Currently, major concerns about the safety and efficacy of RNA interference (RNAi)-based bone anabolic strategies still exist because of the lack of direct osteoblast-specific delivery systems for ...osteogenic siRNAs. Here we screened the aptamer CH6 by cell-SELEX, specifically targeting both rat and human osteoblasts, and then we developed CH6 aptamer-functionalized lipid nanoparticles (LNPs) encapsulating osteogenic pleckstrin homology domain-containing family O member 1 (Plekho1) siRNA (CH6-LNPs-siRNA). Our results showed that CH6 facilitated in vitro osteoblast-selective uptake of Plekho1 siRNA, mainly via macropinocytosis, and boosted in vivo osteoblast-specific Plekho1 gene silencing, which promoted bone formation, improved bone microarchitecture, increased bone mass and enhanced mechanical properties in both osteopenic and healthy rodents. These results indicate that osteoblast-specific aptamer-functionalized LNPs could act as a new RNAi-based bone anabolic strategy, advancing the targeted delivery selectivity of osteogenic siRNAs from the tissue level to the cellular level.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, UILJ, UKNU, UL, UM, UPUK
The impact of extreme heat on crop yields is an increasingly pressing issue given anthropogenic climate warming. However, some of the physical mechanisms involved in these impacts remain unclear, ...impeding adaptation-relevant insight and reliable projections of future climate impacts on crops. Here, using a multiple regression model based on observational data, we show that while extreme dry heat steeply reduced U.S. corn and soy yields, humid heat extremes had insignificant impacts and even boosted yields in some areas, despite having comparably high dry-bulb temperatures as their dry heat counterparts. This result suggests that conflating dry and humid heat extremes may lead to underestimated crop yield sensitivities to extreme dry heat. Rainfall tends to precede humid but not dry heat extremes, suggesting that multivariate weather sequences play a role in these crop responses. Our results provide evidence that extreme heat in recent years primarily affected yields by inducing moisture stress, and that the conflation of humid and dry heat extremes may lead to inaccuracy in projecting crop yield responses to warming and changing humidity.
This paper presents experimental investigations on influence of different coolant strategies such as dry, wet, minimum quantity lubrication (MQL) and MQL with cooling air on performance in milling of ...the Ti–6Al–4V alloy with uncoated cemented carbide inserts. Cutting force, tool wear, surface roughness and chip morphology are experimentally studied to compare the effects of different cooling air temperatures. The results showed that minimum quantity lubrication (MQL) with cooling air significantly reduces cutting force, tool wear and surface roughness. Unfortunately, MQL (without cooling air) condition cannot produce evident effect on cutting performance, and flaking wear on the flank surface of the insert has been found under this condition. Four different cooling air temperatures are used to investigate the effects of cooling air temperature on the machinability characteristics of Ti–6Al–4V alloy. Based on the experimental results, MQL with cooling air of −15
°C provides more favourable effects compared to other cooling air temperatures (0
°C, −30
°C,−45
°C). Short chips are produced under MQL with cooling air conditions due to the high velocity of cooling air enhances the chip brittleness for easy chip breaking, and the effective penetration of lubricant to the chip–tool interface results in lower friction. However, due to the dramatic increase in chip hardness at lower temperature, MQL with cooling air environments cannot promote chip curl to some extent.
We report on the observation of the accreting pulsar GRO J1008-57 performed by Insight-Hard X-ray Modulation Telescope (HXMT) at the peak of the source's 2017 outburst. Pulsations are detected with a ...spin period of 93.283(1) s. The pulse profile shows double peaks at soft X-rays, and only one peak above 20 keV. The spectrum is well described by the phenomenological models of X-ray pulsars. A cyclotron resonant scattering feature (CRSF) is detected with very high statistical significance at a centroid energy of keV, for the reference continuum and line models, HIGHECUT and GABS, respectively. Detection is very robust with respect to different continuum models. The line energy is significantly higher than what is suggested from previous observations, which provided very marginal evidence for the line. This establishes a new record for the centroid energy of a fundamental CRSF observed in accreting pulsars. We also discuss the accretion regime of the source during the Insight-HXMT observation.
Using first-principles methods, we investigated the reaction pathways of the formic acid oxidation on Pd(111) and PdAu(111) surfaces. The dehydrogenation of formic acid can simultaneously occur via ...C–H and O–H activation on different Pd ensembles. However, on the contiguous ensembles without threefold Pd hollow, the reaction of COOH → CO + OH proceeds with a high activation energy (∼1.00 eV), and the direct pathway is predominant for H production from formic acid. Our results indicates that the proper arrangement of Au and Pd sites can significantly improve electrocatalytic activity of PdAu catalyst for formic acid oxidation attributed to the reduction of poisoning species of COad.
► First-principles calculations and NEB simulations for HCOOH's decomposition on PdAu(111) surfaces. ► Ensemble effects on formic acid oxidation on Pd-decorated Au(111) surface. ► H production from formic acid through the direct pathway on Pd-decorated Au(111) surface.
