The ACE2/Ang-(1-7)/MasR axis alleviates brain injury after cardiopulmonary resuscitation in rabbits by activating PI3K/Akt signaling.

Background: Death among resuscitated patients is mainly caused by brain injury after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The angiotensin converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor (MasR) axis has beneficial effects on brain injury. Therefore, we examined the roles of the ACE2/Ang-(1-7)/MasR axis in brain injury after CA/CPR. Method: We used a total of 76 male New Zealand rabbits, among which 10 rabbits underwent sham operation and 66 rabbits received CA/CPR. Neurological functions were determined by assessing serum levels of neuron-specific enolase and S100 calcium-binding protein B and neurological deficit scores. Brain water content was estimated. Neuronal apoptosis in the hippocampus was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assays. The expression levels of various genes were measured by enzyme-linked immunosorbent assay and western blotting. Results: Ang-(1-7) (MasR activator) alleviated CA/CPR-induced neurological deficits, brain edema, and neuronal damage, and A779 (MasR antagonist) had the opposite functions. The stimulation of ACE2/Ang-(1-7)/MasR inactivated the ACE/Ang II/AT1R axis and activated PI3K/Akt signaling. Inhibiting PI3K/Akt signaling inhibited Ang-(1-7)-mediated protection against brain damage after CA/CPR. Conclusion: Collectively, the ACE2/Ang-(1-7)/MasR axis alleviates CA/CPR-induced brain injury through attenuating hippocampal neuronal apoptosis by activating PI3K/Akt signaling.

Changes in the lodging resistance of winter wheat from 1950s to the 2020s in Henan Province of China.

BACKGROUND: Lodging is a major factor contributing to yield loss and constraining the mechanical harvesting of wheat crops. Genetic improvement through breeding effectively reduced the lodging and improved the grain yield, however, the physiological mechanisms involved in providing resistance to lodging are different in the breeding stage and are not clearly understood. The purpose of this study was to compare the differences in the lodging resistance (LR) of the wheat varieties released during the different decades and to explore the effect of the application of nitrogen (N) fertilizer on the plasticity of LR. RESULTS: A field study was conducted during the cultivation seasons of 2019-2020 and 2020-2021, in soil supplemented with three N levels: N0 (0 kg ha-1), N180 (200 kg ha-1), and N360 (360 kg ha-1) using eight varieties of wheat released for commercial cultivation from 1950 to date. The results obtained showed that genetic improvement had significantly enhanced the LR and grain yield in wheat. In the first breeding stage (from 1950 to 1980s) the lodging resistant index increased by 15.0%, which was primarily attributed to a reduced plant height and increased contents of cellulose, Si, and Zn. In the second breeding stage (the 1990s-2020s) it increased by 172.8%, which was mainly attributed to an increase in the stem diameter, wall thickness, and the contents of K, Ca, Fe, Mn, and Cu. The application of N fertilizer improved the grain yield but reduced the LR in wheat. This was mainly due to an increase in plant height resulting in an elevation of the plant center of gravity, a decrease in the contents of cellulose, and a reduction in the area of large-sized vascular bundles in the stems, even if N supplementation increased the concentrations of K, Ca, and Si. CONCLUSION: Although breeding strategies improved the stem strength, the trade-off between the grain yield and LR was more significantly influenced by the addition of N. Overcoming this peculiar situation will serve as a breakthrough in improving the seed yield in wheat crops in the future.

Astragalus polysaccharide promotes osteogenic differentiation of human bone marrow derived mesenchymal stem cells by facilitating ANKFY1 expression through miR-760 inhibition.

