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BACKGROUND: Preeclampsia is a serious disease of pregnancy that lacks early diagnosis methods or effective treatment, except delivery. Dysregulated uterine immune cells and spiral arteries are implicated in preeclampsia, but the mechanistic link remains unclear. METHODS: Single-cell RNA sequencing and spatial transcriptomics were used to identify immune cell subsets associated with preeclampsia. Cell-based studies and animal models including conditional knockout mice and a new preeclampsia mouse model induced by recombinant mouse galectin-9 were applied to validate the pathogenic role of a CD11chigh subpopulation of decidual macrophages (dMφ) and to determine its underlying regulatory mechanisms in preeclampsia. A retrospective preeclampsia cohort study was performed to determine the value of circulating galectin-9 in predicting preeclampsia. RESULTS: We discovered a distinct CD11chigh dMφ subset that inhibits spiral artery remodeling in preeclampsia. The proinflammatory CD11chigh dMφ exhibits perivascular enrichment in the decidua from patients with preeclampsia. We also showed that trophoblast-derived galectin-9 activates CD11chigh dMφ by means of CD44 binding to suppress spiral artery remodeling. In 3 independent preeclampsia mouse models, placental and plasma galectin-9 levels were elevated. Galectin-9 administration in mice induces preeclampsia-like phenotypes with increased CD11chigh dMφ and defective spiral arteries, whereas galectin-9 blockade or macrophage-specific CD44 deletion prevents such phenotypes. In pregnant women, increased circulating galectin-9 levels in the first trimester and at 16 to 20 gestational weeks can predict subsequent preeclampsia onset. CONCLUSIONS: These findings highlight a key role of a distinct perivascular inflammatory CD11chigh dMφ subpopulation in the pathogenesis of preeclampsia. CD11chigh dMφ activated by increased galectin-9 from trophoblasts suppresses uterine spiral artery remodeling, contributing to preeclampsia. Increased circulating galectin-9 may be a biomarker for preeclampsia prediction and intervention.
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Decidua , Galectinas , Macrófagos , Preeclampsia , Remodelación Vascular , Preeclampsia/metabolismo , Preeclampsia/inmunología , Embarazo , Femenino , Animales , Galectinas/metabolismo , Macrófagos/metabolismo , Macrófagos/inmunología , Macrófagos/patología , Ratones , Humanos , Decidua/metabolismo , Decidua/patología , Ratones Noqueados , Útero/metabolismo , Útero/irrigación sanguínea , Modelos Animales de Enfermedad , Receptores de Hialuranos/metabolismo , Receptores de Hialuranos/genética , Estudios Retrospectivos , Ratones Endogámicos C57BL , Antígenos CD11RESUMEN
Lactic acid bacteria (LAB) have been recognized as safe microorganism that improve micro-flora disturbances and enhance immune response. A well-know traditional herbal medicine, Acanthopanax senticosus (As) was extensively utilized in aquaculture to improve growth performance and disease resistance. Particularly, the septicemia, skin wound and gastroenteritis caused by Aeromonas hydrophila threaten the health of aquatic animals and human. However, the effects of probiotic fermented with A. senticosus product on the immune regulation and pathogen prevention in fish remain unclear. Here, the aim of the present study was to elucidate whether the A. senticosus fermentation by Lactobacillus rhamnosus improve immune barrier function. The crucian carp were fed with basal diet supplemented with L. rhamnosus fermented A. senticosus cultures at 2 %, 4 %, 6 % and 8 % bacterial inoculum for 8 weeks. After trials, the weight gain rate (WGR), specific growth rate (SGR) were significantly increased, especially in LGG-6 group. The results confirmed that the level of the CAT, GSH-PX, SOD, lysozyme, and MDA was enhanced in fish received with probiotic fermented product. Moreover, the L. rhamnosus fermented A. senticosus cultures could trigger innate and adaptive immunity, including the up-regulation of the C3, C4, and IgM concentration. The results of qRT-PCR revealed that stronger mRNA transcription of IL-1ß, IL-10, IFN-γ, TNF-α, and MyD88 genes in the liver, spleen, kidney, intestine and gills tissues of fish treated with probiotic fermented with A. senticosus product. After infected with A. hydrophila, the survival rate of the LGG-2 (40 %), LGG-4 (50 %), LGG-6 (60 %), LGG-8 (50 %) groups was higher than the control group. Meanwhile, the pathological damage of the liver, spleen, head-kidney, and intestine tissues of probiotic fermentation-fed fish could be alleviated after pathogen infection. Therefore, the present work indicated that L. rhamnosus fermented A. senticosus could be regard as a potential intestine-target therapy strategy to protecting fish from pathogenic bacteria infection.
