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Plant exosome-like nanoparticles (ELNs) have shown great potential in treating tumor and inflammatory diseases, but the neuroprotective effect of plant ELNs remains unknown. In the present study, we isolated and characterized novel ELNs from Momordica charantia (MC) and investigated their neuroprotective effects against cerebral ischemia-reperfusion injury. In the present study, MC-ELNs were isolated by ultracentrifugation and characterized. Male Sprague–Dawley rats were subjected to middle cerebral artery occlusion (MCAO) and MC-ELN injection intravenously. The integrity of the blood–brain barrier (BBB) was examined by Evans blue staining and with the expression of matrix metalloproteinase 9 (MMP-9), claudin-5, and ZO-1. Neuronal apoptosis was evaluated by TUNEL and the expression of apoptotic proteins including Bcl2, Bax, and cleaved caspase 3. The major discoveries include: 1) Dil-labeled MC-ELNs were identified in the infarct area; 2) MC-ELN treatment significantly ameliorated BBB disruption, decreased infarct sizes, and reduced neurological deficit scores; 3) MC-ELN treatment obviously downregulated the expression of MMP-9 and upregulated the expression of ZO-1 and claudin-5. Small RNA-sequencing revealed that MC-ELN-derived miRNA5266 reduced MMP-9 expression. Furthermore, MC-ELN treatment significantly upregulated the AKT/GSK3β signaling pathway and attenuated neuronal apoptosis in HT22 cells. Taken together, these findings indicate that MC-ELNs attenuate ischemia-reperfusion–induced damage to the BBB and inhibit neuronal apoptosis probably via the upregulation of the AKT/GSK3β signaling pathway.

Blood brain barrier dysfunction (BBB) causing edema and hemorrhagic transformation is one of the pathophysiological characteristics of stroke. Protection of BBB integrity have shown great potential in improving stroke outcome. Here, we assessed the efficacy of exosomes extracted from healthy rat serum in protection against ischemic stroke in vivo and in vitro. Exosomes were isolated by gradient centrifugation and ultracentrifugation, and exosomes were characterized by transmission electron microscope (TEM) and nanoparticle tracking video microscope. Exosomes were applied to middle cerebral artery occlusion (MCAO) rats or brain microvascular endothelial cell line (bEnd.3) subjected to oxygen-glucose deprivation (OGD) injury. Serum-derived exosomes were injected intravenously into adult male rats 2 hours after transient MCAO. Infarct volume and gross cognitive function were assessed 24 hours after reperfusion. Post-stroke rats treated with serum-derived exosomes exhibited significantly reduced infarct volumes and enhanced neurological function. Apoptosis was assessed via TdT-mediated dUTP nick end labeling (TUNEL) staining and the expression of Bcl-2, Bax and cleaved caspase-3 24 hours after injury. Our data showed that serum exosomes treatment strikingly decreased TUNEL+CD31+ cells in the striatum, enhanced the ratio of Bcl-2 to Bax and inhibited cleaved caspase-3 production in MCAO rats and OGD/reoxygenation insulted bEnd.3 cells. Under the consistent treatment, the expression of LC3B-II, LC3B-I and SQSTM1/p62 was detected by western blotting. Autolysosomes were observed via TEM. We found that serum exosomes reversed the ratio of LC3B-II to LC-3I, prevented SQSTM1/p62 degradation, autolysosome formation and autophagic flux. Together, these results indicated that exosomes isolated from healthy serum provided neuroprotection against experimental stroke partially via inhibition of endothelial cell apoptosis, and autophagy-mediated BBB breakdown. Intravenous serum-derived exosome treatment may therefore provide a novel clinical therapeutic strategy for ischemic stroke.

Caspase-12 is a caspase family member for which functions in regulating cell death and inflammation have previously been suggested. In this study, we used caspase-12 lacZ reporter mice to elucidate the expression pattern of caspase-12 in order to obtain an idea about its possible in vivo function. Strikingly, these reporter mice showed that caspase-12 is expressed explicitly in Purkinje neurons of the cerebellum. As this observation suggested a function for caspase-12 in Purkinje neurons, we analyzed the brain and behavior of caspase-12 deficient mice in detail. Extensive histological analyses showed that caspase-12 was not crucial for establishing cerebellum structure or for maintaining Purkinje cell numbers. We then performed behavioral tests to investigate whether caspase-12 deficiency affects memory, motor, and psychiatric functions in mice. Interestingly, while the absence of caspase-12 did not affect memory and motor function, caspase-12 deficient mice showed depression and hyperactivity tendencies, together resembling manic behavior. Next, suggesting a possible molecular mechanistic explanation, we showed that caspase-12 deficient cerebella harbored diminished signaling through the brain-derived neurotrophic factor/tyrosine kinase receptor B/cyclic-AMP response binding protein axis, as well as strongly enhanced expression of the neuronal activity marker c-Fos. Thus, our study establishes caspase-12 expression in mouse Purkinje neurons and opens novel avenues of research to investigate the role of caspase-12 in regulating psychiatric behavior.

