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Cyanobacteria are important primary producers, contributing to 25% of the global carbon fixation through photosynthesis. They serve as model organisms to study the photosynthesis, and are important cell factories for synthetic biology. To enable efficient genetic dissection and metabolic engineering in cyanobacteria, effective and accurate genetic manipulation tools are required. However, genetic manipulation in cyanobacteria by the conventional homologous recombination-based method and the recently developed CRISPR-Cas gene editing system require complicated cloning steps, especially during multi-site editing and single base mutation. This restricts the extensive research on cyanobacteria and reduces its application potential. In this study, a highly efficient and convenient cytosine base editing system was developed which allows rapid and precise C â T point mutation and gene inactivation in the genomes of Synechocystis and Anabaena. This base editing system also enables efficient multiplex editing and can be easily cured after editing by sucrose counter-selection. This work will expand the knowledge base regarding the engineering of cyanobacteria. The findings of this study will encourage the biotechnological applications of cyanobacteria.
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Anabaena , Sistemas CRISPR-Cas , Edición Génica , Synechocystis , Edición Génica/métodos , Synechocystis/genética , Anabaena/genética , Anabaena/metabolismo , Genoma Bacteriano , Cianobacterias/genética , Cianobacterias/metabolismoRESUMEN
OBJECTIVES: One of the largest health concerns, postpartum depression (PPD), has detrimental effects on new mothers, their child, and their family. Investigating under-researched risk factors for postpartum depression in Asian women is the goal of this review of the literature. METHODS: The literature was searched using a number of electronic research databases. This review included studies that meet the following requirements: (a) they evaluated risk variables; (b) they were conducted in Asian countries using quantitative or qualitative methods; and (c) they were published in English in peer-reviewed journals between 2007 and 2023. A total of 90 studies from 14 different countries were reviewed, compiled, and synthesized. RESULTS: In Asian countries, where rates ranged from 0.82 % to 93 %, South Korea and Japan had the lowest and highest rates of postpartum depression, respectively. The risk factors for postpartum depression were divided into five main categories: biological/physical (e.g., ABO blood group, oxytocin level), psychological (e.g., antenatal depression, body dissatisfaction, child care stress), obstetric/pediatric (e.g., loss of baby, abortions, pain), socio-demographic (e.g., low social support, poverty, loss of autonomy), and cultural (e.g., gender preference). CONCLUSION: This phenomenon is prevalent in Asian cultures as it is in European Countries. The repercussions of untreated postpartum depression can lead to long-term psychological and developmental issues in children and strain the familial bonds essential for a nurturing environment. Moreover, understanding the specific risk factors faced by Asian women can pave the way for culturally sensitive interventions and support systems designed to address and mitigate these challenges effectively.
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Fake news impacts individuals' behavior and decision-making while also disrupting political processes, perceptions of medical advice, and societal trends. Improving individuals' ability to accurately assess fake news can reduce its harmful effects. However, previous research on media literacy interventions designed for improving fake news credibility assessments has yielded inconsistent results. We systematically collected 33 independent studies and performed a meta-analysis to examine the effects of media literacy interventions on assessing fake news credibility (n = 36,256). The results showed that media literacy interventions significantly improved fake news credibility assessments (Hedges' g = 0.53, 95% confidence interval [0.29-0.78], p < 0.001). Gaming interventions were the most effective intervention form. Conversely, the intervention channel, outcome measurement, and subject characteristics (age, gender, and country development level) did not influence the intervention effects.
