A series of NENU-3 materials loaded with functional guests were rapidly synthesized by a mechanochemical method, which display remarkably increased proton conductivities.
This study documents the temporal and organ-specific effects of Igf1 gene deletion on postnatal growth patterns. Igf1−/− mice are 63 ± 4% the size of wildtype (wt) littermates at birth and this ratio persists through postnatal day 20 (P20). After P20, Igf1−/− mice virtually stop growing, while wt littermates double in size from P20 to P40, after which their growth markedly decelerates. As a result,' full-grown' Igf1−/− mice are less than one third the size of wt littermates. Igf1 gene deletion has disproportionate effects on organ growth. For example, at P10 and P40, Igf1−/− body weights are 63% and 31% of wt,respectively, while Igf1−/− lungs weigh only 34% and 22% of wt at these ages. In contrast, the Igf1−/−heart is disproportionately enlarged, representing ∼85% of wt at P10 and ∼56% at P40. Igf1−/− kidney, spleen and liver are slightly but significantly increased in size relative to the degree of reduction in Igf1−/− body weight. These data demonstrate that Igf1 has two major phases or modes of growth promotion. There is an early, growth hormone (GH)-independent Igf1 growth augmentation during perinatal development, responsible for about 35% of growth prior to P20. Then there are later effects due to GH-induced Igf1, which are responsible for increasing animal size by∼ 100% between P20 and 40. The fact that there is virtually no GH-induced growth in the Igf1−/− mice supports the view that Igf1 mediates GH's major effects on somatic growth. Finally, this study shows that Igf1−/− has discordant effects on pulmonary and cardiac growth parameters, with relative hypoplasia of Igf1−/−lungs and hypertrophy of Igf1−/− hearts.
Our study aimed to identify the appropriate evaluation time point and assessment forthe CSF tap test(TT) to predict the shunting responsiveness of patients with idiopathic normal-pressure hydrocephalus (iNPH). Eighty-eight inpatients with clinically possible iNPH who underwent CSF TT at multiple time points (baseline, 8 hours, 24 hours, and 72 hours after CSF TT) at Peking Union Medical College Hospital were recruited. The multidomain assessment included the timed up and go test(TUG), 10-meter walking tests, and a brief executive function battery. Performance in multidomain assessment at the indicated time points were compared. The positive response rate and cumulative positive rate of multidomain assessment at multiple time points were calculated. And their corresponding specificity and sensitivity of predicting shunting response were calculated according to the follow-up results after shunting. The multidomain assessment performance except TUG at 8 hours were significantly improved at each time point after CSF TT compared with baseline (P<0.01). Reduction more than 10% in the 10-meter walking time and number of steps at 24 hours showed the highest specificity (both 85.7%) and sensitivity (37.5% and 46.7%, respectively) for predicting shunting response. Additionally, an improvement of more than 20% in the composite z score at 72 hours showed 100% specificity and 80% sensitivity for predicting shunting response. Multiple time points and multidomain assessment were helpful to identify more shunting responders. Executive function evaluation might be a candidate tool to increase the effectiveness of CSF TT.
Soil moisture is a key variable that affects ecosystem carbon and water cycles and that can directly affect climate change. Remote sensing is the best way to obtain global soil moisture data. Currently, soil moisture remote sensing products have coarse spatial resolution, which limits their application in agriculture, the ecological environment, and urban planning. Soil moisture downscaling methods rely mainly on optical data. Affected by weather, the spatial discontinuity of optical data has a greater impact on the downscaling results. The synthetic aperture radar (SAR) backscatter coefficient is strongly correlated with soil moisture. This study was based on the Google Earth Engine (GEE) platform, which integrated Moderate-Resolution Imaging Spectroradiometer (MODIS) optical and SAR backscattering coefficients and used machine learning methods to downscale the soil moisture product, reducing the original soil moisture with a resolution of 10 km to 1 km and 100 m. The downscaling results were verified using in situ observation data from the Shandian River and Wudaoliang. The results show that in the two study areas, the downscaling results after adding SAR backscattering coefficients are better than before. In the Shandian River, the R increases from 0.28 to 0.42. In Wudaoliang, the R value increases from 0.54 to 0.70. The RMSE value is 0.03 (cm3/cm3). The downscaled soil moisture products play an important role in water resource management, natural disaster monitoring, ecological and environmental protection, and other fields. In the monitoring and management of natural disasters, such as droughts and floods, it can provide key information support for decision-makers and help formulate more effective emergency response plans. During droughts, affected areas can be identified in a timely manner, and the allocation and scheduling of water resources can be optimized, thereby reducing agricultural losses.