Hidradenitis suppurativa (HS) is a chronic inflammatory disorder characterized by painful nodules, sinus tracts, and scars occurring predominantly in intertriginous regions. The prevalence of HS is ...currently 0.053-4%, with a predominance in African-American women and has been linked to low socioeconomic status. The majority of the reported literature is retrospective, population based, epidemiologic studies. In this regard, there is a need to establish a repository of biospecimens, which represent appropriate gender and racial demographics amongst HS patients. These efforts will diminish knowledge gaps in understanding the disease pathophysiology. Hence, we sought to outline a step-by-step protocol detailing how we established our HS biobank to facilitate the formation of other HS tissue banks. Equipping researchers with carefully detailed processes for collection of HS specimens would accelerate the accumulation of well-organized human biological material. Over time, the scientific community will have access to a broad range of HS tissue biospecimens, ultimately leading to more rigorous basic and translational research. Moreover, an improved understanding of the pathophysiology is necessary for the discovery of novel therapies for this debilitating disease. We aim to provide high impact translational research methodology for cutaneous biology research and foster multidisciplinary collaboration and advancement of our understanding of cutaneous diseases.
Here we report the first study of the effect of thermochemical sulphate reduction (TSR) on the hydrogen isotopes of natural gas. Variably sour (H2S-bearing) and very dry (>97% methane) gas samples ...from Lower Triassic, Permian and Carboniferous marine carbonate reservoirs in the Sichuan Basin, China, have been analysed. All gases seem to have been sourced from mature marine kerogen and contain H2S that resulted from TSR. The Carboniferous samples are largely unaffected by TSR and were used to assess the effects of normal thermal maturation processes on the carbon and hydrogen isotopes of methane and ethane as a function of gas dryness (a proxy for thermal maturity). Maturation led to heavier carbon isotopes of methane and ethane and hydrogen isotopes of ethane; in contrast methane hydrogen isotopes seem to have little systematic variation with increasing maturity. TSR did not have a systematic effect on the hydrogen isotopes of methane, although the spread of values diminished (ending up at a constant −120‰) as TSR proceeded. This was possibly due to the partial thermochemical sulphate reduction of ethane adding isotopically light methane and thus offsetting the Rayleigh fractionation effects of TSR of methane. In contrast, hydrogen isotopes of ethane became much heavier as TSR proceeded, to values greater than those for samples only influenced by maturation. Under some circumstances, the effects of TSR can be identified and discerned from the effects of normal thermal maturation by plotting the difference between the carbon isotope compositions of methane and ethane and the difference between the hydrogen isotope compositions of methane and ethane.
Controlling and guiding elastic waves in solids is more complicated compared with electromagnetic and acoustic waves; design and fabrication of an elastic wave cloak with non-singular, homogeneous, ...and isotropic material parameters is a challenging task. Recent studies in the literature that focus on manipulating flexural waves in elastic thin plates mainly use a linear transformation with a linear radial-dependent mapping function, which has drawbacks of being narrowly banded or even having negative cloaking efficiency that results from singular material parameters on the internal boundary of the cloak. This paper presents a theory of nonlinear transformation-based flexural waves and derives the nonlinear ray-tracing equation for flexural waves. A broadband cylindrical cloak for flexural waves in an elastic thin plate is realized based on a nonlinear transformation, whose materials can be simplified as layered non-singular, homogeneous, and isotropic materials using an effective medium theory. Some advantages and improvements of the invisibility nonlinear-transformation cloak are analyzed by comparison with the linear-transformation cloak. The invisibility capability of the nonlinear-transformation cloak can be tuned by adjusting an impact parameter that is shown to have influence on flexural wave energy emitting into the region inside the cloak. Numerical simulations show that the nonlinear-transformation cloak is more effective for guiding flexural waves that propagate in the region outside the cloak than the linear-transformation cloak in a broad frequency range. They also show that the nonlinear-transformation cloak can accurately control ray tracing of different types of flexural waves under disturbances outside the cloak. The methodology developed here can be used to construct nonlinear-transformation cloaks for other types of waves.
•A nonlinear-transformation cloak is proposed to control flexural wave propagation.•A nonlinear ray trajectory equation is derived to construct a cylindrical cloak.•Two parameters are introduced to adjust efficiency of the cylindrical cloak.•Qualities of the invisibility nonlinear-transformation cloak were analyzed.•Control of flexural waves under disturbances outside the cloak is confirmed.
Summary Objective The International Hip Outcome Tool (iHOT-33) is a questionnaire designed for young, active patients with hip disorders. It has proven to be a highly reliable and valid ...questionnaire. The main purpose of our study was to adapt the iHOT-33 questionnaire into simplified Chinese and to assess its psychometric properties in Chinese patients. Method The iHOT-33 was cross culturally adapted into Chinese and 138 patients completed the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the EuroQol-5D (EQ-5D), and the Chinese version of the iHOT-33(SC-iHOT-33) pre- or postoperatively within 6 months’ follow-up. The Cronbach’s alpha, intraclass correlation coefficient (ICC), Pearson’s correlation coefficient (r), effect size (ES), and standardized response mean (SRM) were calculated to assess the reliability, validity, and responsiveness of the SC- iHOT-33, respectively. Results Total Cronbach’s alpha was 0.965, which represented excellent internal consistency of the SC-iHOT-33. The ICC ranges from 0.866 to 0.929, which shows excellent test–retest reliability. The subscales of SC-iHOT-33 had the highest correlation coefficient (r = 0.812) with the physical function subscales of the WOMAC, as well as good correlation between the social/emotional subscale of the SC-iHOT-33 and the EQ-5D (r = 0.740, r = 0.743). No floor or ceiling effects were found. The ES and SRM values indicated good responsiveness of 2.44 and 2.67, respectively. Conclusion The SC-iHOT-33 questionnaire is reliable, valid, and responsive for the evaluation of young, Chinese, active patients with hip disorders.
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