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BACKGROUND: End-stage renal disease (ESRD) necessitating hemodialysis pose substantial cardiovascular risks, with cardiovascular disease (CVD) as a leading cause of mortality. Biomarkers like copeptin have emerged as potential indicators of cardiovascular stress and prognosis in CKD populations. OBJECTIVE: This study aimed to assess the prognostic value of copeptin in predicting major adverse cardiovascular events (MACEs) among hemodialysis patients, alongside traditional cardiac biomarkers. METHODS: ESRD patients undergoing maintenance hemodialysis were enrolled. Copeptin levels were measured, and patients were followed for MACEs, defined as cardiovascular deaths, myocardial infarction, stroke, or heart failure-related hospitalizations. Cox proportional-hazards models were used to evaluate the association between copeptin and outcomes, adjusting for relevant covariates. RESULTS: Among 351 patients followed for a median of 22.7 months, elevated copeptin levels were significantly associated with an increased risk of MACEs (HR 1.519, 95 % CI 1.140 to 2.023; p = 0.00425). Copeptin demonstrated predictive capability across multiple statistical tests (Log-rank p = 0.024; Gehan p < 0.001; Tarone-Ware p < 0.001; Peto-Peto p = 0.027), although significance was attenuated in pairwise comparisons post-adjustment for multiple testing. Combining copeptin with NT-proBNP or hs-cTnT further enhanced risk stratification for MACEs. CONCLUSION: Elevated copeptin levels independently predict adverse cardiovascular outcomes in hemodialysis patients. Integrating copeptin with traditional cardiac biomarkers may refine risk stratification and guide personalized therapeutic strategies in this high-risk population.
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Smart textiles capable of both energy harvesting and multifunctional sensing are highly desirable for next-generation portable electronics. However, there are still challenges that need to be conquered, such as the innovation of an energy-harvesting model and the optimization of interface bonding between fibers and active materials. Herein, inspired by the spiral structure of natural vines, a highly stretchable triboelectric helical yarn (TEHY) was manufactured by twisting the carbon nanotube/polyurethane nanofiber (CNT/PU NF) Janus membrane. The TEHY had a zebra-stripe-like design that was composed of black interval conductive CNTs and white insulative PU NFs. Due to the different electron affinity, the zebra-patterned TEHY realized a self-frictional triboelectric effect because the numerous microscopic CNT/PU triboelectric interfaces generated an alternating current in the external conductive circuit without extra external friction layers. The helical geometry combined with the elastic PU matrix endowed TEHY with superelastic stretchability and outstanding output stability after 1000 cycles of the stretch-release test. By virtue of the robust mechanical and electrical stability, the TEHY can not only be used as a high-entropy mechanical energy harvester but also serve as a self-powered sensor to monitor the stretching or deforming stimuli and human physiological activities in real time. These merits manifested the versatile applications of TEHY in smart fabrics, wearable power supplies, and human-machine interactions.
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BACKGROUND: Saline lakes are home to various archaea that play special and crucial roles in the global biogeochemical cycle. The Qinghai-Tibet Plateau hosts a large number of lakes with diverse salinity ranging from 0.1 to over 400 g/L, harboring complex and diverse archaea. To the best of our knowledge, the formation mechanisms and potential ecological roles of archaea in Qinghai-Tibetan Plateau saline lakes remain largely unknown. RESULTS: Using High-throughput Illumina sequencing, we uncovered the vastly distinct archaea communities between two typical saline lakes with significant salinity differences on the Qinghai Tibet Plateau (Qinghai saline lake and Chaka hypersaline lake) and suggested archaea played different important roles in methanogenesis-related and nitrate reduction-related functions of these two lakes, respectively. Rather than the individual effect of salinity, the composite effect of salinity with diverse environmental parameters (e.g., temperature, chlorophyll a, total nitrogen, and total phosphorus) dominated the explanation of the variations in archaeal community structure in different habitats. Based on the network analysis, we further found the correlations between dominant archaeal OTUs were tight but significantly different between the two habitats, implying that archaeal interactions may also largely determine the shape of archaeal communities. CONCLUSION: The present study improved our understanding of the structure and function of archaea in different saline lakes on the Qinghai-Tibet Plateau and provided a new perspective on the mechanisms underlying shaping their communities.
