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Introduction: Fuqi Guben Gao (FQGBG) is a botanical drug formulation composed of FuZi (FZ; Aconitum carmichaelii Debeaux [Ranunculaceae; Aconiti radix cocta]), Wolfberry (Lycium barbarum L. [Solanaceae; Lycii fructus]), and Cinnamon (Neolitsea cassia (L.) Kosterm. [Lauraceae; Cinnamomi cortex]). It has been used to clinically treat nocturia caused by kidney-yang deficiency syndrome (KYDS) for over 30 years and warms kidney yang. However, the pharmacological mechanism and the safety of FQGBG in humans require further exploration and evaluation.Methods: We investigated the efficacy of FQGBG in reducing urination and improving immune organ damage in two kinds of KYDS model rats (hydrocortisone-induced model and natural aging model), and evaluated the safety of different oral FQGBG doses through pharmacokinetic (PK) parameters, metabonomics, and occurrence of adverse reactions in healthy Chinese participants in a randomized, double-blind, placebo-controlled, single ascending dose clinical trial. Forty-two participants were allocated to six cohorts with FQGBG doses of 12.5, 25, 50, 75, 100, and 125 g. The PKs of FQGBG in plasma were determined using a fully validated LC-MS/MS method.Results: FQGBG significantly and rapidly improved the symptoms of increased urination in both two KYDS model rats and significantly resisted the adrenal atrophy in hydrocortisone-induced KYDS model rats. No apparent increase in adverse events was observed with dose escalation. Major adverse drug reactions included toothache, thirst, heat sensation, gum pain, diarrhea, abdominal distension, T-wave changes, and elevated creatinine levels. The PK results showed a higher exposure level of benzoylhypaconine (BHA) than benzoylmesaconine (BMA) and a shorter half-life of BMA than BHA. Toxic diester alkaloids, aconitine, mesaconitine, and hypaconitine were below the lower quantitative limit. Drug-induced metabolite markers primarily included lysophosphatidylcholines, fatty acids, phenylalanine, and arginine metabolites; no safety-related metabolite changes were observed.Conclusion: Under the investigated dosing regimen, FQGBG was safe. The efficacy mechanism of FQGBG in treating nocturia caused by KYDS may be related to the improvement of the hypothalamus-pituitary-adrenal axis function and increased energy metabolism.Clinical Trial Registration:https://www.chictr.org.cn/showproj.html?proj=26934, identifier ChiCTR1800015840.

Knowledge of the spatial and temporal variations in soil nutrients is crucial for designing efficient site-specific nutrient management plans, which can improve crop yields and maximize nutrient use efficiency. The present study was conducted to evaluate and compare the status and spatio-temporal distribution pattern of available nitrogen (AHN), phosphorus (AP) and potassium (AK) and some selected soil properties [soil pH and soil organic matter (SOM)] in cultivated soils of Southwestern China over a 15-year period (2007–2022). We visualized the correlations among soil properties, AHN, AP and AK and analyzed the spatial structures of these parameters. A total of 3845 topsoil (0–20 cm) samples (3331 in 2007 and 514 in 2022) were collected from the cultivated areas of Jiangjin District, Chongqing, Southwestern China. Soil pH, SOM, AHN and AK showed moderate variability with coefficient of variation (CV) values varying between 10 and 100%, except AP (CV > 100%, high variability). The mean soil pH, SOM, AP and AK in 2022 were significantly higher than those in 2007. AHN was significantly positively correlated with SOM (r = 0.531, p < 0.01 in 2007, r = 0.768, p < 0.01 in 2022) and significantly negatively correlated with soil pH (r = −0.186, p < 0.01 in 2007, r = −0.102, p < 0.05 in 2022). AP was significantly negatively correlated with soil pH (r = −0.075, p < 0.01 in 2007, r = −0.126, p < 0.01 in 2022). AK was significantly positively correlated with SOM (r = 0.164, p < 0.01 in 2007, r = 0.229, p < 0.01 in 2022), ANH (r = 0.131, p < 0.01 in 2007, r = 0.251, p < 0.01 in 2022) and AP (r = 0.145, p < 0.01 in 2007, r = 0.52, p < 0.01 in 2022). The exponential function performed best for the soil properties and all three nutrients, with higher R2 values (0.203 to 0.93 in 2007 and 0.316 to 0.796 in 2022) in both years. The nugget/sill ratios (which varied from 31.58% to 72% in 2007 and from 29.31% to 47.02% in 2022) indicated the moderate spatial dependence of all soil parameters, except AK in 2022 (nugget/sill ratio = 23.81%, strong spatial dependence). During the study period, soil pH, AP and AK increased in the central and northern areas; SOM increased in the northern and southwestern parts; AHN decreased in the central areas. The current study highlighted the change in spatial variability of soil pH, AHN, AP and AK in the study area over 15 years.

Objectives: Long-term use of evidence-based antiplatelet therapy is recommended for management of stable coronary artery disease (SCAD). However, non-adherence to antiplatelet drugs is common in older patients. This study aimed to evaluate the incidence and impact of antiplatelet therapy cessation on clinical outcomes of older patients with SCAD.Methods: A total of 351 consecutive eligible very older patients (≥80 years) with SCAD from the PLA General Hospital were included. Baseline demographics, clinical characteristics, and clinical outcomes were collected during follow-up. Patients were divided into cessation group and standard group based on whether discontinuing of antiplatelet drugs. The primary outcome was major adverse cardiovascular events (MACE) and secondary outcomes were minor bleeding and all-cause mortality.Results: A total of 351 participants, with a mean age of 91.76 ± 5.01 years old (range 80–106 years) were included in statistical analysis. The antiplatelet drug cessation rate was 60.1%. There were 211 patients in cessation group and 140 patients in standard group. During a median follow-up of 98.6 months, the primary outcome of MACE occurred in 155 patients (73.5%) in the cessation group and 84 patients (60.0%) in the standard group (HR = 1.476, 95% CI:1.124-1.938, p = 0.005). Cessation of antiplatelet drugs increased the rates of angina (HR = 1.724, 95% CI:1.211-2.453, p = 0.002) and non-fatal MI (HR = 1.569, 95% CI:1.093-2.251, p = 0.014). The secondary outcomes of minor bleeding and all-cause mortality were similar between the two groups.Conclusion: Among very older patients with SCAD, antiplatelet therapy cessation significantly increased the risk of MACE, and continuous antiplatelet drug therapy didn’t increase the risk of minor bleeding.

