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Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight in rice. Polyhydroxyalkanoates (PHAs) consitute a diverse group of biopolyesters synthesized by bacteria under nutrient-limited conditions. The phaC gene is important for PHA polymerization. We investigated the effects of phaC gene mutagensis in Xoo strain PXO99A. The phaC gene knock-out mutant exhibited reduced swarming ability relative to that of the wild-type. Under conditions where glucose was the sole sugar source, extracellular polysaccharide (EPS) production by ΔphaC declined by 44.8%. ΔphaC showed weak hypersensitive response (HR) induction in the leaves of non-host Nicotiana tabacum, concomitant with downregulation of hpa1 gene expression. When inoculated in rice leaves by the leaf-clipping method, ΔphaC displayed reduced virulence in terms of lesion length compared with the wild-type strain. The complemented strain showed no significant difference from the wild-type strain, suggesting that the deletion of phaC in Xoo induces significant alterations in various physiological and biological processes. These include bacterial swarming ability, EPS production, transcription of hrp genes, and glucose metabolism. These changes are intricately linked to the energy utilization and virulence of Xoo during plant infection. These findings revealed involvement of phaC in Xoo is in the maintaining carbon metabolism by functioning in the PHA metabolic pathway.
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Proteínas Bacterianas , Carbono , Oryza , Enfermedades de las Plantas , Polisacáridos Bacterianos , Xanthomonas , Xanthomonas/patogenicidad , Xanthomonas/genética , Xanthomonas/metabolismo , Oryza/microbiología , Carbono/metabolismo , Enfermedades de las Plantas/microbiología , Virulencia/genética , Polisacáridos Bacterianos/metabolismo , Polisacáridos Bacterianos/biosíntesis , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Mutación , Regulación Bacteriana de la Expresión Génica , Polihidroxialcanoatos/biosíntesis , Polihidroxialcanoatos/metabolismo , Nicotiana/microbiología , Hojas de la Planta/microbiologíaRESUMEN
A smartphone-assisted portable dual-mode immunoassay was constructed based on curcumin nanoparticles (CNPs) and carbon dots (CDs) for gentamicin (GEN) detection. CNPs were labeled with goat anti-mouse IgG (Ab2) to create a conjugation that coupled dual signals to concentrations of GEN antigens. CNPs were introduced to pH 7.4 water and showed insignificant color and optical responses. When exposed to the high pH environment, the structure of CNPs changed and color and optical properties were restored. Because of the inner filter effect (IFE) between CNPs and CDs, the fluorescence of CNPs at 550 nm quenched the fluorescence of CDs at 450 nm. Colorimetry and ratiometric fluorescence (F550 nm/F450 nm) dual-mode immunoassay linearly correlated with GEN ranged from 10-4 to 100 µg/mL with a detection limit (LOD) of 8.98 × 10-5 µg/mL and 4.66 × 10-5 µg/mL, respectively. This work supplied a portable, sensitive, and specific platform to detect GEN.