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Aeromonas hydrophila , Antioxidantes , Carpas , Eleutherococcus , Fermentación , Enfermedades de los Peces , Lacticaseibacillus rhamnosus , Probióticos , Animales , Lacticaseibacillus rhamnosus/metabolismo , Carpas/microbiología , Probióticos/farmacología , Probióticos/administración & dosificación , Antioxidantes/metabolismo , Enfermedades de los Peces/prevención & control , Enfermedades de los Peces/microbiología , Enfermedades de los Peces/inmunología , Infecciones por Bacterias Gramnegativas/veterinaria , Infecciones por Bacterias Gramnegativas/prevención & control , Infecciones por Bacterias Gramnegativas/inmunología , Alimentación Animal , Inflamación/prevención & control , Citocinas/metabolismo , AcuiculturaRESUMEN
Long time series of vegetation monitoring can be carried out by remote sensing data, the level of urban greening is objectively described, and the spatial characteristics of plant pollen are indirectly understood. Pollen is the main allergen in patients with seasonal allergic rhinitis. Meteorological factors affect the release and diffusion of pollen. Therefore, studying of the complex relationship between meteorological factors and allergic rhinitis is essential for effective prevention and treatment of the disease. In this study, we leverage remote sensing data for a comprehensive decade-long analysis of urban greening in Tianjin, which exhibits an annual increase in vegetative cover of 0.51 per annum, focusing on its impact on allergic rhinitis through changes in pollen distribution. Utilizing high-resolution imagery, we quantify changes in urban Fractional Vegetation Coverage (FVC) and its correlation with pollen types and allergic rhinitis cases. Our analysis reveals a significant correlation between FVC trends and pollen concentrations, with a surprising value of 0.71, highlighting the influence of urban greenery on allergenic pollen levels. We establish a robust connection between the seasonal patterns of pollen outbreaks and allergic rhinitis consultations, with a noticeable increase in consultations during high pollen seasons. our findings indicate a higher allergenic potential of herbaceous compared to woody vegetation. This nuanced understanding underscores the importance of pollen sensitivity, alongside concentration, in driving allergic rhinitis incidents. Utilizing a Generalized Linear Model, significant features influencing the number of visits for allergic rhinitis (P < 0.05) were identified. Both GLM and LSTM models were employed to forecast the visitation volumes for rhinitis during the spring and summer-autumn of 2022. Upon validation, it was found that the R² values between the simulated and actual values for both GLM and LSTM models surpassed the 95% confidence threshold. Moreover, the R² values for the summer-autumn seasons (GLM: 0.56, LSTM: 0.72) were higher than those for spring (GLM: 0.22, LSTM: 0.47). Comparing the errors between the simulated and actual values of GLM and LSTM models, LSTM exhibited higher simulation precision in both spring and summer-autumn seasons, demonstrating superior simulation performance. Overall, our study pioneers the integration of remote sensing with meteorological and health data for allergic rhinitis forecasting. This integrative approach provides valuable insights for public health planning, particularly in urban settings, and lays the groundwork for advanced, location-specific allergenic pollen forecasting and mitigation strategies.