The low-temperature environment significantly inhibits the growth and metabolism of denitrifying bacteria, leading to an excessive concentration of ammonia nitrogen and total nitrogen in sewage treatment plants during the cold season. In this study, an efficient denitrifying strain of heterotrophic nitrification–aerobic denitrification (HN–AD) bacteria named HS2 was isolated and screened from industrial sewage of a chemical factory in Inner Mongolia at 8 °C. The strain was confirmed to be Achromobacter spiritinus, a colorless rod-shaped bacterium. When cultured with sodium succinate as the carbon source, a carbon-to-nitrogen ratio of 20–30, a shaking rate of 150–180 r/min, and an initial pH of 6–10, the strain HS2 exhibited excellent nitrogen removal at 8 °C. Through the results of whole-genome sequencing, gene amplification, and gas product detection, the strain HS2 was determined to possess key enzyme genes in both nitrification and denitrification pathways, suggesting a HN–AD pathway of NH4+-N → NH2OH → NO2−N → NO → N2O → N2. At 8 °C, the strain HS2 could completely remove ammonia nitrogen from industrial sewage with an initial concentration of 127.23 mg/L. Microbial species diversity analysis of the final sewage confirmed Achromobacter sp. as the dominant genus, which indicated that the low-temperature denitrifying strain HS2 plays an important role in nitrogen removal in actual low-temperature sewage.

The effects of long-term monocropping systems combined with climate on soil water aggregate stability (WSA) and soil fertility in the karst region of Southwest China (KRSWC) are unclear. Our research was conducted in the KRSWC, wherein tobacco (Nicotiana tabacum) production is characterized by heavy fertilization and continuous monocropping. The tobacco fields in the study area have similar soil types and fertilization and tillage practices and are spread over an area of 11,500 km2. A total of 568 topsoil samples were collected in 2021. Soil fertility was reflected using the soil fertility index (SFI), which was calculated using the minimum data set method with six soil fertility-related factors, namely, soil pH, soil organic matter, cation exchange capacity, available nitrogen, available phosphorus, and available potassium. Results showed that long-term planting generally promoted soil fertility levels and WSA content. WSA and SFI had inconsistent spatial distribution patterns likely due to different climate-driven effects. WSA variability was greatly controlled by precipitation (Spearman correlation coefficient [r] = −0.49, p < 0.01), whereas SFI variability was mostly dominated by temperature (r = −0.36, p < 0.01). The levels of SFI and WSA were optimal under conditions of low temperature and precipitation and poor under conditions of high temperature and precipitation. Moreover, long-term planting could alleviate the negative effects of climate on SFI and WSA in the KRSWC. The results of this study could provide valuable information on fertilization and climate-adapted strategies for tobacco fields in the KRSWC.

Straw incorporation is a widespread practice to promote agricultural sustainability. However, the potential effects of straw incorporation with the prolonged time on nitrogen (N) runoff loss from paddy fields are not well studied. The current study addresses the knowledge gap by assessing the effects of straw incorporation on the processes influencing N runoff patterns and its impacts on crop yield, N uptake, total N (TN), and soil organic matter (SOM). We conducted field experiments with rice (Oryzasativa L.)–wheat (Triticumaestivum L.) rotation, rice–tobacco (Nicotianatabacum L.) rotation, and double-rice cropping in subtropical China from 2008 to 2012. Each rotation had three N treatments: zero N fertilization (CK), chemical N fertilization (CF), and chemical N fertilization combined with straw incorporation (CFS). The treatment effects were assessed on TN runoff loss, crop yield, N uptake, soil TN stock, and SOM. Results showed that TN runoff was reduced by substituting part of the chemical N fertilizer with straw N in the double rice rotation, while crop N uptake was significantly (P

BackgroundLactate has long been considered an intermediate by-product of glucose metabolism. However, in recent years, accumulating evidence reveals that lactate has unique biological activities. In previous studies, lactate signaling was shown to inhibit inflammation. Furthermore, in vitro experiments have shown that lactate can promote the transformation of pro-inflammatory macrophages into anti-inflammatory macrophages. However, no in vivo studies have shown whether lactate can alleviate inflammation.MethodsRAW 264.7 macrophages were stimulated by LPS to induce an M1 phenotype, and cultured with low and high concentrations of lactate. The cells were then observed for phenotypic transformations and expression of inflammatory mediators and surface markers. The expression of inflammatory factors was also analyzed in the cell-free supernatant fraction. Further, a mouse model of DSS-induced colitis was established and treated with lactate. Colonic tissue injury was monitored by histopathological examinations.ResultsThe in vitro experiments showed that lactate promoted the transformation of activated macrophages to M2 phenotype and decreased the expression of TLR4-mediated NF-κB signaling proteins and inflammatory factors. In the DSS-induced colitis mouse model, lactate promoted the phenotypic transformation of macrophages in colonic tissue, reduced inflammation and organ damage, inhibited the activation of TLR4/NF-κB signaling pathway, decreased the serum levels of pro-inflammatory factors, increased the expression of anti-inflammatory factors, promoted the repair of the intestinal mucosal barrier and reduced the severity of colitis.ConclusionsLactate inhibits the TLR/NF-κB signaling pathway and the production of pro-inflammatory factors by promoting polarization of macrophages. In addition, lactate promotesthe repair of the intestinal mucosal barrier and protects intestinal tissue in inflammation. Furthermore, lactate is relatively safe. Therefore, lactate is a promising and effective drug for treating inflammation through immunometabolism regulation.