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Carbono , Curcumina , Gentamicinas , Límite de Detección , Nanopartículas , Puntos Cuánticos , Teléfono Inteligente , Curcumina/química , Inmunoensayo/métodos , Carbono/química , Gentamicinas/análisis , Gentamicinas/inmunología , Gentamicinas/química , Puntos Cuánticos/química , Nanopartículas/química , Animales , RatonesRESUMEN
Arsenic (As) and cadmium (Cd) accumulation in rice grains is a global food safety issue, and various methods and materials have been used to remove or reduce As and Cd in agricultural soils and rice grains. Despite the availability of synthesized materials capable of simultaneous As and Cd reduction from soil and rice grains, the contributions, efficiency, and main ingredients of the materials for As and Cd immobilization remain unclear. The present study first summarized the biogeochemistry of As and Cd in paddy soils and their transfer in the soil-food-human continuum. We also reviewed a series of reported inorganic and organic materials for simultaneous immobilization of As and Cd in paddy soils, and their reduction efficiency of As and Cd bioavailability were listed and compared. Based on the abovementioned materials, the study conducted a meta-analysis of 38 articles with 2565 observations to quantify the impacts of materials on simultaneous As and Cd reduction from soil and rice grains. Meta-analysis results showed that combining organic and inorganic amendments corresponded to effect sizes of -62.3% and -67.8% on As and Cd accumulation in rice grains, while the effect sizes on As and Cd reduction in paddy soils were -44.2% and -46.2%, respectively. Application of Fe based materials significantly (P < 0.05) reduced As (-54.2%) and Cd (-74.9%), accounting for the highest immobilization efficiency of As and Cd in rice grain among all the reviewed materials, outweighing S, Mn, P, Si, and Ca based materials. Moreover, precipitation, surface complexation, ion exchange, and electrostatic attraction mechanisms were involved in the co-immobilization tactics. The present study underlines the application of combined organic and inorganic amendments in simultaneous As and Cd immobilization. It also highlighted that employing Fe-incorporated biochar material may be a potential strategy for co-mitigating As and Cd pollution in paddy soils and accumulation in rice grains.
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Arsénico , Cadmio , Oryza , Contaminantes del Suelo , Suelo , Suelo/química , Contaminantes del Suelo/análisis , Arsénico/análisis , AgriculturaRESUMEN
Moderate non-covalent interaction of protein and polyphenols can improve the emulsifying property of protein itself. The corn protein hydrolysate (CPH) and tannic acid (TA) complex was successfully used to construct nanoemulsion for algal oil delivery. There has been no study on the feasibility of this nanoemulsion delivery system for other food functional components, for example, ß-carotene (ß-CE). CPH/TA complex-based nanoemulsion system for ß-CE delivery was studied, focusing on the effect of ß-CE content on the physicochemical stability of the nanoemulsions. The nanoemulsion delivery systems (dia. 150 nm) with low viscosity and good liquidity were easily fabricated by two-step emulsification. The nanoemulsions with high ß-CE content (>71.5 µg/mL) significantly increased (p < .05) the emulsion droplet size. However, there was no significant (p > .05) effect of ß-CE content on polydispersity index (PDI) and zeta potential of the nanoemulsions. The storage (30 days) experiment results demonstrated that the droplet size of the nanoemulsions with varying ß-CE content increased slightly during storage. However, the PDI values showed a slightly decreasing trend. Zeta potentials of the nanoemulsions showed no noticeable change during storage. Moreover, after storage of 30 days, the retention ratios of ß-CE were found to be up to 90%, which suggests an excellent protective effect for ß-CE by the nanoemulsion systems. The CPH/TA complex stabilized nanoemulsions could aggregate in gastric condition, but the ß-CE content did not have obvious effect on the digestive stability of the nanoemulsions. The CPH/TA complex could be employed as an emulsifier to construct a physicochemical stable nanoemulsion delivery system for lipophilic active components.
