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C3-functionalized dihydroquinolinones represent a class of important biologically active compounds. Although methods for synthesizing C2/4-functionalized dihydroquinolinones have been extensively reported, research on the synthesis of C3-functionalized dihydroquinolinone is extremely rare. Herein, we report for the first time a method for C3-alkenylated dihydroquinolinones via iron(III)-catalyzed amine-release triple condensation of enaminones. These reactions exhibit broad substrate scope and offer operationally simple, low-cost catalyzed procedures in a single step. Subsequent intramolecular and intermolecular additions to the alkene moiety provide diverse C3-functionalized dihydroquinolinone derivatives.
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BACKGROUND: Kobreisa littledalei, belonging to the Cyperaceae family is the first Kobresia species with a reference genome and the most dominant species in Qinghai-Tibet Plateau alpine meadows. It has several resistance genes which could be used to breed improved crop varieties. Reverse Transcription Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR) is a popular and accurate gene expression analysis method. Its reliability depends on the expression levels of reference genes, which vary by species, tissues and environments. However, K.littledalei lacks a stable and normalized reference gene for RT-qPCR analysis. RESULTS: The stability of 13 potential reference genes was tested and the stable reference genes were selected for RT-qPCR normalization for the expression analysis in the different tissues of K. littledalei under two abiotic stresses (salt and drought) and two hormonal treatments (abscisic acid (ABA) and gibberellin (GA)). Five algorithms were used to assess the stability of putative reference genes. The results showed a variation amongst the methods, and the same reference genes showed tissue expression differences under the same conditions. The stability of combining two reference genes was better than a single one. The expression levels of ACTIN were stable in leaves and stems under normal conditions, in leaves under drought stress and in roots under ABA treatment. The expression of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) expression was stable in the roots under the control conditions and salt stress and in stems exposed to drought stress. Expression levels of superoxide dismutase (SOD) were stable in stems of ABA-treated plants and in the roots under drought stress. Moreover, RPL6 expression was stable in the leaves and stems under salt stress and in the stems of the GA-treated plants. EF1-alpha expression was stable in leaves under ABA and GA treatments. The expression levels of 28 S were stable in the roots under GA treatment. In general, ACTIN and GAPDH could be employed as housekeeping genes for K. littledalei under different treatments. CONCLUSION: This study identified the best RT-qPCR reference genes for different K. littledalei tissues under five experimental conditions. ACTIN and GAPDH genes can be employed as the ideal housekeeping genes for expression analysis under different conditions. This is the first study to investigate the stable reference genes for normalized gene expression analysis of K. littledalei under different conditions. The results could aid molecular biology and gene function research on Kobresia and other related species.
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Genes de Plantas , Reacción en Cadena en Tiempo Real de la Polimerasa , Plantones , Plantones/genética , Cyperaceae/genética , Estándares de Referencia , Perfilación de la Expresión Génica/métodos , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genética , Sequías , Reproducibilidad de los Resultados , Ácido Abscísico/metabolismo , Giberelinas/metabolismoRESUMEN
Anti-CDK4/6 therapy has been employed for the treatment for head and neck squamous cell carcinoma (HNSCC) with CDK4/6 hyperactivation, but the response rate is relatively low. In this study, we first showed that CDK4 and CDK6 was over-expressed and conferred poor prognosis in HNSCC. Moreover, in RB-positive HNSCC, STAT3 signaling was activated induced by CDK4/6 inhibition and STAT3 promotes RB deficiency by upregulation of MYC. Thirdly, the combination of Stattic and CDK4/6 inhibitor results in striking anti-tumor effect in vitro and in Cal27 derived animal models. Additionally, phospho-STAT3 level negatively correlates with RB expression and predicts poor prognosis in patients with HNSCC. Taken together, our findings suggest an unrecognized function of STAT3 confers to CDK4/6 inhibitors resistance and presenting a promising combination strategy for patients with HNSCC.