The dynamic monitoring technology of inorganic ions using ion selective electrodes has some problems such as low precision, vulnerability to other ions, short service life, and high price. Due to the difficulty of dynamic control based on ionic concentration of nutrient solution, EC and pH values of nutrient solution are often used as feedback control indexes in hydroponic system. In this study, estimation algorisms of EC and ionic EC contribution percentage based on ionic activity were proposed to understand the quantitative relationship between ionic concentration and EC. With a view to predicting the EC accurately by mean ionic activities of specific salts in nutrient solution based on a specific formula, ionic concentration could also be calculated by the actual measurement of EC combined with ionic EC contribution percentage. With Japanese horticultural experimental nutrient formula and Yamasaki tomato nutrient formula, significant linear correlations between estimated EC and measured EC were found with determination coefficients over 0.99. Ionic EC contribution percentage was not affected by different relative concentrations of nutrient solutions. However, ionic EC contribution percentage changed significantly when adding specific salts with different concentrations, and different changes were found in each anions and cations of specific salt added. When the same K+ concentration was added in different forms of KNO3, K2SO4, KCl, and KH2PO4, the changes of ionic EC contribution percentage of K+ were similar, but those of other anions in potassium salts varied greatly. The relative errors of estimated EC of nutrient solutions based on ionic activities were only 1.3% in horticultural experimental nutrient solution and 1.8% in Yamasaki tomato nutrient solution with different relative concentrations compared to measured EC. The relative errors of estimated EC of nutrient solutions with specific salt added were only 0.1%-0.5% compared to measured EC in two nutrient solution. Therefore, the dynamic feedback control of ionic concentration of nutrient solution could be realized by using EC measurement combined with ionic EC contribution percentage to improve the ionic quantitative control in nutrient solution. The EC control of nutrient solution in automatic irrigation system might be upgraded to ionic concentration control by using algorisms above of ionic EC contribution percentage and EC estimation to meet dynamic demands of hydroponic crops for ionic concentration in different growth stages.

Conventional light sources have been successfully used to cultivate a wide variety of horticultural crops. However, they are of limited use due to uncontrollability of spectra and energy inefficiency. Light-emitting diodes (LEDs) emerged with tremendous potential in controlled environment agriculture due to their energy efficiency, longevity, and spectral specificity, but the effects of different types of LEDs on plant growth and development must be examined. In this study, cucumber (Cucumis sativus L. cv. Zhongnong 26) seedlings were grown under four different lighting treatments that each delivered a photo synthetic photon flux density of 200 ^mol/m2-s at plant canopy including triphosphate fluorescent lamps (TF), high-frequency fluorescent lamps (HF), white LEDs (WL), and red and blue LEDs (RBL). Cucumber seedlings were grown in a growth chamber at (25.0±1.5)°C with 12-hour light and 12-hour dark for 30 days after sowing, and data were subsequently collected. Seedlings grown under the WL were 45%, 12%, and 40% taller than those grown under the TF, HF and RBL, respectively. The leaf area was 23% smaller under the TF than under the HF. The shoot dry weight was 16%-22% lower under the TF than under the other lighting treatments. The transplants grown under the RBL had the lowest root dry weight and root to shoot ratio. The seedling quality index was similar among all the lighting treatments. The LEDs treatment yielded more total dry weight with unit electric power compared to the fluorescent lamps. The chlorophyll content was 13%-15% higher in plants grown under the HF and WL than that under the TF and RBL. Plants grown under the WL and RBL had greater photosynthetic rate, transpiration rate, and stomatal conductance than those grown under the TF and HF. It was concluded that high quality cucumber seedlings can be efficiently produced under the broad-spectrum WL that emit a reasonable amount of blue, green and red light, and the lack of green light and/or high ratio of red to blue light under the RBL may cause undesired plant attributes.

In this study, spectral transmittances were measured in the wavelength range from 300 nm to 1100 nm of tomato leaves with different chlorophyll contents and compositions, and the correlations between the spectral transmittances and the contents of chlorophyll a, chlorophyll b and total chlorophyll were analyzed. With the characteristic wavelengths of 560 nm, 650 nm, 720 nm and the reference wavelength of 940 nm, nine sets of characteristic spectral parameters were obtained. According to the results of correlation analysis and regression model exploration, characteristic spectral parameters of T940/T560, T940/T650 and log (T940/T560) among the nine sets of parameters were highly correlated to the estimated contents of chlorophyll a, chlorophyll b and total chlorophyll of tomato leaves. The relative errors of total chlorophyll and chlorophyll a/b ratio were (5.1±3.7)% and (4.9±4.3)%, respectively. Therefore, the above three characteristic spectral parameters could be applied in the rapid non-destructive estimation of the contents of chlorophyll a, chlorophyll b and total chlorophyll as well as chlorophyll a/b ratio of tomato leaves.