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Background: Heart failure is a common cause of adverse cardiovascular outcomes in patients with chronic kidney disease (CKD). Left atrial (LA) characteristics are thought to be involved in the development of heart failure. However, LA assessment is complex. Though a variety of parameters have been defined, there is no single parameter that best defines LA function. Pilot data indicate that left atrial volumetric/mechanical coupling index (LACI) may be useful, but data with CKD are lacking. Aim: The objective of this study was to define LACI in a cohort of patients with CKD and to assess its value in evaluating LA function and predicting heart failure. Methods: A cohort of patients with CKD was enrolled at our hospital between 2021 and 2023. Follow-up was performed for heart failure. LACI is a volumetric to mechanical coupling index, calculated as the ratio of the LA volume index to the tissue-Doppler myocardial velocity at atrial contraction. Spearman's rank correlation or Pearson's correlation was used to calculate the correlation between LACI and echocardiographic/hemodynamic variables. Receiver operating characteristic curve (ROC) analysis was utilised to derive the area under the curve (AUC) for LACI, LVGLS, LASr, LASct and LASI for the detection of heart failure. Kaplan-Meier survival curves were employed to compare clinical outcomes based on LACI thresholds. A multivariable logistic regression analysis was employed to assess the relationship between risk factors and elevated LACI. Cox proportional hazards regression was used to identify risk factors for heart failure. Results: LACI showed a positive correlation with NT-proBNP, CK-MB, LAVI, E/e' and LASI (r = 0.504, 0.536, 0.856, 0.541 and 0.509, p < 0.001); and a negative correlation with LASr (r = -0.509, p < 0.001). On the ROC analysis for the determination of heart failure, the AUC of LACI was comparable to those of LVGLS (0.588 vs. 509, p = 0.464), LASr (0.588 vs. 0.448, p = 0.132), LASct (0.588 vs. 0.566, p = 0.971) and LASI (0.588 vs. 0.570, p = 0.874). The cardiovascular risk factors increased by LACI were age, BMI, diabetes, triglycerides, LA size, LASr, LASI, E/A, E/e' and EF (p < 0.05). During a median follow-up of 16 months (range, 6-28 months), the event-free survival curves demonstrated a higher risk of heart failure in the group with LACI > 5.0 (log-rank test: P < 0.001). LACI > 5.0 was an independent predictor of heart failure [OR: 0.121, 95% CI (0.020-0.740), p = 0.022]. Conclusion: LACI may prove to be a valuable tool for assessing LA function in patients with CKD, and could be integrated into the routine assessment of LA for the purpose of prognostic assessment and clinical decision-making in patients with CKD.
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Aquaculture is one of the fastest growing sectors in global food production, recognized as a significant contributor to poverty alleviation, food security, and income generation. However, the frequent occurrence of diseases caused by pathogen infections result in reduced yields and economic losses, posing a substantial constraint to the sustainable development of aquaculture. Here, our study identified that four catechol compounds, quercetin, luteolin, caffeic acid, and chlorogenic acid, exhibited potent antiparasitic effects against Ichthyophthirius multifiliis in both, in vitro and in vivo. The parasite is recognized as one of the most pathogenic to fish worldwide. Using a combination of in silico methods, the dipeptidyl peptidase (DPP) was identified as a critical target for catechol compounds. The two hydroxyl radicals of the catechol group were essential for its binding to and interacting with the DPP protein. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that catechol compounds disrupt pathways associated with the metabolism and growth of I. multifiliis, thereby exerting antiparasitic effects. Furthermore, these compounds attenuated the expression of proinflammatory cytokines in vivo in fish and promoted macrophage polarization toward M2 phenotype by inhibiting the STAT1 signaling pathway. The dual activity of catechol compounds, acting as both direct antiparasitic and anti-inflammatory agents in fish, offers a promising therapeutic approach for combating I. multifiliis infections in aquaculture.
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Catecoles , Infecciones por Cilióforos , Enfermedades de los Peces , Hymenostomatida , Animales , Enfermedades de los Peces/inmunología , Enfermedades de los Peces/parasitología , Enfermedades de los Peces/prevención & control , Hymenostomatida/efectos de los fármacos , Catecoles/farmacología , Infecciones por Cilióforos/veterinaria , Infecciones por Cilióforos/inmunología , Infecciones por Cilióforos/parasitología , Infecciones por Cilióforos/prevención & control , Antiparasitarios/farmacologíaRESUMEN
Zinc (Zn) is an important trace element; it is involved in the regulation and maintenance of many physiological functions in organisms and has anti-inflammatory and antioxidant properties. Chronic gastritis is closely associated with damage to the gastric mucosa, which is detrimental to the health of humans and animals. There are few studies on the effects of zinc on, for example, gastric mucosal damage, oxidative stress, inflammation and cell death in mice. Therefore, we established in vivo and in vitro models of inflammatory injury and investigated the effects of zinc supplementation in C57BL/6 mice and Ges-1 cells and examined the expression of factors associated with oxidative stress, inflammation and cell death. In this study, the results of in vivo and in vitro experiments showed that reactive oxygen species (ROS) levels increased after sodium salicylate exposure. Malondialdehyde levels increased, the activity of the antioxidant enzymes catalase and superoxide dismutase decreased, and the activity of glutathione decreased. The NF-κB signaling pathway was activated, the levels of proinflammatory factors (TNF-α, IL-1ß, and IL-6) increased, and the expression of cell death-related factors (Bax, Bcl-2, Caspase3, Caspase7, Caspase9, RIP1, RIP3, and MLKL) increased. Zinc supplementation attenuated the level of oxidative stress and reduced the level of inflammation and cell death. Our study indicated that sodium salicylate induced the production of large amounts of reactive oxygen species and activated the NF-κB pathway, leading to inflammatory damage and cell death in the mouse stomach. Zinc supplementation modulated the ROS/NF-κB pathway, reduced the level of oxidative stress, and attenuated inflammation and cell death in the mouse stomach and Ges-1 cells.