Aims: Astragalus polysaccharide (APS) participates in various processes, such as the enhancement of immunity and inhibition of tumours. APS can affect osteoporosis (OP) by regulating the osteogenic differentiation of human bone mesenchymal stem cells (hBMSCs). This study was designed to elucidate the mechanism of APS in hBMSC proliferation and osteoblast differentiation. Methods: Reverse transcriptase polymerase chain reaction (RT-PCR) and Western blotting were performed to determine the expression of microRNA (miR)-760 and ankyrin repeat and FYVE domain containing 1 (ANKFY1) in OP tissues and hBMSCs. Cell viability was measured using the Cell Counting Kit-8 assay. The expression of cyclin D1 and osteogenic marker genes (osteocalcin (OCN), alkaline phosphatase (ALP), and runt-related transcription factor 2 (RUNX2)) was evaluated using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Mineral deposits were detected through Alizarin Red S staining. In addition, Western blotting was performed to detect the ANKFY1 protein levels following the regulation of miR-760. The relationship between miR-760 and ANKFY1 was determined using a luciferase reporter assay. Results: The expression of miR-760 was upregulated in OP tissues, whereas ANKFY1 expression was downregulated. APS stimulated the differentiation and proliferation of hBMSCs by: increasing their viability; upregulating the expression levels of cyclin D1, ALP, OCN, and RUNX2; and inducing osteoblast mineralization. Moreover, APS downregulated the expression of miR-760. Overexpression of miR-760 was found to inhibit the promotive effect of APS on hBMSC differentiation and proliferation, while knockdown of miR-760 had the opposite effect. ANKFY1 was found to be the direct target of miR-760. Additionally, ANKFY1 participated in the APS-mediated regulation of miR-760 function in hBMSCs. Conclusion: APS promotes the osteogenic differentiation and proliferation of hBMSCs. Moreover, APS alleviates the effects of OP by downregulating miR-760 and upregulating ANKFY1 expression.

Hormonal changes with uniconazole trigger canopy apparent photosynthesis and grain filling in wheat crop in a semi-arid climate.

Phytohormones are important for the growth and development of plants. The objective of the experiment was to investigate the effect of foliar application of uniconazole (UCZ) at the four-leaf stage on hormone crosstalk and production of winter wheat. An experiment was carried out during 2015-2016 and 2016-2017 growth season in a semi-arid region, where UCZ at a concentration of 0 (CK, distilled water), 15 (FU15), 30 (FU30), and 45 (FU45) mg L-1 were sprayed on wheat crop at the four-leaf stage at a rate of 138.8 mL m-2. UCZ alters the endogenous hormone contents in flag leaves and in grains. UCZ inhibited gibberellic acid (GA) in flag leaves and in grains where the lower GA with UCZ improved the zeatin + zeatin riboside (Z + ZR) and abscisic acid (ABA) contents. The lower GA and higher Z + ZR and ABA contents with UCZ-treated plants improved the chlorophyll content and canopy apparent photosynthesis (CAP) as well as the grain-filling characteristics. The Z + ZR and ABA in flag leaves were positively correlated with chlorophyll content and CAP value while negatively with GA. Moreover, the Z + ZR and ABA were positively correlated with maximum grain weight, mean grain-filling rate, and maximum grain-filling rate, while negatively with GA level. Treatment FU30 significantly improved the chlorophyll content, CAP value, spike weight, grain-filling characteristics, and hormone contents of Z + ZR and ABA while it decreased the GA level. The hormone crosstalk with UCZ significantly increased the yield of wheat crop, where FU30 treatment performs better.

miR-145 attenuates cardiac fibrosis through the AKT/GSK-3ß/ß-catenin signaling pathway by directly targeting SOX9 in fibroblasts.