Tuberculosis (TB) is now the world's second deadliest infectious killer after COVID-19. Human-macrophages and their secreted exosomes play important roles in combating invading Mtb. However, the panoramic analysis of the underlying immune mechanism for the infected macrophages, package or secretion mechanism, and anti-TB effect of Mtb treated exosomes remain poorly understood. Here we conducted comprehensive analyses of the macrophages infected with avirulent and virulent Mtb (H37Ra & H37Rv) and their secreted exosomes, collected cells and corresponding exosomes for omics and phenotypic analysis. The results showed that avirulent Mtb stimulated robust immune-responses and apoptosis in macrophages to eliminate the invading Mtb; virulent Mtb induced severe necrosis and immune-escape for survival. The HMGB1 signaling pathway and TNFRSF1B plays important roles in the immune escape of virulent Mtb. Interestingly, our results suggest that macrophages kill Mtb in an IFN-γ independent but simulative way, highlighting the central role of IFN signaling pathway in anti-TB immune response. Moreover, we observed selective transport of host and Mtb RNAs from macrophages to exosomes. Notably, "H37Ra-treated exosomes" displayed a higher anti-TB effect than "H37Rv-treated exosomes" due to some enriched pro-inflammation and immune-escape related Mtb proteins in these two exosomes, respectively. Conclusively, our findings shed new light on the immune mechanism of macrophages in response to Mtb infection, offering a new TB-treatment strategy and some promising vaccine candidates.
Enantiomers have generally been reported mostly for racemic mixtures with a 1:1 ratio, as in that case there were weak Cotton effects in the ECD spectrum and negligible optical rotations. A furofuran lignan (sesamin), with a remarkable rotation and significant Cotton effects, was isolated from Juglans mandshurica Maxim. Subsequently, sesamin was resolved by chiral HPLC to afford a pair of enantiomers, (+)-sesamin (a) and (−)-sesamin (b), in a ratio of approximately 1:3. Their absolute configurations were determined by computational analysis of their electronic circular dichroism (ECD) spectrum. In addition, the pair of enantiomers were evaluated for the inhibition of self-induced Aβ aggregation. Interestingly, (+)-sesamin (a) (67.7%) and (−)-sesamin (b) (80.6%) exhibited different degrees of anti-Aβ aggregation activity. The different inhibition profiles were further explained by molecular dynamics and docking simulation study.
Ophiopogonis Radix, also known as "Maidong" (MD) in China, is frequently sulfur-fumigated (SF) in the pretreatment process of MD to improve the appearance and facilitate preservation. However, the process leads to changes in chemical composition, so it is essential to develop an approach to identify the chemical characteristics between nonfumigated and sulfur-fumigated products. This paper provided a practical method based on UPLC-QTOF-MS combined Global Natural Products Social Molecular Networking (GNPS) with multivariate statistical analysis for the characterization and discrimination of MD with different levels of sulfur fumigation, high concentration sulfur fumigation (HS), low concentration sulfur fumigation (LS) and without sulfur fumigation (WS). First, a number of 98 compounds were identified in those MD samples. Additionally, the results of Principal component analysis (PCA) and Orthogonal partial least-squares-discriminant analysis (OPLS-DA) demonstrated that there were significant chemical differences in the chemical composition of MD with different degrees of SF. Finally, fourteen and sixteen chemical markers were identified upon the comparison between HS and WS, LS and WS, respectively. Overall, these results can be able to discriminate MD with different levels of SF as well as establish a solid foundation for further quality control and pharmacological research.
Abstract Background Early nutritional programming affects a series of metabolism, growth and development in mammals. Fish also exhibit the developmental plasticity by early nutritional programming. However, little is known about the effect of early amino acid programming on growth and metabolism. Methods In the present study, zebrafish ( Danio rerio ) was used as the experimental animal to study whether early leucine stimulation can programmatically affect the mechanistic target of rapamycin (mTOR) signaling pathway, growth and metabolism in the later life, and to undercover the mechanism of epigenetic regulation. Zebrafish larvas at 3 days post hatching (dph) were raised with 1.0% leucine from 3 to 13 dph during the critical developmental stage, then back to normal water for 70 days (83 dph). Results The growth performance and crude protein content of zebrafish in the early leucine programming group were increased, and consistent with the activation of the mTOR signaling pathway and the high expression of genes involved in the metabolism of amino acid and glycolipid. Furthermore, we compared the DNA methylation profiles between the control and leucine-stimulated zebrafish, and found that the methylation levels of CG-differentially methylated regions (DMGs) and CHH-DMGs of genes involved in mTOR signaling pathway were different between the two groups. With quantitative PCR analysis, the decreased methylation levels of CG type of Growth factor receptor-bound protein 10 ( Grb10 ), eukaryotic translation initiation factor 4E ( eIF4E ) and mTOR genes of mTOR signaling pathway in the leucine programming group, might contribute to the enhanced gene expression. Conclusions The early leucine programming could improve the protein synthesis and growth, which might be attributed to the methylation of genes in mTOR pathway and the expression of genes involved in protein synthesis and glycolipid metabolism in zebrafish. These results could be beneficial for better understanding of the epigenetic regulatory mechanism of early nutritional programming.
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