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Suplementos Dietéticos , Gastritis , Estrés Oxidativo , Especies Reactivas de Oxígeno , Transducción de Señal , Zinc , Animales , Humanos , Masculino , Ratones , Antioxidantes/farmacología , Línea Celular , Modelos Animales de Enfermedad , Mucosa Gástrica/metabolismo , Mucosa Gástrica/efectos de los fármacos , Gastritis/metabolismo , Gastritis/tratamiento farmacológico , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , FN-kappa B/genética , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Zinc/farmacologíaRESUMEN
Complex traits are widely considered to be the result of a compound regulation of genes, environmental factors, and genotype-by-environment interaction (G × E). The inclusion of G × E in genome-wide association analyses is essential to understand animal environmental adaptations and improve the efficiency of breeding decisions. Here, we systematically investigated the G × E of growth traits (including weaning weight, yearling weight, 18-month body weight, and 24-month body weight) with environmental factors (farm and temperature) using genome-wide genotype-by-environment interaction association studies (GWEIS) with a dataset of 1350 cattle. We validated the robust estimator's effectiveness in GWEIS and detected 29 independent interacting SNPs with a significance threshold of 1.67 × 10-6, indicating that these SNPs, which do not show main effects in traditional genome-wide association studies (GWAS), may have non-additive effects across genotypes but are obliterated by environmental means. The gene-based analysis using MAGMA identified three genes that overlapped with the GEWIS results exhibiting G × E, namely SMAD2, PALMD, and MECOM. Further, the results of functional exploration in gene-set analysis revealed the bio-mechanisms of how cattle growth responds to environmental changes, such as mitotic or cytokinesis, fatty acid ß-oxidation, neurotransmitter activity, gap junction, and keratan sulfate degradation. This study not only reveals novel genetic loci and underlying mechanisms influencing growth traits but also transforms our understanding of environmental adaptation in beef cattle, thereby paving the way for more targeted and efficient breeding strategies.
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Copy number variation (CNV) serves as a significant source of genetic diversity in mammals and exerts substantial effects on various complex traits. Pingliang red cattle, an outstanding indigenous resource in China, possess remarkable breeding value attributed to their tender meat and superior marbling quality. However, the genetic mechanisms influencing carcass and meat quality traits in Pingliang red cattle are not well understood. We generated a comprehensive genome-wide CNV map for Pingliang red cattle using the GGP Bovine 100K SNP chip. A total of 755 copy number variable regions (CNVRs) spanning 81.03 Mb were identified, accounting for approximately 3.24% of the bovine autosomal genome. Among these, we discovered 270 potentially breed-specific CNVRs in Pingliang red cattle, including 143 gains, 73 losses, and 54 mixed events. Functional annotation analysis revealed significant associations between these specific CNVRs and important traits such as carcass and meat quality, reproduction, exterior traits, growth traits, and health traits. Additionally, our network and transcriptome analysis highlighted CACNA2D1, CYLD, UBXN2B, TG, NADK, and ITGA9 as promising candidate genes associated with carcass weight and intramuscular fat deposition. The current study presents a genome-wide CNV map in Pingliang red cattle, highlighting breed-specific CNVRs, and transcriptome findings provide valuable insights into the underlying genetic characteristics of Pingliang red cattle. These results offer potential avenues for enhancing meat quality through a targeted breeding program.