Soil carbon is the largest terrestrial carbon pool. Reliable mapping of soil organic carbon (SOC) and soil total carbon content (STC) is essential for agricultural ecosystem management and carbon accounting under global warming conditions. This study was conducted at a fine scale and aimed to perform spatial distribution prediction and uncertainty mapping of SOC and STC and quantify the contribution of environmental variables affecting the variability of SOC and STC. Three machine learning models, namely, Random Forest (RF), eXtreme Gradient Boosting (XGBoost), and Random Forest plus residuals Kriging (RFRK), were developed using 4345 agricultural topsoil samples and 16 environmental covariates. Mean absolute error (MAE), root mean square error (RMSE), Nash–Sutcliffe model efficiency coefficient (NSE), and Lin’s concordance correlation coefficient (LCCC) were used to evaluate the prediction global accuracy. Accuracy plot was used to quantify the uncertainty (i.e. local accuracy) of SOC and STC predictions. RFRK performed best with MAE, RMSE, NSE, and LCCC of 20.76%, 27.61%, 0.39, and 0.56 for SOC and 27.20%, 38.59%, 0.35, and 0.53 for STC, respectively. RF outperformed XGBoost in terms of NSE (0.33 vs 0.29 for SOC and 0.36 vs 0.32 for STC). Accuracy plots showed that RFRK produced higher local accuracy than RF both in quantifying the prediction uncertainty of SOC and STC. XGBoost performed excellently in the uncertainty estimation of SOC. Land use types, mean annual Normalized Difference Vegetation Index, and elevation were the top three important indicators in determining the spatial variability of SOC and STC. These results could provide inspiration and support for monitoring soil carbon in complex terrain areas.

Selenium (Se) is a beneficial microelement for humans, and its varying abundances and shortages have attracted widespread concern. The accumulation process of soil Se is quite complicated, being controlled by multiple factors. However, the influence mechanism of soil properties, climate, and topographic conditions on Se distribution is still unclear in Se-deficient areas. For this study, we collected 2804 samples from cropland soil to assess the levels of Se and the factors that influence those levels in Se-deficient areas of southwestern China. The Se content in this area (0.17 mg/kg) was less than the mean value of China as a whole (0.29 mg/kg). Moran’s I index and a random forest (RF) model showed that higher Se levels were mostly observed in the southern and northern sections of the area we studied. The RF model had excellent performance in predicting soil Se content, with an accuracy of 64%. The use of Shapley additive explanations indicated that soil organic matter (SOM) and mean annual precipitation (MAP) were the critical factors determining Se distribution. The areas with high SOM and MAP showed high Se levels. The information obtained from this work can provide guidance for agricultural planning in Se-deficient areas.

As a crucial transcription factor for spermatogenesis, GATA-binding protein 4 (GATA4) plays important roles in the functioning of Sertoli and Leydig cells. Conditional knockout of GATA4 in mice results in age-dependent testicular atrophy and loss of fertility. However, whether GATA4 is associated with human azoospermia has not been reported. Herein, we analyzed the GATA4 gene by direct sequencing of samples obtained from 184 Chinese men with idiopathic nonobstructive azoospermia (NOA). We identified a missense mutation (c.191G>A, p.G64E), nine single-nucleotide polymorphisms (SNPs), and one rare variant (c.*84C>T) in the 3´ untranslated region (UTR). Functional studies demonstrated that the p.G64E mutation did not affect transactivation ability of GATA4 for spermatogenesis-related genes (claudin-11 and steroidogenic acute regulatory protein, Star), and the 3´ UTR rare variant c.*84C>T did not generate microRNA-binding sites to repress GATA4 expression. To our knowledge, this is the first report to investigate the association between GATA4 and azoospermia; our results indicate that mutations in GATA4 may not be pathogenic for NOA in Chinese men.

There are many unknown genetic factors that lead to infertility in nonobstructive azoospermia men. Here, we performed whole-exome sequencing in blood samples obtained from 40 azoospermia patients with meiotic arrest and found a novel c.151_154del (p.D51fs) frame-shift mutation in exon 3 of the testis expressed 11 (TEX11) gene in one patient. Sanger sequencing analysis of the patient and 288 fertile men was performed to validate the mutation. Immunohistochemical analysis showed TEX11 expression in late-pachytene spermatocytes and in round spermatids in fertile human testes. In contrast, testes of the patient with TEX11 mutation underwent meiotic arrest and lacked TEX11 expression. Western blotting of human embryonic kidney (HEK293) cells transfected with a vector for the p.D51fs TEX11 variant detected no TEX11 expression. In conclusion, we identified a novel frame-shift mutation in the TEX11 gene in an azoospermia patient, emphasizing that this gene should be included in genetic screening panels for the clinical evaluation of azoospermia patients.

BackgroundChronic coronary syndrome (CCS) is a newly proposed concept and is hallmarked by more long-term major adverse cardiovascular events (MACEs), calling for accurate prognostic biomarkers for initial risk stratification.MethodsData-independent acquisition liquid chromatography tandem mass spectrometry (DIA LC-MS/MS) quantitative proteomics was performed on 38 patients with CCS; 19 in the CCS events group and 19 in the non-events group as the controls. We also developed a machine-learning-based pipeline to identify proteins as potential biomarkers and validated the target proteins by enzyme-linked immunosorbent assay in an independent prospective cohort.ResultsFifty-seven differentially expressed proteins were identified by quantitative proteomics and three final biomarkers were preliminarily selected from the machine-learning-based pipeline. Further validation with the prospective cohort showed that endothelial protein C receptor (EPCR) and cholesteryl ester transfer protein (CETP) levels at admission were significantly higher in the CCS events group than they were in the non-events group, whereas the carboxypeptidase B2 (CPB2) level was similar in the two groups. In the Cox survival analysis, EPCR and CETP were independent risk factors for MACEs. We constructed a new prognostic model by combining the Framingham coronary heart disease (CHD) risk model with EPCR and CETP levels. This new model significantly improved the C-statistics for MACE prediction compared with that of the Framingham CHD risk model alone.ConclusionPlasma proteomics was used to find biomarkers of predicting MACEs in patients with CCS. EPCR and CETP were identified as promising prognostic biomarkers for CCS.

