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The proteins that coordinate the complex transcriptional networks of aging have not been completely documented. Protein 14-3-3zeta is an adaptor protein that coordinates signaling and transcription factor networks, but its function in aging is not fully understood. Here, we showed that the protein expression of 14-3-3zeta gradually increased during aging. High levels of 14-3-3zeta led to shortened lifespan and imbalance of intestinal immune homeostasis in Drosophila, but the decrease in 14-3-3zeta protein levels by RNAi was able to significantly promote the longevity and intestinal immune homeostasis of fruit flies. Importantly, we demonstrate that adult-onset administration of TIC10, a compound that reduces the aging-related AKT and extracellular signal-regulated kinase (ERK) signaling pathways, rescues the shortened lifespan of 14-3-3zeta-overexpressing flies. This finding suggests that 14-3-3zeta plays a critical role in regulating the aging process. Our study elucidates the role of 14-3-3zeta in natural aging and provides the rationale for subsequent 14-3-3zeta-based antiaging research.
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Proteínas 14-3-3 , Envejecimiento , Proteínas de Drosophila , Drosophila melanogaster , Intestinos , Animales , Proteínas 14-3-3/genética , Proteínas 14-3-3/metabolismo , Envejecimiento/genética , Drosophila melanogaster/crecimiento & desarrollo , Drosophila melanogaster/inmunología , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , Longevidad , Transducción de Señal , Intestinos/inmunologíaRESUMEN
The decline in global plant diversity has raised concerns about its implications for carbon fixation and global greenhouse gas emissions (GGE), including carbon dioxide (CO2), nitrous oxide (N2O) and methane (CH4). Therefore, we conducted a comprehensive meta-analysis of 2103 paired observations, examining GGE, soil organic carbon (SOC) and plant carbon in plant mixtures and monocultures. Our findings indicate that plant mixtures decrease soil N2O emissions by 21.4% compared to monocultures. No significant differences occurred between mixtures and monocultures for soil CO2 emissions, CH4 emissions or CH4 uptake. Plant mixtures exhibit higher SOC and plant carbon storage than monocultures. After 10 years of vegetation development, a 40% reduction in species richness decreases SOC content and plant carbon storage by 12.3% and 58.7% respectively. These findings offer insights into the intricate connections between plant diversity, soil and plant carbon storage and GGE-a critical but previously unexamined aspect of biodiversity-ecosystem functioning.
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Biodiversidad , Carbono , Gases de Efecto Invernadero , Plantas , Suelo , Suelo/química , Gases de Efecto Invernadero/análisis , Carbono/metabolismo , Carbono/análisis , Plantas/metabolismo , Óxido Nitroso/análisis , Óxido Nitroso/metabolismo , Ecosistema , Dióxido de Carbono/metabolismo , Dióxido de Carbono/análisis , Metano/metabolismo , Efecto InvernaderoRESUMEN
BACE1 is essential for the generation of amyloid-ß (Aß) that likely initiates the toxicity in Alzheimer's disease (AD). BACE1 activity is mainly regulated by post-translational modifications, but the relationship between these modifications is not fully characterized. Here, we studied the effects of BACE1 SUMOylation on its phosphorylation and ubiquitination. We demonstrate that SUMOylation of BACE1 inhibits its phosphorylation at S498 and its ubiquitination in vitro. Conversely, BACE1 phosphorylation at S498 suppresses its SUMOylation, which results in promoting BACE1 degradation in vitro. Furthermore, an increase in BACE1 SUMOylation is associated with the progression of AD pathology, while its phosphorylation and ubiquitination are decreased in an AD mouse model. Our findings suggest that BACE1 SUMOylation reciprocally influences its phosphorylation and competes against its ubiquitination, which might provide a new insight into the regulations of BACE1 activity and Aß accumulation.