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Decepción , Medios de Comunicación de Masas , Humanos , ConfianzaRESUMEN
OBJECTIVES: To investigate the efficacy and required indicators of Children Neuropsychological and Behavioral Scale-Revision 2016 (CNBS-R2016) in the differential diagnosis of autism spectrum disorder (ASD) and global developmental delay (GDD). METHODS: A total of 277 children with ASD and 415 children with GDD, aged 18-48 months, were enrolled as subjects. CNBS-R2016 was used to assess the developmental levels of six domains, i.e., gross motor, fine motor, adaptive ability, language, social behavior, and warning behavior, and a total of 13 indicators on intelligence age and developmental quotient (DQ) were obtained as the input features. Five commonly used machine learning classifiers were used for training to calculate the classification accuracy, sensitivity, and specificity of each classifier. RESULTS: DQ of warning behavior was selected as the first feature in all five classifiers, and the use of this indicator alone had a classification accuracy of 78.90%. When the DQ of warning behavior was used in combination with the intelligence age of warning behavior, gross motor, and language, it had the highest classification accuracy of 86.71%. CONCLUSIONS: Machine learning combined with CNBS-R2016 can effectively distinguish children with ASD from those with GDD. The DQ of warning behavior plays an important role in machine learning, and its combination with other features can improve classification accuracy, providing a basis for the efficient and accurate differential diagnosis of ASD and GDD in clinical practice.
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Trastorno del Espectro Autista , Niño , Humanos , Trastorno del Espectro Autista/diagnóstico , Trastorno del Espectro Autista/psicología , Diagnóstico Diferencial , Aprendizaje Automático , Conducta SocialRESUMEN
HIV infection is known to have significant effects on central nervous system. This study conducted a meta-analysis of whole voxel-based morphometry (VBM) in HIV patients (Nâ¯=â¯435) and HIV-uninfected controls (Nâ¯=â¯397). This study observed a reduction of limbic lobe, cingulate gyrus, frontal lobe, middle frontal gyrus, sub-lobar, insula, inferior frontal gyrus and superior frontal gyrus volume in HIV patients. These morphological differences may be responsible for cognitive decline in HIV patients, as these brain regions are closely related to motor and memory functions. These results contribute to a better understanding of the neural mechanisms underlying brain injury in HIV patients and could help develop targeted brain targets, provide more personalized treatment and predict neurodevelopmental outcomes.
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Sustancia Gris , Infecciones por VIH , Humanos , Sustancia Gris/diagnóstico por imagen , Infecciones por VIH/complicaciones , Infecciones por VIH/diagnóstico por imagen , Imagen por Resonancia Magnética , Corteza Cerebral/diagnóstico por imagen , Encéfalo/diagnóstico por imagenRESUMEN
BACKGROUND: The prevalence of misinformation poses a substantial threat to individuals' daily lives, necessitating the deployment of effective remedial approaches. One promising strategy is psychological inoculation, which pre-emptively immunizes individuals against misinformation attacks. However, uncertainties remain regarding the extent to which psychological inoculation effectively enhances the capacity to differentiate between misinformation and real information. OBJECTIVE: To reduce the potential risk of misinformation about digital health, this study aims to examine the effectiveness of psychological inoculation in countering misinformation with a focus on several factors, including misinformation credibility assessment, real information credibility assessment, credibility discernment, misinformation sharing intention, real information sharing intention, and sharing discernment. METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, we conducted a meta-analysis by searching 4 databases (Web of Science, APA PsycINFO, Proquest, and PubMed) for empirical studies based on inoculation theory and outcome measure-related misinformation published in the English language. Moderator analyses were used to examine the differences in intervention strategy, intervention type, theme, measurement time, team, and intervention design. RESULTS: Based on 42 independent studies with 42,530 subjects, we found that psychological inoculation effectively reduces misinformation credibility assessment (d=-0.36, 95% CI -0.50 to -0.23; P<.001) and improves real information credibility assessment (d=0.20, 95% CI 0.06-0.33; P=.005) and real information sharing intention (d=0.09, 95% CI 0.03-0.16; P=.003). However, psychological inoculation does not significantly influence misinformation sharing intention (d=-0.35, 95% CI -0.79 to 0.09; P=.12). Additionally, we find that psychological inoculation effectively enhances credibility discernment (d=0.20, 95% CI 0.13-0.28; P<.001) and sharing discernment (d=0.18, 95% CI 0.12-0.24; P<.001). Regarding health misinformation, psychological inoculation effectively decreases misinformation credibility assessment and misinformation sharing intention. The results of the moderator analyses showed that content-based, passive inoculation was more effective in increasing credibility and sharing intention. The theme of climate change demonstrates a stronger effect on real information credibility. Comparing intervention types showed that pre-post interventions are more effective for misinformation credibility assessment, while post-only interventions are better for credibility discernment. CONCLUSIONS: This study indicated that psychological inoculation enhanced individuals' ability to discern real information from misinformation and share real information. Incorporating psychological inoculation to cultivate an informed public is crucial for societal resilience against misinformation threats in an age of information proliferation. As a scalable and cost-effective intervention strategy, institutions can apply psychological inoculation to mitigate potential misinformation crises.