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Archaea , Lagos , Salinidade , Lagos/microbiologia , Lagos/química , Archaea/genética , Archaea/classificação , Archaea/metabolismo , Tibet , Sequenciamento de Nucleotídeos em Larga Escala , Filogenia , Biodiversidade , Ecossistema , RNA Ribossômico 16S/genética , Nitrogênio/metabolismo , Nitrogênio/análise , DNA Arqueal/genéticaRESUMO
BACKGROUND: This study was designed to assess the associations between emerging cardiometabolic indices-the atherogenic index of plasma (AIP), the stress hyperglycemia ratio (SHR), the triglyceride-glucose (TyG) index, and the homeostasis model assessment of insulin resistance (HOMA-IR)-and the incidence of diabetic kidney disease (DKD) in type 2 diabetes (T2D) patients. METHODS: We consecutively enrolled 4351 T2D patients. The AIP, SHR, TyG index, and HOMA-IR were calculated from baseline parameters. DKD was defined as a urine albumin/creatinine ratio > 30 mg/g or an eGFR < 60 mL/min per 1.73 m. All participants were categorized into tertiles based on the cardiometabolic indices. Multivariate logistic regression models, restricted cubic splines, and receiver operating characteristic (ROC) curves were used for analysis. RESULTS: A total of 1371 (31.5%) patients were diagnosed with DKD. A restricted cubic spline showed a J-shaped association of the AIP and TyG index with DKD, a log-shaped association between HOMA-IR and DKD, and a U-shaped association between the SHR and DKD incidence. Multivariate logistic regression revealed that individuals in the highest tertile of the four cardiometabolic indices had a significantly greater risk of DKD than did those in the lowest tertile (AIP: OR = 1.08, 95% CI = 1.02-1.14, P = 0.005; SHR: OR = 1.42, 95% CI = 1.12-1.81, P = 0.004; TyG index: OR = 1.86, 95% CI = 1.42-2.45, P < 0.001; HOMA-IR: OR = 2.24, 95% CI = 1.52-3.30, P < 0.001). The receiver operating characteristic curves showed that the HOMA-IR score was better than other indices at predicting the risk of DKD, with an optimal cutoff of 3.532. CONCLUSIONS: Elevated AIP, SHR, TyG index and HOMA-IR are associated with a greater risk of DKD in patients with T2D. Among these indices, the HOMA-IR score demonstrated the strongest association with and predictive value for DKD incidence.
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Biomarcadores , Glicemia , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Medição de Risco , Incidência , Nefropatias Diabéticas/epidemiologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/sangue , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Triglicerídeos/sangue , Fatores de Risco Cardiometabólico , Estudos Transversais , Valor Preditivo dos Testes , Prognóstico , Fatores de RiscoRESUMO
This study aims to investigate the quality changes of germinated soybeans during refrigerated storage (4 °C), with an emphasis on the stimulatory effect of refrigeration on their special functional compounds. After germinating for two days, germinated soybeans were stored at 4 °C for seven days, while the germinated soybeans stored at 25 °C served as control group. The results showed that refrigerated storage significantly affected the physiological changes in germinated soybeans. The weight loss rate, browning rate, malondialdehyde (MDA) content and H2O2 content all decreased dramatically during refrigerated storage compared to the control group. The total phenolic and total flavonoid contents of germinated soybeans under refrigeration exhibited a trend of increasing and then decreasing over time. Additionally, during refrigerated storage, the total isoflavone content reached a peak of 8.72 g/kg on the fifth day, in which the content of daidzein and glycitin increased by 45% and 49% respectively, when compared with the control group. Moreover, the content of γ-aminobutyric acid (GABA) peaked on the first day, and kept a high level during storage. In which, the refrigerated group was 2.35-, 2.88-, 1.67-fold respectively after storage for three to seven days. These results indicated that refrigeration stimulated the biosynthesis of isoflavones and GABA in germinated soybeans during storage. More importantly, there was a sequential difference in the timing of the stimulation of the two functional components under refrigeration.
