RESUMEN
Sustainably feeding a growing population is a grand challenge, and one that is particularly difficult in regions that are dominated by smallholder farming. Despite local successes, mobilizing vast smallholder communities with science- and evidence-based management practices to simultaneously address production and pollution problems has been infeasible. Here we report the outcome of concerted efforts in engaging millions of Chinese smallholder farmers to adopt enhanced management practices for greater yield and environmental performance. First, we conducted field trials across China's major agroecological zones to develop locally applicable recommendations using a comprehensive decision-support program. Engaging farmers to adopt those recommendations involved the collaboration of a core network of 1,152 researchers with numerous extension agents and agribusiness personnel. From 2005 to 2015, about 20.9 million farmers in 452 counties adopted enhanced management practices in fields with a total of 37.7 million cumulative hectares over the years. Average yields (maize, rice and wheat) increased by 10.8-11.5%, generating a net grain output of 33 million tonnes (Mt). At the same time, application of nitrogen decreased by 14.7-18.1%, saving 1.2 Mt of nitrogen fertilizers. The increased grain output and decreased nitrogen fertilizer use were equivalent to US$12.2 billion. Estimated reactive nitrogen losses averaged 4.5-4.7 kg nitrogen per Megagram (Mg) with the intervention compared to 6.0-6.4 kg nitrogen per Mg without. Greenhouse gas emissions were 328 kg, 812 kg and 434 kg CO2 equivalent per Mg of maize, rice and wheat produced, respectively, compared to 422 kg, 941 kg and 549 kg CO2 equivalent per Mg without the intervention. On the basis of a large-scale survey (8.6 million farmer participants) and scenario analyses, we further demonstrate the potential impacts of implementing the enhanced management practices on China's food security and sustainability outlook.
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Agricultura/métodos , Conservación de los Recursos Naturales , Productos Agrícolas/crecimiento & desarrollo , Eficiencia Organizacional , Agricultores , China , Técnicas de Apoyo para la Decisión , Grano Comestible/crecimiento & desarrollo , Política Ambiental , Fertilizantes/estadística & datos numéricos , Abastecimiento de Alimentos/métodos , Efecto Invernadero , Nitrógeno/metabolismo , Oryza/crecimiento & desarrollo , Triticum/crecimiento & desarrollo , Zea mays/crecimiento & desarrolloRESUMEN
We aimed to investigate the role of Synbiotic preparations on the interaction of gut microbiota with AD development. APP/PS1 mice were randomized into APP/PS1 and Synbiotics groups, and C57BL/6J mice were used as wild type (WT) control group. The mice in the Synbiotics group and the APP/PS1 group were given Synbiotics and xylo-oligosaccharides for 3 months, respectively. The mice in the WT group were given the same amount of normal saline. Cognitive function was measured. Positron emission computed tomography/magnetic resonance imaging (PET/MRI) was used to detect fasting blood glucose level. Immunohistochemical assay, ELISA, western blot and qRT-PCR were carried out to detect inflammatory factors. DNA extraction of fecal sample was performed to carry out sequencing. Bioinformatics analysis, metabolites sample preparation and Liquid Chromatograph Mass Spectrometer (LC/MS) analysis were also performed. Synbiotics treatment can significantly ameliorate learning and memory competence by inhibiting Aß protein deposition. Different bacteria in the intestine were significantly improved and changes in gut microbiota can affect the intestinal metabolism to affect multiple potential pathways after Synbiotics treatment. Synbiotics treatment can activate peroxisome proliferator activated receptor (PPARs) signaling pathway and significantly reduce neuroinflammation in APP/PS1 mice brains. Synbiotics treatment can effectively reduce neuro-inflammatory response through the regulation of intestinal microflora to delay AD development.
