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Light as a source of information regulates morphological and physiological processes of fungi, including development, primary and secondary metabolism, or the circadian rhythm. Light signaling in fungi depends on photoreceptors and downstream components that amplify the signal to govern the expression of an array of genes. Here, we investigated the effects of red and far-red light in the mycoparasite Trichoderma guizhouense on its mycoparasitic potential. We show that the invasion strategy of T. guizhouense depends on the attacked species and that red and far-red light increased aerial hyphal growth and led to faster overgrowth or invasion of the colonies. Molecular experiments and transcriptome analyses revealed that red and far-red light are sensed by phytochrome FPH1 and further transmitted by the downstream MAPK HOG pathway and the bZIP transcription factor ATF1. Overexpression of the red- and far-red light-induced fluffy gene fluG in the dark resulted in abundant aerial hyphae formation and thereby improvement of its antagonistic ability against phytopathogenic fungi. Hence, light-induced fluG expression is important for the mycoparasitic interaction. The increased aggressiveness of fluG-overexpressing strains was phenocopied by four random mutants obtained after UV mutagenesis. Therefore, aerial hyphae formation appears to be a trait for the antagonistic potential of T. guizhouense.
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Regulación Fúngica de la Expresión Génica , Hifa , Luz , Fitocromo , Trichoderma , Hifa/crecimiento & desarrollo , Hifa/genética , Fitocromo/metabolismo , Fitocromo/genética , Trichoderma/genética , Trichoderma/fisiología , Trichoderma/crecimiento & desarrollo , Enfermedades de las Plantas/microbiología , Proteínas Fúngicas/metabolismo , Proteínas Fúngicas/genética , Ascomicetos/genética , Ascomicetos/crecimiento & desarrollo , Rhizoctonia/crecimiento & desarrollo , Luz RojaRESUMEN
Accurate approaches for quantifying muscle fibers are essential in biomedical research and meat production. In this study, we address the limitations of existing approaches for hematoxylin and eosin-stained muscle fibers by manually and semiautomatically labeling over 660 000 muscle fibers to create a large dataset. Subsequently, an automated image segmentation and quantification tool named MyoV is designed using mask regions with convolutional neural networks and a residual network and feature pyramid network as the backbone network. This design enables the tool to allow muscle fiber processing with different sizes and ages. MyoV, which achieves impressive detection rates of 0.93-0.96 and precision levels of 0.91-0.97, exhibits a superior performance in quantification, surpassing both manual methods and commonly employed algorithms and software, particularly for whole slide images (WSIs). Moreover, MyoV is proven as a powerful and suitable tool for various species with different muscle development, including mice, which are a crucial model for muscle disease diagnosis, and agricultural animals, which are a significant meat source for humans. Finally, we integrate this tool into visualization software with functions, such as segmentation, area determination and automatic labeling, allowing seamless processing for over 400 000 muscle fibers within a WSI, eliminating the model adjustment and providing researchers with an easy-to-use visual interface to browse functional options and realize muscle fiber quantification from WSIs.
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Aprendizaje Profundo , Humanos , Animales , Ratones , Procesamiento de Imagen Asistido por Computador/métodos , Fibras Musculares Esqueléticas , Redes Neurales de la Computación , AlgoritmosRESUMEN
Low temperature (LT) greatly restricts grain filling in maize (Zea mays L.), but the relevant molecular mechanisms are not fully understood. To better understand the effect of LT on grain development, 17 hybrids were subjected to LT stress in field trials over 3 years, and two hybrids of them with contrasting LT responses were exposed to 30/20°C and 20/10°C for 7 days during grain filling in a greenhouse. At LT, thousand-kernel weight declined, especially in LT-sensitive hybrid FM985, while grain-filling rate was on average about 48% higher in LT-tolerant hybrid DK159 than FM985. LT reduced starch synthesis in kernel mainly by suppression of transcript levels and enzyme activities for sucrose synthase and hexokinase. Brassinolide (BR) was abundant in DK159 kernel, and genes involved in BR and cytokinin signals were inducible by stress. LT downregulated the genes in light-harvesting complex and photosystem I/II subunits, accompanied by reduced photosynthetic rate and Fv/Fm in ear leaf. The LT-tolerant hybrid could maintain a high soluble sugar content and fast interconversion between sucrose and hexose in the stem internode and cob, improving assimilate allocation to kernel at LT stress and paving the way for simultaneous growth and LT stress responses.