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Armazenamento de Alimentos , Germinação , Glycine max , Isoflavonas , Refrigeração , Ácido gama-Aminobutírico , Glycine max/metabolismo , Glycine max/crescimento & desenvolvimento , Isoflavonas/metabolismo , Ácido gama-Aminobutírico/metabolismo , Armazenamento de Alimentos/métodos , Malondialdeído/metabolismo , Peróxido de Hidrogênio/metabolismoRESUMO
Social mobility beliefs play a significant role in shaping adolescents' adaptive developmental outcomes, including well-being and academic functioning. Nevertheless, existing research may not cast light on the distinct trajectories and potential protective factors of social mobility beliefs. The present study aims to identify heterogeneity in trajectory patterns of social mobility beliefs among Chinese adolescents (Mage = 12.45, SDage = 2.60; 55.1% boys; 40.0% rural adolescents) in a four-wave (i.e., fall 2017, fall 2018, spring 2019, and fall 2019) longitudinal design, and examines the protective roles of parental academic involvement and adolescent future orientation. Three distinct trajectories of social mobility beliefs were identified: high-increasing (35.1%; a positive trajectory with the best developmental outcomes, including the lowest problem behaviors and depression symptoms, and the highest life satisfaction and academic competence), moderate-stable (49.8%), and low-decreasing (15.1%; a negative trajectory with the worst developmental outcomes, including the highest problem behaviors and depression symptoms, and the lowest life satisfaction and academic competence). Apart from the main effects of parental academic involvement and future orientation, a significant interaction effect of these two protective factors and adolescent group was detected, and only rural adolescents who reported both high levels of parental academic involvement and future orientation have a greater chance of being placed in the high-increasing trajectory than the low-decreasing trajectory. These findings highlight the significance of clarifying individual differences in the dynamic process of social mobility beliefs during adolescence, and elucidate rural-urban disparities in the influences of protective factors on social mobility beliefs trajectories, and inform individualized intervention strategies.
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Comportamento do Adolescente , Mobilidade Social , Humanos , Adolescente , Masculino , Feminino , Estudos Longitudinais , China , Comportamento do Adolescente/psicologia , Relações Pais-Filho , Satisfação Pessoal , População Rural/estatística & dados numéricos , Criança , População do Leste AsiáticoRESUMO
The process of reconstructing an arterial graft is a complex and dynamic process that is subject to the influence of various mechanical factors, including tissue regeneration and blood pressure. The attainment of favorable remodeling outcomes is contingent upon the biocompatibility and biomechanical properties of the arterial graft. A promising strategy involves the emulation of the three-layer structure of the native artery, wherein the inner layer is composed of polycaprolactone (PCL) fibers aligned with blood flow, exhibiting excellent biocompatibility that fosters endothelial cell growth and effectively prevents platelet adhesion. The middle layer, consisting of PCL and polyurethane (PU), offers mechanical support and stability by forming a contractile smooth muscle ring and antiexpansion PU network. The outer layer, composed of PCL fibers with an irregular arrangement, promotes the growth of nerves and pericytes for long-term vascular function. Prioritizing the reconstruction of the inner and outer layers establishes a stable environment for intermediate smooth muscle growth. Our three-layer arterial graft is designed to provide the blood vessel with mechanical support and stability through nondegradable PU, while the incorporation of degradable PCL generates potential spaces for tissue ingrowth, thereby transforming our graft into a living implant.
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Variants which disrupt splicing are a frequent cause of rare disease that have been under-ascertained clinically. Accurate and efficient methods to predict a variant's impact on splicing are needed to interpret the growing number of variants of unknown significance (VUS) identified by exome and genome sequencing. Here, we present the results of the CAGI6 Splicing VUS challenge, which invited predictions of the splicing impact of 56 variants ascertained clinically and functionally validated to determine splicing impact. The performance of 12 prediction methods, along with SpliceAI and CADD, was compared on the 56 functionally validated variants. The maximum accuracy achieved was 82% from two different approaches, one weighting SpliceAI scores by minor allele frequency, and one applying the recently published Splicing Prediction Pipeline (SPiP). SPiP performed optimally in terms of sensitivity, while an ensemble method combining multiple prediction tools and information from databases exceeded all others for specificity. Several challenge methods equalled or exceeded the performance of SpliceAI, with ultimate choice of prediction method likely to depend on experimental or clinical aims. One quarter of the variants were incorrectly predicted by at least 50% of the methods, highlighting the need for further improvements to splicing prediction methods for successful clinical application.