Background: Despite the risk of lymph node metastasis (LNM), the indications of endoscopic submucosal dissection (ESD) has expanded to undifferentiated type (UD-type) early gastric cancer (EGC). There is debate as to whether the endoscopic resection can be used. This study was conducted to evaluate risk factors for LNM in undifferentiated early gastric cancer, implications for the indication of the ESD so as to providing evidence for proper clinical management for UD-type EGC. Method: We retrospectively analyzed 203 patients with UD-type EGC who underwent gastrectomy for primary gastric adenocarcinoma between 2012 and 2017. We evaluated the relationship between the clinicopathological factors and the presence of LNM using univariable and multivariable logistic regression analyses. Results: A total of 203 UD-type EGC patients were enrolled, and LNM was positive in 40 cases (19.7%). Multivariable logistic regression analysis identified three independent risk factors for LNM, the tumor size (≥2.0 cm, P

Abstract Background Growth differentiation factor-15 (GDF-15) is a marker of inflammation, oxidative stress and it is associated with adverse prognosis in cardiovascular disease. The aim of the present cohort study is to investigate the prognostic value of GDF-15 in patients with coronary artery disease (CAD) during long-term follow up. Methods A total of 3641 consecutive patients with CAD were prospectively enrolled into the study and followed up for major adverse cardiovascular events (MACEs) and all-cause death up to 5.3–7.6 years. Plasma GDF-15 was measured and clinical data and long-term events were registered. The patients were subsequently divided into three groups by the levels of GDF-15 and the prognostic value of GDF-15 level with MACEs and all-cause death was evaluated. Results After a median follow-up at 6.4 years later, 775 patients (event rate of 21%) had developed MACEs and 275 patients died (event rate of 7.55%). Kaplan–Meier analysis indicated that the patients with GDF-15 > 1800 ng/L were significantly associated with an increased risk of MACEs and all-cause death. Cox regression analysis indicated that GDF-15 > 1800 ng/L were independently associated with the composite of MACEs (HR 1.74; 95% CI 1.44–2.02; P

Meteorological imagery prediction is an important and challenging problem for weather forecasting. It can also be seen as a video frame prediction problem that estimates future frames based on observed meteorological imageries. Despite it is a widely-investigated problem, it is still far from being solved. Current state-of-the-art deep learning based approaches mainly optimise the mean square error loss resulting in blurry predictions. We address this problem by introducing a Meteorological Predictive Learning GAN model (in short MPL-GAN) that utilises the conditional GAN along with the predictive learning module in order to handle the uncertainty in future frame prediction. Experiments on a real-world dataset demonstrate the superior performance of our proposed model. Our proposed model is able to map the blurry predictions produced by traditional mean square error loss based predictive learning methods back to their original data distributions, hence it is able to improve and sharpen the prediction. In particular, our MPL-GAN achieves an average sharpness of 52.82, which is 14% better than the baseline method. Furthermore, our model correctly detects the meteorological movement patterns that traditional unconditional GANs fail to do.

Abstract The regulation of cardiomyocyte differentiation is a fundamental aspect of cardiac development and regenerative medicine. PTEN plays important roles during embryonic development. However, its role in cardiomyocyte differentiation remains unknown. In this study, a low‐cost protocol for cardiomyocyte differentiation from mouse embryonic stem cells (ESCs) is presented and it is shown that Pten deletion potently suppresses cardiomyocyte differentiation. Transcriptome analysis shows that the expression of a series of cardiomyocyte marker genes is downregulated in Pten−/− cardiomyocytes. Pten ablation induces Dnmt3b expression via the AKT/FoxO3a pathway and regulates the expression of a series of imprinted genes, including Igf2. Double knockout of Dnmt3l and Dnmt3b rescues the deficiency of cardiomyocyte differentiation of Pten−/− ESCs. The DNA methylomes from wild‐type and Pten−/− embryoid bodies and cardiomyocytes are analyzed by whole‐genome bisulfite sequencing. Pten deletion significantly promotes the non‐CG (CHG and CHH) methylation levels of genomic DNA during cardiomyocyte differentiation, and the non‐CG methylation levels of cardiomyocyte genes and Igf2 are increased in Pten−/− cardiomyocytes. Igf2 or Igf1r deletion also suppresses cardiomyocyte differentiation through the MAPK/ERK signaling pathway, and IGF2 supplementation partially rescues the cardiomyocyte differentiation. Finally, Pten conditional knockout mice are generated and the role of PTEN in cardiomyocyte differentiation is verified in vivo.

Intercropping is an important agronomic practice. However, assessment of intercropping systems using field experiments is often limited by time and cost. In this study, the suitability of using the DeNitrification DeComposition (DNDC) model to simulate intercropping of maize (Zea mays L.) and soybean (Glycine max L.) and its aftereffect on the succeeding wheat (Triticum aestivum L.) crop was tested in the North China Plain. First, the model was calibrated and corroborated to simulate crop yield and nitrogen (N) uptake based on a field experiment with a typical double cropping system. With a wheat crop in winter, the experiment included five treatments in summer: maize monoculture, soybean monoculture, intercropping of maize and soybean with no N topdressing to maize (N0), intercropping of maize and soybean with 75 kg N ha−1 topdressing to maize (N75), and intercropping of maize and soybean with 180 kg N ha−1 topdressing to maize (N180). All treatments had 45 kg N ha−1 as basal fertilizer. After calibration and corroboration, DNDC was used to simulate long-term (1955 to 2012) treatment effects on yield. Results showed that DNDC could stringently capture the yield and N uptake of the intercropping system under all N management scenarios, though it tended to underestimate wheat yield and N uptake under N0 and N75. Long-term simulation results showed that N75 led to the highest maize and soybean yields per unit planting area among all treatments, increasing maize yield by 59% and soybean yield by 24%, resulting in a land utilization rate 42% higher than monoculture. The results suggest a high potential to promote soybean production by intercropping soybean with maize in the North China Plain, which will help to meet the large national demand for soybean.