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Frío , Regulación de la Expresión Génica de las Plantas , Zea mays , Zea mays/crecimiento & desarrollo , Zea mays/genética , Zea mays/metabolismo , Zea mays/fisiología , Glucosiltransferasas/metabolismo , Glucosiltransferasas/genética , Fotosíntesis , Almidón/metabolismo , Grano Comestible/crecimiento & desarrollo , Grano Comestible/genética , Grano Comestible/fisiología , Proteínas de Plantas/metabolismo , Proteínas de Plantas/genética , Semillas/crecimiento & desarrollo , Semillas/genética , Semillas/metabolismo , Brasinoesteroides/metabolismo , Esteroides Heterocíclicos/farmacología , Esteroides Heterocíclicos/metabolismoRESUMEN
Where does one draw the line between primary and secondary metabolism? The answer depends on the perspective. Microbial secondary metabolites (SMs) were at first believed not to be very important for the producers because they are dispensable for growth under laboratory conditions. However, such compounds become important in natural niches of the organisms, and some are of prime importance for humanity. Polyketides are an important group of SMs with aflatoxin as a well-known and well-characterized example. In Aspergillus spp., all 34 afl genes encoding the enzymes for aflatoxin biosynthesis are located in close vicinity on chromosome III in a so-called gene cluster. This led to the assumption that most genes required for polyketide biosynthesis are organized in gene clusters. Recent research, however, revealed an enormous complexity of the biosynthesis of different polyketides, ranging from individual polyketide synthases to a gene cluster producing several compounds, or to several clusters with additional genes scattered in the genome for the production of one compound. Research of the last decade furthermore revealed a huge potential for SM biosynthesis hidden in fungal genomes, and methods were developed to wake up such sleeping genes. The analysis of organismic interactions starts to reveal some of the ecological functions of polyketides for the producing fungi.
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Aflatoxinas , Policétidos , Metabolismo Secundario/genética , Sintasas Poliquetidas/genética , Sintasas Poliquetidas/metabolismo , Genoma Fúngico , Policétidos/metabolismo , Familia de Multigenes , Aflatoxinas/metabolismo , Genes FúngicosRESUMEN
Unconscious acquisition of sequence structure from experienced events can lead to explicit awareness of the pattern through extended practice. Although the implicit-to-explicit transition has been extensively studied in humans using the serial reaction time (SRT) task, the subtle neural activity supporting this transition remains unclear. Here, we investigated whether frequency-specific neural signal transfer contributes to this transition. A total of 208 participants (107 females) learned a sequence pattern through a multisession SRT task, allowing us to observe the transitions. Session-by-session measures of participants' awareness for sequence knowledge were conducted during the SRT task to identify the session when the transition occurred. By analyzing time course RT data using switchpoint modeling, we identified an increase in learning benefit specifically at the transition session. Electroencephalogram (EEG)/magnetoencephalogram (MEG) recordings revealed increased theta power in parietal (precuneus) regions one session before the transition (pretransition) and a prefrontal (superior frontal gyrus; SFG) one at the transition session. Phase transfer entropy (PTE) analysis confirmed that directional theta transfer from precuneus â SFG occurred at the pretransition session and its strength positively predicted learning improvement at the subsequent transition session. Furthermore, repetitive transcranial magnetic stimulation (TMS) modulated precuneus theta power and altered transfer strength from precuneus to SFG, resulting in changes in both transition rate and learning benefit at that specific point of transition. Our brain-stimulation evidence supports a role for parietal â prefrontal theta signal transfer in igniting conscious awareness of implicitly acquired knowledge.SIGNIFICANCE STATEMENT There exists a pervasive phenomenon wherein individuals unconsciously acquire sequence patterns from their environment, gradually becoming aware of the underlying regularities through repeated practice. While previous studies have established the robustness of this implicit-to-explicit transition in humans, the refined neural mechanisms facilitating conscious access to implicit knowledge remain poorly understood. Here, we demonstrate that prefrontal activity, known to be crucial for conscious awareness, is triggered by neural signal transfer originating from the posterior brain region, specifically the precuneus. By employing brain stimulation techniques, we establish a causal link between neural signal transfer and the occurrence of awareness. Our findings unveil a mechanism by which implicit knowledge becomes consciously accessible in human cognition.