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Enfermedad de Alzheimer , Modelos Animales de Enfermedad , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , Receptores Activados del Proliferador del Peroxisoma , Simbióticos , Animales , Ratones , Simbióticos/administración & dosificación , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Progresión de la Enfermedad , Transducción de Señal , Masculino , Ratones TransgénicosRESUMEN
Humic substances (HS) are widely known as important components in soil and significantly affect the mobility of metals due to their large surface area and abundant organic functional groups. Calcareous substances (CSs) are also commonly used as robust and cost-effective amendments for increasing the pH of acidic soils and decreasing the mobility of metals in soils. In this study, we developed a new remediation scheme for cadmium (Cd)-contaminated soil remediation by coupling HS and CS. The results showed that regardless of the addition of fulvic acid (FA), all the CS-containing treatments significantly increased the soil pH by 0.32-0.60, and the concentration of bioavailable Cd decreased in the moderately (field experiment soil, maximum 62%) and highly (pot experiment soil, maximum 57%) Cd-contaminated soils. The Cd content in rice (Oryza sativa L.) tissues significantly decreased after all the treatments. The bioaccumulation factors (BAFs) decreased by over 50% in the roots, stems, leaves and husks in all treatments, while the translocation factors (TFs) only significantly decreased in the highly contaminated soil. Among all treatments, the two HS+CS treatments (FA+CaCO3 and FA+CaO) had the greatest effect on decreasing the concentration of bioavailable Cd in soil and Cd in brown rice grains. The suggested mechanism for the effectiveness of coupled HS and CS was that CS first mitigated the pH and precipitated Cd, followed by a complexation effect between HS and Cd. Although the Cd in rice grains in both cases was higher than the standard limit, HS+CS remediation can be advocated as a robust, simple and cost-effective scheme for Cd remediation if the additive dose is slightly increased, as this approach can simultaneously improve the pH of acidic soil and adsorb Cd in soil.
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Oryza , Contaminantes del Suelo , Cadmio/análisis , Raíces de Plantas/química , Suelo , Contaminantes del Suelo/análisisRESUMEN
Phytochemical investigation on the 90% EtOH extract of the seeds of Cipadessa cinerascensa led to the isolation of three new limonoids, cinerascenoids A-C (1-3). Structural elucidation of all the compounds were performed by spectral methods such as 1 D and 2 D (1H-1H COSY, HMQC, and HMBC) NMR spectroscopy. All the limonoids were in vitro evaluated for their antimicrobial activities against six pathogenic microorganisms. Limonoids 1 and 2 exhibited some activities against three Gram negative bacteria with MIC values less than 60 µg/ml.
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Antiinfecciosos , Limoninas , Meliaceae , Antiinfecciosos/farmacología , Limoninas/farmacología , Estructura Molecular , SemillasRESUMEN
BACKGROUND: GROWTH-REGULATING FACTORs (GRFs), a type of plant-specific transcription factors, play important roles in regulating plant growth and development. Although GRF gene family has been identified in various plant species, a genome-wide analysis of this family in lettuce (Lactuca sativa L.) has not been reported yet. RESULTS: Here we identified 15 GRF genes in lettuce and performed comprehensive analysis of them, including chromosomal locations, gene structures, and conserved motifs. Through phylogenic analysis, we divided LsaGRFs into six groups. Transactivation assays and subcellular localization of LsaGRF5 showed that this protein is likely to act as a transcriptional factor in the cell nucleus. Furthermore, transgenic lettuce lines overexpressing LsaGRF5 exhibited larger leaves, while smaller leaves were observed in LsaMIR396a overexpression lines, in which LsaGRF5 was down-regulated. CONCLUSIONS: These results in lettuce provide insight into the molecular mechanism of GRF gene family in regulating leaf growth and development and foundational information for genetic improvement of the lettuce variations specialized in leaf character.