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Enfermedad de Alzheimer , Secretasas de la Proteína Precursora del Amiloide , Animales , Ratones , Enfermedad de Alzheimer/metabolismo , Péptidos beta-Amiloides/metabolismo , Precursor de Proteína beta-Amiloide/metabolismo , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Ácido Aspártico Endopeptidasas/metabolismo , Fosforilación , Sumoilación , Ubiquitinación , HumanosRESUMEN
Oxygen defects are among essential issues and required to be manipulated in correlated electronic oxides with insulator-metal transition (IMT). Besides, surface and interface control are necessary but challenging in field-induced electronic switching towards advanced IMT-triggered transistors and optical modulators. Herein, we demonstrated reversible entropy-driven oxygen defect migrations and reversible IMT suppression in vanadium dioxide (VO2 ) phase-change electronic switching. The initial IMT was suppressed with oxygen defects, which is caused by the entropy change during reversed surface oxygen ionosorption on the VO2 nanostructures. This IMT suppression is reversible and reverts when the adsorbed oxygen extracts electrons from the surface and heals defects again. The reversible IMT suppression observed in the VO2 nanobeam with M2 phase is accompanied by large variations in the IMT temperature. We also achieved irreversible and stable IMT by exploiting an Al2 O3 partition layer prepared by atomic layer deposition (ALD) to disrupt the entropy-driven defect migration. We expected that such reversible modulations would be helpful for understanding the origin of surface-driven IMT in correlated vanadium oxides, and constructing functional phase-change electronic and optical devices.
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Calibration and compensation techniques are essential to improve the accuracy of the strap-down inertial navigation system. Especially for the new uniaxial rotation module inertial navigation system (URMINS), replacing faulty uniaxial rotation modules introduces installation errors between modules and reduces navigation accuracy. Therefore, it is necessary to calibrate these systems effectively and compensate for the installation error between modules. This paper proposes a new self-calibration and compensation method for installation errors without additional information and equipment. Using the attitude, velocity, and position differences between the two sets of navigation information output from URMINS as measurements, a Kalman filter is constructed and the installation error is estimated. After URMINS is compensated for the installation error, the average of the demodulated redundant information is taken to calculate the carrier's navigation information. The simulation results show that the proposed method can effectively assess the installation error between modules with an estimation accuracy better than 5". Experimental results for static navigation show that the accuracy of heading angle and positioning can be improved by 73.12% and 81.19% after the URMINS has compensated for the estimated installation errors. Simulation and experimental results further validate the effectiveness of the proposed self-calibration and compensation method.
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The aging of mammals is accompanied by the progressive atrophy of tissues and organs and the accumulation of random damage to macromolecular DNA, protein, and lipids. Flavonoids have excellent antioxidant, anti-inflammatory, and neuroprotective effects. Recent studies have shown that flavonoids can delay aging and prolong a healthy lifespan by eliminating senescent cells, inhibiting senescence-related secretion phenotypes (SASPs), and maintaining metabolic homeostasis. However, only a few systematic studies have described flavonoids in clinical treatment for anti-aging, which needs to be explored further. This review first highlights the association between aging and macromolecular damage. Then, we discuss advances in the role of flavonoid molecules in prolonging the health span and lifespan of organisms. This study may provide crucial information for drug design and developmental and clinical applications based on flavonoids.
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Flavonoides , Longevidad , Envejecimiento/genética , Animales , Senescencia Celular/genética , Flavonoides/farmacología , Flavonoides/uso terapéutico , Donaciones , Promoción de la Salud , MamíferosRESUMEN
Escherichia coli, Staphylococcus aureus, Shigella, Pseudomonas aeruginosa, and Klebsiella pneumoniae are common foodborne pathogens. In this study, the light-induced PMAxx-coupled multiplex PCR (PMAxx-mPCR) was established to detect the aforementioned five foodborne pathogens in fresh juice at the same time. Moreover, PMAxx pretreatment could effectively distinguish live bacteria from dead bacteria. The optimized PMAxx pretreatment conditions were incubation with a final concentration of 10 µmol/L PMAxx for 10 min and then photolysis for 8 min. After PMAxx pretreatment, the difference in Ct values with or without PMAxx was determined by quantitative real-time PCR. The results showed a significant difference in Ct value before and after PMAxx treatment. Finally, the bacteria-contaminated fresh juice samples treated with PMAxx dye were detected by mPCR. The detection limit of PMAxx-mPCR was 102 colony-forming units (CFU)/mL for E. coli, Shigella, P. aeruginosa, and K. pneumoniae and 103 CFU/mL for S. aureus. Compared with mPCR detection of samples without PMAxx treatment, the proposed method solved the false-positive problem due to dead bacteria. Hence, an accurate and efficient method for the simultaneous detection of five types of pathogenic bacteria was established. This method could be applied to analytical procedures for ensuring food safety.