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Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness (AHR), inflammation, and remodeling. Epithelial-mesenchymal transition (EMT) is an essential player in these alterations. Scutellarin is isolated from Erigeron breviscapus. Its vascular relaxative, myocardial protective, and anti-inflammatory effects have been well established. This study was designed to detect the biological roles of scutellarin in asthma and its related mechanisms. The asthma-like conditions were induced by ovalbumin challenges. The airway resistance and dynamic compliance were recorded as the results of AHR. Bronchoalveolar lavage fluid (BALF) was collected and processed for differential cell counting. Hematoxylin and eosin staining, periodic acid-Schiff staining, and Masson staining were conducted to examine histopathological changes. The levels of asthma-related cytokines were measured by enzyme-linked immunosorbent assay. For in vitro analysis, the 16HBE cells were stimulated with 10 ng/mL transforming growth beta-1 (TGF-ß1). Cell migration was estimated by Transwell assays and wound healing assays. E-cadherin, N-cadherin, and α-smooth muscle actin (α-SMA) were analyzed by western blotting, real-time quantitative polymerase chain reaction, immunofluorescence staining, and immunohistochemistry staining. The underlying mechanisms of the mitogen-activated protein kinase (MAPK) and Smad pathways were investigated by western blotting. In an ovalbumin-induced asthmatic mouse model, scutellarin suppressed inflammation and inflammatory cell infiltration into the lungs and attenuated AHR and airway remodeling. Additionally, scutellarin inhibited airway EMT (upregulated E-cadherin level and downregulated N-cadherin and α-SMA) in ovalbumin-challenged asthmatic mice. For in vitro analysis, scutellarin prevented the TGF-ß1-induced migration and EMT in 16HBE cells. Mechanistically, scutellarin inhibits the phosphorylation of Smad2, Smad3, ERK, JNK, and p38 in vitro and in vivo. In conclusion, scutellarin can inactivate the Smad/MAPK pathways to suppress the TGF-ß1-stimulated epithelial fibrosis and EMT and relieve airway inflammation and remodeling in asthma. This study provides a potential therapeutic strategy for asthma.
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Remodelação das Vias Aéreas , Apigenina , Asma , Glucuronatos , Ovalbumina , Proteína Smad2 , Proteína Smad3 , Apigenina/farmacologia , Apigenina/uso terapêutico , Remodelação das Vias Aéreas/efeitos dos fármacos , Animais , Camundongos , Glucuronatos/farmacologia , Glucuronatos/uso terapêutico , Ovalbumina/toxicidade , Humanos , Asma/tratamento farmacológico , Asma/induzido quimicamente , Asma/metabolismo , Asma/patologia , Proteína Smad3/metabolismo , Proteína Smad2/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Fibrose/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Linhagem Celular , Brônquios/patologia , Brônquios/efeitos dos fármacos , Brônquios/metabolismo , Camundongos Endogâmicos BALB C , Transição Epitelial-Mesenquimal/efeitos dos fármacos , FenótipoRESUMO
INTRODUCTION: Pathogenic variant in the KCNQ2 gene is a common genetic etiology of neonatal convulsion. However, it remains a question in KCNQ2-related disorders that who will develop into atypical developmental outcomes. METHODS: We established a prediction model for the neurodevelopmental outcomes of newborns with seizures caused by KCNQ2 gene defects based on the Gradient Boosting Machine (GBM) model with a training set obtained from the Human Gene Mutation Database (HGMD, public training dataset). The features used in the prediction model were, respectively, based on clinical features only and optimized features. The validation set was obtained from the China Neonatal Genomes Project (CNGP, internal validation dataset). RESULTS: With the HGMD training set, the prediction results showed that the area under the receiver-operating characteristic curve (AUC) for predicting atypical developmental outcomes was 0.723 when using clinical features only and was improved to 0.986 when using optimized features, respectively. In feature importance ranking, both variants pathogenicity and protein functional/structural features played an important role in the prediction model. For the CNGP validation set, the AUC was 0.596 when using clinical features only and was improved to 0.736 when using optimized features. CONCLUSION: In our study, functional/structural features and variant pathogenicity have higher feature importance compared with clinical information. This prediction model for the neurodevelopmental outcomes of newborns with seizures caused by KCNQ2 gene defects is a promising alternative that could prove to be valuable in clinical practice.