Myocardial infarction (MI) will inevitably result in cardiac fibrosis. In this study, we investigated the effect of microRNA-145 (miR-145) and transcription factor sex-determining region Y box 9 (SOX9) in the production of cardiac fibrosis induced by MI. MI rat models were established by left anterior descending coronary artery (LAD) occlusion. Four weeks after LAD, the cardiac fibrosis level was assessed by Masson's trichrome staining. Cardiac fibroblasts (CFs) exposed to hypoxia were used to simulate MI-induced fibrosis. Flow cytometry, cell counting kit-8, and transwell assays were used to examine changes in CF apoptosis, proliferation, and migration, respectively. miR-145 expression was measured by quantitative real-time polymerase chain reaction. Immunofluorescence and Western blot analysis were performed to determine the relative expression of proteins. In comparison to the sham-operated group, the expression of miR-145 was significantly downregulated in the infarction peripheral area, whereas, SOX9 was upregulated. In the infarcted heart, the overexpression of miR-145 significantly ameliorated cardiac fibrosis and cardiac function, and there was a negative correlation between miR-145 and SOX9 expressions in hypoxic CFs in vitro. In addition, SOX9 was verified to be a functional target of miR-145. Overexpression of miR-145 or inhibition of SOX9 decreased CF proliferation, migration, and fibrosis, but augmented their apoptotic rate. Moreover, the upregulation of miR-145 or suppression of SOX9 inhibited AKT and ß-catenin signaling in hypoxic CFs. Taken together, this study highlights a potential treatment for cardiac fibrosis through the targeted regulation of SOX9 by miR-145, and our findings indicate that miR-145 exerts anti-fibrotic effects in MI via the negative regulation of SOX9 and its downstream AKT/GSK-3ß/ß-catenin pathways.

Melatonin improves the seed filling rate and endogenous hormonal mechanism in grains of summer maize.

The unpredictable precipitation and water deficit conditions in semiarid regions significantly reduce the yield of summer maize. The exogenous application of plant growth regulators can be used as a strategy to enhance plant stress tolerance and improve the growth and yield of maize under semiarid conditions. Here, we studied the protective role of melatonin application on maize yield using grain filling rate and hormonal crosstalk in maize grains. In the first field experiment, seeds were soaked with melatonin at a concentration of 0 (SM0 ), 25 (SM1 ), 50 (SM2 ), and 75 µM (SM3 ) µM. In contrast, in the second experiment, melatonin was applied on the foliage at the ninth leaf stage at a concentration of 0 (FM0 ), 25 (FM1 ), 50 (FM2 ), and 75 (FM3 ) µM. Our findings showed that melatonin treatments as seed soaking significantly increased single seed weight, seed filling rate in superior, medium and inferior seeds by regulating the hormone levels compared to foliar application. Application of melatonin significantly increased the zeatin+zeatin riboside (Z+ZR), indole-3-acetic acid (IAA), and gibberellic acid (GA) contents. However, it significantly inhibited the contents of abscisic acid (ABA) during the seed filling period. The content of Z+ZR, IAA, and GA was positively correlated with the maximum seed filling rate, seed weight, and mean filling rate in middle, superior and lower seeds, while the ABA was negatively correlated. The ABA content in inferior seeds was positively correlated with the maximum and mean seed filling rate. In semiarid regions, melatonin treatment of SM2 and FM2 significantly increased the dry matter per plant, 100-grain weight, seed filling rate, IAA, Z+ZR, GA contents, ear characteristics, and maize yield.

Foliar application of melatonin delay leaf senescence in maize by improving the antioxidant defense system and enhancing photosynthetic capacity under semi-arid regions.

Melatonin is an important plant growth regulator which plays a key role in plant growth and development. The objective of the current research was to evaluate the effect of foliar application of melatonin (MF) on photosynthetic efficiency, antioxidant defense mechanism, and its relation with leaf senescence in maize crop grown in a semi-arid region. A field experiment was conducted during 2017 and 2018 growth season, where melatonin was applied to the foliage at concentrations of 0 (MF0), 25 (MF1), 50 (MF2), and 75 (MF3) µM at the ninth leaf stage. Foliar application of melatonin significantly improved chlorophyll content, net photosynthetic rate, soluble sugar content, and soluble protein content during the process of leaf senescence. The application of melatonin also enhanced antioxidant enzyme activities including superoxide dismutase, catalase, and peroxidase, while reduced malondialdehyde and reactive oxygen species accumulation. Melatonin foliar application also increased total leaf area per plant, grains per ear, thousand grain weight and grain yield of maize crop in a semi-arid region. The application of melatonin significantly improved photosynthetic activity, antioxidant defense mechanism, and yield of maize crop in a semi-arid region, where the most effective treatment was MF2.

Exogenous melatonin confers drought stress by promoting plant growth, photosynthetic capacity and antioxidant defense system of maize seedlings.

