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Beneficial bacteria remain largely unexplored. Lacking systematic methods, understanding probiotic community traits becomes challenging, leading to various conclusions about their probiotic effects among different publications. We developed language model-based metaProbiotics to rapidly detect probiotic bins from metagenomes, demonstrating superior performance in simulated benchmark datasets. Testing on gut metagenomes from probiotic-treated individuals, it revealed the probioticity of intervention strains-derived bins and other probiotic-associated bins beyond the training data, such as a plasmid-like bin. Analyses of these bins revealed various probiotic mechanisms and bai operon as probiotic Ruminococcaceae's potential marker. In different health-disease cohorts, these bins were more common in healthy individuals, signifying their probiotic role, but relevant health predictions based on the abundance profiles of these bins faced cross-disease challenges. To better understand the heterogeneous nature of probiotics, we used metaProbiotics to construct a comprehensive probiotic genome set from global gut metagenomic data. Module analysis of this set shows that diseased individuals often lack certain probiotic gene modules, with significant variation of the missing modules across different diseases. Additionally, different gene modules on the same probiotic have heterogeneous effects on various diseases. We thus believe that gene function integrity of the probiotic community is more crucial in maintaining gut homeostasis than merely increasing specific gene abundance, and adding probiotics indiscriminately might not boost health. We expect that the innovative language model-based metaProbiotics tool will promote novel probiotic discovery using large-scale metagenomic data and facilitate systematic research on bacterial probiotic effects. The metaProbiotics program can be freely downloaded at https://github.com/zhenchengfang/metaProbiotics.
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Metagenoma , Probióticos , Humanos , Algoritmos , Metagenômica/métodos , Bactérias/genética , IdiomaRESUMO
Hexavalent chromium (Cr(VI)) exposure has been linked with gastrointestinal toxicity, whereas the molecular pathways and key targets remain elusive. Computational toxicology analysis predicted the correlation between protein phosphatase 2A (PP2A) and genes regarding Cr(VI)-induced intestinal injury. Here, we generated a mouse model with intestinal epithelium-specific knock-out of Ppp2r1a (encoding PP2A Aα subunit) to investigate the mechanisms underlying Cr(VI)-induced small intestinal toxicity. Heterozygous mice (HE) and matched wild-type (WT) littermates were administrated with Cr(VI) at 0, 5, 20, 80 mg/L for 28 successive days. Cr(VI) treatment led to crypt hyperplasia, epithelial cell apoptosis, and intestinal barrier dysfunction, accompanied by the decline of goblet cell counts and Occludin expression in WT mice. Notably, these effects were aggravated in HE mice, indicating that PP2A Aα deficiency conferred mice with susceptibility to Cr(VI)-induced intestinal injury. Integrated data analysis and biological experiments revealed Cr(VI) exposure could decrease YAP1 phosphorylation at Ser127 but increase protein expression and activity, together with elevated TAZ protein driving epithelial crypt cells proliferation following damage, suggesting the involvement of Hippo/YAP1 signaling pathway in Cr(VI)-induced intestinal toxicity. Nevertheless, the enhanced phosphorylation of YAP1 in HE mice resulted in proliferation/repair defects in intestinal epithelium, thereby exacerbating Cr(VI)-induced gut barrier dysfunction. Notably, by molecular docking and further studies, we identified Urolithin A, a microbial metabolite, attenuated Cr(VI)-induced disruption of intestinal barrier function, partly by modulating YAP1 expression and activity. Our findings reveal the novel molecular pathways participated in Cr(VI)-caused small intestinal injury and urolithin A could potentially protect against environmental hazards-induced intestinal diseases.
