Western pattern diets induce neuroinflammation and impair cognitive behavior in humans and animals. Neuroinflammation and cognitive impairment have been associated with microbiota dysbiosis, through ...the gut-brain axis. Furthermore, microbiota-accessible carbohydrates (MACs) found in dietary fiber are important in shaping the microbial ecosystem and have the potential to improve the gut-brain-axis. However, the effects of MACs on neuroinflammation and cognition in an obese condition have not yet been investigated. The present study aimed to evaluate the effect of MACs on the microbiota-gut-brain axis and cognitive function in obese mice induced by a high-fat and fiber deficient (HF-FD) diet.
C57Bl/6 J male mice were fed with either a control HF-FD or a HF-MAC diet for 15 weeks. Moreover, an additional group was fed with the HF-MAC diet in combination with an antibiotic cocktail (HF-MAC + AB). Following the 15-week treatment, cognitive behavior was investigated; blood, cecum content, colon, and brain samples were collected to determine metabolic parameters, endotoxin, gut microbiota, colon, and brain pathology.
We report MACs supplementation prevented HF-FD-induced cognitive impairment in nesting building and temporal order memory tests. MACs prevented gut microbiota dysbiosis, including increasing richness, α-diversity and composition shift, especially in Bacteroidetes and its lower taxa. Furthermore, MACs increased colonic mucus thickness, tight junction protein expression, reduced endotoxemia, and decreased colonic and systemic inflammation. In the hippocampus, MACs suppressed HF-FD-induced neuroglia activation and inflammation, improved insulin IRS-pAKT-pGSK3β-pTau synapse signaling, in addition to the synaptic ultrastructure and associated proteins. Furthermore, MACs' effects on improving colon-cognitive parameters were eliminated by wide spectrum antibiotic microbiota ablation.
These results suggest that MACs improve cognitive impairments via the gut microbiota-brain axis induced by the consumption of an HF-FD. Supplemental MACs to combat obesity-related gut and brain dysfunction offer a promising approach to prevent neurodegenerative diseases associated with Westernized dietary patterns and obesity.
Background. Freeze-thaw influences soil-dissolved nitrogen (N) pools due to variations in bacterial communities in temperate regions. The availability of soil water is important to soil ...biogeochemical cycles under frozen conditions. However, it is unclear how soil water content (SWC) mediates the effects of freeze-thaw on soil-dissolved N pools and bacterial communities. Method. In this study, freeze-thaw microcosms were incubated at three levels of SWC, including 10% (air-dried soils), 15% (natural SWC), and 30% (wet soils). In addition to measuring soil-dissolved N pools, variations in bacterial communities were examined using high-throughput sequencing. Results and Conclusions. Total dissolved N (TDN), NO3--N, NH4+-N, microbial biomass N (MBN), and net N mineralization rate (NNMR) were significantly influenced by SWC, freeze-thaw, and their interaction (NH4+-N excluded). N immobilization was inhibited under both low and high SWC, which was accompanied by varied bacterial community composition. However, only higher SWC substantially modified the freeze-thaw effects on the soil-dissolved N pools, characterized by a decrease in N mineralization (especially for the content of NO3--N and NNMR) and an increase in N immobilization (MBN). These scenarios could be significantly correlated to variations in bacterial community composition based on redundancy analysis, especially by species belonging to Bacteroidetes, Nitrospirae, Alphaproteobacteria, Gemmatimonadetes, and Verrucomicrobia (Spearman’s correlations). In conclusion, bacterial species passed through biotic (bacterial species) and abiotic filters (soil N pools) in response to freeze-thaw under varied SWC.
Non-intrusive load monitoring (NILM) provides fine-grained consumption information at the appliance level by analyzing the terminal voltage and total current measured. It shows prospective ...applications in demand side management, such as demand response, energy efficiency, and home energy management system. However, most cutting-edge NILM models have a critical assumption that switching events are triggered by known appliances in the training set, which may be unrealistic. In reality, new appliances are constantly being added, reducing the effectiveness of current methods for load monitoring. In this paper, we propose a conditional generative adversarial network (CGAN) to correctly classify all the known appliances while simultaneously detecting unknown ones using the V-I trajectory features. We integrate variational autoencoder and capsule networks in the generator network, the capsule features of the same known appliance class are forced to match a pre-defined Gaussian and a group of Gaussian priors (one for each appliance class) as the posterior distribution approximately. Furthermore, using an additional encoder network maps the generated V-I trajectory to its latent representation, minimizing the distance between the latent representations and the feature vectors of the generator aids in learning the data distribution for known appliance samples during the training process. In these ways, we can improve the ability of the model to detect unknown appliances. Experimental results on two public datasets demonstrate the effectiveness and superiority of our method.
