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The nonpeptide AVE0991 is an agonist of the angiotensin-(1–7) (Ang-(1–7)) Mas receptor and is expected to be a putative new drug for treatment of cardiovascular disease. However, the mechanisms involved in the antiproliferative effects of AVE0991 are not fully understood. We saw that the compound attenuated proliferation in an angiotensin II-induced rat vascular smooth muscle cells (VSMC) proliferation model. Moreover, treatment with AVE0991 (10−5 mol/L or 10−7 mol/L) significantly attenuated reactive oxygen species (ROS) production, phosphorylation of p38 MAPK, and dose-dependently (10−8 to 10−5 mol/L) inhibited Ang II-induced VSMC proliferation. Meanwhile, heme oxygenase-1 (HO-1) expression increased in the AVE0991 + Ang II group (10−5 mol/L or 10−6 mol/L). However, the beneficial effects of AVE0991 were completely abolished when the VSMC were pretreated with A-779 (10−6 mol/L). Furthermore, treatment with the HO-1 inhibitor ZnPPIX attenuated the inhibitory effect of AVE0991 on Ang II-induced p38MAPK phosphorylation. These results suggest that AVE0991 attenuates Ang II-induced VSMC proliferation in a dose-dependent fashion and that this effect is associated with the Mas/HO-1/p38 MAPK signaling pathway.

The role of CD3+CD56+ natural killer T (NKT) cells and its co-signaling molecules in patients with sepsis-associated encephalopathy (SAE) is unknown. In this prospective observational cohort study, we initially recruited 260 septic patients and eventually analyzed 90 patients, of whom 57 were in the SAE group and 37 were in the non-SAE group. Compared to the non-SAE group, 28-day mortality was significantly increased in the SAE group (33.3% vs. 12.1%, p = 0.026), while the mean fluorescence intensity (MFI) of CD86 in CD3+CD56+ NKT cells was significantly lower (2065.8 (1625.5 ~ 3198.8) vs. 3117.8 (2278.1 ~ 5349), p = 0.007). Multivariate analysis showed that MFI of CD86 in NKT cells, APACHE II score, and serum albumin were independent risk factors for SAE. Furthermore, the Kaplan–Meier survival analysis indicated that the mortality rate was significantly higher in the high-risk group than in the low-risk group (χ2 = 14.779, p < 0.001). This study showed that the decreased expression of CD86 in CD3+CD56+ NKT cells is an independent risk factor of SAE; thus, a prediction model including MFI of CD86 in NKT cells, APACHE II score, and serum albumin can be constructed for diagnosing SAE and predicting prognosis. [ABSTRACT FROM AUTHOR]

Introduction: The aim of this study was to explore whether the antibrain edema of hypertonic saline (HS) is associated with alleviating ischemic blood‐brain barrier (BBB) permeability by downregulating astrocyte‐derived vascular endothelial growth factor (VEGF), which is mediated by microglia‐derived NOD‐like receptor protein 3 (NLRP3) inflammasome. Methods: The infarct volume and BBB permeability were detected. The protein expression level of VEGF in astrocytes in a transient focal brain ischemia model of rats was evaluated after 10% HS treatment. Changes in the NLRP3 inflammasome, IL‐1β protein expression, and the interleukin‐1 receptor (IL1R1)/pNF‐кBp65/VEGF signaling pathway were determined in astrocytes. Results: HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulates IL‐1β expression by inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulates VEGF expression by inhibiting the phosphorylation of NF‐кBp65 mediated by IL‐1β in astrocytes. Conclusions: HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulated IL‐1β expression via inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulated VEGF expression through inhibiting the phosphorylation of NF‐кBp65 mediated by IL‐1β in astrocytes. [ABSTRACT FROM AUTHOR]