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OBJECTIVE: Our study aimed to explore the influence of gut microbiota and their metabolites on intracranial aneurysms (IA) progression and pinpoint-related metabolic biomarkers derived from the gut microbiome. DESIGN: We recruited 358 patients with unruptured IA (UIA) and 161 with ruptured IA (RIA) from two distinct geographical regions for conducting an integrated analysis of plasma metabolomics and faecal metagenomics. Machine learning algorithms were employed to develop a classifier model, subsequently validated in an independent cohort. Mouse models of IA were established to verify the potential role of the specific metabolite identified. RESULTS: Distinct shifts in taxonomic and functional profiles of gut microbiota and their related metabolites were observed in different IA stages. Notably, tryptophan metabolites, particularly indoxyl sulfate (IS), were significantly higher in plasma of RIA. Meanwhile, upregulated tryptophanase expression and indole-producing microbiota were observed in gut microbiome of RIA. A model harnessing gut-microbiome-derived tryptophan metabolites demonstrated remarkable efficacy in distinguishing RIA from UIA patients in the validation cohort (AUC=0.97). Gut microbiota depletion by antibiotics decreased plasma IS concentration, reduced IA formation and rupture in mice, and downregulated matrix metalloproteinase-9 expression in aneurysmal walls with elastin degradation reduction. Supplement of IS reversed the effect of gut microbiota depletion. CONCLUSION: Our investigation highlights the potential of gut-microbiome-derived tryptophan metabolites as biomarkers for distinguishing RIA from UIA patients. The findings suggest a novel pathogenic role for gut-microbiome-derived IS in elastin degradation in the IA wall leading to the rupture of IA.
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The alterations in DNA methylation and transcriptome in trophoblast cells under conditions of low oxygen and oxidative stress have major implications for pregnancy-related disorders. However, the exact mechanism is still not fully understood. In this study, we established models of hypoxia (H group) and oxidative stress (HR group) using HTR-8/SVneo trophoblast cells and performed combined analysis of genome-wide DNA methylation changes using reduced representation bisulphite sequencing and transcriptome expression changes using RNA sequencing. Our findings revealed that the H group exhibited a higher number of differentially methylated genes and differentially expressed genes than the HR group. In the H group, only 0.90% of all differentially expressed genes displayed simultaneous changes in DNA methylation and transcriptome expression. After the threshold was expanded, this number increased to 6.29% in the HR group. Notably, both the H group and HR group exhibited concurrent alterations in DNA methylation and transcriptome expression within Axon guidance and MAPK signalling pathway. Among the top 25 differentially methylated KEGG pathways in the promoter region, 11 pathways were commonly enriched in H group and HR group, accounting for 44.00%. Among the top 25 KEGG pathways in transcriptome with significant differences between the H group and HR group, 10 pathways were consistent, accounting for 40.00%. By integrating our previous data on DNA methylation from preeclamptic placental tissues, we identified that the ANKRD37 and PFKFB3 genes may contribute to the pathogenesis of preeclampsia through DNA methylation-mediated transcriptome expression under hypoxic conditions.
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Hipóxia Celular , Metilação de DNA , Estresse Oxidativo , Transcriptoma , Trofoblastos , Humanos , Trofoblastos/metabolismo , Estresse Oxidativo/genética , Transcriptoma/genética , Hipóxia Celular/genética , Linhagem Celular , Feminino , Gravidez , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Fosfofrutoquinase-2/genética , Fosfofrutoquinase-2/metabolismoRESUMO
