Irrigated rice in China accounts for nearly 30% of global rice production and about 7% of global nitrogen (N) consumption. The low agronomic N use efficiency (AE
N, kg grain yield increase per kg N ...applied) of this system has become a threat to the environment. The objective of this study was to determine the possibility to improve the AE
N of irrigated rice in China by comparing the farmers’ N-fertilizer practices with other N management strategies such as real-time N management (RTNM) and fixed-time adjustable-dose N management (FTNM). Field experiments were conducted in farmers’ fields in four major rice-growing provinces in China in 2001 and 2002. The same experiment was repeated at the International Rice Research Institute (IRRI) farm in the dry seasons of 2002 and 2003. Agronomic N use efficiency was determined by the “difference method” using an N-omission plot. Maximum yield was achieved mostly at 60–120
kg
N
ha
−1, which was significantly lower than the 180–240
kg
N
ha
−1 applied in farmers’ practices at the Chinese sites. With the modified farmers’ fertilizer practice, a 30% reduction in total N rate during the early vegetative stage did not reduce yield but slightly increased yield and doubled AE
N compared with the farmers’ practice at the Chinese sites. The total N rate in RTNM and FTNM ranged from 30 to 120
kg
ha
−1 at the Chinese sites, but their yields were similar to or higher than that of the farmers’ practice. Compared with the modified farmers’ practice, RTNM and FTNM further increased AE
N at the Chinese sites. Overall, FTNM performed better than RTNM at the Chinese sites because the total N rate of FTNM was closer to the optimal level than RTNM. A quantum leap in AE
N is possible in the intensive rice-growing areas in China by simply reducing the current N rate and by allocating less N at the early vegetative stage.
Pulsatile blood pressure (BP) confers cardiovascular risk. Whether associations of cardiovascular end points are tighter for central systolic BP (cSBP) than peripheral systolic BP (pSBP) or central ...pulse pressure (cPP) than peripheral pulse pressure (pPP) is uncertain. Among 5608 participants (54.1% women; mean age, 54.2 years) enrolled in nine studies, median follow-up was 4.1 years. cSBP and cPP, estimated tonometrically from the radial waveform, averaged 123.7 and 42.5 mm Hg, and pSBP and pPP 134.1 and 53.9 mm Hg. The primary composite cardiovascular end point occurred in 255 participants (4.5%). Across fourths of the cPP distribution, rates increased exponentially (4.1, 5.0, 7.3, and 22.0 per 1000 person-years) with comparable estimates for cSBP, pSBP, and pPP. The multivariable-adjusted hazard ratios, expressing the risk per 1-SD increment in BP, were 1.50 (95% CI, 1.33–1.70) for cSBP, 1.36 (95% CI, 1.19–1.54) for cPP, 1.49 (95% CI, 1.33–1.67) for pSBP, and 1.34 (95% CI, 1.19–1.51) for pPP (P<0.001). Further adjustment of cSBP and cPP, respectively, for pSBP and pPP, and vice versa, removed the significance of all hazard ratios. Adding cSBP, cPP, pSBP, pPP to a base model including covariables increased the model fit (P<0.001) with generalized R increments ranging from 0.37% to 0.74% but adding a second BP to a model including already one did not. Analyses of the secondary end points, including total mortality (204 deaths), coronary end points (109) and strokes (89), and various sensitivity analyses produced consistent results. In conclusion, associations of the primary and secondary end points with SBP and pulse pressure were not stronger if BP was measured centrally compared with peripherally.
Titanium alloy Ti-6Al-4V processed by electron beam melting (EBM) has a great potential for orthopedic and aerospace applications. However, the process induced porosity and microstructure anisotropy ...will have a significant impact on the material properties. This work has found that spherical and elongated pores with strong size effect are common characteristics for the as-EBM samples made with horizontal, diagonal, and vertical orientations w.r.t. the substrate. Furthermore, the major axis of the elongated pores is perpendicular to build direction for samples with different build orientations. The microstructure consists of columnar prior β grains delineated by grain boundary α and transformed α/β structures with α’ marteniste and basket weave morphology. Of note is that a high fraction of twin boundaries are prevalent in α (α’) phase. The configuration of the applied load w.r.t. the major axis of the elongated pores is the most significant influencing factor to mechanical properties, while the columnar prior β grain structure is secondary. Fractography reveals that microcracks tend to originate from elongated pores for cleavage fracture. In addition, the co-existing local terrace-like and shallow dimples are attributed to the intergranular crack propagation from the lamella α grain boundaries. Thus, the anisotropy of porosity and microstructure is of significance to enhance mechanical properties in process development.