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Variaciones en el Número de Copia de ADN , Estudio de Asociación del Genoma Completo , Carne , Animales , Bovinos/genética , Variaciones en el Número de Copia de ADN/genética , Estudio de Asociación del Genoma Completo/métodos , Polimorfismo de Nucleótido Simple , Sitios de Carácter Cuantitativo , Fenotipo , Cruzamiento , Genoma , Calidad de los Alimentos , Carácter Cuantitativo HeredableRESUMEN
Low ionic conductivity and poor interface stability of poly(ethylene oxide) (PEO) restrict the practical application as polymeric electrolyte films to prepare solid-state lithium (Li) metal batteries. In this work, biomass-based carboxymethyl chitosan (CMCS) is designed and developed as organic fillers into PEO matrix to form composite electrolytes (PEO@CMCS). Carboxymethyl groups of CMCS fillers can promote the decomposition of Lithium bis(trifluoromethane sulfonimide) (LiTFSI) to generate more lithium fluoride (LiF) at CMCS/PEO interface, which not only forms ionic conductive network to promote the rapid transfer of Li+ but also effectively enhances the interface stability between polymeric electrolyte and Li metal. The enrichment of carboxyl, hydroxyl, and amidogen functional groups within CMCS fillers can form hydrogen bonds with ethylene oxide (EO) chains to improve the tensile properties of PEO-based electrolyte. In addition, the high hardness of CMCS additives can also strengthen mechanical properties of PEO-based electrolyte to resist penetration of Li dendrites. LiLi symmetric batteries can achieve stable cycle for 2500 h and lithium iron phosphate full batteries can maintain 135.5 mAh g-1 after 400 cycles. This work provides a strategy for the enhancement of ion conductivity and interface stability of PEO-based electrolyte, as well as realizes the resource utilization of biomass-based CMCS.
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Quitosano , Conductividad Eléctrica , Suministros de Energía Eléctrica , Electrólitos , Litio , Polietilenglicoles , Quitosano/química , Quitosano/análogos & derivados , Polietilenglicoles/química , Litio/química , Electrólitos/química , Iones/químicaRESUMEN
Erdheim-Chester disease (ECD) is a rare histiocytosis that tends to co-exist with other myeloid malignancies. Here, we use genetic and transcriptomic sequencing to delineate a case of co-occurring BRAFV600E-mutated ECD and acute myeloid leukemia (AML), followed by AML remission and relapse. The AML relapse involved the extinction of clones with KMT2A-AFDN and FLT3-ITD, and the predominance of PTPN11-mutated subclones with distinct transcriptomic features. This case report has highlighted the screening for other myeloid malignancies at the diagnosis of ECD and the clinical significance of PTPN11-mutated AML subclones that require meticulous monitoring.