BACKGROUND: Stroke often damages the basal ganglia, leading to atypical and transient aphasia, indicating that post-stroke basal ganglia aphasia (PSBGA) may be related to different anatomical structural damage and functional remodeling rehabilitation mechanisms. The basal ganglia contain dense white matter tracts (WMTs). Hence, damage to the functional tract may be an essential anatomical structural basis for the development of PSBGA. METHODS: We first analyzed the clinical characteristics of PSBGA in 28 patients and 15 healthy controls (HCs) using the Western Aphasia Battery and neuropsychological test batteries. Moreover, we investigated white matter injury during the acute stage using diffusion magnetic resonance imaging scans for differential tractography. Finally, we used multiple regression models in correlation tractography to analyze the relationship between various language functions and quantitative anisotropy (QA) of WMTs. RESULTS: Compared with HCs, patients with PSBGA showed lower scores for fluency, comprehension (auditory word recognition and sequential commands), naming (object naming and word fluency), reading comprehension of sentences, Mini-Mental State Examination, and Montreal Cognitive Assessment, along with increased scores in Hamilton Anxiety Scale-17 and Hamilton Depression Scale-17 within 7 days after stroke onset (P < 0.05). Differential tractography revealed that patients with PSBGA had damaged fibers, including in the body fibers of the corpus callosum, left cingulum bundles, left parietal aslant tracts, bilateral superior longitudinal fasciculus II, bilateral thalamic radiation tracts, left fornix, corpus callosum tapetum, and forceps major, compared with HCs (FDR < 0.02). Correlation tractography highlighted that better comprehension was correlated with a higher QA of the left inferior fronto-occipital fasciculus (IFOF), corpus callosum forceps minor, and left extreme capsule (FDR < 0.0083). Naming was positively associated with the QA of the left IFOF, forceps minor, left arcuate fasciculus, and uncinate fasciculus (UF) (FDR < 0.0083). Word fluency of naming was also positively associated with the QA of the forceps minor, left IFOF, and thalamic radiation tracts (FDR < 0.0083). Furthermore, reading was positively correlated with the QA of the forceps minor, left IFOF, and UF (FDR < 0.0083). CONCLUSION: PSBGA is primarily characterized by significantly impaired word fluency of naming and preserved repetition abilities, as well as emotional and cognitive dysfunction. Damaged limbic pathways, dorsally located tracts in the left hemisphere, and left basal ganglia pathways are involved in PSBGA pathogenesis. The results of connectometry analysis further refine the current functional localization model of higher-order neural networks associated with language functions.
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Afasia , Gânglios da Base , Imagem de Tensor de Difusão , Acidente Vascular Cerebral , Substância Branca , Humanos , Masculino , Feminino , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Pessoa de Meia-Idade , Idoso , Imagem de Tensor de Difusão/métodos , Gânglios da Base/diagnóstico por imagem , Gânglios da Base/patologia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Afasia/diagnóstico por imagem , Afasia/etiologia , Afasia/fisiopatologia , Afasia/patologia , Idioma , Adulto , Imagem de Difusão por Ressonância MagnéticaRESUMO
Ischemic stroke has been demonstrated to cause an imbalance of gut microbiota. However, the change in gut microbiota-mediated bile acids (BAs) metabolites remains unclear. Here, we observed a decrease in gut microbiota-mediated BAs, especially ursodeoxycholic acid (UDCA), in the serum of stroke patients as well as in the intestine, serum and brain of stroke mice. Restoration of UDCA could decrease the area of infarction and improve the neurological function and cognitive function in mice in association with inhibition of NLRP3-related pro-inflammatory cytokines through TGR5/PKA pathway. Furthermore, knocking out TGR5 and inhibiting PKA activity reduce the protective effect of UDCA. Taken together, our results suggest that microbiota-mediated UDCA plays an important role in alleviating inflammatory responses and might be a promising therapeutic target in ischemic stroke.
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Microbioma Gastrointestinal , AVC Isquêmico , Acidente Vascular Cerebral , Animais , Humanos , Camundongos , Ácidos e Sais Biliares , Inflamação , Microglia/metabolismo , Ácido Ursodesoxicólico/metabolismoRESUMO
One-pot synthesis of tetrahydro-ß-carbolines, fused with an isoindole core, was proposed starting from maleic anhydride and azomethines easily available from tryptamines and 3-(hetaryl)acroleins. This sequence includes four key steps: an acylation of the aldimine with maleic anhydride, a Pictet-Spengler cyclization, an intramolecular Diels-Alder reaction, and a concluding [1,3]-H shift. As a result, six- or seven-nuclear alkaloid-like heterocyclic systems, containing a benzo[1,2]indolizino[8,7-b]indole fragment annulated with furan, thiophene, or pyrrole, are formed in a diastereoselective manner.
