Simulations of the dust cycle and its interactions with the changing Earth system are hindered by the empirical nature of dust emission parameterizations in weather and climate models. Here we take a ...step towards improving dust cycle simulations by using a combination of theory and numerical simulations to derive a physically based dust emission parameterization. Our parameterization is straightforward to implement into large-scale models, as it depends only on the wind friction velocity and the soil's threshold friction velocity. Moreover, it accounts for two processes missing from most existing parameterizations: a soil's increased ability to produce dust under saltation bombardment as it becomes more erodible, and the increased scaling of the dust flux with wind speed as a soil becomes less erodible. Our treatment of both these processes is supported by a compilation of quality-controlled vertical dust flux measurements. Furthermore, our scheme reproduces this measurement compilation with substantially less error than the existing dust flux parameterizations we were able to compare against. A critical insight from both our theory and the measurement compilation is that dust fluxes are substantially more sensitive to the soil's threshold friction velocity than most current schemes account for.
The recovery of the stratospheric ozone layer relies on the continued decline in the atmospheric concentrations of ozone-depleting gases such as chlorofluorocarbons
. The atmospheric concentration of ...trichlorofluoromethane (CFC-11), the second-most abundant chlorofluorocarbon, has declined substantially since the mid-1990s
. A recently reported slowdown in the decline of the atmospheric concentration of CFC-11 after 2012, however, suggests that global emissions have increased
. A concurrent increase in CFC-11 emissions from eastern Asia contributes to the global emission increase, but the location and magnitude of this regional source are unknown
. Here, using high-frequency atmospheric observations from Gosan, South Korea, and Hateruma, Japan, together with global monitoring data and atmospheric chemical transport model simulations, we investigate regional CFC-11 emissions from eastern Asia. We show that emissions from eastern mainland China are 7.0 ± 3.0 (±1 standard deviation) gigagrams per year higher in 2014-2017 than in 2008-2012, and that the increase in emissions arises primarily around the northeastern provinces of Shandong and Hebei. This increase accounts for a substantial fraction (at least 40 to 60 per cent) of the global rise in CFC-11 emissions. We find no evidence for a significant increase in CFC-11 emissions from any other eastern Asian countries or other regions of the world where there are available data for the detection of regional emissions. The attribution of any remaining fraction of the global CFC-11 emission rise to other regions is limited by the sparsity of long-term measurements of sufficient frequency near potentially emissive regions. Several considerations suggest that the increase in CFC-11 emissions from eastern mainland China is likely to be the result of new production and use, which is inconsistent with the Montreal Protocol agreement to phase out global chlorofluorocarbon production by 2010.
The objective of this study was to evaluate the evidence on whether childhood obesity is a risk factor for adult disease, independent of adult body mass index (BMI). Ovid MEDLINE (1948–May 2011), ...EMBASE (1980–2011 week 18) and the Cochrane Library (1990–2011) were searched for published studies of BMI from directly measured weight and height in childhood (2–19 years) and disease outcomes in adulthood. Data were synthesized in a narrative fashion. Thirty‐nine studies (n 181–1.1 million) were included in the review. There was evidence for associations between childhood BMI and type 2 diabetes, hypertension and coronary heart disease. Few studies examined associations independent of adult BMI; these showed that effect sizes were attenuated after adjustment for adult BMI in standard regression analyses. Although there is a consistent body of evidence for associations between childhood BMI and cardiovascular outcomes, there is a lack of evidence for effects independent of adult BMI. Studies have attempted to examine independent effects using standard adjustment for adult BMI, which is subject to over‐adjustment and problems with interpretation. Studies that use more robust designs and analytical techniques are needed to establish whether childhood obesity is an independent risk factor for adult disease.
Micro (mi)RNAs are small, highly conserved noncoding RNAs that control gene expression post-transcriptionally either via the degradation of target mRNAs or the inhibition of protein translation. Each ...miRNA is believed to regulate the expression of multiple mRNA targets, and many miRNAs have been linked to the initiation and progression of human cancer. miRNAs control various activities of the immune system and different stages of hematopoietic development, and their misexpression is the cause of various blood malignancies. Certain miRNAs have oncogenic activities, whereas others have the potential to act as tumor suppressors. Because they control fundamental processes such as differentiation, cell growth and cell death, the study of the role of miRNAs in human neoplasms holds great promise for novel forms of therapy. Here, we summarize the role of miRNAs and their targets in contributing to human cancers and their function as regulators of apoptotic pathways and the immune system.
Aim
Nonalcoholic hepatic fat accumulation has been hypothesized to be associated with alterations in gut microbiota composition, although mechanistic explanations for this link are largely ...insufficient. The aim of this study was to elucidate the microbiota‐driven mechanisms involved in the development of nonalcoholic hepatic steatosis.