Cardiomyocyte apoptosis is a key event in the process of doxorubicin (DOX)-induced cardiotoxicity. Our previous study found that rosmarinic acid (RA) could attenuate pressure overload-induced cardiac dysfunction via cardiac fibroblasts (CFs), however its effect in DOX-induced cardiotoxicity remains unknown. In the present study, mice were subjected to a single intraperitoneal injection of DOX (15mg/kg) to generate DOX-induced cardiotoxicity. Histological examination, echocardiography, and molecular markers were used to evaluate the effects of RA. Neonatal rat cardiomyocytes (CMs) and CFs were used to verify the protective effect of RA in vitro. Conditioned medium derived from RA-treated CFs were prepared to illustrate the effect of RA on paracrine interplay between CFs and CMs. We found that RA significantly alleviated DOX-induced cardiomyocyte apoptosis and cardiac dysfunction in vivo, which, however, had almost negligible beneficial effect on DOX directly induced cardiomyocyte apoptosis in vitro. Mechanistically, CFs-derived Fas L was responsible for DOX-induced cardiomyocyte apoptosis, and RA treatment could decrease Fas L expression in CFs and its release to the conditioned medium by suppressing nuclear factor of activated T cells (NFAT) activation and metalloproteinase 7 (MMP7) expression, and exerted the anti-apoptotic effect on CMs via CFs. Ionomycin, and activator of NFAT, abrogated RA-mediated protective effect on cardiomyocyte apoptosis and cardiac dysfunction. In summary, RA alleviated cardiomyocyte apoptosis by inhibiting the expression and release of Fas L in CFs via a paracrine manner, moreover, NFAT as well as MMP7 inhibition were responsible for the suppression of Fas L. RA could be a powerful new therapeutic agent to mitigate cardiomyocyte apoptosis, thereby improving DOX-induced cardiotoxicity.

The remarkable advances in next-generation sequencing technology have enabled the wide usage of sequencing as a clinical tool. To promote the advance of precision oncology for breast cancer in China, here we report a large-scale prospective clinical sequencing program using the Fudan-BC panel, and comprehensively analyze the clinical and genomic characteristics of Chinese breast cancer. The mutational landscape of 1,134 breast cancers reveals that the most significant differences between Chinese and Western patients occurred in the hormone receptor positive, human epidermal growth factor receptor 2 negative breast cancer subtype. Mutations in p53 and Hippo signaling pathways are more prevalent, and 2 mutually exclusive and 9 co-occurring patterns exist among 9 oncogenic pathways in our cohort. Further preclinical investigation partially suggests that NF2 loss-of-function mutations can be sensitive to a Hippo-targeted strategy. We establish a public database (Fudan Portal) and a precision medicine knowledge base for data exchange and interpretation. Collectively, our study presents a leading approach to Chinese precision oncology treatment and reveals potentially actionable mutations in breast cancer. Chinese breast cancer patients have not been well represented in clinical sequencing studies. Here the authors analyse the mutational landscape of 1,134 Chinese breast cancer patients, finding actionable targets and a higher prevalence of p53 and Hippo pathway mutations compared to Western cohorts.

Accurate diagnosis of pear tree nutrient deficiency symptoms is vital for the timely adoption of fertilization and treatment. This study proposes a novel method on the fused feature multi-head attention recording network with image depth and shallow feature fusion for diagnosing nutrient deficiency symptoms in pear leaves. First, the shallow features of nutrient-deficient pear leaf images are extracted using manual feature extraction methods, and the depth features are extracted by the deep network model. Second, the shallow features are fused with the depth features using serial fusion. In addition, the fused features are trained using three classification algorithms, F-Net, FC-Net, and FA-Net, proposed in this paper. Finally, we compare the performance of single feature-based and fusion feature-based identification algorithms in the nutrient-deficient pear leaf diagnostic task. The best classification performance is achieved by fusing the depth features output from the ConvNeXt-Base deep network model with shallow features using the proposed FA-Net network, which improved the average accuracy by 15.34 and 10.19 percentage points, respectively, compared with the original ConvNeXt-Base model and the shallow feature-based recognition model. The result can accurately recognize pear leaf deficiency images by providing a theoretical foundation for identifying plant nutrient-deficient leaves.

Improving winter wheat water use efficiency in the North China Plain (NCP), China is essential in light of current irrigation water shortages. In this study, the AquaCrop model was used to calibrate, and validate winter wheat crop performance under various planting dates and irrigation application rates. All experiments were conducted at the Xiaotangshan experimental site in Beijing, China, during seasons of 2008/2009, 2009/2010, 2010/2011 and 2011/2012. This model was first calibrated using data from 2008/2009 and 2009/2010, and subsequently validated using data from 2010/2011 and 2011/2012. The results showed that the simulated canopy cover (CC), biomass yield (BY) and grain yield (GY) were consistent with the measured CC, BY and GY, with corresponding coefficients of determination (R(2)) of 0.93, 0.91 and 0.93, respectively. In addition, relationships between BY, GY and transpiration (T), (R(2) = 0.57 and 0.71, respectively) was observed. These results suggest that frequent irrigation with a small amount of water significantly improved BY and GY. Collectively, these results indicate that the AquaCrop model can be used in the evaluation of various winter wheat irrigation strategies. The AquaCrop model predicted winter wheat CC, BY and GY with acceptable accuracy. Therefore, we concluded that AquaCrop is a useful decision-making tool for use in efforts to optimize wheat winter planting dates, and irrigation strategies.