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BACKGROUND: Narcolepsy type 1 (NT1) is a sleep disorder characterized by excessive daytime sleepiness accompanied by cataplexy. Sleep disorders have been shown to affect the glymphatic system. This study aimed to evaluate changes in the diffusion tensor imaging along the perivascular space (DTI-ALPS) index and choroid plexus (CP) volume in NT1 participants, and to further explore their clinical significance. METHODS: We prospectively enrolled participants diagnosed with NT1 based on cerebrospinal fluid hypocretin-1 concentration and multiple sleep latency tests at our hospital. All participants underwent MRI to allow analysis of the DTI-ALPS index and CP volume. We subsequently performed correlation analyses between the DTI-ALPS index, CP volume, and important clinical parameters, including the Epworth Sleepiness Scale (ESS) score, Narcolepsy Severity Scale (NSS) score, stage rapid eye movement sleep (REM) ratio, stage 1 non-REM (N1) ratio, stage 2 non-REM (N2) ratio, and stage 3 non-REM (N3) ratio, among the NT1 participants. Inter-group and correlation analyses of DTI-ALPS index and CP volume were performed using age, sex, body mass index, and lateral ventricle volume as covariates. RESULTS: This study enrolled 41 NT1 participants and 42 healthy controls (HC). The DTI-ALPS index of NT1 participants was significantly lower than HC (1.444 ± 0.119 vs.1.661 ± 0.135, P < 0.001), while the CP volume of NT1 participants was significantly larger than those of HC (0.831 ± 0.146 vs. 0.645 ± 0.137, P < 0.001). The DTI-ALPS index was negatively correlated with both the ESS (PFDR-corrected<0.001) and NSS scores (PFDR-corrected = 0.010), but positively correlated with the Stage N3 ratio (PFDR-corrected = 0.033). The CP volume of NT1 participants was positively correlated with ESS (PFDR-corrected = 0.047) and NSS scores (PFDR-corrected = 0.047), but negatively correlated with the stage N3 ratio (PFDR-corrected = 0.047). CONCLUSION: Our study suggests that the DTI-ALPS index was lower and CP volume was larger in NT1 participants. The DTI-ALPS index and CP volume in the NT1 participants were related to disease severity and sleep structure. These findings may provide new insights into the mechanisms underlying NT1.
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The gut microbiome is an emerging factor in preventing hypertension, yet the influence of gut bacteriophages, viruses infecting bacteria, on this condition remains unclear. Bacteriophage-bacteria interactions, which impact the gut microbiome, are influenced differentially by temperate and virulent bacteriophages. However, the standard technique for studying viral populations, viral-like particles (VLPs)-metagenomes, often overlook prophages, the intracellular stage of temperate bacteriophages, creating a knowledge gap. To address this, we investigated alterations in extracellular and intracellular bacteriophages, alongside bacterial populations, in the angiotensin II-hypertension model. We sequenced VLPs and bulk DNA from cecal-colonic samples collected from male C57BL/6J mice implanted with minipumps containing saline or angiotensin II. We assembled 106 bacterial and 816 viral genomes and found that gut viral and bacterial populations remained stable between hypertensive and normotensive mice. A higher number of temperate viruses were observed across all treatments. Although temperate viruses outnumbered virulent viruses, sequencing of both VLPs and bulk revealed that virions from virulent viruses were more abundant in the murine gut. We then evaluated the impact of low- and high-fiber intake on gut microbiome composition in the angiotensin II model. Fiber intake significantly influenced the gut microbiome composition and hypertension development. Mice receiving high-fiber had lower blood pressure, a higher bacterial-encoded carbohydrate-associated enzyme, and a higher total relative abundance of temperate viruses than those receiving low-fiber. Our findings suggest that phages are not associated with hypertension development in the angiotensin II model. However, they support a complex diet-bacteria/phage interaction that may be involved in blood pressure regulation.