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Tannery sludge with high chromium content has been identified as hazardous solid waste due to its potential toxic effects. The safety disposal and valorization of the tannery sludge remains a challenge. In this study, the chromium stabilization mechanism was systematically investigated during chromium-rich tannery sludge was converted to biochar and the removal performance of the sludge biochar (SBC) for Cr(VI) from tannery wastewater was also investigated. The results showed that increase in pyrolysis temperature was conductive to the stabilization of Cr and significant reduction of the proportion of Cr(VI) in SBC. It was confirmed that the stabilization of chromium mainly was attributed to the embedding of chromium in the C matrix and the transformation of the chromium-containing substances from the amorphous Cr(OH)3 to the crystalline state, such as (FeMg)Cr2O5. The biochar presented high adsorption capacity of Cr(VI) at low pH and the maximal theoretical adsorption capacity of SBC produced at 800°C can reach 352 mg Cr(VI)/g, the process of which can be well expressed by Langmuir adsorption isotherm and pseudo second order model. The electrostatic effect and reduction reaction were dominantly responsible for the Cr(VI) adsorption by SBC800. Overall, this study provided a novel strategy for the harmless disposal and resource utilization for the solid waste containing chromium in leather industry.
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Aguas Residuales , Contaminantes Químicos del Agua , Aguas del Alcantarillado , Residuos Sólidos , Carbón Orgánico/química , Cromo/química , Adsorción , Contaminantes Químicos del Agua/análisisRESUMEN
OBJECTIVES: To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus (SLE) and lupus nephritis (LN) in children, as well as their diagnostic value for active SLE and LN. METHODS: A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital, Central South University from January 2016 to March 2019 as the SLE group, all of whom were tested for anti-C1q antibodies. A control group was formed by collecting 70 hospitalized children with other autoimmune diseases (OAD) during the same period. The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed, and the diagnostic value of anti-C1q in SLE and LN was evaluated. RESULTS: The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group (P<0.05). The SLE disease activity index score was positively correlated with anti-C1q antibodies (rs=0.371, P<0.001) and positively correlated with anti-double-stranded DNA antibodies (rs=0.370, P<0.001). The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90% and 53.90%, respectively, with an area under the curve of 0.720 (P<0.05) and a critical value of 5.45 U/mL. The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50% and 85.00%, respectively, with an area under the curve of 0.675 (P<0.05) and a critical value of 22.05 U/mL. CONCLUSIONS: Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.
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Complemento C1q , Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Complemento C1q/inmunología , Nefritis Lúpica/inmunología , Nefritis Lúpica/sangre , Femenino , Niño , Masculino , Lupus Eritematoso Sistémico/inmunología , Estudios Retrospectivos , Adolescente , Autoanticuerpos/sangre , Preescolar , Anticuerpos Antinucleares/sangre , Anticuerpos Antinucleares/inmunologíaRESUMEN
Recycled asphalt pavement (RAP) mixtures are widely adopted due to their significant economic and social benefits from utilizing pavement recycling materials. This study incorporates basalt fibers (BF) and polyester fibers (PF) into plant-mixed hot recycled asphalt mixtures to analyze their enhancement effects on the high-temperature, low-temperature, and fatigue performance at different RAP content levels. Additionally, the study investigates the impact of fiber and RAP additions on the compaction characteristics of the mixtures using gyratory compaction tests, aiming to increase the RAP content of plant-mixed hot recycled asphalt mixtures. Experimental results demonstrate that at 30% and 50% RAP content levels, basalt fibers exhibit more pronounced enhancement effects on the performance of recycled asphalt mixtures compared to polyester fibers. Incorporating basalt fibers increases the fracture energy of recycled asphalt mixtures by 8.63% and 13.9%, and improves fatigue life by 154% and 135%, respectively. Moreover, the addition of both types of fibers increases compaction difficulty, with polyester fibers showing a more significant influence on the compaction energy index (CEI).