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Enfermedad de Erdheim-Chester , Leucemia Mieloide Aguda , Mutación , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Tirosina Quinasa 3 Similar a fms , Humanos , Enfermedad de Erdheim-Chester/genética , Enfermedad de Erdheim-Chester/complicaciones , Enfermedad de Erdheim-Chester/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/diagnóstico , Tirosina Quinasa 3 Similar a fms/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Masculino , Evolución Clonal/genética , Femenino , Proteínas Proto-Oncogénicas B-raf/genética , Persona de Mediana EdadRESUMEN
Background: Radiotherapy has become a standard treatment for chest tumors, but a common complication of radiotherapy is radiation lung injury. Currently, there is still a lack of effective treatment for radiation lung injury. Methods: A mouse model of radioactive lung injury (RILI) was constructed and then treated with different cycles of hydrogen inhalation. Lung function tests were performed to detect changes in lung function.HE staining was used to detect pathological changes in lung tissue. Immunofluorescence staining was used to detect the polarization of macrophages in lung tissue. Immunohistochemistry was used to detect changes in cytokine expression in lung tissues. Western Blot was used to detect the expression of proteins related to the NF-κB signalling pathway. Results: Lung function test results showed that lung function decreased in the model group and improved in the treatment group.HE staining showed that inflammatory response was evident in the model group and decreased in the treatment group. Immunohistochemistry results showed that the expression of pro-inflammatory factors was significantly higher in the model group, and the expression of pro-inflammatory factors was significantly higher in the treatment group. The expression of pro-inflammatory factors in the treatment group was significantly lower than that in the model group, and the expression of anti-inflammatory factors in the treatment group was higher than that in the model group. Immunofluorescence showed that the expression of M1 subtype macrophages was up-regulated in the model group and down-regulated in the treatment group. The expression of M2 subtype macrophages was up-regulated in the treatment group relative to the model group. Western Blot showed that P-NF-κB p65/NF-κB p65 was significantly increased in the model group, and P-NF-κB p65/NF-κB p65 was decreased in the treatment group. Conclusion: Hydrogen therapy promotes macrophage polarization from M1 to M2 subtypes by inhibiting the NF-κB signalling pathway, thereby attenuating the inflammatory response to radiation lung injury.
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Early tumor response prediction can help avoid overtreatment with unnecessary chemotherapy sessions. It is important to determine whether multiple apparent diffusion coefficient indices (S index, ADC-diff) are effective in the early prediction of pathological response to neoadjuvant chemotherapy (NAC) in breast cancer (BC). Patients with stage II and III BCs who underwent T1WI, diffusion-weighted imaging (DWI), and dynamic contrast-enhanced MRI using a 3 T system were included. They were divided into two groups: major histological responders (MHRs, Miller-Payne G4/5) and nonmajor histological responders (nMHRs, Miller-Payne G1-3). Three b values were used for DWI to derive the S index; ADC-diff values were obtained using b = 0 and 1000 s/mm2. The different interquartile ranges of percentile S-index and ADC-diff values after treatment were calculated and compared. The assessment was performed at baseline and after two and four NAC cycles. A total of 59 patients were evaluated. There are some correlations of interquartile ranges of S-index parameters and ADC-diff values with histopathological prognostic factors (such as estrogen receptor and human epidermal growth factor receptor 2 expression, all p < 0.05), but no significant differences were found in some other interquartile ranges of S-index parameters or ADC-diff values between progesterone receptor positive and negative or for Ki-67 tumors (all P > 0.05). No differences were found in the dynamic contrast-enhanced MRI characteristics between the two groups. HER-2 expression and kurtosis of the S-index distribution were screened out as independent risk factors for predicting MHR group (p < 0.05, area under the curve (AUC) = 0.811) before NAC. After early NAC (two cycles), only the 10th percentile S index was statistically significant between the two groups (p < 0.05, AUC = 0.714). No significant differences were found in ADC-diff value at any time point of NAC between the two groups (P > 0.1). These findings demonstrate that the S-index value may be used as an early predictor of pathological response to NAC in BC; the value of ADC-diff as an imaging biomarker of NAC needs to be further confirmed by ongoing multicenter prospective trials.
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The effect of varying proportions (w/w) of natural aromatic extract of black tea (NAEBT) with pre-emulsification on the water-holding capacity (WHC) of pork meat batter was investigated. The addition of NAEBT significantly reduced the cooking loss (CL) of pork meat batter from 23.95 % to 18.30 % (P < 0.05). Furthermore, NAEBT with pre-emulsification significantly improved the color stability and increased the springiness (P < 0.05). The results of TBARS and carbonyls indicated that NAEBT with pre-emulsification significantly alleviated oxidative damage to proteins (P < 0.05), resulting in an increased level of ß-sheet (P < 0.05), as confirmed by FT-IR analysis. As a result, the water mobility of pork meat batter was restricted (P < 0.05), resulting in an increase in the energy storage modulus (P < 0.05) and a decrease in the pore size. In summary, the WHC of pork meat batter was improved by the antioxidant effect of the NAEBT.