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Concienciación , Aprendizaje , Femenino , Humanos , Concienciación/fisiología , Aprendizaje/fisiología , Corteza Prefrontal/fisiología , Tiempo de Reacción/fisiología , ElectroencefalografíaRESUMEN
Drought is a major abiotic stress reducing maize (Zea mays) yield worldwide especially before and during silking. The mechanism underlying drought tolerance in maize and the roles of different organs have not been elucidated. Hence, we conducted field trials under pre-silking drought conditions using two maize genotypes: FM985 (drought-tolerant) and ZD958 (drought-sensitive). The two genotypes did not differ in plant height, grain number, and yield under control conditions. However, the grain number per ear and the yield of FM985 were 38.1 and 35.1% higher and plants were 17.6% shorter than ZD958 under drought conditions. More 13 C photosynthates were transported to the ear in FM985 than in ZD958, which increased floret fertility and grain number. The number of differentially expressed genes was much higher in stem than in other organs. Stem-ear interactions are key determinants of drought tolerance, in which expression of genes related to abscisic acid, lignin, and flavonoid biosynthesis and carbon metabolism in the stem was induced by drought, which inhibited stem elongation and promoted assimilate allocation to the ear in FM985. In comparison with ZD958, the activities of trehalose 6-phosphate phosphatase and sucrose non-fermentation-associated kinase 1 were higher in the stem and lower in the kernel of FM985, which facilitated kernel formation. These results reveal that, beyond the ear response, stem elongation is involved in the whole process of drought tolerance before silking. Abscisic acid together with trehalose 6-phosphate, lignin, and flavonoid suppresses stem elongation and allocates assimilates into the ear, providing a novel and systematic regulatory pathway for drought tolerance in maize.
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Ácido Abscísico , Resistencia a la Sequía , Ácido Abscísico/metabolismo , Zea mays/metabolismo , Lignina/metabolismo , Flavonoides/metabolismo , Trehalosa/metabolismo , Grano Comestible , Sequías , Fosfatos/metabolismo , Estrés FisiológicoRESUMEN
Blue aleurone of barley is caused by the accumulation of delphinidin-based derivatives. Although these compounds are ideal nutrients for human health, they are undesirable contaminants in malt brewing. Therefore, the ability to add and remove this trait easily would facilitate breeding barley for different purposes. Here we identified a glutathione S-transferase gene (HvGST) that was responsible for the blue aleurone trait in Tibetan qingke barley by performing a genome-wide association study and RNA-sequencing analysis. Gene variation and expression analysis indicated that HvGST also participates in the transport and accumulation of anthocyanin in purple barley. Haplotype and the geographic distribution analyses of HvGST alleles revealed two independent natural variants responsible for the emergence of white aleurone: a 203-bp deletion causing premature termination of translation in qingke barley and two key single nucleotide polymorphisms in the promoter resulting in low transcription in Western barley. This study contributes to a better understanding of mechanisms of colored barley formation, and provides a comprehensive reference for marker-assisted barley breeding.
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Antocianinas , Hordeum , Antocianinas/metabolismo , Estudio de Asociación del Genoma Completo , Haplotipos , Hordeum/genética , Hordeum/metabolismo , FitomejoramientoRESUMEN
Emotions are fundamental to social interaction and deeply intertwined with interpersonal dynamics, especially in romantic relationships. Although the neural basis of interaction processes in romance has been widely explored, the underlying emotions and the connection between relationship quality and neural synchronization remain less understood. Our study employed EEG hyperscanning during a non-interactive video-watching paradigm to compare the emotional coordination between romantic couples and close friends. Couples showed significantly greater behavioral and prefrontal alpha synchronization than friends. Notably, couples with low relationship quality required heightened neural synchronization to maintain robust behavioral synchronization. Further support vector machine analysis underscores the crucial role of prefrontal activity in differentiating couples from friends. In summary, our research addresses gaps concerning how intrinsic emotions linked to relationship quality influence neural and behavioral synchronization by investigating a natural non-interactive context, thereby advancing our understanding of the neural mechanisms underlying emotional coordination in romantic relationships.