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A study was conducted on a long-term (13 years) tillage and rotation experiment on black soil in northeast China to determine the effects of tillage, time and soil depth on soil microbial biomass carbon (MBC). Tillage systems included no tillage (NT), ridge tillage (RT) and mouldboard plough (MP). Soil sampling was done at 0-5, 5-10 and 10-20 cm depths in June, August and September, 2013, and April, 2014 in the corn phase of corn-soybean rotation plots. MBC content was measured by the chloroform fumigation extraction (CFE) method. The results showed that the MBC content varied with sampling time and soil depth. Soil MBC content was the lowest in April for all three tillage systems, and was highest in June for MP, and highest in August for NT and RT. At each sampling time, tillage system had a significant effect on soil MBC content only in the top 0-5 cm layer. The MBC content showed obvious stratification under NT and RT with a higher MBC content in the top 0-5 cm layer than under MP. The stratification ratios under NT and RT were greatest in September when they were respectively 67.8% and 95.5% greater than under MP. Our results showed that soil MBC contents were greatly affected by the time and soil depth, and were more apparently accumulated in the top layer under NT and RT. [ABSTRACT FROM AUTHOR]

In order to realize precise fertilization and high yield management of Pinus massoniana clonal seed orchard, clones with different fruiting abilities were used as the materials. Four P fertilization levels were at 0, 400, 800 and 1600 g per plant (P 0 , P 4 , P 8 and P 16 respectively). Fertilization was applied before floral primordia formation and after cone picked, respectively. The effects of P fertilizer on the female strobilus of P. massoniana clones and the changes of N, P contents in needles of different positions during floral primordia formation stage and early stage of flower bud differentiation were investigated. The results showed that compared with P 0 , the female strobilus of P 8 and P 16 were significantly increased by 67.4% and 61.2% in 2018 and 28.9% and 14.1% in 2019, respectively. There was a significant negative correlation between the female strobilus with the N content and N/P, a significant positive correlation between the female strobilus and the P content in needles. The responses of N and P contents in needles to P fertilization differed in clones with different fruiting abilities. In floral primordia formation stage, the N content of clones with weak fruiting ability was high, and the N/P was 11.5-12.5, while the P content of clones with strong fruiting abilities was high, and the N/P was 9.5-10.5. During this period, the P content of most clones under P 8 treatment was the highest, while the N/P was lowest. In the early stage of flower bud differentiation, the N/P of two fruiting clones was 15.3-17.0 and 13.2-15.1, respectively. The P content in upside layer was significantly higher while N/P was significantly lower than that in middle and lower layers. In conclusion, the 800 g P fertilization per plant could increase the P content and reduce the N/P of needles during the floral primordia formation stage of clones with diffe-rent fruiting abilities, which was beneficial to the formation of female strobilus and promote the yield of clone seed orchards.

Background: Around the globe, moderate cases account for the largest proportion of all coronavirus disease 2019 (COVID-19) patients, and deteriorated moderate patients contribute the most in mortality. However, published articles failed to address the deterioration details of moderate cases, especially on when and how they deteriorated. Methods: All moderate COVID-19 patients hospitalized in Guangdong Province from January 14 to March 16, 2020, were included in this multicenter retrospective cohort study and were divided into deteriorated and non-deteriorated groups according to clinical status. Symptoms and demographic, therapeutic, and laboratory test result characteristics were collected to explore the features of disease deterioration. Results: Of 1,168 moderate patients included, 148 (13%) deteriorated to severe (130 cases) or critical (18 cases) status. Over 20% of the older subgroup (>50 years old) showed deterioration. The median time for deterioration was 11 days after onset [interquartile range (IQR) 9-14 days]. In addition, 12.2% severe cases could further develop to critical status after 3 days (IQR 2-6.5 days) of having a severe condition. Respiratory dysfunction and hypoxia were the major manifestations as disease deterioration, while 76 cases (52.1%) showed respiratory rate >30 breaths/min, 119 cases (80.4%) showed SaO 2 <93%, 100 cases (67.5%) had 201 < PaO 2 /FiO 2 < 300, and 27 cases (18.9%) had blood lactic acid >2.0 mmol/L. In view of multiple organ dysfunction, 87.8% of acute respiratory distress syndrome (ARDS), 20.2% of acute kidney injury (AKI), 6.8% of coagulopathy, 4% of acute heart failure (AHF), 3.4% of acute hepatic injury (AHI), and 5.4% of shock occurred in deteriorated patients, while organ injury occurred in the following sequence: ARDS, AKI, AHF, coagulopathy, AHI, and shock. Conclusions: The deteriorated pattern of moderate COVID-19 patients is characterized as the 11th day from onset (IQR 9-14 days) being an important time point of disease deterioration with further exacerbation to critical condition in 3 days (IQR 2-6.5 days), A RDS followed by AKI being the typical modes of sequential organ damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2020 Chen, Feng, Xu, Huang, Sun, Zhou, He, Song, Wang, Li and Fang.)