Identifying the factors controlling the spatial variability of soil metal elements could be a challenge task due to the interaction of environmental attributes and human activities. This study aimed to investigate the critical explanatory variables controlling total Ca, Cd, Cr, Cu, Zn, Fe, Mn, Mg, Pb, and Zn variations in the arable topsoil using classical statistics, principal component analysis, and random forest techniques. The work was conducted in the core region of the Three Gorges Reservoir of China. The explanatory variables included soil, topography, climate, vegetation, land use type, and distance-related parameters. Average concentrations of the metal elements were in order of Fe > Mg > Ca > Mn > Zn > Cr > Ni > Pb > Cu > Cd. Soil Cr, Fe, and Pb showed low variability while others presented medium variability. Average concentrations of Cr, Fe, Cd, and Mg exceeded their corresponding background values. There were highly positive correlations between all metal elements except Pb, Cd and Cr. The principal component analysis further demonstrated that the sources of Pb, Cd, and Cr differed with other elements. The results of random forest suggested that soil properties followed by topography were critical parameters affecting the variations of Ca, Mg, Mn, Fe, Ni, Zn, and Cu. Agricultural activities and soil properties were major factors controlling the variations of Pb, Cr, and Cd. Further study should be conducted to understand the relations between the metal elements and soil properties.

Utilization and transfer of nitrogen (N) in a strip intercropping system of garlic (Allium sativum L.) and broad bean (Vicia faba L.) have been investigated rarely. The objectives of this study were to quantify N uptake and utilization by intercropped broad bean and garlic and determine the magnitude of N transfer from broad bean to garlic. Field and pot trials were carried out in the Erhai Lake Basin in China using 15N tracer applied to the soil or injected into broad bean plants. Strip intercropping of garlic and broad bean increased N absorption (47.2%) compared with sole crop broad bean (31.9%) or sole crop garlic (40.7%) and reduced soil residual N. Nearly 15% of 15N injected into petioles of broad bean intercropped with garlic was recovered in garlic at harvest, suggesting that N could be transferred from broad bean to strip intercropped garlic. The findings provide a basis for evaluating legumes' role in optimizing N fertilization when intercropped with non-legumes.

A better understanding of the mechanism of primordial follicle activation will help us better understand the causes of premature ovarian insufficiency (POI), and will help us identify new drugs that can be applied to the clinical treatment of infertility. In this study, single oocytes were isolated from primordial and primary follicles, and were used for gene profiling with TaqMan array cards. Bioinformatics analysis was performed on the gene expression data, and Ingenuity Pathway Analysis was used to analyze and predict drugs that affect follicle activation. An ovarian in vitro culture system was used to verify the function of the drug candidates, and we found that curcumin maintains the ovarian reserve. Long-term treatment with 100 mg/kg curcumin improved the ovarian reserve indicators of AMH, FSH, and estradiol in aging mice. Mechanistic studies show that curcumin can affect the translocation of FOXO3, thereby inhibiting the PTEN-AKT-FOXO3a pathway and protecting primordial follicles from overactivation. These results suggest that curcumin is a potential drug for the treatment of POI patients and for fertility preservation.

Abstract: Crop modelling can facilitate researchers' ability to understand and interpret experimental results, and to diagnose yield gaps. In this paper, the Decision Support Systems for Agrotechnology Transfer 4.6 (DSSAT) model together with the CENTURT soil model were employed to investigate the effect of low nitrogen (N) input on wheat (Triticum aestivum L.) yield, grain N concentration and soil organic carbon (SOC) in a long-term experiment (19 years) under a wheat-maize (Zea mays L.) rotation at Changping, Beijing, China. There were two treatments including N0 (no N application) and N150 (150 kg N ha−1) before wheat and maize planting, with phosphorus (P) and potassium (K) basal fertilizers applied as 75 kg P2O5 ha−1 and 37.5 kg K2O ha−1, respectively. The DSSAT-CENTURY model was able to satisfactorily simulate measured wheat grain yield and grain N concentration at N0, but could not simulate these parameters at N150, or SOC in either N treatment. Model simulation and field measurement showed that N application (N150) increased wheat yield compared to no N application (N0). The results indicated that inorganic fertilizer application at the rates used did not maintain crop yield and SOC levels. It is suggested that if the DSSAT is calibrated carefully, it can be a useful tool for assessing and predicting wheat yield, grain N concentration, and SOC trends under wheat-maize cropping systems.

Abstract A number of genes involved in zygotic genome activation (ZGA) have been identified, but the RNA‐binding maternal factors that are directly related to ZGA in mice remain unclear. The present study shows that maternal deletion of Igf 2bp2 (also commonly known as Imp2) in mouse embryos causes early embryonic developmental arrest in vitro at the 2‐cell‐stage. Transcriptomics and proteomics analyses of 2‐cell‐stage embryos in mice reveal that deletion of IMP2 downregulates the expression of Ccar1 and Rps14, both of which are required for early embryonic developmental competence. IGF2, a target of IMP2, when added in culture media, increases the proportion of wild‐type embryos that develop successfully to the blastocyst stage: from 29% in untreated controls to 65% (50 × 10−9 m IGF2). Furthermore, in an experiment related to embryo transfer, foster mothers receiving IGF2‐treated embryos deliver more pups per female than females who receive untreated control embryos. In clinically derived human oocytes, the addition of IGF2 to the culture media significantly enhances the proportion of embryos that develop successfully. Collectively, the findings demonstrate that IMP2 is essential for the regulation and activation of genes known to be involved in ZGA and reveal the potential embryonic development‐related utility of IGF2 for animal biotechnology and for assisted reproduction in humans.