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Comunicación , Intención , Humanos , Difusión de la Información , Lenguaje , Evaluación de Resultado en la Atención de SaludRESUMEN
Misinformation affects various aspects of people's lives, such as politics, entertainment, and social interactions. However, effective intervention measures to combat misinformation are lacking. The inoculation theory has become a prevalent measure of misinformation. This study employed inoculation theory and developed an interactive game to help the public counter misinformation. In this game, players take on the role of the misinformation spreader, intending to add more followers to their virtual accounts using different strategies. A total of 180 Chinese participants were randomly assigned to game-based inoculation, graphic-based inoculation, and control groups. The results indicated that both types of inoculation interventions significantly decreased the perceived credibility and sharing intention of misinformation. Game-based inoculation was more effective than graphic-based inoculation in terms of misinformation perceived credibility, and the intervention effects were stable after 2 weeks. The graphic-based inoculation contained the sleeper effect, which interventions required a period of time to take effect. Neither inoculation produced countereffects on perceived credibility and nor sharing intention of accurate information.
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Comunicación , Intención , Humanos , PolíticaRESUMEN
Fibroblast activation protein-α (FAP), a type-II transmembrane serine protease, is rarely expressed in normal tissues but highly abundant in pathological diseases, including fibrosis, arthritis, and cancer. Ever since its discovery, we have deciphered its structure and biological properties and continue to investigate its roles in various diseases while attempting to utilize it for targeted therapy. To date, no significant breakthroughs have been made in terms of efficacy. However, in recent years, several practical applications in the realm of imaging diagnosis have been discovered. Given its unique expression in a diverse array of pathological tissues, the fundamental biological characteristics of FAP render it a crucial target for disease diagnosis and immunotherapy. To obtain a more comprehensive understanding of the research progress of FAP, its biological characteristics, involvement in diseases, and recent targeted application research have been reviewed. Moreover, we explored its development trend in the direction of clinical diagnoses and treatment.
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Structural magnetic resonance imaging (sMRI) studies have shown abnormalities in the brain structure of ASD patients, but the relationship between structural changes and social communication problems is still unclear. This study aims to explore the structural mechanisms of clinical dysfunction in the brain of ASD children through voxel-based morphometry (VBM). After screening T1 structural images from the Autism Brain Imaging Data Exchange (ABIDE) database, 98 children aged 8-12 years old with ASD were matched with 105 children aged 8-12 years old with typical development (TD). Firstly, this study compared the differences in gray matter volume (GMV) between the two groups. Then, this study evaluated the relationship between GMV and the subtotal score of communications and social interaction on the Autism Diagnostic Observation Schedule (ADOS) in ASD children. Research has found that abnormal brain structures in ASD include the midbrain, pontine, bilateral hippocampus, left parahippocampal gyrus, left superior temporal gyrus, left temporal pole, left middle temporal gyrus and left superior occipital gyrus. In addition, in ASD children, the subtotal score of communications and social interaction on the ADOS were only significantly positively correlated with GMV in the left hippocampus, left superior temporal gyrus and left middle temporal gyrus. In summary, the gray matter structure of ASD children is abnormal, and different clinical dysfunction in ASD children is related to structural abnormalities in specific regions.