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Electroencefalografía , Emociones , Amigos , Relaciones Interpersonales , Humanos , Masculino , Amigos/psicología , Emociones/fisiología , Femenino , Adulto Joven , Adulto , Corteza Prefrontal/fisiología , Interacción SocialRESUMEN
Spontaneous generation of H2O2 in sub-10 µm-sized water microdroplets has received increasing interest since its first discovery in 2019. On the other hand, due to the short lifetime of these microdroplets (rapid evaporation) and lack of suitable tools to real-time monitor the generation of H2O2 in individual microdroplets, such a seemingly thermodynamically unfavorable process has also raised vigorous debates on the origin of H2O2 and the underlying mechanism. Herein, we prepared water microdroplets with a long lifetime (>1 h) by virtue of microwell confinement and dynamically monitored the spontaneous generation of H2O2 in individual microdroplets via time-lapsed fluorescence imaging. It was unveiled that H2O2 was continuously generated in the as-prepared water microdroplets and an apparent equilibrium concentration of â¼3 µM of H2O2 in the presence of a H2O2-consuming reaction can be obtained. Through engineering the geometry of these microdroplets, we further revealed that the generation rates of H2O2 in individual microdroplets were positively proportional to their surface-to-volume ratios. This also allowed us to extract a maximal H2O2 generation rate of 7.7 nmol m-2 min-1 in the presence of a H2O2-consuming reaction and derive the corresponding probability of spontaneous conversion of interfacial H2O into H2O2 for the first time, that is, â¼1 of 65,000 water molecules in 1 s. These findings delivered strong evidence that the spontaneous generation of H2O2 indeed occurs at the surface of microdroplets and provided us with an important starting point to further enhance the yield of H2O2 in water microdroplets for future applications.
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BACKGROUND: Increased oxidative stress contributes to enhanced osteoclastogenesis and age-related bone loss. Melatonin (MT) is an endogenous antioxidant and declines with aging. However, it was unclear whether the decline of MT was involved in the enhanced osteoclastogenesis during the aging process. METHODS: The plasma level of MT, oxidative stress status, bone mass, the number of bone marrow-derived monocytes (BMMs) and its osteoclastogenesis were analyzed in young (3-month old) and old (18-month old) mice (n = 6 per group). In vitro, BMMs isolated from aged mice were treated with or without MT, followed by detecting the change of osteoclastogenesis and intracellular reactive oxygen species (ROS) level. Furthermore, old mice were treated with MT for 2 months to investigate the therapeutic effect. RESULTS: The plasma level of MT was markedly lower in aged mice compared with young mice. Age-related decline in MT was accompanied by enhanced oxidative stress, osteoclastogenic potential and bone loss. MT intervention significantly suppressed the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, decreased intracellular ROS and enhanced antioxidant capacity of BMMs from aged mice. MT supplementation significantly attenuated oxidative stress, osteoclastogenesis, bone loss and deterioration of bone microstructure in aged mice. CONCLUSIONS: These results suggest that age-related decline of MT enhanced osteoclastogenesis via disruption of redox homeostasis. MT may serve as a key regulator in osteoclastogenesis and bone homeostasis, thereby highlighting its potential as a preventive agent for age-related bone loss.
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Melatonina , Osteoporosis , Animales , Ratones , Osteogénesis , Osteoclastos/metabolismo , Melatonina/farmacología , Especies Reactivas de Oxígeno , Antioxidantes/farmacología , Oxidación-Reducción , Homeostasis , Diferenciación Celular , FN-kappa B/metabolismoRESUMEN
Single-nanoparticle studies often need one or a series of nanoparticle populations that are designed with differences in a nominally particular structural parameter to clarify the structure-activity relationship (SAR). However, the heterogeneity of various properties within any population would make it rather difficult to approach an ideal one-parameter control. In situ modification ensures the same nanoparticle to be investigated and also avoids complicating effects from the otherwise often needed ex situ operations. Herein, we apply electrochemical cycling to single platinum nanoparticles and optically examine their SAR. An electrocatalytic fluorescent microscopic method is established to evaluate the apparent catalytic activity of a number of single nanoparticles toward the oxygen reduction reaction. Meanwhile, dark-field microscopy with the substrate electrode under a cyclic potential control is found to be able to assess the electrochemically active surface area (ECSA) of single nanoparticles via induced chloride redox electrochemistry. Consequently, nanoparticles with drastically increased catalytic activity are discovered to have larger ECSAs upon potential regulation, and interestingly, there are also a few particles with decreased activity, as opposed to the overall trend, that all develop a smaller ECSA in the process. The deactivated nanoparticles against the overall enhancement effects of potential cycling are revealed for the first time. As such, the SAR of single nanoparticles when subjected to an in situ structural control is optically demonstrated.