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Bacterias , Bacteriófagos , Fibras de la Dieta , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Hipertensión , Ratones Endogámicos C57BL , Animales , Fibras de la Dieta/administración & dosificación , Ratones , Masculino , Hipertensión/virología , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Bacteriófagos/fisiología , Bacteriófagos/genética , Angiotensina II/metabolismo , Genoma ViralRESUMEN
Bronchopulmonary dysplasia (BPD) is a chronic lung disease of preterm infants, with its incidence rising due to improved survival rates of these infants. BPD results from a combination of prenatal and postnatal factors, such as mechanical ventilation, oxygen toxicity, and infections, all of which significantly impact the prognosis and growth of affected infants. Current treatment options for BPD are largely supportive and do not address the underlying pathology. Exosomes are cell-derived bilayer-enclosed membrane structures enclosing proteins, lipids, RNAs, growth factors, cytokines and metabolites. They have become recognized as crucial regulators of intercellular communication in various physiological and pathological processes. Previous studies have revealed the therapeutic potential of human umbilical cord mesenchymal stem cells-derived exosomes (HUCMSCs-Exos) in promoting tissue repair and regeneration. Therefore, HUCMSCs-Exos maybe a promising and effective therapeutic modality for BPD. In this review, we firstly provide a comprehensive overview of BPD, including its etiology and the mechanisms of lung injury. Then we detail the isolation, characterization, and contents of HUCMSCs-Exos, and discuss their potential mechanisms of HUCMSCs-Exos in BPD treatment. Additionally, we summarize current clinical trials and discuss the challenges in translating these findings from bench to bedside. This review aims to lay the groundwork for future clinical applications of HUCMSCs-Exos in treating BPD.
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Displasia Broncopulmonar , Exosomas , Células Madre Mesenquimatosas , Cordón Umbilical , Humanos , Exosomas/metabolismo , Exosomas/trasplante , Displasia Broncopulmonar/terapia , Displasia Broncopulmonar/metabolismo , Células Madre Mesenquimatosas/metabolismo , Cordón Umbilical/citología , Trasplante de Células Madre Mesenquimatosas/métodos , Recién Nacido , Animales , Recien Nacido PrematuroRESUMEN
In recent years, with the rapid development of new energy vehicles, the safety issues of lithium-ion batteries have attracted attentions from all sectors of society. Research has found that during the thermal runaway process of lithium-ion batteries, aerosol emissions usually occur earlier than other gases. Accurate and timely measurement of these aerosol concentrations can help to warn the power battery pack fires. However, existing aerosol sensors are unable to meet the requirements of real-time monitoring and high precision. This article proposes an ionization mechanism based aerosol sensor that works at principles of field emission, field charging and gas discharge, and investigates its static and dynamic response characteristics. The sensor is manufactured and assembled using Microelectro Mechanical Systems processing technology. The sensor exhibits superior performances in terms of range, sensitivity, nonlinearity, repeatability, response time, and other aspects. The study provides a new solution for current aerosol detection with great potential for application.
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Multiple resonance (MR) boron-nitrogen doped polycyclic aromatic hydrocarbons (BN-PAHs) have shown compelling thermally activated delayed fluorescence (TADF), surpassing those of their hydrocarbon analogues. However, the structural variety of π-extended BN-PAHs remains narrow. In this study, we synthesized three double helical BN-doped nanographenes (BN-NGs), 2 a-2 c, and three heptagon-embedded BN-NGs, 1 a-1 c, by π-extension of the MR core. During the formation of 2 a, a nanographene with one heptagon (1 a) was obtained, whereas further dehydrocyclization of the [6]helicene units within 2 b and 2 c led to heptagon structures, yielding other two BN-NGs containing double heptagons (1 b and 1 c). These BN-NGs (2 a-2 c and 1 a-1 c) showed pronounced redshifts of 100-190â nm compared to the parent MR core, while preserving the TADF characteristics and prolonging the delayed fluorescence lifetime to the millisecond level. Furthermore, the integration of a heptagon ring into 1 a-1 c expanded the conjugation, reduced the oxidation potentials, and yielded a more flexible framework compared to those of 2 a-2 c. The enantiomers of 2 a-2 c, 1 a, and 1 c were resolved and their chiroptical properties were studied. Notably, 1 a and 1 c exhibited increased chiroptical dissymmetry factors.