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Quinasa 4 Dependiente de la Ciclina , Quinasa 6 Dependiente de la Ciclina , Neoplasias de Cabeza y Cuello , Inhibidores de Proteínas Quinasas , Factor de Transcripción STAT3 , Carcinoma de Células Escamosas de Cabeza y Cuello , Ensayos Antitumor por Modelo de Xenoinjerto , Humanos , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Animales , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Línea Celular Tumoral , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas/genética , Femenino , Masculino , Ratones Desnudos , Ratones , Proteína de Retinoblastoma/metabolismo , Proliferación Celular/efectos de los fármacos , Sinergismo Farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Resistencia a Antineoplásicos/efectos de los fármacos , FosforilaciónRESUMEN
BACKGROUND: Cold stress has negative effects on the growth and health of mammals, and has become a factor restricting livestock development at high latitudes and on plateaus. The gut-liver axis is central to energy metabolism, and the mechanisms by which it regulates host energy metabolism at cold temperatures have rarely been illustrated. In this study, we evaluated the status of glycolipid metabolism and oxidative stress in pigs based on the gut-liver axis and propose that AMP-activated protein kinase (AMPK) is a key target for alleviating energy stress at cold temperatures by dietary fat supplementation. RESULTS: Dietary fat supplementation alleviated the negative effects of cold temperatures on growth performance and digestive enzymes, while hormonal homeostasis was also restored. Moreover, cold temperature exposure increased glucose transport in the jejunum. In contrast, we observed abnormalities in lipid metabolism, which was characterized by the accumulation of bile acids in the ileum and plasma. In addition, the results of the ileal metabolomic analysis were consistent with the energy metabolism measurements in the jejunum, and dietary fat supplementation increased the activity of the mitochondrial respiratory chain and lipid metabolism. As the central nexus of energy metabolism, the state of glycolipid metabolism and oxidative stress in the liver are inconsistent with that in the small intestine. Specifically, we found that cold temperature exposure increased glucose transport in the liver, which fully validates the idea that hormones can act on the liver to regulate glucose output. Additionally, dietary fat supplementation inhibited glucose transport and glycolysis, but increased gluconeogenesis, bile acid cycling, and lipid metabolism. Sustained activation of AMPK, which an energy receptor and regulator, leads to oxidative stress and apoptosis in the liver; dietary fat supplementation alleviates energy stress by reducing AMPK phosphorylation. CONCLUSIONS: Cold stress reduced the growth performance and aggravated glycolipid metabolism disorders and oxidative stress damage in pigs. Dietary fat supplementation improved growth performance and alleviated cold temperature-induced energy stress through AMPK-mediated mitochondrial homeostasis. In this study, we highlight the importance of AMPK in dietary fat supplementation-mediated alleviation of host energy stress in response to environmental changes.
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This work presents a novel use of fibrous egg white protein (FEWP) in food preservation and nutraceutical applications. In this study, food-grade FEWP was used as an encapsulating material, along with chitosan (CS), to stabilize emulsions. The emulsion system was then used as a delivery system to improve the stability of retinyl acetate (RA). The structural and functional properties, as well as the stability and rheological behavior of the FEWP/CS copolymer, was investigated. The stability of RA-enriched emulsions was also evaluated. FEWP and CS stabilized emulsions exhibited smaller particle size and enhanced stability against different ionic strengths and storage periods. Additionally, RA-encapsulated emulsions stabilized by FEWP:CS (25:1 w/w) effectively inhibited apple browning. This study provides a promising strategy for delivering antioxidant components, highlighting its potential in food preservation and nutraceutical applications.