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Reacción en Cadena de la Polimerasa Multiplex , Staphylococcus aureus , Bacterias/genética , Escherichia coli , Microbiología de Alimentos , Reacción en Cadena en Tiempo Real de la Polimerasa , Staphylococcus aureus/genéticaRESUMEN
OBJECTIVE: To evaluate the effects of Xihuang Pills (XHP) and its main components on PI3K, AKT and mTOR signaling pathways and cell apoptosis of castration-resistant human PCa PC-3 cell subcutaneously transplanted tumors in nude mice. METHODS: We assigned 36 PC-3 tumor-bearing model mice to six groups of equal numbers to be treated with XHP, musk, calculus bovis (CB), musk + CB and docetaxel, respectively. After 14 days of intervention, we calculated the tumor-inhibition rate in different groups, observed the morphology of the tumor cells by HE staining, determined the levels of PI3K, Akt and mTOR mRNA by RT-qPCR, and determined the expressions of PI3K, Akt and mTOR signaling pathways and caspase-3 and caspase-9 proteins by Western blot. RESULTS: After 14 days of medication, the tumor-inhibition rates in the XHP, musk, CB, musk + CB and docetaxel groups were 29.67%, 5.52%, 7.26%, 12.88% and 6.26%, respectively. HE staining showed the formation of apoptotic bodies in the tumor tissues after intervention, especially in the XHP and musk + CB groups. The mRNA and phosphorylated protein expressions of PI3K, Akt and mTOR were significantly down-regulated (P < 0.01), and so were the expressions of caspase-3 and caspase-9 proteins in the XHP and musk + CB groups in comparison with the control (P < 0.01). CONCLUSIONS: Xihuang Pills, musk and calculus bovis can inhibit the growth of castration-resistant human PCa PC-3 cell subcutaneously transplanted tumors, which is associated with their effects of suppressing the abnormally activated PI3K, Akt and mTOR signaling pathways and promoting the apoptosis of PCa PC3 cells.
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Apoptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Neoplasias de la Próstata , Transducción de Señal/efectos de los fármacos , Animales , Humanos , Masculino , Ratones , Ratones Desnudos , Células PC-3 , Fosfatidilinositol 3-Quinasas/metabolismo , Neoplasias de la Próstata/tratamiento farmacológico , Proteínas Proto-Oncogénicas c-akt/metabolismo , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Regenerating islet-derived protein (Reg) could participate in the occurrence of diabetes mellitus, inflammation, tumors, and other diseased or damaged tissues. However, the correlation of Reg with acute hepatic failure (AHF) and hepatocellular carcinoma (HCC) is poorly defined. To reveal the expression profiles of Reg family and their possible regulatory roles in AHF and HCC, rat models of HCC and AHF were separately established, and Rat Genome 230 2.0 was used to detect expression profiles of Reg-mediated signaling pathways-associated genes from liver tissues in AHF and HCC. The results showed that a total of 79 genes were significantly changed. Among these genes, 67 genes were the AHF-specific genes, 45 genes were the HCC-specific genes, and 33 genes were the common genes. Then, K-means clustering classified these genes into 4 clusters based on the gene expression similarity, and DAVID analysis showed that the above altered genes were mainly associated with stress response, inflammatory response, and cell cycle regulation. Thereafter, IPA software was used to analyze potential effects of these genes, and the predicted results suggested that the Reg-mediated JAK/STAT, NF-κB, MAPK (ERK1/2, P38 and JNK), PLC, and PI3K/AKT signaling pathways may account for the activated inflammation and cell proliferation, and the attenuated apoptosis and cell death during the occurrence of AHF and HCC.