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Lactuca/crecimiento & desarrollo , Lactuca/genética , Desarrollo de la Planta/genética , Reguladores del Crecimiento de las Plantas/genética , Hojas de la Planta/anatomía & histología , Hojas de la Planta/crecimiento & desarrollo , Hojas de la Planta/genética , China , Productos Agrícolas/genética , Productos Agrícolas/crecimiento & desarrollo , Regulación de la Expresión Génica de las Plantas , Genes de Plantas , Genoma de Planta , Filogenia , Factores de TranscripciónRESUMEN
Microorganisms play an important role in nutrient cycling and ecosystem stability. This experiment studied the conservation management approaches [control without fertilizer (CK); fertilizer and different mulching based straw mulching (SM), plastic mulching (PM), ridge-furrow with plastic mulching (RFPFM), and green manure (GM)] effects on the soil microbial community structures in spring corn (Zea Mayis) dry land. The results showed that the bacterial phylum mainly included Proteobacteria (28.2%-36.8%), Acidobacteriota (9.1%-17.9%), Bacteroidota (5.6%-8.9%) and Actinobacteria (3.1-6.2%). The most richness fungal components were Ascomycota (35.2%-44.2%), Basidiomycota (3.3%-12%) and Mortierellomycota (3.4%-6.6%). Additionally, the highest Chao1 and abundance-based coverage estimator (ACE) indexes of bacteria (2931.9 and 2953.7) and fungi (1083.316 and 1100.650) were present in RFPFM that indicating the richest microbial abundance, the highest Shannon and Simpson indexes was exist in PM (9.332 and 0.996) for bacteria and RFPFM (6.753 and 0.974) for fungi. Therefore, this study reveals the conservation management of fertilizer addition and mulching management obviously promoted microbial diversity and altered the superior microbial distribution that provides a potential way for agricultural sustainable management approaches in production practice during circular economy.
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Microbiota , Suelo , Bacterias , Hongos , Microbiología del SueloRESUMEN
BACKGROUND: Helicobacter pylori (H. pylori) infection remains a global public health issue, especially in Asia. Due to the emergence of antibiotic-resistant strains and the complexity of H. pylori infection, conventional vaccination is the best way to control the disease. Our previous study found that the N-acetyl-neuroaminyllactose-binding hemagglutinin protein (HpaA) is an effective protective antigen for vaccination against H. pylori infection, and intranasal immunization with the immunodominant HpaA epitope peptide (HpaA 154-171, P22, MEGVLIPAGFIKVTILEP) in conjunction with a CpG adjuvant decreased bacterial colonization in H. pylori-infected mice. However, to confer more robust and effective protection against H. pylori infection, an optimized delivery system is needed to enhance the P22-specific memory T cell response. RESULTS: In this study, an intranasal nanoemulsion (NE) delivery system offering high vaccine efficacy without obvious cytotoxicity was designed and produced. We found that this highly stable system significantly prolonged the nasal residence time and enhanced the cellular uptake of the epitope peptide, which powerfully boosted the specific Th1 responses of the NE-P22 vaccine, thus reducing bacterial colonization without CpG. Furthermore, the protection efficacy was further enhanced by combining the NE-P22 vaccine with CpG. CONCLUSION: This epitope-loaded nanoemulsion delivery system was shown to extend antigen release and elicit potent Th1 response, it is an applicable delivery system for intranasal vaccine against H. pylori.
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Portadores de Fármacos , Epítopos , Infecciones por Helicobacter , Helicobacter pylori/inmunología , Factores de Transcripción/inmunología , Administración Intranasal , Animales , Antígenos Bacterianos/inmunología , Sistemas de Liberación de Medicamentos , Emulsiones , Epítopos/administración & dosificación , Epítopos/inmunología , Femenino , Infecciones por Helicobacter/inmunología , Infecciones por Helicobacter/prevención & control , Humanos , Ratones , Ratones Endogámicos BALB C , Nanopartículas , VacunasRESUMEN
With more and more drug-resistant Staphylococcus aureus strains emerging in hospitals, there is an urgent need to develop an effective vaccine to combat S. aureus infection. In this study, we constructed a novel bivalent fusion vaccine, SpA-DKKAA-FnBPA37-507 (SF), based on the D domain of staphylococcal protein A (SpA) and the A domain of fibronectin-binding protein A (FnBPA). Immunisation with SF induced a more ideal protective effect compared with the single components alone in a sepsis model. It also showed broad immunoprotection against seven FnBPA isotypes. Vaccination with SF induced strong antibodies responses and Th1/Th17 polarized cellular responses. Further we demonstrated the protective effect of antibodies by the opsonophagocytic assay (OPA) and passive immunisation. Moreover, vaccination with SF showed protective efficacy in a murine pneumonia model and skin abscess model. These results suggest that SF can be regarded as a promising vaccine candidate for the prevention of S. aureus infections.