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Diterpenos , Clara de Huevo , Emulsiones , Ésteres de Retinilo , Vitamina A , Emulsiones/química , Diterpenos/química , Ésteres de Retinilo/química , Clara de Huevo/química , Vitamina A/química , Tamaño de la Partícula , Conservación de Alimentos/métodos , Proteínas del Huevo/química , Malus/química , Quitosano/química , Reología , PollosRESUMEN
Alfalfa, an essential forage crop known for its high yield, nutritional value, and strong adaptability, has been widely cultivated worldwide. The yield and quality of alfalfa are frequently jeopardized due to environmental degradation. Lignin, a constituent of the cell wall, enhances plant resistance to abiotic stress, which often causes osmotic stress in plant cells. However, how lignin responds to osmotic stress in leaves remains unclear. This study explored the effects of osmotic stress on lignin accumulation and the contents of intermediate metabolites involved in lignin synthesis in alfalfa leaves. Osmotic stress caused an increase in lignin accumulation and the alteration of core enzyme activities and gene expression in the phenylpropanoid pathway. We identified five hub genes (CSE, CCR, CADa, CADb, and POD) and thirty edge genes (including WRKYs, MYBs, and UBPs) by integrating transcriptome and metabolome analyses. In addition, ABA and ethylene signaling induced by osmotic stress regulated lignin biosynthesis in a contradictory way. These findings contribute to a new theoretical foundation for the breeding of high-quality and resistant alfalfa varieties.
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Lignina , Medicago sativa , Medicago sativa/genética , Lignina/metabolismo , Presión Osmótica , Fitomejoramiento , Perfilación de la Expresión Génica , Hojas de la Planta/metabolismo , Estrés Fisiológico/genética , Regulación de la Expresión Génica de las PlantasRESUMEN
This paper was dedicated to the study of the effect of sucrose-phosphate on aspects of physicochemical properties, lipid distribution and protein structure during the picklig of reduced-salt salted egg yolk (SEY). This work constructed a reduced-salt pickling system from a new perspective (promoting osmosis) by using a sucrose-phosphate-salt. Results showed that SEY-28d achieved a desirable salt content (1.07 %), hardness (573.46 g) and springiness (0.65 g). The matured SEY was in excellent quality with orange-red color and loose sandy texture. This was because the lipoprotein aggregated with each other through hydrophobic interaction to form a stable network structure. In addition, the hypertonic environment accelerated salt penetration. These also created good condition for lipid spillage. The results of confocal laser scanning microscope also verified this phenomenon. This work provides important guidance for new reduced-salt curing of traditional pickled foods, deep processing of SEY, and industry development in the field of poultry egg.
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Yema de Huevo , Fosfatos , Yema de Huevo/química , Fosfatos/farmacología , Huevos , Cloruro de Sodio/química , Cloruro de Sodio Dietético/análisis , Lípidos/análisis , ÓsmosisRESUMEN
The label transition matrix has emerged as a widely accepted method for mitigating label noise in machine learning. In recent years, numerous studies have centered on leveraging deep neural networks to estimate the label transition matrix for individual instances within the context of instance-dependent noise. However, these methods suffer from low search efficiency due to the large space of feasible solutions. Behind this drawback, we have explored that the real murderer lies in the invalid class transitions, that is, the actual transition probability between certain classes is zero but is estimated to have a certain value. To mask the invalid class transitions, we introduced a human-cognition-assisted method with structural information from human cognition. Specifically, we introduce a structured transition matrix network (STMN) designed with an adversarial learning process to balance instance features and prior information from human cognition. The proposed method offers two advantages: 1) better estimation effectiveness is obtained by sparing the transition matrix and 2) better estimation accuracy is obtained with the assistance of human cognition. By exploiting these two advantages, our method parametrically estimates a sparse label transition matrix, effectively converting noisy labels into true labels. The efficiency and superiority of our proposed method are substantiated through comprehensive comparisons with state-of-the-art methods on three synthetic datasets and a real-world dataset. Our code will be available at https://github.com/WheatCao/STMN-Pytorch.