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OBJECTIVE: This study aimed to investigate the potential causal relationship between domain-specific sedentary behaviors (including television watching, computer use, and driving) and hypertension risk in European populations. METHODS: Initially, we conducted a multivariable Cox regression analysis to evaluate the associations between domain-specific sedentary behaviors and the risk of developing hypertension using data from 261,829 hypertension-free participants in the UK Biobank. To validate the findings of observational analysis, we employed two-sample univariable mendelian randomization (UVMR) analysis utilizing summary statistics from genome-wide association study conducted on European populations. We then performed multivariable mendelian randomization (MVMR) analysis to account for the influence of the risk factors for hypertension. RESULTS: In this prospective observational analysis, individuals who spent >3 h per day watching television had significantly higher risk of developing hypertension (HR = 1.24, 95% CI: 1.20-1.29, P < 0.001) compared to those who watched television for 0-1 h per day. The mendelian randomization analysis provided consistent evidence for a causal relationship between prolonged television watching time and hypertension risk (OR = 1.45, 95% CI: 1.25-1.69, P < 0.001; all PMVMR < 0.05) in both UVMR and MVMR results. No significant associations were found between computer use, driving behaviors and the risk of hypertension in either the observational or UVMR/MVMR analyses. CONCLUSIONS: These findings provide evidence for a causal effect specifically linking higher television watching time to an increased risk of hypertension and indicate the potential effectiveness of reducing television viewing time as a preventive measure to mitigate the risk of hypertension.
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Hipertensão , Comportamento Sedentário , Humanos , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Estudos Prospectivos , Recreação , Hipertensão/etiologia , Hipertensão/genética , Polimorfismo de Nucleotídeo ÚnicoRESUMO
PURPOSE: Blood culture (BC) remains the gold standard for the diagnosis of bloodstream infections. Improving the quality of clinical BC samples, optimizing BC performance, and accelerating antimicrobial susceptibility test (AST) results are essential for the early detection of bloodstream infections and specific treatments. METHODS: We conducted a retrospective multicenter study using 450,845 BC specimens from clinical laboratories obtained from 19 teaching hospitals between 1 January 2021 and 31 December 2021. We evaluated key performance indicators (KPIs), turnaround times (TATs), and frequency distributions of processing in BC specimens. We also evaluated the AST results of clinically significant isolates for four different laboratory workflow styles. RESULTS: Across the 10 common bacterial isolates (n = 16,865) and yeast isolates (n = 1011), the overall median (interquartile range) TATs of AST results were 2.67 (2.05-3.31) and 3.73 (2.98-4.64) days, respectively. The specimen collections mainly occurred between 06:00 and 24:00, and specimen reception and loadings mainly between 08:00 and 24:00. Based on the laboratory workflows of the BCs, 16 of the 19 hospitals were divided into four groups. Time to results (TTRs) from specimen collection to the AST reports were 2.35 (1.95-3.06), 2.61 (1.98-3.32), 2.99 (2.60-3.87), and 3.25 (2.80-3.98) days for groups I, II, III, and IV, respectively. CONCLUSION: This study shows the related BC KPIs and workflows in different Chinese hospitals, suggesting that laboratory workflow optimization can play important roles in shortening time to AST reports and initiation of appropriate timely treatment.
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Laboratórios , Sepse , Humanos , Hemocultura , Laboratórios Clínicos , Fatores de Tempo , Hospitais de Ensino , Sepse/diagnósticoRESUMO
Detecting and localizing standing dead trees (SDTs) is crucial for effective forest management and conservation. Due to challenges posed by mountainous terrain and road conditions, conducting a swift and comprehensive survey of SDTs through traditional manual inventory methods is considerably difficult. In recent years, advancements in deep learning and remote sensing technology have facilitated real-time and efficient detection of dead trees. Nevertheless, challenges persist in identifying individual dead trees in airborne remote sensing images, attributed to factors such as small target size, mutual occlusion and complex backgrounds. These aspects collectively contribute to the increased difficulty of detecting dead trees at a single-tree scale. To address this issue, the paper introduces an improved You Only Look Once version 7 (YOLOv7) model that incorporates the Simple Parameter-Free Attention Module (SimAM), an unparameterized attention mechanism. This improvement aims to enhance the network's feature extraction capabilities and increase the model's sensitivity to small target dead trees. To validate the superiority of SimAM_YOLOv7, we compared it with four widely adopted attention mechanisms. Additionally, a method to enhance model robustness is presented, involving the replacement of the Complete Intersection over Union (CIoU) loss in the original YOLOv7 model with the Wise-IoU (WIoU) loss function. Following these, we evaluated detection accuracy using a self-developed dataset of SDTs in forests. The results indicate that the improved YOLOv7 model can effectively identify dead trees in airborne remote sensing images, achieving precision, recall and mAP@0.5 values of 94.31%, 93.13% and 98.03%, respectively. These values are 3.67%, 2.28% and 1.56% higher than those of the original YOLOv7 model. This improvement model provides a convenient solution for forest management.