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Microwave-induced thermoacoustic (TA) imaging (MTAI), which exploits dielectric contrasts to provide images with high contrast and spatial resolution, holds the potential to serve as an additional means of clinical diagnosis and treatment. However, conventional MTAI usually uses large and heavy metal antennas to radiate pulsed microwaves, making it challenging to image different target areas flexibly. In this work, we presented the design and evaluation of a portable microwave-acoustic coaxial TA probe (51 mm × 63 mm × 138 mm) that can flexibly image the region of interest. The TA probe contains two miniaturized symmetrically distributed Vivaldi antennas (7.5 g) and a 128-element linear ultrasonic transducer. By adjusting the geometry of the antennas and the ultrasonic transducer, the TA probe's acoustic field and microwave field can be designed to be coaxial, which helps achieve homogeneous microwave illumination and high-sensitivity ultrasonic detection. The practical feasibility of the proposed probe was tested on an in vitro ewe breast and a healthy volunteer. The results demonstrate that the MTAI system with the proposed TA probe can visualize the anatomical structure of the breast tumor in ewe breast and a healthy volunteer breast with resolutions in hundreds of microns (transverse: 910 µm, axial: 780 µm) and an excellent signal-to-noise ratio can be obtained in deep adipose tissue (10 dB in 6 cm fat). The miniaturized portable TA probe takes a solid step forward in translating MTAI technology to clinical breast tumor diagnosis.
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Neoplasias de la Mama , Microondas , Ultrasonido , Ultrasonido/instrumentación , Ultrasonido/métodos , Neoplasias de la Mama/diagnóstico por imagen , Humanos , Animales , Femenino , Ovinos , Fantasmas de ImagenRESUMEN
Background: Fetal ventriculomegaly (VM) is one of the most common abnormalities of the central nervous system (CNS), which can be significantly identified by brain anomalies prenatally by magnetic resonance imaging (MRI). Aberrant white blood cells (WBCs) levels indicate that the maternal is suffering from the infection. Previous studies have confirmed that prenatal infection can affect fetal brain structure, but there is no research revealed the association between maternal blood parameters with fetal VM until now. Methods: We measured the width of the lateral ventricle of 142 fetuses, which were divided into the fetal VM group (n = 70) and the normal lateral ventricle group (n = 72). We compared maternal blood cell levels between the two groups and investigate potential biomarkers of fetal VM. Result: High levels of maternal WBC and neutrophil (NE#) levels were observed in fetuses with VM (p < 0.001), while lymphocyte percentage, monocytes (MO#), neutrophil/lymphocyte ratio (NLR), and platelet were also increased in the fetal VM group (p = 0.033, 0.027, 0.034, and 0.025, respectively). receiver-operator curve (ROC) analysis suggested that WBC and NE# counts might be useful to distinguish fetuses with enlarged lateral ventricles (AUC = 0.688, 0.678, respectively). Conclusion: The current study emphasizes the importance of maternal infection for fetal brain growth, which could provide important information for prenatal diagnosis of CNS anomalies. Future research needs longitudinal analysis and exploration of the influence of maternal blood inflammatory marker levels on fetal brain development.
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Developing single molecule-assembled nanoprodrugs that can reverse the glutathione (GSH)-mediated drug resistance of tumors provides promising potentials for precision and effective cancer theranostics. Herein, we developed a novel single molecule-assembled nanoprodrug for effective photodynamic/chemotherapeutic eradication of drug-resistant tumors via the multistage GSH-depletion. The nanoprodrug MSSP-NP could be fancily fabricated by self-assembly of an amphiphilic activatable molecular MSSP, which is synthesized by covalently conjugating the photosensitizer methylene blue (MB) with a GSH-sensitive cisplatin prodrug via a tumor targeting thiolated polypeptide. Upon the nanoprodrug MSSP-NP systematic administrated, its photoactivities and pharmacological effects can be thoroughly switched on by intracellular GSH to produce the photosensitizer MB and chemotherapeutic drug cisplatin, along with the multi-step consumption of GSH, which could remarkably boost oxidative stress and reverse the drug resistance. As a result, the nanoprodrug could effectively disrupt the tumor GSH-defense system to afford high-efficiency photodynamic/chemotherapeutic inhibition of drug resistance tumors (96.4%) with minimum side effects.