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Structural neuroimaging data have been used to compute an estimate of the biological age of the brain (brain-age) which has been associated with other biologically and behaviorally meaningful measures of brain development and aging. The ongoing research interest in brain-age has highlighted the need for robust and publicly available brain-age models pre-trained on data from large samples of healthy individuals. To address this need we have previously released a developmental brain-age model. Here we expand this work to develop, empirically validate, and disseminate a pre-trained brain-age model to cover most of the human lifespan. To achieve this, we selected the best-performing model after systematically examining the impact of seven site harmonization strategies, age range, and sample size on brain-age prediction in a discovery sample of brain morphometric measures from 35,683 healthy individuals (age range: 5-90 years; 53.59% female). The pre-trained models were tested for cross-dataset generalizability in an independent sample comprising 2101 healthy individuals (age range: 8-80 years; 55.35% female) and for longitudinal consistency in a further sample comprising 377 healthy individuals (age range: 9-25 years; 49.87% female). This empirical examination yielded the following findings: (1) the accuracy of age prediction from morphometry data was higher when no site harmonization was applied; (2) dividing the discovery sample into two age-bins (5-40 and 40-90 years) provided a better balance between model accuracy and explained age variance than other alternatives; (3) model accuracy for brain-age prediction plateaued at a sample size exceeding 1600 participants. These findings have been incorporated into CentileBrain (https://centilebrain.org/#/brainAGE2), an open-science, web-based platform for individualized neuroimaging metrics.
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Envejecimiento , Encéfalo , Imagen por Resonancia Magnética , Humanos , Adolescente , Femenino , Anciano , Adulto , Niño , Adulto Joven , Masculino , Encéfalo/diagnóstico por imagen , Encéfalo/anatomía & histología , Encéfalo/crecimiento & desarrollo , Anciano de 80 o más Años , Preescolar , Persona de Mediana Edad , Envejecimiento/fisiología , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Neuroimagen/normas , Tamaño de la MuestraRESUMEN
BACKGROUND: The trajectory of attention-deficit hyperactivity disorder (ADHD) symptoms in children and adolescents, encompassing descending, stable, and ascending patterns, delineates their ADHD status as remission, persistence or late onset. However, the neural and genetic underpinnings governing the trajectory of ADHD remain inadequately elucidated. METHODS: In this study, we employed neuroimaging techniques, behavioral assessments, and genetic analyses on a cohort of 487 children aged 6-15 from the Children School Functions and Brain Development project at baseline and two follow-up tests for 1 year each (interval 1: 1.14 ± 0.32 years; interval 2: 1.14 ± 0.30 years). We applied a Latent class mixed model (LCMM) to identify the developmental trajectory of ADHD symptoms in children and adolescents, while investigating the neural correlates through gray matter volume (GMV) analysis and exploring the genetic underpinnings using polygenic risk scores (PRS). RESULTS: This study identified three distinct trajectories (ascending-high, stable-low, and descending-medium) of ADHD symptoms from childhood through adolescence. Utilizing the linear mixed-effects (LME) model, we discovered that attention hub regions served as the neural basis for these three developmental trajectories. These regions encompassed the left anterior cingulate cortex/medial prefrontal cortex (ACC/mPFC), responsible for inhibitory control; the right inferior parietal lobule (IPL), which facilitated conscious focus on exogenous stimuli; and the bilateral middle frontal gyrus/precentral gyrus (MFG/PCG), accountable for regulating both dorsal and ventral attention networks while playing a crucial role in flexible modulation of endogenous and extrinsic attention. Furthermore, our findings revealed that individuals in the ascending-high group exhibited the highest PRS for ADHD, followed by those in the descending-medium group, with individuals in the stable-low group displaying the lowest PRS. Notably, both ascending-high and descending-medium groups had significantly higher PRS compared to the stable-low group. CONCLUSIONS: The developmental trajectory of ADHD symptoms in the general population throughout childhood and adolescence can be reliably classified into ascending-high, stable-low, and descending-medium groups. The bilateral MFG/PCG, left ACC/mPFC, and right IPL may serve as crucial brain regions involved in attention processing, potentially determining these trajectories. Furthermore, the ascending-high pattern of ADHD symptoms exhibited the highest PRS for ADHD.