Methods and Results
Ob/ob mice and their wild‐type lean control mice were fed an AIN‐93G diet for 12 weeks. Faecal microbiota composition, faecal bile acid (BA) profile and intestinal and hepatic markers of BA metabolism were analysed. Ob/ob mice had significantly less faecal taurine‐conjugated BAs compared to their lean controls. The proportions of butyrate‐producing bacteria were lower in ob/ob mice compared to those in lean mice. Intestinal expression of farnesoid X receptor (FXR) mRNA was significantly higher, whereas hepatic expression of cholesterol‐7α‐hydroxylase 1 (CYP7A1) and small heterodimer partner (SHP) were significantly lower in ob/ob mice compared to those in control mice.
Conclusion
Microbiota‐associated BAs deconjugation may induce nonalcoholic fatty liver disease (NAFLD) by activating intestinal FXR signalling and blocking hepatic FXR‐SHP pathway, thereby accelerating fat synthesis.
Significance and Impact of the Study
We provided evidences that changes in the gut microbiota and their metabolites can alter the profile of BAs, thereby providing a mechanism by which an altered microbiota profile contributes to the development of NAFLD.
BACKGROUND AND PURPOSE
Ginsenosides are the main constituents for the pharmacological effects of Panax ginseng. Such effects of ginsenosides including cardioprotective and anti‐platelet activities ...have shown stability and bioavailability limitations. However, information on the anti‐platelet activity of ginsenoside‐Rp1 (G‐Rp1), a stable derivative of ginsenoside‐Rg3, is scarce. We examined the ability of G‐Rp1 to modulate agonist‐induced platelet activation.
EXPERIMENTAL APPROACH
G‐Rp1 in vitro and ex vivo effects on agonist‐induced platelet‐aggregation, granule‐secretion, Ca2+i mobilization, integrin‐αIIbβ3 activation were examined. Vasodilator‐stimulated phosphoprotein (VASP) and MAPK expressions and levels of tyrosine phosphorylation of the glycoprotein VI (GPVI) signalling pathway components were also studied. G‐Rp1 effects on arteriovenous shunt thrombus formation in rats or tail bleeding time and ex vivo coagulation time in mice were determined.
KEY RESULT
G‐Rp1 markedly inhibited platelet aggregation induced by collagen, thrombin or ADP. While G‐Rp1 elevated cAMP levels, it dose‐dependently suppressed collagen‐induced ATP‐release, thromboxane secretion, p‐selectin expression, Ca2+i mobilization and αIIbβ3 activation and attenuated p38MAPK and ERK2 activation. Furthermore, G‐Rp1 inhibited tyrosine phosphorylation of multiple components (Fyn, Lyn, Syk, LAT, PI3K and PLCγ2) of the GPVI signalling pathway. G‐Rp1 inhibited in vivo thrombus formation and ex vivo platelet aggregation and ATP secretion without affecting tail bleeding time and coagulation time, respectively.
CONCLUSION AND IMPLICATIONS
G‐Rp1 inhibits collagen‐induced platelet activation and thrombus formation through modulation of early GPVI signalling events, and this effect involves VASP stimulation, and ERK2 and p38‐MAPK inhibition. These data suggest that G‐Rp1 may have therapeutic potential for the treatment of cardiovascular diseases involving aberrant platelet activation.
The levels of nitrate in 52 drinking water wells in rural Central Java, Indonesia were evaluated in April 2014, and the results were used for a health risk assessment for the local populations by ...using probabilistic techniques. The concentrations of nitrate in drinking water had a range of 0.01–84 mg/L, a mean of 20 mg/L and a medium of 14 mg/L. Only two of the 52 samples exceeded the WHO guideline values of 50 mg/L for infant methaemoglobinaemia. The hazard quotient values as evaluated against the WHO guideline value at the 50 and 95 percentile points were HQ50 at 0.42 and HQ95 at 1.2, respectively. These indicated a low risk of infant methaemoglobinaemia for the whole population, but some risk for the sensitive portion of the population. The HQ50 and HQ95 values based on WHO acceptable daily intake dose for adult male and female were 0.35 and 1.0, respectively, indicating a generally a low level of risk. A risk characterisation linking birth defects to nitrate levels in water consumed during the first three months of pregnancy resulted in a HQ50/50 values of 1.5 and a HQ95/5 value of 65. These HQ values indicated an elevated risk for birth defects, in particular for the more sensitive population. A sanitation improvement program in the study area had a positive effect in reducing nitrate levels in wells and the corresponding risk for public health. For example, the birth defect HQ50/50 values for a subset of wells surveyed in both 2014 and 2015 was reduced from 1.1 to 0.71.
Probabilistic risk assessment was used to predict health effects of nitrate in Indonesia groundwaters and demonstrates the potential of improved sanitation to reduce the incidence of associated health effects.