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Objective. The decline in the performance of electromyography (EMG)-based silent speech recognition is widely attributed to disparities in speech patterns, articulation habits, and individual physiology among speakers. Feature alignment by learning a discriminative network that resolves domain offsets across speakers is an effective method to address this problem. The prevailing adversarial network with a branching discriminator specializing in domain discrimination renders insufficiently direct contribution to categorical predictions of the classifier.Approach. To this end, we propose a simplified discrepancy-based adversarial network with a streamlined end-to-end structure for EMG-based cross-subject silent speech recognition. Highly aligned features across subjects are obtained by introducing a Nuclear-norm Wasserstein discrepancy metric on the back end of the classification network, which could be utilized for both classification and domain discrimination. Given the low-level and implicitly noisy nature of myoelectric signals, we devise a cascaded adaptive rectification network as the front-end feature extraction network, adaptively reshaping the intermediate feature map with automatically learnable channel-wise thresholds. The resulting features effectively filter out domain-specific information between subjects while retaining domain-invariant features critical for cross-subject recognition.Main results. A series of sentence-level classification experiments with 100 Chinese sentences demonstrate the efficacy of our method, achieving an average accuracy of 89.46% tested on 40 new subjects by training with data from 60 subjects. Especially, our method achieves a remarkable 10.07% improvement compared to the state-of-the-art model when tested on 10 new subjects with 20 subjects employed for training, surpassing its result even with three times training subjects.Significance. Our study demonstrates an improved classification performance of the proposed adversarial architecture using cross-subject myoelectric signals, providing a promising prospect for EMG-based speech interactive application.
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Electromiografía , Humanos , Electromiografía/métodos , Masculino , Femenino , Redes Neurales de la Computación , Adulto , Software de Reconocimiento del Habla , Adulto Joven , Reconocimiento de Normas Patrones Automatizadas/métodos , Habla/fisiologíaRESUMEN
Depression and anxiety disorders are prevalent stress-related neuropsychiatric disorders and involve multiple molecular changes and dysfunctions across various brain regions. However, the specific and shared pathophysiological mechanisms occurring in these regions remain unclear. Previous research used a rat model of chronic mild stress (CMS) to segregate and identify depression-susceptible, anxiety-susceptible, and insusceptible groups; then the proteomes of six distinct brain regions (the hippocampus, prefrontal cortex, hypothalamus, pituitary, olfactory bulb, and striatum) were separately and quantitatively analyzed. To gain a comprehensive and systematic understanding of the molecular abnormalities, this study aimed to investigate and compare differential proteomics data from the six regions. Differentially expressed proteins (DEPs) were identified in between specific regions and across all regions and subjected to a series of bioinformatics analyses. Regional comparisons showed that stress-induced proteomic changes and corresponding gene ontology and pathway enrichments were largely distinct, attributable to differences in cell populations, protein compositions, and brain functions of these areas. Additionally, a notable degree of overlap in the significantly enriched terms was identified, potentially suggesting strong connections in the enrichment across different regions. Furthermore, intra-regional and inter-regional protein-protein interaction networks and drug-target-DEP networks were constructed. Integrated analysis of the three association networks in the six regions, along with the DisGeNET database, identified ten DEPs as potential targets for anti-depression/anxiety drugs. Collectively, these findings revealed commonalities and differences across different brain regions at the protein level induced by CMS, and identified several novel protein targets for the development of new therapeutics for depression and anxiety.