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With the development and popularization of the Beidou-3 navigation satellite system (BDS-3), to ensure its unique short message function, it is necessary to integrate a radio frequency (RF) transmitting circuit with high performance in the BDS-3 terminal. As the key device in an RF transmitting circuit, the RF power amplifier (PA) largely determines the comprehensive performance of the circuit with its transmission power, efficiency, linearity, and integration. Therefore, in this paper, an L-band highly integrated PA chip compatible with 3 W and 5 W output power is designed in InGaP/GaAs heterojunction bipolar transistor (HBT) technology combined with temperature-insensitive adaptive bias technology, class-F harmonic suppression technology, analog pre-distortion technology, temperature-insensitive adaptive power detection technology, and land grid array (LGA) packaging technology. Additionally, three auxiliary platforms are proposed, dedicated to the simulation and optimization of the same type of PA designs. The simulation results show that at the supply voltage of 5 V and 3.5 V, the linear gain of the PA chip reaches 39.4 dB and 38.7 dB, respectively; the output power at 1 dB compression point (P1dB) reaches 37.5 dBm and 35.1 dBm, respectively; the saturated output power (Psat) reaches 38.2 dBm and 36.2 dBm, respectively; the power added efficiency (PAE) reaches 51.7% and 48.2%, respectively; and the higher harmonic suppression ratios are less than -62 dBc and -65 dBc, respectively. The size of the PA chip is only 6 × 4 × 1 mm3. The results also show that the PA chip has high gain, high efficiency, and high linearity under both output power conditions, which has obvious advantages over similar PA chip designs and can meet the short message function of the BDS-3 terminal in various application scenarios.
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Spectrometers are key instruments in diverse fields, notably in medical and biosensing applications. Recent advancements in nanophotonics and computational techniques have contributed to new spectrometer designs characterized by miniaturization and enhanced performance. This paper presents a comprehensive review of miniaturized computational spectrometers (MCS). We examine major MCS designs based on waveguides, random structures, nanowires, photonic crystals, and more. Additionally, we delve into computational methodologies that facilitate their operation, including compressive sensing and deep learning. We also compare various structural models and highlight their unique features. This review also emphasizes the growing applications of MCS in biosensing and consumer electronics and provides a thoughtful perspective on their future potential. Lastly, we discuss potential avenues for future research and applications.
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The time-delay integration (TDI) technique is increasingly used to improve the signal-to-noise ratio (SNR) of remote sensing and imaging by exposing the scene multiple times. Inspired by the principle of TDI, we propose a TDI-like pushbroom multi-slit hyperspectral imaging (MSHSI) approach. In our system, multiple slits are used to significantly improve the throughput of the system, thereby enhancing the sensitivity and SNR through multiple exposures of the same scene during pushbroom scan. Meanwhile, a linear dynamic model for the pushbroom MSHSI is established, where the Kalman filter (KF) is employed to reconstruct the time-varying overlapped spectral images on a single conventional image sensor. Further, we designed and fabricated a customized optical system that can operate in both multi-slit and single slit modes to experimentally verify the feasibility of the proposed method. Experimental results indicate that the developed system improved SNR by a factor of about 7 compared to that of the single slit mode, while demonstrating excellent resolution in both spatial and spectral dimensions.
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Background: Severe acute respiratory syndrome coronavirus (SARS-CoVs) have emerged as a global health threat, which had caused a high rate of mortality. There is an urgent need to find effective drugs against these viruses. Objective: This study aims to predict the activity of unsymmetrical aromatic disulfides by constructing a QSAR model, and to design new compounds according to the structural and physicochemical attributes responsible for higher activity towards SARS-CoVs main protease. Methods: All molecules were constructed in ChemOffice software and molecular descriptors were calculated by CODESSA software. A regression-based linear heuristic method was established by changing descriptors datasets and calculating predicted IC50 values of compounds. Then, some new compounds were designed according to molecular descriptors from the heuristic method model. The compounds with predicted values smaller than a set point were constantly screened out. Finally, the properties analysis and molecular docking were conducted to further understand the structure-activity relationships of these finalized compounds. Results: The heuristic method explored the various descriptors responsible for bioactivity and gained the best linear model with R2 0.87. The success of the model fully passed the testing set validation, proving that the model has both high statistical significance and excellent predictive ability. A total of 5 compounds with ideal predicted IC50 were found from the 96 newly designed derivatives and their properties analyze was carried out. Molecular docking experiments were conducted for the optimal compound 31a, which has the best compound activity with good target protein binding capability. Conclusion: The heuristic method was quite reliable for predicting IC50 values of unsymmetrical aromatic disulfides. The present research provides meaningful guidance for further exploration of the highly active inhibitors for SARS-CoVs.