Background: Blood-brain barrier (BBB) impairment plays a significant role in the pathogenesis of sepsis-associated encephalopathy (SAE). However, the molecular mechanisms are poorly understood. In the present study, we aimed to investigate the regulatory relationship between the Janus kinase/signal transducers and activators of transcription (JAK/STAT) signaling pathway, microRNA (miR)-181b and its target genes in sepsis in vivo and in vitro ., Methods: Four rat models (sham, sepsis, sepsis plus STAT3 inhibitor (Stattic), and sepsis plus miR-181b inhibitor [sepsis + anta-miR-181b]) were established. For the in vitro experiments, rat brain microvascular endothelial cells (rBMECs) and rat brain astrocytes (rAstrocytes) were cultured with 10% serum harvested from sham, sepsis, and sepsis + anta-miR-181b rats. Chromatin immunoprecipitation-quantitative polymerase chain reaction (ChIP-QPCR) analysis was carried out to detect the binding and enrichment of the JAK/STAT3 signal core transcription complex in the miR-181b promoter region. Dual-luciferase reporter gene assay was conducted to test miR-181b and its target genes. The cell adhesion rate of rBMECs was also measured., Results: During our investigations, the expression levels of miR-181b, p-JAK2, p-STAT3, and C/EBPβ were found to be significantly increased in the septic rats compared with the sham rats. STAT3 inhibitor halted BBB damage by downregulating the expression of miR-181b. In addition, miR-181b targeted sphingosine-1-phosphate receptor 1 ( S1PR1 ) and neurocalcin delta ( NCALD ). The up-regulated miR-181b significantly decreased the cell adhesion rate of rBMECs. The administration of miR-181b inhibitor reduced damage to the BBB through increasing the expression of S1PR1 and NCALD , which again proved that miR-181b negatively regulates SIPR1 and NCALD to induce BBB damage., Conclusions: Our study demonstrated that JAK2/STAT3 signaling pathway induced expression of miR-181b, which promoted BBB impairment in rats with sepsis by downregulating S1PR1 and decreasing BBB cell adhesion. These findings strongly suggest JAK2/STAT3/miR-181b axis as therapeutic target in protecting against sepsis-induced BBB damage., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/atm-20-7024). The authors have no conflicts of interest to declare., (2020 Annals of Translational Medicine. All rights reserved.)