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Ansiolíticos , Encéfalo , Proteoma , Ratas Sprague-Dawley , Estrés Psicológico , Animales , Estrés Psicológico/metabolismo , Estrés Psicológico/tratamiento farmacológico , Proteoma/metabolismo , Masculino , Encéfalo/metabolismo , Encéfalo/efectos de los fármacos , Ansiolíticos/farmacología , Ansiolíticos/uso terapéutico , Ansiedad/metabolismo , Ansiedad/tratamiento farmacológico , Depresión/metabolismo , Depresión/tratamiento farmacológico , Mapas de Interacción de Proteínas , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Ratas , ProteómicaRESUMEN
Purpose: To label entecavir (ETV) with radioiodine and evaluate its effect on inhibiting hepatitis B virus (HBV) secretion and replication in vitro as well as its biodistribution in BALB/c mice. Methods: 125I-ETV was synthesized via binding a vinyl tributyltin group to ETV and producing electrophilic iodination of the group. Its chemical properties were assessed using traditional methods. Upon intravenous injection of 125I-ETV into BALB/c mice, the radioactivity of the critical organs was detected. In vitro, the anti-HBV activity of 125I-ETV was investigated using HepG2.2.15 cell culture model. Confocal microscopy was used to analyze the cell apoptosis. Culture supernatant samples were used for measuring HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) by enzyme-linked immunosorbent assay. Intracellular HBV pregenomic RNA (pgRNA), DNA, and covalently closed circular DNA (cccDNA) were measured by real-time fluorescence quantitative PCR. Results: The radiochemical purity of 125I-ETV was greater than 95% after incubation in freshly serum within 48 h. The three highest radioactivities were in the stomach, intestine, and liver after intravenous injection at 0.5 h, 2 h, and 24 h. The confocal fluorescence imaging showed that 125I-ETV did not induce cell apoptosis after treatment for 96 h. 125I-ETV decreases HBsAg and HBeAg secretions as well as intracellular HBV pgRNA, DNA, and cccDNA copies in a dose-dependent manner. Moreover, the anti-HBV activity of 125I-ETV is greater than that of ETV. Conclusions: The study outcome establishes 125I-ETV as a candidate for anti-HBV. However, it is still in need of further endorsement and optimization by animal model studies before using 125I-ETV to treat chronic HBV disease.
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[This corrects the article DOI: 10.1155/2014/237067.].
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BACKGROUND: Symptoms of depression and anxiety are common complications of narcolepsy. Earlier studies have shown that narcolepsy type 1 (NT1) is an autoimmune inflammatory disease and symptoms of depression and anxiety are closely related to fluctuations in inflammatory cytokines. The objective of the current research was to investigate the potential correlation between cytokines and symptoms of depression and anxiety in patients with NT1. METHODS: We collected demographic and clinical data and information on cytokine levels from 50 patients with NT1 and used Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS) to assess the severity of depression and anxiety symptoms. Patients with SDS scores ≥ 53 points were defined as depressive narcolepsy type 1 (D-NT1) and those with SDS scores < 53 points as non-depressive narcolepsy type 1 (ND-NT1). Patients with SAS scores ≥ 50 points were defined as anxious narcolepsy type 1 (A-NT1) and those with SAS scores < 50 points as non-anxious narcolepsy type 1 (NA-NT1). A binary logistic regression model was employed to identify the influencing factors of depressive and anxiety symptoms. RESULTS: Levels of IL-10 (p = 0.02), IL-4 (p = 0.049) and disease duration (p = 0.049) were decreased, while SAS scores (p < 0.001) and total sleep duration (p = 0.03) were increased in D-NT1 relative to ND-NT1 patients. A-NT1 patients had higher SDS scores (p < 0.001) compared to NA-NT1 patients. Binary logistic regression analysis revealed associations of longer disease duration (OR=0.83; 95 % CI: 0.70-0.97) and increased IL-10 (OR=0.40; 95 % CI: 0.17-0.90) with reduced risk of depression and worsening anxiety (SAS score; OR=1.17; 95 % CI: 1.06-1.30) with increased risk of depression in patients with NT1. Consistently, worsening depression (SDS score; OR=1.22; 95 % CI: 1.07-1.39) was correlated with increased risk of anxiety in the NT1 group. CONCLUSION: Our finding that higher IL-10 levels correlate with a lower risk of depression in NT1 patients provides a reference for further exploration of the pathophysiological mechanisms of depressive symptoms in NT1 patients.