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Carcinoma Hepatocelular/genética , Perfilación de la Expresión Génica , Litostatina/metabolismo , Fallo Hepático Agudo/genética , Neoplasias Hepáticas/genética , Transducción de Señal/genética , Animales , Carcinoma Hepatocelular/patología , Ciclo Celular/genética , Modelos Animales de Enfermedad , Humanos , Inflamación/genética , Hígado/patología , Fallo Hepático Agudo/patología , Neoplasias Hepáticas/patología , Masculino , Familia de Multigenes , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Reproducibilidad de los Resultados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Estrés Fisiológico/genéticaRESUMEN
In practice, a high-dynamic vibration sensor is often plagued by the problem of drift, which is caused by thermal effects. Conversely, low-drift sensors typically have a limited sample rate range. This paper presents a system combining different types of sensors to address general drift problems that occur in measurements for high-dynamic vibration signals. In this paper, the hardware structure and algorithms for fusing high-dynamic and low-drift sensors are described. The algorithms include a drift state estimation and a Kalman filter based on a linear prediction model. Key issues such as the dimension of the drift state vector, the order of the linear prediction model, are analyzed in the design of algorithm. The performance of the algorithm is illustrated by a simulation example and experiments. The simulation and experimental results show that the drift can be removed while the high-dynamic measuring ability is retained. A high-dynamic vibration measuring system with the frequency range starting from 0 Hz is achieved. Meanwhile, measurement noise was improved 9.3 dB through using the linear-prediction-based Kalman filter.
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Dead time estimation is important in the design process of quartz flexure accelerometers. However, to the authors' knowledge, the dead time existing in quartz flexure accelerometers is not well investigated in conventional identification studies. In this paper, the dead time, together with the open-loop transfer function of quartz flexure accelerometers, is identified from step excitation experiments using two steps. Firstly, a monotonicity number was proposed to estimate the dead time. Analysis showed that the monotonicity number was robust enough to measurement noise and sensitive to step excitation. Secondly, parameters of the open-loop transfer function were identified using the least mean squares algorithm. A simulation example was applied to demonstrate the validity of the proposed method. The verified method was used to test a quartz flexure accelerometer. The experimental result shows that the dead time was 500 µs.
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White rot fungi (WRF) are important environmental microorganisms that have been widely applied in many fields. To our knowledge, the application performance of WRF in bioremediation can be greatly improved by the combination with nanotechnology. And the preparation of metallic nanoparticles using WRF is an emerging biosynthesis approach. Understanding the interrelation of WRF and nanoparticles is important to further expand their applications. Thus, this mini-review summarizes the currently related reports mainly from the two different point of views. We highlight that nanoparticles as supports or synergistic agents can enhance the stability and bioremediation performance of WRF in wastewater treatment and the biosynthesis process and conditions of several important metallic nanoparticles by WRF. Furthermore, the potential toxicity of nanoparticles on WRF and challenges encountered are also discussed. Herein, we deem that this mini-review will strengthen the basic knowledge and provide valuable insight for the applications of WRF and nanoparticles.
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Basidiomycota/fisiología , Biodegradación Ambiental , Nanopartículas del Metal , Vías Biosintéticas , Nanotecnología/métodos , Aguas ResidualesRESUMEN
In the process of X-ray computed tomography (CT) imaging, the traditional single-energy X-ray CT imaging technology is only applicable to structural analysis but can't meet the needs of functioning for substance distinction and identification because of the multispectral hardening artifacts and inconsistency between the projection acquisition process and reconstruction assumption. A multispectral CT imaging method based on the spectrum matching priors is presented. First, energy spectrum filtering matching model is built and range spectrum parameters are set according to the material composition; then multi-spectrum projection sequence is acquired by filtering. Second, the different reference energy is selected according to the material composition, befor using the improved Algebraic Reconstruction Techniques (ART) to achieve a multi-spectral CT imaging. Simulation result shows that we improved the contrast of the reconstructed image effectively, while meeting the needs of substance distinction. The actual data collection process is achieved by reconstructing in different spectrum and different corresponding reference energy.