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Modelos Animales de Enfermedad , Infecciones Estafilocócicas/inmunología , Staphylococcus aureus/inmunología , Vacunas/inmunología , Animales , Anticuerpos Antibacterianos/inmunología , Interacciones Huésped-Patógeno/efectos de los fármacos , Interacciones Huésped-Patógeno/inmunología , Humanos , Inmunidad Celular/inmunología , Inmunización/métodos , Ratones , Neumonía/inmunología , Neumonía/microbiología , Neumonía/prevención & control , Sepsis/inmunología , Sepsis/microbiología , Sepsis/prevención & control , Infecciones Estafilocócicas/microbiología , Infecciones Estafilocócicas/prevención & control , Proteína Estafilocócica A/inmunología , Proteína Estafilocócica A/metabolismo , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/fisiología , Vacunas/administración & dosificaciónRESUMEN
Multi-drug resistant MRSA (methicillin-resistant Staphylococcus aureus) is a global problem for human health, especially skin burn wound patients. Therefore, we estimated the antibacterial and anti-biofilm activity of a chlorhexidine acetate nanoemulsion (CNE) by previously ourselves designed against skin burn wound MRSA infections. Compared with its water solution (CHX), CNE showed a better and faster action against MRSA both in vitro and in vivo. Importantly, CNE was more effective at inhibiting biofilm formation and clearing the biofilm. We also found that the cell walls and membranes of MRSA were severely disrupted after treatment with CNE. Moreover, the relative electrical conductivity and the leakage of alkaline phosphates, K(+), Mg(2+), DNA and protein obviously increased because the cell wall and membrane were damaged. These data show that novel CNE is a promising potential antimicrobial candidate, especially for skin burn wound MRSA infections.
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Antiinfecciosos/administración & dosificación , Biopelículas , Quemaduras/microbiología , Staphylococcus aureus Resistente a Meticilina , Nanopartículas , Antibacterianos , Quemaduras/tratamiento farmacológico , Emulsiones , Humanos , Infecciones EstafilocócicasRESUMEN
Because of its high Cd uptake and translocation, lettuce is often used in Cd contamination studies. However, there is a lack of information on Cd accumulation in the above-ground parts of lettuce during the entire growing season. In this study, a field experiment was carried out in a Cd-contaminated area. Above-ground lettuce parts were sampled, and the Cd content was measured using a flame atomic absorption spectrophotometer (AAS). The results showed that the Cd concentration in the above-ground parts of lettuce increased from 2.70 to 3.62mgkg(-1) during the seedling stage, but decreased from 3.62 to 2.40mgkg(-1) during organogenesis and from 2.40 to 1.64mgkg(-1) during bolting. The mean Cd concentration during the seedling stage was significantly higher than that during organogenesis (a=0.05) and bolting (a=0.01). The Cd accumulation in the above-ground parts of an individual lettuce plant could be described by a sigmoidal curve. Cadmium uptake during organogenesis was highest (80% of the total), whereas that during bolting was only 4.34%. This research further reveals that for Rome lettuce: (1) the highest Cd content of above-ground parts occurred at the end of the seedling phase; (2) the best harvest time with respect to Cd phytoaccumulation is at the end of the organogenesis stage; and (3) the organogenesis stage is the most suitable time to enhance phytoaccumulation efficiency by adjusting the root:shoot ratio.