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Ansiedad , Citocinas , Depresión , Narcolepsia , Humanos , Narcolepsia/psicología , Narcolepsia/complicaciones , Masculino , Femenino , Adulto , Depresión/etiología , Ansiedad/etiología , Ansiedad/psicología , Citocinas/sangre , Adulto Joven , Adolescente , Escalas de Valoración Psiquiátrica , Índice de Severidad de la Enfermedad , Persona de Mediana EdadRESUMEN
Orexin in cerebrospinal fluid (CSF) is a neuropeptide synthesized by a cluster of neurons in the lateral hypothalamus. It mainly functions to maintain arousal, regulate feeding, and participate in reward mechanisms. Radioimmunoassay (RIA) and enzyme-linked immunosorbent assay (ELISA) can detect CSF orexin. At present, RIA is widely used but is limited by various conditions, which is not conducive to its widespread development. We aimed to determine whether ELISA can replace RIA in detecting orexin in CSF. We investigated the results of 20 patients with central disorders of hypersomnolence, including 11 with narcolepsy type 1, 2 with narcolepsy type 2, 5 with idiopathic hypersomnia, and 2 with other causes of somnolence. RIA and ELISA were used to detect CSF orexin, and P valuesâ <.05 were considered to be significant. In the narcolepsy and non-narcolepsy type 1 groups, there was no correlation between the RIA and ELISA results (Pâ >â .05). In the narcolepsy type 1 group, the ELISA and RIA results were significantly different (Pâ <â .05), but this was not observed in the non-narcolepsy type 1 group (Pâ >â .05). The accuracy of ELISA to detect CSF orexin was lower than that of RIA (Pâ <â .05). ELISA cannot replace RIA in the measurement of CSF orexin, and RIA is recommended as the first choice when narcolepsy is suspected.
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Ensayo de Inmunoadsorción Enzimática , Narcolepsia , Orexinas , Radioinmunoensayo , Humanos , Orexinas/líquido cefalorraquídeo , Narcolepsia/líquido cefalorraquídeo , Narcolepsia/diagnóstico , Ensayo de Inmunoadsorción Enzimática/métodos , Masculino , Radioinmunoensayo/métodos , Femenino , Adulto , Persona de Mediana Edad , Adulto Joven , AdolescenteRESUMEN
Plant virus-derived vectors are rapid and cost-effective for protein expression and gene functional studies in plants, particularly for species that are difficult to genetically transform. However, few efficient viral vectors are available for functional studies in Asteraceae plants. Here, we identified a potyvirus named zinnia mild mottle virus (ZiMMV) from common zinnia (Zinnia elegans Jacq.) through next-generation sequencing. Using a yeast homologous recombination strategy, we established a full-length infectious cDNA clone of ZiMMV under the control of the cauliflower mosaic virus 35S promoter. Furthermore, we developed an efficient expression vector based on ZiMMV for the persistent and abundant expression of foreign proteins in the leaf, stem, root, and flower tissues with mild symptoms during viral infection in common zinnia. We showed that the ZiMMV-based vector can express ZeMYB9, which encodes a transcript factor inducing dark red speckles in leaves and flowers. Additionally, the expression of a gibberellic acid (GA) biosynthesis gene from the ZiMMV vector substantially accelerated plant height growth, offering a rapid and cost-effective method. In summary, our work provides a powerful tool for gene expression, functional studies, and genetic improvement of horticultural traits in Asteraceae plant hosts.