Soil pH is a critical soil quality index and controls soil microbial activities, soil nutrient availability, and plant roots growth and development. The current study aims to evaluate various pedotransfer functions for predicting soil pH using different geochemical indices (CaO, ratios of Al2O3, Fe2O3, TiO2, SiO2, MgO, and K2O to CaO) in forest soils. Various models including empirical functions (quadratic, cubic, sigmoid, logarithmic) and artificial neural network with these geochemical indices were assessed by independent testing set. Mean bias error (MBE), root mean square error (RMSE), mean absolute percentage error (MAPE), mean absolute error (MAE), coefficient of determination (R2), t-statistics (t-stat), and Akaike's Information Criterion (AIC) were applied to evaluate the model performances. Additionally, a new indicator (global performance indictor, GPI) was originally introduced in this study and was used to rank these models. According to GPI, the sigmoid functions and ANNs performed better than others. On average, they could explain above 70% of the variability in soil pH. Both model structure and dataset shape impact on model performance. The best input was CaO for ANNs, sigmoid, and logarithmic functions. The ratios of K2O to CaO and Al2O3 to CaO were the best inputs for quadratic and cubic equations, respectively.

Pollution of residual plastic film in arable lands is a severe problem in China. In this study, the status of residual film and influential factors were investigated using the methods of farm survey in combination with questionnaires and quadrat sampling at a large number of field sites in Xinjiang Uygur Autonomous Region, China. The results showed that the amount of film utilization increased largely and reached to 1.8×105 t in 2013. Similarly, the mulching area also substantially increased in recent decades, and reached to 2.7×105 ha in the same year. According to the current survey, 60.7% of the sites presented a greater mulch residue than the national film residue standard (75 kg ha−1), and the maximum residual amount reached 502.2 kg ha−1 in Turpan, Xinjiang. The film thickness, the mulching time and the crop type all influenced mulch residue. The thickness of the film had significantly negative correlation with the amount of residual film (P

Phosphorus (P) losses from agricultural soils contribute to eutrophication of surface waters. This field plot study investigated effects of rainfall regimes and P applications on P loss by surface runoff from rice (Oryza sativa L.) and wheat (Triticum aestivum L.) cropping systems in Lake Taihu region, China. The study was conducted on two types of paddy soils (Hydromorphic at Anzhen site, Wuxi City, and Degleyed at Xinzhuang site, Changshu City, Jiangsu Province) with different P status, and it covered 3 years with low, high and normal rainfall regimes. Four rates of mineral P fertilizer, i.e., no P (control), 30 kg P ha–1 for rice and 20 kg P ha–1 for wheat (P30+20), 75 plus 40 (P75+40), and 150 plus 80 (P150+80), were applied as treatments. Runoff water from individual plots and runoff events was recorded and analyzed for total P and dissolved reactive P concentrations. Losses of total P and dissolved reactive P significantly increased with rainfall depth and P rates (P

Sufficient soil phosphorus (P) content is essential for achieving optimal crop yields, but accumulation of P in the soil due to excessive P applications can cause a risk of P loss and contribute to eutrophication of surface waters. Determination of a critical soil P value is fundamental for making appropriate P fertilization recommendations to ensure safety of both environment and crop production. In this study, agronomic and environmental critical P levels were determined by using linear-linear and linear-plateau models, and two segment linear model, for a maize (Zea mays L.)-winter wheat (Triticum aestivum L.) rotation system based on a 22-yr field experiment on a Haplic Luvisol soil in northern China. This study included six treatments: control (unfertilized), no P (NoP), application of mineral P fertilizer (MinP), MinP plus return of maize straw (MinP+StrP), MinP plus low rate of farmyard swine manure (MinP+L.Man) and MinP plus high rate of manure (MinP+ H.Man). Based on the two models, the mean agronomic critical levels of soil Olsen-P for optimal maize and wheat yields were 12.3 and 12.8 mg kg−1, respectively. The environmental critical P value as an indicator for P leaching was 30.6 mg Olsen-P kg−1, which was 2.4 times higher than the agronomic critical P value (on average 12.5 mg P kg−1). It was calculated that soil Olsen-P content would reach the environmental critical P value in 41 years in the MinP treatment, but in only 5–6 years in the two manure treatments. Application of manure could significantly raise soil Olsen-P content and cause an obvious risk of P leaching. In conclusion, the threshold range of soil Olsen-P is from 12.5 to 30.6 mg P kg−1 to optimize crop yields and meanwhile maintain relatively low risk of P leaching in Haplic Luvisol soil, northern China.

The pine wood nematode (PWN) Bursaphelenchus xylophilus is the pathogen that causes pine wilt disease (PWD), a devastating forest disease. PWN-associated bacteria may play a role in PWD. However, little is known about the endo-bacteria in PWN. We analyzed the diversity of endo-bacteria in nine isolates of PWNs from Pinus massoniana Lamb. in nine epidemic areas from three Chinese provinces by high-throughput sequencing of 16S rDNA and isolated and identified culturable endo-bacteria through construction of a 16S rDNA phylogenetic tree and Biolog microbial identification. We also examined the effects of endo-bacteria on PWN fecundity, antioxidant capacity, and virulence using sterile nematodes as a control. While the dominant endo-bacteria in PWNs from different regions exhibited no significant difference in the classification levels of class and genus, their proportions differed. Pseudomonas and Stenotrophomonas were highly abundant in all PWN isolates. A total of 15 endo-bacterial strains were successfully isolated and identified as six species: Stenotrophomonas maltophilia, Pseudomonas fluorescens, Kocuria palustris, Microbacterium testaceum, Rhizobium radiobacter, and Leifsonia aquatica. We also found that P. fluorescens significantly increased the egg production of PWN, and that both P. fluorescens and S. maltophilia enhanced the mobility of PWN under oxidative stress and reduced the content of reactive oxygen species by increasing antioxidant enzyme activity in PWN. These strains also accelerated the development of PWD, and P. fluorescens had a more beneficial effect on PWN than S. maltophilia. Diversity exists among the endo-bacteria in PWNs from different regions, and some endo-bacteria can promote PWN infestation by enhancing the fecundity and antioxidant capacity of the nematode. Our study contributes to clarifying the interaction between endo-bacteria and PWN.

