Dual‐selective enrichment of phosphopeptides and glycopeptides of post‐translational modifications (PTMs) in the complex biological samples are challenging. In this work, considering the versatile ...properties including surface abundant metal sites and electrostatic attraction between Ti3C2‐layers and Al‐layers, layered ternary carbides Ti3AlC2 nanomaterials was successfully applied for the first time as an affinity adsorbent for the dual‐selective capture of phosphopeptides and glycopeptides. Especially, the Ti3AlC2 nanomaterials had an excellent detection sensitivity for phosphopeptides (1×10−11 M) and a good selectivity for glycopeptides with a low molar ratio of 1 : 500 of HRP (horseradish peroxidase) to BSA (bovine serum albumin). Furthermore, Ti3AlC2 nanomaterials was also applied for dual‐selective enrichment of phosphopeptides and glycopeptides from mouse brain neocortex lysate and human serum lysate respectively before mass spectrometry (MS) analysis, yielding twenty‐two unique phosphopeptides from thirteen phosphoproteins and fifty‐three unique glycopeptides from thirty‐seven glycoproteins, respectively. This work will open a new avenue and will greatly promote sample preparation for mass spectrometric analysis in phosphoproteomics and glycoproteomics research.
Ti3AlC2 nanomaterials was successfully applied for the first time as an affinity adsorbent for dual‐selective capture of phosphopeptides in acidic conditions and glycopeptides in weak acidic conditions. Compared with V2AlC nanomaterials, Ti3C2 nanosheets and V2C nanosheets, Ti3AlC2 exhibited best enrichment selectivity for phosphopeptides and showed a superior detection limit (1×10−11 M). Also, Ti3AlC2 showed an excellent selectivity for glycopeptides with a low molar ratio of 1 : 500 of HRP to BSA.
The morphology of TiCx nanoparticles is one of the most significant inherent factors that influence their comprehensive performances and extensional applications. However, the design of TiCx ...nanoparticles and their growth morphologies manipulating in the Al melt are always in challenges, while the stoichiometric ratios controlled synthesis will show a promising prospect. In this study, TiCx ceramic nanoparticles with different stoichiometric ratios (x = 0.5, 0.625, 0.75, 0.875 and 1.0) were fabricated successfully by combustion synthesis in Al-Ti-C reaction system. Based on the evaluation of nanosized TiCx specific exposed planes in the Al melt, the stoichiometric ratios manipulated the Al/TiCx interface performances, including interfacial stability, the nature of bonding and the interface electron transfer were analyzed via first-principle calculation. With the increasing stoichiometric ratios, the TiCx(100) exposed planes in the Al melt gradually stabilized and became exposed, while the TiCx(111) planes showed poor stability and gradually shrank and disappeared. The corresponding morphology will also evolve from octahedron to truncated-octahedron then spheroid with increasing x. Moreover, those interface performances can be selectively controlled by the stoichiometric ratio of TiCx nanoparticles. Finally, morphologies with specific exposed crystal planes in the Al melt can be effectively designed and manipulated for various applications.
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•TiCx nanoparticles with specific exposed surfaces were in-situ synthesized controllably in Al melt by combustion synthesis.•TiCx nanoparticles evolved from octahedrons, truncated-octahedrons to spheroids with the increasing of x from 0.5 to 1.0.•The morphology manipulating mechanism of TiCx nanoparticles was revealed by the first principle calculation of the Al/TiCx interface.•With x increasing, TiCx (100) in the Al melt gradually stabilized and exposed while (111) planes shrank and disappeared.
Solution heat treatment (SHT), immediately followed by water quenching, can significantly improve the strength of precipitation-hardenable metallic materials, but frequently compromises the ...well-defined dimensional design of the geometrically complex or thin-wall engineering components. Here, to avoid this catastrophic high-temperature scheme, we introduce an alternative conceptual strategy to design a novel hypoeutectic Al–10Si–Mg alloy especially for “as-cast” services, i.e., extraordinarily high Mg addition and trace co-incorporation of innovative in situ TiCN–TiB2 particles coupled with a direct post-solidification isothermal low-temperature stabilization treatment (LTST). The performance was carefully characterized by multi-scale characterization techniques. Solidification kinetics and the resultant microstructural arrangement response to the TiCN–TiB2 particle additions were systematically investigated. Results demonstrated that both α-Al dendrites and eutectic Si structures were substantially refined by the TiCN–TiB2 particles. In the absence of conventional SHT, the precipitation kinetics associated with the customized LTST was also thoroughly studied. Interestingly, an extremely fine dispersion and high number density of perfectly coherent GP zones and pre-β'' nanoprecipitates were found coexisting after LTST. As a result, well-combined strength and ductility were therefore achieved by the synergistic effects of trace TiCN–TiB2 particles and LTST in this Al–10Si-2.0 Mg system.
•In situ TiCN–TiB2 particles enabled significant microstructure refinement.•More highly supersaturated solid solutions were obtained by TiCN–TiB2 particles.•GP zones and pre-β'' coexisted after low-temperature stabilization treatment.•Excellent strength-ductility was yielded after direct thermal exposure at 150 °C.