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Introduction: 2-Amino-1-methyl-6-phenylimidazole [4,5-b] pyridine (PhIP), a heterocyclic amine (HAA), is found in meat products heated at high temperatures. However, PhIP is a mutagenic and potential carcinogenic compound. Cassiae semen, a type of medicine and food homology plant, is abundant in China and has been less applied for inhibiting heterocyclic amines. Methods: To investigate the inhibitory effect of cassiae semen extract on PhIP formation within a model system and elucidate the inhibitory mechanism, an ultrasonic-assisted method with 70% ethanol was used to obtain cassiae semen extract, which was added to a model system (0.6 mmol of phenylalanine: creatinine, 1:1). PhIP was analyzed by LC-MS to determine inhibitory effect. The byproducts of the system and the mechanism of PhIP inhibition were verified by adding the extract to a model mixture of phenylacetaldehyde, phenylacetaldehyde and creatinine. Results: The results indicated that PhIP production decreased as the concentration of cassiae semen extract increased, and the highest inhibition rate was 91.9%. Byproduct (E), with a mass-charge ratio of m/z 199.9, was detected in the phenylalanine and creatinine model system but was not detected in the other systems. The cassiae semen extract may have reacted with phenylalanine to produce byproduct (E), which prevented the degradation of phenylalanine by the Strecker reaction to produce phenylacetaldehyde. Discussion: Cassiae semen extract consumed phenylalanine, which is the precursor for PhIP, thus inhibiting the formation of phenylacetaldehyde and ultimately inhibiting PhIP formation. The main objective of this study was to elucidate the mechanism by which cassiae semen inhibit PhIP formation and establish a theoretical and scientific foundation for practical control measures.
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An important factor for investigating climate change in the Sanjiangyuan is the evolution of the spatio-temporal pattern of lakes in this region. The present study used the Google Earth Engine (GEE) platform to extract lakes from 2000 to 2020. The present approach created a lake distribution dataset yearly and analyzed spatial and temporal patterns over 20 years. The analysis of lakes focused on the reaction of the Sanjiangyuan Lakes area to changes in climate, glaciers, and permafrost. The findings indicated that the Sanjiangyuan region contains 143 lakes, the majority of which are predominantly small, measuring 1-10 km2. The small lakes account for 60.14 % of the total and are primarily located in the source regions of the Yangtze River and Yellow River. The findings demonstrated that the Sanjiangyuan lakes experienced a significant expansion over the past two decades, particularly from 2011 to 2020. These lakes are divided into expanded, atrophic, and stable categories. Expanded lakes showed significant inter-annual trends in expansion, while atrophic lakes showed smaller fluctuations. The area of stable lakes experienced a consistent decline after 2010, despite a consistent expansion tendency from 2001 to 2010. Moreover, the results indicated that alterations in the size of glaciers and ice reserves in the Sanjiangyuan region have had the greatest influence on the fluctuation in lake area. Among the factors that affect the climate, temperature had the most significant effect on the change in lake area, followed by precipitation.
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Unicystic ameloblastoma (UAM) of the jaw can be effectively reduced in volume through decompression, which promotes bone regeneration and restores jaw symmetry. This study quantitatively evaluated changes in mandible volume and symmetry following decompression of mandibular UAM. This study included 17 patients who underwent surgical decompression followed by second-stage curettage for mandibular UAM. Preoperative and postoperative three-dimensional computed tomography (CT) images were collected. Bone volume and the area of cortical perforation were measured to assess bone growth during decompression. Mandibular volumetric symmetry was analyzed by calculating the volumetric ratio of the two sides of the mandible. Twelve pairs of landmarks were identified on the surface of the lesion regions, and their coordinates were used to calculate the mean asymmetry index (AI) of the mandible. Paired t-tests and the Mann-Whitney U test were used for statistical analysis, with p < 0.05 considered indicative of statistical significance. The mean duration of decompression was 9.41 ± 3.28 months. The mean bone volume increased by 8.07 ± 2.41%, and cortical perforation recovery was 71.97 ± 14.99%. The volumetric symmetry of the mandible improved significantly (p < 0.05), and a statistically significant decrease in AI was observed (p < 0.05). In conclusion, UAM decompression enhances bone growth and symmetry recovery of the mandible. The present evaluation technique is clinically useful for quantitatively assessing mandibular asymmetry.