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Trastorno por Déficit de Atención con Hiperactividad , Humanos , Trastorno por Déficit de Atención con Hiperactividad/genética , Trastorno por Déficit de Atención con Hiperactividad/fisiopatología , Niño , Adolescente , Masculino , Femenino , Imagen por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Encéfalo/crecimiento & desarrollo , Sustancia Gris/diagnóstico por imagen , Sustancia Gris/patología , Neuroimagen , Estudios de CohortesRESUMEN
Oral submucous fibrosis (OSF) is a potentially malignant disorder of the oral mucosa; however, whether and how the fibrotic matrix of OSF is involved in the malignant transformation of epithelial cells remains unknown. Herein, oral mucosa tissue from patients with OSF, OSF rat models, and their controls were used to observe the extracellular matrix changes and epithelial-mesenchymal transformation (EMT) in fibrotic lesions. Compared with controls, oral mucous tissues from patients with OSF showed an increased number of myofibroblasts, a decreased number of blood vessels, and increased type I and type III collagen levels. In addition, the oral mucous tissues from humans and OSF rats showed increased stiffness, accompanied by increased EMT activities of epithelial cells. The EMT activities of stiff construct-cultured epithelial cells were increased significantly by exogenous piezo-type mechanosensitive ion channel component 1 (Piezo1) activation, and decreased by yes-associated protein (YAP) inhibition. During ex vivo implantation, oral mucosal epithelial cells of the stiff group showed increased EMT activities and increased levels of Piezo1 and YAP compared with those in the sham and soft groups. These results indicate that increased stiffness of the fibrotic matrix in OSF led to increased proliferation and EMT of mucosal epithelial cells, in which the Piezo1-YAP signal transduction is important.
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Fibrosis de la Submucosa Bucal , Humanos , Ratas , Animales , Fibrosis de la Submucosa Bucal/metabolismo , Fibrosis de la Submucosa Bucal/patología , Mucosa Bucal/metabolismo , Mucosa Bucal/patología , Transición Epitelial-Mesenquimal , Miofibroblastos/metabolismo , Células Epiteliales/metabolismoRESUMEN
Uncovering the immune response to an inactivated SARS-CoV-2 vaccine (In-Vac) and natural infection is crucial for comprehending COVID-19 immunology. Here we conducted an integrated analysis of single-cell RNA sequencing (scRNA-seq) data from serial peripheral blood mononuclear cell (PBMC) samples derived from 12 individuals receiving In-Vac compared with those from COVID-19 patients. Our study reveals that In-Vac induces subtle immunological changes in PBMC, including cell proportions and transcriptomes, compared with profound changes for natural infection. In-Vac modestly upregulates IFN-α but downregulates NF-κB pathways, while natural infection triggers hyperactive IFN-α and NF-κB pathways. Both In-Vac and natural infection alter T/B cell receptor repertoires, but COVID-19 has more significant change in preferential VJ gene, indicating a vigorous immune response. Our study reveals distinct patterns of cellular communications, including a selective activation of IL-15RA/IL-15 receptor pathway after In-Vac boost, suggesting its potential role in enhancing In-Vac-induced immunity. Collectively, our study illuminates multifaceted immune responses to In-Vac and natural infection, providing insights for optimizing SARS-CoV-2 vaccine efficacy.
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COVID-19 , Humanos , COVID-19/prevención & control , Vacunas contra la COVID-19 , Leucocitos Mononucleares , FN-kappa B , SARS-CoV-2 , Vacunas de Productos Inactivados , Inmunidad , Análisis de Secuencia de ARN , Anticuerpos AntiviralesRESUMEN
The overlapping peaks of the target chemical exchange saturation transfer (CEST) solutes and other unknown CEST solutes affect the quantification results and accuracy of the chemical exchange parameters-the fractional concentration, f b , exchange rate, k b , and transverse relaxation rate, R 2 b -for the target solutes. However, to date, no method has been established for assessing the overlapping peaks. This study aimed to develop a method for quantifying the f b , k b , and R 2 b values of a specific CEST solute, as well as assessing the overlap between the CEST peaks of the specific solute(s) and other unknown solutes. A simplified R 1 ρ model was proposed, assuming linear approximation of the other solutes' contributions to R 1 ρ . A CEST data acquisition scheme was applied with various saturation offsets and saturation powers. In addition to fitting the f b , k b , and R 2 b values of the specific solute, the overlapping condition was evaluated based on the root mean square error (RMSE) between the trajectories of the acquired and synthesized data. Single-solute and multi-solute phantoms with various phosphocreatine (PCr) concentrations and pH values were used to calculate the f b and k b of PCr and the corresponding RMSE. The feasibility of RMSE for evaluating the overlapping condition, and the accurate fitting of f b and k b in weak overlapping conditions, were verified. Furthermore, the method was employed to quantify the nuclear Overhauser effect signal in rat brains and the PCr signal in rat skeletal muscles, providing results that were consistent with those reported in previous studies. In summary, the proposed approach can be applied to evaluate the overlapping condition of CEST peaks and quantify the f b , k b , and R 2 b values of specific solutes, if the weak overlapping condition is satisfied.