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Tuning the lattice spacing or stop bands holds great significance in the design and application of materials with colloidal crystals. Typically, particle surface modifications or the application of external physical fields are needed. In this study, we demonstrated the ability to expand or compress the lattice of colloidal crystals simply by utilizing a salt solution, without the need for any special treatments to the colloidal particles. We found that by only considering the diffusiophoresis effect we cannot explain the reversion of lattice expansion to lattice compression with the increase in the salt concentration and that the diffusioosmotic flow originating from the container wall must be taken into account. Further analysis revealed that variations in the salt concentration altered the relative amplitudes between diffusiophoresis and diffusioosmosis through changing the zeta potentials of the particles and the wall, and the competition between the particle diffusiophoresis and wall diffusioosmosis lay at the center of the underlying mechanism.
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The emitter-cavity strong coupling manifests crucial significance for exploiting quantum technology, especially in the scale of individual emitters. However, due to the small light-matter interaction cross-section, the single emitter-cavity strong coupling has been limited by its harsh requirement on the quality factor of the cavity and the local density of optical states. Herein, we present a strategy termed waveguide-assisted energy quantum transfer (WEQT) to improve the single emitter-cavity coupling strength by extending the interaction cross-section. Multiple ancillary emitters are optically linked by a waveguide, providing an indirect coupling channel to transfer the energy quantum between target emitter and cavity. An enhancement factor of coupling strength g Ì / g > 10 can be easily achieved, which dramatically release the rigorous design of cavity. As an extension of concept, we further show that the ancillae can be used as controlling bits for a photon gate, opening up new degrees of freedom in quantum manipulation.
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BACKGROUND: Mobilization typing (MOB) is a classification scheme for plasmid genomes based on their relaxase gene. The host ranges of plasmids of different MOB categories are diverse, and MOB is crucial for investigating plasmid mobilization, especially the transmission of resistance genes and virulence factors. However, MOB typing of plasmid metagenomic data is challenging due to the highly fragmented characteristics of metagenomic contigs. RESULTS: We developed MOBFinder, an 11-class classifier, for categorizing plasmid fragments into 10 MOB types and a nonmobilizable category. We first performed MOB typing to classify complete plasmid genomes according to relaxase information and then constructed an artificial benchmark dataset of plasmid metagenomic fragments (PMFs) from those complete plasmid genomes whose MOB types are well annotated. Next, based on natural language models, we used word vectors to characterize the PMFs. Several random forest classification models were trained and integrated to predict fragments of different lengths. Evaluating the tool using the benchmark dataset, we found that MOBFinder outperforms previous tools such as MOBscan and MOB-suite, with an overall accuracy approximately 59% higher than that of MOB-suite. Moreover, the balanced accuracy, harmonic mean, and F1-score reached up to 99% for some MOB types. When applied to a cohort of patients with type 2 diabetes (T2D), MOBFinder offered insights suggesting that the MOBF type plasmid, which is widely present in Escherichia and Klebsiella, and the MOBQ type plasmid might accelerate antibiotic resistance transmission in patients with T2D. CONCLUSIONS: To the best of our knowledge, MOBFinder is the first tool for MOB typing of PMFs. The tool is freely available at https://github.com/FengTaoSMU/MOBFinder.
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Metagenômica , Plasmídeos , Plasmídeos/genética , Metagenômica/métodos , Humanos , Software , MetagenomaRESUMO
Polyaniline-supported metal nanoparticles (M@PANIs) have been widely employed as catalysts for organic reactions. Traditionally, the catalytic activities of the materials can be improved by introducing functional groups onto the aniline monomers, but it may enhance the catalyst cost and reduce the production yield of the material. This work reports a new strategy for improving the catalytic activity of M@PANIs. It was found that induced by visible light in the presence of a polymeric carbon nitride catalyst and copper dopant, the oxidative polymerization of simple aniline occurred slowly and orderly to produce the copper-doped polyaniline nanotubes. The unique tubular structure protected the catalytically active Cu(I) inside and endowed even more sufficient contact of the catalytic sites with reactants so that the material exhibited excellent catalytic performances in C-N coupling reactions.