IntroductionOver-the-scope clip (OTSC) has been used recently for primary haemostasis of peptic ulcers. This study aimed to compare the efficacy of OTSC to standard endoscopic therapy in primary ...treatment of patients with peptic ulcer bleeding that are of size ≥1.5 cm. The target population accounts for only 2.5% of all upper GI bleeders.MethodsThis was a multicentre international randomised controlled trial from July 2017 to October 2020. All patients with Forest IIa or above peptic ulcers of ≥1.5 cm were included. Primary outcome was 30-day clinical rebleeding. Secondary endpoints include 3-day all-cause mortality, transfusion requirement, hospital stay, technical and clinical success, and further interventions. 100 patients are needed to yield a power of 80% to detect a difference of −0.15 at the 0.05 significance level (alpha) using a two-sided Z-test (pooled).Results100 patients were recruited. Success in achieving primary haemostasis was achieved in 46/50 (92%) and 48/50 (96%) in the OTSC and conventional arm, respectively. Among patients who had success in primary haemostasis, 2/46 (4.35%) patients in the OTSC arm and 9/48 (18.75%) patients in the conventional arm developed 30-day rebleeding (p=0.03). However, in an intention-to-treat analysis, there was no difference in rebleeding within 30 days (5/50 (10%) OTSC vs 9/50 (18%) standard, p=0.23) or all-cause mortality (2/50 (4%) OTSC vs 4/50 (8%) standard, p=0.68; OR=2.09, 95% CI 0.37 to 11.95). There was also no difference in transfusion requirement, hospital stay, intensive care unit admission and further interventions.ConclusionThe routine use of OTSC as primary haemostasis in large bleeding peptic ulcers was not associated with a significant decrease in 30-day rebleeding.Trial registration number NCT03160911.
NK T cells are a unique subset of T cells that recognize lipid antigens presented by CD1d. After activation, NK T cells promptly produce large amounts of cytokines, which may modulate the upcoming ...immune responses. Previous studies have documented an association between decreased numbers of NK T cells and the progression of some autoimmune diseases, suggesting that NK T cells may control the development of autoimmune diseases. To investigate the role of NK T cells in autoimmune diabetes, we crossed CD1 knockout (CD1KO) mutation onto the nonobese diabetic (NOD) genetic background. We found that male CD1KO NOD mice exhibited significantly higher incidence and earlier onset of diabetes compared with the heterozygous controls. The diabetic frequencies in female mice showed a similar pattern; however, the differences were less profound between female CD1KO and control mice. Early treatment of NOD mice with alpha-galactosylceramide, a potent NK T cell activator, reduced the severity of autoimmune diabetes in a CD1-dependent manner. Our results not only suggest a protective role of CD1-restricted NK T cells in autoimmune diabetes but also reveal a causative link between the deficiency of NK T cells and the induction of insulin-dependent diabetes mellitus.
Chlorpyrifos (CPF), an organophosphate insecticide, has been linked to adverse neurodevelopmental effects in animal studies. However, little is known about long-term neurotoxicity of early-life CPF ...exposure in humans. We aimed to evaluate the associations of both prenatal and early childhood CPF exposure with neurodevelopment of children. In this observational study based on Sheyang Mini Birth Cohort, pregnant women were recruited from an agricultural region between June 2009 and January 2010, and their children were followed up from birth to age three. Urinary 3,5,6-Trichloro-2-pyridinol (TCPy), a specific metabolite of CPF, was quantified using large-volume-injection gas chromatography-tandem mass spectrometry. Developmental quotients (DQs) of children in motor, adaptive, language, and social areas were assessed by trained pediatricians. Data from 377 mother-child pairs were used in the current study. Associations between CPF exposure and neurodevelopmental indicators were estimated using generalized linear models with adjustment for potential confounders. The median concentrations of TCPy in maternal and children's urine were 5.39 μg/L and 5.34 μg/L, respectively. No statistically significant association was found between maternal urinary TCPy concentrations and children neurodevelopment. While for postnatal exposure, we found lower motor area DQ score 0.61 95% confidence interval (CI): −1.13, −0.09; p = 0.02 and social area DQ score 0.55 (95% CI: −1.07, −0.03; p = 0.04) per one-unit increase in the ln-transformed childhood urinary TCPy concentrations. Further stratification by sex indicated that the inverse associations were only observed in boys, but not in girls. Our findings suggest that adverse neurodevelopmental effects were associated with early childhood CPF exposure, but not prenatal exposure. Additional longitudinal studies are needed to replicate these results and to further understand the toxicological mechanisms of CPF.
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•Chlorpyrifos (CPF) is ubiquitous in maternal and children's urinary samples.•Adverse effects of postnatal CPF exposure on children's motor and social function were found.•No association was observed between prenatal CPF exposure and children's neurodevelopment.•Boys appeared to be more sensitive to neurotoxicity of CPF than girls.
Motor and social function of 3-year-old children were adversely associated with childhood rather than prenatal exposure to chlorpyrifos.