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Asteraceae , Vectores Genéticos , Potyvirus , Potyvirus/fisiología , Potyvirus/genética , Asteraceae/genética , Asteraceae/virología , Vectores Genéticos/genética , Giberelinas/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Lycium ruthenicum Murray possesses significant applications in both food and medicine, including antioxidative, anti-tumor, anti-fatigue, anti-inflammatory, and various other effects. Consequently, there has been a surge in research endeavors dedicated to exploring its potential benefits, necessitating the organization and synthesis of these findings. This article systematically reviews the extraction and content determination methods of active substances such as polysaccharides, anthocyanins, flavonoids, and polyphenols in LRM in the past five years, as well as some active ingredient composition determination methods, biological activities, and product development. This review is divided into three main parts: extraction and determination methods, their bioactivity, and product development. Building upon prior research, we also delve into the economic and medicinal value of Lycium ruthenicum Murray, thereby contributing significantly to its further exploration and development. It is anticipated that this comprehensive review will serve as a valuable resource for advancing research on Lycium ruthenicum Murray.
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Lycium , Extractos Vegetales , Lycium/química , Extractos Vegetales/química , Antocianinas/química , Humanos , Flavonoides/química , Antioxidantes/química , Antioxidantes/farmacología , Polifenoles/química , Fitoquímicos/química , Fitoquímicos/farmacología , Polisacáridos/químicaRESUMEN
BACKGROUND: Whether hyperbaric oxygen therapy (HBOT) can cause paradoxical herniation is still unclear. CASE SUMMARY: A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after surgery. HBOT was administered 22 d after surgery due to speech impairment. Paradoxical herniation appeared on the second day after treatment, and the patient's condition worsened after receiving mannitol treatment at the rehabilitation hospital. After timely skull repair, the paradoxical herniation was resolved, and the patient regained consciousness and had a good recovery as observed at the follow-up visit. CONCLUSION: Paradoxical herniation is rare and may be caused by HBOT. However, the underlying mechanism is unknown, and the understanding of this phenomenon is insufficient. The use of mannitol may worsen this condition. Timely skull repair can treat paradoxical herniation and prevent serious complications.
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To develop a scheme for distinguishing Kikuchi-Fujimoto disease (KFD) from lymphoma in patients presenting enlarged lymph nodes (LNs) predominantly on the upper side of the diaphragm. From November 2015 to August 2023, 32 KFD patients and 38 lymphoma patients were pathologically confirmed and enrolled in this retrospectively study. Clinical and 18F-fluorodeoxyglucose positron emission tomography (PET)/computed tomography (CT) features were collected. When comparing those PET/CT parameters, we set 5 models with different research objects: (1) all affected LNs; (2) the 5 largest affected LNs in terms of maximum diameter; (3) the 5 largest affected LNs in terms of maximum standard uptake values (SUVmax); (4) the largest affected LNs in terms of maximum diameter; (5) the largest affected LNs in terms of SUVmax. Compared to lymphoma patients, KFD patients were younger; and with higher incidence of fever, arthralgia, abnormal serum white blood cell, lactate dehydrogenase (LDH) and splenomegaly; lower incidence of affected LNs perinodal infiltration, necrosis and conglomeration; more affected LNs in Head and Neck nodes (particularly in level II) and Axillary in KFD (P Ë .05). PET/CT parameters presented as various difference in each model. Finally, 11 clinical and PET/CT features (ageâ ≤â 34, with fever, arthralgia, abnormal white blood cell, abnormal LDH, and without node necrosis and node conglomeration have a score of 2 each; splenomegaly, perinodal infiltration, median maximum diameterâ ≤â 20.5 and median SUVmax ≤ 7.1 of affected LNs in model 2 have score of 1 each) were selected as scheme items for distinguishing KFD from lymphoma. Individuals who have a total scoreâ >â 8, meet the criteria for KFD. Sensitivity and specificity were high: 86.8% (95% CI: 71.9%, 95.5%) and 96.9% (95% CI: 83.7%, 99.5%), AUCâ =â 0.975 (95% CI: 90.5%, 99.6%), respectively. It can effectively distinguish KFD from lymphoma by clinical and PET/CT parameters.