Background: Short-term recurrence of positive severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ribonucleic acid (RNA) polymerase chain reaction (PCR) in discharged coronavirus disease 2019 (COVID-19) patients attracts the public's concern. This study aimed to determine the clinical and epidemiological results of such patients., Methods: This retrospective study was conducted on 32 designated hospitals for COVID-19 patients discharged from January 14 to March 10, 2020. After 28-day followed-up, patients who tested positive again for SARS-CoV-2 RNA and confirmed by reverse-transcriptase polymerase chain reaction were re-admitted to hospital for further treatments. All of the close contacts of patients who tested positive again were asked to self-segregate for 14 days. Data of epidemiology, symptoms, laboratory tests, and treatments were analyzed in those patients, and their close contacts were investigated., Results: Of 1282 discharged patients, 189 (14.74%) tested positive again for SARS-CoV-2 RNA during 28-day follow-up. The median time from discharge to the next positive test was 8 days (interquartile range [IQR], 5-13). Patients in the group that tested positive again were younger (34 vs 45 years, P < .001) with a higher proportion of moderate symptoms (95.77% vs 84.35%, P < .001) in the first hospitalization than in the negative group. During the second hospitalization, all patients who tested positive again showed normal peripheral white blood cells and lymphocytes and no new symptoms of COVID-19; 78.31% further improved on chest computed tomography scan compared with the first discharge, yet 25.93% accepted antiviral therapy. The median time of re-positive to negative test was 8 days (IQR, 4-15). None of the close contacts developed COVID-19., Conclusions: Our data suggest that the short-term recurrence of positive SARS-CoV-2 RNA in discharged patients is not a relapse of COVID-19, and the risk of onward transmission is very low. This provides important information for managing COVID-19 patients., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: The total survival rate in patients with acute aortic dissection (AAD) has been greatly improved because of surgical technique advances. However, the pre-operative mortality rate remained high. In this study, we sought to evaluate the effects of dexmedetomidine (DEX) on heart rate control and preoperative outcome in AAD., Methods: Retrospectively enrolled 461 patients who were diagnosed with AAD during the first 7-day after admission and divided into two groups according to the use of intravenous DEX: DEX group (91 patients) and Control group (370 patients). The heart rate and systolic blood pressure (SBP) level in both groups were recorded, and the incidence of aortic dissection rupture and pre-operative survival rates within 7 days were considered as the primary clinical outcomes., Results: Compared to the Control group, heart rate of DEX group in the early 3 hours was significantly higher (P=0.009), and the 24-hour heart rate fluctuation was smaller (P=0.012). There was no difference in the systolic blood pressure (SBP) between the two groups, but the 24-hour fluctuation of SBP in DEX group was less (P=0.003). We performed a propensity-matched analysis to minimize selection bias and found that there were 7 (7.9%) patients in the DEX group occurred acute pulmonary edema, 17 (19.1%) patients in the Control group (P=0.047). And the pre-operative survival rates within 7 days were significantly improved in DEX group (P=0.004). And the pre-operative survival rates within 7 days were significantly improved in DEX group (P=0.004)., Conclusions: DEX can be beneficial to facilitate heart rate control, keep SBP more steady, and reduce the incidence of pre-operative aortic rupture in patients with AAD.

In the early stage of an incubation experiment, soil respiration has a sensitive response to different levels of soil moisture. To investigate the effects of soil moisture on soil respiration under different tillage practices, we designed an incubation trial using air-dried soil samples collected from tillage experiment station established on black soils in 2001. The tillage experiment consisted of no-tillage (NT), ridge tillage (RT), and conventional tillage (CT). According to field capacity (water-holding capacity, WHC), we set nine moisture levels including 30%, 60%, 90%, 120%, 150%, 180%, 210%, 240%, 270% WHC. During the 22-day short-term incubation, soil CO₂ emission was measured. In the early stage of incubation, the priming effects occurred under all tillage practices. There were positive correlations between soil respiration and soil moisture. In addition to drought and flood conditions, soil CO₂ fluxes followed the order of NT > RT > CT. We fitted the relationship between soil moisture and soil CO₂ fluxes under different tillage practices. In the range of 30%-270% WHC, soil CO₂ fluxes and soil moisture fitted a quadratic regression equation under NT, and linear regression equations under RT and CT. Under the conditions of 30%-210% WHC of both NT and RT, soil CO₂ fluxes and soil moisture were well fitted by the logarithmic equation with fitting coefficient R² = 0.966 and 0.956, respectively.

In this study, the CO2 emission characteristics and its relationships with C and N concentration in soil amended with different types of residues were studied by thermostatic incubation method to investigate the decomposition characteristics of different types of residues after adding to the soil and the effect of C, N concentration in residues on carbon sequestration. The results showed that during 61 days incubation, the CO2 efflux rates in the soils added with the different residues changed over time and exhibited an initial decrease, followed by a stable low plateau, and then an increase to a high plateau and finally followed by a decrease. The characteristics of CO2 emissions varied with residues, with the differences mainly occurring in the starting and duration of the high plateau CO2 emission period. The cumulative CO2-C emission was significantly affected by residue type. The cumulative CO2-C emissions from soils amended with corn roots, bottom corn stalks, corn leaves, and soybean leaves (about 160 µmol · g(-1) of soil and residue) were significantly greater than those from soils amended with other residues for the initial 21 days. Except for soybean leaves, the cumulative soil CO2 emissions over the 61 day incubation period from soils amended with soybean residues were higher than that from soil amended with corn residues. There were significant linear relationships between the ratio of cumulative CO2-C emission to residue carbon concentration (CR), and both C/N and nitrogen concentration of residues in the initial 21 days incubation, but not for the entire 61 days incubation. Our study suggested that soil CO2 emission was closely dependent upon the type of residue. Soybean residues decomposed more easily than corn residues. However, the decay rate of soybean residues was slower than that of corn residues at the initial stage of incubation. Soil CO2 emission was significantly affected by the C/N ratios and nitrogen concentrations of crop residues only at the early phase of incubation.

