish muscle. Pre-rigor and post-rigor muscle were mixed with 0.3% or 3% NaCl (w/w) and made into surimi gels, respectively. Results showed that pre-rigor muscle had a higher content of ATP, longer sarcomere, higher pH and greater protein solubility. Metabolic profile suggested that pre-rigor muscle had higher content (a 28-fold increase) of antioxidants such as butyryl-l-carnitine. Transmission electron microscopy showed more damage of mitochondria in post-rigor muscle. Surimi paste from pre-rigor meat chopped with 3% NaCl generally showed greater radical scavenging ability and had higher content of free sulfhydryl. Surimi gel made from pre-rigor muscle salted with 3% NaCl showed a larger gel strength (3.18 kg*mm vs. 2.22 kg*mm) and better water-holding (86% vs. 80%) than that of post-rigor group. Based on these findings, we hypothesized that: In addition to other factors such as pH, degree of denaturation, etc., less protein oxidation in pre-rigor salted surimi also contributes to the improved gel properties.
Asunto(s)
Productos Pesqueros , Proteínas de Peces , Geles , Oxidación-Reducción , Animales , Geles/química , Productos Pesqueros/análisis , Proteínas de Peces/química , Cloruro de Sodio/química , Cloruro de Sodio/análisis , Peces , Manipulación de Alimentos , Agua/química , Perciformes/metabolismo , Concentración de Iones de HidrógenoRESUMEN
Deep learning techniques have been applied to medical image segmentation and demonstrated expert-level performance. Due to the poor generalization abilities of the models in the deployment in different centres, common solutions, such as transfer learning and domain adaptation techniques, have been proposed to mitigate this issue. However, these solutions necessitate retraining the models with target domain data and annotations, which limits their deployment in clinical settings in unseen domains. We evaluated the performance of domain generalization methods on the task of MRI segmentation of nasopharyngeal carcinoma (NPC) by collecting a new dataset of 321 patients with manually annotated MRIs from two hospitals. We transformed the modalities of MRI, including T1WI, T2WI and CE-T1WI, from the spatial domain to the frequency domain using Fourier transform. To address the bottleneck of domain generalization in MRI segmentation of NPC, we propose a meta-learning approach based on frequency domain feature mixing. We evaluated the performance of MFNet against existing techniques for generalizing NPC segmentation in terms of Dice and MIoU. Our method evidently outperforms the baseline in handling the generalization of NPC segmentation. The MF-Net clearly demonstrates its effectiveness for generalizing NPC MRI segmentation to unseen domains (Dice = 67.59%, MIoU = 75.74% T1W1). MFNet enhances the model's generalization capabilities by incorporating mixed-feature meta-learning. Our approach offers a novel perspective to tackle the domain generalization problem in the field of medical imaging by effectively exploiting the unique characteristics of medical images.
Asunto(s)
Imagen por Resonancia Magnética , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Imagen por Resonancia Magnética/métodos , Carcinoma Nasofaríngeo/diagnóstico por imagen , Neoplasias Nasofaríngeas/diagnóstico por imagen , Aprendizaje Profundo , Procesamiento de Imagen Asistido por Computador/métodos , Femenino , Masculino , AlgoritmosRESUMEN
Introduction: The brown planthopper (BPH) poses a significant threat to rice production in Asia. The use of resistant rice varieties has been effective in managing this pest. However, the adaptability of BPH to resistant rice varieties has led to the emergence of virulent populations, such as biotype Y BPH. YHY15 rice, which carries the BPH resistance gene Bph15, exhibits notable resistance to biotype 1 BPH but is susceptible to biotype Y BPH. Limited information exists regarding how resistant rice plants defend against BPH populations with varying levels of virulence. Methods: In this study, we integrated miRNA and mRNA expression profiling analyses to study the differential responses of YHY15 rice to both avirulent (biotype 1) and virulent (biotype Y) BPH. Results: YHY15 rice demonstrated a rapid response to biotype Y BPH infestation, with significant transcriptional changes occurring within 6 hours. The biotype Y-responsive genes were notably enriched in photosynthetic processes. Accordingly, biotype Y BPH infestation induced more intense transcriptional responses, affecting miRNA expression, defenserelated metabolic pathways, phytohormone signaling, and multiple transcription factors. Additionally, callose deposition was enhanced in biotype Y BPH-infested rice seedlings. Discussion: These findings provide comprehensive insights into the defense mechanisms of resistant rice plants against virulent BPH, and may potentially guide the development of insect-resistant rice varieties.
RESUMEN
BACKGROUND: The efficacy and safety of the novel immunotherapy method, intra-cervical lymphatic immunotherapy (ICLIT), need to be investigated. Comparing it with subcutaneous immunotherapy (SCIT), we clarified the long-term efficacy and safety of intra-cervical lymphatic immunotherapy on allergic rhinitis (AR), and investigated the improvement of clinical efficacy of the booster injection at 1 year after ICLIT treatment. METHODS: Ninety adult patients with dust mite allergy were randomly divided into 3 groups: 30 in the SCIT group, 30 in the ILCLIT group, and 30 in ICLIT booster group. Changes in total symptom score (TSS), nasal symptom score (TNSS), ocular symptom score (TOSS) and total medication score (TMS) were evaluated in the three groups. Adverse reactions were recorded, and serum dust mite specific IgE (sIgE) and specific IgG4 were assessed in the ICLIT group and ICLIT booster group. RESULTS: TSS, TNSS, TOSS, and TMS scores were significantly lower in the three groups at 36 months after treatment (p < 0. 05). And at 36 months the ICLIT-booster group showed results similar to SCIT and superior to ICLIT (p < 0. 05). Serum specific IgE decreased in all three groups at 12 and 36 months after treatment, p < 0.01. The ICLIT group and the ICLIT booster group showed a significant increase in sIgG4, p < 0.01. None of the patients in the three groups had any serious systemic adverse effects during the 3-year follow-up. CONCLUSION: The ICLIT treatment is effective and safe on AR. One booster injection of allergens at 1 year can greatly improve its long-term efficacy. TRIAL REGISTRY: Clinical trial registration number: ChiCTR1800017130.