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Coal, a reliable and economical fuel, is expected to remain the primary energy source for power generation for the foreseeable future. However, conventional mining and utilization of coal has caused environmental degradation and infrastructure damage. An in situ coal conversion method has been proposed to mitigate environmental problems and reduce CO2 emissions resulting from coal extraction and utilization. This method involves the in situ conversion and utilization of coal, backfilling of waste rock, and CO2 mineralization to backfill the goaf. In this study, the impact of mining and conversion activities on the surrounding strata was evaluated to ascertain the effectiveness and advantages of the in situ coal conversion method. Transparent stope models were created using three-dimensional printing technology. The stress distribution and deformation characteristics of the surrounding strata were examined using photoelasticity and digital image correlation methods. The results were compared with those obtained using the traditional backfill mining method. The comparison revealed that the disturbance to the surrounding strata was 14.4 times less in the in situ conversion method than in the traditional backfill mining method. Additionally, the disturbance height at the roof and the disturbance depth at the floor were 4.2 and 2.1 times lower, respectively. The roof subsidence in the in situ conversion method was 1.97 times less than that in the traditional backfill mining method. These results confirm the advantages of minimizing the disturbance to surrounding rocks and controlling the subsidence of roof strata.
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Photocatalytic CO2 conversion towards C2+ fuels is a promising technology for simultaneously achieving carbon neutrality and alleviating the energy crisis. However, this strategy is inefficient due to the difficulty of both multi-electron transfer and C-C coupling during C2+ formation. In this work, CuInS2/MXene heterostructure with Cu vacancy is rationally designed by inâ situ hydrothermal synthesis. The VCu-CuInS2/MXene heterostructure has a suitable band structure and tight interface contact. Catalytic performances under different testing conditions, inâ situ spectroscopy, and COMSOL simulation reveal that LSPR-activated MXene promotes the formation of crucial intermediate CH2* and triggers the C-C coupling process under near-infrared light, as the key to acetate. Moreover, inâ situ XPS analysis, DFT calculations, and photoelectrochemical characterizations unveil that copper vacancy can promote charge transfer from CuInS2 to MXene and boost local electron aggregation on the MXene, further enhancing the photocatalytic efficiency and selectivity of C2 products. Contributing to the synergistic effect of copper vacancy and plasmonic MXene, VCu-CuInS2/MXene achieved excellent CO2RR activity with an acetate evolution rate of 250.0â µmol/h/g and a selectivity of 97.5 % under the full spectrum irradiation, which is 38.8 and 3.3 times higher than that of VCu-CuInS2 and CuInS2/MXene, respectively.
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In this study, dynamic behaviors of proteins and water during fresh noodles processing associated with the quality of fresh noodles were systematically investigated by using wheat near-isogenic lines carrying high-molecular-weight glutenin subunits (HMW-GS) 2 + 12, 3 + 12 or 5 + 10 at the Glu-D1 locus. The results showed that subunits 5 + 10 tend to form a complex gluten network and had a poorly hydrated ability, that prevent the intrusion of external water during cooking; subunits 3 + 12 formed a moderate strength gluten network that generated a medium ability to resist the hydrated and mechanical treatment, which explained the highest water absorption and less cooking loss of cooked noodles; while subunits 2 + 12 formed fragile protein aggregates that had a poor ability to resist mechanical. The findings demonstrated that subunits 3 + 12 provided a suitable gluten network which was crucial for intrusion and hydration of external water thus formed a uniform gluten network and excellent fresh noodle quality.