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Doenças do Recém-Nascido , Canal de Potássio KCNQ2 , Recém-Nascido , Humanos , Canal de Potássio KCNQ2/genética , Convulsões/genética , Mutação , PrognósticoRESUMO
Adherens junctions between tubular epithelial cells are disrupted in renal ischemia/reperfusion (I/R) injury. Syndecan-1 (SDC-1) is involved in maintaining cell morphology. We aimed to study the role of SDC-1 shedding induced by renal I/R in the destruction of intracellular adherens junctions. We found that SDC-1 shedding was increased while the expression of E-cadherin was decreased. This observation was accompanied by the activation of STAT3 in the kidneys. Inhibiting the shedding of SDC-1 induced by I/R could alleviate this effect. Mild renal I/R could induce more severe renal injury, lower E-cadherin expression, damaged cell junctions, and activated STAT3 in knockout mice with the tubule-specific deletion of SDC-1 mice. The results in vitro were consistent with those in vivo. Inhibiting the shedding of SDC-1 could alleviate the decreased expression of E-cadherin and damage of cell adherens junctions through inhibiting the activation of STAT3 during ischemic acute kidney injury.
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Tannic acid (TA) has been recently considered as a new dough additive for improving the bread-making quality of wheat. However, the effects of TA supplementation on the sensory quality parameters (color, crumb grain structure, and sensory properties) of bread have not been studied. Further, the potential of TA supplementation in bread-making quality improvement has not been evaluated by using commercial flour. In the present study, three commercial wheat flours (namely, XL, QZG, and QZZ) with different gluten qualities were used to evaluate the effects of TA supplementation (in concentrations of 0.1% and 0.3%, respectively). TA supplementation did not change the proximate composition of the breads but increased the volumes and specific volumes of XL and QZG breads. TA supplementation enhanced antioxidant activities, with 0.3% TA significantly increasing the antioxidant capacities of bread made from all three flour samples by approximately four-fold (FRAP method)/three-fold (ABTS method). Positive effects of TA on the reduction in crumb hardness, gumminess, and chewiness were observed in the XL bread, as determined by the texture profile analysis. For the analyses on visual and sensory attributes, our results suggest that TA did not affect the crust color, but only slightly reduced the L* (lightness) and b* (yellowness) values of the crumb and increased the a* (redness) value. TA supplementation also increased the porosity, total cell area, and mean cell area. Satisfactorily, the sensory evaluation results demonstrate that TA-supplemented breads did not exhibit negative sensory attributes when compared to the non-TA-added breads; rather, the attributes were even increased. In summary, TA-supplemented breads generally had not only better baking quality attributes and enhanced antioxidant activities, but, more importantly, presented high consumer acceptance in multiple commercial flour samples. Our results support the commercial potential of TA to be used as a dough improver.
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We report external bias driven switchable photocurrent (anodic and cathodic) in 2.3 eV indirect band gap perovskite (BiFeO3) photoactive thin films. Depending on the applied bias our BiFeO3 films exhibit photocurrents more usually found in p- or n-type semiconductor photoelectrodes. In order to understand the anomalous behaviour ambient photoemission spectroscopy and Kelvin-probe techniques have been used to determine the band structure of the BiFeO3. We found that the Fermi level (Ef) is at -4.96 eV (vs. vacuum) with a mid-gap at -4.93 eV (vs. vacuum). Our photochemically determined flat band potential (Efb) was found to be 0.3 V vs. NHE (-4.8 V vs. vacuum). These band positions indicate that Ef is close to mid-gap, and Efb is close to the equilibrium with the electrolyte enabling either cathodic or anodic band bending. We show an ability to control switching from n- to p-type behaviour through the application of external bias to the BiFeO3 thin film. This ability to control majority carrier dynamics at low applied bias opens a number of applications in novel optoelectronic switches, logic and energy conversion devices.
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BACKGROUND: The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking. RESULTS: Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression. CONCLUSION: This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.