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Linfadenitis Necrotizante Histiocítica , Linfoma , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Linfadenitis Necrotizante Histiocítica/diagnóstico por imagen , Linfadenitis Necrotizante Histiocítica/patología , Estudios Retrospectivos , Esplenomegalia , Linfoma/diagnóstico por imagen , Linfoma/patología , Fluorodesoxiglucosa F18 , Artralgia/patología , Necrosis/patología , Ganglios Linfáticos/diagnóstico por imagen , Ganglios Linfáticos/patologíaRESUMEN
The low cost and high efficiency of microwave-assisted regeneration render it a viable alternative to conventional regeneration methods. To enhance the regeneration performance, we developed a coupled electromagnetic, heat, and mass transfer model to investigate the heat and mass transfer mechanisms of activated carbon during microwave-assisted regeneration. Simulation results demonstrated that the toluene desorption process is governed by temperature distribution. Changing the input power and flow rate can promote the intensity of hot spots and adjust their distribution, respectively, thereby accelerating toluene desorption, inhibiting readsorption, and promoting regeneration efficiency. Ultimately, controlling the input power and flow rate can flexibly adjust toluene emissions to satisfy the processing demands of desorbed toluene. Taken together, this study provides a comprehensive understanding of the heat and mass transfer mechanisms of microwave-assisted regeneration and insights into adsorbent regeneration.
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Carbón Orgánico , Calor , Microondas , Tolueno , Tolueno/química , Adsorción , Carbón Orgánico/química , Modelos QuímicosRESUMEN
AIMS: Animal models are regularly used to test the role of the gut microbiome in hypertension. Small-scale pre-clinical studies have investigated changes to the gut microbiome in the angiotensin II hypertensive model. However, the gut microbiome is influenced by internal and external experimental factors, which are not regularly considered in the study design. Once these factors are accounted for, it is unclear if microbiome signatures are reproduceable. We aimed to determine the influence of angiotensin II treatment on the gut microbiome using a large and diverse cohort of mice and to quantify the magnitude by which other factors contribute to microbiome variations. METHODS AND RESULTS: We conducted a retrospective study to establish a diverse mouse cohort resembling large human studies. We sequenced the V4 region of the 16S rRNA gene from 538 samples across the gastrointestinal tract of 303 male and female C57BL/6J mice randomized into sham or angiotensin II treatment from different genotypes, diets, animal facilities, and age groups. Analysing over 17 million sequencing reads, we observed that angiotensin II treatment influenced α-diversity (P = 0.0137) and ß-diversity (i.e. composition of the microbiome, P < 0.001). Bacterial abundance analysis revealed patterns consistent with a reduction in short-chain fatty acid producers, microbial metabolites that lower blood pressure. Furthermore, animal facility, genotype, diet, age, sex, intestinal sampling site, and sequencing batch had significant effects on both α- and ß-diversity (all P < 0.001). Sampling site (6.8%) and diet (6%) had the largest impact on the microbiome, while angiotensin II and sex had the smallest effect (each 0.4%). CONCLUSION: Our large-scale data confirmed findings from small-scale studies that angiotensin II impacted the gut microbiome. However, this effect was modest relative to most of the other factors studied. Accounting for these factors in future pre-clinical hypertensive studies will increase the likelihood that microbiome findings are replicable and translatable.
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Angiotensina II , Bacterias , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Animales , Femenino , Masculino , Angiotensina II/farmacología , Bacterias/genética , Bacterias/efectos de los fármacos , Bacterias/metabolismo , Bacterias/crecimiento & desarrollo , Bacterias/clasificación , Disbiosis , Microbioma Gastrointestinal/efectos de los fármacos , Hipertensión/microbiología , Hipertensión/fisiopatología , Hipertensión/tratamiento farmacológico , Hipertensión/metabolismo , Intestinos/microbiología , Intestinos/efectos de los fármacos , Ratones Endogámicos C57BL , Estudios Retrospectivos , Ribotipificación , ARN Ribosómico 16S/genéticaRESUMEN
Supramolecular hydrogels derived from nucleosides have been gaining significant attention in the biomedical field due to their unique properties and excellent biocompatibility. However, a major challenge in this field is that there is no model for predicting whether nucleoside derivative will form a hydrogel. Here, we successfully develop a machine learning model to predict the hydrogel-forming ability of nucleoside derivatives. The optimal model with a 71% (95% Confidence Interval, 0.69-0.73) accuracy is established based on a dataset of 71 reported nucleoside derivatives. 24 molecules are selected via the optimal model external application and the hydrogel-forming ability is experimentally verified. Among these, two rarely reported cation-independent nucleoside hydrogels are found. Based on their self-assemble mechanisms, the cation-independent hydrogel is found to have potential applications in rapid visual detection of Ag+ and cysteine. Here, we show the machine learning model may provide a tool to predict nucleoside derivatives with hydrogel-forming ability.