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Culinária , Glutens , Peso Molecular , Triticum , Água , Glutens/química , Triticum/química , Água/química , Farinha/análise , Proteínas de Plantas/química , Manipulação de AlimentosRESUMO
Hydrogels are increasingly used in flexible electronic devices, but the mechanical and electrochemical stabilities of hydrogel devices are often limited under specific harsh conditions. Herein, chemically/physically cross-linked double-network (DN) hydrogels containing binary cations Zn2+ and Li+ are constructed in order to address the above challenges. Double networks of chemically cross-linked polyacrylamide (PAM) and physically cross-linked κ-Carrageenan (κ-CG) are designed to account for the mechanical robustness while binary cations endow the hydrogels with excellent ionic conductivity and outstanding environmental adaptability. Excellent mechanical robustness and ionic conductivity (25 °C, 2.26 S·m-1; -25 °C, 1.54 S·m-1) have been achieved. Utilizing the DN hydrogels containing binary cations as signal-converting materials, we fabricated flexible mechanosensors. High gauge factors (resistive strain sensors, 2.4; capacitive pressure sensors, 0.82 kPa-1) and highly stable sensing ability have been achieved. Interestingly, zinc-ion hybrid supercapacitors containing the DN hydrogels containing binary cations as electrolytes have achieved an initial capacity of 52.5 mAh·g-1 at a current density of 3 A·g-1 and a capacity retention rate of 82.9% after 19,000 cycles. Proper working of the zinc-ion hybrid supercapacitors at subzero conditions and stable charge-discharge for more than 19,000 cycles at -25 °C have been demonstrated. Overall, DN hydrogels containing binary cations have provided promising materials for high-performance flexible electronic devices under harsh conditions.
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Curcumin, a compound derived from turmeric, is traditionally utilized in East Asian medicine for treating various health conditions, including epilepsy. Despite its involvement in numerous cellular signaling pathways, the specific mechanisms and targets of curcumin in epilepsy treatment have remained unclear. Our study focused on identifying the primary targets and functional pathways of curcumin in the brains of epileptic mice. Using drug affinity responsive target stabilization (DARTS) and affinity chromatography, we identified key targets in the mouse brain, revealing 232 and 70 potential curcumin targets, respectively. Bioinformatics analysis revealed a strong association of these proteins with focal adhesions and cytoskeletal components. Further experiments using DARTS, along with immunofluorescence staining and cell migration assays, confirmed curcumin's ability to regulate the dynamics of focal adhesions and influence cell migration. This study not only advances our understanding of curcumin's role in epilepsy treatment but also serves as a model for identifying therapeutic targets in neurological disorders.
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Background and purpose: Early blood-brain barrier (BBB) disruption in patients with acute ischemic stroke (AIS) can be detected on perfusion computed tomography (PCT) images before undergoing reperfusion therapy. In this study, we aimed to determine whether early disruption of the BBB predicts intracranial hemorrhage transformation (HT) in patients with AIS undergoing endovascular therapy and further identify factors influencing BBB disruption. Methods: We retrospectively analyzed general clinical and imaging data derived from 159 consecutive patients with acute anterior circulation stroke who were admitted to the Department of Neurology of the First Hospital of Jilin University, and who underwent endovascular treatment between January 1, 2021, and March 31, 2023. We evaluated the relationship between BBB destruction and intracranial HT before endovascular reperfusion therapy and examined the risk factors for early BBB destruction. Results: A total of 159 patients with assessable BBB leakage were included. The median (interquartile range, IQR) age was 63 (54-70) years, 108 (67.9%) patients were male, and the median baseline National Institutes of Health Stroke Scale (NHISS) score was 12 (10-15). Follow-up non-contrast computed tomography (NCCT) detected HT in 63 patients. After logistic regression modeling adjustment, we found that BBB leakage in the true leakage area was slightly more than 2-fold risk of HT (odds ratio [OR], 2.01; 95% confidence interval [CI] 1.02-3.92). Heart rate was also associated with HT (OR, 1.03, 95% CI, 1.00-1.05). High Blood-brain barrier permeability (BBBP) in the true leakage area was positively correlated with infarct core volume (OR, 1.03; 95% CI, 1.01-1.05). Conclusion: Early BBB destruction before endovascular reperfusion therapy was associated with HT, whereas high BBBP correlated positively with infarct core volume.