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Antioxidantes , Productos de la Carne , Extractos Vegetales , Carne de Cerdo , Té , Agua , Agua/química , Extractos Vegetales/química , Carne de Cerdo/análisis , Animales , Té/química , Productos de la Carne/análisis , Antioxidantes/análisis , Porcinos , Culinaria , Sustancias Reactivas al Ácido Tiobarbitúrico/análisis , Espectroscopía Infrarroja por Transformada de FourierRESUMEN
OBJECTIVES: Systemic lupus erythematosus (SLE) is a multi-organ autoimmune disease, of which the pathogens is remains obscure. Viral infection, particularly Epstein Barr viru (EBV) infection, has been considered a common pathogenic factor. This study suggests that c-Maf may be an important target in T cell differentiation during SLE progression, providing a potentially new perspective on the role of viral infection in the pathogenesis of autoimmune diseases. METHODS: Cytokines of EBV-infected SLE patients were measured by ELISA and assessed in conjunction with their clinical data. IFN-α, c-Maf, and the differentiation of Th17/Treg cells in SLE patients and MRL/LPR mice were analyzed using FCM, WB, RT-PCR, etc. Following the infection of cells and mice with EBV or viral mimic poly (dA:dT), the changes of the aforementioned indicators were investigated. The relationship among IFN-α, STAT3, c-Maf and Th17 cells was determined by si-RNA technique. RESULTS: Many SLE patients are found to be complicated by viral infections; Further, studies have demonstrated that viral infection, especially EBV, is involved in SLE development. This study showed that viral infections might promote IFN-α secretion, inhibit c-Maf expression by activating STAT3, increase Th17 cell differentiation, and lead to the immune imbalance of Th17/Treg cells, thus playing a role in the onset and progression of SLE. CONCLUSION: This study demonstrates that EBV infections may contribute to SLE development by activating STAT3 through IFN-α, inhibiting c-Maf, and causing Th17/Treg immune imbalance. Our work provided a new insight into the pathogenesis and treatment of SLE.
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Infecciones por Virus de Epstein-Barr , Herpesvirus Humano 4 , Interferón-alfa , Lupus Eritematoso Sistémico , Ratones Endogámicos MRL lpr , Proteínas Proto-Oncogénicas c-maf , Linfocitos T Reguladores , Células Th17 , Lupus Eritematoso Sistémico/inmunología , Lupus Eritematoso Sistémico/virología , Células Th17/inmunología , Humanos , Animales , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/virología , Infecciones por Virus de Epstein-Barr/complicaciones , Linfocitos T Reguladores/inmunología , Ratones , Interferón-alfa/inmunología , Interferón-alfa/metabolismo , Femenino , Adulto , Herpesvirus Humano 4/inmunología , Proteínas Proto-Oncogénicas c-maf/inmunología , Proteínas Proto-Oncogénicas c-maf/genética , Masculino , Diferenciación Celular/inmunología , Progresión de la Enfermedad , Persona de Mediana Edad , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/inmunología , Adulto JovenRESUMEN
We previously conducted a systematic study on the metabolic process and products of hederasaponin B in rats. We hypothesized that the sugar chain structures play a key role in the metabolism of triterpenoid saponins. To verify this hypothesis, we conducted metabolic research on ciwujianoside B ascribed to the same sugar chains and a distinct aglycone and compared it with hederasaponin B. Specifically, we collected feces, urine, and plasma of rats after gavage with ciwujianoside B and identified 42 metabolites by UPLC-Fusion Lumos Orbitrap mass spectrometry. Finally, ciwujianoside B metabolism and hederasaponin B metabolism were compared, reaching the following conclusions: (i) more than 40 metabolites were identified in both, with the majority of metabolites identified in feces; (ii) the corresponding metabolic pathways in vivo were basically similar, including deglycosylation, acetylation, hydroxylation, glucuronidation, oxidation, and glycosylation; and (iii) deglycosylation was considered the main metabolic reaction, and its metabolites accounted for approximately 50% of all metabolites. Overall, this study provides a foundation for further research on the metabolism of triterpenoid saponins.