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Cadmio/análisis , Lactuca/metabolismo , Raíces de Plantas/metabolismo , Contaminantes del Suelo/análisis , Contaminación de Alimentos/análisis , Plantones/metabolismo , Espectrofotometría AtómicaRESUMEN
A two-year in-situ phytoremediation trial was launched in Shenyang Zhangshi (Sewage) Irrigation Area (SZIA). The phytoremediation efficiency of Solanum nigrum L. was determined, by both monitoring the change of soil Cadmium level in the upper 20 cm of soil, and calculating the plant uptake of soil Cd. After two years experimental, by monitoring the soil Cd concentrations, The Cd concentrations decreased on average from 2.75 mg kg(-1)to 2.45 mg kg(-1) in the first year and from 2.33 mg kg(-1) to 1.53 mg kg(-1) in the second year, amounting to a decrease by a factor of 10.6% in the first year and 12% in the second year. After two years phytoremediation by S. nigrum, Cd concentrations of the seven experimental plots with S. nigrum growth decreased from 2.75 mg kg(-1) to 1.53 mg kg(-1), a decrease by a factor of 24.9%. And the soil Cd concentration decreased only 2.1% and 1.7% in the bared experimental plot. And the calculating of Cd uptake by S. nigrum shown that, the plants uptake 4.46% and 5.18% of the total soil Cd in 2008 and 2009, while the soil Cd concentrations decreased by a factor of 10.6% in 2008 and 12.1% in 2009.
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Cadmio/metabolismo , Contaminantes del Suelo/metabolismo , Solanum nigrum/metabolismo , Biodegradación Ambiental , Cadmio/análisis , China , Monitoreo del Ambiente , Estaciones del Año , Contaminantes del Suelo/análisisRESUMEN
A microcosm experiment with artificially contaminated soils was conducted in a greenhouse to evaluate the effect of gibberellic acid 3 (GA3) on phytoremediation efficiency of Solanum nigrum L. The GA3 was applied at three different concentrations (10, 100, 1000 mg L(-1)) to S. nigrum. Results indicated that GA3 can significantly (p < 0.05) increase the biomass of S. nigrum by 56 % at 1000 mg L(-1). Concurrently, GA3 application increased Cd concentrations in the shoot of S. nigrum by 16 %. The combined effects resulted in an increase in the amount of Cd extracted by a single plant by up to 124 %. Therefore, it is possible to use GA3 to promote the Cd phytoremediation efficiency of S. nigrum.
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Cadmio/metabolismo , Giberelinas/farmacología , Contaminantes del Suelo/metabolismo , Solanum nigrum/metabolismo , Biodegradación Ambiental , Biomasa , Cadmio/análisis , Contaminantes del Suelo/análisis , Solanum nigrum/efectos de los fármacos , Solanum nigrum/crecimiento & desarrolloRESUMEN
PURPOSE: The objective of this study was to investigate the value of delayed 18F fluorodeoxyglucose PET/computed tomography (18F-FDG PET/CT) images in patients with small colorectal cancer liver metastases (CRLMs) with hypothyroidism. METHOD: We performed a retrospective analysis of 66 small-CRLM patients with hypothyroidism and 66 small-CRLM patients with euthyroidism, all of whom underwent dual-time-point 18 F-FDG PET/CT imaging. First, the diagnostic accuracy of PET/CT early imaging and PET/CT delayed imaging on lesions was analyzed. Next, the correlation of metabolic parameters between PET/CT early imaging and PET/CT delayed imaging was analyzed according to the grouping of all lesions. Finally, PET/CT parameters were analyzed for correlation with thyroid hormones. RESULTS: The diagnostic accuracy of delayed imaging in small-CRLM patients with hypothyroidism is not as good as that in small-CRLM patients with euthyroidism; PET/CT metabolic parameters are also unfavorable for the diagnosis of small-CRLM. For small-CRLM patients with hypothyroidism, the greater the thyroid-stimulating hormone level, the greater the uptake of 18 F-FDG in normal liver tissue, and the smaller the ratio of tumor lesion uptake to normal liver tissue uptake. CONCLUSION: PET/CT-delayed imaging has better performance than early imaging in small-CRLM patients with euthyroidism. However, the more severe the hypothyroidism, the worse the diagnostic delayed imaging performance. The scan time can be extended appropriately to optimize the imaging efficacy.