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Ameloblastoma , Descompresión Quirúrgica , Imagenología Tridimensional , Mandíbula , Tomografía Computarizada por Rayos X , Humanos , Ameloblastoma/cirugía , Ameloblastoma/diagnóstico por imagen , Femenino , Masculino , Mandíbula/cirugía , Mandíbula/diagnóstico por imagen , Adulto , Descompresión Quirúrgica/métodos , Imagenología Tridimensional/métodos , Tomografía Computarizada por Rayos X/métodos , Adulto Joven , Adolescente , Persona de Mediana Edad , Neoplasias Mandibulares/cirugía , Neoplasias Mandibulares/diagnóstico por imagen , Desarrollo Óseo , Regeneración ÓseaRESUMEN
OBJECTIVES: The objective of this study was to evaluate the early predictors of bacterial pneumonia infection in children with congenital heart disease (CHD) after cardiopulmonary bypass (CPB). DESIGN: Retrospective study. SETTING: A freestanding tertiary paediatric hospital in China. PARTICIPANTS: Patients admitted to the hospital due to CHD who underwent open-heart surgery. OUTCOME MEASURES: We retrospectively reviewed and analysed data from 1622 patients with CHD after CPB from June 2018 to December 2020 at the Children's Hospital of Nanjing Medical University. Enrolled patients were assigned to an infection group or a non-infection group according to the presence of postoperative bacterial pneumonia infection, and the differences in clinical indicators were compared. Potential predictors were analysed by multivariate logistic regression analysis and area under the curve (AUC) analysis. RESULTS: Among the 376 patients (23.2%) in the infection group, the three most common bacteria were Streptococcus pneumoniae in 67 patients (17.8%), Escherichia coli in 63 patients (16.8%) and Haemophilus influenzae in 53 patients (14.1%). The infection group exhibited a lower weight (8.0 (6.0-11.5) kg vs 11.0 (7.5-14.5) kg, p<0.001). In the infection group, procalcitonin (PCT) (ng/mL: 4.72 (1.38-9.52) vs 1.28 (0.47-3.74), p<0.001) and C reactive protein (CRP) (mg/L: 21.0 (12.1-32.0) vs 17.0 (10.0-27.0), p<0.001) levels were significantly greater than those in the non-infection group. Binary logistic regression analysis revealed that weight, PCT and CRP were independent risk factors for pulmonary bacterial infection after CPB. The AUCs of weight, PCT, CRP and PCT+CRP for predicting pulmonary bacterial infection after CPB were 0.632 (95% CI 0.600 to 0.664), 0.697 (95% CI 0.667 to 0.727), 0.586 (95% CI 0.554 to 0.618) and 0.694 (95% CI 0.664 to 0.724), respectively, and the cut-off values were ≤10.25 kg, ≥4.25 ng/mL, ≥6.50 mg/L and ≥0.20, respectively. The sensitivities were 69.7%, 54.0%, 93.9% and 70.2%, and the specificities were 53.5%, 77.7%, 19.4% and 59.1%, respectively. CONCLUSIONS: In our study, weight, PCT and CRP were found to be independent predictors of pulmonary bacterial infection after CPB. Moreover, PCT was the most specific predictor, and CRP was the most sensitive independent predictor that might be beneficial for the early diagnosis of pulmonary bacterial infection after CPB in patients with CHD.
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Cardiopatías Congénitas , Neumonía Bacteriana , Humanos , Niño , Estudios Retrospectivos , Puente Cardiopulmonar/efectos adversos , Calcitonina , Péptido Relacionado con Gen de Calcitonina , Precursores de Proteínas , Polipéptido alfa Relacionado con Calcitonina , Proteína C-Reactiva/análisis , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Neumonía Bacteriana/diagnóstico , Neumonía Bacteriana/etiología , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/cirugía , Centros de Atención Terciaria , BiomarcadoresRESUMEN
The occurrence and development of human diseases are influenced by both genetic and environmental factors. Research models that describe disease occurrence only from the perspective of genetics present certain limitations. In recent years, effects of environment factors on the occurrence and development of diseases have attracted extensive attentions. Exposomics focuses on the measurement of all exposure factors in an individual's life and how these factors are related to disease development. Exposomics provides new ideas to promote studies on the relationship between human health and environmental factors. Environmental exposures are characterized with different physical and chemical properties, as well as very low concentrations in vivo, which contribute great challenges in the comprehensive measurement of chemical residues in the human body. Chromatography-mass spectrometry-based technologies combine the high-efficiency separation ability of chromatography with the high resolution and sensitive detection characteristics of mass spectrometry; the combination of these techniques can achieve the high-coverage, high-throughput, and sensitive detection of environmental exposures, thus providing a powerful tool for measuring chemical exposures. Exposomics-analysis methods based on chromatography-mass spectrometry mainly include targeted quantitative analysis, suspect screening, and non-targeted screening. To explore the relationship between environmental exposure and the occurrence and development of diseases, researchers have developed research paradigms, including exposome wide association study, mixed-exposure study, exposomics and multi-omics (genome, transcriptome, proteome, metabolome)-association study, and so on. The emergence of these methods has brought about unprecedented developments in exposomics studies. In this manuscript, analytical methods based on chromatography-mass spectrometry, exposomics research paradigms, and their relevant prospects are reviewed.