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Polyphenols, polysaccharides, and proteins are essential nutrients and functional substances present in food, and when present together these components often interact with each other to influence their structure and function. Proteins and polysaccharides are also excellent carrier materials for polyphenols. In this context, this study investigated the non-covalent interactions between taxifolin (TAX), Lentinus edodes mycelia polysaccharide (LMP), and ß-casein (ß-CN). ß-CN and LMP spontaneously formed nanocomplexes by hydrogen bonds and van der Waals forces. The quenching constant and binding constant were (1.94 ± 0.02) × 1013 L mol-1 s-1 and (3.22 ± 0.17) × 105 L mol-1 at 298 K, respectively. The altered conformation of ß-CN, resulting from the binding to LMP, affected the interaction with TAX. LMP significantly enhanced the binding affinity of TAX and ß-CN, but did not change the static quenching binding mode. The binding constant for ß-CN-TAX was (3.96 ± 0.09) × 1013 L mol-1, and that for the interaction between TAX and ß-CN-LMP was (32.06 ± 0.05) × 1013 L mol-1. In summary, ß-CN-LMP nanocomplexes have great potential as a nanocarrier for polyphenols, and this study provides a theoretical foundation for the rational design of non-covalent complexes involving LMP and ß-CN, both in binary and ternary configurations.
Asunto(s)
Caseínas , Quercetina , Hongos Shiitake , Caseínas/química , Quercetina/química , Quercetina/análogos & derivados , Hongos Shiitake/química , Enlace de Hidrógeno , Polisacáridos Fúngicos/química , Unión ProteicaRESUMEN
Precise imaging-guided therapy of a pulmonary metastasis tumor is of great significance for tumor management and prognosis. Persistent luminescence nanoparticles (PLNPs) are promising probes due to their in situ excitation-free and low-background imaging characteristics. However, most of the PLNP-based probes cannot intelligently distinguish between normal and tumor tissues or balance the needs of targeted accumulation and rapid metabolism, resulting in false positive signals and potential side effects. Besides, the luminescence intensity of single-emissive PLNPs is affected by external factors. Herein, we report a self-evolving double-emissive PLNP-based nanoprobe ZGMC@ZGC-TAT for pulmonary metastatic tumor imaging and therapy. Acid-degradable green-emitting PLNPs (ZGMC) with good afterglow performance and therapeutic potential are synthesized by systematic optimization of dopants. Ultra-small red-emitting PLNPs (ZGC) are then prepared as imaging and reference probes. The two PLNPs are finally covalently coupled and further modified with a cell-penetrating peptide (TAT) to obtain ZGMC@ZGC-TAT. Dual emission ensures a stable luminescence ratio (I700/I537) independent of probe concentration, test voltage and time gate. ZGMC degrades and phosphorescence disappears in a tumor microenvironment (TME), resulting in an increase in I700/I537, thus enabling tumor-specific ratiometric imaging. Cu2+ and Mn2+ released by ZGMC degradation achieve GSH depletion and enhance CDT, effectively inhibiting tumor cell proliferation. Meanwhile, the size of ZGMC@ZGC-TAT decreases sharply, and the resulting ZGC-TAT further causes nuclear pyknosis and quickly clear metabolism. The developed ZGMC@ZGC-TAT turns non-targeted lung aggregation of nanomaterials into a unique advantage, and integrates TME-triggered phosphorescence and size self-evolution, and on-demand therapeutic functions, showing outstanding prospects in precise imaging and efficient treatment of pulmonary metastatic tumors.