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Autoimmune diseases such as ankylosing spondylitis (AS) can be driven by emerging neoantigens that disrupt immune tolerance. Here, we developed a workflow to profile posttranslational modifications involved in neoantigen formation. Using mass spectrometry, we identified a panel of cysteine residues differentially modified by carboxyethylation that required 3-hydroxypropionic acid to generate neoantigens in patients with AS. The lysosomal degradation of integrin αIIb [ITGA2B (CD41)] carboxyethylated at Cys96 (ITGA2B-ceC96) generated carboxyethylated peptides that were presented by HLA-DRB1*04 to stimulate CD4+ T cell responses and induce autoantibody production. Immunization of HLA-DR4 transgenic mice with the ITGA2B-ceC96 peptide promoted colitis and vertebral bone erosion. Thus, metabolite-induced cysteine carboxyethylation can give rise to pathogenic neoantigens that lead to autoreactive CD4+ T cell responses and autoantibody production in autoimmune diseases.
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Autoanticuerpos , Enfermedades Autoinmunes , Cisteína , Cadenas HLA-DRB1 , Integrina alfa2 , Procesamiento Proteico-Postraduccional , Espondilitis Anquilosante , Animales , Ratones , Autoanticuerpos/metabolismo , Enfermedades Autoinmunes/genética , Enfermedades Autoinmunes/metabolismo , Autoinmunidad/genética , Autoinmunidad/inmunología , Cisteína/metabolismo , Cadenas HLA-DRB1/genética , Cadenas HLA-DRB1/metabolismo , Ratones Transgénicos , Integrina alfa2/metabolismo , Microbioma Gastrointestinal , Humanos , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/metabolismoRESUMEN
Mammals in northern regions chronically suffer from low temperatures during autumn-winter seasons. The aim of this study was to investigate the response of intestinal amino acid transport and the amino acid pool in muscle to chronic cold exposure via Min pig models (cold adaptation) and Yorkshire pig models (non-cold adaptation). Furthermore, this study explored the beneficial effects of glucose supplementation on small intestinal amino acid transport and amino acid pool in muscle of cold-exposed Yorkshire pigs. Min pigs (Exp. 1) and Yorkshire pigs (Exp. 2) were divided into a control group (17 °C, n = 6) and chronic cold exposure group (7 °C, n = 6), respectively. Twelve Yorkshire pigs (Exp. 3) were divided into a cold control group and cold glucose supplementation group (8 °C). The results showed that chronic cold exposure inhibited peptide transporter protein 1 (PepT1) and excitatory amino acid transporter 3 (EAAT3) expression in ileal mucosa and cationic amino acid transporter-1 (CAT-1) in the jejunal mucosa of Yorkshire pigs (P < 0.05). In contrast, CAT-1, PepT1 and EAAT3 expression was enhanced in the duodenal mucosa of Min pigs (P < 0.05). Branched amino acids (BCAA) in the muscle of Yorkshire pigs were consumed by chronic cold exposure, accompanied by increased muscle RING-finger protein-1 (MuRF1) and muscle atrophy F-box (atrogin-1) expression (P < 0.05). More importantly, reduced concentrations of dystrophin were detected in the muscle of Yorkshire pigs (P < 0.05). However, glycine concentration in the muscle of Min pigs was raised (P < 0.05). In the absence of interaction between chronic cold exposure and glucose supplementation, glucose supplementation improved CAT-1 expression in the jejunal mucosa and PepT1 expression in the ileal mucosa of cold-exposed Yorkshire pigs (P < 0.05). It also improved BCAA and inhibited MuRF1 and atrogin-1 expression in muscle (P < 0.05). Moreover, dystrophin concentration was improved by glucose supplementation (P < 0.05). In summary, chronic cold exposure inhibits amino acid absorption in the small intestine, depletes BCAA and promotes protein degradation in muscle. Glucose supplementation ameliorates the negative effects of chronic cold exposure on amino acid transport and the amino acid pool in muscle.