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Neoplasias Colorrectales , Hipotiroidismo , Neoplasias Hepáticas , Humanos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Fluorodesoxiglucosa F18 , Estudios Retrospectivos , Radiofármacos , Tomografía de Emisión de Positrones/métodos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Neoplasias Colorrectales/complicaciones , Neoplasias Colorrectales/diagnóstico por imagen , Neoplasias Colorrectales/patología , Hipotiroidismo/complicaciones , Hipotiroidismo/diagnóstico por imagenRESUMEN
Objective: Atrial fibrillation (AF) is a common arrhythmia. This study explored serum miR-29b-3p expression in AF patients and its value in predicting AF recurrence after radiofrequency catheter ablation (RFCA). Methods: Totally 100 AF patients who underwent RFCA were enrolled, with 100 individuals without AF as controls. Serum miR-29b-3p expression in participants was determined using RT-qPCR. The correlation between miR-29b-3p and atrial fibrosis markers (FGF-21/FGF-23) was assessed by Pearson analysis. The diagnostic efficacy of serum miR-29b-3p and FGF-21/FGF-23 in predicting AF recurrence after RFCA was analyzed by the receiver operating characteristic (ROC) curves. The Kaplan-Meier method was adopted to evaluate the effect of miR-29b-3p expression on the incidence of AF recurrence after RFCA. The independent risk factors for AF recurrence after RFCA were analyzed by logistic regression analysis. Results: Serum miR-29b-3p was poorly expressed in AF patients. After RFCA, AF patients showed elevated serum miR-29b-3p expression. Serum miR-29b-3p expression in AF patients negatively correlated with serum FGF-21 and FGF-23 concentrations. The cut-off values of serum miR-29b-3p, FGF-21, and FGF-23 in identifying AF recurrence were 0.860 (sensitivity: 100.00%, specificity: 39.71%), 222.2 pg/mL (sensitivity: 96.88%, specificity: 32.35%) and 216.3 ng/mL (sensitivity: 53.13%, specificity: 70.59%), respectively. Patients with low miR-29b-3p expression had a significantly higher incidence of AF recurrence than patients with high miR-29b-3p expression. Serum miR-29b-3p expression was one of the independent risk factors for AF recurrence after RFCA. Conclusion: Low miR-29b-3p expression in AF patients has certain predictive values and is one of the independent risk factors for AF recurrence after RFCA.
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Fibrilación Atrial , Ablación por Catéter , MicroARNs , Recurrencia , Humanos , Fibrilación Atrial/sangre , Masculino , Femenino , MicroARNs/sangre , Persona de Mediana Edad , Factor-23 de Crecimiento de Fibroblastos , Anciano , Factores de Riesgo , Curva ROC , Valor Predictivo de las Pruebas , Biomarcadores/sangre , Factores de Crecimiento de Fibroblastos/sangreRESUMEN
In this study, Solanum nigrum L. was used as a hyperaccumulator for remediation of cadmium contaminated soil, and 3 different cultivation protocols were investigated. The results showed that a double cropping treatment enhanced the phytoremediation efficiency significantly, since it increased the amount of Cd extracted in one growing season by a factor of 1.62 compared to single cropping. However, the labor cost for double cropping was twice that of single cropping. If the time consumed is considered as a cost of phytoremediation, the double cropping treatment might be considered as an effective and economic cultivation protocol by reducing the overall time required to reach the targeted soil quality.