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Nanopartículas , Neoplasias , Fotoquimioterapia , Profármacos , Humanos , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Cisplatino/uso terapéutico , Profármacos/química , Glutatión , Neoplasias/tratamiento farmacológico , Línea Celular Tumoral , Nanopartículas/químicaRESUMEN
BACKGROUND: The immune system has been implicated in synaptic plasticity, inflammation, and the progression of Alzheimer's disease (AD). However, there were few studies on improving the niche microenvironment of neural stem cells (NSCs) in the brain of AD to promote adult hippocampal neurogenesis (AHN) by regulating the function of non-parenchymal immune cells. METHODS: The lymph nodes of amyloid precursor protein/presenilin 1 (APP/PS1) and 3xTg (APP/PS1/tau) mouse models of AD were treated with photobiomodulation therapy (PBMT) for 10 J/cm2 per day for 1 month (10 min for each day), T lymphocytes isolated from these two AD models were treated with PBMT for 2 J/cm2 (5 min for each time). The NSCs isolated from hippocampus of these two AD models at E14, and the cells were co-cultivated with PBMT-treated T lymphocyte conditioned medium for NSCs differentiation. RESULTS: Our results showed that PBMT treatment could promote AHN and reverse cognitive deficits in AD mouse model. The expression of interferon-γ (IFN-γ) and interleukin-10 (IL-10) was upregulated in the brain of these two AD models after PBMT treated, which was induced by the activation of Janus kinase 2 (JAK2)-mediated signal transducer and activator of transcription 4 (STAT4)/STAT5 signaling pathway in CD4+ T cells. In addition, elevated CD4+ T cell levels and upregulated transforming growth factor-ß1 (TGFß1)/insulin-like growth factors-1 (IGF-1)/brain-derived neurotrophic factor (BDNF) protein expression levels were also detected in the brain. More importantly, co-cultivated the PBMT-treated T lymphocyte conditioned medium with NSCs derived from these two AD models was shown to promote NSCs differentiation, which was reflected in the upregulation of both neuronal class-III ß-tubulin (Tuj1) and postsynaptic density protein 95 (PSD95), but the effects of PBMT was blocked by reactive oxygen species (ROS) scavenger or JAK2 inhibitor. CONCLUSION: Our research suggests that PBMT exerts a beneficial neurogenesis modulatory effect through activating the JAK2/STAT4/STAT5 signaling pathway to promote the expression of IFN-γ/IL-10 in non-parenchymal CD4+ T cells, induction of improvement of brain microenvironmental conditions and alleviation of cognitive deficits in APP/PS1 and 3xTg-AD mouse models.
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Enfermedad de Alzheimer , Terapia por Luz de Baja Intensidad , Enfermedad de Alzheimer/complicaciones , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/terapia , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Cognición , Medios de Cultivo Condicionados/farmacología , Modelos Animales de Enfermedad , Homólogo 4 de la Proteína Discs Large/metabolismo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Interferón gamma/metabolismo , Interleucina-10/metabolismo , Janus Quinasa 2/metabolismo , Ratones , Ratones Transgénicos , Neurogénesis/fisiología , Presenilina-1/genética , Presenilina-1/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Factor de Transcripción STAT4/metabolismo , Factor de Transcripción STAT5/metabolismo , Factor de Transcripción STAT5/farmacología , Linfocitos T/metabolismo , Factor de Crecimiento Transformador beta1/metabolismo , Tubulina (Proteína)/metabolismoRESUMEN
In this contribution, we empirically investigated the effect of small talk on the users' non-verbal behaviors and emotions when users interacted with a crowd of virtual humans (VHs) with positive behavioral dispositions. Users were tasked with collecting items in a virtual marketplace via natural speech-based dialogue with a crowd of virtual pedestrians and vendors. The users were able to engage in natural speech-based conversation in a predefined corpus of small talk content that covered various commonplace small talk topics such as conversations about the weather, general concerns, and entertainment based on similar real-life situations. For instance, the VHs with the small talk ability would ask the users some simple questions to make small talk or remind the users of their belongings. We conducted a between-subjects empirical evaluation to investigate whether the user behaviors and emotions were different between a small talk condition and a non-small talk condition, and examined gender effects of the participants. We collected objective and subjective measures of the users to analyze users' emotions and social interaction behaviors, when in conversation with VHs that either possessed small-talk capability or not, besides task or goal oriented dialogue capabilities. Our result revealed that the VHs with small talk capability could alter the emotions and non-verbal behaviors of the users. Furthermore, the non-verbal behaviors between female and male participants differed greatly in the presence or absence of small talk.