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Algoritmos , Imagen por Resonancia Magnética , Ratas , Animales , Imagen por Resonancia Magnética/métodos , Fantasmas de ImagenRESUMEN
Excessive angiogenesis in subchondral bone is a pathological feature of osteoarthritis (OA). Tanshinone IIA (TIIA), an active compound found in Salvia miltiorrhiza, demonstrates significant anti-angiogenic properties. However, the effect of TIIA on abnormal subchondral angiogenesis in OA is still unclear. This study aims to investigate the mechanism of TIIA in modulating subchondral bone angiogenesis during OA and assess its therapeutic potential in OA. Our findings demonstrate that TIIA attenuated articular cartilage degeneration, normalized subchondral bone remodeling, and effectively suppressed aberrant angiogenesis within subchondral bone in monosodium iodoacetate (MIA)-induced OA mice. Additionally, the angiogenesis capacity of primary CD31hiEmcnhi endothelial cells was observed to be significantly reduced after treatment with TIIA in vitro. Mechanically, TIIA diminished the proportion of hypertrophic chondrocytes, ultimately leading to a substantial reduction in the secretion of vascular endothelial growth factor A (VEGFA). The supernatant of hypertrophic chondrocytes promoted the tube formation of CD31hiEMCNhi endothelial cells, whereas TIIA inhibited this process. Furthermore, TIIA effectively suppressed the expression of vascular endothelial growth factor receptor 2 (VEGFR2) along with its downstream MAPK pathway in CD31hiEmcnhi endothelial cells. In conclusion, our data indicated that TIIA could effectively inhibit the abnormal angiogenesis in subchondral bone during the progression of OA by suppressing the VEGFA/VEFGR2/MAPK pathway. These findings significantly contribute to our understanding of the abnormal angiogenesis in OA and offer a promising therapeutic target for OA treatment.
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Abietanos , Cartílago Articular , Osteoartritis , Ratones , Animales , Factor A de Crecimiento Endotelial Vascular , Células Endoteliales/metabolismo , Angiogénesis , Osteoartritis/metabolismoRESUMEN
A Gram-stain-negative, aerobic, motile with flagella and rod- or ovoid-shaped bacterium, designated GG15T, was isolated from tidal flat sediment sampled in Zhoushan, Zhejiang Province. Strain GG15T grew at 20-40â°C (optimum, 30â°C), at pH 5.5-9.5 (optimum, pH 7.0-8.0) and with 1.0-10.0â% (w/v) NaCl (optimum, 1.5â%). Colony diameters ranged from 1 to 3 mm within the first week, reaching a maximum of 6-7 mm after 15 days of cultivation. Strain GG15T exhibited highest 16S rRNA gene sequence similarity to Microbulbifer taiwanensis CCM 7856T (98.1 %), with similarity to other species within the genus Microbulbifer ranging from 97.8 to 93.8â%. Similarity values to other genera were below 93.8â%. Strain GG15T exhibited positive activity for ß-glucosidase, trypsin and chymotrypsin, whereas the reference strain showed negative activity. Chemotaxonomic analyses indicated that strain GG15T contained Q-8 as the sole respiratory quinone, C16â:â0 (9.1â%), iso-C15â:â0 (30.9â%) and iso-C11â:â0 3-OH (7.2â%) as the predominant fatty acids, and phosphatidylethanolamine, phosphatidylglycerol, three unidentified lipids, four unidentified glycolipids, one unidentified phospholipid, two unidentified aminolipids and two unidentified aminophospholipids as the main polar lipids. The genome of strain GG15T was 4â307â641 bp long, comprising 3861 protein-coding genes. The G+C content of strain GG15T was 61.5âmol% based on its genomic sequence. Strain GG15T showed low digital DNA-DNA hybridization (<70â%) and average nucleotide identity values (<95â%) with other Microbulbifer species. As a result, a novel species within the genus Microbulbifer, named Microbulbifer magnicolonia sp. nov., is proposed. The type strain is GG15T (MCCC 1K08802T=KCTC 8210T).