Melatonin is an important biologically active hormone that plays a vital role in plant growth and development. In particular, it has been investigated for its roles in abiotic stress management. The current experiment was carried out to investigate the protective role of melatonin in photosynthetic traits and the antioxidant defense system of maize seedling under drought stress. Maize seedlings were subjected to drought stress (40-45% FC) after two weeks of seedling emergence, followed by a foliar spray (0, 25, 50, 75 and 100 µM) and soil drench of melatonin (0, 25, 50, 75 and 100 µM). Our results indicated that drought stress negatively affected maize seedling and decreased plant growth and development, biomass accumulation, reduced chlorophyll, and carotenoid content, and significantly declined photosynthetic rate and stomatal conductance. On the other hand, reactive oxygen species, soluble protein, and proline content increased under drought stress. However, the application of exogenous melatonin reduced the reactive oxygen species burst and enhanced the photosynthetic activity by protecting from damages through activation of various antioxidant enzymes under drought stress. Foliar application of 100 µM and soil drench of 50 µM melatonin was the most effective treatment concentrations under drought stress. Our current findings hereby confirmed the mitigating potential of melatonin application for drought stress by maintaining plant growth, improving the photosynthetic characteristics and activities of antioxidants enzymes.

Shoot and root traits of summer maize hybrid varieties with higher grain yields and higher nitrogen use efficiency at low nitrogen application rates.

Breeding high-yielding and nitrogen-efficient maize (Zea mays L.) hybrid varieties is a strategy that could simultaneously solve the problems of resource shortages and environmental pollution. We conducted a 2-year field study using four nitrogen application rates (0, 150, 225, and 300 kg N hm-2) and two maize hybrid varieties (ZD958 and QS101) to understand the plant traits related to high grain yields and high nitrogen use efficiency (NUE). We found that ZD958 had a higher grain yield and nitrogen accumulation in the shoots at harvest as well as a higher NUE at lower nitrogen application rates (0 and 150 kg hm-2) than QS101. The grain yields and NUE were almost identical for the two hybrid varieties at nitrogen application rates of 225 and 300 kg N hm-2. Compared with QS101, ZD958 had higher above-ground and below-ground biomass amounts, a deeper root distribution, longer root length, root active absorption area, greater grain filling rate, and higher photosynthetic NUE than QS101 at lower nitrogen application rates. Our results showed that ZD958 can maintain a higher grain yield at lower nitrogen rates in a similar manner to N-efficient maize hybrid varieties. The selection of hybrids such as ZD958 with a deeper root distribution and higher photosynthetic NUE can increase the grain yield and NUE under low nitrogen conditions.

Different influences on mitochondrial function, oxidative stress and cytotoxicity of antibiotics on primary human neuron and cell lines.

Although antibiotics are generally well tolerated, their toxic effects on the central nervous system have been gained attention. In this study, we systematically investigated the neuron toxicity of antibiotics from six different classes. We show that clinically relevant concentrations of metronidazole, tigecycline, azithromycin and clindamycin but not ampicillin or sulfamethoxazole induce apoptosis of human primary neuron cells and lines. Notably, tigecycline, azithromycin and clindamycin cause neuron cell oxidative damage whereas metronidazole has no effect on reactive oxygen species (ROS) production, suggesting that metronidazole induces neuron death via ROS-independent mechanism. Tigecycline, azithromycin and clindamycin induce mitochondrial dysfunctions via targeting different mitochondrial respiratory complexes, leading to mitochondrial membrane potential disruption and energy crisis. The deleterious effects of antibiotics are reversed by pretreatment of neuron cells with antioxidant. Our work highlights the different influences of antibiotics on mitochondrial dysfunction, oxidative damage and cytotoxicity in neuron cells. We also provide a strategy to prevent the neurotoxicity.

Exogenous Hormonal Application Regulates the Occurrence of Wheat Tillers by Changing Endogenous Hormones.