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Gráficos por Computador , Emociones , Humanos , Masculino , Femenino , Emociones/fisiología , Comunicación , MotivaciónRESUMEN
Microwave-induced thermoacoustic (TA) technology transforms microwave into acoustic waves useable for imaging or therapy, based on the power density of the pulsed microwaves. Exploiting nanoparticles with high biocompatibility, safe metabolism, and high microwave-acoustic conversion is the key to the clinical translational application of TA therapy. In this paper, we proposed a biodegradable and high microwave absorption nanoparticle for TA therapy. The proposed nanoparticle uses iron ions to regulate the atomic defects of biodegradable black phosphorus (BP) nanosheets to augment the dielectric loss. The iron ions adsorb with the lone pair electrons indicated of BP through the conjugated π bond to increase the permanent electric dipoles. With pulsed microwave irradiation, a large number of electric dipoles are repeatedly polarized, causing instantaneous temperature rise and then generating significant TA shockwave via TA cavitation effect. TA shockwave can disrupt cell membranes in situ to trigger programmed apoptosis and produce precise anti-tumor effects. Additionally, the nanoparticle-mediated TA process generates images that deliver valuable data, such as the size, shape, and location of the tumor for treatment planning and monitoring. This hypothesis has been tested in vitro and in vivo with animal models of glioblastoma tumors. The experimental results demonstrate the high theragnostic efficiency for tumor inhibition and TA imaging, exhibiting low systemic cytotoxicity and good biocompatibility after systemic administration. The established BP-based nanoparticle with both safe metabolism and high microwave-acoustic conversion is a promising candidate for precision theranostics without obvious side effects.
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Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder with unclear etiology, and due to the lack of effective treatment, ASD patients bring enormous economic and psychological burden to families and society. In recent years, many studies have found that children with ASD are associated with gastrointestinal diseases, and the composition of intestinal microbiota (GM) is different from that of typical developing children. Thus, many researchers believe that the gut-brain axis may play an important role in the occurrence and development of ASD. Indeed, some clinical trials and animal studies have reported changes in neurological function, behavior, and comorbid symptoms of autistic children after rebalancing the composition of the GM through the use of antibiotics, prebiotics, and probiotics or microbiota transfer therapy (MMT). In view of the emergence of new therapies based on the modulation of GM, characterizing the individual gut bacterial profile evaluating the effectiveness of intervention therapies could help provide a better quality of life for subjects with ASD. This article reviews current studies on interventions to rebalance the GM in children with ASD. The results showed that Lactobacillus plantarum may be an effective strain for the probiotic treatment of ASD. However, the greater effectiveness of MMT treatment suggests that it may be more important to pay attention to the overall balance of the patient's GM. Based on these findings, a more thorough assessment of the GM is expected to contribute to personalized microbial intervention, which can be used as a supplementary treatment for ASD.
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Phototheranostics based on upconversion nanoparticles (UCNPs) offer the integration of imaging diagnostics and phototherapeutics. However, the programmable control of the photoactivation of imaging and therapy with minimum side effects is challenging due to the lack of ideal switchable UCNPs agents. Here we demonstrate a facile strategy to switch the near infrared emission at 800 nm from rationally designed UCNPs by modulating the irradiation laser into pulse output. We further synthesize a theranostic nanoagent by combining with a photosensitizer and a photoabsorbing agent assembled on the UCNPs. The orthogonal activation of in vivo photoacoustic imaging and photodynamic therapy can be achieved by altering the excitation modes from pulse to continuous-wave output upon a single 980 nm laser. No obvious harmful effects during photoexcitation was identified, suggesting their use for long-term imaging-guidance and phototherapy. This work provides an approach to the orthogonal activation of imaging diagnostics and photodynamic therapeutics.