Optogenetic techniques allow intracellular manipulation of Ca
by illumination of light-absorbing probe molecules such as channelrhodopsins and melanopsins. The consequences of optogenetic stimulation ...would optimally be recorded by non-invasive optical methods. However, most current optical methods for monitoring Ca
levels are based on fluorescence excitation that can cause unwanted stimulation of the optogenetic probe and other undesirable effects such as tissue autofluorescence. Luminescence is an alternate optical technology that avoids the problems associated with fluorescence. Using a new bright luciferase, we here develop a genetically encoded Ca
sensor that is ratiometric by virtue of bioluminescence resonance energy transfer (BRET). This sensor has a large dynamic range and partners optimally with optogenetic probes. Ca
fluxes that are elicited by brief pulses of light to cultured cells expressing melanopsin and to neurons-expressing channelrhodopsin are quantified and imaged with the BRET Ca
sensor in darkness, thereby avoiding undesirable consequences of fluorescence irradiation.
Slope failure in municipal solid waste (MSW) landfills is a common environmental disaster that poses serious ecological and health risks. Landfill slope stability (SS) is sensitive to leachate levels ...and gas pressure (GP) caused by the degradation of organic material, but the extent of these combined effects remains poorly understood. In this study, a simplified landfill GP calculation method is presented and a circular slide method that considers the combined effects of leachate and GP is established. The results show that the landfill GP is mainly affected by the gas production rate, gas conductivity of the solid waste (SW), and landfill depth. The safety factor of landfill SS is also significantly lower when GP is considered. The distribution of GP is affected by the depth of the failure circle and SW. Landfill slope instability can be explained by localized damage caused by GP breakthrough of the filled SW. This study probably provides important guidance for the design, operation, and management of MSW landfills.
A comprehensive investigation of the trace additions of in situ novel bimodal-sized (nano and submicron) TiB2 particles on the solidification behavior, microstructure and mechanical property ...evolution of Al–7Si–4Cu alloys were carried out through remelting and dilution-assisted ultrasonic vibration. The results showed that both the primary α-Al dendrites and eutectic Si structure were greatly refined in the presence of 0.7 wt% bimodal-sized TiB2 particles, with a reduction of 79.0% and 53.7% compared to the base alloy, which is far beyond the efficiency of micron-sized TiB2 particles. Additionally, the average diameter of the θ′ precipitates was greatly reduced by 32.7%. Thermal analysis revealed that the bimodal-sized TiB2 particles sharply shifted the nucleation temperature of primary α-Al from 600.7 °C to 607.1 °C; meanwhile, the corresponding recalescence undercooling decreased by 3.6 °C. More importantly, in contrast with the common dilemma of strength-ductility trade-off, the yield strength and elongation to fracture of the inoculated Al–7Si–4Cu alloy were simultaneously and significantly improved by 26.3% and 71.1%, respectively. In this work, the mechanisms of multiscale microstructure refinement and mechanical property enhancement by bimodal-sized TiB2 particles were systematically discussed.
•Bimodal-sized TiB2 particles were in situ synthesized.•α-Al, eutectic Si and θ′ phases were highly refined by bimodal-sized TiB2 particles.•Both the strength and elongation were enhanced by bimodal-sized TiB2 particles.
Photolyase is a blue-light-activated enzyme that repairs ultraviolet-induced DNA damage that occurs in the form of cyclobutane pyrimidine dimers (CPDs) and pyrimidine-pyrimidone (6-4) photoproducts. ...Previous studies on microbial photolyases have revealed an electrontunneling pathway that is critical for the repair mechanism. In this study, we used femtosecond spectroscopy to deconvolute seven electron-transfer reactions in 10 elementary steps in all classes of CPD photolyases. We report a unified electron-transfer pathway through a conserved structural configuration that bifurcates to favor direct tunneling in prokaryotes and a two-step hopping mechanism in eukaryotes. Both bifurcation routes are operative, but their relative contributions, dictated by the reduction potentials of the flavin cofactor and the substrate, determine the overall quantum yield of repair.
Hepatic osteodystrophy (HOD) is a metabolic bone disease that is often associated with chronic liver disease and is marked by bone loss. Here, we demonstrate that hepatic expression of the ...phosphatase PP2Acα is upregulated during HOD, leading to the downregulation of expression of the hepatokine lecithin-cholesterol acyltransferase (LCAT). Loss of LCAT function markedly exacerbates the bone loss phenotype of HOD in mice. In addition, we found that alterations in cholesterol levels are involved in the regulation of osteoblast and osteoclast activities. We also found that LCAT improves liver function and relieves liver fibrosis in the mouse HOD model by promoting reversal of cholesterol transport from the bone to the liver. In summary, defects in a liver-bone axis occur during HOD that can be targeted to ameliorate disease progression.