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Tomografía Computarizada por Rayos X , Algoritmos , Artefactos , Procesamiento de Imagen Asistido por Computador , Fantasmas de ImagenRESUMEN
OBJECTIVE: To determine serum vascular endothelial growth factor B (VEGF-B) levels in polycystic ovary syndrome, their association with insulin resistance and ß-cell dysfunction, and the effect of metformin on serum VEGF-B levels. DESIGN: A cross-sectional, interventional study. PATIENTS: We recruited 103 women with polycystic ovary syndrome and 96 age-matched healthy controls. Serum VEGF-B levels were determined in all participants, and 44 polycystic ovary syndrome patients randomly received metformin. MEASUREMENTS: We measured VEGF-B levels in healthy controls and women with polycystic ovary syndrome before and after metformin treatment. RESULTS: Women with polycystic ovary syndrome had higher serum VEGF-B levels, which decreased with metformin treatment. In the lean and overweight/obese groups, patients with polycystic ovary syndrome had higher plasma VEGF-B levels than did healthy controls (P < 0·05). VEGF-B levels were correlated with body mass index, body fat percentage, M values, homeostasis model assessment of insulin resistance and ß-cell function indices. A multiple linear regression analysis showed that VEGF-B level was associated with M values after adjusting for age, body mass index, serum sex hormones and serum lipids in women with polycystic ovary syndrome. CONCLUSIONS: Serum VEGF-B is significantly higher in women with polycystic ovary syndrome and is closely and positively related to insulin resistance. Metformin treatment reduces VEGF-B levels and ameliorates insulin resistance.
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Metformina/uso terapéutico , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Factor B de Crecimiento Endotelial Vascular/sangre , Adulto , Índice de Masa Corporal , Estudios Transversales , Femenino , Hormonas Esteroides Gonadales/sangre , Humanos , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina , Modelos Lineales , Lípidos/sangre , Obesidad/sangre , Sobrepeso/sangre , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: The triglyceride glucose-body mass index (TyG-BMI) has been considered a surrogate marker for assessing insulin resistance. We aimed to correlate the TyG-BMI, triglyceride glucose combined with body mass index, with femoral neck bone mineral density (FN BMD) in non-diabetic elderly men. METHODS: Using data from the National Health and Nutrition Examination Survey (NHANES) database, totally, 1182 eligible men aged ≥ 50 years without diabetes were included in the current study. Smoothed curves were obtained by a two-piecewise linear regression model and the threshold effects were explored by using a smoothing function. RESULTS: TyG-BMI was positive related with and FN BMD with or without adjustment for confounders. However, no typical dose-dependent positive association between TyG-BMI and FN BMD was observed across the TyG-BMI tertiles, indicating a non-linear association. Further analysis by the weighted two-piecewise linear regression model and recursive algorithm suggested that per SD increase in TyG-BMI increased FN BMD by 0.266 gm/cm2 when TyG-BMI lower than 168.20. However, when TyG-BMI is higher than 168.20, FN BMD only increased 0.046 gm/cm2 for per SD increase of TyG-BMI after fully adjustment (OR = 11.258, 95%CI: 6.034, 16.481). Moreover, subgroup analyses showed that higher TyG-BMI levels were related to elevated FN BMD in all groups, suggesting the consistency of the positive association within these stratas. CONCLUSIONS: This study demonstrated that TyG-BMI is positively associated with FN BMD in a nonlinear fashion among elderly men without diabetes, which may be a reliable marker for the early identification of individuals with lower FN BMD.