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Nanopartículas , Técnicas Fotoacústicas , Fotoquimioterapia , Fármacos Fotosensibilizantes/uso terapéutico , FototerapiaRESUMEN
Glioblastoma has a dismal prognosis and is a critical and urgent health issue that requires aggressive research and determined clinical efforts. Due to its diffuse and infiltrative growth in the brain parenchyma, complete neurosurgical resection is rarely possible. Here, pulsed microwave-induced thermoacoustic (MTA) therapy is proposed as a potential alternative modality to precisely and effectively eradicate in vivo orthotopic glioblastoma. A nanoparticle composed of polar amino acids and adenosine-based agonists is constructed with high microwave absorbance and selective penetration of the blood-brain barrier (BBB) at the tumor site. This nanoparticle can activate the adenosine receptor on the BBB to allow self-passage and tumor accumulation. The nanoparticle converts absorbed microwaves into ultrasonic shockwaves via the thermoacoustic cavitation effect. The ultrasonic shockwave can mechanically destroy tumor cells within a short range with minimal damage to adjacent normal brain tissue due to the rapid decay of the ultrasonic shockwave intensity. The deep tissue penetration characteristics of the microwave and the rapid decay of the ultrasonic shockwave make MTA therapy a promising glioblastoma cure including intact skin and skull.
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Glioblastoma , Microondas , Pemetrexed , Humanos , Acústica , Glioblastoma/terapia , CráneoRESUMEN
Deep-located tumor specific imaging has broad clinical applications in improving the accuracy of tumor diagnosis. Microwave-induced thermoacoustic imaging (MTAI), combining the high-contrast of microwave imaging with the high-resolution of ultrasound imaging, is a potential candidate for noninvasive tumor detection. Herein, a deep-located tumor specific MTAI method by tumor microenvironment (TME) activated nanoprobe is reported. In principle, manganous-manganic oxide-based nanoprobe can be triggered by TME with overexpressed glutathione and weak acidity, causing to release manganese ions and increase conductivity. With pulsed microwaves, manganese ions move repeatedly in gigahertz alternating electric field, resulting in a transient heating and thermoelastic expansion through the Joule effect, which yields a strong thermoacoustic (TA) wave in tumor site. In vitro and in vivo experiments demonstrate that manganous-manganic oxide-based nanoprobe could high-selectively amplify the TA signal in deep-located tumor. Our proposed tumor-specific MTAI method based on TME activation provides a potential approach for deep-located tumor detection.
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Inducing gamma oscillations with non-invasive light flicker has been reported to impact Alzheimer's disease-related pathology. However, it is unclear which signaling pathways are involved in reducing amyloid load. Here, we found that gamma frequency light flicker increased anchoring of amyloid precursor protein (APP) to the plasma membrane for non-amyloidogenic processing, and then physically interacted with KCC2, a neuron-specific K+ -Cl- cotransporter, suggesting that it is essential to maintain surface GABAA receptor α1 levels and reduce ß-amyloid (Aß) production. Stimulation with such light flicker limited KCC2 internalization and subsequent degradation via both tyrosine phosphorylation and ubiquitination, leading to an increase in surface-KCC2 levels. Specifically, PKC-dependent phosphorylation of APP on a serine residue was induced by gamma frequency light flicker, which was responsible for maintaining plasma membrane levels of full-length APP, leading to its reduced trafficking to endosomes and inhibiting the ß-secretase cleavage pathway. The activated PKC from the gamma frequency light flicker subsequently phosphorylated serine of KCC2 and stabilized it onto the cell surface, which contributed to the upregulation of surface GABAA receptor α1 levels. Together, these data indicate that enhancement of APP trafficking to the plasma membrane via light flicker plays a critical modulatory role in reduction of Aß load in Alzheimer's disease.