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Agricultura/métodos , Cadmio/metabolismo , Restauración y Remediación Ambiental/métodos , Contaminantes del Suelo/metabolismo , Solanum nigrum/metabolismo , Biodegradación Ambiental , China , Monitoreo del Ambiente , Restauración y Remediación Ambiental/economía , Solanum nigrum/efectos de los fármacos , Espectrofotometría AtómicaRESUMEN
Digital logistics techniques are important for business applications that contribute to economic growth. The modern supply chain or logistics seeks to implement a large-scale smart infrastructure incorporating data, physical objects, information, products, and business progressions. The business applications are utilized various intelligent techniques to maximize the logistic process. However, the logistic process suffers due to transportation costs, quality, and multinational transportation. These factors frequently affect the region's economic growth. In addition, most cities are located in remote areas that receive improper logistic support, which minimizes business growth. So, this work analyzes the impact of digital logistics on the region's economy. The Yangtze River economic belt region, which includes almost 11 cities, is chosen for analysis. The gathered information is processed by Dynamic Stochastic Equilibrium with Statistical Analysis Modelling (DSE-SAM), which predicts the correlation and influence of digital logistics on economic development. Here, the judgment matrix is constructed to reduce the difficulties of data standardization and normalization processes. Then entropy model and statistical correlation analysis are utilized to improve the overall impact analysis process. Finally, the developed DSE-SAM based created system efficiency is compared with the other economic models, such as Spatial Durbin Model (SDM), Coupling Coordination Degree Model (CCDM), and Collaborative Degree Model (CDM). The results of the suggested DSE-SAM model achieve a high correlation of urbanization, logistics, and ecology in the Yangtze River economic belt region compared to other regions.
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Desarrollo Económico , Modelos Económicos , Humanos , Ciudades , Comercio , Progresión de la Enfermedad , Ríos , ChinaRESUMEN
Introduction: Fusobacterium nucleatum (F. nucleatum) infection has been confirmed to be associated with the development, chemoresistance, and immune evasion of colorectal cancer (CRC). The complex relationship between the microorganism, host cells, and the immune system throughout all stages of CRC progression, which makes the development of new therapeutic methods difficult. Methods: We developed a new dendritic cell (DC) vaccine to investigate the antitumor efficacy of CRC immunotherapy strategies. By mediating a specific mode of interaction between the bacteria, tumor, and host, we found a new plant-derived adjuvant, tubeimuside I (TBI), which simultaneously improved the DC vaccine efficacy and inhibited the F. nucleatum infection. Encapsulating TBI in a nanoemulsion greatly improved the drug efficacy and reduced the drug dosage and administration times. Results: The nanoemulsion encapsulated TBI DC vaccine exhibited an excellent antibacterial and antitumor effect and improved the survival rate of CRC mice by inhibiting tumor development and progression. Discussion: In this study, we provide a effective strategy for developing a DC-based vaccine against CRC and underlies the importance of further understanding the mechanism of CRC processes caused by F. nucleatum.