The decomposed rate of crop residues is a major determinant for carbon balance and nutrient cycling in agroecosystem. In this study, a constant temperature incubation study was conducted to evaluate CO2 emission and microbial biomass based on four different parts of corn straw (roots, lower stem, upper stem and leaves) and two soils with different textures (sandy loam and clay loam) from the black soil region. The relationships between soil CO2 emission, microbial biomass and the ratio of carbon (C) to nitrogen (N) and lignin of corn residues were analyzed by the linear regression. Results showed that the production of CO2 was increased with the addition of different parts of corn straw to soil, with the value of priming effect (PE) ranged from 215. 53 µmol . g-1 to 335. 17 µmol . g -1. Except for corn leaves, the cumulative CO2 production and PE of clay loam soil were significantly higher than those in sandy loam soil. The correlation of PE with lignin/N was obviously more significant than that with lignin concentration, nitrogen concentration and C/N of corn residue. The addition of corn straw to soil increased the contents of MBC and MBN and decreased MBC/MBN, which suggested that more nitrogen rather than carbon was conserved in microbial community. The augmenter of microbial biomass in sandy loam soil was greater than that in clay loam soil, but the total dissolved nitrogen was lower. Our results indicated that the differences in CO2 emission with the addition of residues to soils were primarily ascribe to the different lignin/N ratio in different corn parts; and the corn residues added into the sandy loam soil could enhance carbon sequestration, microbial biomass and nitrogen holding ability relative to clay loam soil.

1. Previously, we showed that long-term treatment of rats after myocardial infarction (MI) with B-type natriuretic peptide (BNP) prevented ventricular remodelling. However, it is unclear whether long-term BNP treatment affects cardiac hypertrophy and, if so, its mechanism of action. In the present study, we investigated the effects of long-term BNP treatment on cardiac hypertrophy and the molecular mechanisms involved. 2. Cardiac hypertrophy was established in rats by ligation of the left anterior descending coronary artery. After treatment with BNP (5 or 15 microg/kg per day) for 8 weeks, indices of cardiac hypertrophy were determined. In separate in vitro experiments, cardiomyocyte hypertrophy was induced by treatment of cardiomyocytes with 10(-6) mol/L angiotensin (Ang) II for 48 h and cell surface area and [(3)H] incorporation were measured. Transforming growth factor (TGF)-beta1 and smad7 mRNA and protein expression in vivo and in vitro were detected using reverse transcription-polymerase chain reaction and western blotting. 3. Long-term BNP treatment dose-dependently attenuated cardiac hypertrophy and improved cardiac function in rats after MI. Furthermore, BNP attenuated the upregulation of TGF-beta1 and downregulation of smad7 mRNA and protein expression. The in vitro experiments further proved that BNP inhibited cardiac hypertrophy and changes in the TGF-beta1/smad7 pathway, which were completely blocked by the cyclic GMP-dependent protein kinase (PKG) inhibitor, KT5823 (cells were treated with 10(-6) mol/L KT5823 for 48 h). 4. The results of the present study demonstrate that long-term treatment of rats with BNP dose-dependently attenuates cardiac hypertrophy and that this is associated with downregulation of TGF-beta1 and upregulation of smad7 via PKG signalling. Long-term BNP treatment may be a new therapeutic strategy to prevent cardiac hypertrophy and progression to heart failure.