Objective: To evaluate the efficacy and short term prognosis of Tirofiban in different treatment duration in patients with acute ST segment elevation myocardial infarction (STEMI) and percutaneous coronary intervention (PCI) combined with intracoronary injection. Methods: A total of 125 patients with acute STEMI were enrolled in this study. They were randomly divided into two groups: control group (n = 61) and Tirofiban group (n = 64). The Tirofiban was used by intracoronary and intravenous administration in Tirofiban group which was randomly divided into three sub-groups according to the duration of Tirofiban by persistent intravenous injection for 12 hours, 24 hours or 36 hours. Thrombolysis in myocardial infarction flow and myocardial perfusion grades were recorded immediately after PCI. The adverse cardiac events and cardiac death within 180 days of PCI, and the adverse effects (hemorrhage and thrombocytopenia) were compared between the two groups and within Tirofiban sub-groups. Results: Grade 3 in myocardial perfusion was significantly better in Tirofiban group than control group (85.94% vs. 72.13%, P = 0.03) after PCI. There was one cardiac death in control group in 180 days after PCI. The adverse cardiac event rates between two groups was significant difference (16 patients in control group and only 8 in Tirofiban group, P = 0.047). There was no significant difference in incidence of hemorrhage complications and platelet counts between two groups. Nevertheless, hemorrhage complications in the 12- and 24-hour subgroups were less than 36-hour subgroup (P = 0.01). Conclusions: Intravenous Tirofiban treatment reduced the adverse cardiac events and improved short term prognosis without increasing the adverse reactions of the drugs in patients undergoing PCI. The less rate of hemorrhage complication can be achieved in short-duration of Tirofiban by intravenous injection after PCI. Keywords: Platelet glycoprotein IIb/IIIa inhibitor, Acute ST segment elevation myocardial infarction, Coronary artery, Percutaneous coronary intervention

In this study, Aspergillus niger 1107 was isolated and identified as an efficient phosphate-solubilizing fungus (PSF). This strain generated 689 mg soluble P L−1 NBRIP medium after 10 d of culture. To produce an affordable biofertilizer using A. niger 1107, the potential of widely available carrier materials for growth and maintenance of this strain were evaluated. The effects of sterilization procedures (autoclaving and gamma-ray irradiation) on the suitability of these carriers to maintain growth of the fungus were also investigated. The carrier materials were peat, corn cobs with 20% (w/w) perlite (CCP), wheat husks with 20% (w/w) perlite (WHP), and composted cattle manure with 20% (w/w) perlite (CCMP). In the first 5–6 mon of storage, the carriers sterilized by gamma-ray irradiation maintained higher inoculum loads than those in carriers sterilized by autoclaving. However, this effect was not detectable after 7 mon of storage. For the P-biofertilizer on WHP, more than 2.0×107 viable spores of A. niger g−1 inoculant survived after 7 mon of storage. When this biofertilizer was applied to Chinese cabbage in a pot experiment, there were 5.6×106 spores of A. niger g−1 soil before plant harvesting. In the pot experiment, Chinese cabbage plants grown in soil treated with peat- and WHP-based P-biofertilizers showed significantly greater growth (P

Background: Premature ventricular contractions (PVCs) are common in the general population, and frequent PVCs may result in the poor quality of life or even the damage of cardiac function. We examined the efficacy and safety of a traditional Chinese medicine Wenxin Keli for the treatment of frequent PVCs among a relatively large Chinese cohort. Methods: We performed a randomized, double-blind, placebo-controlled, parallel-group, multicenter trial. A total of 1200 eligible participants were randomly assigned in a ratio of 1:1 to receive Wenxin Keli or the placebo for 4 weeks. The primary and secondary endpoint was the change of PVC numbers and PVC-related symptoms after a 4-week treatment compared with baseline, respectively. In addition, vital signs, laboratory values, and electrocardiographic parameters were assessed in a safety analysis. Results: At the initial evaluation, no significant differences in the baseline characteristics were observed between the Wenxin Keli group and the placebo group. A smaller number of PVCs was observed after the 4-week treatment than at baseline, in both the Wenxin Keli group (5686 ± 5940 vs. 15,138 ± 7597 beats/d, P < 0.001) and the placebo group (10,592 ± 8009 vs. 14,529 ± 5929 beats/d, P < 0.001); moreover, the Wenxin Keli group demonstrated a significantly greater reduction in the frequency of PVCs than the placebo group (P < 0.001). In a full analysis set, patients in the Wenxin Keli group exhibited significantly higher total effective responses in the reduction of PVCs compared to those in the placebo group (83.8% vs. 43.5%,P < 0.001). The per-protocol analysis yielded similar results (83.0% vs. 39.3%,P < 0.001). Treatment with Wenxin Keli also demonstrated superior performance compared to the placebo with respect to PVC-related symptoms. No severe adverse effects attributable to Wenxin Keli were reported. Conclusions: Wenxin Keli treatment effectively reduced the overall number of PVCs and alleviated PVC-related symptoms in patients without structural heart diseases and had no severe side effects.

The pine wood nematode (PWN), Bursaphelenchus xylophilus, is the pathogen responsible for pine wilt disease (PWD), a devastating forest disease with a pathogenic mechanism that remains unclear. Autophagy plays a crucial role in physiological and pathological processes in eukaryotes, but its regulatory mechanism and significance in PWN are unknown. Therefore, we cloned and characterized three autophagy genes, BxATG5, BxATG9, and BxATG16, in PWN. BxATG9 and BxATG16 were efficiently silenced through RNA interference, and we found that BxATG16 positively regulated the expression of BxATG5. Silencing BxATG9 and BxATG16 severely inhibited feeding and reproduction in PWN, indicating that autophagy is essential for these processes. We then examined the expression patterns of these three autophagy genes in PWN under the stresses of α-pinene and H2O2, the main defense substances of pine trees, and during the development of PWD using quantitative reverse transcription polymerase chain reaction. The expression levels of BxATG5, BxATG9, and BxATG16 all significantly increased after nematodes were stressed with α-pinene and H2O2 and inoculated into pine trees, suggesting that autophagy plays an important role in the defense and pathogenesis of PWN. In this study, the molecular characteristics and functions of the autophagy genes BxATG5, BxATG9, and BxATG16 in PWN were elucidated.