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Exposición a Riesgos Ambientales , Metaboloma , Humanos , Cromatografía Liquida , Espectrometría de Masas , Análisis EspectralRESUMEN
The co-pyrolysis of oily sludge (OS) and municipal solid waste incineration fly ash (IFA) is a promising strategy for sustainable waste management. This study delves into the distinct catalytic roles of individual IFA components during co-pyrolysis and assesses their impact on the inherent Fe species in OS, highlighting their contributions to overall catalytic activity. Notably, in comparison to IFA, CaCl2 and KCl significantly enhance pyrolysis oil upcycling, while IFA components collectively exhibit a positive catalytic effect on pyrolysis gas and coke production. Ca(OH)2 notably boosts H2 yield by 137.16 %. Alkali chlorides facilitate gaseous hydrocarbon formation and convert oxygen-containing compounds to CO and CO2 which are subsequently consumed and absorbed by CaO and Ca(OH)2. CaCl2 and KCl promote heavy compound decomposition and alkane aromatization, reducing coke formation and increasing light aromatic production. Conversely, NaCl increases alkane proportions. However, CaSO4 and CaCO3 hinder catalytic reactions, promoting carbon conversion to coke. Importantly, IFA compounds aid the dispersion of inherent Fe-based species from OS on char surface, enhancing in-situ catalytic pyrolysis. Additionally, the augmented H2 production accelerates the reduction of Fe-based species. The findings expand waste utilization possibilities and provide insights for co-processing solid wastes.
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Glioblastoma (GBM) presents a significant therapeutic challenge due to the limited efficacy of existing treatments. Chimeric antigen receptor (CAR) T-cell therapy offers promise, but its potential in solid tumors like GBM is undermined by the physical barrier posed by the extracellular matrix (ECM). To address the inadequacies of traditional 2D cell culture, animal models, and Matrigel-based 3D culture in mimicking the mechanical characteristics of tumor tissues, we employed biomaterials and digital light processing-based 3D bioprinting to fabricate biomimetic tumor models with finely tunable ECM stiffness independent of ECM composition. Our results demonstrated that increased material stiffness markedly impeded CAR-T cell penetration and tumor cell cytotoxicity in GBM models. The 3D bioprinted models enabled us to examine the influence of ECM stiffness on CAR-T cell therapy effectiveness, providing a clinically pertinent evaluation tool for CAR-T cell development in stiff solid tumors. Furthermore, we developed an innovative heat-inducible CAR-T cell therapy, effectively overcoming the challenges posed by the stiff tumor microenvironment.