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Diabetes Mellitus , Cuello Femoral , Anciano , Masculino , Humanos , Índice de Masa Corporal , Encuestas Nutricionales , Glucosa , TriglicéridosRESUMEN
Gesture recognition has emerged as a significant research domain in computer vision and human-computer interaction. One of the key challenges in gesture recognition is how to select the most useful channels that can effectively represent gesture movements. In this study, we have developed a channel selection algorithm that determines the number and placement of sensors that are critical to gesture classification. To validate this algorithm, we constructed a Force Myography (FMG)-based signal acquisition system. The algorithm considers each sensor as a distinct channel, with the most effective channel combinations and recognition accuracy determined through assessing the correlation between each channel and the target gesture, as well as the redundant correlation between different channels. The database was created by collecting experimental data from 10 healthy individuals who wore 16 sensors to perform 13 unique hand gestures. The results indicate that the average number of channels across the 10 participants was 3, corresponding to an 75% decrease in the initial channel count, with an average recognition accuracy of 94.46%. This outperforms four widely adopted feature selection algorithms, including Relief-F, mRMR, CFS, and ILFS. Moreover, we have established a universal model for the position of gesture measurement points and verified it with an additional five participants, resulting in an average recognition accuracy of 96.3%. This study provides a sound basis for identifying the optimal and minimum number and location of channels on the forearm and designing specialized arm rings with unique shapes.
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Algoritmos , Gestos , Reconocimiento de Normas Patrones Automatizadas , Humanos , Masculino , Femenino , Adulto , Reconocimiento de Normas Patrones Automatizadas/métodos , Adulto Joven , Miografía/métodos , Mano/fisiología , Voluntarios Sanos , Reproducibilidad de los ResultadosRESUMEN
Aging is a gradual process of natural change that occurs after reaching sexual maturity. It is also a known risk factor for many chronic diseases. Recent research has shown that senolytics can extend the lifespans and health spans of model organisms, and they have also been demonstrated effective in treating age-related diseases. In this study, we conducted a high-throughput screening of 156 drugs that targeted the PI3K/AKT/mTOR pathway to identify potential senolytic medications. Among these drugs, PF-04691502 was selected for further investigation to understand its molecular mechanism of action. Our findings indicate that PF-04691502, a dual inhibitor of PI3K/AKT and mTOR, specifically eliminates senescent cells. It reduces the expression levels of key markers of cellular senescence, such as SA-ß-Gal, senescence-associated secretory phenotypes (SASPs) and p16INK4a. Additionally, PF-04691502 inhibits the phosphorylation of S6K and AKT, leading to the apoptosis of senescent cells. These results suggest that PF-04691502 holds promise as a new senolytic drug. This paper provides important insights into the potential application of PF-04691502 in the study of cell senescence.
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Proteínas Proto-Oncogénicas c-akt , Piridonas , Pirimidinas , Senoterapéuticos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Senescencia Celular , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
Understanding the responses of soybean rhizosphere and functional microbiomes in intercropping scenarios holds promise for optimizing nitrogen utilization in legume-based intercropping systems. This study investigated three cropping layouts under film mulching: sole soybean (S), soybean-maize intercropping in one row (IS), and soybean-maize intercropping in two rows (IIS), each subjected to two nitrogen levels: 110 kg N ha-1 (N110) and 180 kg N ha-1 (N180). Our findings reveal that cropping patterns alter bacterial and nifh communities, with approximately 5 % of soybean rhizosphere bacterial amplicon sequence variants (ASVs) and 42 % of rhizosphere nifh ASVs exhibiting altered abundances (termed sensitive ASVs). Root traits and soil properties shape these communities, with root traits exerting greater influence. Sensitive ASVs drive microbial co-occurrence networks and deterministic processes, predicting 85 % of yield variance and 78 % of partial factor productivity of nitrogen, respectively. These alterations impact bacterial and nifh diversity, complexity, stability, and deterministic processes in legume-based intercropping systems, enhancing performance in terms of yield, nitrogen utilization efficiency, land equivalent ratio, root nodule count, and nodule dry weight under IIS patterns with N110 compared to other treatments. Our findings underscore the importance of field management practices in shaping rhizosphere-sensitive ASVs, thereby altering microbial functions and ultimately impacting the productivity of legume-based intercropping systems. This mechanistic understanding of soybean rhizosphere microbial responses to intercropping patterns offers insights for sustainable intercropping enhancements through microbial manipulation.