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Aedes aegypti abundance in residential estates is hypothesized to contribute to localised outbreaks of dengue in Singapore. Knowing the factors in the urban environment underlying high Ae. aegypti abundance could guide intervention efforts to reduce Ae. aegypti breeding and the incidence of dengue. In this study, objective data on Ae. aegypti abundance in public apartment blocks estimated by Singapore's nationally representative Gravitrap surveillance system was obtained from the National Environmental Agency. Low and high abundance status public apartment blocks were classified based on the Gravitrap Aegypti Index, corresponding to the lowest and highest quartiles respectively. An environmental case-control study was conducted, wherein a blinded assessment of urban features hypothesised to form breeding habitats was conducted in 50 randomly sampled public apartment blocks with low and high abundance statuses each. Logistic regression was performed to identify features that correlated with abundance status. A multivariable logistic model was created to determine key urban features found in corridors and void decks which were predictive of the Ae. aegypti abundance status of the public apartment block. At a statistical level of significance of 0.20, the presence of gully traps [Odds Ratio (OR): 1.34, 95% Confidence Interval (CI): 1.10, 1.66], age of the public apartment block [OR: 2.23, 95% CI: 1.48, 3.60], housing price [OR: 0.33, 95% CI: 0.16, 0.61] and corridor cleanliness [OR: 0.67, 95% CI: 0.40, 1.07] were identified as important predictors of abundance status. To reduce Ae. aegypti abundance around public apartment blocks and potential onward dengue transmission, gully traps could be remodelled or replaced by other drainage types. Routine inspections of Ae. aegypti breeding should be targeted at older and low-income neighbourhoods. Campaigns for cleaner corridors should be promoted.
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Aedes , Dengue , Animales , Humanos , Singapur/epidemiología , Estudios de Casos y Controles , EcosistemaRESUMEN
To analyze alterations of the liver appearance during the hepatobiliary phase of individuals with type 2 diabetes who are receiving gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI). Fifty-seven individuals who received Gd-EOB-DTPA-enhanced MRI and had normal liver and renal function but did not have (control group) or have type 2 diabetes (observation group) were retrospectively included in this study. The liver enhancement ratio (LER) and contrast between liver parenchyma and portal vein (LPC) were calculated from hepatobiliary phase images. Utilizing liver to kidney signal intensity, signs of the biliary system, and signs of the portal vein, a functional liver imaging score (FLIS) was calculated. Wilcoxon rank-sum test was used to assess the between-group differences in LER, LPC, and FLIS. FLIS constituent ratios between the two groups were tested using the χ2 test. The effectiveness of LER, LPC, and FLIS for identifying type 2 diabetes was assessed by receiver operating characteristic curves (ROCs). The interobserver consistency of FLIS was evaluated using the intraclass correlation coefficients. The observation group's LER and LPC were lower than the control group. The constituent ratio of the FLIS score (liver to kidney signal intensity, p = 0.011) showed a significant between-group difference. According to ROCs, LER and LPC were associated with the identification of type 2 diabetes. LER = 0.54 and LPC = 1.46 were the optimal cutoff for identifying type 2 diabetes, respectively. FLIS demonstrated excellent inter-reader agreement. The relative signal intensity of the liver during the hepatobiliary phase is decreased in patients with type 2 diabetes. This should be considered when individuals with type 2 diabetes undergo Gd-EOB-DTPA-enhanced MRI to avoid misdiagnoses, such as small hepatocellular carcinoma or abnormal liver function.