Plant hormones play important roles in regulating the occurrence of crop tillers. However, little is known about the relationships and the underlying mechanisms between endogenous hormones and the occurrence of wheat tillers induced by exogenous hormones. In this study, two winter wheat cultivars, Xinong 979 and Xiaoyan 22, were used to investigate the effects of the exogenous application of indole-3-acetic acid (IAA) and zeatin (Z) on the occurrence of wheat tillers and investigate underlying mechanisms regulating the occurrence of tillers. The results showed that the application of IAA inhibited the occurrence of tillers, and external Z application promoted the occurrence rate of tillers under low nitrogen conditions. Further analysis of the results showed that exogenous IAA completely inhibited the growth of tiller buds, while exogenous Z significantly promoted the growth rate of tiller buds in low nitrogen conditions. Endogenous hormones exhibit important functions in regulating the growth of tiller buds, which contents were affected by exogenous hormones. Furthermore, according to the principal component analysis and correlation analysis, the growth of tiller buds was significantly positively correlated with the content of endogenous Z, whereas it was significantly negatively correlated with the ratios of endogenous IAA to endogenous Z (IAA:Z) and endogenous abscisic acid (ABA) to endogenous Z (ABA:Z). Moreover, no significant correlation was observed between the growth of the tiller buds and the endogenous IAA, endogenous gibberellins (GAs), and endogenous ABA content. These results suggested that Z played key roles in regulating the tiller occurrence, and exogenous hormones regulated the growth of wheat tiller buds via affecting the Z contents, thus regulating the occurrence of wheat tiller.

Strategies for reducing the fertilizer application rate in the ridge and furrow rainfall harvesting system in semiarid regions.

The ridge and furrow rainwater harvesting (RFRH) system is a promising water-saving planting technique for dryland farming, but we lack a full understanding of the effects of different fertilizer rates (N:P) on plant nutrient uptake and nutrient use efficiency (NuUE) in foxtail millet using this planting method, as well as the available nutrient residues in the soil. We conducted field studies (Loess Plateau, China) comparing RFRH planting (R) and traditional flat planting (T) at four different fertilizer rates to determine suitable fertilizer application rates for R during 2013-2015. Compared with T, R improved the soil moisture and the utilization of rainwater and fertilizer, thereby enhancing the grain yield, water use efficiency (WUE), grain nutrient uptake, and NUE in a dry year, but with no improvements in a rainy year. The grain yield and WUE exhibited parabolic increasing trends as the fertilizer application rate increased over three years, but no significant increase was found when the fertilizer rate exceeded 189:96 kg N:P ha-1 under R, which significantly reduced the NuUE and might waste nutrients. Therefore, we recommend R combined with 189:96 kg N:P ha-1 as a promising planting strategy for foxtail millet in semiarid areas.

[Protective effect of mouse 2.5s nerve growth factor on PC12 cells from injury induced by 2, 5-hexanedione].

OBJECTIVE: To explore whether the nerve growth factor has protective effects on PC12 cells from injury induced by 2, 5-hexanedione. METHODS: With PC12 cells as the model of neurons, different concentrations of NGF were added into the culture of PC12 cells. Then cell viability was tested with MTT. The DNA fragment was observed with agarose gel electrophoresis. The apoptosis ratio was tested with flow cytometry (FACS). The p53 protein was detected with western blot. The differences among the groups were compared. RESULTS: Cell viabilities were increased with the increase of the concentrations of NGF (P < 0.05). The DNA fragment, the apoptosis ratio and the expression of p53 were all decreased with the increase of the concentrations of NGF (P < 0.05). CONCLUSION: The NGF might have direct nutritional effects on PC12 cells, and protect them from injury induced by 2, 5 HD. Moreover, it might also have anti-apoptosis effect to some extent.

[Study on extraction process of the volatile oil for biyuan dropping pills].

OBJECTIVE: To determine the optimal extracting process of the volatile oil for Biyuan Dropping Pills. METHODS: Conditions for the extraction were studied by orthogonal design guided by the increasement of the volatile oil. RESULTS: The distilling time is the main factor,and the fineness of the herbal material is the second. The optimal process is as follows: crush the herbal material into coarse powder, macerate 1 hour with 9 times water and distill 4 hours. CONCLUSION: The optimized process is feasible and stable.