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Neoplasias Colorrectales , Infecciones por Fusobacterium , Vacunas , Animales , Ratones , Fusobacterium nucleatum , Células DendríticasRESUMEN
Objectives: The low immunogenicity of tumor antigens and unacceptable toxicity of adjuvants has hindered the application and development of tumor vaccines. Hence, we designed a novel anti-tumor vaccine composed of a plant-derived immunostimulant molecular nanoadjuvant (a self-nanoemulsifying system, SND) and the antigen OVA, to reinvigorate the immune response and inhibit tumor progression. Methods: In this study, this novel nanoadjuvant with Saponin D (SND) was designed and prepared by low-energy emulsification methods. Several important characteristics of the SND, including morphology, size, polymer dispersity index (PDI), zeta potential, and stability, were estimated, and the cytotoxicity of the SND was evaluated by MTT assay. Additionally, the immune response in terms of antibody titer levels and cellular immunity were evaluated in vivo after immunization with the vaccine, and the preventative and therapeutic effects of this novel vaccine against tumors were estimated. Finally, the antigen release profile was determined by IVIS imaging and by in vivo assay. Results: This SND nanoadjuvant had good characteristics including the average particle size of 26.35 ± 0.225 nm, narrow distribution of 0.221 ± 1.76, and stability zeta potential of -12.9 ± 0.83 mV. And also, it had good stability (size, PDI, zeta potential, antigen stability) and low toxicity in vitro and in vivo, and delayed antigen release in vivo. The humoral immune response (IgG, IgG1, IgG2a, and IgG2b) and cellular immune level (cytokines of splenocytes including IFN-γ, IL-4, IL-1ß andIL-17A) were both improved greatly after injected immunization at 0, 14, 28 days with the novel nanoadjuvant and antigen OVA. Importantly, this novel nanoadjuvant combined with OVA might lead to the induction of the prevent and treatment efficacy in the E.G7-OVA tumor-bearing mice. Conclusions: These results suggested that this novel nanoadjuvant encapsulated natural plant immunostimulant molecular OPD could be a good candidate of tumor vaccine adjuvant for reinvigorating the immune response and powerfully inhibiting tumor growth effect.
Asunto(s)
Vacunas contra el Cáncer , Neoplasias , Saponinas , Ratones , Animales , Adyuvantes Inmunológicos/farmacología , Inmunidad Humoral , Antígenos de Neoplasias/farmacología , Inmunoglobulina G , Saponinas/farmacologíaRESUMEN
Persistent Fusobacterium nucleatum infection is associated with the development of human colorectal cancer (CRC) and promotes tumorigenicity, but the underlying mechanisms remain unclear. Here, we reported that F. nucleatum promoted the tumorigenicity of CRC, which was associated with F. nucleatum-induced microRNA-31 (miR-31) expression in CRC tissues and cells. F. nucleatum infection inhibited autophagic flux by miR-31 through inhibiting syntaxin-12 (STX12) and was associated with the increased intracellular survival of F. nucleatum. Overexpression of miR-31 in CRC cells promoted their tumorigenicity by targeting eukaryotic initiation factor 4F-binding protein 1/2 (eIF4EBP1/2), whereas miR-31 knockout mice were resistant to the formation of colorectal tumors. In conclusion, F. nucleatum, miR-31, and STX12 form a closed loop in the autophagy pathway, and continuous F. nucleatum-induced miR-31 expression promotes the tumorigenicity of CRC cells by targeting eIF4EBP1/2. These findings reveal miR-31 as a potential diagnostic biomarker and therapeutic target in CRC patients with F. nucleatum infection.
RESUMEN
As a principal ingredient of vaccines, adjuvants can directly induce or enhance the powerful, widespread, innate, and adaptive immune responses associated with antigens. Ophiopogonin D (OP-D), a purified component extracted from the plant Ophiopogon japonicus, has been found to be useful as a vaccine adjuvant. The problems of the low solubility and toxicity of OP-D can be effectively overcome by using a low-energy emulsification method to prepare nanoemulsion ophiopogonin D (NOD). In this article, a series of in vitro protocols for cellular activity evaluation are examined. The cytotoxic effects of L929 were determined using a cell counting kit-8 assay. Then, the secreted cytokine levels and corresponding immune cell numbers after the stimulation and culture of splenocytes from immunized mice were detected by ELISA and ELISpot methods. In addition, the antigen uptake ability in bone marrow-derived dendritic cells (BMDCs), which were isolated from C57BL/6 mice and matured after incubation with GM-CSF plus IL-4, was observed by laser scanning confocal microscopy (CLSM). Importantly, macrophage activation was confirmed by measuring the levels of IL-1ß, IL-6, and tumor necrosis factor alpha (TNF-α) cytokines by ELISA kits after coculturing peritoneal macrophages (PMs) from blank mice with the adjuvant for 24 h. It is hoped that this protocol will provide other researchers with direct and effective experimental approaches to evaluate the cellular response efficacies of novel vaccine adjuvants.