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Diabetes Mellitus Tipo 2 , Hígado , Humanos , Carcinoma Hepatocelular/diagnóstico por imagen , Medios de Contraste , Diabetes Mellitus Tipo 2/diagnóstico por imagen , Diabetes Mellitus Tipo 2/patología , Gadolinio DTPA , Hígado/diagnóstico por imagen , Hígado/patología , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/patología , Imagen por Resonancia Magnética/métodos , Estudios RetrospectivosRESUMEN
Glyphosate-based herbicides (GBHs), the most widely used pesticide worldwide, have been reported to impair organ function in humans and animals. However, research on the effect of maternal GBHs exposure on the intestinal health of offspring has received little attention. Based on the glyphosate limits defined by Codex Alimentarius Commission and European Food Safety Authority, this study established pregnant sow exposure models to investigate the influence of low (L-GBHs, 20 mg/kg) and high concentration GBHs (H-GBHs, 100 mg/kg) on the intestinal health of offspring and proposed the protective mechanism mediated by betaine. The results showed that the intestinal morphology and barrier function of suckling piglets were damaged in the H-GBHs group. H-GBHs increased the activity of glutathione peroxidase (GPX) and levels of methane dicarboxylic aldehyde (MDA), hydrogen peroxide (H2O2) and inflammatory factors (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), interleukin-10 (IL-10)) in suckling piglets and activated Nrf2-mediated antioxidant signaling pathway. Subsequently, we found that exposure to H-GBHs triggered endoplasmic reticulum stress (ERS) and further induced apoptosis by upregulating the expression of Bcl-2-associated X protein (Bax), Caspase3, Caspase9 and Caspase12. Moreover, H-GBHs exposure perturbed mitochondrial membrane fusion and electron transport in mitochondrial respiratory chains by increasing the mRNA expression of mitofusin-2 (MFN2) and succinate dehydrogenase subunit A (SDHA), causing mitochondrial dysfunction. Dietary supplementation with betaine provided modest protection against GBHs-induced intestinal damage in suckling piglets. These findings reveal the mechanism of GBHs-induced intestinal damage in offspring, improving our understanding of the risk of GBHs exposure in pregnant women and suggesting the potential protective effects of betaine against GBHs poisoning.
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Herbicidas , Humanos , Animales , Femenino , Porcinos , Embarazo , Herbicidas/toxicidad , Betaína , Peróxido de Hidrógeno/farmacología , Estrés del Retículo Endoplásmico , Apoptosis , GlifosatoRESUMEN
Immune checkpoint blockade therapy targeting programmed cell death protein 1 (PD-1) has revolutionized the landscape of multiple human cancer types, including head and neck squamous carcinoma (HNSCC). Programmed death ligand-2 (PD-L2), a PD-1 ligand, mediates cancer cell immune escape (or tolerance independent of PD-L1) and predicts poor prognosis of patients with HNSCC. Therefore, an in-depth understanding of the regulatory process of PD-L2 expression may stratify patients with HNSCC to benefit from anti-PD-1 immunotherapy. In this review, we summarised the PD-L2 expression and its immune-dependent and independent functions in HNSCC and other solid tumours. We focused on recent findings on the mechanisms that regulate PD-L2 at the genomic, transcriptional, post-transcriptional, translational, and post-translational levels, also in intercellular communication of tumour microenvironment (TME). We also discussed the prospects of using small molecular agents indirectly targeting PD-L2 in cancer therapy. These findings may provide a notable avenue in developing novel and effective PD-L2-targeted therapeutic strategies for immune combination therapy and uncovering biomarkers that improve the clinical efficacy of anti-PD-1 therapies.
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Neoplasias de Cabeza y Cuello , Inmunoterapia , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Ligandos , Terapia Combinada , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/terapia , Microambiente TumoralRESUMEN
There is an urgent need to explore the salt penetration and water migration in the cooked salted egg yolk (CSEY) gel. The aim of this study was to investigate the effect of salt and water on the physicochemical, structural and flavor characteristics of CSEY gel stored at 25 °C. The hardness of the yolk increased significantly (608.0 g â 2730.7 g) during storage. The results of LF-NMR showed that the free water content in the yolk gel was enhanced. The microstructure of CSEY could be observed by SEM, which showed that during storage, polyhedral particles were dispersed due to the heating process. In addition, ethyl acetate (71.9 %) was completely undetectable in the CSEY-21 d. In summary, the sample at and before 14 d of storage had good processing value. Therefore, this work would provide theoretical guidance for the low-sodium pickling of SEY (salted egg yolk) and its suitable storage methods.