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Microbioma Gastrointestinal , Falência Renal Crônica , Microbiota , Insuficiência Renal Crônica , Humanos , Metagenoma , Insuficiência Renal Crônica/genética , Insuficiência Renal Crônica/metabolismo , Fezes , ClostridialesRESUMO
Soy allergy is a common health problem. Food structure may change the gastroduodenal digestion and absorption of soy proteins, thus leading to the modulation of the immunoreactivity of soy proteins. In this study, lactic acid bacterium (LAB)-fermented soy protein isolates (FSPIs) were prepared at four concentrations (0.2 %-5.0 %, w/v) to present various matrix structures (nongel, NG; weak gel, WG; medium gel, MG; and firm gel, FG) and subjected to in vitro dynamic gastroduodenal digestion model. The results of sandwich enzyme-linked immunosorbent and human serum IgE binding capacity assays demonstrated that FSPI gels, especially the FSPI-MG/WG digestates obtained at the early and medium stages of duodenal digestion (D-5 and D-30), possessed greater potency in immunoreactivity reduction than FSPI-NG and reduced to 1.9 %-68.3 %. The transepithelial transport study revealed that the immunoreactivity of FSPI-MG/WG D-5 and D-30 digestates decreased through the stimulation of interferon-γ production and the induction of dominant Th1/Th2 differentiation. Peptidomics and bioinformatics analyses illustrated that compared with FSPI-NG, the FSPI-gel structure promoted the epitope degradation of the major allergens glycinin G2/G5, ß-conglycinin α/ß subunit, P34, lectin, trypsin inhibitor, and basic 7S globulin. Spatial structure analysis showed that FSPI-gel elicited an overall promotion in the degradation of allergen epitopes located in interior and exterior regions and was dominated by α-helix and ß-sheet secondary structures, whereas FSPI-MG/WG promoted the degradation of epitopes located in the interior region of glycinin/ß-conglycinin and exterior region of P34/basic 7S globulin. This study suggested that the FSPI-gel structure is a promising food matrix for decreasing the allergenic potential of allergenic epitopes during gastroduodenal digestion and provided basic information on the production of hypoallergenic soy products.
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Globulinas , Proteínas de Soja , Humanos , Proteínas de Soja/química , Glycine max/química , Epitopos/química , Globulinas/química , DigestãoRESUMO
INTRODUCTION: Reverse genetic studies conducted in the plant with a complex or polyploidy genome enriched with large gene families (like wheat) often meet challenges in identifying the key candidate genes related to important traits and prioritizing the genes for functional experiments. OBJECTIVE: To overcome the above-mentioned challenges of reverse genetics, this work aims to establish an efficient multi-species strategy for genome-wide gene identification and prioritization of the key candidate genes. METHODS: We established the integrative gene duplication and genome-wide analysis (iGG analysis) as a strategy for pinpointing key candidate genes deserving functional research. The iGG captures the evolution, and the expansion/contraction of large gene families across phylogeny-related species and integrates spatial-temporal expression information for gene function inference. Transgenic approaches were also employed to functional validation. RESULTS: As a proof-of-concept for the iGG analysis, we took the wheat calcineurin B-like protein-interacting protein kinases (CIPKs) family as an example. We identified CIPKs from seven monocot species, established the orthologous relationship of CIPKs between rice and wheat, and characterized Triticeae-specific CIPK duplicates (e.g., CIPK4 and CIPK17). Integrated with our analysis of CBLs and CBL-CIPK interaction, we revealed that divergent expressions of TaCBLs and TaCIPKs could play an important role in keeping the stoichiometric balance of CBL-CIPK. Furthermore, we validated the function of TaCIPK17-A2 in the regulation of drought tolerance by using transgenic approaches. Overexpression of TaCIPK17 enhanced antioxidant capacity and improved drought tolerance in wheat. CONCLUSION: The iGG analysis leverages evolutionary and comparative genomics of crops with large genomes to rapidly highlight the duplicated genes potentially associated with speciation, domestication and/or particular traits that deserve reverse-genetic functional studies. Through the identification of Triticeae-specific TaCIPK17 duplicates and functional validation, we demonstrated the effectiveness of the iGG analysis and provided a new target gene for improving drought tolerance in wheat.