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Agricultura , Glycine max , Microbiota , Rizosfera , Microbiología del Suelo , Glycine max/microbiología , Glycine max/crecimiento & desarrollo , Agricultura/métodos , Nitrógeno/metabolismo , Producción de Cultivos/métodos , Raíces de Plantas/microbiología , Bacterias/metabolismoRESUMEN
Alzheimer's disease (AD) is a progressive neurodegenerative disorder, and moderate exercise holds promise in ameliorating the ongoing neurodegeneration and cognitive decline. Here, we investigated whether exercise-enriched blood plasm could yield a beneficial therapeutic effect on AD pathologies and cognitive decline in transgenic AD (P301S) mice. In this investigation, a cohort of 2-month-old C57BL/6 mice were granted continuous access to either a running wheel or a fixed wheel for 6 weeks. After that, their plasmas were extracted and subsequently injected intravenously into 4.5-month-old P301S mice biweekly over a 6-week period. A comprehensive methodology was then employed, integrating behavioral tests, pathology assessments, and biochemical analyses to unveil the potential anti-dementia implications of exercise-enriched blood plasma in P301S mice. Upon systemic administration, the findings revealed a noteworthy attenuation of hippocampus-dependent behavioral impairments in P301S mice. Conversely, blood plasma from sedentary counterparts exhibited no discernible impact. These effects were intricately associated with the mitigation of neuroinflammation, the augmentation of hippocampal adult neurogenesis, and a reduction of synaptic impairments following the administration of exercise-enriched blood plasma. These findings advance the proposition that administering exercise-enriched blood plasma may serve as an effective prophylactic measure against AD, opening avenues for further exploration and potential therapeutic interventions.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Modelos Animales de Enfermedad , Hipocampo , Ratones Endogámicos C57BL , Ratones Transgénicos , Condicionamiento Físico Animal , Animales , Enfermedad de Alzheimer/terapia , Enfermedad de Alzheimer/sangre , Hipocampo/metabolismo , Hipocampo/patología , Condicionamiento Físico Animal/métodos , Disfunción Cognitiva/terapia , Disfunción Cognitiva/sangre , Ratones , Plasma/metabolismo , Masculino , NeurogénesisRESUMEN
Alzheimer's disease (AD) is the most prevailing form of dementia, with long-term high-fat diet (HFD) consumption being a pivotal contributor to AD pathogenesis. As microglial dysfunction is a crucial factor in the AD onset, it becomes imperative to explore the effects of HFD on microglial function and AD pathogenesis. In the present study, 3xTg-AD model mice at the age of 9-month are subjected to random allocation, with one group receiving a standard diet (ND) and the other an HFD for 3 months. Subsequently, transcriptomic profiling of microglia unveils that HFD alters fatty acid metabolism and mediates T cell infiltration. Within the hippocampus, microglia exhibit aberrant morphology and lipid accretion in response to the HFD, evidenced by conspicuously enlarged microglial cell bodies and accumulation of lipid droplets. These lipid-droplet-accumulating microglia exhibit diminished migratory capacity and compromise plaque consolidation, thereby exacerbating the accumulation of ß-amyloid. Noteworthy, the HFD induces T cell infiltration, thereby aggravating neuroinflammation and Tau phosphorylation. Morris water maze test reveals that HFD-consuming mice display marked impairment in memory performance. In summary, this study demonstrates that prolonged HFD consumption exacerbates amyloid deposition, tau pathology, and cognitive deficits, which is associated with the accumulation of lipid droplets within microglia.