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•High levels of PP2Acα in the liver correlate with bone loss in individuals with HOD•Upregulation of LCAT expression in the liver ameliorates bone loss in HOD mice•PP2Acα downregulates LCAT expression through dephosphorylation of USF1•LCAT improves liver function by reversing cholesterol transport from bone to liver
Hepatic osteodystrophy (HOD) is a metabolic bone disease caused by chronic liver injuries. Lu et al. discovered a novel liver-bone axis in the pathogenesis of HOD involving the upregulation of hepatic PP2Acα that leads to reduced expression of the hepatokine lecithin-cholesterol acyltransferase (LCAT) and defects in reverse cholesterol transport from the bone to the liver.
A new design method of Al-Si-Mg alloy manipulated by in situ nanosized crystals was proposed. Starting from source design of the microstructure manipulation agent with a high crystallographic ...matching relationship with the α-Al, eutectic Si and Mg2Si phases in Al-Si-Mg alloy, the interatomic misfit (fr) between NiTi(B2) and α-Al or Mg2Si is 5.0% or 5.3%, respectively, and that between NiTi(B2) and Si is 9.9%, corresponding to good crystallographic matching. Based on calculations, in situ nanosized crystals could be considered as heterogeneous nucleation sites of α-Al, eutectic Si and Mg2Si, thus, uniformly fine α-Al grains, near-spherical eutectic Si and fine precipitated Mg2Si were obtained. The solidification behavior analysis also highly corresponded to the E2EM calculations. In the alloy manipulated by 0.05 wt% NiNbTi manipulation agent, the average sizes of α-Al, eutectic Si and Mg2Si were greatly decreased by nearly 8, 2 and 20 times, respectively, thus achieving comprehensive multiscale manipulation of the microstructure of the alloy in one step. Specially, the huge energy stemmed from the B2 to B19’ phase transformation will generate a large number of crystal defects, which provides nucleation sites and driving force for the formation of Mg2Si and greatly refines the Mg2Si.Moreover, the yield stress, tensile stress and fracture strain of the manipulated alloy were simultaneously improved by 34.1%, 20.4% and 35.0%, respectively. The excellent strength and plasticity could be ascribed to grain-refinement strengthening, Orowan strengthening and eutectic Si refinement and spheroidization, which reduced the stress concentration during deformation. The comprehensive microstructure manipulation of Al-Si-Mg alloy using nanosized crystals formed by in situ physical crystallization, especially the manipulation of the precipitated phase, is an innovative work that not only avoids the “poisoning” effect between multiple manipulation agents but also realizes comprehensive manipulation of the overall microstructure, consequently broadening further industrial applications.
•The low fr shows good mismatch between Al, Si, Mg2Si and NiTi.•The new method achieves multiscale manipulation of the alloy in one step.•The mean sizes of α-Al, eutectic Si and Mg2Si were decreased by nearly 8, 2 and 20 times.•The yield strength and plasticity were simultaneously improved by 34.1% and 35.0%.
The presence of depressive symptoms is associated with increasing risks of hip fractures (HFs). However, few studies investigated the longitudinal relationship between depressive symptoms and ...incident HFs among Chinese older adults, and the underlying mechanisms remain unclear.
To investigate the association between depressive symptoms and incident HFs, and the mediating role of cognitive function and impairment in activities of daily living (ADL) in the association among the older adults in China.
This population-based cohort study included 6336 Chinese older adults (age range, 60–101 years) without the history of HFs at baseline and with complete data during the follow-up. Discrete-time Cox regression was used to evaluate the relationship between depressive symptoms and incident HFs, and bootstrapped multiple mediation analyses were conducted to examine the effects of cognitive function and ADL impairment on the association.
Among 6336 participants (3172 women 50.1%; mean SD age, 67.9 6.6 years), 264 (4.2%) subjects had HFs onset. After adjusting for age, sex, education, marital status, current residence, smoking status, drinking status, body mass index, number of chronic conditions, and falls history, elevated depressive symptoms were independently associated with increasing risks of HFs (adjusted hazard ratio aHR: 1.42; 95% CI: 1.07 to 1.88). However, this association was no longer significant (aHR: 1.09; 95% CI: 0.78 to 1.53) after adjusting for cognitive function and ADL impairment. When mortality and incident HFs were modeled as a composite outcome, the association between depressive symptoms and combined outcomes also remained non-significant after adjusting for cognitive function and ADL impairment. Furthermore, the mediation model demonstrated that cognitive decline (indirect effect: β = 0.002, 95% CI: 0.001 to 0.003) and ADL impairment (indirect effect: β = 0.002, 95% CI: 0.000 to 0.003) fully mediated the association between depressive symptoms and incident HFs after adjusting for age, sex, falls history, and number of chronic conditions.
The positive association between depressive symptoms and incident HFs was confirmed among Chinese older adults, which was fully mediated by cognitive decline and ADL impairment. This study shed new light on the potential role played by depressive symptoms in incident HFs.
•Depressive symptoms were associated with increased risks of hip fractures (HFs).•The close association was fully mediated by cognitive decline and ADL impairment.•Interventions in cognitive and physical functions might be helpful to prevent HFs.
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