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Hidrogeles , Nucleósidos , Aprendizaje Automático , CationesRESUMEN
Previous resting-state functional magnetic resonance imaging (rs-fMRI) studies have widely explored the temporal connection changes in the human brain following long-term sleep deprivation (SD). However, the frequency-specific topological properties of sleep-deprived functional networks remain virtually unclear. In this study, thirty-seven healthy male subjects underwent resting-state fMRI during rested wakefulness (RW) and after 36â¯hours of SD, and we examined frequency-specific spectral connection changes (0.01-0.08â¯Hz, interval = 0.01â¯Hz) caused by SD. First, we conducted a multivariate pattern analysis combining linear SVM classifiers with a robust feature selection algorithm, and the results revealed that accuracies of 74.29%-84.29% could be achieved in the classification between RW and SD states in leave-one-out cross-validation at different frequency bands, moreover, the spectral connection at the lowest and highest frequency bands exhibited higher discriminative power. Connection involving the cingulo-opercular network increased most, while connection involving the default-mode network decreased most following SD. Then we performed a graph-theoretic analysis and observed reduced low-frequency modularity and high-frequency global efficiency in the SD state. Moreover, hub regions, which were primarily situated in the cerebellum and the cingulo-opercular network after SD, exhibited high discriminative power in the aforementioned classification consistently. The findings may indicate the frequency-dependent effects of SD on the functional network topology and its efficiency of information exchange, providing new insights into the impact of SD on the human brain.
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Mapeo Encefálico , Privación de Sueño , Humanos , Masculino , Privación de Sueño/diagnóstico por imagen , Vías Nerviosas/patología , Encéfalo/patología , Vigilia , Imagen por Resonancia Magnética/métodosRESUMEN
Proteasome activator subunit 3 (PA28γ) is a member of the proteasome activator family, which mainly regulates the degradation and stability of proteins. Studies have shown that it plays crucial roles in lipid formation, stemness maintenance, and blood vessel formation. However, few studies have clarified the association between PA28γ and bone diseases. Herein, we identified PA28γ as a previously unknown regulator of bone homeostasis that coordinates bone formation and lipid accumulation. PA28γ-knockout mice presented with the characteristics of low bone mass and accumulation of lipids. Suppressed expression of PA28γ restrained the osteogenic differentiation and enhanced the adipogenic differentiation of bone marrow stromal cells (BMSCs). Overexpression of PA28γ promoted osteogenic differentiation and inhibited adipogenic differentiation of BMSCs. Mechanistically, PA28γ interacted with Wnt5α, and the two interactors appeared to be positively correlated. PA28γ mainly activated the downstream Wnt/ß-catenin signaling pathway, which affects BMSCs differentiation homeostasis. Deletion of Wnt5α significantly delayed the promotion of osteogenic differentiation and partially alleviated the inhibitory effect of adipogenic differentiation of BMSCs in the PA28γ-overexpressing group. Furthermore, we demonstrated that PA28γ-knockout mice had an inhibited rate of bone healing in a drill-hole femoral bone defect model in vivo. Therefore, our results confirm the effects of PA28γ on bone formation and bone defect repair, indicating that PA28γ mainly interacts with Wnt5α to activate the Wnt/ß-catenin signaling pathway regulating BMSCs differentiation homeostasis. Our results reveal the function of PA28γ in bone diseases and provide a new theoretical basis for expanding the treatment of bone diseases.