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The PEG/salt aqueous two-phase system (ATPS) is the most common ATPS, but its application is still limited due to the restricted polarity difference between the two phases and the poor enhancement effect of adjuvants on ATPS performance so far. Unlike the adjuvants used so far, calixarenes can bind ions and molecules via multiple noncovalent interactions. In the present study, a water-soluble calixarene, p-sulfonatocalix[4]arene (SC[4]), was used for the first time as the adjuvant to improve the performance of the PEG 600/(NH4)2SO4 ATPS through multiple interactions. It is found that when the SC[4] and the SC[4]/imidazole ionic liquid ([Cnmim]Br) complex were used as the adjuvants, the formation of PEG 600/(NH4)2SO4 ATPS was enhanced, and the transfer of the extracts (including S-mandelic acid, L-tryptophan, and L-phenylalanine) into the PEG phase was promoted. Moreover, although the single [Cnmim]Br, a commonly used adjuvant, does not promote the migration of the target molecules into the polymer phase, the SC[4]/[Cnmim]Br complex is superior to SC[4] in enhancing the performance of the ATPS because the SC[4]/[Cnmim]Br aggregates enable more binding sites to combine with the extract. Besides, the partition coefficient of SC[4] in the PEG/trisodium citrate ATPS is much smaller than that in the PEG/(NH4)2SO4 ATPS, which is helpful for the recovery of extracts into the citrate phase.
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Partial root-zone drying (PRD) is an effective water-saving irrigation strategy that improves stress tolerance and facilitates efficient water use in several crops. It has long been considered that abscisic acid (ABA)-dependent drought resistance may be involved during partial root-zone drying. However, the molecular mechanisms underlying PRD-mediated stress tolerance remain unclear. It's hypothesized that other mechanisms might contribute to PRD-mediated drought tolerance. Here, rice seedlings were used as a research model and the complex transcriptomic and metabolic reprogramming processes were revealed during PRD, with several key genes involved in osmotic stress tolerance identified by using a combination of physiological, transcriptome, and metabolome analyses. Our results demonstrated that PRD induces transcriptomic alteration mainly in the roots but not in the leaves and adjusts several amino-acid and phytohormone metabolic pathways to maintain the balance between growth and stress response compared to the polyethylene glycol (PEG)-treated roots. Integrated analysis of the transcriptome and metabolome associated the co-expression modules with PRD-induced metabolic reprogramming. Several genes encoding the key transcription factors (TFs) were identified in these co-expression modules, highlighting several key TFs, including TCP19, WRI1a, ABF1, ABF2, DERF1, and TZF7, involved in nitrogen metabolism, lipid metabolism, ABA signaling, ethylene signaling, and stress regulation. Thus, our work presents the first evidence that molecular mechanisms other than ABA-mediated drought resistance are involved in PRD-mediated stress tolerance. Overall, our results provide new insights into PRD-mediated osmotic stress tolerance, clarify the molecular regulation induced by PRD, and identify genes useful for further improving water-use efficiency and/or stress tolerance in rice.
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Plant biology research has currently entered the post-genomics era with the advances in genomic technologies [...].
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Genômica , Multiômica , Plantas/genética , TecnologiaRESUMO
BACKGROUND: Hemodynamically significant patent ductus arteriosus (hsPDA) is associated with increased comorbidities in neonates. Early evaluation of hsPDA risk is critical to implement individualized intervention. The aim of the study was to provide a powerful reference for the early identification of high-risk hsPDA population and early treatment decisions. METHODS: We enrolled infants who were diagnosed with PDA and performed exome sequencing. The collapsing analyses were used to find the risk gene set (RGS) of hsPDA for model construction. The credibility of RGS was proven by RNA sequencing. Multivariate logistic regression was performed to establish models combining clinical and genetic features. The models were evaluated by area under the receiver operating curve (AUC) and decision curve analysis (DCA). RESULTS: In this retrospective cohort study of 2199 PDA patients, 549 (25.0%) infants were diagnosed with hsPDA. The model [all clinical characteristics selected by least absolute shrinkage and selection operator regression (all CCs)] based on six clinical variables was acquired within three days of life, including gestational age (GA), respiratory distress syndrome (RDS), the lowest platelet count, invasive mechanical ventilation, and positive inotropic and vasoactive drugs. It has an AUC of 0.790 [95% confidence interval (CI) = 0.749-0.832], while the simplified model (basic clinical characteristic model) including GA and RDS has an AUC of 0.753 (95% CI = 0.706-0.799). There was a certain consistency between RGS and differentially expressed genes of the ductus arteriosus in mice. The AUC of the models was improved by RGS, and the improvement was significant (all CCs vs. all CCs + RGS: 0.790 vs. 0.817, P < 0.001). DCA demonstrated that all models were clinically useful. CONCLUSIONS: Models based on clinical factors were developed to accurately stratify the risk of hsPDA in the first three days of life. Genetic features might further improve the model performance. Video Abstract (MP4 86834 kb).