This study was designed to find out an optimised planting system of reducing non-point (source) pollution by analyzing the reasons and the factors of influence non-point pollution in farmland of Erhai Lake basin. The results showed that incomes, residual nitrogen in soil, and the loss of nitrogen in surface water in rice-garlic system were higher than those in rice-fava bean system. There were positive correlations between the nitrogen loss of farmland, nitrogen inputs, residual nitrogen in soil, and incomes of farmland. Economic benefits and environment benefits are both appropriate, if the area of rice-garlic system would be reduced to 53% and the area of rice-fava bean system increased to 36% of total cropping area in the investigated watershed. Adjustment of planting structure and introduction of reasonable rotation systems is considered an effective measure of controlling agricultural non-point pollution in watersheds of Erhai Lake.

The pine wood nematode (PWN), Bursaphelenchus xylophilus, is the pathogen of pine wilt disease (PWD) and causes huge economic losses in pine forests and shows a remarkable ability to survive under unfavorable and changing environmental conditions. This ability may be related to autophagy, which is still poorly understood in B. xylophilus. Our previous studies showed that autophagy exists in PWN. Therefore, we tested the effects of autophagy inducer rapamycin on PWN and the results revealed that the feeding rate and reproduction were significantly promoted on fungal mats. The gene expression patterns of BxATG1 and BxATG8 under the different stress were determined by quantitative reverse transcription PCR (qRT-PCR). We tested the effects of RNA interference on BxATG1 and BxATG8 in PWN during different periods of infection in Pinus thunbergii. The results revealed that BxATG1 and BxATG8 may play roles in allowing PWN to adapt to changing environmental conditions and the virulence of PWN was influenced by the silence of autophagy-related genes BxATG1 and BxATG8. These results provided fundamental information on the relationship between autophagy and PWN, and on better understanding of gene function of BxATG1 and BxATG8 in PWN.

For females, menarche is a most significant physiological event. Age at menarche (AAM) is a trait with high genetic determination and is associated with major complex diseases in women. However, specific genes for AAM variation are largely unknown. To identify genetic factors underlying AAM variation, a genome-wide association study (GWAS) examining about 380,000 SNPs was conducted in 477 Caucasian women. A follow-up replication study was performed to validate our major GWAS findings using two independent Caucasian cohorts with 854 siblings and 762 unrelated subjects, respectively, and one Chinese cohort of 1,387 unrelated subjects--all females. Our GWAS identified a novel gene, SPOCK (Sparc/Osteonectin, CWCV, and Kazal-like domains proteoglycan), which had seven SNPs associated with AAM with genome-wide false discovery rate (FDR) q

BACKGROUND: Growth differentiation factor 15 (GDF-15) has been explored as a potential biomarker for various inflammatory diseases and cardiovascular events. This study aimed to assess the predictive role of GDF-15 levels in cardiovascular events and all-cause mortality, considering traditional risk factors and other biomarkers. METHODS: A prospective study was conducted and 3699 patients with stable coronary artery disease (CAD) were enrolled into the research. Baseline GDF-15 levels were measured. Median follow-up was 3.1 years during the study. We analyzed clinical variables and several biomarkers. Multivariable Cox regression analysis was performed to evaluate prognostic performance of GDF-15 levels in predicting myocardial infarction (MI), heart failure, stroke, cardiovascular death, and non-cardiovascular death. RESULTS: Baseline GDF-15 levels for 3699 patients were grouped by quartile (= 1153, 1153-1888, 1888-3043, > 3043 ng/L). Higher GDF-15 levels were associated with older age, male gender, history of hypertension, and elevated levels of N-terminal pro Btype natriuretic peptide (NT-pro BNP), soluble suppression of tumorigenesis-2 (sST2), and creatine (each with P < 0.001). Adjusting for established risk factors and biomarkers in Cox proportional hazards models, a 1 standard deviation (SD) increase in GDF- 15 was associated with elevated risk of clinical events [hazard ratio (HR) = 2.18, 95% confidence interval (CI): (1.52-3.11)], including: MI [HR = 2.83 95% CI: (1.03-7.74)], heart failure [HR = 2.71 95% CI: (1.18-6.23)], cardiovascular and non-cardiovascular death [HR = 2.48, 95% CI (1.49-4.11)] during the median follow up of 3.1 years. CONCLUSIONS: Higher levels of GDF-15 consistently provides prognostic information for cardiovascular events and all cause death, independent of clinical risk factors and other biomarkers. GDF-15 could be considered as a valuable addition to future risk prediction model in secondary prevention for predicting clinical events in patient with stable CAD. [ABSTRACT FROM AUTHOR]

Chemotherapy can significantly reduce follicle counts in ovarian tissues and damage ovarian stroma, causing endocrine disorder, reproductive dysfunction, and primary ovarian insufficiency (POI). Recent studies have suggested that extracellular vesicles (EVs) secreted from mesenchymal stem cells (MSCs) exert therapeutic effects in various degenerative diseases. In this study, transplantation of EVs from human induced pluripotent stem cell-derived MSCs (iPSC-MSC-EVs) resulted in significant restoration of ovarian follicle numbers, improved granulosa cell proliferation, and inhibition of apoptosis in chemotherapy-damaged granulosa cells, cultured ovaries, and in vivo ovaries in mice. Mechanistically, treatment with iPSC-MSC-EVs resulted in up-regulation of the integrinlinked kinase (ILK) -PI3K/AKT pathway, which is suppressed during chemotherapy, most likely through the transfer of regulatory microRNAs (miRNAs) targeting ILK pathway genes. This work provides a framework for the development of advanced therapeutics to ameliorate ovarian damage and POI in female chemotherapy patients. [ABSTRACT FROM AUTHOR]