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A series of membrane materials suitable for high-temperature proton exchange membranes (HT-PEM) were successfully prepared by introducing polymeric ionic liquids (PILs) containing quaternary ammonium groups into ether-bonded polybenzimidazole (OPBI). The structure of the cross-linked membrane has a strong interaction with phosphoric acid (PA), which enhances proton transport and PA retention. To ensure better overall performance of the cross-linked membrane, the optimal PIL content is 30 wt% (OPBI-PIL-30 %). The PA uptake of OPBI-PIL-30 % membrane was 323.24 %, and the proton conductivity at 180 â was 113.94 mS cm-1, which was much higher than that of OPBI membrane. It is noteworthy that the PA retention of OPBI-PIL-30 % membrane could reach 71.38 % after 240 h of testing under the harsh environment of 80 â/40 % RH. The membrane showed better acid retention capacity of 86.89 % at 160 â under anhydrous environment. The OPBI-PIL-20 % membrane achieved the maximum power density of 436.19 mW cm-2, attributed to its favorable mechanical characteristics and proton conductivity. By these excellent properties, it is shown that OPBI-PIL-X membranes containing quaternary ammonium groups have the potential to be applied in high temperature proton exchange membrane fuel cells (HT-PEMFCs).
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Glioma, with its heterogeneous microenvironments and genetic subtypes, presents substantial challenges for treatment prediction and development. We integrated 3D bioprinting and multi-algorithm machine learning as a novel approach to enhance the assessment and understanding of glioma treatment responses and microenvironment characteristics. The bioprinted patient-derived glioma tissues successfully recapitulated molecular properties and drug responses of native tumors. We then developed GlioML, a machine learning workflow incorporating nine distinct algorithms and a weighted ensemble model that generated robust gene expression-based predictors, each reflecting the diverse action mechanisms of various compounds and drugs. The ensemble model superseded the performance of all individual algorithms across diverse in vitro systems, including sphere cultures, complex 3D bioprinted multicellular models, and 3D patient-derived tissues. By integrating bioprinting, the evaluative scope of the treatment expanded to T cell-related therapy and anti-angiogenesis targeted therapy. We identified promising compounds and drugs for glioma treatment and revealed distinct immunosuppressive or angiogenic myeloid-infiltrated tumor microenvironments. These insights pave the way for enhanced therapeutic development for glioma and potentially for other cancers, highlighting the broad application potential of this integrative and translational approach.
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A mechanistic connection between aging and development is largely unexplored. Through profiling age-related chromatin and transcriptional changes across 22 murine cell types, analyzed alongside previous mouse and human organismal maturation datasets, we uncovered a transcription factor binding site (TFBS) signature common to both processes. Early-life candidate cis-regulatory elements (cCREs), progressively losing accessibility during maturation and aging, are enriched for cell-type identity TFBSs. Conversely, cCREs gaining accessibility throughout life have a lower abundance of cell identity TFBSs but elevated activator protein 1 (AP-1) levels. We implicate TF redistribution toward these AP-1 TFBS-rich cCREs, in synergy with mild downregulation of cell identity TFs, as driving early-life cCRE accessibility loss and altering developmental and metabolic gene expression. Such remodeling can be triggered by elevating AP-1 or depleting repressive H3K27me3. We propose that AP-1-linked chromatin opening drives organismal maturation by disrupting cell identity TFBS-rich cCREs, thereby reprogramming transcriptome and cell function, a mechanism hijacked in aging through ongoing chromatin opening.
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Envejecimiento , Cromatina , Factor de Transcripción AP-1 , Animales , Envejecimiento/genética , Envejecimiento/metabolismo , Factor de Transcripción AP-1/metabolismo , Cromatina/metabolismo , Ratones , Humanos , Ratones Endogámicos C57BL , Sitios de UniónRESUMEN
Dipeptides have been shown to be an important taste substance in alcoholic beverages. However, the characterization of dipeptides in Chinese liquors was poor. Here, dansylation combined with liquid chromatography - mass spectrometry was employed to analyze dipeptides in eight liquors of two flavors. Consequently, 35 dipeptides were identified from liquors and 32 of them were quantified. Dipeptide quantification showed LODs smaller than 2.5 ng/mL. The calibration curves showed concentration spans from two to three orders of magnitude with satisfactory linearity. The matrix effects in low and high concentrations were from -25.71 % to 24.19 % and -14.82 % to 20.73 %, respectively. Intra- and inter-day precision is lower than 15 % for both low and high concentrations. The dipeptide contents in sauce flavor liquors were higher than those in strong flavor liquors. Ala- and -Phe dipeptides showed their unique trends between sauce and strong flavor liquors. This study provides new clues to evaluate taste of liquors.