Dectin-1 signalling in dendritic cells (DCs) has an important role in triggering protective antifungal Th17 responses. However, whether dectin-1 directs DCs to prime antitumour Th9 cells remains ...unclear. Here, we show that DCs activated by dectin-1 agonists potently promote naive CD4(+) T cells to differentiate into Th9 cells. Abrogation of dectin-1 in DCs completely abolishes their Th9-polarizing capability in response to dectin-1 agonist curdlan. Notably, dectin-1 stimulation of DCs upregulates TNFSF15 and OX40L, which are essential for dectin-1-activated DC-induced Th9 cell priming. Mechanistically, dectin-1 activates Syk, Raf1 and NF-κB signalling pathways, resulting in increased p50 and RelB nuclear translocation and TNFSF15 and OX40L expression. Furthermore, immunization of tumour-bearing mice with dectin-1-activated DCs induces potent antitumour response that depends on Th9 cells and IL-9 induced by dectin-1-activated DCs in vivo. Our results identify dectin-1-activated DCs as a powerful inducer of Th9 cells and antitumour immunity and may have important clinical implications.
Spermatogonial stem cells (SSCs) provide the foundation for spermatogenesis and fertility throughout the adult life of a male. Genetic manipulations of SSCs combined with germ cell transplantation ...present a novel approach for gene therapy and production of genetically modified animals. However, the rarity of SSCs within mammalian testes remains an impediment to related applications, making in vitro expansion of SSCs a prerequisite. Nevertheless, long-term culture systems of SSCs from large animals have not been established yet. In this study, we developed an optimized in vitro culture condition for porcine undifferentiated spermatogonia. The germ cells were isolated and enriched from 7-day-old porcine testes by an optimized differential planting. We tested different feeder layers and found that neonatal autologous Sertoli cells acted better than the SIM mouse embryo-derived thioguanine- and ouabain-resistant (STO) cell line and adult Sertoli cells. The effects of several growth factors were also investigated. Using neonatal Sertoli cells as feeder and Dulbecco's modified eagle medium: nutrient mixture F-12 (DMEM/F12) culture medium supplemented with 10% KSR and four cytokines, the undifferentiated spermatogonia can proliferate in vitro for at least 2 months without loss of stemness. The expression of SSC markers indicated that the cultured cells maintained SSC expression profiles. Moreover, xenotransplantation and in vitro induction showed that the long-term cultured cells preserved the capacity to colonize in vivo and differentiate in vitro, respectively, demonstrating the presence of SSCs in the cultured cells. In conclusion, the conditions described in this study can support the normal proliferation of porcine undifferentiated spermatogonia with stemness and normal karyotype for at least 2 months. This culture system will serve as a basic refinement in the future studies and facilitate studies on SSC biology and genetic manipulation of male germ cells.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective ...antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers (P < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.