Background and purpose
We analyzed the incidence and causes of oral anticoagulant (OAC) cessation and subsequent stroke after OAC withdrawal in a cohort of Korean stroke patients with atrial ...fibrillation.
Methods
The Korean Atrial Fibrillation Evaluation Registry in Ischemic Stroke patients (K‐ATTENTION) is a multicenter cohort study, merging stroke registries from 11 tertiary centers in Korea. The number of OAC interruption episodes and the reasons were reviewed from hospital records. Stroke after OAC withdrawal was defined when a patient experienced ischaemic stroke within 31 days after OAC withdrawal. Clinical variables were compared between patients who experienced stroke recurrence during OAC interruption and those who did not experience recurrence.
Results
Among 3213 stroke patients with atrial fibrillation, a total of 329 episodes of OAC interruption were detected in 229 patients after index stroke (mean age 72.9 ± 8.3 years, 113 female patients). The most frequent reason for OAC withdrawal was poor compliance 103 episodes (31.3%) followed by extracranial bleeding 96 episodes (29.2%). Stroke after OAC withdrawal was noted in 13 patients. Mean age, vascular risk factor profile and mean CHA2DS2‐VASc score were not significantly different between patients with and without recurrent stroke.
Conclusions
A considerable number of stroke patients with atrial fibrillation experienced temporary interruption of OAC after index stroke, which was associated with stroke recurrence of 4.0 cases per 100 interruption episodes.
Background and purpose
The prognostic value of contrast accumulation from non‐contrast brain computed tomography taken immediately after endovascular reperfusion treatment in acute ischaemic stroke ...patients to predict symptomatic hemorrhage was studied.
Methods
Between July 2007 and August 2014, acute anterior circulation ischaemic stroke patients who were treated by intra‐arterial thrombolysis or thrombectomy were included. Contrast accumulation was defined as a high attenuation area from non‐contrast brain computed tomography immediately taken after endovascular reperfusion treatment, and patients were categorized into three groups according to the presence and location of contrast: (i) negative, (ii) cortical involvement and (iii) non‐cortical involvement. The rates of symptomatic hemorrhage after 24 h and functional outcome at discharge were compared between patients with and without cortical involvement.
Results
Of 64 patients who were treated by endovascular intervention, contrast accumulation was detected in 56, including 33 patients with cortical involvement and 23 patients without cortical involvement. The cortical involvement pattern was more frequently associated with symptomatic hemorrhage (13 vs. 1 patient, P = 0.003) and with grave outcome at discharge with modified Rankin Scale 5 or 6 (14 vs. 4, P = 0.048) than the non‐cortical involvement group. Multivariate logistic regression analysis including initial collateral status and occlusion site disclosed that cortical involvement pattern independently predicted symptomatic hemorrhage after endovascular treatment (odds ratio 19.0, confidence interval 1.6–227.6, P = 0.020).
Conclusion
Our study provides evidence that the cortical involvement of contrast accumulation is associated with symptomatic hemorrhage after endovascular reperfusion treatment.
Summary Objective The objectives were to investigate the in vivo effects of treatment with rebamipide on pain severity and cartilage degeneration in an experimental model of rat osteoarthritis (OA) ...and to explore its mode of action. Materials and methods OA was induced in rats by intra-articular injection of monosodium iodoacetate (MIA). Oral administration of rebamipide was initiated on the day of MIA injection, 3 or 7 days after. Limb nociception was assessed by measuring the paw withdrawal latency and threshold. We analyzed the samples macroscopically and histomorphologically, and used immunohistochemistry to investigate the expression of matrix metalloproteinase-13 (MMP-13), interleukin-1β (IL-1β), hypoxia-inducible factor-2α (HIF-2α), inducible nitric oxide synthase (iNOS), and nitrotyrosine in knee joints. Real-time quantitative reverse transcription–polymerase chain reaction was used to quantify the mRNA for catabolic and anticatabolic factors in human OA chondrocytes. Results Rebamipide showed an antinociceptive property and attenuated cartilage degeneration. Rebamipide reduced the expression of MMP-13, IL-1β, HIF-2α, iNOS, and nitrotyrosine in OA cartilage in a dose-dependent manner. Nitrotyrosine expression in the subchondral bone region was decreased in the rebamipide-treated joints. mRNA expression of MMP-1, -3, and -13, and ADAMTS5 was attenuated in IL-1β-stimulated human OA chondrocytes. By contrast, rebamipide induced the mRNA expression of tissue inhibitor of metalloproteinase-1 and -3. Conclusion The results show the inhibitory effects of rebamipide on pain production and cartilage degeneration in experimentally induced OA. The suppression of oxidative damage and the restoration of extracellular matrix homeostasis of articular chondrocyte suggest that rebamipide is a potential therapeutic strategy for OA.
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