Hepatocellular carcinoma (HCC) is the third most common cause of death from cancer, with increasing prevalence worldwide. The mortality rate of HCC is similar to its incidence rate, which reflects ...its poor prognosis. At present, the diagnosis of HCC is still mostly dependent on invasive biopsy, imaging methods, and serum α-fetoprotein (AFP) testing. Because of the asymptomatic nature of early HCC, biopsy and imaging methods usually detect HCC at the middle-late stages. AFP has limited sensitivity and specificity, as many other nonmalignant liver diseases can also result in a very high serum level of AFP. Therefore, better biomarkers with higher sensitivity and specificity at earlier stages are greatly needed. Since metabolic reprogramming is an essential hallmark of cancer and the liver is the metabolic hub of living systems, it is useful to investigate HCC from a metabolic perspective. As a noninvasive and nondestructive approach, metabolomics provides holistic information on dynamically metabolic responses of living systems to both endogenous and exogenous factors. Therefore, it would be conducive to apply metabolomics in investigating HCC. In this review, we summarize recent metabolomic studies on HCC cellular, animal, and clinicopathologic models with attention to metabolomics as a biomarker in cancer diagnosis. Recent applications of metabolomics with respect to therapeutic and prognostic evaluation of HCC are also covered, with emphasis on the potential of treatment by drugs from natural products. In the last section, the current challenges and trends of future development of metabolomics on HCC are discussed. Overall, metabolomics provides us with novel insight into the diagnosis, prognosis, and therapeutic evaluation of HCC.
miR-30d has been observed to be significantly down-regulated in human anaplastic thyroid carcinoma (ATC), and is believed to be an important event in thyroid cell transformation. In this study, we ...found that miR-30d has a critical role in modulating sensitivity of ATC cells to cisplatin, a commonly used chemotherapeutic drug for treatment of this neoplasm. Using a mimic of miR-30d, we demonstrated that miR-30d could negatively regulate the expression of beclin 1, a key autophagy gene, leading to suppression of the cisplatin-activated autophagic response that protects ATC cells from apoptosis. A reporter gene assay demonstrated that the binding sequences of miR-30d in the beclin 1-3′ UTR was the region required for the inhibition of beclin 1 expression by this miRNA. We further showed that inhibition of the beclin 1-mediated autophagy by the miR-30d mimic sensitized ATC cells to cisplatin both in vitro (cell culture) and in vivo (animal xenograft model). These results suggest that dysregulation of miR-30d in ATC cells is responsible for the insensitivity to cisplatin by promoting autophagic survival. Thus, miR-30d may be exploited as a potential target for therapeutic intervention in the treatment of ATC.
Bisphenol A (BPA) exposure during early life may increase risk of childhood obesity, however, prospective evidence of birth cohort is limited and inconclusive. We aimed to explore the associations of ...maternal and childhood BPA exposure with child adiposity measures, including body mass index, waist circumference and skinfold thickness and waist to height ratio of children at 7 years. 430 mother-child pairs were examined from a population-based prospective cohort in a rural area of East China. BPA concentrations of spot urine samples were quantified in mothers and their children aged 3 and 7 years. Maternal urinary BPA concentration was significantly positively associated with waist circumference in children aged 7 years (β = 0.508 cm, 95% CI: 0.067, 0.950). These significant associations were not modified by child sex, but they were only observed among girls in sex-stratified analyses. Risk of central obesity related to prenatal BPA exposure was significantly higher in the second and the third tertile than those in the first tertile (odds ratio, OR = 2.510, 95% CI = 1.146, 5.499; OR = 2.584, 95% CI = 1.186, 5.631, respectively; p for trend = 0.022). The present findings suggested that prenatal exposure to BPA may enhance waist circumference of children and thereby increase risk of central obesity in school-age girls.
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•BPA exposure was ubiquitous in studied pregnant women and children.•Prenatal BPA exposure was associated with central obesity in school-age children.•Prenatal was vulnerable period for obesogenic effects of BPA exposure.•Girls were more susceptible to obesogenic effects of BPA exposure than boys.
Abstract
Aims
Cardiovascular side effects caused by non-steroidal anti-inflammatory drugs (NSAIDs), which all inhibit cyclooxygenase (COX)-2, have prevented development of new drugs that target ...prostaglandins to treat inflammation and cancer. Microsomal prostaglandin E synthase-1 (mPGES-1) inhibitors have efficacy in the NSAID arena but their cardiovascular safety is not known. Our previous work identified asymmetric dimethylarginine (ADMA), an inhibitor of endothelial nitric oxide synthase, as a potential biomarker of cardiovascular toxicity associated with blockade of COX-2. Here, we have used pharmacological tools and genetically modified mice to delineate mPGES-1 and COX-2 in the regulation of ADMA.
Methods and results
Inhibition of COX-2 but not mPGES-1 deletion resulted in increased plasma ADMA levels. mPGES-1 deletion but not COX-2 inhibition resulted in increased plasma prostacyclin levels. These differences were explained by distinct compartmentalization of COX-2 and mPGES-1 in the kidney. Data from prostanoid synthase/receptor knockout mice showed that the COX-2/ADMA axis is controlled by prostacyclin receptors (IP and PPARβ/δ) and the inhibitory PGE2 receptor EP4, but not other PGE2 receptors.
Conclusion
These data demonstrate that inhibition of mPGES-1 spares the renal COX-2/ADMA pathway and define mechanistically how COX-2 regulates ADMA.
Graphical Abstract
Graphical Abstract
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