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Alteromonadaceae , Ácidos Grasos , Composición de Base , Ácidos Grasos/química , ARN Ribosómico 16S/genética , Filogenia , Análisis de Secuencia de ADN , ADN Bacteriano/genética , Técnicas de Tipificación Bacteriana , ChinaRESUMEN
PURPOSE: To examine the relationship between hyperdense artery sign (HAS)/susceptibility vessel sign (SVS) and thrombus composition and evaluate the effect of HAS/SVS status on the association between first-line thrombectomy techniques and outcomes in patients with acute anterior circulation large vessel occlusion (LVO). MATERIALS AND METHODS: From January 2018 to June 2021, 103 consecutive patients with acute anterior circulation LVO (75 [63.1%] men; median age, 66 years) who underwent thrombectomy and for whom the removed clot was available for histological analyses were retrospectively reviewed. The presence of HAS and SVS was assessed on unenhanced computed tomography (CT) and susceptibility-weighted imaging, respectively. Association of first-line thrombectomy techniques (stent retriever [SR] combined with contact aspiration [CA] vs CA alone) with outcomes was assessed according to HAS/SVS status. RESULTS: Among the included patients, 55 (53.4%) were HAS/SVS-negative, and 69 (67.0%) underwent first-line SR + CA. Higher relative densities of fibrin/platelets (0.56 vs 0.51; P < .001) and lower relative densities of erythrocytes (0.32 vs 0.42; P < .001) were observed in HAS/SVS-negative patients compared with HAS/SVS-positive patients. First-line SR + CA was associated with reduced odds of distal embolization (adjusted odds ratio, 0.18; 95% CI, 0.04-0.83; P = .027) and a more favorable 90-day functional outcome (adjusted odds ratio, 5.29; 95% CI, 1.06-26.34; P = .042) in HAS/SVS-negative patients and a longer recanalization time (53 vs 25 minutes; P = .025) and higher risk of subarachnoid hemorrhage (24.2% vs 0%; P = .044) in HAS/SVS-positive patients. CONCLUSIONS: Absence of HAS/SVS may indicate a higher density of fibrin/platelets in the thrombus, and first-line SR + CA yielded superior functional outcomes than CA alone in patients with acute LVO without HAS/SVS.
Asunto(s)
Procedimientos Endovasculares , Stents , Trombectomía , Humanos , Masculino , Femenino , Trombectomía/efectos adversos , Trombectomía/instrumentación , Estudios Retrospectivos , Anciano , Resultado del Tratamiento , Persona de Mediana Edad , Succión , Procedimientos Endovasculares/instrumentación , Procedimientos Endovasculares/efectos adversos , Valor Predictivo de las Pruebas , Factores de Riesgo , Anciano de 80 o más Años , Factores de Tiempo , Trombosis Intracraneal/diagnóstico por imagen , Trombosis Intracraneal/terapia , Trombosis Intracraneal/fisiopatologíaRESUMEN
The diffusion dynamics of small molecules into polymer entities is crucial for driving their morphology and function, which can be applied to research fields such as optical identification, medical implantation and intelligent sensing platforms. Herein, we demonstrate a nondestructive bright-field imaging strategy to monitor and control the morphology of polymer microspheres by varying the interfacial interaction and diffusion in a penetrant bath. The nanoscale interface movement of single polymer microspheres was tracked and converted into the diameter variation during the swelling event with sub-pixel accuracy, which is consistent with the calculation using Li-Tanaka's kinetic equations. More interestingly, the solvent diffusion dynamics along different directions of one particle are heterogeneous, indicating the non-uniform internal structure of a soft confined assembly. The swelling characteristics of single polymer microspheres can be quantified by this simple imaging strategy, and the transient intermediate swelling states are captured. To model the lifetime and stabilization times of microplastic entities, solvent selectivity and thermodynamic regulation were introduced to obtain the activation energy down to the single micro-entity level. This optical methodology shows capability for decoding the complex diffusion mechanism in polymer entities and provides guidance for the design of drug delivery systems, sensor platforms, and optical responsive materials.