Dipyridamole bound to the SARS-CoV-2 protease Mpro after identified via the virtual screening and bioassay validation, and thus suppressed viral replication in vitro. As a result, dipyridamole supplementation was associated with significantly decreased concentrations of D-dimers, increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. Display omitted
To analyze the incidence of PICC associated venous thrombosis. To predict the risk factors of thrombosis. To validate the best predictive model in predicting PICC associated thrombosis. Consecutive ...oncology cases in 341 who initially naive intended to be inserted central catheter for chemotherapy, were recruited to our dedicated intravenous lab. All patients used the same gauge catheter, Primary endpoint was thrombosis formation, the secondary endpoint was infusion termination without thrombosis. Two patients were excluded. 339 patients were divided into thrombosis group in 59 (17.4%) and non-thrombosis Group in 280 (82.6%), retrospectively. Tumor, Sex, Age, Weight, Height, BMI, BSA, PS, WBC, BPC, PT, D-dimer, APTT, FIB, Smoking history, Location, Catheter length, Ratio and Number as independent variables were analyzed by Fisher's scoring, then Logistic risk regression, ROC analysis and nomogram was introduced. Total incidence was 17.4%. Venous mural thrombosis in 2 (3.4%), "fibrin sleeves" in 55 (93.2%), mixed thrombus in 2 (3.4%), symptomatic thrombosis in 2 (3.4%), asymptomatic thrombosis in 57 (96.6%), respectively. Height (χ² = 4.48, P = 0.03), D-dimer (χ² = 37.81, P < 0.001), Location (χ² = 7.56, P = 0.006), Number (χ² = 43.64, P < 0.001), Ratio (χ² = 4.38, P = 0.04), and PS (χ² = 58.78, P < 0.001), were statistical differences between the two groups analyzed by Fisher's scoring. Logistic risk regression revealed that Height (β = -0.05, HR = 0.95, 95%CI: 0.911-0.997, P = 0.038), PS (β = 1.07, HR = 2.91, 95%CI: 1.98-4.27, P < 0.001), D-dimer (β0.11, HR = 1.12, 95%CI: 1.045-1.200, P < 0.001), Number (β = 0.87, HR = 2.38, 95% CI: 1.619-3.512, P < 0.001) was independently associated with PICC associated thrombosis. The best prediction model, D-dimer + Number as a novel co-variable was validated in diagnosing PICC associated thrombosis before PICC. Our research revealed that variables PS, Number, D-dimer and Height were risk factors for PICC associated thrombosis, which were slightly associated with PICC related thrombosis, in which, PS was the relatively strongest independent risk factor of PICC related thrombosis.
Coarse aggregate in concrete is basically free from sulfate corrosion. If the influence of the coarse aggregate in the concrete is not eliminated, the change amount of the concrete ultrasonic pulse ...velocity value is directly used to evaluate the damage degree of sulfate corrosion in the concrete, and the results are often inaccurate. This paper presents an evaluation method of corrosion damage for the sulfate-attacked concrete by CT, ultrasonic velocity testing and AHP methods. CT was used to extract the coarse aggregate information in the specimen, and the proportion of coarse aggregate on the ultrasonic test line was calculated based on CT image analysis. Then, the correction value of ultrasonic pulse velocity (UPV) of the concrete structure was calculated, and the sulfate corrosion degree of concrete structure was evaluated using the analytic hierarchy process (AHP). The results show that the evaluation method proposed in this paper could more accurately evaluate the corrosion damage in the sulfate-attacked concrete structures, and the evaluation results were more in line with reality.
Designing efficient heterogeneous catalysts for the atmospheric fixation of CO2 at room temperature remains a formidable challenge due to their high thermodynamic stability and kinetic inertness. ...Herein, a versatile nanocomposite of Aza-Por-TAPM-immobilized silver nanoparticles (AgNPs), Ag/Azo-Por-TAPM, has been successfully fabricated by adopting a three-dimensional azo-bridged porous porphyrin framework (Azo-Por-TAPM) as the porous support through a simple “liquid impregnation and in situ reduction” strategy. After adjusting the chemical structure of the porphyrin framework, the experimental results reveal that the presence of abundant azo groups and distorted tetrahedral structures is conducive to the preparation of highly dispersed and small-sized AgNPs at its surface. Further studies discover that Ag/Azo-Por-TAPM exhibits a record-level catalytic activity in the carboxylative cyclization of propargylic alcohols with CO2 at room temperature, achieving maximum turnover frequencies of 4600 h–1 at 10 bar and 1050 h–1 at 1 bar, which far exceed that of the previously reported catalysts. In addition, Ag/Aza-Por-TAPM has a high catalytic efficiency with simulated industrial fuel gas under ambient conditions and can be easily recovered and reused at least six times without a significant decrease in catalytic activity. The significantly reduced activation energy, together with the analytical results of NMR spectra, demonstrate that AgNPs-driven alkyne activation is considered as the rate-determining step of the cyclization reaction. This work not only reports a kind of porous porphyrin polymers loaded AgNPs for mild CO2 conversion but also brings some inspiration to designing highly efficient catalysts for the integration of CO2 capture and utilization.
PDF
